News

Design Lab #13: Material Legacies
The exhibition »Design Lab #13: Material Legacies« at Kunstgewerbemuseum Berlin, opening on November 3rd, 2022, explores contingencies and ruptures between traditional crafts and the most recent developments at the crossroads of material research, design, engineering, and architecture. It brings together artifacts from the museum’s collection with work-in-progress installations by designers and researchers from the Cluster of Excellence »Matters of Activity. Image Space Material« in order to initiate a dialogue about the historical, contemporary, and future conditions under which materiality unfolds.

By engaging with a series of different materials and techniques the exhibition encompasses both the problematization of unsustainable pasts and presents as well as the imagination of speculative material futures. Taking materiality as a starting point, each of the exhibits will investigate its sociocultural, economic, and political context in order to disentangle the multiple interrelations that arise from and with materials. As such »Design Lab #13: Material Legacies« aims to challenge the passive understandings of materiality and associate with the widening discourse on relational knowledge practices in arts, design, humanities, and social science.

The exhibition will be running from 4 November 2022 to 26 February 2023. For the exhibition announcement on the website of the
Staatliche Museen zu Berlin – Preußischer Kulturbesitz.

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Exhibition Opening

3 November 2022, 6 pm

The opening event will include an introduction to the exhibition by Dr. Claudia Banz, Curator of Design at the Kunstgewerbemuseum Berlin, and Prof. Dr. Claudia Mareis, co-director of the Cluster of Excellence »Matters of Activity. Image Space Material«. Moreover, exhibition curators Michaela Büsse and Emile De Visscher will provide background on the exhibition, its goals, and how the curatorial process was undertaken.
The exhibition opening is part of the Berlin Science Week 2022.
Prof. Dr. Georg Lurje
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In recognition of his exceptional achievements in research and teaching, Georg Lurje was honoured to receive an associate professorship in surgery at the Charité – Universitätsmedizin Berlin.

CONGRATULATIONS !
BMBF funds KIARA
With the programme "AI-based assistance systems for process-accompanying health applications", the Federal Ministry of Education and Research (BMBF) is funding innovative research and development work on interactive assistance systems that support processes in clinical health care using artificial intelligence methods.

Together with the partners Gebrüder Martin GmbH & Co. KG, Tuttlingen, HFC Human-Factors-Consult GmbH, Berlin and the Fraunhofer Institute for Telecommunications Heinrich-Hertz-Institut (HHI), Berlin, we successfully applied with the project "AI-based recording of work processes in the operating theatre for the automated compilation of the operating theatre report" (KIARA).


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Operating theatre reports document all relevant information during surgical interventions. They serve to ensure therapeutic safety and accountability and as proof of performance. The preparation of the OR report is time-consuming and ties up valuable working time – time that is then not available for the treatment of patients.

In the KIARA project, we are working on a system that automatically drafts operating theatre reports. The KIARA system is intended to relieve medical staff: it documents operating theatre activities and creates a draft of the report, which then only needs to be checked, completed and approved. The system works via cameras integrated into operating theatre lamps. Their image data is then analysed with the help of artificial intelligence to recognise and record objects, people and all operating theatre activities. The ambitious system is to be developed and tested in a user-centred manner for procedures in the abdominal cavity and in oral and maxillofacial surgery.

KIARA is intended to continuously learn through human feedback and to simplify clinical processes for the benefit of medical staff by automating the creation of operating theatre reports. The system can also be applied to other operating theatre areas in the future.

The project has a financial volume of € 2.16 million.
The kick-off meeting took place on 16.09.2022 at the Charité.
„Si-M-Day“ | November 24th, 2022
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Join us – at our online networking event.
We, the Si-M spokespersons and coordinators, are pleased to invite you to our first symposium „Si-M-Day“ on 24th November from 9 to 14 h – online.
It is dedicated to networking and initiation of projects between investigators of both partner institutions.
Click
here to register until November 18th (abstract submission deadline October 17th).
DFG Walter-Benjamin grant for the investigation of sex as a biological variable in alloimmunity
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With a DFG Walter-Benjamin grant Dr. med. Friederike Martin will join the laboratory of Transplant Surgery Research at Harvard under the direction of Professor Stefan G. Tullius in Boston to investigate the role of biological sex for transplantation outcome.

Influences of donor and recipient sex on transplantation outcome have been described manifold, as well as an influence of sex hormones on the innate and adaptive immune response. So far, research, investigating the impact of sex hormones and different sex- and age-dependent sex-hormone levels on alloimmune response after solid organ transplantation is lacking. The aim of the project “Sex as a biological Variable in Alloimmunity” is, to delineate the impact of sex hormones and especially estrogens and age-dependent changes in estrogen-levels on alloimmune response after allogenic transplantation.  The project is based on the publication “Recipient sex and estradiol levels affect transplant outcomes in an age-specific fashion” published in the AJT in 2021 by the workgroup of Prof. Tullius.

Friederike, who already received the Sanofi Women in Transplantation fellowship grant for research in gender and sex in transplantation in 2021, will work as a Postdoc on this project in the Tullius Lab for an expected 2 years period, starting in January 2023.


Congratulations!
2022 TTS Mentee-Mentor-Award
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Dr. Barbara Kern und Prof. Dr. Stefan G. Tullius received the 2022 Mentee-Mentor-Award of The Transplant Society during the 29th Conference in Buenos Aires.

In collaboration with National and International Societies, TTS acknowledges and recognizes the efforts of scientists who have advanced our understanding of transplantation science and fostered the development of young investigators.
The Mentee-Mentor Awards are designed to encourage dialogue and interactions between trainees and established investigators, and provide financial support for their joint participation in the Congress.

Congratulations!
Active Matter in Robotic-Assisted Surgery
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Tuesday, 12.09.2022 | Cluster Retreat | Matters of Activity

2:30 – 2:45 pm Welcome & Intro
2:45 – 4:15 pm Panel 1
Rasa Weber Product Design (20 Minutes)
Felix Rasehorn Product Design (20 Minutes)
Binru Yang Engineering (20 Minutes)
Panel Discussion (30 Minutes)

4:15 – 4:45 pm Coffee Break
4:45 – 6:15 pm Panel 2
Jakub Rondomanski Mathematics (20 Minutes)
Babette Werner Art and Visual History (20 Minutes)
Anna Schäffner & Dominic Eger Domingos Product Design (20 Minutes)
Panel Discussion (30 Minutes)

6:15–7:30 pm Opening Exhibition und Aperitivo
Solid fraction determines stiffness and viscosity in decellularized pancreatic tissues
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The article „Solid fraction determines stiffness and viscosity in decellularized pancreatic tissues“ in Biomaterials Advances is now available online.
There is free access to a PDF of the article here until August 20, 2022!

The role of extracellular matrix (ECM) composition and turnover in mechano-signaling and the metamorphic fate of cells seeded into decellularized tissue can be elucidated by recent developments in non-invasive imaging and biotechnological analysis methods. Because these methods allow accurate quantification of the composition and structural integrity of the ECM, they can be critical in establishing standardized decellularization protocols. This study proposes quantification of the solid fraction, the single-component fraction and the viscoelasticity of decellularized pancreatic tissues using compact multifrequency magnetic resonance elastography (MRE) to assess the efficiency and quality of decellularization protocols. MRE of native and decellularized pancreatic tissues showed that viscoelasticity parameters depend according to a power law on the solid fraction of the decellularized matrix. The parameters can thus be used as highly sensitive markers of the mechanical integrity of soft tissues. Compact MRE allows consistent and noninvasive quantification of the viscoelastic properties of decellularized tissue. Such a method is urgently needed for the standardized monitoring of decellularization processes, evaluation of mechanical ECM properties, and quantification of the integrity of solid structural elements remaining in the decellularized tissue matrix.

Authors are Joachim Snellings, Eriselda Keshi, Peter Tang, Assal Daneshgar, Esther C. Willma, Luna Haderer, Oliver Klein, Felix Krenzien, Thomas Malink, Patrick Asbach, Johann Pratschke, Igor M. Sauer, Jürgen Braun, Ingolf Sack, and Karl Hillebrandt.

Inaugural Lectures
We are pleased to announce that four members of staff have successfully completed their habilitation work in the last few months!

On
Friday, 08.07.2022 at 15:00 in lecture hall 3 of the teaching building (Forum 3, CVK), Dr. med. habil. Linda Feldbrügge and Dr. med. habil. Paul Ritschl will give their inaugural lectures entitled "New role of surgery in modern tumour and transplant medicine".

On
Friday, 15.07.2022 at 16:30 in the Friedrich Kopsch lecture theatre of the Anatomy Department at Campus Mitte Dr. med. habil. Eva Dobrindt and Dr. med. habil. Rosa Schmuck will present their inaugural lectures with the topic "An Operating Room of One's Own - The Surgeon in Ancient Tradition and Modernity".
This will be followed by a small reception in the park in front of the venue.
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Si-M | Topping-out Ceremony
Today, representatives of Charité – Universitätsmedizin Berlin and Technische Universität Berlin celebrated the topping-out ceremony for the research building "Der Simulierte Mensch" (Si-M, "The Simulated Human") together with political representatives. Guests included the Governing Mayor Franziska Giffey, Senator for Health and Science and Charité Supervisory Board Chair Ulrike Gote and Finance Senator Daniel Wesener.

We are very excited: this will be a great building with even greater content.

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VolumetricOR | Surgical Innovation
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Our paper "VolumetricOR: A new Approach to Simulate Surgical Interventions in Virtual Reality for Training and Education" is available in the latest issue of Surgical Innovation.

Surgical training is primarily carried out through observation during assistance or on-site classes, by watching videos as well as by different formats of simulation. The simulation of physical presence in the operating theatre in virtual reality might complement these necessary experiences. A prerequisite is a new education concept for virtual classes that communicates the unique workflows and decision-making paths of surgical health professions (i.e. surgeons, anesthesiologists, and surgical assistants) in an authentic and immersive way. For this project, media scientists, designers and surgeons worked together to develop the foundations for new ways of conveying knowledge using virtual reality in surgery.
A technical workflow to record and present volumetric videos of surgical interventions in a photorealistic virtual operating room was developed. Situated in the virtual reality demonstrator called VolumetricOR, users can experience and navigate through surgical workflows as if they are physically present . The concept is compared with traditional video-based formats of digital simulation in surgical training.

VolumetricOR let trainees experience surgical action and workflows a) three-dimensionally, b) from any perspective and c) in real scale. This improves the linking of theoretical expertise and practical application of knowledge and shifts the learning experience from observation to participation.
Discussion: Volumetric training environments allow trainees to acquire procedural knowledge before going to the operating room and could improve the efficiency and quality of the learning and training process for professional staff by communicating techniques and workflows when the possibilities of training on-site are limited.

Authors are Moritz Queisner, Michael Pogorzhelskiy, Christopher Remde, Johann Pratschke, and Igor M. Sauer.
Tissue Engineering for the Diaphragm
"Tissue Engineering for the Diaphragm and its Various Therapeutic Possibilities – A Systematic Review" is available here in Advanced Therapeutics (open access).

Diaphragmatic impairments exhibit high morbidity as well as mortality while current treatment options remain unsatisfactory. Tissue engineering (TE) approaches have explored the generation of an optimal biocompatible scaffold for diaphragmatic repair through tissue decellularization or de novo construction, with or without the addition of cells. The authors conducted a systematic review on the current state of the art in diaphragmatic tissue engineering (DTE) and found 24 articles eligible for final synthesis. The included approaches studied decellularization-based graft generation and de novo bioscaffold construction. Three studies focused on in vitro host-scaffold interaction with synthesized, recellularized grafts and decellularized extracellular matrix scaffolds. Another three studies investigated evaluation tools for decellularization efficacy. Among all studies, recellularization is performed in both decellularization-based and de novo generated scaffolds. De novo constructed biocomposites as well as decellularized and recellularized scaffolds induced pro-regenerative remodeling and recovery of diaphragmatic function in all examined animal models. Potential therapeutic applications comprise substance defects requiring patch repair, such as congenital diaphragmatic hernia, and functional diseases demanding an entire organ transplant, like muscular dystrophies or dysfunction after prolonged artificial respiration.

Autors are Agnes K. Boehm, Karl H. Hillebrandt, Tomasz Dziodzio, Felix Krenzien, Jens Neudecker, Simone Spuler, Johann Pratschke, Igor M. Sauer, and Marco N. Andreas.
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Detection of nicotinamide adenine dinucleotide (NAD) in cells and blood plasma
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Priv,-Doz. Dr. med. Felix Krenzien and Dr. Jennifer Kirwan (Technologieplattform Metabolomik, Max-Delbrück-Centrum für Molekulare Medizin, Berlin) successfully applied for a grant within the Else Kröner Fresenius Stiftung funding line: Translational Research.

Recently, the molecule nicotinamide adenine dinucleotide (NAD) has attracted attention as it is involved in various important regulatory mechanisms, immune signaling, aging and regenerative processes. In this regard, it occupies key positions in many redox reactions of the body due to its role as a redox couple (NAD as an oxidized species and NADH as a reduced species). Consequently, NAD homeostasis (the maintenance of NAD in cells) is considered essential. The scientific consensus for many years was that the oxidized species resides exclusively in the intracellular milieu (iNAD). However, recent findings indicate that NAD also exists extracellularly (eNAD) and it is present in virtually all body fluids (from lymph to saliva to blood plasma). Based on these findings, precursors of NAD have recently been approved by the FDA and are commercially available. Measurement of eNAD in blood plasma is problematic due to its low concentration in the nanomolar range. However, quantifying eNAD plasma levels but also eNAD concentrations in cells is necessary to monitor the intake of NAD or its precursors and to adjust their dosage precisely.
The primary objective of this project is to validate, bioanalyze,and to document the assay for eNAD according to the ICH-M10 guidance document endorsed by the U. S. Food and Drug Administration (FDA). Adherence to the principles presented in this guideline should improve the quality and consistency of bioanalytical data, thereby supporting assay development and market approval. In addition, the assay will also be established for the measurement of intracellular NAD (iNAD), and validation of iNAD quantification will also be performed according to the guideline.

In the second part of the project, a clinical study will be conducted to determine whether the intake of nicotinamide riboside (precursor of NAD) leads to a change in eNAD and iNAD. Thus, the basis for an indication-dependent bioanalysis of the measurement of NAD will be developed to monitor the intake of NAD and its precursor or to adjust the dosage specifically on the basis of the quantification.
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DFG Funds Extension of the Digital Clinician Scientist Program
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Following the successful application for approval of the continuation of the BIH Charité Digital Clinician Scientist Program (DCSP) by the DFG, additional funding of around 1.3 million euros is now available over a period of two years: The DFG funding benefits physicians at Charité who have embarked on a scientific medical career path and, with their innovative research projects, are already playing a key role in shaping the digital transformation of healthcare during their residency training.

The Digital Clinician Scientist Program (DCSP) was jointly initiated by the German Research Foundation (DFG), the BIH, and the faculty of Charité - Universitätsmedizin Berlin in early 2019. The DCSP is an extension of the successful BIH Charité Clinician Scientist Program, which has set standards in the medical research landscape throughout Germany. The structured career path enables researching physicians to build the foundation for a successful career as a clinician scientist by providing protected time for research activities and non-clinical training during their residency. The DCSP is intended for clinically active physicians who are already actively shaping the digital transformation process of healthcare with their innovative research projects during their residency training. The main applicant of the continuation application is Prof. Dr. Igor M. Sauer, Director of the BIH Charité Digital Clinician Scientist Program, Deputy Clinic Director of the Department of Surgery, and Head of the Experimental Surgery at Charité. Since the start of the program in 2019, 24 physicians have benefited from funding, thus a broad spectrum of digital topics is already being addressed in various clinics at the Charité. The DFG originally funded the program for three years with more than three million euros. With the approved extension, the funding program now has a further 1.3 million euros available over a period of two years.
Development of human-based hydrogels as a substitute for mouse-derived Matrigel for cancer research
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With a new funding line, Charité 3R wants to support the development of animal-free cell cultures at Charité.

For in vitro cancer research, mini-tumours are grown in a gel-like cultivation structure that serves the three-dimensional growth of the mini-tumours. This gel-like cultivation substance is obtained from mouse tumours, an unnatural cultivation environment for human mini-tumours. The aim of the project "Development of human-based hydrogels as a substitute for mouse-derived Matrigel for cancer research" by Björn Papke from the Institute of Pathology and Karl Hillebrandt is to produce a cultivation structure without animal additives. For this purpose, a cultivation structure, also gel-like, is to be produced from tissue obtained from patients during surgical procedures, which better corresponds to the natural environment of the human mini-tumours.


Congratulations!
AI-based Risk Assessment in Pancreatic Surgery
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Our work on „Perioperative Risk Assessment in Pancreatic Surgery Using Machine Learning“ was published on the occasion of the 43rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

Pancreatic surgery is associated with a high risk for postoperative complications and death of patients. Complications occur in a variable interval after the procedure. Often, a patient has already left the ICU and is not properly monitored anymore when the complication occurs. Risk stratification models can assist in identifying patients at risk in order to keep these patients in ICU for longer. This, in turn, helps to identify complications earlier and increase survival rates. We trained multiple machine learning models on pre-, intra- and short term postoperative data from patients who underwent pancreatic resection at the Department of Surgery, Campus Charité Mitte | Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin. The presented models achieve an area under the precision-recall curve (AUPRC) of up to 0.51 for predicting patient death and 0.53 for predicting a specific major complication. Overall, we found that a classical logistic regression model performs best for the investigated classification tasks. As more patient data becomes available throughout the perioperative stay, the performance of the risk stratification model improves and should therefore repeatedly be computed.

Authors are Bjarne Pfitzner, Jonas Chromik, Rachel Brabender, Eric Fischer, Alexander Kromer, Axel Winter, Simon Moosburner, Igor M. Sauer, Thomas Malinka, Johann Pratschke, Bert Arnrich, and Max M. Maurer.
Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021:2211-2214. doi: 10.1109/EMBC46164.2021.9630897.
Dr. med. Hannah Everwien
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Hannah Everwien successfully defended her doctoral thesis entitled "Construction of a neo-pancreas by means of decellularisation and recellularisation" (summa cum laude)!

Congratulations!

Position for Student Assistant
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Project: This project aims to analyse purinergic signal pathways, especially ecto-enzymes of the CD39 family and their role in tumor immunology. Tissue expression as well as the activity of the associated purinergic molecules (receptors, signaling molecules and degrading enzymes) will be examined in a patient cohort of different gastrointestinal tumors with and without (peritoneal) metastases.

Methods: Clinical tissue acquisition (perioperative of patients undergoing surgery), FACS, immunohistology, qPCR, cell culture.

Requirements: Medical student with clinical experience with patients (i.e. "Famulaturen") and drawing blood. Above average scientific interest and engagement. Teamwork and self sufficiency.

What we offer: Learning of scientific methods in an excellently equipped laboratory, teamwork. Mentoring in the clinical and lab. Publication of results and potential of a doctoral thesis.

Data: 10h/week. Project duration: 9 months. Begin: November 2021 (flexible). Salary according to TV Stud III for Berlin.

If you're the right person: please send all application documents, e.g. cover letter, curriculum vitae, certificates, attestations, etc. to the following address, quoting the reference number by e-mail to
Charité – Universitätsmedizin Berlin
Chirurgische Klinik, Exp. Chirurgie
z.Hd. Dr. Linda Feldbrügge
Augustenburger Platz 1
D-13353 Berlin
linda.feldbruegge@charite.de
BMBF grant – GreifbAR
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The Federal Ministry of Education and Research (BMBF) funds the project "Tangible reality - skilful interaction of user hands and fingers with real tools in mixed reality worlds (GreifbAR)" – a cooperation of the Augmented Vision group of the DFKI (Prof. Dr. Didier Stricker), the Department of Psychology and Human-Machine Interaction of the University of Passau (Prof. Dr. Susanne Mayr), the company NMY Mixed Reality Communication (Christoph Lenk), and the Experimental Surgery of Charité – Universitätsmedizin Berlin (Prof. Dr. Igor M. Sauer).

The goal of the GreifbAR project is to make extended reality (XR) worlds, including virtual (VR) and mixed reality (MR), tangible and graspable by allowing users to interact with real and virtual objects with their bare hands. Hand accuracy and dexterity is paramount for performing precise tasks in many fields, but the capture of hand-object interaction in current XR systems is woefully inadequate. Current systems rely on hand-held controllers or capture devices that are limited to hand gestures without contact with real objects. GreifbAR solves this limitation by proposing a sensing system that detects both the full hand grip including hand surface and object pose when users interact with real objects or tools. This sensing system will be integrated into a mixed reality training simulator.

Competent handling of instruments and suture material is the basis of every surgical activity. The main instruments used in surgery are in the hands of the surgical staff. Their work is characterised by the targeted use of a large number of instruments that have to be operated and controlled in different ways. Until now, surgical knotting techniques have been learned by means of personal instruction by experienced surgeons, blackboard images and video-based tutorials. A training and teaching concept based on the acquisition of finger movement does not yet exist in surgical education and training. Learning surgical account techniques through participant observation and direct instruction by experienced surgeons is cost-intensive and hardly scalable. This type of training is increasingly reaching its limits in daily clinical practice, which can be attributed in particular to the changed economic, social and regulatory conditions in surgical practice. Students and trainees as well as specialist staff in further training are therefore faced with the problem of applying and practising acquired theoretical knowledge in a practice-oriented manner. Text- and image-based media allow scalable theoretical knowledge acquisition independent of time and place. However, gestures and work steps can only be passively observed and subsequently imitated. Moreover, the learning success cannot be quantitatively measured and verified.

The aim of the Charité's sub-project is therefore to develop a surgical application scenario for Mixed/Augmented Reality (MR/AR) for the spatial guidance and verifying recording of complex fine motor finger movements for the creation of surgical knots, the practical implementation and technical testing of the developed concept within the framework of a demonstrator, and the evaluation of the usability of the system for use in a clinical context.
Two new research grants by Berliner Krebsgesellschaft
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The Berliner Krebsgesellschaft will fund two very interesting research projects by Dr. Linda Feldbrügge and Dr. Karl Hillebrandt in collaboration with Dr. Björn Papke.

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„Purinergic immune regulation in peritoneal metastases of gastric cancer via CD39 and ENTPD3 – target for a novel immune Checkpoint inhibition?“ – PI: Dr. Linda Feldbrügge

Peritoneal metastasis, especially derived from gastric cancer (GC), has a poor prognosis with a median survival of only months. Treatment is usually confined to palliative systemic chemotherapy, complemented individually by checkpoint inhibitors that block PD1-signaling. Innovative therapies combining surgery with local drug application such as hyperthermic intraperitoneal chemotherapy (HIPEC) or pressurized intraperitoneal aerosol chemotherapy (PIPAC) are still pending confirmation in clinical trials. Purinergic signaling, which involves ATP hydrolysis and generation of adenosine, regulated through CD39 (ENTPD1) and related enzymes, has been recognized as a critical immunoregulatory pathway in the tumor microenvironment (TME). The objective of the current project is to characterize the immune environment in the unique setting of peritoneal metastasis of gastric cancer with a focus on ectonucleotidases CD39 and ENTPD3 on T cells, macrophages and MDSC as well as mechanisms of ectonucleotidase-mediated immune regulation in tumor associated macrophages in vitro. As a high-volume center for surgical therapy of peritoneal malignancies and with years of experience in ectonucleotidase research, we aim to advance the understanding of peritoneal metastasis and contribute to improving treatment options for our patients.

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"The influence of decellularised tumour matrix heterogeneity in relation to KRAS/MAPK inhibition of in vitro colorectal liver metastases." PI: Dr. Karl Hillebrandt and Dr. Björn Papke (Dept. of Pathology)

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide, with approximately 900,000 annual deaths. 30-50% of patients develop colorectal liver metastases (CRLM) during their disease. More than 50% of these tumors have mutations in the KRAS oncogene, making them usually poorly treatable. Despite multimodal therapy concepts have improved the outcome of these patients, a large proportion of patients suffer a recurrence of their disease. For better therapeutic concepts, we need to better understand the tumor biology and metastatic mechanisms of these diseases. In vitro models, such as two-dimensional cell culture, are primarily used for this purpose. These models can only reflect the physiological complexity to a limited extent. Recently, it was shown that the use of organ-specific and tumor-specific extracellular matrix (ECM) has an impact on the behavior of human CRC cell lines. Culture of cell lines with decellularized matrix resulted in cells adopting a metastatic cell state and forming significantly more metastases in a mouse model than cells cultured on plastic or collagen. The goal of our project is to study the growth (with and without inhibition of the RAS/MAPK signaling pathway) of patient-derived tumor organoids growing on different decellularized metastatic matrices (dMM) and decellularized liver matrices (dLM). These studies of tumor matrix heterogeneity are essential to define which starting materials, for in vitro modeling of our three-dimensional tumor organoid culture, can be used to develop the most physiological, personalized dLM/dMM-based CRLM in vitro model possible. Based on these results, we plan to conduct small-scale therapy evaluations for personalized tumor therapy using our in vitro dLM/dMM-based CRLM in the near future.

Congratulations!
Robert-Koch-Prize awarded to Simon Moosburner
Today, Dr. med. Simon Moosburner received the Robert-Koch-Prize for one of the three best dissertations of the Charité - Universitätsmedizin Berlin in 2020 for his thesis titled  "Erweiterung der Spenderpopulation bei Lebertransplantation: Klinischer Bedarf und Entwicklung eines Kleintier-Lebermaschinenperfusionssystems (Expanding the donor pool for liver transplantation: clinical need and development of small animal liver perfusion system)".


Congratulations!
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ADBoard | Therapeutic Assist and Decision Algorithms for Hepatobiliary Tumor Boards
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The Gemeinsamer Bundesausschuss (Federal Joint Committee, G-BA) will fund a new collaborative project of the Charité's Dept. of Surgery and the Deutsches Forschungszentrum für Künstliche Intelligenz (German Research Center for Artificial Intelligence, DFKI), Speech and Language Technology.

The aim of the project Therapeutic Assist and Decision Algorithms for Hepatobiliary Tumor Boards (ADBoard) is the validation and evaluation of decision support systems based on linguistic and semantic methods of artificial intelligence (AI) for interdisciplinary tumour conferences in the care of tumour patients. Natural language processing (NLP) and machine learning (ML) will provide the technical basis for data extraction, data filtration and decision support for the automated generation of therapy recommendations. Interdisciplinary tumour board conferences are medical conferences, usually held on a weekly basis, which are required by the respective medical societies to determine a therapy or monitoring plan for patients with malignant diseases. Participants are representatives of the required medical disciplines who, taking into account the tumour characteristics and the general health of the patient, review the treatment options and make a therapy recommendation.

The Gemeinsamer Budesausschuss (Federal Joint Committee, G-BA) has the mandate to promote new forms of health care that go beyond the current standard provision of statutory health insurance, and health care research projects that are aimed at gaining knowledge to improve existing health care.

ADBoard is a collaboration of Priv.-Doz. Dr. Felix Krenzien, Priv.-Doz. Dr. Christian Benzing, Prof. Dr. Dominik Modest, Prof. Dr. Johann Pratschke (Charité – Universitätsmedizin Berlin) and Prof. Dr.-Ing. Sebastian Möller, Head of Research Department Speech and Language Technology, German Research Center for Artificial Intelligence.
BIH Charité Clinician Scientist Symposium in Honor and Memory of Duška Dragun
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28 May 2021 - 29 May 2021
BIH Charité Clinician Scientist Symposium in Honor and Memory of Duška Dragun

The symposium is composed of several components: First and foremost, it will commemorate Prof. Duška Dragun, the former Director of the BIH Biomedical Innovation Academy (BIA) and Director of the BIH Charité Clinician Scientist Program, who passed away in December 2020, and will be joined by stakeholders from academia and science policy. In addition, there will be scientific sessions, which will form tandems of program fellows and invited speaker. During a digital certificate ceremony on the evening of 28 May 2021, some 50 alumni will be bid farewell. The event language is English.

When
28 and 29 May 2021
10:00 - 6:30 pm

How
Online Event (semi-digital)

Registration
To receive the login link please register here.
Advanced Clinician Scientists
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Priv.-Doz. Dr. Nathanael Raschzok and Priv.-Doz. Dr. Felix Krenzien successfully applied for the BIH Charité Advanced Clinician Scientist Pilot Programme (AdCSP) in a highly competitive process.

The BIH Charité AdCSP is designed as a career-phase-specific, sustainable funding programme that aims to closely interlink individual and institutional funding. The primary goal of the programme is to simultaneously incentivise the fellows and recognise the permissive academic culture of the respective clinics or institutes. Like the BIH Charité Clinician Scientist Programme (CSP) and the "Digital Clinician Scientist Programme" (DCSP), which has been additionally funded by the DFG since 2019, it is intended to be open to all clinical disciplines and to offer multiple networking opportunities for the funded fellows and participating clinics and institutes.

Congratulations!
Grant provided by the Berliner Krebsgesellschaft e.V.
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Dr. med. M. Felsenstein receives a grant provided by the Berliner Krebsgesellschaft e.V. for his project "Deciphering the molecular determinants of pancreatic duct dysplasia by analysis of single-cell transcriptomics (RNAseq) in precursor lesions".

Besides great advances in the molecular and genetic understanding of pancreatic duct adenocarcinoma (PDAC), this tumor entity remains particularly aggressive with dismal prognosis. Recent single-cell sequencing studies underline the eminent urgency to understand tumor heterogeneity in the setting of PDAC. More detailed knowledge about the molecular mechanisms of pancreatic cancer evolution, carcinogenesis and heterogeneity could direct ideas for earlier detection and more effective targeted therapies, also preventing disease recurrence. Future therapeutic approaches in precision medicine will likely focus on the disease relevant sub-populations, specifically driving cancer progression, dissemination and exerting tumor escape mechanisms. In-depth transcriptomic data of single carcinoma environmental cells and respective cell clusters may help to discover novel biomarkers, which can be clinically instrumented for earlier detection and putatively increase the fraction of patients, amenable to curatively intended therapies. This study aims to analyze sorted single cells of macro-dissected precursor and cancerous lesions of the pancreas by single nuclei RNA sequencing (snRNAseq). In this feasibility study, we will include 10 patients, who will undergo resection of the pancreas due to “worrisome” or malignant lesions. We will perform in-depth transcriptomic analysis of pancreatic dysplasia in order to broaden our understanding of the molecular mechanisms of pancreatic carcinogenesis.

Congratulations!
Recellularization of decellularized bovine carotid arteries
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"In vitro recellularization of decellularized bovine carotid arteries using human endothelial colony forming cells" was published in the latest issue of Journal of Biological Engineering.
Many patients suffering from peripheral arterial disease (PAD) are dependent on bypass surgery. However, in some patients no suitable replacements (i.e. autologous or prosthetic bypass grafts) are available. Advances have been made to develop autologous tissue engineered vascular grafts (TEVG) using endothelial colony forming cells (ECFC) obtained by peripheral blood draw in large animal trials. Clinical translation of this technique, however, still requires additional data for usability of isolated ECFC from high cardiovascular risk patients.
Bovine carotid arteries (BCA) were decellularized using a combined SDS (sodium dodecyl sulfate) -free mechanical-osmotic-enzymatic-detergent approach to show the feasibility of xenogenous vessel decellularization. Decellularized BCA chips were seeded with human ECFC, isolated from a high cardiovascular risk patient group, suffering from diabetes, hypertension and/or chronic renal failure. ECFC were cultured alone or in coculture with rat or human mesenchymal stromal cells (rMSC/hMSC). Decellularized BCA chips were evaluated for biochemical, histological and mechanical properties. Successful isolation of ECFC and recellularization capabilities were analyzed by histology.

Decellularized BCA showed retained extracellular matrix (ECM) composition and mechanical properties upon cell removal. Isolation of ECFC from the intended target group was successfully performed (80% isolation efficiency). Isolated cells showed a typical ECFC-phenotype. Upon recellularization, co-seeding of patient-isolated ECFC with rMSC/hMSC and further incubation was successful for 14 (n = 9) and 23 (n = 5) days. Reendothelialization (rMSC) and partial reendothelialization (hMSC) was achieved. Seeded cells were CD31 and vWF positive, however, human cells were detectable for up to 14 days in xenogenic cell-culture only. Seeding of ECFC without rMSC was not successful.

Using our refined decellularization process we generated easily obtainable TEVG with retained ECM- and mechanical quality, serving as a platform to develop small-diameter (< 6 mm) TEVG. ECFC isolation from the cardiovascular risk target group is possible and sufficient. Survival of diabetic ECFC appears to be highly dependent on perivascular support by rMSC/hMSC under static conditions. ECFC survival was limited to 14 days post seeding.
Authors are N. Seiffert, P. Tang, E. Keshi, A. Reutzel-Selke, S. Moosburner, H. Everwien, D. Wulsten, H. Napierala, J. Pratschke, I.M. Sauer, K. Hillebrandt, and B. Struecker.
J Biol Eng 15, 15 (2021). https://doi.org/10.1186/s13036-021-00266-5
Position for Research Associate / Research Fellow
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Priv.-Doz. Dr. Nathanael Raschzok and his team are working on strategies for (re-) conditioning of marginal liver grafts by ex vivo liver machine perfusion. The aim for the proposed job offer, which is funded by grants of the Else Kröner-Fresenius-Stiftung, is to make steatotic liver grafts, which are usually discarded from transplantation due to the high risk for the recipient, acceptable for transplantation. We have already established a small animal model of ex vivo liver machine perfusion as well as transplantation. Aim of this project is to test a clinically approved drug in dose-response studies (based on preliminary data), followed by in vivo studies in the rat liver transplantation model.

Your responsibility will be:
  • Organ perfusion of murine livers in our established small animal modell for ex vivo liver machine perfusion
  • Support of in rat liver transplantation experiments
  • Organ recovery and transplantation (not mandatory)
  • Biochemical analysis of the perfusat and the lipid metabolism (ELISA), tissue analysis (qRT-PCR, Wester Blot, immunochemistry, immunofluorescence)
  • We fully support the application and submission of a doctoral thesis (e.g. Dr. rer.medic or MD/PhD)
Require­ments
  • Degree in biology, biochemistry, biotechnology or medicine
  • Pevious experience in molecular cell biology and/or proteinbiochemistry, or surgical research
  • Proficiency in standard methods, especially histology, immunhistochemistry, qPCR, FACS, microscopy, cell culture/cell isolation
  • Excellent english language skills
Personal characteristics
  • innovative spirit and extraordinary motivation, interest in purposeful work
  • team work orientated
  • organized, ability for analytic and independent work ethic

If you're the right person: please send all application documents, e.g. cover letter, curriculum vitae, certificates, attestations, etc. to the following address, quoting the reference number by e-mail to
Charité – Universitätsmedizin Berlin
Chirurgische Klinik, Exp. Chirurgie
z.Hd. PD Dr. Nathanael Raschzok
Augustenburger Platz 1
D-13353 Berlin
nathanael.raschzok@charite.de
Prof. Dr. Moritz Schmelzle
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In appreciation of his extraordinary achievements in research and teaching Moritz Schmelzle received an extraordinary professorship for Surgery at the Charité – Universitätsmedizin Berlin.

CONGRATULATIONS !
Notch Signaling Pathway in Pancreatobiliary Tumors
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The Notch signaling pathway plays an important role both in the development of the ductal systems of the pancreas and the bile ducts as well as in cancer development and progression. The aim of this study was to examine the expression of central proteins of the Notch signaling pathway in pancreatobiliary tumors and its influence on patient survival.

Materials and Methods: We compared the receptors (Notch1, Notch4), activating splicing factors (ADAM17), and target genes (HES1) of the Notch pathway and progenitor cell markers with relevance for the Notch signaling pathway (CD44, MSI1) between pancreatic adenocarcinomas (PDAC, n = 14), intrahepatic cholangiocarcinoma (iCC, n = 24), and extrahepatic cholangiocarcinoma (eCC, n = 22) cholangiocarcinomas.

A significant overexpression of almost all studied components of the Notch signaling pathway can be found in the tumor tissue, however, without a significant influence on patient survival. Therefore, further studies are warranted to draw conclusions on Notch pathway's relevance for patient survival.

The paper "Notch Signaling Pathway in Pancreatobiliary Tumors" is available via Medicina, 2021;57(2):105. Authors are Francesca Borlak, Anja Reutzel-Selke, Anja Schirmeier, Julia Gogolok, Ellen von Hoerschelmann, Igor M Sauer, Johann Pratschke, Marcus Bahra, and Rosa B Schmuck.
Extended liver resection in mice: state of the art and pitfalls
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"Extended liver resection in mice: state of the art and pitfalls – a systematic review" is available in ur J Med Res. 2021; 26(1):6.
Rodent models of liver resection have been used to investigate and evaluate the liver's complex physiology and pathology since 1931. First documented by Higgins and Anderson, such models were created to understand liver regeneration mechanisms to improve outcomes in patients undergoing extensive liver resection for liver cancer or other underlying liver diseases. A systematic search was conducted using Pubmed, gathering publications up to January 2019, which engaged with the mouse model of extended liver resection as a method itself. The results of this search were filtered according to their language, novelty, and relevancy.
Through the overview, laid out in the selected publications, this paper reviews the shift of the extended liver resection model from rat to the mouse, describes the state of the art in the experimental setting, and discusses the possible limitations and pitfalls. Clearly, the extended liver resection in mice is a reproducible, practical and easy to learn method.
Authors are Can Kamali, Kaan Kamali, Philipp Brunnbauer, Katrin Splith, Johann Pratschke, Moritz Schmelzle, and Felix Krenzien.
Duška Dragun
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We have received the sad news that Professor Duška Dragun, Director of the Biomedical Innovation Academy (BIA) of the Berlin Institute of Health (BIH) and Head of the Charité BIH Clinician Scientist Program, succumbed to her long, severe, bravely endured illness on December 28, 2020 at the age of 51.
 
Her tireless efforts were devoted to her life's work: the Charité BIH Clinician Scientist Program. Ten years ago, she launched the first Clinician Scientist Program in Berlin and over the decade established and continuously expanded it as "best practice" for the German-speaking region. She has played a key role in developing and shaping the various programs for scientifically active physicians: from the Clinician Scientist Program, which enables aspiring specialists to spend up to 50 percent of their working time on research, to the Junior Clinician Scientist Program with 20 percent working time on research, which begins in the first year of specialist training, to the Advanced Clinician Scientist Program for specialists with postdoctoral qualifications. Two years ago, she successfully applied to the German Research Foundation (DFG) for the first and only Digital Clinician Scientist Program in Germany. This enables young physicians and scientists to conduct research and work in the field of digitalization in medicine and healthcare. Thus, within a few years, Duška Dragun made a significant contribution to building a new generation of young professionals for medicine – the impact of her programs will last for a long time, via promising individual careers as well as via the programmatic strengthening of a patient-oriented science.  
 
As a physician herself, Professor Duška Dragun has always been committed to research: As acting senior physician and deputy to the acting director of the Department of Nephrology and Intensive Care Medicine at the Charité Campus Virchow-Klinikum, as well as head of the nephrology research laboratory, she made highly regarded, internationally distinguished contributions to transplantation research with the goal of improving graft approach and long-term survival, preventing cardiovascular comorbidity, and thus improving the quality of life and life expectancy of transplanted patients.  She pursued her great goals with tremendous energy and passion, impressive perseverance and clear determination. She devoted her full attention to her employees, colleagues, and students, being equally attentive, understanding, and demanding.
 
The death of Duška Dragun is a great and painful loss. We will miss her greatly as director of the Charité BIH Clinician Scientist Program, as a physician, university professor and scientist. To us she was an inspiration, a mentor and an ever driving force.

Above all, however, we will greatly miss Duška as a friend.  
Karl Hillebrandt | Charité 3R Tandem project for early career researchers
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Together with Dr. Björn Papke (Molecular tumour pathology), Dr. Karl Hillebrandt was able to acquire funding for a "Tandem project for early career researchers" from the Charité 3R. The project is entitled "A personalised therapy approach implementing individually matched matrix-based in vitro colorectal liver metastases to reduce metastatic mouse models".
Although modern multimodal therapy strategies have improved the clinical outcome of patients with colorectal liver metastases (CRLM), the overall prognosis is still poor. To further improve treatment options for patients, it is necessary to develop and test new targeted therapeutic approaches. To date, mouse models have often been used to study metastatic colorectal cancer. However, the rate of successful translation of animal models into clinical trials is less than 8%, highlighting the urgent need for alternative models to study the biology of metastatic cancer. This project aims to develop a novel personalised extracellular matrix-based in vitro model of human CRLM. This model will be validated against existing data from patient-derived organoids and xenografts (histology, single cell RNA sequencing and targeted gene sequencing). After internal comparison of our in vitro CRLM with the original CRLM, we will translate it into a personalised drug screening platform to test drug response from standard therapy to novel inhibitor combinations.
Dr. Moritz Queisner
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Dr. rer. medic. Moritz Queisner received his doctorate certificate today (magna cum laude)! This is in recognition of his work in the field of extended reality technology in visceral surgery. His thesis is entitled XR in surgery – spatial end embodied computing in digital surgery: technology, application, design.

CONGRATULATIONS !
CLOUZ | spinoff from the Charité
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Dr. Panagiotis Fikatas invented a surgical device using a knot technology for minimally invasive surgery. Early prototyping and development work was significantly supported by the SPARK-BIH program with the Validation Fund and funds from the Stiftung Charité.

The startup Clouz GmbH, a spinoff from the Charité – Universitätsmedizin Berlin, has developed a novel surgical knot-tying device for use in restrictive access surgery. Clouz GmbH has signed a purchasing agreement for the knot patent with the Charité Technology Transfer Office. The medical device startup was founded by Dr. Panagiotis Fikatas, Marco Climaco and Anne-Mette Jensen.

The novel surgical closure device allows surgical knots to be tied easily, quickly, and most importantly, safely, even in surgeries with severely limited access (e.g. minimally invasive procedures). The products are based on a patented knotting technology that can be used in a range of device types: from manual application by the surgeon to devices for robotic surgery. CLOUZ OneKnot ensures consistent closure for the surgeon and saves valuable time in the operating room.

Two new (Junior) Clinician Scientitsts
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Dr. Simon Moosburner and Dr. Tomasz Dziodzio successfully applied for the BIH Charité (Junior) Clinician Scientist Program.

Dr. Dziodzio is studying pathomechanisms of obesity in the context of kidney transplantation and investigates the impact of obesity on the immune response in the kidney transplant recipient. In addition, a clinical trial will investigate whether surgical weight reduction in obese patients prior to kidney transplantation leads to improved graft function.

Dr. Moosburner is working on the extracorporeal evaluation of liver grafts from older donors. The aim is to characterise old liver grafts during normothermic machine perfusion. For this purpose, a model for normothermic ex vivo machine perfusion of small animal livers as well as liver transplantation in the rat model was established.

CASSANDRA | Clinical ASSist AND aleRt Algorithms
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The Innovationsausschuss beim Gemeinsamen Bundesausschuss (G-BA) is funding 33 new projects in healthcare research. A total of 186 project applications were received in response to the funding announcements of December 2019. Nine project proposals from the open topic area and 24 project proposals from the topic-specific area received a positive funding decision.

Our project CASSANDRA (Clinical ASSist AND aleRt Algorithms – Early detection of postoperative complications with machine learning algorithms) is one of the projects funded for three years.

The aim of the project is to evaluate Machine Learning (ML) in the detection of postoperative complications after major abdominal surgery. By means of digital records and ML-driven analysis of perioperative risk factors, postoperative parameters as well as telemedical vital parameter monitoring, it is to be examined whether complications requiring treatment – in particular infections of the abdominal cavity after liver, pancreas, stomach and intestinal surgery – can be automatically detected and predicted, in order to develop the basis for an autonomous real-time monitoring system on normal wards.
CASSANDRA is a collaboration of Axel Winter, Dr. Max Maurer, Prof. Dr. Igor M. Sauer (Charité – Universitätsmedizin Berlin) and Prof. Dr. Bert Arnrich, Head of the Chair, Professor for Digital Health - Connected Healthcare, Hasso Plattner Institut.
DICOM_XR | XR4ALL 2nd Open Call: Project Selected for Phase 1
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XR4ALL is an initiative by the European Commission to strengthen the European XR industry.

After 140 applications, 18 projects have been selected for Phase 1 of the 2nd Cut-off date of the XR4ALL Open Call. In this phase, projects need to expand upon and validate their concept from a business and a technical perspective during two months.
Based on an evaluation at the end of the first phase, only the best-rated projects will be admitted to Phase 2 and therefore be able to develop the proposed solution.

Our project DICOM_XR (PI: Christoph Rüger) is one of them (and one of three from Germany)!

One of the most common use-cases for XR in medicine is the visualization of medical imaging data like computed tomography (CT) scans. The well-established standard for storing and transferring such data is DICOM (Digital Imaging and Communications in Medicine). It is used in all major hospitals in the European Union – XR applications that involve medical images need to be built upon this standard. Existing open-source DICOM frameworks offer data interoperability and are compatible with 3D engines, like Unity. However, while DICOM is well-established and very feature rich, it is also a complex standard to work with as a developer. In addition to data interoperability provided by DICOM, most medical XR applications also require: 1) Data transfer from a machine with access to the hospital’s image network to mobile XR devices such as HMDs, 2) performant visualization, particularly for stereographic displays, and 3) view manipulation with 3D input (e.g. hand tracking) instead of mouse input. These requirements are, at best, additional workloads for technically skilled teams and, at worst, insurmountable hurdles for projects lacking programmers.
DICOM_XR is a framework aiming to solve all three of these requirements: data transfer, performant visualization and utilization of three-dimensional input. Building upon an existing open-source DICOM solution, DICOM_XR will offer a ‘plug and play’ solution for XR developers. It will significantly decrease technical hurdles for e.g. medical studies evaluating XR, which are still sorely needed. It can also streamline the development of commercial XR applications: Medical open-source projects such as SlicerIGT have been successfully used as a foundation for certified medical products. In short, DICOM_XR will allow medical XR developers to focus on features that their users want, rather than technical infrastructure.
Engineering an endothelialized, endocrine NeoPancreas
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Acta Biomaterialia accepted our latest paper on "Engineering an endothelialized, endocrine Neo-Pancreas: evaluation of islet functionality in an ex vivo model".

Islet-based recellularization of decellularized, repurposed rat livers may form a transplantable Neo-Pancreas. The aim of this study is the establishment of the necessary protocols, the evaluation of the organ structure and the analysis of the islet functionality ex vivo.
After perfusion-based decellularization of rat livers, matrices were repopulated with endothelial cells and mesenchymal stromal cells, incubated for 8 days in a perfusion chamber and finally repopulated on day 9 with intact rodent islets. Integrity and quality of re-endothelialization was assessed by histology and FITC-dextran perfusion assay. Functionality of the islets of Langerhans was determined on day 10 and day 12 via glucose stimulated insulin secretion.
Blood gas analysis variables confirmed the stability of the perfusion cultivation. Histological staining showed that cells formed a monolayer inside the intact vascular structure. These findings were confirmed by electron microscopy. Islets infused via the bile duct could histologically be found in the parenchymal space. Adequate insulin secretion after glucose stimulation after 1-day and 3-day cultivation verified islet viability and functionality after the repopulation process.
We provide the first proof-of-concept for the functionality of islets of Langerhans engrafted in a decellularized rat liver. Furthermore, a re-endothelialization step was implemented to provide implantability. This technique can serve as a bioengineered platform to generate implantable and functional endocrine Neo-Pancreases.

Authors are Hannah Everwien, Eriselda Keshi, Karl H. Hillebrandt, Barbara Ludwig, Marie Weinhart, Peter Tang, Anika S. Beierle, Hendrik Napierala, Joseph MGV Gassner, Nicolai Seiffert, Simon Moosburner, Dominik Geisel, Anja Reutzel-Selke, Benjamin Strücker, Johann Pratschke, Nils Haep, and Igor M. Sauer.
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Best Poster prize for Anna Pfefferkorn
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Anna Pfefferkorn won the Best Poster prize for our work on "Molecular and cellular mechanisms of Lipocalin-2 mediated renoprotection in kidney transplantation" at the Kongress für Nephrologie 2020, held in Berlin 1.-4. October, 2020!

Lipocalin-2 (Lcn2) is distinctly upregulated in kidney transplants and serves as an early marker of AKI, DGF and acute rejection. However, the functional role and mechanisms underlying Lcn2 upregulation remain largely unknown. Using a mouse model of kidney transplantation we recently demonstrated a renoprotective role of recombinant Lcn2:Siderophore:Fe (rLcn2). However, the molecular and cellular events underlying the renoprotective effects of rLcn2 in kidney allografts remain unclear. Elucidating these events forms the primary focus of the current study.
rLcn2 significantly lowered CD8+ T cells in the allograft, LN and blood at POD 7, whereas their number remained unaffected in spleen. Nevertheless, the number of CD4+ T Lymphocytes was reduced only in lymph nodes. NKG2D+CD8+T cells and CD27+CD11b+NKp46+NK cells were the most prominent subpopulations of the cytotoxic lymphocytes whose frequencies were significantly reduced in graft, spleen and blood with the treatment of rLcn2. Besides, a significantly reduced infiltration of monocytes/macrophages was also observed at POD-7 with the said treatment. Importantly, degranulation capacity and IFNg production of intragraft and splenic CD4+ and CD8+ T cells were impaired in the treated animals. Besides, rLcn2 lowered hypoxia and reoxygenation induced cytotoxicity of the primary RTECs, associated with reduced caspase-3 cleavage and activation of Erk and AKt signaling.

rLcn2 treatments differentially affects the relative frequencies and activation of various immune cell. Besides, rLcn2 depicts cytoprotective effect on murine primary RTECs during H/R, possibly via activation of Erk and Akt signaling.

CONGRATULATIONS !
Declined Liver Grafts – Analysis of the German Donor Population from 2010 to 2018
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"Declined Liver Grafts – Analysis of the German Donor Population from 2010 to 2018" was published in the Zeitschrift für Gastroenterologie.
The lack of suitable allografts limits the availability of liver transplantation in Germany. The quality of potentially available German donor livers has to date not been analyzed.
Analysis of all donors for potential liver transplantations reported to the Eurotransplant by the German Organ Transplantation Foundation from 2010 to 2018. Categorization of transplanted and discarded organs utilizing available histopathological reports and predefined extended criteria for organ donation.
A total of 8594 livers were offered for transplantation, of which 15.2 % were discarded. During the analysis period the proportion of donor livers from extended criteria donors increased from 65 % to 70 % (p = 0.005). In 2018, 21.3 % of offered donor livers were discarded, more than half (56.4 %) of these organs came from donors meeting multiple extended criteria. Livers were significantly more likely to be not transplanted, when from donors of older age (> 65 years; 41 vs. 28 %), BMI > 30 kg/m2 (29 vs. 14 %) or elevated transaminase levels (all p < 0.001).
Despite the consistent organ scarcity in Germany, a relevant amount of livers cannot be transplanted due to a multitude of organ quality limitations. This should stimulate the search for concepts such as normothermic ex vivo machine perfusion to evaluate, protect and potentially improve organ quality.

Authors are Simon Moosburner, Nathanael Raschzok, Christina Schleicher, Detlef Bösebeck, Joseph M.G.V. Gaßner, Paul V. Ritschl, Axel Rahmel, Igor M. Sauer, and Johann Pratschke.
Z Gastroenterol. 2020 Aug 24. doi: 10.1055/a-1199-7432. Online ahead of print.
Felix Krenzien received Ferdinand-Sauerbruch Prize 2020
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Priv.-Doz. Dr. Felix Krenzien received the Ferdinand-Sauerbruch Prize 2020 for his project and publication „The ILLS Laparoscopic Liver Surgery Fellow Skills Curriculum“ published in Annals of Surgery (online ahead of print).

Congratulations!

Laparoscopy is becoming the standard approach in liver surgery. As the degree of difficulty varies greatly from core skills to advanced procedures, strategies for teaching young surgeons need to be reconsidered. We here aimed to design a skills curriculum for LLR. Using the nominal group technique, 22 substeps of LLR were identified by 61 hepatobiliary surgeons. The raters were asked to rate (1) the difficulty of substeps and (2) the minimum number of times that the substep must be performed for mastery of the technique. According to the frequency of defined substeps, being estimated on the basis of high volume center experiences (n = 222 LLR; 1/2017-12/2018), the center's training capacity and defined goals for a 2-year fellowship were calculated.
Ten surgical substeps (45%) are routinely performed and can thus be taught sufficiently at centers carrying out ≥50 LLR in 2 years. As the mobilization of the right liver lobe and the dissection of the hepatic artery or portal vein is performed in only 27% and 28% of all LLR, respectively, sufficient training can only be provided at centers with ≥100 LLRs in 2 years. Mastery of complex parenchymal dissection (19%) and hilar lymphadenectomy (8%) can only be achieved in center performing ≥200 LLR in 2 years.
The authors suggest a stepwise approach for training of hepatobiliary fellows in LLR. Based on the estimated complexity of the substeps and the size of the center, not every substep can be learned within 2 years.

Authors are Felix Krenzien, Wenzel Schöning, Philipp Brunnbauer, Christian Benzing, Robert Öllinger, Matthias Biebl, Marcus Bahra, Nathanael Raschzok, Daniel Cherqui, David Geller, Ho-Seong Han, Go Wakabayashi, Moritz Schmelzle, Johann Pratschke, and the study group of the International Laparoscopic Liver Society (ILLS).
EKFS grant | Metabolic reconditioning of steatotic rat liver grafts by normothermic ex vivo machine perfusion
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The Else Kröner Fresenius Stiftung will fund the project "Metabolic reconditioning of steatotic rat liver grafts by normothermic ex vivo machine perfusion" (PI: Priv.-Doz. Dr. Nathanael Raschzok) for two years.

Liver transplantation is the treatment of choice for end-stage liver disease, yet the number of transplant candidates constantly exceeds the organ supply. The imbalance between demand and supply of liver grafts is dramatically exacerbated by the rising prevalence of obesity and the metabolic syndrome, which both show a strong correlation with steatosis hepatis. Liver grafts with macrovesicular steatosis above 30% are associated with delayed graft function and lower graft and patient survival, and livers with >60% steatosis are generally discarded from transplantation. Within the next 10 years, the overall liver graft utilization could potentially be halved due to the rising prevalence of steatosis, emphasizing the urgent clinical need to find solutions to make steatotic livers acceptable for transplantation.

In this project the hypothesis is tested whether metabolic reprogramming of steatotic liver grafts will 1) restore hepatocyte function, 2) activate lipid catabolism, 3) increase resistance to ischemia reperfusion damage, and 4) alleviate overwhelming inflammatory processes in the early phase of post-transplant regeneration with beneficial long-term impact for graft function and recipient survival.
The Human Liver Matrisome
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Biomaterials accepted our latest paper on „The Human Liver Matrisome – Proteomic Analysis of Native and Fibrotic Human Liver Extracellular Matrices for Organ Engineering Approaches“.

The production of biomaterials that endow significant morphogenic and microenvironmental cues for the constitution of cell integration and regeneration remains a key challenge in the successful implementation of functional organ replacements. Despite the vast development in the production of biological and architecturally native matrices, the complex compositions and pivotal figures by which the human matrisome mediates many of its essential functions are yet to be defined. Here we present a thorough analysis of the native human liver proteomic landscape using decellularization and defatting protocols to extract create extracellular matrix scaffolds of natural origin that can further be used in both bottom-up and top-down approaches in tissue engineering based organ replacements. Furthermore, by analyzing human liver extracellular matrices in different stages of fibrosis and cirrhosis, we have identified distinct attributes of these tissues that could potentially be exploited therapeutically and thus require further investigation. The general experimental pipeline presented in this study is applicable to any type of tissue and can be widely used for different approaches in regenerative medicine and in the construction of novel biomaterials for organ engineering approaches.

Authors are A. Daneshgar, O. Klein, G. Nebrich, M. Weinhart, P. Tang, A. Arnold, I. Ullah, J. Pohl, S. Moosburner, N. Raschzok, B. Strücker, M. Bahra, J. Pratschke, I.M. Sauer, and K.H. Hillebrandt. The authors acknowledge the support of the Cluster of Excellence Matters of Activity. Image Space Material funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany´s Excellence Strategy – EXC 2025.
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Ex vivo machine perfusion: current applications and future directions in liver transplantation
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Langenbeck's Archives of Surgery accepted the manuscript „Ex vivo machine perfusion: current applications and future directions in liver transplantation“ for publication.

Liver transplantation is the only curative treatment option for end-stage liver disease, however, its use remains limited due to a shortage of suitable organs. In recent years, ex vivo liver machine perfusion has been introduced to liver transplantation, as a means to expand the donor organ pool.
To present a narrative review of prospective clinical studies on ex vivo liver machine perfusion, in order to assess current applications and highlight future directions.
Methods: A systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed.
Twenty articles on prospective clinical trials on ex vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, nine on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of ex vivo liver machine perfusion in both standard and expanded criteria donors. Currently, there are 12 studies enrolled in the clinicaltrials.gov registrar, and these focus on use of ex vivo perfusion in extended criteria donors as well as declined organs.
Ex vivo liver machine perfusion seems to be a suitable strategy to expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs.

Authors are Julian Michelotto, Joseph MGV Gaßner, Simon Moosburner, Vanessa Muth, Madhukar S Patel, Markus Selzner, Johann Pratschke, Igor M. Sauer, and Nathanael Raschzok.
SiM | Der Simulierte Mensch
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„Der Simulierte Mensch“ ("The Simulated Human", Si-M) is a new research building which is currently under construction and is expected to be finished in 2023. The building site is directly adjacent to the Charité Campus Virchow-Klinikum of the Charité - Universitätsmedizin in Berlin-Wedding and is also the birthplace of biotechnology at the TU Berlin.

The initiators of Si-M are Roland Lauster (Head of the Department of Medical Biotechnology at TU Berlin) and Andreas Thiel (Head of the research group Regenerative Immunology and Aging at Charité – Universitätsmedizin Berlin). They applied for the research building in 2018 (GG §91b) and successfully defended it before the German Science Council.

In the building, scientists from both institutions will work together to simulate the functions of human cells and tissues with new technologies of 3D cultivation, multi-organ chips or 3D bioprinting. In contrast to already existing collaborative projects, the building will be used to practice the joint development of models "side by side" in the same laboratory environment. In this way, both the development of organ models and technological developments can be adapted and optimized at the same time.

More information via https://www.si-m.org .

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Ultrasound in augmented reality: a mixed-methods evaluation of head-mounted displays in image-guided interventions
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The International Journal of Computer Assisted Radiology and Surgery accepted Christoph Rüger's paper on "Ultrasound in augmented reality: a mixed-methods evaluation of head-mounted displays in image-guided interventions" for publication.

Augmented reality (AR) and head-mounted displays (HMD) are current subjects of investigation in medical practice. A commonly proposed use-case of AR-HMDs is to display data in image-guided interventions. Although technical feasibility has been thoroughly shown, effects of AR-HMDs on interventions are not yet well researched, hampering clinical applicability. Therefore, the goal of this study is to better understand the benefits and limitations of this technology in ultrasound-guided interventions.
We used an AR-HMD system (based on Hololens, Microsoft Corp.) which overlays live ultrasound images spatially correctly at the location of the ultrasound transducer. We chose ultrasound-guided needle placements as a representative task for image-guided interventions. To examine the effects of the AR-HMD, we used mixed methods and conducted two studies in a lab setting: (1) in an experimental study, we asked participants to place needles into a training model and evaluated task duration and accuracy with the AR- HMD as compared to the standard procedure without visual overlay and (2) in a qualitative study, we analysed the user experience with AR-HMD using think-aloud protocols during ultrasound examinations and semi-structured interviews after the task.
Participants (n=20) placed needles more accurately (mean error of 7.4 mm vs. 4.9 mm, p=0.022) but not significantly faster (mean task duration of 74.4 s vs. 66.4 s, p=0.211) with the AR-HMD. All participants in the qualitative study (n=6) reported limitations of and unfamiliarity with the AR-HMD, yet all but one also clearly noted benefits and/or that they would like to test the technology in practice.
We present additional, though still preliminary, evidence that AR-HMDs provide benefits in image-guided procedures. Our data also contribute insights into potential causes underlying the benefits, such as improved spatial perception. Still, more comprehensive studies are needed to ascertain benefits for clinical applications and to clarify underlying mechanisms.

Authors are Christoph Rüger, Markus A. Feufel, Simon Moosburner, Christopher Özbek, Johann Pratschke, and Igor M. Sauer.
Brigitta Globke: Digital Clinician Scientist
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Dr. Brigitta Globke successfully applied for participation in the BIH Charite Digital Clinician Scientist Program.

The aim of the project is the development and evaluation of an augmented reality assist system for intraoperative photoplethysmographic control of perfusion. The project is carried out in collaboration with Benjamin Kossack, Fraunhofer | Heinrich Hertz Institute Computer Vision and Graphics.

Charité and BIH are jointly organizing the new "Digital Clinician Scientist Program" (D-CSP). The program is primarily aimed at physicians who are already working on innovative research projects to meet the technological challenges of data-driven medicine during their specialist training. The German Research Foundation (DFG) is funding the project for an initial period of three years.

The BIH Charité Digital Clinician Scientist Program will provide a new career path for the creators of digital change in medicine and will expand the successful Germany-wide model of the BIH Charité Clinician Scientist Program. In addition to the three-year individual funding, which is based on protected time for research, the focus is on modules for the acquisition of scientific skills (Big Data, bioinformatics or artificial intelligence) as well as mandatory mentoring. For the new program, various experts* from the Charité, the BIH, the Max Delbrück Center for Molecular Medicine (MDC), the Berlin Institute for Medical Systems Biology (BIMSB), the Einstein Center for Digital Future, and the Bernstein Center for Computational Neuroscience will be involved in the design of the D-CSP and in the recruitment and supervision of program participants.
Dual versus single vessel normothermic ex vivo perfusion of rat liver grafts using metamizole for vasodilatation
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F. Claussen, J.M.G.V. Gassner, S. Moosburner, D. Wyrwal, M. Nösser, P. Tang, L. Wegener, J. Pohl, A. Reutzel-Selke, R. Arsenic, J. Pratschke, I.M. Sauer, and N. Raschzok published their trecent work on "Dual versus single vessel normothermic ex vivo perfusion of rat liver grafts using metamizole for vasodilatation" in PLoS One 2020;15(7): e0235635.

Normothermic ex vivo liver perfusion (NEVLP) is a promising strategy to increase the donor pool in liver transplantation. Small animal models are essential to further investigate questions regarding organ preservation and reconditioning by NEVLP. A dual vessel small animal NEVLP (dNEVLP) model was developed using metamizole as a vasodilator and compared to conventional portovenous single vessel NEVLP (sNEVLP).

Livers of male Wistar rats were perfused with erythrocyte-supplemented culture medium for six hours by either dNEVLP via hepatic artery and portal vein or portovenous sNEVLP. dNEVLP was performed either with or without metamizole treatment. Perfusion pressure and flow rates were constantly monitored. Transaminase levels were determined in the perfusate at the start and after three and six hours of perfusion. Bile secretion was monitored and bile LDH and GGT levels were measured hourly. Histopathological analysis was performed using liver and bile duct tissue samples after perfusion.

Hepatic artery pressure was significantly lower in dNEVLP with metamizole administration. Compared to sNEVLP, dNEVLP with metamizole treatment showed higher bile production, lower levels of transaminases during and after perfusion as well as significantly lower necrosis in liver and bile duct tissue. Biochemical markers of bile duct injury showed the same trend.

Our miniaturized dNEVLP system enables normothermic dual vessel rat liver perfusion. The administration of metamizole effectively ameliorates arterial vasospasm allowing for six hours of dNEVLP, with superior outcome compared to sNEVLP.

Development of GelMA/PCL and dECM/PCL resins for 3D printing of acellular in vitro tissue scaffolds by stereolithography
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Gelatin methacryloyl (GelMA) is a chemically modified extracellular matrix (ECM)-derived biopolymer that is widely used for 3D fabrication of tissue engineering scaffolds. However, its tendency for physical gelation limits its use in aqueous 3D printing resins to low concentrations, yielding a poor printing resolution in stereolithography (SLA).
To obtain a GelMA-based resin that can be printed into high-resolution tissue scaffolds, we formulated resins of fish and porcine-derived GelMA in formamide using GelMA alone or mixed with star-shaped poly(ε-caprolactone) methacrylate (PCL-MA). We identified GelMA resins and GelMA/PCL-MA hybrid resins with a ratio of 70/30 wt-% to yield a suitable viscosity for SLA at 32 °C and demonstrated the resolution of the new resins in SLA by 3D printing acellular human small intestine-mimicking tissue scaffolds. The presence of PCL-MA in the hybrid resins improved the 3D printing fidelity compared to the neat GelMA resins, while GelMA provided the hybrid materials with enhanced swelling and proliferation of seeded cells. We further demonstrated the transferability of our resin formulation to native organ-derived materials by successfully replacing GelMA in the hybrid resin with solubilized, methacryloyl-functionalized decellularized liver ECM (dECM-MA) and by 3D printing multi-layer dECM/PCL-MA hydrogels.

"Development of GelMA/PCL and dECM/PCL resins for 3D printing of acellular in vitro tissue scaffolds by stereolithography" was published in Mater Sci Eng C Mater Biol Appl. 2020 Jul;112:110958. Authors are L. Elomaa, E. Keshi, I.M. Sauer, and M. Weinhart.
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