julilili42/papers huggingface dataset:
Photodynamic therapy with double duration for circumscribed choroidal haemangioma: functional and anatomical results based on initial parameters
2017-12-06

Abstract Importance Pre‐treatment symptoms longer than 12 months and foveal cystoid changes are indicators for poor anatomical and functional outcome after photodynamic therapy (PDT). Background To evaluate the prognostic factors on the effectiveness of PDT with double duration for treatment of exudative circumscribed choroidal haemangioma. Design Retrospective study. Participants Twenty‐seven patients with symptomatic exudative circumscribed choroidal haemangioma treated with PDT. Methods Clinical charts of patients with exudative circumscribed choroidal haemangioma treated with PDT were analysed with regard to visual acuity , duration of symptoms, subfoveal fluid, foveal cystoid changes and foveal thickness in optical coherence tomography. Main Outcome Measures Change of best‐corrected visual acuity, sub‐ and intrafoveal fluid and foveal thickness measured with optical coherence tomography from baseline to last follow‐up. Results Mean visual acuity improved by 0.05 from 0.42 logMAR (standard deviation [SD] 0.34) to 0.37 logMAR (SD 0.47). In 70% of the patients, PDT stopped exudation and revealed a dry fovea. The recurrence or persistence of sub‐ or intrafoveal fluid was significantly associated with pre‐therapeutic symptoms existing for more than 12 months ( P = 0.046). Mean foveal thickness in optical coherence tomography decreased from 324 μm (SD 223 μm) to 209 μm (SD 109 μm). Conclusions and Relevance PDT proved to be a safe and effective treatment procedure for exudative circumscribed choroidal haemangioma in our series, with few side effects. We observed a more successful treatment with regard to anatomical and functional results in cases with pre‐existing symptoms less than 12 months and in cases without pre‐therapeutic foveal cystoid changes.
Authoritarian Regimes
2017-12-06

Abstract This article first discusses the term “authoritarian regimes” and makes a claim for studying such regimes. An overview of the young but burgeoning research on authoritarian regimes structures the field in eight thematic clusters: (1) typological efforts and regime characteristics such as coalition formation and origins, (2) institutionalist approaches, (3) state-society relations beyond formal institutions, (4) repression, (5) political economy approaches, (6) international dimensions, (7) performance, and (8) linking the concepts of regimes and states. Although this wave of research has been extremely prolific, it still remains unsystematic and disparate in various regards. It is therefore necessary for this field of research to consolidate and thereby to contribute to genuine knowledge accumulation.
SNPViz - Visualization of SNPs in proteins
2017-12-06

In personalized medicine, SNPs are used to identify specific diseases of a patient. However, for many SNPs, no information about the pathogenicity is available. Current programs try to predict the effect of a SNP on the function of a protein, but give no possibility for visual interpretation. We have developed SNPViz, a program that first finds 3D structures of affected proteins and then highlights the affected amino acid in the 3D structure. This can give researchers and doctors more information about the probable pathogenicity of the SNP. In the future, we plan to add also further information, such as whether the position of the SNP is in a binding domain, or is involved in a protein-protein interaction.
Deuterated Molecular Ruby with Record Luminescence Quantum Yield
2017-12-07

Abstract The recently reported luminescent chromium(III) complex 1 3+ ([Cr(ddpd) 2 ] 3+ ; ddpd= N , N ′‐dimethyl‐ N , N ′‐dipyridine‐2‐yl‐pyridine‐2,6‐diamine) shows exceptionally strong near‐IR emission at 775 nm in water under ambient conditions ( Φ =11 %) with a microsecond lifetime as the ligand design in 1 3+ effectively eliminates non‐radiative decay pathways, such as photosubstitution, back‐intersystem crossing, and trigonal twists. In the absence of energy acceptors, such as dioxygen, the remaining decay pathways are energy transfer to high energy solvent and ligand oscillators, namely OH and CH stretching vibrations. Selective deuteration of the solvents and the ddpd ligands probes the efficiency of these oscillators in the excited state deactivation. Addressing these energy‐transfer pathways in the first and second coordination sphere furnishes a record 30 % quantum yield and a 2.3 millisecond lifetime for a metal complex with an earth‐abundant metal ion in solution at room temperature.
A critical assessment of the Protoaurignacian lithic technology at Fumane Cave and its implications for the definition of the earliest Aurignacian
2017-12-07

In the scenario of the spread of the anatomically modern humans (AMHs) into Europe, the techno-complex known as Protoaurignacian is defined by the production of blades and bladelets within a single and continuous stone knapping sequence from the same core as the result of its progressive reduction. However, the growing re-evaluation of some assemblages is revealing that bladelets are frequently obtained from independent reduction sequences, hence discouraging the direct application of the model developed in southwestern France. High-resolution regional signatures are thus needed to reconstruct a more accurate portrait of the AMH colonization dynamic. Northeastern Italy, with the key site of Fumane Cave, is one among the regions of Mediterranean Europe worthy of consideration for reconstructing this colonization process and its cultural dynamics. Within the framework of a critical discussion of the technological definition of the Protoaurignacian and its relationship with contemporaneous industries on a regional and supra-regional scale, we present the results of a detailed analysis of the lithic technology from units A2-A1 based on reduction sequence and attribute analyses. Results show that bladelets are the first goal of production and they do not originate from reduced blade cores but from a broad range of independent and simultaneous core reduction strategies. One implication is that the most commonly used technological trait that is said to define the Protoaurignacian has been over-emphasized and that the Protoaurignacian is technologically consistent across its geographical extent. Additional data based on carinated core technology imply that this techno-complex shares a common technological background with the Early Aurignacian and that no features are restricted to one of the two facies. Furthermore, the major difference between the Protoaurignacian and Early Aurignacian appears to be more typological in nature, with retouched bladelets being less common in the Early Aurignacian.
Controlling Scarce Working Time in a Multi-task Incentive Problem
2017-12-07

Even though working time is one of the firm's scarcest resources, there are very few insights into how to optimally control it. In this paper we analyze the optimal allocation of scarce working time to two tasks in a contracting problem. Since each hour devoted to one specific task is not available for the other task, and vice versa, the agent accounts for opportunity cost when allocating his time to the tasks. We analyze this trade-off assuming that the agent's contribution is not contractible, such that a contract must be written based on an alternative measure. Time scarcity restricts total output. At the same time, however, it changes the agent's focus of attention towards the task with the higher performance sensitivity. Thus, by increasing the incentive coefficient the principal induces the agent to shift time from the less sensitive to the more sensitive task. The main contribution of our paper is that we show that time scarcity can improve the congruence of the agent's behavior with the principal's objectives. Under certain conditions an improved alignment of effort under time scarcity offsets the reduction of output and increases the agency's surplus.
Zebrafish differentially process colour across visual space to match natural scenes
2017-12-07

Summary Animal eyes evolve to process behaviourally important visual information, but how retinas deal with statistical asymmetries in visual space remains poorly understood. Using hyperspectral imaging in the field, in-vivo 2-photon imaging of retinal neurons and anatomy, here we show that larval zebrafish use a highly anisotropic retina to asymmetrically survey their natural visual world. First, different neurons dominate different parts of the eye, and are linked to a systematic shift in inner retinal function: Above the animal, there is little colour in nature and retinal circuits are largely achromatic. Conversely, the lower visual field and horizon are colour-rich, and are predominately surveyed by chromatic and colour-opponent circuits that are spectrally matched to the dominant chromatic axes in nature. Second, above the frontal horizon, a high-gain ultraviolet-system piggy-backs onto retinal circuits, likely to support prey-capture. Our results demonstrate high functional diversity among single genetically and morphologically defined types of neurons.
Definition and Characterization of a Peptide Warehouse for the Patient-Individualized Peptide Vaccination Study (iVAC-L-CLL01) after First Line Therapy of CLL
2017-12-07

Abstract The treatment of chronic lymphocytic leukemia (CLL) has substantially advanced over the last decade with chemo/immunotherapy as standard of care achieving overall response rates up to 90%. However, besides allogeneic stem cell transplantation, so far no curative treatment for CLL is available. This is mostly due to the persistence of residual CLL cells after therapy (minimal residual disease, MRD), which cause disease relapse. Thus, novel strategies such as peptide-based immunotherapy aiming to eliminate MRD are needed to achieve lasting disease remission or even cure. With this aim, we implemented a first-in-man multi-centric clinical phase II study (iVAC-L-CLL01, NCT02802943), in which patient-individualized peptide vaccination with or without lenalidomide as systemic immune modulator is applied after first-line therapy of CLL. The peptide vaccine cocktail consists of 10 tumor-associated peptides selected according to the HLA ligandome of the individual patients from a pre-manufactured “peptide warehouse”. This peptide warehouse contains CLL-associated antigens, which are frequently and exclusively presented by HLA molecules on the surface of CLL cells. The peptides have been selected using a direct mass spectrometry based comparative analysis of the HLA ligandome of 30 CLL patients and a normal tissue ligandome database (Kowalewski et al. PNAS, 2015). The warehouse includes 35 HLA class I and 5 HLA class II peptides. The HLA class I peptides are restricted by the 7 most common HLA class I allotypes (A*01, A*02, A*03, A*24, B*07, B*08 and B*44). Prior to clinical application, the immunogenicity of the warehouse peptides was validated using different T-cell assays. We performed IFNg ELISpot assays using PBMC obtained from CLL patients and healthy donors. Peptide-specific memory T-cell responses were detected for 20/35 (57%) HLA class I peptides (A*01, A*02, A*03 and B*08) and 5/5 (100%) HLA class II peptides in samples obtained from CLL patients. Immune responses in healthy donors could not be detected for any of the 40 warehouse peptides, indicating a strictly CLL directed T-cell response. The immunogenicity of the remaining peptides could not be approved by detection of spontaneous memory T-cell responses in CLL patients due to lack of HLA-matched CLL-patient samples. Hence, we implemented artificial APC-based in vitro priming assays using CD8+ T cells of healthy donors proofing the ability of the peptides to prime naive CD8+ T cells. For all 15 analyzed peptides (HLA A*24, B*07 and B*44), an induction of tetramer positive CD8+ T cell populations with frequencies of 0.1-35.1% could be detected. Therefore, all 40 warehouse peptides could be confirmed as immunogenic T-cell epitopes The iVAC-L-CLL01 study is recruiting since October 2016. Vaccination of the first included study patient was performed in July 2017. Disclosures No relevant conflicts of interest to declare.
The Heroine and the Meme: Participating in Feminist Discourses Online
2017-12-07

This article examines the relationship between feminist participatory culture and online ativism. I argue that Internet users participate in feminist discourses online by creating memes that present popular fictional female heroes such as Katniss Everdeen (The Hunger Games), Buffy Summers (Buffy the Vampire Slayer), or the Disney Princess Merida (Brave). Emphasizing specific characteristics and plot points of the respective stories, memes project, spread, and celebrate feminist ideas such as female empowerment, agency, and equality.
Constructing ‘Arab Terrorism’—The Slow Emergence of Terrorism Discourse in the United States in the 1960s and 1970s
2017-12-07

This article traces the beginnings of the discourse on “Arab terrorism” in the U.S. after World War II. I argue that the discourse emerged slowly in the early 1970s, growing out of political concerns in the aftermath of the 1972 “Munich Massacre” as well as previous work by scholars on political violence. Prominent cultural products like Leon Uris’ Exodus and Thomas Harris’ Black Sunday contributed to the vilification of Arab populations in the Middle East and merged with these political and academic discourses to construct Arab aggression in terms of terrorism.
Platelet Programmed Cell Death Ligand 1 (pPDL-1) Is a Prognostic Marker in Advanced Lung Cancer
2017-12-07

Abstract Introduction. PDL-1 (Programmed Cell Death Ligand-1) expressed on non small cell lung cancer (NSCLC) cells mediates immune escape, and inhibition of PDL-1/PD-1 interaction with blocking antiboides induces long-term responses in a subpopulation of patients with metastatic NSCLC. PDL-1 immunohistochemistry is a controversial means of predicting responders, and further biomarkers are urgently needed. Herein, we report on the phenomenon of PDL-1 expressed on the surface of platelets (platelet PDL-1, pPDL-1) in patients with advanced NSCLC. Methods. Blood samples were prospectively collected from patients, and platelet-expressed PDL-1 expression was measured by flow cytometry utilizing flow monoclonal antibodies clones MIH1 and 28-8. Correlations of pPDL-1 expression levels with histopathological data, laboratory data, and survival were analyzed. Results. 79 NSCLC patients (53 with adenocarcinoma and 26 with squamous cell carcinoma) and 42 healthy controls were analyzed. 61 patients (77.2%) had stage IV disease. Platelets derived from healthy controls expressed little if any pPDL-1. Mean pPDL-1 expression in tumor patients was significantly increased compared with controls. PPDL-1 was not correlated with histological subtypes, mutational status, smoking history, clinical stage or laboratory data. However, overall survival (OS) and progression free survival (PFS) were significantly reduced in patients with a high (above median) percentage of PDL-1-positive platelets as compared with low pPDL-1(OS: 29 vs. 45 months, p = 0.027, PFS: 6 vs. 9 months, p = 0.036). The accuracy of our system was validated by calculating the area under the receiver-operator characteristic (ROC) curve. Here, platelet-derived PDL-1 expression was also significantly associated with a reduced OS (AUC=0.719, 95 CI: 0.587- 0.851) and PFS (AUC=0.768, 95 CI: 0.59- 0.89). Conclusion. To our knowledge, this is the first report of PDL-1 expression on platelets. In NSCLC patients, high pPDL-1 - similar to tumor PDL-1 - is clearly prognostic. The functional significance and predictive value of pPDL-1 remains to be established. Disclosures No relevant conflicts of interest to declare.
Effects of CSF3R mutations on Myeloid Differentiation and Proliferation of Hematopoietic Cells of Congenital Neutropenia Patients
2017-12-07

Abstract Over the last 25 years, with the clinical approval of recombinant human granulocyte colony-stimulating factor (rhG-CSF) remarkable progress has been achieved in the therapy of severe congenital neutropenia (CN). Nevertheless, CN patients have a high rate of transformation to myelodysplasia (MDS) or acute myeloid leukemia (AML). This risk is especially high in the group of patients who harbor acquired G-CSFR mutations, suggesting that these mutations are involved in the leukemogenesis. Deep sequencing of the intracellular part of G-CSFR allowed us to identify a subset of CN patients with a high mutant allele frequency (MAF) of G-CSFR mutations in the granulocytic compartment. We performed CSF3R mutation analysis of myeloid colonies from colony forming unit (CFU) assay of BM and CD34+ samples of 3 ELANE -CN patients, in which the percentage of granulocytes with G-CSFR mutation varied between 22.6% and 81%. Average number of sequenced colonies per CFU sample was 18. Intriguingly, we found that only cell clones with WT G-CSFR were grown in CFU assay. We hypothesized that lack of G-CSFR mutant clones in CFU assay is due to abnormal signaling downstream of truncated G-CSFR. To compare myeloid differentiation of G-CSFR mutant and WT G-CSFR hematopoietic cells, we generated ELANE -CN patient-derived induced pluripotent stem cells (CN-iPSCs) and performed CRISPR/Cas9 genome editing of CSF3R . Using 2 different sgRNAs specific for the intracellular region of G-CSFR, we introduced nucleotide indels at amino acid positions 740 and 735 (NP_000751.1) in CN-iPSCs. Subsequently, homozygous and heterozygous CN-iPSCs clones with truncated distal part of cytoplasmic domain of G-CSF receptor and subsequent loss of 3 out of 4 conserved tyrosine residues were generated. We compared myeloid differentiation of healthy donor iPSCs (HD-iPSCs), CN-iPSCs and CN-iPSCs with heterozygous and homozygous truncated G-CSF receptor (G-CSFR*HET CN-iPSCs and G-CSFR*HOM CN-iPSCs, respectively). Absolute cell count during myeloid differentiation (18-32 day) of HD-iPSCs, G-CSFR*HET CN-iPSCs and G-CSFR*HOM CN-iPSCs didn't differ significantly (p>0.05). In contrast, absolute cell count was found to be elevated from day 25 to day 32 of differentiation when G-CSFR*HET CN-iPSCs and G-CSFR*HOM CN-iPSCs hematopoietic progenitors were compared with CN-iPSCs-derived hematopoietic cells (p Using a combination of patient CN-iPSCs and CRISPR/Cas9 gene editing we were able to recapitulate main features of G-CSFR mutant versus G-CSFR WT CN cells - defective neutrophil differentiation and increased proliferation of human hematopoietic progenitors. Since virtually all studies of truncated G-CSFR receptor signaling have been performed in murine cytokine-responsive myeloid cell lines, our approach is more suitable to explore human aberrant G-CSF receptor signaling in depth. Disclosures No relevant conflicts of interest to declare.
Cover Feature: Methyl Fumarate‐Derived Iron Carbonyl Complexes (FumET‐CORMs) as Powerful Anti‐inflammatory Agents (ChemMedChem 23/2017)
2017-12-07

The Cover Feature shows the “championship” of anti-inflammatory agents for dendritic cells. The winners are FumET-CORMs which were developed by fusing a methyl fumarate and an enzyme-triggered carbon monoxide releasing molecule (ET-CORM). The intracellular activation of the FumET-CORMs by an esterase leads to the simultaneous release of CO and methyl fumarate. In contrast to the clinically used dimethyl fumarate or CO alone, the strong cellular response of dendritc cells towards FumET-CORMs reflects the synergetic action of the two agents as indicated by the suppression of secretion of inflammatory interleukins IL-12 and IL-23. More information can be found in the Communication by Thomas Wieder, Hans-Günther Schmalz et al. on page 1927 in Issue 23, 2017 (DOI: 10.1002/cmdc.201700488).
Low-frequency alternating current stimulation rhythmically suppresses stimulus-induced gamma-band oscillations in visual cortex and impairs perceptual performance
2017-12-07

Abstract Alpha oscillations (8-12 Hz) are hypothesized to rhythmically gate sensory processing, reflected by activity in the 40-100 Hz gamma band, via the mechanism of pulsed inhibition. We applied transcranial alternating current stimulation (TACS) at individual alpha frequency (IAF) and flanking frequencies (IAF-4 Hz, IAF+4 Hz) to the occipital cortex of healthy human volunteers during concurrent magnetoencephalography (MEG), while participants performed a visual detection task inducing strong gamma-band responses. Occipital (but not frontal) TACS phasically suppressed stimulus-induced gamma oscillations in the visual cortex and impaired target detection, with stronger phase-to-amplitude coupling predicting behavioral impairments. Frontal control TACS ruled out retino-thalamo-cortical entrainment resulting from (subthreshold) retinal stimulation. All TACS frequencies tested were effective, suggesting that visual gamma-band responses can be modulated by a range of low frequency oscillations. We propose that TACS-induced cortical excitability fluctuations mimic the mechanism of pulsed inhibition, which mediates the function of alpha oscillations in gating sensory processing.
Antiemetic Prophylaxis with Granisetron and Fosaprepitant during Moderate and High Emetogenic Chemotherapy in Pediatric Patients
2017-12-07

Abstract Background Pediatric patients that undergo chemotherapy and hematopoietic stem cell transplantation regularly experience chemotherapy-induced nausea and vomiting (CINV), which represents a major impairment of the patients' quality of life. Antiemetic prophylaxis is thus an important factor in cancer therapy management. Risk for CINV is defined by >30-60% in moderate and by >60% in high emetogenic therapy. International guidelines recommend antiemetic prophylaxis with a combination of corticosteroids, 5-HT3R-antagonists (5-hydroxytryptamine-3 receptor) and NK1R-antagonists (neurokinin-1 receptor). Especially the water-soluble NK1R-antagonist fosaprepitant has shown favorable results in adult patients when used in a combination prophylaxis with the 5-HT3R-antagonist granisetron. This is the first comparative analysis to assess the efficacy and safety of a combination of intravenous fosaprepitant, granisetron and dexamethasone versus a standard prophylaxis regimen with granisetron and dexamethasone alone in 86 pediatric patients. Results In this retrospective single-center chart analysis, a total of 86 pediatric patients with a median age of 7 years (2-17 years) were enrolled between 2015 and 2017. The patients received either antiemetic prophylaxis with intravenous infusion ( Both prophylaxis regimens were similarly safe and not significantly different (p>0.05) with respect to clinical or laboratory drug-related adverse events. Discontinuation of the antiemetic medication was not indicated for any of the patients of the CG or FG. Percentages of patients experiencing vomiting was significantly lower in the FG, both in the acute CINV phase (p Conclusion In conclusion, additional single-dose fosaprepitant in combination with the standard antiemetic regimen with granisetron and dexamethasone proved to be safe and effective as antiemetic prophylaxis in pediatric patients receiving moderate or high emetogenic therapy. Observed drug-related side effects were similar in both study groups. Efficacy of a triple-prophylaxis with the NK1R-antagonists fosaprepitant in combination with the 5-HT3R-antagonist granisetron and the corticosteroid dexamethasone was significantly superior when compared to a prophylaxis regimen with granisetron plus dexamethasone alone. Acknowledgments This study was supported by the Stefan-Morsch-Stiftung, Birkenfeld, Germany. Disclosures Handgretinger: Miltenyi Biotec GmbH: Patents & Royalties, Research Funding.