julilili42/papers huggingface dataset:
S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma – short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality‐of‐care indicators
2020-03-01

Summary Actinic keratoses (AK) are common lesions in light‐skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence‐based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guideline is aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office‐based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AK and cSCC. The guideline is also aimed at affected patients, their relatives, policy makers and insurance funds. In the first part, we will address aspects relating to diagnosis, interventions for AK, care structures and quality‐of‐care indicators.
Combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis: a DeCOG* study in 380 patients
2020-03-01

Background Nivolumab combined with ipilimumab have shown activity in melanoma brain metastasis (MBM). However, in most of the clinical trials investigating immunotherapy in this subgroup, patients with symptomatic MBM and/or prior local brain radiotherapy were excluded. We studied the efficacy of nivolumab plus ipilimumab alone or in combination with local therapies regardless of treatment line in patients with asymptomatic and symptomatic MBM. Methods Patients with MBM treated with nivolumab plus ipilimumab in 23 German Skin Cancer Centers between April 2015 and October 2018 were investigated. Overall survival (OS) was evaluated by Kaplan-Meier estimator and univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic factors associated with OS. Results Three hundred and eighty patients were included in this study and 31% had symptomatic MBM (60/193 with data available) at the time of start nivolumab plus ipilimumab. The median follow-up was 18 months and the 2 years and 3 years OS rates were 41% and 30%, respectively. We identified the following independently significant prognostic factors for OS: elevated serum lactate dehydrogenase and protein S100B levels, number of MBM and Eastern Cooperative Oncology Group performance status. In these patients treated with checkpoint inhibition first-line or later, in the subgroup of patients with BRAFV600-mutated melanoma we found no differences in terms of OS when receiving first-line either BRAF and MEK inhibitors or nivolumab plus ipilimumab (p=0.085). In BRAF wild-type patients treated with nivolumab plus ipilimumab in first-line or later there was also no difference in OS (p=0.996). Local therapy with stereotactic radiosurgery or surgery led to an improvement in OS compared with not receiving local therapy (p=0.009), regardless of the timepoint of the local therapy. Receiving combined immunotherapy for MBM in first-line or at a later time point made no difference in terms of OS in this study population (p=0.119). Conclusion Immunotherapy with nivolumab plus ipilimumab, particularly in combination with stereotactic radiosurgery or surgery improves OS in asymptomatic and symptomatic MBM.
Spotlight on the fetus: how physical activity during pregnancy influences fetal health: a narrative review
2020-03-01

Before and during pregnancy, women often aim to improve their lifestyle so as to provide a healthier environment for their developing child. It remains unresolved, however, as to whether physical activity (PA) during pregnancy poses a possible risk or whether it might even have beneficial effects on the developing child. There is increasing evidence that PA during pregnancy is indeed beneficial to maternal physiological and psychological health and that it is generally not detrimental to the fetal cardiovascular system and neuronal function in the developing child. This also led to international recommendations for PAs during pregnancy. In the current review, we aimed to comprehensively assess the evidence of beneficial and harmful effects of maternal PA, including high-performance sports, on fetal development. The different mental and body-based relaxation techniques presented here are frequently performed during pregnancy. We found a considerable number of studies addressing these issues. In general, neither low key, moderate maternal PA nor relaxation techniques were observed to have a harmful effect on the developing child. However, we identified some forms of PA which could have at least a transient unfavourable effect. Notably, the literature currently available does not provide enough evidence to enable us to make a general conclusive statement on this subject. This is due to the lack of longitudinal studies on the metabolic and cognitive effects of regular PA during pregnancy and the wide diversity of methods used. In particular, the kind of PA investigated in each study differed from study to study.
A Novel Self-Supervised Re-labeling Approach for Training with Noisy Labels
2020-03-01

The major driving force behind the immense success of deep learning models is the availability of large datasets along with their clean labels. This is very difficult to obtain and thus has motivated research on training deep neural networks in the presence of label noise. In this work, we build upon the seminal work in this area, Co-teaching and propose a simple, yet efficient approach termed mCT-S2R (modified co-teaching with self-supervision and relabeling) for this task. Firstly, to deal with significant amount of noise in the labels, we propose to use self-supervision to generate robust features without using any labels. Furthermore, using a parallel network architecture, an estimate of the clean labeled portion of the data is obtained. Finally, using this data, a portion of the estimated noisy labeled portion is re-labeled, before resuming the network training with the augmented data. Extensive experiments on three standard datasets show the effectiveness of the proposed framework.
Update Breast Cancer 2020 Part 1 – Early Breast Cancer: Consolidation of Knowledge About Known Therapies
2020-03-01

Abstract This review is intended to present the latest developments in the prevention and treatment of early breast cancer. The risk of breast cancer can be increasingly better characterised with large epidemiological studies on genetic and non-genetic risk factors. Through new analyses, the evidence for high-penetrance genes as well as for low-penetrance genes was able to be improved. New data on denosumab and atezolizumab are available in the neoadjuvant situation as is a pooled appraisal of numerous studies on capecitabine in the curative situation. There is also an update to the overall survival data of pertuzumab in the adjuvant situation with a longer follow-up observation period. Finally, digital medicine is steadily finding its way into science. A recently conducted study on automated breast cancer detection using artificial intelligence establishes the basis for a future review in clinical studies.
Dead Cells Induce Innate Anergy via Mertk after Acute Viral Infection
2020-03-01

Summary: Infections can result in a temporarily restricted unresponsiveness of the innate immune response, thereby limiting pathogen control. Mechanisms of such unresponsiveness are well studied in lipopolysaccharide tolerance; however, whether mechanisms of tolerance limit innate immunity during virus infection remains unknown. Here, we find that infection with the highly cytopathic vesicular stomatitis virus (VSV) leads to innate anergy for several days. Innate anergy is associated with induction of apoptotic cells, which activates the Tyro3, Axl, and Mertk (TAM) receptor Mertk and induces high levels of interleukin-10 (IL-10) and transforming growth factor β (TGF-β). Lack of Mertk in Mertk−/− mice prevents induction of IL-10 and TGF-β, resulting in abrogation of innate anergy. Innate anergy is associated with enhanced VSV replication and poor survival after infection. Mechanistically, Mertk signaling upregulates suppressor of cytokine signaling 1 (SOCS1) and SOCS3. Dexamethasone treatment upregulates Mertk and enhances innate anergy in a Mertk-dependent manner. In conclusion, we identify Mertk as one major regulator of innate tolerance during infection with VSV. : Adomati et al. show that the cytopathic virus VSV leads to innate immune cell anergy. Innate anergy is associated with apoptotic cells through activation of the TAM receptor Mertk and induction of the cytokines IL-10 and TGF-β.
Attention Flow: End-to-End Joint Attention Estimation
2020-03-01

This paper addresses the problem of understanding joint attention in\\nthird-person social scene videos. Joint attention is the shared gaze behaviour\\nof two or more individuals on an object or an area of interest and has a wide\\nrange of applications such as human-computer interaction, educational\\nassessment, treatment of patients with attention disorders, and many more. Our\\nmethod, Attention Flow, learns joint attention in an end-to-end fashion by\\nusing saliency-augmented attention maps and two novel convolutional attention\\nmechanisms that determine to select relevant features and improve joint\\nattention localization. We compare the effect of saliency maps and attention\\nmechanisms and report quantitative and qualitative results on the detection and\\nlocalization of joint attention in the VideoCoAtt dataset, which contains\\ncomplex social scenes.\\n
<p>Novel Resolution Mediators of Severe Systemic Inflammation</p>
2020-03-01

Nonresolving inflammation, a hallmark of underlying severe inflammatory processes such as sepsis, acute respiratory distress syndrome and multiple organ failure is a major cause of admission to the intensive care unit and high mortality rates. Many survivors develop new functional limitations and health problems, and in cases of sepsis, approximately 40% of patients are rehospitalized within three months. Over the last few decades, better treatment approaches have been adopted. Nevertheless, the lack of knowledge underlying the complex pathophysiology of the inflammatory response organized by numerous mediators and the induction of complex networks impede curative therapy. Thus, increasing evidence indicates that resolution of an acute inflammatory response, considered an active process, is the ideal outcome that leads to tissue restoration and organ function. Many mediators have been identified as immunoresolvents, but only a few have been shown to contribute to both the initial and resolution phases of severe systemic inflammation, and these agents might finally substantially impact the therapeutic approach to severe inflammatory processes. In this review, we depict different resolution mediators/immunoresolvents contributing to resolution programmes specifically related to life-threatening severe inflammatory processes.
iTAG-RNA Isolates Cell-Specific Transcriptional Responses to Environmental Stimuli and Identifies an RNA-Based Endocrine Axis
2020-03-01

Biofluids contain various circulating cell-free RNAs (ccfRNAs). The composition of these ccfRNAs varies among biofluids. They constitute tantalizing biomarker candidates for several pathologies and have been demonstrated to be mediators of cellular communication. Little is known about their function in physiological and developmental settings, and most works are limited to in vitro studies. Here, we develop iTAG-RNA, a method for the unbiased tagging of RNA transcripts in mice in vivo. We use iTAG-RNA to isolate hepatocytes and kidney proximal epithelial cell-specific transcriptional responses to a dietary challenge without interfering with the tissue architecture and to identify multiple hepatocyte-secreted ccfRNAs in plasma. We also identify specific transfer of liver-derived ccfRNAs to adipose tissue and skeletal muscle, where they likely constitute a buffering system to maintain lipid homeostasis under acute high-fat-diet feeding. Our findings directly demonstrate in vivo transfer of RNAs between tissues and highlight its implications for endocrine signaling and homeostasis.
High-Level Expression, Purification and Initial Characterization of Recombinant Arabidopsis Histidine Kinase AHK1
2020-03-01

Plants employ a number of phosphorylation cascades in response to a wide range of environmental stimuli. Previous studies in Arabidopsis and yeast indicate that histidine kinase AHK1 is a positive regulator of drought and osmotic stress responses. Based on these studies AHK1 was proposed a plant osmosensor, although the molecular basis of plant osmosensing still remains unknown. To understand the molecular role and signaling mechanism of AHK1 in osmotic stress, we have expressed and purified full-length AHK1 from Arabidopsis in a bacterial host to allow for studies on the isolated transmembrane receptor. Purification of the recombinant protein solubilized from the host membranes was achieved in a single step by metal-affinity chromatography. Analysis of the purified AHK1 by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting show a single band indicating that the preparation is highly pure and devoid of contaminants or degradation products. In addition, gel filtration experiments indicate that the preparation is homogenous and monodisperse. Finally, CD-spectroscopy, phosphorylation activity, dimerization studies, and protein–protein interaction with plant phosphorylation targeting AHP2 demonstrate that the purified protein is functionally folded and acts as phospho-His or phospho-Asp phosphatase. Hence, the expression and purification of recombinant AHK1 reported here provide a basis for further detailed functional and structural studies of the receptor, which might help to understand plant osmosensing and osmosignaling on the molecular level.
Training choices toward low value options
2020-03-01

Abstract Food decisions are driven by differences in value of choice alternatives such that high value items are preferred over low value items. However, recent research has demonstrated that by implementing the Cue-Approach Training (CAT) the odds of choosing low value items over high value items can be increased. This effect was explained by increased attention to the low value items induced by CAT. Our goal was to replicate the original findings and to address the question of the underlying mechanism by employing eye-tracking during participants’ choice making. During CAT participants were presented with images of food items and were instructed to quickly respond to some of them when an auditory cue was presented (cued items), and not without this cue (uncued items). Next, participants made choices between two food items that differed on whether they were cued during CAT (cued versus uncued) and in pre-training value (high versus low). As predicted, results showed participants were more likely to select a low value food item over a high value food item for consumption when the low value food item had been cued compared to when the low value item had not been cued. Important, and against our hypothesis, there was no significant increase in gaze time for low value cued items compared to low value uncued items. Participants did spend more time fixating on the chosen item compared to the unchosen alternative, thus replicating previous work in this domain. The present research thus establishes the robustness of CAT as means of facilitating choices for low value over high value food but could not demonstrate that this increased preference was due to increased attention for cued low value items. The present research thus raises the question how CAT may increase choices for low value options.
ESA Athena WFI Onboard Electronics - Distributed Control and Data Processing
2020-03-01

Within this paper, we describe architecture and functionality of the Wide Field Imager (WFI) control and data processing electronics. WFI is one of two scientific instruments of the next European X-ray observatory ATHENA whose development started five years ago. A conceptual design, development models and a number of technology development activities have been performed and results will be shown.
Reaching the Goal of Alchemy – or: What Happens When You Finally Have Created the Philosophers’ Stone?
2020-03-01

Abstract Alchemy is the art of transforming base metals into precious ones, usually silver and/or gold. The most important method conceived to reach this goal was the creation of the elixir, also called the philosophers’ stone, which, applied to the prime-matter, would lead to an accelerated process of ripening of metals, eventually ending in gold. How did Arabo-Islamic alchemists suppose that the transmutation worked? What were the conditions the adept had to fulfil in order to succeed? And what did they think would happen when one finally has created the philosophers’ stone? Will the economy collapse because gold and silver will lose their validity? Will the alchemist simply lean back and enjoy? Or will the world end, because man has finally attained the knowledge that should be God’s only?
The Role of the Sublime in Kant’s Religion: Moral Motivation and Empirical Possibility
2020-03-01

I show that Kant’s depiction of the christic figure in Religion within the Boundaries of Mere Reason is not contingent but explains how this figure functions in two essential ways: as a representation of a maximum of morality that can ground our moral disposition and in so doing acts as a standard for morality. More precisely, the following argument is made: 1) the sublime nature of the image of Christ — as an image of universal respect for the law — awakens the moral feeling of subjects in the sense of the possibility of overcoming one’s perverted nature; 2) as moral perfection it provides immediate transparency to the end goal of morality; 3) just as in the case of associative construction of empirical concepts, the sublime provides the prototype for association through which empirical acts are determined as moral ones; 4) the image of Christ also acts as motivator by encompassing said transparency and standard in the idea of moral perfection. These four points show that the image of Christ functions in a dual manner. Points 1) to 3) address Christ as a prototype/archetype (Urbild) — awakening and making possible a moral redefinition of the subject — while point 4) addresses Christ as an example (Vorbild) — sustaining and entertaining the moral redefinition as a motivating model.
Book reviews
2020-03-01

The two first decades of the 21st century witnessed rapid progress in the field of the study of the Crimea in the early modern period.This phenomenon can be explained first of all by improvements in accessibility of post-Soviet (Russian and Ukrainian) and Turkish archives.As a result, scholars working in the area of Crimean Studies discovered a great number of new, hitherto unknown sources pertaining to the history of the Crimean Khanate, and also began publishing already known ones.Especially significant in this regard is the fact that scholars began analysing and translating such important corpus of sources as texts of the Crimean sharia court records (şer'iye sicilleri), whose originals are kept in the Russian National Library in St. Petersburg. 1 At the same time, one should notice that these publications focus mostly on the history of the Crimean Khanate while the study of the Ottoman possessions in the Crimean peninsula (i.e."Kefe province" or Eyālet-i Kefê) still remains at a very superficial level.Only one of the Crimea-related defters (i.e.Ottoman tax registers) was published so far (Inalcik 1996), while attempts to study defters from the 16th and 17th centuries date back to the 1970s and the 1980s (Fisher 1979: 215-226 and 1981: 1 These sources became accessible to the scholars only since the beginning of the 1990s.This is why it was only recently that first translations and analyses of the sicils began to appear (Çavuş
Collectively Enhanced Chiral Photon Emission from an Atomic Array near a Nanofiber
2020-03-02

Emitter ensembles interact collectively with the radiation field. In the case of a one-dimensional array of atoms near a nanofiber, this collective light-matter interaction does not only lead to an increased photon coupling to the guided modes within the fiber, but also to a drastic enhancement of the chirality in the photon emission. We show that near-perfect chirality can be achieved already for moderately sized ensembles, containing 10 to 15 atoms, by phase matching a superradiant collective guided emission mode via an external laser field. This is of importance for developing an efficient interface between atoms and waveguide structures with unidirectional coupling, with applications in quantum computing and communication such as the development of nonreciprocal photon devices or quantum information transfer channels.
Asymmetric Disulfanylbenzamides as Irreversible and Selective Inhibitors of Staphylococcus aureus Sortase A
2020-03-02

Abstract Staphylococcus aureus is one of the most frequent causes of nosocomial and community‐acquired infections, with drug‐resistant strains being responsible for tens of thousands of deaths per year. S. aureus sortase A inhibitors are designed to interfere with virulence determinants. We have identified disulfanylbenzamides as a new class of potent inhibitors against sortase A that act by covalent modification of the active‐site cysteine. A broad series of derivatives were synthesized to derive structure‐activity relationships (SAR). In vitro and in silico methods allowed the experimentally observed binding affinities and selectivities to be rationalized. The most active compounds were found to have single‐digit micromolar K i values and caused up to a 66 % reduction of S. aureus fibrinogen attachment at an effective inhibitor concentration of 10 μM. This new molecule class exhibited minimal cytotoxicity, low bacterial growth inhibition and impaired sortase‐mediated adherence of S. aureus cells.
Systematic Investigation of the Effect of Non-Ionic Emulsifiers on Skin by Confocal Raman Spectroscopy—A Comprehensive Lipid Analysis
2020-03-02

Non-ionic emulsifiers are commonly found in existing pharmaceutical and cosmetic formulations and have been widely employed to enhance the penetration and permeation of active ingredients into the skin. With the potential of disrupting skin barrier function and increasing fluidity of stratum corneum (SC) lipids, we herein examined the effects of two kinds of non-ionic emulsifiers on intercellular lipids of skin, using confocal Raman spectroscopy (CRS) with lipid signals on skin CRS spectrum. Non-ionic emulsifiers of polyethylene glycol alkyl ethers and sorbitan fatty acid esters were studied to obtain a deep understanding of the mechanism between non-ionic emulsifiers and SC lipids. Emulsifier solutions and dispersions were prepared and applied onto excised porcine skin. Water and sodium laureth sulfate solution (SLS) served as controls. SC lipid signals were analysed by CRS regarding lipid content, conformation and lateral packing order. Polyethylene glycol (PEG) sorbitan esters revealed no alteration of intercellular lipid properties while PEG-20 ethers appeared to have the most significant effects on reducing lipid content and interrupting lipid organization. In general, the polyoxyethylene chain and alkyl chain of PEG derivative emulsifiers might indicate their ability of interaction with SC components. HLB values remained critical for complete explanation of emulsifier effects on skin lipids. With this study, it is possible to characterize the molecular effects of non-ionic emulsifiers on skin lipids and further deepen the understanding of enhancing substance penetration with reduced skin barrier properties and increased lipid fluidity.