Quality-dependent Deep Learning for Safe Autonomous Guidewire Navigation

Cardiovascular diseases are the main cause ofdeath worldwide. State-of-the-art treatment often includes theprocess of navigating endovascular instruments through thevasculature. Automation of the procedure receives much at-tention lately and may increase treatment quality and unburdenclinicians. However, in order to ensure the patient’s safety theendovascular device needs to be steered carefully through thebody. In this work, we present a collection of medical criteriathat are considered by physicians during an intervention andthat can be evaluated automatically enabling a highly objectiveassessment. Additionally, we trained an autonomous controllerwith deep reinforcement learning to gently navigate within a2D simulation of an aortic arch. Among others, the controllerreduced the maximum and mean contact force applied to thevessel walls by 43% and 29%, respectively

Learning-based autonomous vascular guidewire navigation without human demonstration in the venous system of a porcine liver

Purpose The navigation of endovascular guidewires is a dexterous task where physicians and patients can benefit from automation. Machine learning-based controllers are promising to help master this task. However, human-generated training data are scarce and resource-intensive to generate. We investigate if a neural network-based controller trained without human-generated data can learn human-like behaviors. Methods We trained and evaluated a neural network-based controller via deep reinforcement learning in a finite element simulation to navigate the venous system of a porcine liver without human-generated data. The behavior is compared to manual expert navigation, and real-world transferability is evaluated. Results The controller achieves a success rate of 100% in simulation. The controller applies a wiggling behavior, where the guidewire tip is continuously rotated alternately clockwise and counterclockwise like the human expert applies. In the ex vivo porcine liver, the success rate drops to 30%, because either the wrong branch is probed, or the guidewire becomes entangled. Conclusion In this work, we prove that a learning-based controller is capable of learning human-like guidewire navigation behavior without human-generated data, therefore, mitigating the requirement to produce resource-intensive human-generated training data. Limitations are the restriction to one vessel geometry, the neglected safeness of navigation, and the reduced transferability to the real world

B Cell Characteristics at Baseline Predict Vaccination Response in RTX Treated Patients

Background: Vaccination is considered as most efficient strategy in controlling SARS-CoV-2 pandemic spread. Nevertheless, patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) are at increased risk to fail humoral and cellular responses upon vaccination. The ability to predict vaccination responses is essential to guide adequate safety and optimal protection in these patients. Methods: B- and T- cell data before vaccination were evaluated for characteristics predicting vaccine responses in altogether 15 patients with autoimmune inflammatory rheumatic diseases receiving RTX. Eleven patients with rheumatoid arthritis (RA) on other therapies, 11 kidney transplant recipients (KTR) on regular immunosuppression and 15 healthy controls (HC) served as controls. A multidimensional analysis of B cell subsets via UMAP algorithm and a correlation matrix were performed in order to identify predictive markers of response in patients under RTX therapy. Results: Significant differences regarding absolute B cell counts and specific subset distribution pattern between the groups were identified at baseline. In this context, the majority of B cells from vaccination responders of the RTX group (RTX IgG+) were naïve and transitional B cells, whereas vaccination non-responders (RTX IgG-) carried preferentially plasmablasts and double negative (CD27-IgD-) B cells. Moreover, there was a positive correlation between neutralizing antibodies and B cells expressing HLA-DR and CXCR5 as well as an inverse correlation with CD95 expression and CD21low expression by B cells among vaccination responders. Summary: Substantial repopulation of the naïve B cell compartment after RTX therapy appeared to be essential for an adequate vaccination response, which seem to require the additional capability of antigen presentation and germinal center formation. Moreover, expression of exhaustion markers represent negative predictors of vaccination responses

Movement disorders after hypoxic brain injury following cardiac arrest in adults

Background and purpose: Post-hypoxic movement disorders and chronic post-hypoxic myoclonus are rare complications after cardiac arrest in adults. Our study investigates the clinical spectrum, neuroimaging results, therapy and prognosis of these debilitating post-hypoxic sequelae. Methods: This retrospective study included 72 patients from the neurological intensive care unit at a university hospital, who were diagnosed with hypoxic-ischaemic encephalopathy after cardiac arrest between January 2007 and September 2018. Clinical records were screened for occurrence of post-hypoxic movement disorders and chronic post-hypoxic myoclonus. Affected patients were further analysed for applied neuroprognostic tests, administered therapy and treatment response, and the outcome of these movement disorders and neurological function. Results: Nineteen out of 72 screened patients exhibited post-hypoxic motor symptoms. Basal ganglia injury was the most likely neuroanatomical correlate of movement disorders as indicated by T1 hyperintensities and hypometabolism of this region in magnetic resonance imaging and positron emission tomography computed tomography. Levomepromazine and intrathecal baclofen showed first promising and mostly prompt responses to control these post-hypoxic movement disorders and even hyperkinetic storms. In contrast, chronic post-hypoxic myoclonus best responded to co-application of clonazepam, levetiracetam and primidone. Remission rates of post-hypoxic movement disorders and chronic post-hypoxic myoclonus were 58% and 50%, respectively. Affected patients seemed to present a rather good recovery of cognitive functions in contrast to the often more severe physical deficits. Conclusions: Post-hypoxic movement disorders associated with pronounced basal ganglia dysfunction might be efficiently controlled by levomepromazine or intrathecal baclofen. Their occurrence might be an indicator for a more unfavourable, but often not devastating, neurological outcome

Altered increase in STAT1 expression and phosphorylation in severe COVID‐19

The interferon pathway, a key antiviral defense mechanism, is being considered as a therapeutic target in COVID-19. Both, substitution of interferon and JAK/STAT inhibition to limit cytokine storms have been proposed. However, little is known about possible abnormalities in STAT signaling in immune cells during SARS-CoV-2 infection. We investigated downstream targets of interferon signaling, including STAT1, STAT2, pSTAT1 and 2, and IRF1, 7 and 9 by flow cytometry in 30 patients with COVID-19, 17 with mild, and 13 with severe infection. We report upregulation of STAT1 and IRF9 in mild and severe COVID-19 cases, which correlated with the IFN-signature assessed by Siglec-1 (CD169) expression on peripheral monocytes. Interestingly, Siglec-1 and STAT1 in CD14+ monocytes and plasmablasts showed lower expression among severe cases compared to mild cases. Contrary to the baseline STAT1 expression, the phosphorylation of STAT1 was enhanced in severe COVID-19 cases, indicating a dysbalanced JAK/STAT signaling that fails to induce transcription of interferon stimulated response elements (ISRE). This abnormality persisted after IFN-alpha and IFN-gamma stimulation of PBMCs from patients with severe COVID-19. Data suggest impaired STAT1 transcriptional upregulation among severely infected patients may represent a potential predictive biomarker and would allow stratification of patients for certain interferon-pathway targeted treatments

dolls/puppets in threat scenarios

Puppen in Bedrohungsszenarien – so lautet der Themenschwerpunkt der ersten Ausgabe der interdisziplinären online-Zeitschrift "denkste: puppe / just a bit of: doll" zu Mensch-Puppen-Diskursen (Akronym: de:do). Die Bezeichnung ‚Puppe’ steht dabei für anthropomorphe ,Wesen’ und Artefakte in all ihren unterschiedlichen Erscheinungsformen und der Begriff der Bedrohung wird hier weit gefasst. Ausgangspunkt der Entscheidung für diesen Fokus war die Annahme, dass Puppen und puppenaffinen Artefakten sowohl in Zeiten existenzieller Bedrohung als auch in Phasen innerpsychischer Beunruhigung und Irritation eine besondere Bedeutung zukommt. Die hier einbezogenen Beiträge stammen aus unterschiedlichen Fachdisziplinen und eröffnen in der bewusst nicht disziplinär ausgerichteten Zusammenstellung reizvolle multiperspektivische Mensch-Puppen-Diskurse. Dabei sind nicht nur die hier angesprochenen Themenbezüge, sondern auch die jeweiligen methodischen Zugänge ausgesprochen heterogen. So werden Puppen-Narrative aufgegriffen, die beispielsweise innerhalb der Literaturwissenschaft an die lange Tradition von Puppen-Erzählungen anknüpfen, aber auch solche, die aktuell in den Diskursen über Zukunftsszenarien und neue Technologien mittels verschiedener medialer Formate und/oder künstlerischer Aktionen für Diskussionsstoff sorgen. Ein erster thematischer Fokus liegt auf der Bedeutung von Puppen im Zuge der Erfahrung von Bedrohung und Verlusten im Kontext von Krieg, Flucht und Verfolgung in politisch unsicheren Zeiten. Hier werden aus verschiedenen fachdisziplinären Perspektiven unterschiedliche Facetten von Bedrohungsszenarien angesprochen. So geht es aus theaterwissenschaftlicher Sicht um zwei Inszenierungen aus dem Bereich des Objekt- und Materialtheaters, in denen bedrohliche Kriegsdarstellungen mittels Plastikpuppen bzw. amorphen Materials aufbereitet werden. Aus psychologischer Perspektive kommen Rollen und Funktionen von Puppen als Übergangsobjekte im Kontext von Umbrüchen, Krieg und Gewalt zur Sprache. In zwei literaturwissenschaftlichen Beiträgen wird jeweils ein Roman aus der Kinder- und Jugendliteratur analysiert, in denen in einem Fall eine Puppe zur psychischen Stabilisierung der literarischen Protagonistin beiträgt und im anderen Fall das Schicksal der Puppe die Geschichte von Abschied und letztendlicher Vernichtung ihrer Besitzerin erzählt und symbolisiert. Und schließlich geht es um den Stellenwert von Puppen und Teddys in verschiedenen Kinderzeitschriften, die – in den politisch unsicheren Zeiten zwischen und nach den beiden Weltkriegen – Identifikationsfiguren und Interaktionspartner für Kinder sein können. Ein zweiter Fokus thematisiert Puppen und ihre Narrative im Kontext verschiedener aversiver Erfahrungen sowie in Zeiten psychischer Irritation. So geht es zum einen um die literaturwissenschaftliche Sicht auf die Bedeutung und Wirkung von Puppen in zwei ‚klassischen’ Puppenerzählungen: „"Nussknacker und Mausekönig" von E.T.A. Hoffmann und "Romeo und Julia auf dem Dorfe" von Gottfried Keller. Zum anderen werden in verschiedenen Beiträgen Entgrenzungs-, Transformations- und Identitätsfragen in Mensch-Puppen-Bezügen aus medien- und kunstwissenschaftlicher sowie kinderliterarischer Perspektive angesprochen, in denen Puppen in Gestalt von Androiden, Kunstwesen oder anthropomorphen Figuren agieren und dabei selber Irritationen auslösen oder Versuche darstellen, Antworten auf beunruhigende Fragen zu finden. Über den Themenschwerpunkt hinaus finden sich zudem eine Reihe weiterer Beitragsformen zu verschiedenen puppenbezogenen Themen und Praxen, die noch einmal das breite Spektrum unterschiedlicher Puppen-Narrative und Zugangsformen dokumentieren: So beschäftigt sich ein freier Beitrag mit dem Puppenspiel als strukturiertes Therapieangebot für Kinder, bei den Miszellen findet sich eine Skizze zu Marlene Dietrich und ihren Puppen sowie ein kurzer Essay zu einer biographischen Erinnerung, ein Interview mit der Begründerin des Berliner Puppentheaters bubales veranschaulicht Möglichkeiten der dramatischen und poetischen Umsetzung von Puppen-Themen, im Diskussionsforum wird ein kritischer Blick auf "Barbie als Diskursmaschine" geworfen und eine Rezension zum Ausstellungskatalog "From Her Wooden Sleep von Ydessa Hendels" lotet Chancen und Grenzen der künstlerischen Arbeit mit Puppen-Artefakten aus.Dolls / Puppets in Threat Scenarios – this is the topic focus of the first issue of the interdisciplinary online magazine "denkste: puppe / just a bit of: doll" on human-doll discourses (acronym: de: do). The term ’doll’ stands for anthropomorphic ’beings’ and artifacts of all kinds and the concept of threat is broadly defined. This focus was stimulated by the assumption that dolls and doll-related artifacts are of particular importance in times of existential threat as well as in phases of inner psychic anxiety and irritation. Yet, the basically ambiguous character of the doll does not necessarily determine a clear effect, so that its usability always involves a certain blurriness and ambivalence. In threatening and adverse situations dolls can act as companions and significant (transitional) objects, thus allowing psychic stabilization, security, and attachment as well as enabling (inner) autonomy, agency, and developmental processes. But dolls can also be a crucial component of threat scenarios themselves and act frightening in this function. All this applies not only to material and real existing dolls and puppets, but also to dolls as literary and / or media figures as well as to doll narratives of any kind. The articles included here come from different disciplines and open up an appealing and deliberately non-disciplinary oriented human-doll discourse from multiple perspectives. Accordingly, the relevant themes as well as the respective methodological approaches are highly heterogeneous. Thus, some contributions follow the long tradition of doll narratives in literature while others discuss currrent topics and discourses on future scenarios and new technologies by means of various doll-related media formats and / or art performances. A first thematic focus is on the significance of dolls in experiencing threats and losses in the context of war, flight and persecution in times of political uncertainty. Here, different facets of threat scenarios are addressed from different disciplinary perspectives. From the field of object and material theater two productions are introduced in which menacing war scenes are processed by means of plastic dolls or amorphous material. From a psychological perspective, dolls are discussed in their roles and functions as transitional objects within the context of upheaval, war and violence. Furthermore, two literary contributions analyze novels from children’s and youth literature. One story deals with a doll which contributes to the psychological stabilization of the literary protagonist. The other story tells of a girl and her doll which symbolizes the final farewell and eventual annihilation of the (Jewish) girl. Finally, the role of dolls and teddy bears in various children’s magazines is exemplified, which serve as identification figures and interaction partners for children in the politically unstable times between and after the two World Wars. A second focus deals with dolls and their narratives in the context of various aversive experiences as well as in times of psychological irritation. Two contributions analyze the meaning and effect of dolls in two ’classical’ doll narratives from a literary perspective: "Nussknacker und Mausekönig" by E.T.A. Hoffmann and "Romeo und Julia auf dem Dorfe" by Gottfried Keller. Further contributions address questions of ego dissolution, transformation and identity processes in human-doll relations from various perspectives such as media, art and children’s literature. Here, dolls appear as androids, artistic or anthropomorphic figures which cause irritation themselves or attempt to find answers to disturbing human-doll questions. In addition to the main topic, there are also a number of other sections and types of contributions on various doll-related topics and practices which once again document the wide range of doll narratives and possible forms of access: For example, a free contribution deals with doll play as a structured therapy for children, the miscellaneous section includes a portrait of Marlene Dietrich and her dolls as well as a short essay on a biographical reminiscence, an interview with the founder of the Berlin Puppet Theater bubales illustrates the possibilities of dramatic and poetic realization of puppet and doll narratives, a critical view on "Barbie as a discourse machine" is presented in the discussion forum and a review of the exhibition catalog "From Her Wooden Sleep by Ydessa Hendels" explores opportunities and limits of artistic work with doll artifacts

B Cell Numbers Predict Humoral and Cellular Response Upon SARS–CoV-2 Vaccination Among Patients Treated With Rituximab

Objective: Patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) therapy are at higher risk of poor COVID-19 outcomes and show substantially impaired humoral immune response to anti-SARS-CoV-2 vaccine. However, the complex relationship between antigen-specific B cells and T cells and the level of B cell repopulation necessary to achieve anti-vaccine responses remain largely unknown. Methods: Antibody responses to SARS-CoV-2 vaccines and induction of antigen-specific B and CD4/CD8 T cell subsets were studied in 19 patients with rheumatoid arthritis (RA) or antineutrophil cytoplasmic antibody-associated vasculitis receiving RTX, 12 patients with RA receiving other therapies, and 30 healthy controls after SARS-CoV-2 vaccination with either messenger RNA or vector-based vaccines. Results: A minimum of 10 B cells per microliter (0.4% of lymphocytes) in the peripheral circulation appeared to be required for RTX-treated patients to mount seroconversion to anti-S1 IgG upon SARS-CoV-2 vaccination. RTX-treated patients who lacked IgG seroconversion showed reduced receptor-binding domain-positive B cells (P = 0.0005), a lower frequency of Tfh-like cells (P = 0.0481), as well as fewer activated CD4 (P = 0.0036) and CD8 T cells (P = 0.0308) compared to RTX-treated patients who achieved IgG seroconversion. Functionally relevant B cell depletion resulted in impaired interferon-γ secretion by spike-specific CD4 T cells (P = 0.0112, r = 0.5342). In contrast, antigen-specific CD8 T cells were reduced in both RA patients and RTX-treated patients, independently of IgG formation. Conclusion: In RTX-treated patients, a minimum of 10 B cells per microliter in the peripheral circulation is a candidate biomarker for a high likelihood of an appropriate cellular and humoral response after SARS-CoV-2 vaccination. Mechanistically, the data emphasize the crucial role of costimulatory B cell functions for the proper induction of CD4 responses propagating vaccine-specific B cell and plasma cell differentiation