University Of Zurich Research Articles

A Single Dose of Local IL-12 Promotes Anti-Tumor Effect of Anti-EGFRvIII-CAR-T Cells in a Syngeneic Murine Model of Glioblastoma

Abstract Background Glioblastoma multiforme (GBM) is one of the most devastating brain tumors with poor prognosis and high mortality. Immunotherapy with chimeric antigen receptor (CAR) T cells is gaining attention as a promising strategy to treat this disease. An ideal candidate to target with CAR T cells is the tumor specific variant III of the epidermal growth factor receptor (EGFRvIII), which represents a mutation found in more than 30% of glioblastoma patients. However, anti-EGFRvIII-CAR modified T cell therapy has shown only limited effects in GBM patients, in all likelihood due to the immunosuppressive microenvironment that CAR T cells encounter in the tumor microenvironment (TME) of gliomas. To make gliomas susceptible to CAR T cell therapy, combinatorial approaches to convert the TME are required. Methods Mice received 5Gy TBI on day 15 post implantation, followed by intra-tumoral injection of IL-12:Fc on day 20 and infusion of EGFRvIII-directed CAR or non-transduced T cells on day 21. To perform functional analysis, we adopted high-parametric flow-cytometric characterization of the TME using 23 independent parameters 8 days after CAR T cells injection. We utilized unsupervised validated clustering approaches (FlowSOM and CellCNN) to discriminate between different cell populations. Results Here, we demonstrate that the combination of a single dose of local IL-12 with anti-EGFRvIII-CAR T cells synergizes to increase long-term survival in a syngeneic mouse model of GBM. IL-12 not only boosted the pro-inflammatory and cytotoxic activity of anti-EGFRvIII-CAR T cells, but also induced a complete remodelling of the tumor microenvironment (TME) with strong endogenous anti-tumor immune T cell responses. These findings highlight the capacity of IL-12 to induce an immunologically “cold” tumor such as GMB to acquire responsiveness to CAR T cells therapy. Conclusion This study demonstrates the capacity of IL-12 as local “adjuvant” therapy to boost the efficacy of CAR T cells and to awake the endogenous anti-tumor T cell responses. Legal entity responsible for the study University of Zurich. Funding University Research Priority Project and Advanced T-cell Engineered for Cancer Therapy. Disclosure M. Pule: Honoraria (self), Honoraria (institution): Autolus LTD. All other authors have declared no conflicts of interest.

Success rate 1 year after apical surgery: a retrospective analysis.

The aim of the current study was the retrospective analysis of the outcomes of teeth treated with apical surgery after a 1-year follow-up period. Furthermore, potential factors associated with the success rate were investigated. All patients were treated at the Clinic of Cranio-Maxillofacial and Oral Surgery at the University of Zurich between 2010 and 2017. To be eligible for inclusion, all patients were required to have undergone apical surgery with a retrograde root-end filling, and a 1-year follow-up examination at the University of Zurich. Treatment success at the 1-year follow-up time-point was defined as an absence of clinical complaints and radiographically determined healing. Parameters that were analysed included tooth localisation, periapical index of the preoperative lesion, administration of antibiotics, smoker status, histopathology of the apical lesion, radiographically determined sufficiency of root canal treatment pain and clinical signs of inflammation at the initial examination. A total of 81 teeth fulfilled all the inclusion criteria. At the 1-year follow-up, 91.4% of the teeth exhibited successful clinical and radiographic healing. The type of tooth was significantly associated with the success of the surgery (p = 0.006), but radiological severity of periapical inflammation, lesion histopathology, administration of antibiotics, smoker status, the quality of the root canal treatment, and preoperative pain and clinical signs of inflammation were not. The results of the present study suggest that apical surgery with retrograde root-end filling is a reliable therapy for the preservation of teeth. Furthermore, there are limited factors that affect the treatment outcome.

Vestibular bone thickness of the mandible in relation to the mandibular canal\u2014a retrospective CBCT-based study

BackgroundThe aim of this study was to assess vestibular bone thickness of the mandible in relation to the mandibular canal and position of the mental foramen in relation to the neighbouring teeth. Measurements were performed on radiographic cone-beam computed tomography (CBCT) images.MethodsThis retrospective study analysed 314 CBCTs, having been taken at the Clinic of Cranio-Maxillofacial and Oral Surgery, University of Zurich, Switzerland.ResultsCBCTs from 168 female and 146 male patients (median age 40.2 years) were analysed. Median bone thickness lateral to the nerve canal to the buccal mandibular cortical plate was ~ 4 mm immediately posterior to the mental foramen, increased to ≤ 6 mm over the next 30 mm, then decreased to ~ 3 mm at the level of the mandibular foramen. In two thirds of cases, both mental foramina were located near the second premolar (66.2% right, 67.7% left). Bone thickness and the position of the mental foramen showed marked intra- and interindividual variance.ConclusionsA preoperative CBCT is recommended for detailed planning of surgical interventions that may reach the mandibular canal (e.g. wisdom teeth removal, root resection, implant placement, bone block harvesting).

ESGCT 27th Annual Congress In collaboration with SETGyc Barcelona, Spain October 22–25, 2019 Abstracts

Xenotransplantation of transgenic porcine pancreatic islets offers a promising alternative source to circumvent current limitations posed by the scarcity of allogeneic donors. We have investigated the feasibility to generate tissue engineered SLA silenced islet cell clusters (ICC) to decrease xenogeneic immune responses Pancreatic islets single cell suspensions were generated by enzymatic digestion of porcine ICCs. Single cells were silenced for SLA expression by lentiviral vectors encoding for Nanoluciferase as reporter gene and for short hairpin RNAs targeting beta2-microglobulin or class II transactivator, respectively. SLA transcripts were evaluated by real-time PCR and protein levels by flow cytometry and fluorescence microscopy analyses. The effect of SLA silencing was evaluated in human T and NK cell cytotoxicity assays. SLA-silenced pancreatic beta-cells were then reassembled into ICCs in stirred bioreactors. SLA class I silencing reached a level of up to 84% and class II by up to 50% on pancreatic islet cell. Silencing SLA expression did not affect cell viability and the insulin-producing beta-cell phenotype. Xenogeneic T-cell immune responses (p < 0.05) as well as antibody-mediated cellular-dependent immune responses (p < 0.01) were significantly decreased. Silencing SLA class I expression did not increase susceptibility to NK-cell cytotoxicity. In stirred bioreactors, tissue engineered islets showing the typical 3D-structure and morphology of ICC were assembled from SLA-silenced pancreatic cell suspensions. These data shows the feasibility to generate low immunogenic porcine ICC from transgenic pigs after single cell engineering and post-transduction islet reassembling that might serve as a robust alternative to allogeneic pancreatic islet cell transplantation.

From rediscovered “niche” to “mainstream” – Glyceria fluitans as a candidate grain for manufacturing premium food products

From rediscovered “niche” to “mainstream” – <i>Glyceria fluitans</i> as a candidate grain for manufacturing premium food products

P5276A prospective pilot study to identify a myocarditis cohort who may safely resume sports activities 3 months after diagnosis

Abstract Background Sports activities may promote arrhythmias in the setting of acute myocarditis. International cardiovascular society recommendations to return to sports activities following acute myocarditis are based on expert consensus in the absence of prospective studies. Purpose We sought to identify patients who may safely resume sports activities 3 months after acute myocarditis. Methods We prospectively enrolled 27 patients with newly diagnosed myocarditis based on clinical parameters, elevated high sensitive troponin (TnT-hs) and cardiac magnetic resonance imaging (CMR) with mildly reduced or preserved LVEF. Follow-up examination included laboratory findings, electrocardiogram (ECG), 48-hour-Holter ECG, echocardiography, exercise stress testing and CMR. Cessation of physical activity was recommended for 3 months. All patients were followed for cardiac events for 12 months. Results Average age was 35 (19–80) years with 73% male patients. All patients performed 3- and 6-month follow-up with above mentioned diagnostic tests. Eight patients did not present for 12-month follow-up, but were contacted by phone. No cardiac events occurred within the interval of 12 months. After 3 months, participants achieved an average of 92% of predicted maximum power on stress test. One case of non-sustained ventricular tachycardia was recorded during 48-hour-Holter ECG. Except for this case, all patients were allowed to resume physical exercise after 3 months. At 6- (n=26) and 12-month (n=19) follow-up no arrhythmias, recurrent myocarditis, worsening left ventricular ejection fraction (LVEF) or physical performance were recorded. TnT-hs, creatine kinase (CK), myoglobin (Mb), and C-reactive protein (CRP) normalized. Conclusion The risk of cardiac events and decreasing LVEF appears to be low after early resumption of exercise in asymptomatic patients who recover from acute myocarditis. Acknowledgement/Funding Forschungskredit of the University of Zurich,the Holcim Foundation, the Hartmann Müller Foundation, and the Walter and Gertrud Siegenthaler Foundation

Participation in research: interest and opinions on participatory research among participants of asenior university

In gerontological research, older people are often used as test subjects. Participatory research means the active and equal involvement of those affected by the research question, i.e., the subjects and the academic researchers. But what is the interest in participatory research among older people who participate in an educational institution of the third age? In order to answer this question, participants of asenior university were interviewed. The survey was conducted as astandardized postal survey combined with an optional online survey of participants from the Senior University of Zurich (Switzerland). The sample consisted of 811 persons aged between 56 and 96years. Of the respondents 24% had already participated in aparticipatory research project and of these, older people and people with ahigh level of education were more likely to be involved, as were people who are more likely to be extraverted and who regularly volunteer. Of all respondents, 62% were interested in participatory research projects. In amultivariate perspective, interest depended on age, education, volunteering and experience with such research projects. The interest in participatory participation among Senior University members was high. This interest was more pronounced among people who already had experience with such projects. Further studies should evaluate the interest in research participation on the basis of implemented participatory projects and define optimal framework conditions.

Solution and Solid‐State Structure of the First NHC‐Substituted Rhenium Heptahydrides

AbstractInvited for the cover of this issue are Dr. Gabriele Grieco from the Zurich University of Applied Science (ZHAW) and Dr. Olivier Blacque from the University of Zurich Irchel (UZH), Switzerland. The cover image shows the crystal structure of a carbene‐ligand‐bearing rhenium heptahydride obtained with an X‐ray diffractometer.

Visual and passive acoustic observations of blue whale trios from two distinct populations

Visual and passive acoustic observations of blue whale trios from two distinct populations

Top 100 cited systematic reviews and meta-analyses in dentistry

Objective: The purpose of the present study was to identify the 100 top cited systematic reviews and meta-analyses on dental journals so as to gain insight into the influential publications in dentistry.Material and methods: The Web of Science was used to comprehensively identify the 100 most cited papers without year and language restriction. Specific parameters regarding the title, journal, publication year, authors, country of origin, institution and university, collaborations, keyword analysis and field of study of each manuscript were retrieved.Results: The citations ranged from 642 to 140. The most productive years were 2008 and 2009. The majority of top cited papers were published in Clinical Oral Implants Research and Journal of Clinical Periodontology. The leading countries were United States, followed by Switzerland. The University of Zurich was the most productive institution with 8 articles. Major topics of interest in the top 100 most-cited papers were dental implants and periodontology. The most frequently occurring keywords were systematic review, dental implants and meta-analyses.Conclusions: Systematic reviews published in high impact factor Dental journals focused on implantology and periodontology had the highest citation rates. Obviously, the top cited list is dynamic, as scientific interests and research tendencies evolve over the years.

How are map-based decisions influenced by uncertainty visualization in risky and time-critical situations?

How are map-based decisions influenced by uncertainty visualization in risky and time-critical situations?

On Eggs

Free AccessOn EggsJana Harper’s Interventions in RealityFrauke BerndtFrauke BerndtFrauke Berndt, PhD Goethe University, is Full Professor for German Literature at the University of Zurich. Having received her Habilitation from the Goethe University, Frankfurt am Main, she holds positions there and in Tübingen. She was Visiting Professor at the University of Chicago, Indiana University, University of Oregon, and Vanderbilt University. Her research focuses on German literary history of the 18th and 19th century, mainly rhetoric, aesthetics, and poetics as well as literary theory and gender studies. She is head of the research group ETHOS that investigates ethical practices in 18th century aesthetic theory. Currently, she works on a monograph Facing Poetry – A. G. Baumgarten’s Literary Theory (forthcoming with de Gruyter in 2020).Search for more papers by this authorPublished Online:Feb 2020https://doi.org/10.7788/figu.2019.20.1.103SectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInRedditEmail About Previous article Next article FiguresReferencesRelatedDetails Download book cover ISSN: 1439-4367eISSN: 2194-363XHistoryPublished online:February 2020 PDF download

Implementation of a Flexible Learning Study Programme in a Blended-Learning Design: Results from the First Two Cohorts

Zurich University of Applied Sciences (ZHAW) launched the flexible learning study format FLEX, a blended learning design allowing students increased flexibility as to when and where they study. FLEX reduces classroom time by about half, while adding an e-learning environment for self-study that includes instructional videos. An analysis of the first two cohorts in the assessment level showed that the new study format was broadly accepted and that students using the FLEX format achieved exam results equivalent to students in the conventional learning format.

3D data related to the publication: A new species of Palaeopython (Serpentes) and other extinct squamates from the Eocene of Dielsdorf (Zurich, Switzerland)

INTRODUCTION CT scanning was conducted in three different-sized snake vertebrae of Palaeopython helveticus sp. nov., including its holotype PIMUZ A/III 634, from Eocene fissure fills at Dielsdorf, near Zurich, Switzerland (e.g., Rosselet, 1991) in order to detect and evaluate ontogenetic variability in these fossils. In addition, a dentary of Palaeovaranus sp. was scanned to elucidate its internal histology and tooth implementation (Fig. 1 and Table METHODS The bones (snake vertebrae; dentary) from Dielsdorf were scanned with a Nikon XTH 225 ST CT Scanner housed at the Anthropological Department of the University of Zurich. The microcomputed tomography scan of the vertebrae was taken with a voltage of 91 kV and a current of 345 μA, yielding a voxel size of 0.03758 mm, with no filter used. The dentary was scanned with a voltage of 162 kV, a current of 102 μA, yielding a voxel size of 0.01654 mm, again with no filter used. Reconstruction of the digital stack for virtual 3D reconstruction was achieved using VG Studio Max 2.2. The 3D surface models are provided in .ply format and the datasets in DICOM format, and can therefore be opened with a wide range of freeware.

Introduction

Orbis LitterarumVolume 74, Issue 3 p. 153-160 EDITORIAL Introduction Style: Industrial, digital, individual Fabian Schwitter, Fabian Schwitter University of Zurich, Zürich, SwitzerlandSearch for more papers by this author Fabian Schwitter, Fabian Schwitter University of Zurich, Zürich, SwitzerlandSearch for more papers by this author First published: 29 May 2019 https://doi.org/10.1111/oli.12226Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume74, Issue3Special Issue: StyleJune 2019Pages 153-160 RelatedInformation

Insomnia in Patients Seeking Care at an Orofacial Pain Unit.

Introduction: Orofacial pain and dysfunction include a broad range of disturbances among which pain and insomnia are some of the most common complaints. Sleep strengthens physiological and psychological resilience and is an absolute requirement for health. Insomnia is a common symptom or sleep disorder, yet data on its prevalence is sparse. Here we extracted data from the insomnia severity index which was part of the web-based interdisciplinary symptom evaluation (WISE) tool given to a large sample of patients seeking care at an orofacial pain unit for analyzing insomnia prevalence in this clinical population.Material and methods: Anonymized data were available from 952 patients who consulted the Orofacial Pain Unit at the Center of Dental Medicine, University of Zurich, Zurich, Switzerland between January 2017 and December 2018. Prevalence data for insomnia stratified by gender and 10 age groups (decades) were calculated. The distribution of four insomnia severity grades was determined, also stratified by age and gender.Results: 952 patients (290 men: 30.5%) with a mean age of 44.8 ± 17.4 years completed a WISE. Three hundred and fifty-two (37.0%) patients with a mean age of 45.8 ± 16.7 years positively responded to a screening question for insomnia and/or hypersomnia. Insomnia was severe in women from the 2nd to 8th decade, ranging from 4.3% (3rd decade) to 14.5% (6th decade), and moderately severe from the 2nd to 9th decade, ranging from 18.8% (6th decade) to 27.8% (2nd decade). In men, severe insomnia was present from the 3rd to 7th decade, ranging from 2.3% (7th decade) to 4.4% (4th decade) and moderately severe insomnia from the 3rd to 7th decade, ranging from 4.6% (7th decade) to 12.2% (5th decade).Conclusions: This is the first study reporting on insomnia in a large sample of patients seeking care at an orofacial pain unit. One in three patients reported some form of sleep disturbances, which for almost half of them was moderate to severe insomnia. The gender ratio was almost equal throughout adulthood, yet younger and older women were more frequently affected and experienced higher insomnia severity than men.

Price for a good idea: $10,000

Students or young professionals can win a $10,000 prize to help realize an idea for reducing carbon emissions from industrial processes and products. Sponsors of the Carbon Footprint Challenge—including Covestro, Evonik Industries, and universities such as ETH Zurich and RWTH Aachen University—are looking for process efficiency, sustainable raw materials, and carbon sequestration technologies. Submissions are due in early July at carbonfootprintchallenge.org. The top five teams will get to pitch their ideas at an event in Zurich in early September.

Editorial

This issue marks the second year since Studies in Communication Sciences (SComS) is published Open Access on the HOPE platform of the University of Zurich (www. scoms.ch). The present issue of SComS perfectly reflects the unique character of the journal. Not only do we present you a thematic section with a very innovative topic, namely Fashion Communication. We also collect three papers in the general section that, despite their different topics, have something in common that is telling for the role of communication in Switzerland.

Challenging cases during clinical clerkships beyond the domain of the "medical expert": an analysis of students' case vignettes.

Background: During clinical clerkships students experience complex and challenging clinical situations related to problems beyond the domain of the “Medical Expert”. Workplace routine may leave little opportunity to reflect on these situations. The University of Zurich introduced a mandatory course directly after the clinical clerkship year (CCY) to work up these situations. Prior to the course each student submitted a vignette on a case he or she had perceived challenging during the CCY and which was not related to the domain of the “Medical Expert” role. In this paper we want to characterize these cases in respect to most prominent themes and related CanMEDS roles. The goal was to inform clinical supervisors about potential teaching demands during the CCY. Methods: All case vignettes submitted by a years’ cohort were analysed by three researchers in two ways: for the clinical characteristics and the main theme of the underlying problem and the most prominent CanMEDS roles involved. Themes of the underlying problem were aggregated to overarching topics and subsequently to main categories by pragmatic thematic analysis.Results: 254 case vignettes covered the whole spectrum of clinical disciplines. A wide range of underlying themes could be assigned to five main categories: “communication within team” (23.2%), “communication with patients and relatives” (24.8%), “patient behavior and attitudes” (18.5%), “clinical decision making” (24.0%), and “social and legal issues” (9.4%). Most frequent CanMEDS roles were “Communicator” (26.9%) and “Professional” (23.5%).Conclusions: Cases students perceived as challenging beyond the “Medical Expert” were reported from all clinical disciplines. These were mainly related to communicational and professional issues, mirrored by the CanMEDS roles “Communicator” and “Professional”. Therefore, supervisors in clinical clerkships should put an additional teaching focus on communication and professionalism.

Preface

PREFACEThe “Victor Villanueva Memorial Meeting” to pay homage to our friend and colleague Victor Manuel Villanueva Sandoval was held at the premises of the Institute of Physics and Mathematics, University of Michoacán in Morelia, Michoacán, Mexico, on December 6, 2013, about 3 months after his tragic demise. This gathering was attended by his close friends, family, collaborators, colleagues and students. Several of those who could not physically be present for this commemorative gathering sent their messages of condolence and/or scientific contributions for this proceedings volume for which we are immensely grateful.The meeting started with personal recollections by Victor’s wife Ana Rosa Tenorio Lúa and his sisters Alejandra and Gabriela Villanueva. His daughters Ana Paola, Daniela and Mariana were also present to grace the solemn occasion and later provided us with their heart-felt messages. The academic part of the meeting started with Adnan Bashir presenting a summary of Victor’s scientific life, his research and its impact.Research talks were then presented by Luis Villaseñor (Ultra energetic cosmic rays - recent results), Mauro Napsuciale (A formalism for higher spins based on parity), Christian Schubert (Amplitudes with many photons in QED), Naser Ahmadiniaz (Amplitudes with gluons in a string inspired formalism), Carlos Vaquera (Second order fermions and renormalization) and Adnan Bashir (Strong interactions - peculiarities and challenges). There were several potential and interested speakers who were unable to physically attend the meeting but, as we have mentioned before, agreed to send their contribution for the proceedings volume at a later date. They are Dmitry Antonov (University of Lisboa, Portugal), Fiorenzo Bastianelli and Roberto Bonezzi (University of Bologna and INFN, Italy), Olindo Corradini (University of Modena and Reggio Emilia, Italy), Pietro Dall’Olio (University of Michoacán, Mexico), Jan Govaerts (Université Catholique de Louvian, Belgium), Emanuele Latini (University of Zurich, Switzerland), Khaled Hassan Ould-Lahoucie (University Ferhat Abbas of Setif, Algeria), Eckehard Mielke (Metropolitan Autonomous University of Iztapalapa, Mexico), Néstor Ortiz, Olivier Sarbach and Thomas Zannias (University of Michoacán, Mexico).We are very grateful to the director Ricardo Becerril and personnel of the Institute of Physics and Mathematics, University of Michoacán, who ensured a smooth and pleasant organization of the meeting. We offer our special thanks to Itzel Alvarez who prepared a beautiful poster to announce the meeting. She also organized the personal part of the material for the proceedings in an outstanding manner.Finally, we would like this meeting and the proceedings volume to serve as a token of our appreciation and admiration for our friend Victor Villanueva. We also hope it serves as an inspiration for Victor’s students and his daughters Paola, Daniela and Mariana to follow in his footsteps and attempt to reach the stars.Adnan BashirChristian Schubert