julilili42/papers huggingface dataset:
On Assessing Trustworthy AI in Healthcare. Machine Learning as a Supportive Tool to Recognize Cardiac Arrest in Emergency Calls
2021-07-08

Artificial Intelligence (AI) has the potential to greatly improve the delivery of healthcare and other services that advance population health and wellbeing. However, the use of AI in healthcare also brings potential risks that may cause unintended harm. To guide future developments in AI, the High-Level Expert Group on AI set up by the European Commission (EC), recently published ethics guidelines for what it terms “trustworthy” AI. These guidelines are aimed at a variety of stakeholders, especially guiding practitioners toward more ethical and more robust applications of AI. In line with efforts of the EC, AI ethics scholarship focuses increasingly on converting abstract principles into actionable recommendations. However, the interpretation, relevance, and implementation of trustworthy AI depend on the domain and the context in which the AI system is used. The main contribution of this paper is to demonstrate how to use the general AI HLEG trustworthy AI guidelines in practice in the healthcare domain. To this end, we present a best practice of assessing the use of machine learning as a supportive tool to recognize cardiac arrest in emergency calls. The AI system under assessment is currently in use in the city of Copenhagen in Denmark. The assessment is accomplished by an independent team composed of philosophers, policy makers, social scientists, technical, legal, and medical experts. By leveraging an interdisciplinary team, we aim to expose the complex trade-offs and the necessity for such thorough human review when tackling socio-technical applications of AI in healthcare. For the assessment, we use a process to assess trustworthy AI, called 1 Z-Inspection ® to identify specific challenges and potential ethical trade-offs when we consider AI in practice.
Immunopeptidomics-Guided Warehouse Design for Peptide-Based Immunotherapy in Chronic Lymphocytic Leukemia
2021-07-08

Antigen-specific immunotherapies, in particular peptide vaccines, depend on the recognition of naturally presented antigens derived from mutated and unmutated gene products on human leukocyte antigens, and represent a promising low-side-effect concept for cancer treatment. So far, the broad application of peptide vaccines in cancer patients is hampered by challenges of time- and cost-intensive personalized vaccine design, and the lack of neoepitopes from tumor-specific mutations, especially in low-mutational burden malignancies. In this study, we developed an immunopeptidome-guided workflow for the design of tumor-associated off-the-shelf peptide warehouses for broadly applicable personalized therapeutics. Comparative mass spectrometry-based immunopeptidome analyses of primary chronic lymphocytic leukemia (CLL) samples, as representative example of low-mutational burden tumor entities, and a dataset of benign tissue samples enabled the identification of high-frequent non-mutated CLL-associated antigens. These antigens were further shown to be recognized by pre-existing and de novo induced T cells in CLL patients and healthy volunteers, and were evaluated as pre-manufactured warehouse for the construction of personalized multi-peptide vaccines in a first clinical trial for CLL (NCT04688385). This workflow for the design of peptide warehouses is easily transferable to other tumor entities and can provide the foundation for the development of broad personalized T cell-based immunotherapy approaches.
Combining EQ-5D-5L items into a level summary score: demonstrating feasibility using non-parametric item response theory using an international dataset
2021-07-08

Abstract Background The EQ-5D-5L is a well-established health questionnaire that estimates health utilities by applying preference-based weights. Limited work has been done to examine alternative scoring approaches when utility weights are unavailable or inapplicable. We examined whether the Mokken scaling approach can elucidate 1) if the level summary score is appropriate for the EQ-5D-5L and 2) an interpretation of such a score. Methods The R package “mokken” was used to assess monotonicity (scaling coefficients H, automated item selection procedure) and manifest invariant item ordering (MIIO: paired item response functions [IRF], H T ). We used a rich dataset (the Multiple Instrument Comparison, MIC) which includes EQ-5D-5L data from six Western countries. Results While all EQ-5D-5L items demonstrated monotonicity, the anxiety/depression (AD) item had weak scalability (H i = 0.377). Without AD, scalability improved from H s = 0.559 to H s = 0.714. MIIO revealed that the 5 items can be ordered, and the ordering is moderately accurate in the MIC data (H T = 0.463). Excluding AD, H T improves to 0.743. Results were largely consistent across disease and country subgroups. Discussion The 5 items of the EQ-5D-5L form a moderate to strong Mokken scale, enabling persons to be ordered using the level summary score. Item ordering suggests that the lower range of the score represents mainly problems with pain and anxiety/depression, the mid-range indicates additional problems with mobility and usual activities, and middle to higher range of scores reveals additional limitations with self-care. Scalability and item ordering are even stronger when the anxiety/depression item is not included in the scale.
Data-driven detection of counterpressing in professional football
2021-07-08

Abstract Detecting counterpressing is an important task for any professional match-analyst in football (soccer), but is being done exclusively manually by observing video footage. The purpose of this paper is not only to automatically identify this strategy, but also to derive metrics that support coaches with the analysis of transition situations. Additionally, we want to infer objective influence factors for its success and assess the validity of peer-created rules of thumb established in by practitioners. Based on a combination of positional and event data we detect counterpressing situations as a supervised machine learning task. Together, with professional match-analysis experts we discussed and consolidated a consistent definition, extracted 134 features and manually labeled more than 20, 000 defensive transition situations from 97 professional football matches. The extreme gradient boosting model—with an area under the curve of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>87.4</mml:mn> <mml:mo>%</mml:mo> </mml:mrow> </mml:math> on the labeled test data—enabled us to judge how quickly teams can win the ball back with counterpressing strategies, how many shots they create or allow immediately afterwards and to determine what the most important success drivers are. We applied this automatic detection on all matches from six full seasons of the German Bundesliga and quantified the defensive and offensive consequences when applying counterpressing for each team. Automating the task saves analysts a tremendous amount of time, standardizes the otherwise subjective task, and allows to identify trends within larger data-sets. We present an effective way of how the detection and the lessons learned from this investigation are integrated effectively into common match-analysis processes.
Changing Gears – DBS For Dopaminergic Desensitization in Parkinson's Disease?
2021-07-08

In Parkinson's disease, both motor and neuropsychiatric complications unfold as a consequence of both incremental striatal dopaminergic denervation and intensifying long‐term dopaminergic treatment. Together, this leads to ‘dopaminergic sensitization’ steadily increasing motor and behavioral responses to dopaminergic medication that result in the detrimental sequalae of long‐term dopaminergic treatment. We review the clinical presentations of ‘dopaminergic sensitization’, including rebound off and dyskinesia in the motor domain, and neuropsychiatric fluctuations and behavioral addictions with impulse control disorders and dopamine dysregulation syndrome in the neuropsychiatric domain. We summarize state‐of‐the‐art deep brain stimulation, and show that STN‐DBS allows dopaminergic medication to be tapered, thus supporting dopaminergic desensitization. In this framework, we develop our integrated debatable viewpoint of “changing gears”, that is we suggest rethinking earlier use of subthalamic nucleus deep brain stimulation, when the first clinical signs of dopaminergic motor or neuropsychiatric complications emerge over the steadily progressive disease course. In this sense, subthalamic deep brain stimulation may help reduce longitudinal motor and neuropsychiatric symptom expression – importantly, not by neuroprotection but by supporting dopaminergic desensitization through postoperative medication reduction. Therefore, we suggest considering STN‐DBS early enough before patients encounter potentially irreversible psychosocial consequences of dopaminergic complications, but importantly not before a patient shows first clinical signs of dopaminergic complications. We propose to consider neuropsychiatric dopaminergic complications as a new inclusion criterion in addition to established motor criteria, but this concept will require validation in future clinical trials. ANN NEUROL 2021;90:699–710
KCND2 variants associated with global developmental delay differentially impair Kv4.2 channel gating
2021-07-08

Abstract Here, we report on six unrelated individuals, all presenting with early-onset global developmental delay, associated with impaired motor, speech and cognitive development, partly with developmental epileptic encephalopathy and physical dysmorphisms. All individuals carry heterozygous missense variants of KCND2, which encodes the voltage-gated potassium (Kv) channel α-subunit Kv4.2. The amino acid substitutions associated with the variants, p.(Glu323Lys) (E323K), p.(Pro403Ala) (P403A), p.(Val404Leu) (V404L) and p.(Val404Met) (V404M), affect sites known to be critical for channel gating. To unravel their likely pathogenicity, recombinant mutant channels were studied in the absence and presence of auxiliary β-subunits under two-electrode voltage clamp in Xenopus oocytes. All channel mutants exhibited slowed and incomplete macroscopic inactivation, and the P403A variant in addition slowed activation. Co-expression of KChIP2 or DPP6 augmented the functional expression of both wild-type and mutant channels; however, the auxiliary β-subunit-mediated gating modifications differed from wild type and among mutants. To simulate the putative setting in the affected individuals, heteromeric Kv4.2 channels (wild type + mutant) were studied as ternary complexes (containing both KChIP2 and DPP6). In the heteromeric ternary configuration, the E323K variant exhibited only marginal functional alterations compared to homomeric wild-type ternary, compatible with mild loss-of-function. By contrast, the P403A, V404L and V404M variants displayed strong gating impairment in the heteromeric ternary configuration, compatible with loss-of-function or gain-of-function. Our results support the etiological involvement of Kv4.2 channel gating impairment in early-onset monogenic global developmental delay. In addition, they suggest that gain-of-function mechanisms associated with a substitution of V404 increase epileptic seizure susceptibility.
Bonding Behavior of Conventional PMMA towards Industrial CAD/CAM PMMA and Artificial Resin Teeth for Complete Denture Manufacturing in a Digital Workflow
2021-07-08

When applying a digital workflow, custom artificial resin teeth have to be integrated into a milled complete denture base, using polymethylmethacrylate (PMMA) applied with a powder–liquid technique. Debonding of denture teeth from dentures is reported to be a frequent complication. No evidence is provided as to which method of surface treatment may enhance the bonding strength. The bonding strength between artificial teeth and PMMA (Group A, n = 60), as well as between the PMMA and industrial PMMA (Group B, n = 60), was investigated following no treatment, monomer application, sandblasting, oxygen plasma, and nitrogen plasma treatment. Surface-roughness values and SEM images were obtained for each group. Shear bond strength (SBS) and fracture mode were analyzed after thermocycling. Within Group A, statistically significant higher SBS was found for all surface treatments, except for nitrogen plasma. In Group B, only nitrogen plasma showed a statistically lower SBS compared to the reference group which was equivalent to all surface treatments. Conclusions: Within the limitations of the present study, the monomer application can be proposed as the most effective surface-treatment method to bond custom artificial teeth into a milled PMMA denture base, whereas nitrogen plasma impairs the bonding strength.
FHL-1 interacts with human RPE cells through the α5β1 integrin and confers protection against oxidative stress
2021-07-08

Abstract Retinal pigment epithelial (RPE) cells that underlie the neurosensory retina are essential for the maintenance of photoreceptor cells and hence vision. Interactions between the RPE and their basement membrane, i.e. the inner layer of Bruch’s membrane, are essential for RPE cell health and function, but the signals induced by Bruch’s membrane engagement, and their contributions to RPE cell fate determination remain poorly defined. Here, we studied the functional role of the soluble complement regulator and component of Bruch’s membrane, Factor H-like protein 1 (FHL-1). Human primary RPE cells adhered to FHL-1 in a manner that was eliminated by either mutagenesis of the integrin-binding RGD motif in FHL-1 or by using competing antibodies directed against the α5 and β1 integrin subunits. These short-term experiments reveal an immediate protein-integrin interaction that were obtained from primary RPE cells and replicated using the hTERT-RPE1 cell line. Separate, longer term experiments utilising RNAseq analysis of hTERT-RPE1 cells bound to FHL-1, showed an increased expression of the heat-shock protein genes HSPA6 , CRYAB , HSPA1A and HSPA1B when compared to cells bound to fibronectin (FN) or laminin (LA). Pathway analysis implicated changes in EIF2 signalling, the unfolded protein response, and mineralocorticoid receptor signalling as putative pathways. Subsequent cell survival assays using H 2 O 2 to induce oxidative stress-induced cell death suggest hTERT-RPE1 cells had significantly greater protection when bound to FHL-1 or LA compared to plastic or FN. These data show a non-canonical role of FHL-1 in protecting RPE cells against oxidative stress and identifies a novel interaction that has implications for ocular diseases such as age-related macular degeneration.
Culture Media Based on Leaf Strips/Root Segments Create Compatible Host/Organ Setup for in vitro Cultivation of Plant Microbiota
2021-07-08

Plant microbiota have co-evolved with their associated plants in the entire holobiont, and their assemblages support diversity and productivity on our planet. Of importance is in vitro cultivation and identification of their hub taxa for possible core microbiome modification. Recently, we introduced the in situ-similis culturing strategy, based on the use of plant leaves as a platform for in vitro growth of plant microbiota. Here, the strategy is further extended by exploring plant organ compatible cultivation of plant microbiota when grown on corresponding leaf/root-based culture media. Pooling the advantages of MPN enrichment methodology together with natural plant-only-based culture media, the introduced method efficiently constructed a nutritional milieu governed by vegan nutrients of plant origin, i.e., leaf strips/root segments, immersed in plain semi-solid water agar. MPN estimates exceeded log 7.0 and 4.0 g −1 of endo-rhizosphere and endo-phyllosphere, respectively, of maize and sunflower; being proportionate to those obtained for standard culture media. With sunflower, PCR-DGGE analyses indicated divergence in community composition of cultivable endophytes primarily attributed to culture media, signaling a certain degree of plant organ affinity/compatibility. Based on 16S rRNA gene sequencing of bacterial isolates, 20 genera comprising 32 potential species were enriched; belonged to Bacteroidetes, Firmicutes, and Alpha-/Gammaproteobacteria. The described cultivation strategy furnished diversified nutritive platform in terms of homologous/heterologous plant organ-based medium and ambient/limited oxygenic cultivation procedure. Duly, cultivability extended to &amp;gt; 8 genera: Bosea, Brevundimonas, Chitinophaga, Pseudoxanthomonas, Sphingobacterium Caulobacter, Scandinavium , and Starkeya ; the latter three genera were not yet reported for Sunflower, and possible unknown species or even one new putative genus. Thus, both potential members of the major microbiome and rare isolates of satellite microbiomes can be isolated using the presented method. It is a feasible addition to traditional cultivation methods to explore new potential resources of PGPB for future biotechnological applications.
Genetics of Paroxysmal Dyskinesia: Novel Variants Corroborate the Role of KCNA1 in Paroxysmal Dyskinesia and Highlight the Diverse Phenotypic Spectrum of KCNA1- and SLC2A1-Related Disorders
2021-07-08

Paroxysmal dyskinesias (PxD) are rare movement disorders with characteristic episodes of involuntary mixed hyperkinetic movements. Scientific efforts and technical advances in molecular genetics have led to the discovery of a variety of genes associated with PxD; however, clinical and genetic information of rarely affected genes or infrequent variants is often limited. In our case series, we present two individuals with PxD including one with classical paroxysmal kinesigenic dyskinesia, who carry new likely pathogenic de novo variants in KCNA1 (p.Gly396Val and p.Gly396Arg). The gene has only recently been discovered to be causative for familial paroxysmal kinesigenic dyskinesia. We also provide genetic evidence for pathogenicity of two newly identified disease-causing variants in SLC2A1 (p.Met96Thr and p.Leu231Pro) leading to paroxysmal exercise-induced dyskinesia. Since clinical information of carriers of variants in known disease-causing genes is often scarce, we encourage to share clinical data of individuals with rare or novel (likely) pathogenic variants to improve disease understanding.
Relative Camera Pose Estimation using Synthetic Data with Domain Adaptation via Cycle-Consistent Adversarial Networks
2021-07-08

Abstract Learning-based visual localization has become prospective over the past decades. Since ground truth pose labels are difficult to obtain, recent methods try to learn pose estimation networks using pixel-perfect synthetic data. However, this also introduces the problem of domain bias. In this paper, we first build a Tuebingen Buildings dataset of RGB images collected by a drone in urban scenes and create a 3D model for each scene. A large number of synthetic images are generated based on these 3D models. We take advantage of image style transfer and cycle-consistent adversarial training to predict the relative camera poses of image pairs based on training over synthetic environment data. We propose a relative camera pose estimation approach to solve the continuous localization problem for autonomous navigation of unmanned systems. Unlike those existing learning-based camera pose estimation methods that train and test in a single scene, our approach successfully estimates the relative camera poses of multiple city locations with a single trained model. We use the Tuebingen Buildings and the Cambridge Landmarks datasets to evaluate the performance of our approach in a single scene and across-scenes. For each dataset, we compare the performance between real images and synthetic images trained models. We also test our model in the indoor dataset 7Scenes to demonstrate its generalization ability.
Search for TeV emission from the Fermi Bubbles at low Galactic latitudes with H.E.S.S. inner Galaxy survey
2021-07-08

The Fermi Bubbles were discovered about a decade ago in the Fermi-LAT data as a double-lobe structure extending up to 55° in Galactic latitudes above and below the Galactic Center. At the moment their origin is still unknown. The H.E.S.S. collaboration is currently performing the first ever survey in TeV gamma rays of the Milky Way inner region: the Inner Galaxy Survey.\\nThis survey is intended to achieve the best sensitivity to faint and diffuse emissions in a region\\nof several degrees around the Galactic Centre. It provides an unprecedented sensitivity to dark\\nmatter signals, new diffuse emissions, and TeV outflows from the Galactic Centre. Understanding the properties of the Fermi Bubbles at low Galactic latitudes will provide key insights into their origin. We search for TeV emission at the base of the Fermi Bubbles using low-latitude spatial templates. The first results obtained with the 2014-2020 H.E.S.S. observations will be reported.
Mattering and parental presence in systemic therapy using nonviolent resistance: The utilization of imaginary methods
2021-07-08

An empowered sense of “self” is crucial for emotional well‐being and positive relationships. Certain family interaction patterns can disrupt the adult's sense of “mattering” to the child, eroding their perceived self‐efficacy. Mattering can be understood as a felt sense of relational agency which is necessary for experiencing one's interactions as meaningful, effective, and self‐determined. When parents generate more positive future narratives in co‐creation with their therapist, their sense of relevance to a child can be restored. In this way, more constructive forms of interaction can emerge with their child which has hitherto eschewed their care. This article aims to provide a conceptual basis for addressing an absence of reciprocity, where children demonstrate harmful or self‐destructive behavior and refuse to cooperate in therapy. In such instances, one‐sided parental action, utilizing nonviolent resistance methods, can influence relational dynamics. Imaginary methods can then facilitate shifts to psychological states in which the parent internally experiences efficacy and mattering more often without requiring validation from the “physical child” in the here and now. We introduce examples of specific imaginary techniques, which in our clinical practice have shown to facilitate such shifts in parents. We discuss neuroscientific theories that may account for their powerful impact we witness in our clinical experience.
Optical Sectioning and Visualization of the Intervertebral Disc from Embryonic Development to Degeneration
2021-07-08

Intervertebral disc (IVD) degeneration is a leading cause of low back pain and it entails a high degree of impairment for the affected individuals. To decode disc degeneration and to be able to develop regenerative approaches a thorough understanding of the cellular biology of the IVD is essential. One aspect of this biology that still remains unanswered is the question of how cells are spatially arranged in a physiological state and during degeneration. The biological properties of the IVD and its availability make this tissue difficult to analyze. The present study investigates spatial chondrocyte organization in the anulus fibrosus from early embryonic development to end-stage degeneration. An optical sectioning method (Apotome) is applied to perform high resolution staining analyses using bovine embryonic tissue as an animal model and human disc tissue obtained from patients undergoing spine surgery. From a very high chondrocyte density in the early embryonic bovine disc, the number of cells decreases during gestation, growth, and maturation. In human discs, an increase in cellular density accompanied the progression of tissue degeneration. As had already been demonstrated in articular cartilage, cluster formation represents a characteristic feature of advanced disc degeneration.