julilili42/papers huggingface dataset:
Effects of Extracorporeal Shockwave Therapy on Functional Recovery and Circulating miR-375 and miR-382-5p after Subacute and Chronic Spinal Cord Contusion Injury in Rats
2022-07-07

Extracorporeal shockwave therapy (ESWT) can stimulate processes to promote regeneration, including cell proliferation and modulation of inflammation. Specific miRNA expression panels have been established to define correlations with regulatory targets within these pathways. This study aims to investigate the influence of low-energy ESWT—applied within the subacute and chronic phase of SCI (spinal cord injury) on recovery in a rat spinal cord contusion model. Outcomes were evaluated by gait analysis, μCT and histological analysis of spinal cords. A panel of serum-derived miRNAs after SCI and after ESWT was investigated to identify injury-, regeneration- and treatment-associated expression patterns. Rats receiving ESWT showed significant improvement in motor function in both a subacute and a chronic experimental setting. This effect was not reflected in changes in morphology, μCT-parameters or histological markers after ESWT. Expression analysis of various miRNAs, however, revealed changes after SCI and ESWT, with increased miR-375, indicating a neuroprotective effect, and decreased miR-382-5p potentially improving neuroplasticity via its regulatory involvement with BDNF. We were able to demonstrate a functional improvement of ESWT-treated animals after SCI in a subacute and chronic setting. Furthermore, the identification of miR-375 and miR-382-5p could potentially provide new targets for therapeutic intervention in future studies.
Visual explanations for the detection of diabetic retinopathy from retinal fundus images
2022-07-07

Abstract In medical image classification tasks like the detection of diabetic retinopathy from retinal fundus images, it is highly desirable to get visual explanations for the decisions of black-box deep neural networks (DNNs). However, gradient-based saliency methods often fail to highlight the diseased image regions reliably. On the other hand, adversarially robust models have more interpretable gradients than plain models but suffer typically from a significant drop in accuracy, which is unacceptable for clinical practice. Here, we show that one can get the best of both worlds by ensembling a plain and an adversarially robust model: maintaining high accuracy but having improved visual explanations. Also, our ensemble produces meaningful visual counterfactuals which are complementary to existing saliency-based techniques. Code is available under https://github.com/valentyn1boreiko/Fundus_VCEs .
The 2021 federal German election: A gender and intersectional analysis
2022-07-07

On 26 September 2021, Germans elected the 20th Bundestag. This election was special in many ways. The article analyses the electoral campaign, voting behaviour, turnout, and the formation of a new coalition government by using a gender and intersectional lens. Against the conceptual background of descriptive, substantive, and symbolic representation, we outline the implications of the election for gender and intersectional politics in the new German Bundestag and the government. In descriptive and symbolic terms, we find higher numbers of women (and of minorities) in the Bundestag and its leadership as well as in government; in substantive terms, we observe the presence of ‘critical actors’ and the commitment to progressive politics in the new ‘Ampel’ coalition. Hence, we see at least a chance for change in several key policy areas and social progress in the next 4 years.
Dynamics of Melanoma-Associated Epitope-Specific CD8+ T Cells in the Blood Correlate With Clinical Outcome Under PD-1 Blockade
2022-07-07

Immune checkpoint blockade (ICB) is standard-of-care for patients with metastatic melanoma. It may re-invigorate T cells recognizing tumors, and several tumor antigens have been identified as potential targets. However, little is known about the dynamics of tumor antigen-specific T cells in the circulation, which might provide valuable information on ICB responses in a minimally invasive manner. Here, we investigated individual signatures composed of up to 167 different melanoma-associated epitope (MAE)-specific CD8+ T cells in the blood of stage IV melanoma patients before and during anti-PD-1 treatment, using a peptide-loaded multimer-based high-throughput approach. Additionally, checkpoint receptor expression patterns on T cell subsets and frequencies of myeloid-derived suppressor cells and regulatory T cells were quantified by flow cytometry. Regression analysis using the MAE-specific CD8+ T cell populations was applied to identify those that correlated with overall survival (OS). The abundance of MAE-specific CD8+ T cell populations, as well as their dynamics under therapy, varied between patients. Those with a dominant increase of these T cell populations during PD-1 ICB had a longer OS and progression-free survival than those with decreasing or balanced signatures. Patients with a dominantly increased MAE-specific CD8+ T cell signature also exhibited an increase in TIM-3+ and LAG-3+ T cells. From these results, we created a model predicting improved/reduced OS by combining data on dynamics of the three most informative MAE-specific CD8+ T cell populations. Our results provide insights into the dynamics of circulating MAE-specific CD8+ T cell populations during ICB, and should contribute to a better understanding of biomarkers of response and anti-cancer mechanisms.
Ultra-low dose CT for scaphoid fracture detection—a simulational approach to quantify the capability of radiation exposure reduction without diagnostic limitation
2022-07-07

The results suggest that ULD-CT at 10% dose compared to high quality CT might offer sufficient image quality to precisely detect and classify scaphoid fractures, if moderate experience of the radiologist is granted.
The Public Sphere of Democracy and the Wisdom Tradition
2022-07-07

Abstract The essay addresses contemporary trends in modern democracy, especially focusing on the transformation of the public sphere. It seeks to answer the following question: how can we strengthen ideologically diverse spaces of public discourse today in light of the social trends toward homophily and echo chambers? Specifically, it addresses the way in which modern political discourse has been transformed by social media and broader social and economic trends. Furthermore, it raises questions about the future challenges of discourse ethics and ideal conceptions of overlapping consensus in our contemporary context of pluralism. The role of the media in this broad public sphere is also addressed. An ideal-type conception of the wisdom tradition, one which can strengthen the channels of communication, is offered as a response to these trends. It is a pattern of thought capable of embracing the ambiguity.
Angling for X-ray pulsar geometry with polarimetry
2022-07-07

<title>Abstract</title> Using observations of X-ray pulsar Her X-1 by the Imaging X-ray Polarimetry Explorer, we report on a highly significant detection of the polarization signal from an accreting neutron star. The observed degree of the linear polarization of ∼ 10% is found to be far below theoretical expectations for this object, and stays low throughout the spin cycle of the pulsar. Both the polarization degree and the angle exhibit variability with pulse phase, which allowed us to measure the pulsar spin position angle and magnetic obliquity of the neutron star, which is an essential step towards detailed modeling of the intrinsic emission of X-ray pulsars. Combining our results with the optical polarimetric data, we find that the spin axis of the neutron star and the angular momentum of the binary orbit are misaligned by at least ∼20 deg, which is a strong argument in support of the models explaining stability of the observed super-orbital variability with the precession of the neutron star.
The Dutch Republic and the Birth of Modern Advertising, by Arthur der Weduwen and Andrew Pettegree
2022-07-07

It is a promising and alluring topic: in their study, Andrew Pettegree and Arthur der Weduwen explore the ‘birth of advertising’ in the seventeenth-century Dutch Republic. They introduce their readers to a fascinating world of information, people and things—a world that proves to be a microcosm of contemporary Dutch society. The authors explain that in some regards, the book itself has grown out of the allure of the topic and material: its first draft was not written with a fully-fledged monograph in mind but was intended to serve as an introduction to the edition of advertisements that the authors have published in the same series (Brill’s Library of the Written Word). The volume at hand sufficiently demonstrates that the topic deserves a book-length treatment and indeed calls for further research, not least in comparative perspective. The study is based, at its core, on the analysis of advertisements published in Dutch newspapers between 1621 and c.1700, with some chapters moving on well into the eighteenth century. While the few previous studies of early modern advertising are often framed within to the paradigm of the ‘consumer revolution’, Pettegree and Weduwen discuss their subject more specifically within the context of the development of newspapers and the history of the printing world. They not only point out the intimate connections between the book trade and the onset of newspaper advertising but also (even if implicitly) help to challenge the well-worn modernising projections which the ‘consumer revolution’ narrative entails. Advertisements are not only directed to customers and buyers but also address—and probably more often than not in the early days—potential competitors, serving as announcements of business ventures and privileges. Furthermore, unlike the dominant image today, the buyers and customers addressed were not consumers and private individuals but, rather, other merchants or manufacturers. Indeed, retail trade only made a relatively late appearance in the printed world of advertisements (with some exceptions with regard to services and the book trade)—and appeared later in Dutch than in English newspapers.
Why Does the Trait-State Relation in Vocational Interests Differ from That in Personality? Exploring Interest Variability in Daily Life
2022-07-07

Interests have been studied from a trait- and state-perspective. Recent studies propose to integrate these two traditions. This preregistered experience-sampling study (N = 217, Nobservations = 5,631) aimed to further the development of trait-state interest models. We sought to replicate and explain that vocational interest states vary within persons and exhibit a pattern of varying mainly below respective trait levels. We tested competing assumptions about the conceptualization of interest states. Across two operationalizations using items that were (not) tailored to participants’ daily lives, states varied mainly below trait levels. This suggests that this pattern is no measurement artifact, but that interest traits generally constrain the experience of states in daily life. Overall, the results refine the conceptualization of trait-state interests, suggesting new research directions.
Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer’s disease: associations with β-amyloid-PET, neurodegeneration and cognition
2022-07-07

Abstract Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer’s disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility. We evaluated plasma, serum, and CSF GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage of disease. Plasma GFAP elevations appear a decade before expected symptom onset, after β-amyloid accumulation and prior to neurodegeneration and cognitive decline. Plasma GFAP distinguished β-amyloid-positive from β-amyloid-negative ADAD participants and showed a stronger relationship with β-amyloid load in asymptomatic than symptomatic ADAD. Higher plasma GFAP was associated with the degree and rate of neurodegeneration and cognitive impairment. Serum GFAP showed similar relationships, but these were less pronounced for CSF GFAP. Our findings support a role for plasma GFAP as a clinical biomarker for β-amyloid-associated cognitive deterioration in AD.
Modeling enhanced firn densification due to strain softening
2022-07-08

Abstract. In the accumulation zone of glaciers and ice sheets snow is transformed into glacial ice by firn densification. Classically, this process is assumed to solely depend on temperature and overburden pressure, which is controlled by the accumulation rate. However, exceptionally thin firn layers have been observed in the high-strain shear margins of ice streams. Previously, it has been proposed that this firn thinning can be explained by an enhancement of firn densification due to the effect of strain softening inherent to power-law creep. This hypothesis has not been validated, and the greater firn densities in the presence of horizontal strain rates have not yet been reproduced by models. Here, we develop a model that corrects the firn densification rate predicted by classical, climate-forced models for the effect of strain softening. With the model it is confirmed that strain softening dominates the firn densification process when high strain rates are present. Firn densities along a cross section of the Northeast Greenland Ice Stream (NEGIS) are reproduced with good agreement, validating the accuracy of the developed model. Finally, it is shown that strain softening has significant implications for ice core dating and that it considerably affects the firn properties over wide areas of the polar ice sheet, even at low strain rates. Therefore, we suggest that, besides temperature and accumulation rate, horizontal strain rates should generally be considered as a forcing parameter in firn densification modeling.
Diet triggers specific responses of hypothalamic astrocytes in time and region dependent manner
2022-07-08

Abstract Hypothalamic astrocytes are particularly affected by energy‐dense food consumption. How the anatomical location of these glial cells and their spatial molecular distribution in the arcuate nucleus of the hypothalamus (ARC) determine the cellular response to a high caloric diet remains unclear. In this study, we investigated their distinctive molecular responses following exposure to a high‐fat high‐sugar (HFHS) diet, specifically in the ARC. Using RNA sequencing and proteomics, we showed that astrocytes have a distinct transcriptomic and proteomic profile dependent on their anatomical location, with a major proteomic reprogramming in hypothalamic astrocytes. By ARC single‐cell sequencing, we observed that a HFHS diet dictates time‐ and cell‐ specific transcriptomic responses, revealing that astrocytes have the most distinct regulatory pattern compared to other cell types. Lastly, we topographically and molecularly characterized astrocytes expressing glial fibrillary acidic protein and/or aldehyde dehydrogenase 1 family member L1 in the ARC, of which the abundance was significantly increased, as well as the alteration in their spatial and molecular profiles, with a HFHS diet. Together, our results provide a detailed multi‐omics view on the spatial and temporal changes of astrocytes particularly in the ARC during different time points of adaptation to a high calorie diet.
Differential Temporal Dynamics of Axial and Appendicular Ataxia in SCA3
2022-07-08

Abstract Background Disease severity in spinocerebellar ataxia type 3 (SCA3) is commonly defined by the Scale for the Assessment and Rating of Ataxia (SARA) sum score, but little is known about the contributions and progression patterns of individual items. Objectives To investigate the temporal dynamics of SARA item scores in SCA3 patients and evaluate if clinical and demographic factors are differentially associated with evolution of axial and appendicular ataxia. Methods In a prospective, multinational cohort study involving 11 European and 2 US sites, SARA scores were determined longitudinally in 223 SCA3 patients with a follow‐up assessment after 1 year. Results An increase in SARA score from 10 to 20 points was mainly driven by axial and speech items, with a markedly smaller contribution of appendicular items. Finger chase and nose‐finger test scores not only showed the lowest variability at baseline, but also the least deterioration at follow‐up. Compared with the full set of SARA items, omission of both tests would result in lower sample size requirements for therapeutic trials. Sex was associated with change in SARA sum score and appendicular, but not axial, subscore, with a significantly faster progression in men. Despite considerable interindividual variability, the average annual progression rate of SARA score was approximately three times higher in subjects with a disease duration over 10 years than in those within 10 years from onset. Conclusion Our findings provide evidence for a difference in temporal dynamics between axial and appendicular ataxia in SCA3 patients, which will help inform the design of clinical trials and development of new (etiology‐specific) outcome measures. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Ophthalmic and Genetic Features of Bardet Biedl Syndrome in a German Cohort
2022-07-08

The aim of this study was to characterize the ophthalmic and genetic features of Bardet Biedl (BBS) syndrome in a cohort of patients from a German specialized ophthalmic care center. Sixty-one patients, aged 5–56 years, underwent a detailed ophthalmic examination including visual acuity and color vision testing, electroretinography (ERG), visually evoked potential recording (VEP), fundus examination, and spectral domain optical coherence tomography (SD-OCT). Adaptive optics flood illumination ophthalmoscopy was performed in five patients. All patients had received diagnostic genetic testing and were selected upon the presence of apparent biallelic variants in known BBS-associated genes. All patients had retinal dystrophy with morphologic changes of the retina. Visual acuity decreased from ~0.2 (decimal) at age 5 to blindness 0 at 50 years. Visual field examination could be performed in only half of the patients and showed a concentric constriction with remaining islands of function in the periphery. ERG recordings were mostly extinguished whereas VEP recordings were reduced in about half of the patients. The cohort of patients showed 51 different likely biallelic mutations—of which 11 are novel—in 12 different BBS-associated genes. The most common associated genes were BBS10 (32.8%) and BBS1 (24.6%), and by far the most commonly observed variants were BBS10 c.271dup;p.C91Lfs*5 (21 alleles) and BBS1 c.1169T&gt;G;p.M390R (18 alleles). The phenotype associated with the different BBS-associated genes and genotypes in our cohort is heterogeneous, with diverse features without genotype–phenotype correlation. The results confirm and expand our knowledge of this rare disease.
eHealth Literacy in German Skin Cancer Patients
2022-07-08

The global incidence of skin cancer has steadily increased in recent years, and malignant melanoma still has one of the fastest-growing incidence rates among all malignant tumors in the western world. Thus, newly diagnosed patients have an increased need for health information concerning their disease. Using a standardized questionnaire, our study aims to investigate our patients’ primary sources of health-related information as well as their self-proclaimed eHealth literacy. We received 714 questionnaires. Regardless of age, the primary source of information was the treating dermato-oncologist, followed by the treating general practitioner and the Internet. However, with increasing age, the usage of the Internet decreased. Hence, younger participants were better equipped to find health-related information while using the Internet. Additionally, comprehending health-related information and gaining medical knowledge was significantly increased in better-educated participants. Overall, our study shows that with increased use of eHealth services, accessing web-based information increased, correlating with a better eHealth literacy of our patients. eHealth technologies are increasingly becoming more prevalent as a primary source of information in our modern health care system. Thus, it is crucial to educate cancer patients in eHealth literacy to make autonomous, informed decisions and gain more confidence in dealing with their disease.
Controversial Role of the Immune Checkpoint OX40L Expression on Platelets in Breast Cancer Progression
2022-07-08

In conventional T cells, OX40 has been identified as a major costimulating receptor augmenting survival and clonal expansion of effector and memory T cell populations. In regulatory T cells, (Treg) OX40 signaling suppresses cellular activity and differentiation. However, clinical trials investigating OX40 agonists to enhance anti-tumor immunity, showed only limited success so far. Here we show that platelets from breast cancer patients express relevant levels of OX40L and platelet OX40L (pOX40L) inversely correlates with platelet-expressed immune checkpoint molecules GITRL (pGITRL) and TACI (pTACI). While high expression of pOX40L correlates with T and NK cell activation, elevated pOX40L levels identify patients with higher tumor grades, the occurrence of metastases, and shorter recurrence-free survival (RFS). Of note, OX40 mRNA levels in breast cancer correlate with enhanced expression of anti-apoptotic, immune-suppressive, and tumor-promoting mRNA gene signatures. Our data suggest that OX40L on platelets might play counteracting roles in cancer and anti-tumor immunity. Since pOX40L reflects disease relapse better than the routinely used predictive markers CA15-3, CEA, and LDH, it could serve as a novel biomarker for refractory disease in breast cancer.
Inside and out: Surface thermodynamics from positive to negative curvature
2022-07-08

To explore the curvature dependence of solid–fluid interfacial thermodynamics, we calculate, using Grand Canonical Monte Carlo simulation, the surface free energy for a 2d hard-disk fluid confined in a circular hard container of radius R as a function of the bulk packing fraction η and wall curvature C̄=−1/R. (The curvature is negative because the surface is concave.) Combining this with our previous data [Martin et al., J. Phys. Chem. B 124, 7938–7947 (2020)] for the positive curvature case (a hard-disk fluid at a circular wall, C̄=+1/R), we obtain a complete picture of surface thermodynamics in this system over the full range of positive and negative wall curvatures. Our results show that γ is linear in C̄ with a slope that is the same for both positive and negative wall curvatures, with deviations seen only at high negative curvatures (strong confinement) and high density. This observation indicates that the surface thermodynamics of this system is consistent with the predictions of so-called morphometric thermodynamics at both positive and negative curvatures. In addition, we show that classical density functional theory and a generalized scaled particle theory can be constructed that give excellent agreement with the simulation data over most of the range of curvatures and densities. For extremely high curvatures, where only one or two disks can occupy the container at maximum packing, it is possible to calculate γ exactly. In this limit, the simulations and density functional theory calculations are in remarkable agreement with the exact results.