julilili42/papers huggingface dataset:
Unicompartmental bipolar osteochondral and meniscal allograft transplantation is effective for treatment of medial compartment gonarthrosis in a canine model
2020-07-16

Abstract Osteochondral allograft (OCA) transplantation can restore large articular defects in the knee. Bipolar OCA transplantations for partial and whole joint resurfacing often have less favorable results than single‐surface transplants. This study was designed to use a large animal model to test the hypothesis that unicompartmental bipolar osteochondral and meniscal allograft transplantation (BioJoint) would be as or more effective for treatment of medial compartment osteoarthritis (OA) compared to standard‐of‐care nonoperative treatment. OA was induced in one knee of each research hound (n = 8) using a meniscal release model and pretreatment assessments were performed. After 3 months, dogs were randomly assigned to either the control group (n = 4, no surgical intervention, daily nonsteroidal antiinflammatory drugs [NSAIDs]) or the BioJoint group (n = 4). Clinical, radiographic, and arthroscopic assessments were performed longitudinally and histopathology was evaluated at the 6‐month endpoint. At study endpoint, functional, pain, and total pressure index measures, as well as radiographic and arthroscopic grading of graft appearance and joint health, demonstrated superior outcomes for BioJoints compared to NSAID controls. Furthermore, histologic assessments showed that osteochondral and meniscal transplants maintain integrity and integrated into host tissues. Clinical significance: The results support the safety and efficacy of unicompartmental bipolar osteochondral and meniscal allograft transplantation in a preclinical model with highly functional outcomes without early OA progression.
Quantifying closeness between black hole spacetimes: a superspace approach
2020-07-16

The set of all metrics that can be placed on a given manifold defines an\\ninfinite-dimensional `superspace' that can itself be imbued with the structure\\nof a Riemannian manifold. Geodesic distances between points on Met measure\\nhow close two different metrics over are to one another. Restricting our\\nattention to only those metrics that describe physical black holes, these\\ndistances may therefore be thought of as measuring the level of geometric\\nsimilarity between different black hole structures. This allows for a\\nsystematic quantification of the extent to which a black hole, possibly arising\\nas an exact solution to a theory of gravity extending general relativity in\\nsome way, might be `non-Kerr'. In this paper, a detailed construction of a\\nsuperspace for stationary black holes with an arbitrary number of hairs is\\ncarried out. As an example application, we are able to strengthen a recent\\nclaim made by Konoplya and Zhidenko about which deviation parameters describing\\na hypothetical, non-Schwarzschild black hole are likely to be most relevant for\\nastrophysical observables.\\n
Combined Endoscopic Negative Pressure and Surgical Treatment of Anastomotic Insufficiencies following Oncological Gastrectomy – Recent Results
2020-07-16

Abstract Background and study aims: Management of esophago-jejunal anastomotic leakages (EJAL) following gastrectomy is challenging. Endoscopic negative pressure therapy (ENPT) is an emerging effective tool for treatment of gastrointestinal and anastomotic leaks. We have been using ENPT as first line therapy for EJAL after oncological gastric resections since 2018. The aim of the study was to present our results with this strategy in a case series. Methods: Nine consecutive patients were treated with ENPT for EJAL after oncological gastrectomy between 01.2018 and 12.2019. A retrospective analysis of patients’ and treatment-related data was performed. Results: Time to leakage detection was 6.00 ± 2.49 days after surgery. After 14.78 ± 9.66 days of ENPT, 6.25 ± 3.65 endoscopies and 38.11 ± 16.46 days of hospitalization, endoscopic treatment with ENPT combined with surgical debridement and drainage for sepsis control was effective in eight of nine patients. In one patient with a complete anastomotic dehiscence, treatment was changed to a stent-based therapy combined with surgery. Conclusions: ENPT is a new and promising option in the complication management of patients with anastomotic insufficiencies following oncological gastrectomy. It can be recommended in combination with limited surgery to preserve the anastomosis and provide sepsis control. The time interval to diagnosis and the size of the insufficiency are important for the success of ENPT in patients with EJAL.
Melanoma brain metastases – Interdisciplinary management recommendations 2020
2020-07-17

Melanoma brain metastases (MBM) are common and associated with a particularly poor prognosis; they directly cause death in 60-70% of melanoma patients. In the past, systemic treatments have shown response rates around 5%, whole brain radiation as standard of care has achieved a median overall survival of approximately three months. Recently, the combination of immune checkpoint inhibitors and combinations of MAP-kinase inhibitors both have shown very promising response rates of up to 55% and 58%, respectively, and improved survival. However, current clinical evidence is based on multi-cohort studies only, as prospectively randomized trials have been carried out rarely in MBM, independently whether investigating systemic therapy, radiotherapy or surgical techniques. Here, an interdisciplinary expert team reviewed the outcome of prospectively conducted clinical studies in MBM, identified evidence gaps and provided recommendations for the diagnosis, treatment, outcome evaluation and monitoring of MBM patients. The recommendations refer to four distinct scenarios: patients (i) with 'brain-only' disease, (ii) with oligometastatic asymptomatic intra- and extracranial disease, (iii) with multiple asymptomatic metastases, and (iv) with multiple symptomatic MBM or leptomeningeal disease. Changes in current management recommendations comprise the use of immunotherapy - preferably combined anti-CTLA-4/PD-1-immunotherapy - in asymptomatic MBM minus/plus stereotactic radiosurgery which remains the mainstay of local brain therapy being safe and effective. Adjuvant whole-brain radiotherapy provides no clinical benefit in oligometastatic MBM. Among the systemic therapies, combined MAPK-kinase inhibition provides, in BRAF<sup>V600</sup>-mutated patients with rapidly progressing or/and symptomatic MBM, an alternative to combined immunotherapy.
Enhancing cognitive control training with transcranial direct current stimulation: a systematic parameter study
2020-07-17

Our results confirm beneficial, non-linear effects of anodal tDCS on cognitive training in a large sample of healthy subjects. The data consolidate the basis for further development of functionally targeted tDCS, supporting cognitive control training in mental disorders and guiding further development of clinical interventions.
Dynamics of cell-free tumour DNA correlate with treatment response of head and neck cancer patients receiving radiochemotherapy
2020-07-17

Monitoring RCTX treatment-response using liquid biopsy in patients with locally advanced HNSCC is feasible. CtDNA can be seen as a surrogate marker of disease burden, tightly correlating with the gross tumour volume prior to the treatment start. The observed kinetic of ctDNA and cvDNA showed a negative correlation with time and treatment dosage in most patients.
Extracellular Ca2+-Sensing Fluorescent Protein Biosensor Based on a Collagen-Binding Domain
2020-07-17

The importance of extracellular gradients of biomolecules is increasingly appreciated in the processes of tissue development and regeneration, in health and disease. In particular, the dynamics of extracellular calcium concentration is rarely studied. Here, we present a low affinity Ca<sup>2+</sup> biosensor based on Twitch-2B fluorescent protein fused with the cellulose- and collagen-binding peptides. These recombinant chimeric proteins can bind cellulose and collagen scaffolds and enable scaffold-based biosensing of Ca<sup>2+</sup> in the proximity of cells in live 3D tissue models. We found that the Twitch-2B mutant is compatible with intensity-based ratiometric and fluorescence lifetime imaging microscopy (FLIM) measurement formats, under one- and two-photon excitation modes. Furthermore, the donor fluorescence lifetime of the biosensor displays response to [Ca<sup>2+</sup>] over a range of ∼2-2.5 ns, making it attractive for multiplexed FLIM assays. To evaluate the performance of this biosensor in physiological measurements, we applied it to the live Lgr5-GFP mouse intestinal organoid culture and measured its responses to the changes in extracellular Ca<sup>2+</sup> upon chelation with EGTA. When combined with spectrally resolved FLIM of lipid droplets using Nile red dye, we observed changes in cytoplasmic and basal membrane-associated lipid droplet composition in response to the extracellular Ca<sup>2+</sup> depletion, suggesting that the intestinal epithelium can respond to and compensate such treatment. Altogether, our results demonstrate Twitch-2B as a prospective Ca<sup>2+</sup> sensor for multiplexed FLIM analysis in a complex 3D tissue environment.
Structure of Merkel Cell Polyomavirus Capsid and Interaction with Its Glycosaminoglycan Attachment Receptor
2020-07-17

The MCPyV genome was found to be clonally integrated in 80% of cases of Merkel cell carcinoma (MCC), a rare but aggressive form of human skin cancer, strongly suggesting that this virus is tumorigenic. In the metastasizing state, the course of the disease is often fatal, especially in immunocompromised individuals, as reflected by the high mortality rate of 33 to 46% and the low 5-year survival rate (&lt;45%). The high seroprevalence of about 60% makes MCPyV a serious health care burden and illustrates the need for targeted treatments. In this study, we present the first high-resolution structural data for this human tumor virus and demonstrate that the full capsid is required for the essential interaction with its GAG receptor(s). Together, these data can be used as a basis for future strategies in drug development.
Going beyond clinical routine in SARS-CoV-2 antibody testing - A multiplex corona virus antibody test for the evaluation of cross-reactivity to endemic coronavirus antigens
2020-07-17

Abstract Given the importance of the humoral immune response to SARS-CoV-2 as a global benchmark for immunity, a detailed analysis is needed to monitor seroconversion in the general population, understand manifestation and progression of COVID-19 disease, and ultimately predict the outcome of vaccine development. In contrast to currently available serological assays, which are only able to resolve the SARS-CoV-2 antibody response on an individual antigen level, we developed a multiplex immunoassay, for which we included spike and nucleocapsid proteins of SARS-CoV-2 and the endemic human coronaviruses (NL63, OC43, 229E, HKU1) in an expanded antigen panel. Compared to three commercial in vitro diagnostic tests, our MULTICOV-AB assay achieved the highest sensitivity and specificity when analyzing a well-characterized sample set of SARS-CoV-2 infected and uninfected individuals. Simultaneously, high IgG responses against endemic coronaviruses became apparent throughout all samples, but no consistent cross-reactive IgG response patterns could be defined. In summary, we have established and validated, a robust, high-content-enabled, and antigen-saving multiplex assay MULTICOV-AB, which is highly suited to monitor vaccination studies and will facilitate epidemiologic screenings for the humoral immunity toward pandemic as well as endemic coronaviruses.
Comparison of Two Ensemble Kalman-Based Methods for Estimating Aquifer Parameters from Virtual 2-D Hydraulic and Tracer Tomographic Tests
2020-07-17

We compare two ensemble Kalman-based methods to estimate the hydraulic conductivity field of an aquifer from data of hydraulic and tracer tomographic experiments: (i) the Ensemble Kalman Filter (EnKF) and (ii) the Kalman Ensemble Generator (KEG). We generated synthetic drawdown and tracer data by simulating two pumping tests, each followed by a tracer test. Parameter updating with the EnKF is performed using the full transient signal. For hydraulic data, we use the standard update scheme of the EnKF with damping, whereas for concentration data, we apply a restart scheme, in which solute transport is resimulated from time zero to the next measurement time after each parameter update. In the KEG, we iteratively assimilate all observations simultaneously, here inverting steady-state heads and mean tracer arrival times. The inversion with the dampened EnKF worked well for the transient pumping-tests, but less for the tracer tests. The KEG produced similar estimates of hydraulic conductivity but at significantly lower costs. We conclude that parameter estimation in well-defined hydraulic tests can be done very efficiently by iterative ensemble Kalman methods, and ambiguity between state and parameter updates can be completely avoided by assimilating temporal moments of concentration data rather than the time series themselves.
V1 neurons encode the perceptual compensation of false torsion arising from Listing’s law
2020-07-17

Significance Eye movements have three degrees of freedom, the ability to move horizontally, vertically, and torsionally. Eye movements serving the fovea strictly control eye torsion. The amount of torsion associated with a particular eye position is specified by Listing’s law. Because of prior knowledge of the torsion set by Listing’s law, we perceive the world as upright although its retinal image may be tilted by varying degrees. We first show that also monkeys use a torsion prior to ensure a veridical perceptual reinterpretation of image tilt. We then demonstrate that this reinterpretation is a consequence of the fact that V1 neurons use the torsion prior to adjust their orientation preferences and to reposition their receptive fields relative to the retina.
Bitcoin Price Risk—A Durations Perspective
2020-07-17

An important aspect of liquidity is price risk, i.e., the risk that a small transaction leads to a large price change. This usually happens in a thin market, when trading opportunities are scarce and the time between subsequent trades is long. We rely on an autoregressive conditional duration model to extract the probability of a substantial price event in a particular time interval and, thus, an intraday risk profile. Our findings show that price risk is highest at times when European and U.S. investors do not trade. In a second step, we relate daily aggregates to characteristics of the Bitcoin blockchain and investigate whether investors account for features like confirmation time or fees when timing their orders.
Is IHL a Sham? A Reply to Eyal Benvenisti and Doreen Lustig
2020-07-17

Abstract This contribution is inspired by the thought-provoking article ‘Monopolizing War’ by Eyal Benvenisti and Doreen Lustig. My Reply argues that early 19th-century IHL codification projects in the eyes of European governments did not primarily serve domestic anti-revolutionary purposes. It also takes a somewhat sceptical stance as to the recent scholarly trend, which reduces historical explanations for the development of international law to domestic contexts in one or more powerful states involved in the respective law- and policy-making process. Building on the intriguing historical critique of early IHL’s ‘humanizing substance’ developed in ‘Monopolizing War’ and by referring to more recent IHL codification projects (small arms, nuclear weapons, aerial bombing, autonomous weapons), the second part of the contribution sketches four ‘de-humanizing’ discursive strategies, which arguably haunt international humanitarian law-making until today: (i) cynical window dressing; (ii) constructing an ontological wall; (iii) utilitarian reasoning; and (iv) excluding the periphery.
ImageNet performance correlates with pose estimation robustness and generalization on out-of-domain data
2020-07-17

Neural networks are highly effective tools for pose estimation. However, robustness to outof-domain data remains a challenge, especially for small training sets that are common for real world applications. Here, we probe the generalization ability with three architecture classes (MobileNetV2s, ResNets, and EfficientNets). We developed a novel dataset of 30 horses that allowed for both “within-domain” and “out-of-domain” (unseen horse) benchmarking - this is a crucial test for robustness that current human pose estimation benchmarks do not directly address. We show that better ImageNet-performing architectures perform better on both within- and out-of-domain data if they are first pretrained on ImageNet. Our results demonstrate that transfer learning is beneficial for out-of-domain robustness.
SemEval-2020 Task 12: Multilingual Offensive Language Identification in Social Media (OffensEval 2020)
2020-07-17

The task involves three subtasks corresponding to the hierarchical taxonomy of the OLID schema (Zampieri et al., 2019) from OffensEval 2019. The task featured five languages and this upload is for the English language. In addition, English also featured Subtasks B and C. OffensEval 2020 was one of the most popular tasks at SemEval-2020 attracting a large number of participants across all subtasks and also across all languages. A total of 528 teams signed up to participate in the task, 145 teams submitted systems during the evaluation period, and 70 submitted system description papers. This upload includes a test set used in the paper describing the dataset used in the shared task as well as the official test set used in the shared task. The evaluation phase for English is available on Codalab: https://competitions.codalab.org/competitions/23285 The Website for the shared task is https://sites.google.com/site/offensevalsharedtask/home
Transformation Products (TPs) of Cyanobacterial Metabolites During Treatment
2020-07-17

Biological and advanced chemical treatment of cyanotoxins and other cyanobacteria-related&#13;\\ncontaminants such as taste and odor compounds, results in the formation of myriad transformation products (TPs) prior to their mineralization to simpler compounds such as H2O and&#13;\\nCO2. This chapter gives an overview of the TPs formed for the major groups of cyanotoxins,&#13;\\nwith both biological and chemical treatment processes. In addition, it provides detailed explanations on the mechanistic steps followed that lead up to the formation of stable TPs for each&#13;\\noxidant used. It becomes apparent that besides the oxidizing ability of each oxidant, TP formation can be affected by the experimental conditions used, including oxidant and catalyst dose,&#13;\\nsolution pH, and presence of scavengers. Finally, the toxic potential of TPs is discussed.
Text comprehension and learning from text: An introduction
2020-07-17

In the past years the domain of text comprehension has been an object of intensive research endeavours. This introduction presents an overview of the key concepts discussed in the subsequent chapters of this book. The book deals with the significance of different text structures and its cognitive processing in learning from texts. It treats the effect of learning abilities and attitudes for learning from texts. The book focuses on the significance of processing and learning strategies for text comprehension. It is concerned with the significance of pragmatic knowledge about rhetorical structures, apart from the content knowledge about a domain, especially concerning more difficult texts. The book describes that process of knowledge acquisition from texts can be fostered by supporting and enhancing appropriate learning activities.
Mitochondrial damage-associated inflammation highlights biomarkers in PRKN/PINK1 parkinsonism
2020-07-19

Abstract There is increasing evidence for a role of inflammation in Parkinson’s disease. Recent research in murine models suggests that parkin and PINK1 deficiency leads to impaired mitophagy, which causes the release of mitochondrial DNA (mtDNA), thereby triggering inflammation. Specifically, the CGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway mitigates activation of the innate immune system, quantifiable as increased interleukin-6 (IL6) levels. However, the role of IL6 and circulating cell-free mtDNA in unaffected and affected individuals harbouring mutations in PRKN/PINK1 and idiopathic Parkinson’s disease patients remain elusive. We investigated IL6, C-reactive protein, and circulating cell-free mtDNA in serum of 245 participants in two cohorts from tertiary movement disorder centres. We performed a hypothesis-driven rank-based statistical approach adjusting for multiple testing. We detected (i) elevated IL6 levels in patients with biallelic PRKN/PINK1 mutations compared to healthy control subjects in a German cohort, supporting the concept of a role for inflammation in PRKN/PINK1-linked Parkinson’s disease. In addition, the comparison of patients with biallelic and heterozygous mutations in PRKN/PINK1 suggests a gene dosage effect. The differences in IL6 levels were validated in a second independent Italian cohort; (ii) a correlation between IL6 levels and disease duration in carriers of PRKN/PINK1 mutations, while no such association was observed for idiopathic Parkinson’s disease patients. These results highlight the potential of IL6 as progression marker in Parkinson’s disease due to PRKN/PINK1 mutations; (iii) increased circulating cell-free mtDNA serum levels in both patients with biallelic or with heterozygous PRKN/PINK1 mutations compared to idiopathic Parkinson’s disease, which is in line with previous findings in murine models. By contrast, circulating cell-free mtDNA concentrations in unaffected heterozygous carriers of PRKN/PINK1 mutations were comparable to control levels; and (iv) that circulating cell-free mtDNA levels have good predictive potential to discriminate between idiopathic Parkinson’s disease and Parkinson’s disease linked to heterozygous PRKN/PINK1 mutations, providing functional evidence for a role of heterozygous mutations in PRKN or PINK1 as Parkinson’s disease risk factor. Taken together, our study further implicates inflammation due to impaired mitophagy and subsequent mtDNA release in the pathogenesis of PRKN/PINK1-linked Parkinson’s disease. In individuals carrying mutations in PRKN/PINK1, IL6 and circulating cell-free mtDNA levels may serve as markers of Parkinson’s disease state and progression, respectively. Finally, our study suggests that targeting the immune system with anti-inflammatory medication holds the potential to influence the disease course of Parkinson’s disease, at least in this subset of patients.