julilili42/papers huggingface dataset:
The relationship between perception and landscape characteristics of recreational places with human mental well-being
2025-02-04

Abstract Being outdoors benefits both humans’ physical and mental well-being, but the reasons for this connection are difficult to pinpoint. This study examines 40 recreational areas to understand their individual characteristics’ impact on mental well-being. We interviewed 1184 visitors on their perception of the place and feeling of mental well-being. In a second survey, 49 participants were shown images of the areas to assess whether they perceived them in the same way as people on-site did. Biologists then evaluated the areas through bird and biotope surveys, also assessing various other landscape characteristics of the study areas. Analysis using a two-level multivariate GLM revealed that perceived naturalness and perceived bird diversity are significant predictors of improved mental well-being. On the flip side, mental well-being declines with increased human impact, as indicated by the amount of infrastructure and the Human Footprint Index value. Notably, perceived naturalness positively correlates with actual bird diversity ( p = 0.005) and negatively with human impact ( p = 0.006). A strong perception of birds enhances the mental well-being of greenspace visitors ( p &lt; 0.001), while a high birding specialization negatively affects recalled restoration ( p = 0.014). The estimated restoration value ( p = 0.001) and estimated beauty ( p &lt; 0.001) from the online survey correlate positively with emotions experienced on-site. The perception of naturalness in images aligns with on-site perception, suggesting pathways for future research and the design of recreational areas.
The landscape of autosomal-dominant Alzheimer’s disease: global distribution and age of onset
2025-02-04

Abstract We present a comprehensive global analysis of genetic variants associated with autosomal-dominant Alzheimer’s disease (ADAD). A total of 550 variants in the APP, PSEN1 and PSEN2 genes were identified, of which 279 were classified as pathogenic or likely pathogenic based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria, utilizing data from the Dominantly Inherited Alzheimer Network (DIAN), literature and public databases. Symptomatic age at onset (AAO) data were estimated for 227 of these variants, allowing detailed characterization of their frequency, pathogenicity and AAO. Importantly, 226 variants met eligibility criteria for inclusion in disease-modifying clinical trials. Furthermore, we demonstrated the predictive value of mean variant AAO and parental AAO in predicting symptomatic AAO, validated against converters who became symptomatic during follow-up in the DIAN Observational Study. This dataset provides critical insights into the global landscape of ADAD and reveals the genetic and AAO heterogeneity of ADAD variants while refining variant trial eligibility criteria.
Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics
2025-02-04

Medulloblastoma is the most frequent malignant primary brain tumor in children. Despite recent advances in integrated genomics, the prognosis in children with high-risk medulloblastoma remains devastating, and new tumor-specific therapeutic approaches are needed. Here, we present an atlas of naturally presented T cell antigens in medulloblastoma. We map the human leukocyte antigen (HLA)-presented peptidomes of 28 tumors and perform comparative immunopeptidome profiling against an in-house benign database. Medulloblastoma is shown to be a rich source of tumor-associated antigens, naturally presented on HLA class I and II molecules. Remarkably, most tumor-associated peptides and proteins are subgroup-specific, whereas shared presentation among all subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) is rare. Functional testing of top-ranking novel candidate antigens demonstrates the induction of peptide-specific T cell responses, supporting their potential for T cell immunotherapy. This study is an in-depth mapping of naturally presented T cell antigens in medulloblastoma. Integration of immunopeptidomics, transcriptomics, and epigenetic data leads to the identification of a large set of actionable targets that can be further used for the translation into the clinical setting by facilitating the informed design of immunotherapeutic approaches to children with medulloblastoma.
Kinetics of quantum reaction-diffusion systems
2025-02-04

We discuss many-body fermionic and bosonic systems subject to dissipative particle losses in arbitrary spatial dimensions d <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mi>d</mml:mi></mml:math> , within the Keldysh path-integral formulation of the quantum master equation. This open quantum dynamics represents a generalisation of classical reaction-diffusion dynamics to the quantum realm. We first show how initial conditions can be introduced in the Keldysh path integral via boundary terms. We then study binary annihilation reactions A+A\\to \\emptyset <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:mi>A</mml:mi><mml:mo>+</mml:mo><mml:mi>A</mml:mi><mml:mo>→</mml:mo><mml:mi>∅</mml:mi></mml:mrow></mml:math> , for which we derive a Boltzmann-like kinetic equation. The ensuing algebraic decay in time for the particle density depends on the particle statistics. In order to model possible experimental implementations with cold atoms, for fermions in d=1 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:mi>d</mml:mi><mml:mo>=</mml:mo><mml:mn>1</mml:mn></mml:mrow></mml:math> we further discuss inhomogeneous cases involving the presence of a trapping potential. In this context, we quantify the irreversibility of the dynamics studying the time evolution of the system entropy for different quenches of the trapping potential. We find that the system entropy features algebraic decay for confining quenches, while it saturates in deconfined scenarios.
Localization Matters: Impacts of PEG‐J Localization in Intestinal Levodopa Therapy for Parkinson's Disease
2025-02-04

Abstract Background Real‐world clinical evidence is missing to understand the resorption characteristics of levodopa through duodenal and jejunal parts of the small intestine. Objective To characterize how different application sites of intestinal levodopa gel would impact on levodopa dosing and clinical outcomes. Methods This multicentre retrospective analysis investigated Parkinson's disease patients (n = 111) and their change in levodopa equivalent dosage when switching from oral treatment to intestinal continuous infusion therapy while stratifying for differences in percutaneous gastrojejunostomy (PEG‐J) tube localizations. We analyzed data from patients treated with both levodopa–carbidopa (LCIG) and levodopa–carbidopa–entacapone (LECIG) intestinal gel. Results In dichotomic analysis, duodenal and jejunal tube positions showed similar levodopa equivalent dosages changes from baseline ( P = 0.143). This was similar when subdividing patients for LCIG and LECIG treatment. In duodenal PEG‐J positions, 44.4% of patients showed persistent motor fluctuations compared to 21.9% in jejunal placements ( P = 0.026). In duodenal positions, fluctuations most often persisted when the PEG‐J tube was placed proximally into the duodenum. In jejunal localizations, several patients displayed a satisfactory outcome from the primary intervention but experienced dislocation of the PEG‐J tube to a duodenal position. This was associated with re‐emergence of motor fluctuations in a majority of them. Conclusions Our real‐world data suggest that LCIG and LECIG are absorbed similarly in both duodenal and jejunal portions of the small intestine. However, clinical data suggest, that jejunal positioning is critical to the stabilization of dopaminergic motor fluctuations.
Patients with Adult-Onset Still’s Disease in Germany: A Retrospective Analysis of Clinical Characteristics and Treatment Practices Ahead of the Release of the German Recommendations
2025-02-04

Background/Objectives: Adult-onset Still’s disease (AOSD) is an autoinflammatory disorder that can be challenging to diagnose and manage. The aim of this study was to analyze retrospective data to provide insights into the clinical presentation, disease activity, and treatment patterns and outcomes of AOSD during routine clinical care prior to the release of new AOSD guidelines. Methods: This retrospective database analysis evaluated adult patients (≥18 years) with a diagnosis of AOSD who engaged in a clinical visit between 1 January 2010 and 31 December 2020. The evaluated outcomes included demographic characteristics, symptoms, disease activity, and treatment. Results: Our study included 120 patients (67 [55.8%] of whom were female) diagnosed with AOSD according to the Yamaguchi criteria at ten German rheumatology centers. The median (quartile [Q] 1, Q3) age was 51 (36, 62) years, and the median (Q1, Q3) time from diagnosis was 9 (4, 11) years. Approximately half (66 [55.0%]) had a polycyclic disease course. The most frequent symptoms at initial diagnosis were arthralgia (105 [87.5%]) and fever (86 [71.7%]), and these symptoms continued for a substantial proportion of patients at the current visit (35 [29.2%] and 22 [18.3%], respectively). High neutrophil and ferritin levels were also common. The mean Still Activity Score, a measure of disease activity, improved from 4.66 at initial diagnosis to 1.97 at the most recent visit. The treatments most frequently used at some point in the disease course were glucocorticoids (118 [98.3%]), interleukin (IL)-1 inhibitors (89 [74.2%]), and methotrexate (85 [70.8%]). The most common current treatments were IL-1 inhibitors (55 [45.8%]), followed by methotrexate (29 [24.2%}) and glucocorticoids (28 [23.3%]). Conclusions: Our cohort of patients with AOSD seen at German rheumatology clinics showed strong improvements in symptoms and disease activity from initial diagnosis, but a high symptom burden remained for some patients. Future studies may be able to build on our data to document the impact of new guidelines on treatment patterns.
Climate change increases toxic cadmium loads more than nutritional metals in spinach
2025-02-04

<title>Abstract</title> In addition to food quantity, food quality is paramount for meeting the demands of a growing global population. Food quality encompasses both nutritional and contaminant contents, yet their transfer within soil-crop systems remains poorly understood under impending climate change. This greenhouse study is the first to demonstrate that future climatic conditions increase the transfer of metals from oxic soils to crops, showcased for four soil-spinach variety combinations (<italic>Spinacia oleracea</italic>). Future conditions raised harmful metal cadmium levels in edible spinach tissues by 26–54%. In contrast, changes in micronutrient (Zn, Mn, Mg) contents were inconsistent and dependent on the specific soil-spinach combination. Climate-induced shifts in soil carbon composition and bacterial communities were linked to greater soil Cd phytoavailability, enhancing Cd transfer from soil to roots. These findings suggest that while spinach's nutritional values may remain stable, future conditions could lead to higher metal contaminants levels in edible tissues.
European Stroke Organisation (ESO) standard operating procedure for white papers (expert consensus based clinical guidance)
2025-02-04

Promoting the highest quality, evidence-based research across Europe is a priority of the European Stroke Organisation (ESO). The ESO Guideline Board communicate and promote evidence-based recommendations for clinical practice through their Guidelines. However, there are many aspects of stroke care where robust scientific evidence may be unavailable or difficult to obtain. Thus, there is a need for practical, consensus guidance, produced following robust, consistent, and transparent methods, that is suitable for high-priority clinical scenarios where evidence is currently lacking. The ESO Guideline Board developed methods for producing practical clinical guidance based on expert consensus in response to this need. These ESO’ White Papers’ are intended to complement standard ESO Guidelines. Here, we outline the ESO White Papers’ standard operating procedure (SOP). We will describe the motivation for creating White Papers, the preferred composition of writing groups and expert consensus panellists, the methods for achieving consensus, and how results will be communicated. To ensure that all voting members have an equal voice, our methods are based upon the Delphi process of repeated rounds of anonymous voting, feedback and review. We hope that the White Papers will add further value to the clinical practice guidance that is offered by ESO. We look forward to receiving suggestions for White Paper topics from the stroke community.
Single-cell transcriptomics reveals a compartmentalized antiviral interferon response in the nasal epithelium of mice
2025-02-04

ABSTRACT Type III interferons (IFNs) primarily act on epithelial cells and protect against virus infection of the mucosa, whereas type I IFNs act more systemically. To date, it has been unknown which epithelial subtypes in the upper airways, the primary site for initial infection for most respiratory viruses, primarily rely on type III IFN or type I IFNs for antiviral protection. To address this question, we performed a single-cell transcriptomics analysis of the epithelial IFN-mediated response focusing on the upper airways of mice. This work identified nine distinct cell types derived from the olfactory epithelium and thirteen distinct cell types from the respiratory epithelium. Interestingly, type I IFNs induced a stronger antiviral transcriptional response than type III IFN in respiratory epithelial cells, whereas in olfactory epithelial cells, including sustentacular (SUS) and Bowman’s gland cells (BGC), type III IFN was more dominant compared to type I IFN. SUS and BGC, which provide structural support and maintain the integrity of olfactory sensory neurons, were highly susceptible to infection with a mouse-adapted variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 MA20) but were protected against infection if the animals were prophylactically treated with type III IFN. These findings demonstrate a high degree of cell type heterogeneity in terms of interferon-mediated antiviral responses and reveal a potent role for type III IFNs in protecting the olfactory epithelium. IMPORTANCE SARS-CoV-2 infects SUS and BGC in the olfactory epithelium, causing an impairment of structural support and integrity of olfactory sensory neurons that can result in severe olfactory dysfunctions. We observed an unexpected compartmentalization of the IFN-mediated transcriptional response within the airway epithelium, and we found that olfactory epithelial cells preferentially respond to type III IFN, which resulted in robust antiviral protection of SUS and BGC. Given the proximity of the olfactory epithelium to the central nervous system, we hypothesize that evolution favored a type III IFN-biased antiviral immune response in this tissue to limit inflammatory responses in the brain. Cell type-specific antiviral responses in the upper airways, triggered by the different types of IFNs, should be investigated in more detail and carefully taken into consideration during the development of IFN-based antivirals for clinical use.
Toward Far-red Emitting Chemogenetic Labelling for Live Cell Super-Resolution Microscopy using Fluorescence-Activating and Absorption-Shifting Tag
2025-02-04

Live cell super-resolution microscopy (SRM) imaging is often limited by the lack of optimal fluorescent labelling approaches. Here, we report two new chemogenetic approaches allowing far-red fluorescence detection to label intracellular protein targets to achieve background free SRM images in fixed and live mammalian cells. These methods are based on Fluorescence-activating and Absorption Shifting Tag (FAST), a small monomeric protein tag that forms reversible fluorescent assembly with various rhodanine fluorophores. We developed a Förster resonance energy transfer based (FRET-FAST) method that allows single molecule localization microscopy (SMLM) imaging of proteins in fixed mammalian cells. Additionally, we applied a far-red emitting variant (frFAST) to conduct fixed and live cell SMLM and stimulated emission depletion (STED) microscopy. Time-lapse SMLM up to 40 minutes revealed cytoskeletal dynamics without significant photobleaching. Additionally, we imaged filopodia in living neuroblastoma cells. Moreover, we succesfully imaged mitochondrial outer membrane, microtubules, cytoskeleton and histone proteins in live cell STED microscopy. It is envisioned that the excellent photostability achieved by the presented far-red emitting FAST labelling techniques provides a new alternative for stochastic and deterministic SRM imaging of living cells, even for longer imaging sessions.
Endovascular Treatment of Stroke Due to Medium-Vessel Occlusion
2025-02-05

Endovascular treatment for acute ischemic stroke due to medium-vessel occlusion within 12 hours did not lead to better outcomes at 90 days than usual care. (Funded by the Canadian Institutes for Health Research and Medtronic; ESCAPE-MeVO ClinicalTrials.gov number, NCT05151172.).
Proteomic analysis reveals distinct cerebrospinal fluid signatures across genetic frontotemporal dementia subtypes
2025-02-05

We used an untargeted mass spectrometric approach, tandem mass tag proteomics, for the identification of proteomic signatures in genetic frontotemporal dementia (FTD). A total of 238 cerebrospinal fluid (CSF) samples from the Genetic FTD Initiative were analyzed, including samples from 107 presymptomatic (44 C9orf72 , 38 GRN , and 25 MAPT ) and 55 symptomatic (27 C9orf72 , 17 GRN , and 11 MAPT ) mutation carriers as well as 76 mutation-negative controls (“noncarriers”). We found shared and distinct proteomic alterations in each genetic form of FTD. Among the proteins significantly altered in symptomatic mutation carriers compared with noncarriers, we found that a set of proteins including neuronal pentraxin 2 and fatty acid binding protein 3 changed across all three genetic forms of FTD and patients with Alzheimer’s disease from previously published datasets. We observed differential changes in lysosomal proteins among symptomatic mutation carriers with marked abundance decreases in MAPT carriers but not other carriers. Further, we identified mutation-associated proteomic changes already evident in presymptomatic mutation carriers. Weighted gene coexpression network analysis combined with gene ontology annotation revealed clusters of proteins enriched in neurodegeneration and glial responses as well as synapse- or lysosome-related proteins indicating that these are the central biological processes affected in genetic FTD. These clusters correlated with measures of disease severity and were associated with cognitive decline. This study revealed distinct proteomic changes in the CSF of patients with genetic FTD, providing insights into the pathological processes involved in the disease. In addition, we identified proteins that warrant further exploration as diagnostic and prognostic biomarker candidates.
The Importance of Monitoring Antigen-Specific Memory B Cells, and How ImmunoSpot Assays Are Suitable for This Task
2025-02-05

Determining an individual’s humoral immune reactivity to a pathogen, autoantigen, or environmental agent is traditionally accomplished through the assessment of specific antibody levels in blood. However, in many instances, titers of specific antibodies decline over time and thus do not faithfully reveal prior antigen exposure or establishment of immunological memory. To estimate an individual’s humoral immune competence, it is therefore necessary to assess functional B cell memory. Here, we describe novel B cell ELISPOT and FluoroSpot assays (collectively referred to as ImmunoSpot) that can be rapidly developed and validated to characterize the memory B cell (Bmem) repertoire specific for any desired antigen ex vivo and at single-cell resolution. Moreover, multiplexed variants of the B cell FluoroSpot assay enable high-throughput testing of antigen-specific B cells secreting distinct antibody classes and/or IgG subclasses, with minimal cell material requirements. B cell ImmunoSpot assays also enable measurement of affinity distributions within the antigen-specific Bmem compartment and permit cross-reactivity measurements that can provide insights into Bmem established against future pathogen variants. Collectively, the ImmunoSpot® system presented here is highly reproducible, and can be readily validated for regulated tests. The newly gained ability to monitor the antigen-specific Bmem compartment should catalyze a more comprehensive understanding of humoral immunity in health and disease.
Outbalanced: The cross-cortical effects of prefrontal neuromodulation in posterior parietal cortex
2025-02-05

Cognitive phenomena such as the Spatial-Numerical Association of Response Codes (SNARC) effect can arise in the fronto-parietal cortical network. Prior neuromodulation studies with cathodal transcranial direct current stimulation (tDCS) over the left prefrontal cortex (PFC) reduced the SNARC effect. Prior neuroimaging studies with functional near-infrared spectroscopy (fNIRS), however, showed signatures of the SNARC effect in the posterior parietal cortex (PPC). In this study, we investigated the distant neural effect of prefrontal neuromodulation on hemodynamic activity in the parietal cortex by combining cathodal tDCS with fNIRS. The SNARC effect and the numerical distance effect (NDE) were assessed in an event-related cross-over design (N = 45), when cathodal tDCS of 1 mA at the left PFC was applied simultaneously during the measurement of fNIRS covering the bilateral PPC. At the behavioral level, prefrontal tDCS did not significantly reduce the SNARC effect, indicating that the replication failed here. Crucially, at the neuronal level, prefrontal tDCS reduced left parietal activation associated with the SNARC effect but not with the NDE. This neuronal effect of tDCS in a remote site was shown in preregistered primary region-of-interest analyses and in secondary all-channel analyses. The results showed how the combination of neuromodulation and neuroimaging shed light on the fronto-parietal network responsible for numerical cognition, and how fNIRS can assess the distant neural effects of cathodal tDCS.