julilili42/papers huggingface dataset:
Tissue‐Resident Myeloid and Histiocytic Cells in Health and Disease: Novel Emerging Concepts
2025-09-12

ABSTRACT Although all myeloid cells are considered to derive from hematopoietic stem cells, the cells in each myeloid lineage are heterogeneous populations, and their distribution and functions vary, depending on underlying physiologic and pathologic processes, age, sex, and genetic and epigenetic signatures. In general, myeloid cells can be separated into circulating and tissue‐resident cells. Tissue‐resident myeloid cells can further be divided into cells derived from circulating monocytes, circulating stem cells, or local tissue‐restricted stem or progenitor cells. Depending on underlying diseases and co‐morbidities, the phenotype, function, and distribution of these cells may change substantially. In this article, we discuss new developments in the field and related emerging concepts around tissue‐resident myeloid cells and their role and function in reactive and clonal disorders. Cell types reviewed in depth in this article include monocytes, macrophages, histiocytes, dendritic cells, and tissue mast cells, with a focus on inflammatory disease processes, vascular pathologies, solid tumors, and hematopoietic malignancies. Moreover, the current article provides an update on patient‐related and disease‐related diagnostic and prognostic variables, multi‐parametric prognostic scoring systems, and therapeutic options and algorithms in these neoplasms. Finally, our article provides an overview on the emerging role and impact of precision medicine approaches, translational research, and artificial intelligence in the diagnosis, prognostication, and management of monocytic, histiocytic, and mast cell disorders.
Context Versus Aiming Under Uncertainty When Both Feedforward and Feedback Control Are Engaged
2025-09-12

Theories of human motor learning commonly assume that movement plans are adjusted in response to the sensory feedback received about their success or failure. The degree to which movement errors drive changes in feedforward motor plans is further assumed to scale inversely with sensory uncertainty. However, support for these assumptions comes primarily from experiments that limit feedback corrections during an ongoing movement. In contrast, we have recently shown that when this restriction is relaxed, a different pattern of behavior emerges. Participants gradually adjust their reaching movements in response to a perturbation from trial-to-trial, following a consistent and incremental envelope of error reduction. Riding on top of this gradual learning envelope, participants also exhibit large and abrupt changes in their initial reach direction that are strongly correlated with the uncertainty level of the sensory feedback experienced on the previous trial, but are insensitive to the size and direction of the movement error made on that trial. A class of models in which sensory uncertainty influences an aiming process best accounted for this pattern. Here, we examine the possibility that uncertainty acts as a contextual cue to shunt motor processes to one of many context-specific internal models.
A multi-group path analysis of medication documentation quality using cross-sectional survey data: Impact of leadership, job satisfaction, patient-related burnout, and patient safety culture
2025-09-12

Medication-related adverse events are a major problem for patient safety and quality of care. This study explored the effects of leadership, job satisfaction, patient-related burnout and patient safety culture, measured through surveys of frontline workers, on documentation quality. Perceptions of physicians and nurses were surveyed using established instruments including the Transformational Leadership Inventory, the Copenhagen Psychosocial Questionnaire, the Copenhagen Burnout Inventory, and the Hospital Survey on Patient Safety Culture. Documentation quality was evaluated using retrospective review of patient records with the MediDoq instrument. Data from 24 departments, covering 282 physicians, 417 nurses, and 802 patient records, were analysed through a multi-group (physicians and nurses) path analysis to evaluate the theoretical model. The theoretical model revealed satisfactory fit, explaining about 76–80% of the variance in Documentation Quality for physicians and nurses. Perceived Patient Safety had a significant effect on Documentation Quality only for nurses. The analyses revealed differences between professional groups. Based on these results, (i) medication documentation quality may be affected by various organizational factors; (ii) perceived Patient Safety reported by the nurses may mediate some of these effects; (iii) the effects of various organizational factors on documentation quality may vary significantly across professional groups.
A deep learning ECG model for localization of occlusion myocardial infarction
2025-09-12

Rapid identification and localization of an acute coronary occlusion are vital to prevent myocardial damage, yet reliance on ST-segment ECG criteria misses many acute occlusion myocardial infarctions (OMI) and triggers unnecessary acute angiographies. Here, we trained and validated a deep learning model using 540,372 emergency ECGs paired with definitive catheterization outcomes. The model achieved a C-statistic of &gt;0.95 for OMI and &gt;0.87 for non-OMI infarctions and could localize culprit lesions in the left main/LAD, LCX, and RCA coronary branches, which can guide the angiographer. Performance was similar across age, sex, and ECG hardware subgroups. Obviating dependence on ST-elevations and troponins, this model for identification and localization of OMI has the potential to shorten time to reperfusion of an acute coronary occlusion and save resources. Because human oversight of OMI detection on the ECG is limited, randomized clinical trials with patient-relevant outcomes are warranted.
Resolving the estrogen paradox in hereditary retinal degeneration: Esr1 activation suppresses Tnf-α signaling as a photoreceptor self-protection mechanism
2025-09-12

Abstract Retinitis pigmentosa (RP) is an inherited retinal degenerative disorder characterized by progressive photoreceptor loss and irreversible blindness. Increasing evidence implicates neuroinflammation as a contributor to photoreceptor degeneration extending beyond the initial genetic insult. Although estrogen has been reported to exert anti-inflammatory effects in the central nervous system, its role in RP remains controversial, with some studies suggesting a paradoxical exacerbation of retinal pathology. To address this discrepancy, we identify estrogen receptor alpha (Esr1) as a central immunoregulatory hub in RP. Transcriptomic analyses of rd1 and rd10 revealed upregulation of estrogen-responsive and inflammatory pathways, with Esr1 expression markedly elevated during degeneration. TUNEL assays demonstrated that systemic estradiol (E2) exerted divergent effects, protective in rd1 yet deleterious in rd10, whereas selective pharmacological activation of Esr1 with propyl pyrazole triol (PPT) consistently reduced photoreceptor death, preserved dark-adapted ERG responses, and downregulated inflammatory mediators including Tnf-α, Cx3cl1/Cx3cr1, Cd68, and Iba1. Mechanistically, Esr1 activation repressed microglial Tnf transcription and disrupted a self-sustaining Cx3cl1/Cx3cr1–Tnf-α signaling loop driving microglial recruitment, activation and neurotoxicity in the outer nuclear layer (ONL). Targeted interventions confirmed tumor necrosis factor receptor 1 (Tnfr1) as the principal mediator of Tnf-induced photoreceptor death: selective inhibition with R7050 conferred superior protection compared with broad-spectrum Tnf-α inhibitors (etanercept, infliximab). Cx3cr1 blockade likewise suppressed microglial activation and improved visual outcomes. Collectively, our findings establish Esr1 activation as not merely an external intervention but the amplification of an intrinsic self-protective program, positioning Esr1, Tnfr1, and Cx3cr1 as actionable therapeutic targets to suppress neuroinflammation and preserve vision in RP and related retinal disorders.
Addressing boundary conditions of cognitive and motivational effects of gamified learning
2025-09-12

There is a growing interest in developing gamified learning solutions to address educational challenges. However, learning is highly influenced by the conditions in which it takes place (e.g., does gamified learning in a laboratory setting replicate the outcomes of gamified learning online at home?). Hence, it is crucial to understand the boundary conditions of different learning contexts to effectively implement gamified interventions that provide optimal learner support. This work contributes to such an understanding by assessing how general contextual aspects of three studies on gamified learning influence cognitive learning and motivational outcomes. Therefore, we re-examined the results of two earlier published online studies (Study 1: n=285; Study 2: n=61) and compared the results to a recently conducted laboratory study (Study 3: n=121), all of which employed the same associative learning task. Comparing results through a Bayesian lens, we find that motivational outcomes induced by gamification differ substantially between contexts. In contrast, cognitive learning outcomes seem comparatively robust across different contextual factors, with some indication of subtle influences in agreement with cognitive learning theories. Implications are discussed for future empirical research on learning, highlighting how a better understanding of boundary conditions of gamified learning interventions could open perspectives for context-aware educational interventions.
Morpho-phonology is not independent of semantics
2025-09-12

Abstract Morpho-phonological alternations in inflectional paradigms are commonly analyzed as purely formal phenomena, in which the mapping of phonological structure and morpho-syntactic categories is organized without recourse to semantic properties of the words involved. The present paper explores the role of semantics using the Discriminative Lexicon approach ( Baayen, et al. 2019 ). The test case explored in this paper is German nominal number, a system involving complex morpho-phonological variation (e.g. Köpcke et al., 2021 ; Heitmeier et al., 2021 ; Plag et al., 2024 ; McCurdy, 2024 ). Using word2vec vectors as semantic representations, and triphones as form representations, we created two-layer linear discriminative learning (LDL) networks that map form representations directly onto semantic representations (modeling comprehension), and semantic representations onto form representations (modeling production). The LDL mappings successfully predict the forms and the meanings of the singular and plural nouns taken from a pertinent study ( Domahs et al., 2017 ). A number of semantic and phonological measures derived from the LDL network also very successfully distinguished between singular and plural forms. Our results demonstrate that semantics, in addition to formal and grammatical properties, may play a decisive role in the representation and processing of German nominal number. The system of German nominal number can be understood as emerging from the distributional properties of words on the one hand, and basic principles of discriminative human learning on the other.
Bioprinting of Hydrogel Tumor Slices as a 3D Model for Mantle Cell Lymphoma
2025-09-12

Mantle cell lymphoma (MCL) is a rare, aggressive B-cell neoplasm that frequently relapses and only shows a limited response to conventional chemotherapy. A major challenge in MCL research is culturing primary MCL cells ex vivo, as cells tend to undergo spontaneous apoptosis when cultured in 2D suspension culture. Although 3D models are known to better recapitulate the in vivo situation of solid tumors, their application is still poorly explored in lymphomas. Developing 3D models that replicate the in vivo conditions of MCL within the lymph node could enhance their survival, facilitate the study of the MCL-tumor microenvironment crosstalk, and mimic the in vivo drug response. Here, a 3D printed model of MCL in the form of hydrogel tumor slices was established, along with an optimized culture method. A standardized process was developed using MCL cell lines or primary MCL cells, in which the cells are immersed in a hydrogel containing alginate, type I collagen, and basement membrane matrix by bioprinting into a gelatin support bath. The resulting MCL hydrogel tumor slices are cultured on a filter support to maintain their stability throughout the culture period. Drug treatments can be applied to the system. The response of single cells inside the hydrogel tumor slice can be tracked by four-color live 3D fluorescence imaging. Primary MCL cells demonstrated a stable viability when cultured in the hydrogel tumor slices. This protocol provides a detailed description of the generation, culture, and analysis of MCL cells in hydrogel tumor slices. By closely mimicking the tumor microenvironment and utilizing an air-liquid interface culture, the presented model enhances physiological relevance compared to the traditional 2D culture. It offers significant potential for advancing both biological and therapeutic studies of MCL.
Impressionable years: How life course transitions shape gender ideologies across adolescence and young adulthood
2025-09-15

This study examines how life course transitions unique to adolescence and young adulthood affect gender ideologies of men and women. After childhood, young people are exposed to new contexts that shape their beliefs in different ways than parents. By integrating a life course perspective with the conceptualisation of gender as a social structure and interest- and exposure-based explanations, this study contributes to a more nuanced understanding of change mechanisms. It extends the literature by examining the role of age-specific transitions: into vocational training, university, employment, romantic relationships, and cohabitation. Using representative data from the German Family Panel pairfam, I conducted fixed-effects regression analyses with gender interaction terms (n = 2888 individuals; ages 15-27). To account for the multidimensionality of gender ideologies, I used separate attitude items. Results show that attending university is associated with increased support for gender equality in the public and private sphere, particularly for young men. Transitions into vocational training are related to an increase in public sphere egalitarianism, while transitions into employment mostly did not have an additional effect. When they enter heterosexual relationships, results are gender-specific: Women become more traditional regarding maternal employment, while men increase their support for equal housework sharing and both women's and men's caretaking roles. With cohabitation, women decrease their support for equal housework sharing. Overall, the findings suggest that young people's gender ideologies can be subject to persistent change beyond early formative years and that life course transitions may be crucial in shaping them.
Age- and gender-specific magnetic resonance imaging findings in paediatric ankle trauma with negative radiographs
2025-09-15

Abstract Background The objective of this study is to investigate the age- and gender-specific frequencies of different pathologies after ankle trauma with negative radiographs in children and adolescents. Methods We retrospectively analysed the MRIs of 100 patients ≤ 18 years within 30 days after acute primary ankle trauma with negative radiographs. Patients were classified into three age groups: 0–11 years, 12–15 years, and 16–18 years. Results MRI detected pathological findings in 96 cases (96%): Lateral collateral ligament (n = 62), deltoid ligament injury (n = 10), syndesmosis injury (n = 12), Salter-Harris Type 1 fracture of the distal fibula (n = 2), bone bruise and marrow oedema (n = 32), soft tissue oedema and hematoma (n = 13), joint effusion and hematoma (n = 8), fracture (n = 12), osteochondral lesion of the talus (n = 2). Among LCL injuries, 21 cases (33.9%) affected the ATFL alone, 34 cases (54.8%) involved both the ATFL and CFL, 2 cases (3.2%) affected only the CFL, and 5 cases (8.1%) involved all three ligaments (ATFL, CFL and PTFL).The percentages of lateral collateral ligament and syndesmotic injuries both increased significantly with age (0–11 years: 43%, 12–15 years: 57%, and 16–18 years: 78%, p = 0.019; 0–11 years: 5%, 12–15 years: 5%, and 16–18 years: 24%, p = 0.015). There were no significant differences between the genders for any of the injuries (p≥ 0.539). In 24% of cases, injuries detected by MRI resulted in a modification of the clinical management. Conclusions There is a high rate of injuries missed by radiographs but detected by MRI, with LCL injuries being the most common. The older the patient, the more likely it is that a syndesmotic injury will be detected with an MRI.
Exploring individual differences in volitional personality state and trait change: The role of motivation and engagement during a 12-week intervention
2025-09-15

Recent studies suggest that personality traits can change through interventions, but little is known about what drives individual differences in intervention gains. Based on personality development and intervention frameworks, we examined whether achieved personality state changes explain differences in trait change and whether these could be explained by participants’ motivation and intervention engagement. The study was based on a 12-week personality intervention with a total of 956 participants, daily and weekly state measures, and trait self- and observer-reports. Participants who showed stronger state deviations from the initial trait level changed more in their traits in the corresponding direction. Both state and trait changes were stronger if participants were more committed to their change goal, completed more implementation intentions, and enjoyed their implementations more (i.e., reinforcement). In contrast, the strength of the desire to change, expected attainability, and beliefs in the changeability of personality had no consistent effects—but individual differences were limited as most participants scored highly on these motivational aspects. The control group exhibited no mean-level changes or effects of any of these covariates. Taken together, these findings support key components of volitional change theories and can help guide future personalized intervention efforts.
A quadratically enriched correspondence theorem
2025-09-15

We quadratically enrich Mikhalkin’s correspondence theorem. That is, we prove a correspondence between algebraic curves on a toric surface counted with Levine’s quadratic enrichment of the Welschinger sign, and tropical curves counted with a quadratic enrichment of Mikhalkin’s multiplicity for tropical curves.
New biosensors and transgenic mice for multiplex cGMP imaging
2025-09-15

Background and Purpose Cyclic guanosine monophosphate (cGMP) is a versatile second messenger that is important for human (patho‐)physiology and pharmacotherapy. Live‐cell imaging of cGMP with biosensors allows to elucidate its spatiotemporal dynamics in real time under close‐to‐native conditions. However, to monitor two separate cGMP pools or cGMP/cAMP crosstalk in the same cell, the respective biosensors must be spectrally compatible. Experimental Approach We describe two new Förster/fluorescence resonance energy transfer (FRET)‐based cGMP indicators, membrane‐targeted mcGi500 and red‐shifted cytosolic red‐cGi500, as well as two transgenic mouse lines for global and cell type‐specific expression of mcGi500. The performance of the new biosensors was characterised in permeabilised and intact primary vascular smooth muscle cells and compared side‐by‐side with existing cGMP sensors. Key Results Both mcGi500 and red‐cGi500 had a high selectivity for cGMP over cAMP and detected cGMP with about 3 times higher sensitivity than the current ‘gold standard’, cytosolic cGi500. Red‐cGi500 allowed robust detection of cGMP in intact vascular smooth muscle cells. By combining red‐cGi500 with the ‘green’ cAMP sensor Epac1‐camps, cGMP and cAMP could be co‐imaged in the same cells. Conclusions and Implications Together, our data suggest that red‐cGi500 and mcGi500 as well as the mcGi500 transgenic mouse lines are useful tools for advanced cGMP imaging, including multiplex imaging of potential cGMP compartments and crosstalk between cGMP and other signalling molecules.
Effects of segmentation errors on downstream-analysis in highly-multiplexed tissue imaging
2025-09-15

Highly multiplexed single-cell imaging technologies have revolutionized our ability to capture spatial protein expression at the single-cell level, thereby enabling a deeper understanding of tissue organization and function. However, these advancements rely on accurate cell segmentation, which defines cell boundaries to generate expression profiles. Despite its importance, there is a gap in quantifying how segmentation inaccuracies propagate through analytical pipelines, particularly affecting cell clustering and phenotyping. We introduce a framework that uses affine transformations to simulate realistic segmentation errors. Our approach mimics the variations induced by segmentation algorithms, allowing us to evaluate the robustness of downstream analyses under controlled perturbation conditions. We show that even moderate segmentation errors can significantly distort estimated protein profiles and disrupt cellular neighborhood relationships in feature space. Effects are most pronounced in clustering analyses, where both unsupervised k-Means and graph-based Leiden algorithms exhibit reduced consistency with increasing perturbation — especially with smaller neighborhood sizes. Similarly, cell phenotyping via Gaussian Mixture Models is adversely impacted, with higher levels of segmentation error leading to notable misclassifications between closely related cell types. These results highlight the importance of ensuring high-quality segmentation and careful data processing strategies to mitigate spurious results for downstream analysis tasks. Considering segmentation inaccuracies, possibly in a probabilistic modeling framework, will improve the reliability and reproducibility of findings in multiplexed tissue imaging studies.