julilili42/papers huggingface dataset:
Treatment at the end of life in patients with advanced melanoma. A multicenter DeCOG study of 1067 patients from the prospective skin cancer registry ADOReg
2025-02-24

Background Although systemic therapies have improved considerably over the last decade, up to 50% of patients with metastatic melanoma still die due to disease progression. Oncological treatment at the end-of-life phase is challenging. The aim of this study was to investigate the frequency and type of systemic therapy received by melanoma patients in their end-of-life phase. Methods Patients with metastatic melanoma who had died between January 1, 2018 and October 31, 2022 were identified from the prospective multicenter skin cancer registry ADOReg. Study endpoints were percentage of patients who had been treated with systemic therapy within the last three months of life, timepoint of initiation of the last-line therapy, overall survival, treatment benefit and the incidence of treatment-related adverse events. Results In total, 1067 patients from 46 skin cancer centers were included. Most of the patients (63%) had received immune checkpoint inhibitors (ICI) as last-line therapy, 22% targeted therapies (TT) and 12% chemotherapy (CTX). Comparing last-line ICI and TT, patients with TT were significantly more likely to benefit from treatment and had significantly fewer and milder treatment-related AE than patients with ICI. Even though two thirds of patients had received ICI as a last-line therapy, the majority of these patients (61%) had stopped therapy within the last 30 days of life, whereas the majority of patients with TT (66%) still continued their treatment to the end of life. We found markedly fewer patients with initiation of ICI within 30 days before their death (19%) compared to a historic cohort including patients who died in 2016 or 2017 (39%). Conclusion Treatment approaches near the end of life have markedly changed in skin cancer centers in Germany over recent years, with ICI prescribed less frequently in the end-of-life phase. In contrast, TT are frequently administered, even within the last 30 days of life. It should also be considered that discontinuation of TT can result in rapid tumor progression. Due to the oral administration and a low rate of severe toxicity, TT appear to be a suitable treatment option, even in the end-of-life situation of melanoma patients.
Fostering Creativity Through Game‐Based Approaches: A Scoping Review
2025-02-24

ABSTRACT Given the increasing emphasis on game‐based approaches (GBAs) and the critical importance of cultivating creativity, there is an urgent need for a comprehensive examination of this emerging interdisciplinary field. The present study employs a scoping review methodology to provide an overview of the existing research that utilized GBAs as a means to foster creativity. Specifically, this article presents a scoping review of 61 studies published between 2000 and 2022 in English focusing on the use of GBAs to enhance creativity across various contexts. The results indicate an increasing trend in publications over the past two decades, with research clusters predominantly located in the United States, Taiwan, and Spain. Target groups primarily studied include adults in higher education, followed by children in K‐12 settings, with the majority of studies conducted within classroom environments. A diverse array of GBAs have been employed in these studies, including video games, game‐based learning, gamification, serious games, escape rooms, board games, and more, across both digital and non‐digital media. These approaches were either developed by the researchers themselves or utilized pre‐existing ones. Furthermore, GBAs have been found to foster various aspects of creativity, including creative thinking and problem‐solving, flow and mastery experience, various aspects of the creative self, among others, pertaining to cognitive, motivational, affective, and sociocultural foundations. As such, this scoping review acts as a stimulus for ongoing research and refinement of game‐based approaches aimed at enhancing creativity within both research and practical domains.
Athletes with eating disorders: clinical-psychopathological features and gender differences
2025-02-24

These results suggest that it may be imperative to better understand the risk factors in the athletic realm which may lead to the development of EDs, and which factors may be protective as well. It may also be helpful to encourage trainers to include preventive and screening strategies for athletes.
Cardiac structure and function 1.5 years after COVID-19: results from the EPILOC study
2025-02-24

Abstract Purpose Impaired left and right ventricular (LV/RV) function during acute SARS-CoV-2 infection has been predominantly reported in hospitalized patients, but long-term cardiac sequelae in large, well-characterized cohorts remain inconclusive. This study evaluated cardiac structure and function in individuals with post-Coronavirus disease (COVID) syndrome (PCS) compared to recovered controls (CON), focusing on associations with cardiopulmonary symptoms and rapid physical exhaustion (RPE). Methods This multicenter, population-based study included 1154 participants (679 PCS, 475 age- and sex matched CON; mean age 49 ± 12 years; 760 women) 1.5 years post-infection. Transthoracic echocardiography assessed LV global longitudinal strain (GLS), RV GLS and RV free wall strain (FWS), and other measures. Cardiopulmonary exercise testing (CPET) measured maximum respiratory oxygen uptake (VO 2 max) as a marker of cardiopulmonary fitness. Results PCS participants exhibited significantly lower LV GLS (-20.25% [-21.28 – -19.22] vs. -20.73% [-21.74 – -19.72], p = 0.003), reduced diastolic function (E/A 1.16 [1.04–1.27] vs. 1.21 [1.1–1.32], p = 0.022) and decreased TAPSE (24.45 mm [22.14–26.77] vs. 25.05 mm [22.78–27.32], p = 0.022) compared to CON, even after adjusting for confounders. RV strain values were similar between groups. LV GLS correlated inversely with VO 2 max ( p = 0.004) and positively with RPE ( p = 0.050), though no associations were observed with other cardiopulmonary symptoms. Conclusions This study demonstrates subtle yet consistent reductions in LV function, specifically LV GLS and diastolic function, and exercise capacity in PCS compared to CON. While these changes are within reference ranges, their potential impact on clinical outcomes warrants further investigation. These findings highlight the need for cardiac assessments and long-term follow-up in symptomatic PCS patients.
Development and validation of a patient knowledge questionnaire for rheumatoid arthritis (PKQ-RA-11) in Danish and German
2025-02-24

PKQ-RA-11 is a standardized tool for assessing disease-related knowledge in individuals with RA. It can be used to provide objective and transparent measures of patient understanding in educational programmes, clinical practice, or research.
Reciprocal associations between confidence in getting social support and academic expectancies and subjective task values: Stronger for first‐generation and transfer students
2025-02-26

Abstract Background Social support is assumed to play a key role in motivation at university, particularly for disadvantaged students, such as first‐generation and community college transfer students. However, longitudinal research investigating reciprocal associations between social support and motivation is lacking. Aims We examined such associations between confidence in getting support from faculty and peers and students' expectancies and subjective task values in their most difficult and most important course. Sample Data stemmed from two cohorts of undergraduate students ( n = 320/417 in Fall 2019/2020) at a diverse Southern Californian university. Methods Students reported on their confidence in getting support and their expectancies and subjective task values at the beginning, in the middle and (only for motivation) at the end of the academic term. Results Results indicated no differences in confidence in getting support based on university generation or transfer student status. Cross‐lagged panel models provided some evidence for reciprocal associations between students' confidence in getting support and their expectancies and subjective task values. Findings were similar across the Fall 2019 and Fall 2020 cohorts, providing support for the generalizability across in‐person vs. remote learning settings. Longitudinal associations tended to be stronger for first‐generation and transfer students. Conclusions Future research should, therefore, examine whether university programmes targeting social support are especially effective for disadvantaged students.
Retinal Responses to Short- and Longer-Term Predominant ON or OFF Stimulation in Emmetropes and Myopes
2025-02-26

Myopes had largest ON-responses with inverted contrast in the perifovea. Emmetropes displayed larger adaptive changes after ON/OFF stimulation. In both groups, inverted contrast still reduced ON-responses, suggesting that efficient activation of retinal ON channels to inhibit myopia might require additional OFF channel suppression.
Transformation of flg22 perception into electrical signals decoded in vasculature leads to sieve tube blockage and pathogen resistance
2025-02-26

This study focuses on the question how and where information acquired by FLS2 perception of flg22 is transformed into electrical signals crucial for generation of local and systemic defense responses. In Arabidopsis thaliana and Vicia faba leaves, FLS2 density was high in the epidermis and vascular parenchyma, low in mesophyll, and absent in sieve elements (SEs). Aequorin-based examinations disclosed dual cytosolic Ca 2+ peaks shortly after flg22 application, which corresponded with two voltage shifts from the epidermis to SEs. These signals were converted into rapid long-range action potentials (APs) or slower short-range variation potentials (VPs). Modified phytohormone-levels demonstrated systemic AP effects. Jasmonic acid up-regulation was significantly higher in wild-type than Atseor1/2 mutants. Abundant Ca 2+ influx associated with VPs was responsible for transient sieve element occlusion (SEO) near the flg22 perception site, whereas SEO was absent in Atseor1/2 and Atfls2 mutants. Biological relevance of SEO was demonstrated by higher susceptibility of Atseor1/2 mutants to Pseudomonas syringae than wild-type plants.
Sex‐Related Differences in Outcomes of Endovascular Treatment in Large Vessel Occlusion Stroke—Analyses From the German Stroke Registry‐Endovascular Treatment
2025-02-26

ABSTRACT Background Sex‐related differences in acute ischemic stroke may affect outcomes, yet evidence remains inconsistent. This large‐scale study investigated sex‐related differences in clinical presentation, peri‐interventional parameters, and outcomes after endovascular thrombectomy (EVT) for large vessel occlusion (LVO) using data from the German Stroke Registry—Endovascular Treatment (GSR‐ET). Methods We analyzed 11.896 EVT patients (52.2% female) from the GSR‐ET (June 2015–December 2021) comparing clinical characteristics, treatment details, and outcomes by sex. Two propensity score matchings (PSM) were applied: (1) logistic regression model with a caliper width of 0.1 on age, pre‐stroke modified Rankin Scale (pmRS), and National Institutes of Health Stroke Scale at admission, and (2) 1:1 nearest neighbor matching with a caliper of 0.01. Primary outcomes were good (mRS 0–2) and excellent (mRS 0–1) outcomes at discharge and 90‐day follow‐up. Results Women were older (76.3 ± 12.7 vs. 70.2 ± 12.9 years, p &lt; 0.001) and had higher pre‐stroke disability (median pmRS 0 (0, 2) vs. 0 (0, 1), p &lt; 0.001). Cardioembolic strokes were more frequent in women, even after PSM. Despite this, women had better odds of achieving good outcomes at discharge (adjusted OR 1.20, 95% CI 1.04–1.38, p = 0.013), but not at follow‐up (OR 0.91, 95% CI 0.78–1.05, p = 0.193). Both PSM analyses confirmed these findings. Conclusions While women demonstrated better short‐term functional outcomes after EVT, these benefits diminished in follow‐up. The persistence of cardioembolic stroke in women suggests potential sex‐specific mechanisms. Understanding and addressing sex‐related differences in stroke is essential to optimize acute stroke care and improve outcomes. Future studies should explore biological and socio‐economic factors influencing sex‐related differences. Trial Registration ClinicalTrials.gov identifier: NCT03356392
Global Spectral Analysis of Polaritonic Coupling of Multiple Organic Dyes to a Tunable Fabry‐Pérot Resonator Operating with Mirror Separations up to 10 μm
2025-02-26

Abstract We study strong optical coupling and the formation of hybrid polaritons by a donor‐acceptor pair of J‐aggregated dyes separated by up to 11 μm in a tunable Fabry‐Pérot resonator. Fitting a phenomenological Hamiltonian to the white light transmission spectra of different cavity‐J‐aggregate‐configurations, for which several hundred spectra were recorded sequentially as function of cavity length, allows us to determine coupling energies as a function of the effective cavity distances. The theoretical analysis shows that certain hybrid polaritons contain contributions from both dyes, making this system a promising platform for polariton‐mediated energy transfer at very large distances.
Noradrenergic and Dopaminergic modulation of meta-cognition and meta-control
2025-02-26

Humans and animals use multiple control systems for decision-making. This involvement is subject to meta-cognitive regulation – as a form of control over control or meta-control. However, the nature of this meta-control is unclear. For instance, Model-based (MB) control may be boosted when decision-makers generally lack confidence as it is more statistically efficient; or it may be suppressed, since the MB controller can correctly assess its own unreliability. Since control and metacontrol are themselves subject to the influence of neuromodulators, we examined the effects of perturbing the noradrenergic (NE) and dopaminergic (DA) systems with propranolol and L-DOPA, respectively. We first administered a simple perceptual task to examine the effects of the manipulations on meta-cognitive ability. Using Bayesian analyses, we found that 81 % of group M-ratio samples were lower under propranolol relative to placebo, suggesting a decrease of meta-cognitive ability; and 60 % of group M-ratio samples were higher under L-DOPA relative to placebo, considered as no effect of L-DOPA on meta-cognitive ability . We then asked subjects to provide choices and confidence ratings in a two-outcome decision-making task that has been used to dissociate Model-free (MF) and MB control. MB behavior was enhanced by propranolol, while MF behavior was not significantly affected by either drug. The interaction between confidence and MF/MB behavior was highly variable under propranolol, but under L-DOPA, the interaction was significantly lower/higher relative to placebo. Our results suggest a decrease in metacognitive ability under the influence of propranolol and an enhancement of MB behavior and meta-control under the influence of propranolol and L-DOPA, respectively. These findings shed light on the role of NE and DA in different aspects of control and meta-control and suggest potential avenues for mitigating dysfunction.
The Delayed Cortisol Peak Effect After Severe Burn Injury: A Prospective Observational Study
2025-02-26

The findings of the current study align with previous studies suggesting a relative cortisol deficit during the acute stages of severe burn injury, supporting the treatment approach of early low-dose hydrocortisone supplementation in patients with severe burn injury.
A Simplified Guide RNA Synthesis Protocol for SNAP- and Halo-Tag-Based RNA Editing Tools
2025-02-26

SNAP-tag and Halo-tag have been employed to achieve targeted RNA editing by directing the deaminase domain of human ADAR to specific sites in the transcriptome. This targeting is facilitated by short guide RNAs (gRNAs) complementary to the target transcript, which are chemically modified with benzylguanine or chloroalkane moieties to enable covalent binding to the respective self-labeling enzymes. However, broad application of this approach has been limited by challenges such as low scalability, the requirement for specialized chemical expertise and equipment, and labor-intensive protocols. In this study, we introduce streamlined, efficient protocols for the synthesis and purification of these linkers, suitable for SNAP-tag and Halo-tag applications, without the need for advanced chemical equipment. Our methods enable linker coupling in a kit-like manner and support the high-yield production of modified gRNAs. We demonstrate that the newly synthesized linkers and gRNA designs perform similarly to previously published constructs with regard to RNA editing efficiency. Moreover, large-scale production of modified gRNAs facilitates their use in studies involving cellular uptake and in vivo experiments.
The Morphology of the Rare Beetle Silphopsyllus desmanae (Leiodidae), a Commensal of the Semiaquatic Russian Desman
2025-02-26

ABSTRACT Silphopsyllus desmanae , a species of the small subfamily Platypsyllinae of Leiodidae, lives in the fur of the semiaquatic Russian desman, and is apparently adapted to this highly specialized life style. Even though the morphology of adults of the species was described almost 70 years ago, we re‐examined it with modern methods and documented its external and internal features in detail, and discuss them with respect to phylogeny and function. Our analyses of morphological data place Leptinillus as the sister group of the remaining genera of Platypsyllinae, and Leptinus as the sister group of Silphopsyllus + Platypsyllus . Platypsyllinae are supported by many putative autapomorphies: supraantennal ridges directed mesad but not extending beyond the antennal insertions and not forming a transverse ridge; tentorium without connected laminatentoria anterior to the tentorial bridge; submentum subrectangular; labrum about as wide as the maxillary‐labial complex; elongate and posteriorly projecting lateral lobes of the mentum; antennomeres lacking periarticular gutters (and Hamann's organs); cervical sclerites absent; precoxal prosternal region distinctly longer than the coxal rests; mesocoxal cavities situated closer to the body midline than to the lateral mesothoracic margins; metanepisterna fused with the metaventrite; metascutum laterally overlapping the meso‐ and metapleural regions; procoxae subglobose or only slightly elongate; mesocoxae subglobose. Platypsyllinae are most likely the sister group of Coloninae + Cholevinae. Eight unique apomorphies differentiating Platypsyllus from all the remaining Platypsyllinae are mainly adaptations for living in the fur of beavers. Silphopsyllus is much less adapted to life on a semiaquatic host than Platypsyllus .
›Epistemisch unfreundliche Umwelten‹ als Bildungsherausforderung
2025-02-26

Abstract ›Epistemically Unfriendly Environments‹ as an Educational Challenge. A Discussion of Intellectual Virtues and Epistemic Mindfulness »Epistemically unfriendly environments« (Pritchard 2013) refer to environments such as echo chambers that make it difficult to acquire knowledge. To mitigate this problem, the following article considers intellectual virtues as an educational approach, particularly in Anglo-Saxon philosophy of education. The discussion takes up the naturalist perspective of philosophy of mind and epistemic mindfulness.
Comprehensive analysis of human dendritic spine morphology and density
2025-02-27

This study presents a dataset of nearly 4,000 morphologically reconstructed human dendritic spines across different ages, gender, and tissue conditions. The dataset was further used to evaluate a deep learning algorithm for three-dimensional spine reconstruction, offering a scalable method for semiautomated spine analysis across various tissues and microscopy setups. The findings enhance understanding of human neurology, indicating potential connections between spine morphology, brain function, and the mechanisms of neurological and psychiatric diseases.
Origins of rings in the Solar System
2025-02-27

Until about a decade ago, ring systems were only known to exist around giant planets. Each one of the four giant planets harbours its own distinctive and unique system of rings and inner satellites. The past decade has been marked by the unexpected discoveries of dense rings around small objects of the outer Solar System: the Centaur object Chariklo (and possibly Chiron), the dwarf planet Haumea and the trans-Neptunian object Quaoar. In the latter case, an additional surprise came from the fact that Quaoar’s rings orbit well beyond the Roche limit of the body. Here, we address the possible origins and evolution of these ring systems. This article is part of the theme issue ‘Major advances in planetary sciences thanks to stellar occultations’.
Preclinical in vitro and in vivo evidence for targeting CD74 as an effective treatment strategy for cutaneous T-cell lymphomas
2025-02-27

Abstract Background Prognosis and quality of life in patients with advanced cutaneous T-cell lymphoma (CTCL), particularly in those with Sézary syndrome (SS) or advanced-stage mycosis fungoides (MF), are poor. Monoclonal antibodies or antibody–drug conjugates (ADCs) have been added into CTCL treatment algorithms, but the spectrum of antibody-targetable cell surface antigens in T-cell non-Hodgkin lymphomas (T-NHLs) is limited. Objectives To evaluate the expression of the major histocompatibility complex class II chaperone CD74 in common subtypes of CTCL by various methods, and to explore the efficacy of targeting CD74 in CTCL cells with an anti-CD74 ADC in vitro and in vivo. Methods We comprehensively investigated the expression of CD74 in well-defined CTCL cell lines by polymerase chain reaction, immunoblotting and flow cytometry. More than 140 primary CTCL samples of all common subtypes were analysed by immunohistochemistry, flow cytometry, immunofluorescence and ‘co-detection by indexing’ (CODEX) multiplexed tissue imaging, as well as by single-cell RNA sequencing (scRNAseq) analyses. DNA methylation of CTCL cell lines was interrogated by the generation of genome-wide methylation profiling. The effect of a maytansinoid-conjugated humanized ADC against CD74 was investigated in CTCL cell lines in vitro, alone or in combination with gemcitabine, and in vivo after xenotransplantation of CTCL cell lines in NOD-scid Il2rgnull mice. Results We demonstrated that CD74 is widely and robustly expressed in CTCL cells. In addition, CD74 expression in SS and MF was confirmed by scRNAseq data analysis and was correlated in CTCL cell lines with CD74 DNA hypomethylation. CD74 was rapidly internalized in CTCL cells and CD74 targeting by the ADC STRO-001 efficiently killed CTCL-derived cell lines. Finally, targeting of CD74 synergized with conventional chemotherapy in vitro and eradicated murine xenotransplants of CTCL cell lines in vivo. Conclusions CD74 is expressed in common CTCL subtypes. Targeting CD74 efficiently killed CTCL cells in vitro and in vivo. We therefore suggest the targeting of CD74 to be a highly promising treatment strategy for CTCL.