Publications by authors named "Florian Huber"

101 Publications

Nanoparticle Additivation Effects on Laser Powder Bed Fusion of Metals and Polymers-A Theoretical Concept for an Inter-Laboratory Study Design All Along the Process Chain, Including Research Data Management.

Materials (Basel) 2021 Aug 27;14(17). Epub 2021 Aug 27.

Technical Chemistry I, Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg Essen, 45141 Essen, Germany.

In recent years, the application field of laser powder bed fusion of metals and polymers extends through an increasing variability of powder compositions in the market. New powder formulations such as nanoparticle (NP) additivated powder feedstocks are available today. Interestingly, they behave differently along with the entire laser powder bed fusion (PBF-LB) process chain, from flowability over absorbance and microstructure formation to processability and final part properties. Recent studies show that supporting NPs on metal and polymer powder feedstocks enhances processability, avoids crack formation, refines grain size, increases functionality, and improves as-built part properties. Although several inter-laboratory studies (ILSs) on metal and polymer PBF-LB exist, they mainly focus on mechanical properties and primarily ignore nano-additivated feedstocks or standardized assessment of powder feedstock properties. However, those studies must obtain reliable data to validate each property metric's repeatability and reproducibility limits related to the PBF-LB process chain. We herein propose the design of a large-scale ILS to quantify the effect of nanoparticle additivation on powder characteristics, process behavior, microstructure, and part properties in PBF-LB. Besides the work and sample flow to organize the ILS, the test methods to measure the NP-additivated metal and polymer powder feedstock properties and resulting part properties are defined. A research data management (RDM) plan is designed to extract scientific results from the vast amount of material, process, and part data. The RDM focuses not only on the repeatability and reproducibility of a metric but also on the FAIR principle to include findable, accessible, interoperable, and reusable data/meta-data in additive manufacturing. The proposed ILS design gives access to principal component analysis (PCA) to compute the correlations between the material-process-microstructure-part properties.
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http://dx.doi.org/10.3390/ma14174892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432694PMC
August 2021

Current status of MSK radiology training: an international survey by the European Society of Musculoskeletal Radiology (ESSR) Young Club.

Insights Imaging 2021 Sep 9;12(1):126. Epub 2021 Sep 9.

IRCCS Istituto Ortopedico Galeazzi, Via Riccardo Galeazzi 4, 20161, Milan, Italy.

Objectives: There is wide variation between Countries in the structures of residency programmes, need for subspecialisation, and health care system organisation. This survey was aimed at gathering information regarding current musculoskeletal (MSK) educational programmes offered both in European and non-European Countries.

Methods: We administered an online survey to European Society of Radiology (ESR) residents and radiologists aged up to 35 years. The questionnaire was further disseminated by delegates of the ESR Radiology Trainees Forum. Survey consisted of 20 questions about the structure and organisation of MSK training programmes.

Results: Overall, 972 participants from 86 Countries completed the survey, with a wide heterogeneity of answers. Of them, 636 were residents (65.9%), 329 were certified radiologists (34.1%), with a mean age of 30.8 ± 3 years. Almost half of the participants had a dedicated MSK rotation/block during residency, with a duration of 3-6 months in 62.5% of cases. A dedicated period in MSK Ultrasound was present in only one-third of residency programmes; 38% of participants were expected to learn interventional MSK procedures, but only 28.2% have been actively involved in interventions during their residency. Overall, 62.7% of participants rated the quality of their MSK training as poor to average. Almost all (93.1%) thought that MSK training could be improved in their residency, especially ultrasound practice (80.7%) and MRI reporting (71.1%).

Conclusions: There are significant inconsistencies in the structure of MSK training offered by different Countries. Radiology trainees are showing substantial interest in MSK training, which necessitates strategic investments to standardise and enhance its quality.
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http://dx.doi.org/10.1186/s13244-021-01070-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427152PMC
September 2021

Correlation of dynamic contrast-enhanced bone perfusion with morphologic ultra-short echo time MR imaging in medication-related osteonecrosis of the jaw.

Dentomaxillofac Radiol 2021 Aug 18:20210036. Epub 2021 Aug 18.

Faculty of Medicine, University of Zurich, Zurich, Switzerland.

Objectives: To investigate whether dynamic contrast-enhanced (DCE)-MR bone perfusion could serve as surrogate for morphologic ultra-short echo time (UTE) bone images and to correlate perfusion with morphologic hallmarks in histologically proven foci of medication-related osteonecrosis of the jaw (MRONJ).

Methods: Retrospective study including 20 patients with established diagnosis of MRONJ. Qualitative consensus assessment of predefined jaw regions by two radiologists was used as reference standard using Likert scale (0-3) for standard imaging hallmarks in MRONJ (osteolysis, sclerosis, periosteal thickening). DCE-MRI measurements performed in corresponding regions of the mandible were then correlated with qualitative scores. Regions were grouped into "non-affected" and "pathologic" based on binarized Likert scores of different imaging hallmarks (0-1 2-3). DCE-MRI measurements among hallmarks were compared using Mann-Whitney--testing. ROC (receiver-operating-characteristic) analysis was performed for each of the perfusion parameters to assess diagnostic performance for identification of MRONJ using morphologic ratings as reference standard.

Results: Median perfusion measurements of "pathologic" regions in wash-in, peak enhancement intensity and integrated area under the curve are significantly higher than those of "non-affected" regions, irrespective of reference imaging hallmark ( < 0.05). No significant perfusion differences were found between "pathologic" regions with and without osteolysis ( = 0.180). ROC analysis showed fair diagnostic performance of DCE-MRI parameters for identification of MRONJ (AUC 0.626-0.727).

Conclusions: DCE bone perfusion parameters are significantly increased in MRONJ compared to non-affected regions, irrespective of osteolysis. Due to certain overlap DCE-MRI bone perfusion cannot serve as full surrogate for UTE bone imaging but may enhance reader confidence.
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http://dx.doi.org/10.1259/dmfr.20210036DOI Listing
August 2021

AI MSK clinical applications: spine imaging.

Skeletal Radiol 2021 Jul 15. Epub 2021 Jul 15.

Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.

Recent investigations have focused on the clinical application of artificial intelligence (AI) for tasks specifically addressing the musculoskeletal imaging routine. Several AI applications have been dedicated to optimizing the radiology value chain in spine imaging, independent from modality or specific application. This review aims to summarize the status quo and future perspective regarding utilization of AI for spine imaging. First, the basics of AI concepts are clarified. Second, the different tasks and use cases for AI applications in spine imaging are discussed and illustrated by examples. Finally, the authors of this review present their personal perception of AI in daily imaging and discuss future chances and challenges that come along with AI-based solutions.
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http://dx.doi.org/10.1007/s00256-021-03862-0DOI Listing
July 2021

Comparison of metal artifact reduction techniques in magnetic resonance imaging of carbon-reinforced PEEK and titanium spinal implants.

Acta Radiol 2021 Jul 6:2841851211029077. Epub 2021 Jul 6.

Department of Diagnostic and Interventional Radiology, University Hospital Zurich, Switzerland.

Background: Carbon-reinforced PEEK (C-FRP) implants are non-magnetic and have increasingly been used for the fixation of spinal instabilities.

Purpose: To compare the effect of different metal artifact reduction (MAR) techniques in magnetic resonance imaging (MRI) on titanium and C-FRP spinal implants.

Material And Methods: Rod-pedicle screw constructs were mounted on ovine cadaver spine specimens and instrumented with either eight titanium pedicle screws or pedicle screws made of C-FRP and marked with an ultrathin titanium shell. MR scans were performed of each configuration on a 3-T scanner. MR sequences included transaxial conventional T1-weighted turbo spin echo (TSE) sequences, T2-weighted TSE, and short-tau inversion recovery (STIR) sequences and two different MAR-techniques: high-bandwidth (HB) and view-angle-tilting (VAT) with slice encoding for metal artifact correction (SEMAC). Metal artifact degree was assessed by qualitative and quantitative measures.

Results: There was a much stronger effect on artifact reduction with using C-FRP implants compared to using specific MRI MAR-techniques (screw shank:  < 0.001; screw tulip:  < 0.001; rod:  < 0.001). VAT-SEMAC sequences were able to reduce screw-related signal loss artifacts in constructs with titanium screws to a certain degree. Constructs with C-FRP screws showed less artifact-related implant diameter amplification when compared to constructs with titanium screws ( < 0.001).

Conclusion: Constructs with C-FRP screws are associated with significantly less artifacts compared to constructs with titanium screws including dedicated MAR techniques. Artifact-reducing sequences are able to reduce implant-related artifacts. This effect is stronger in constructs with titanium screws than in constructs with C-FRP screws.
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http://dx.doi.org/10.1177/02841851211029077DOI Listing
July 2021

In-Situ Alloy Formation of a WMoTaNbV Refractory Metal High Entropy Alloy by Laser Powder Bed Fusion (PBF-LB/M).

Materials (Basel) 2021 Jun 4;14(11). Epub 2021 Jun 4.

Institute of Photonic Technologies, Faculty of Engineering, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Konrad-Zuse-Straße 3/5, 91052 Erlangen, Germany.

High entropy or multi principal element alloys are a promising and relatively young concept for designing alloys. The idea of creating alloys without a single main alloying element opens up a wide space for possible new alloy compositions. High entropy alloys based on refractory metals such as W, Mo, Ta or Nb are of interest for future high temperature applications e.g., in the aerospace or chemical industry. However, producing refractory metal high entropy alloys by conventional metallurgical methods remains challenging. For this reason, the feasibility of laser-based additive manufacturing of the refractory metal high entropy alloy WMoTaNbV by laser powder bed fusion (PBF-LB/M) is investigated in the present work. In-situ alloy formation from mixtures of easily available elemental powders is employed to avoid an expensive atomization of pre-alloyed powder. It is shown that PBF-LB/M of WMoTaNbV is in general possible and that a complete fusion of the powder mixture without a significant number of undissolved particles is achievable by in-situ alloy formation during PBF-LB/M when selecting favorable process parameter combinations. The relative density of the samples with a dimension of 6 × 6 × 6 mm reaches, in dependence of the PBF-LB/M parameter set, 99.8%. Electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM) measurements confirm the presence of a single bcc-phase. Scanning electron microscopy (SEM) images show a dendritic and/or cellular microstructure that can, to some extent, be controlled by the PBF-LB/M parameters.
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http://dx.doi.org/10.3390/ma14113095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201384PMC
June 2021

Whole-body Composition Profiling Using a Deep Learning Algorithm: Influence of Different Acquisition Parameters on Algorithm Performance and Robustness.

Invest Radiol 2021 Jun 1. Epub 2021 Jun 1.

From the Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, and Faculty of Medicine, University of Zurich Computer Vision Lab, ETH Zurich, Zurich, Switzerland.

Objectives: To develop, test, and validate a body composition profiling algorithm for automated segmentation of body compartments in whole-body magnetic resonance imaging (wbMRI) and to investigate the influence of different acquisition parameters on performance and robustness.

Materials And Methods: A segmentation algorithm for subcutaneous and visceral adipose tissue (SCAT and VAT) and total muscle mass (TMM) was designed using a deep learning U-net architecture convolutional neuronal network. Twenty clinical wbMRI scans were manually segmented and used as training, validation, and test datasets. Segmentation performance was then tested on different data, including different magnetic resonance imaging protocols and scanners with and without use of contrast media. Test-retest reliability on 2 consecutive scans of 16 healthy volunteers each as well as impact of parameters slice thickness, matrix resolution, and different coil settings were investigated. Sorensen-Dice coefficient (DSC) was used to measure the algorithms' performance with manual segmentations as reference standards. Test-retest reliability and parameter effects were investigated comparing respective compartment volumes. Abdominal volumes were compared with published normative values.

Results: Algorithm performance measured by DSC was 0.93 (SCAT) to 0.77 (VAT) using the test dataset. Dependent from the respective compartment, similar or slightly reduced performance was seen for other scanners and scan protocols (DSC ranging from 0.69-0.72 for VAT to 0.83-0.91 for SCAT). No significant differences in body composition profiling was seen on repetitive volunteer scans (P = 0.88-1) or after variation of protocol parameters (P = 0.07-1).

Conclusions: Body composition profiling from wbMRI by using a deep learning-based convolutional neuronal network algorithm for automated segmentation of body compartments is generally possible. First results indicate that robust and reproducible segmentations equally accurate to a manual expert may be expected also for a range of different acquisition parameters.
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http://dx.doi.org/10.1097/RLI.0000000000000799DOI Listing
June 2021

Differentiation of inflammatory from degenerative changes in the sacroiliac joints by machine learning supported texture analysis.

Eur J Radiol 2021 Jul 11;140:109755. Epub 2021 May 11.

Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland; Faculty of Medicine, University of Zurich, Switzerland.

Purpose: To compare the diagnostic performance of texture analysis (TA) against visual qualitative assessment in the differentiation of spondyloarthritis (SpA) from degenerative changes in the sacroiliac joints (SIJ).

Method: Ninety patients referred for suspected inflammatory lower back pain from the rheumatology department were retrospectively included at our university hospital institution. MRI at 3 T of the lumbar spine and SIJ was performed with oblique coronal T1-weighted (w), fluid-sensitive fat-saturated (fs) TIRM and fsT1w intravenously contrast-enhanced (CE) images. Subjects were divided into three age- and gender-matched groups (30 each) based on definite clinical diagnosis serving as clinical reference standard with either degenerative, inflammatory (SpA) or no changes of the SIJ. SIJ were rated qualitatively by two independent radiologists and quantitatively by region-of-interest-based TA with 304 features subjected to machine learning logistic regression with randomized ten-fold selection of training and validation data. Qualitative and quantitative results were evaluated for diagnostic performance and compared against clinical reference standard.

Results: Agreement of radiologist's diagnose with clinical reference was fair for both readers (κ = 0.32 and 0.44). ROC statistics revealed significant outperformance of TA compared to qualitative ratings for differentiation of SpA from remainder (AUC = 0.89 vs. 0.75), SpA from degenerative (AUC = 0.91 vs. 0.67) and TIRM-positive SpA (i.e. with bone marrow edema) from remainder cases (AUC = 0.95 vs. 0.76). T1w-CE images were the most important discriminator for detection of SpA.

Conclusions: TA is superior to qualitative assessment for the differentiation of inflammatory from degenerative changes of the SIJ. Intravenous CE-images increase diagnostic yield in quantitative TA.
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http://dx.doi.org/10.1016/j.ejrad.2021.109755DOI Listing
July 2021

Combining shrinkage and sparsity in conjugate vector autoregressive models.

J Appl Econ (Chichester Engl) 2021 Apr-May;36(3):304-327. Epub 2021 Jan 13.

Joint Research Centre European Commission Ispra Italy.

Conjugate priors allow for fast inference in large dimensional vector autoregressive (VAR) models. But at the same time, they introduce the restriction that each equation features the same set of explanatory variables. This paper proposes a straightforward means of postprocessing posterior estimates of a conjugate Bayesian VAR to effectively perform equation-specific covariate selection. Compared with existing techniques using shrinkage alone, our approach combines shrinkage and sparsity in both the VAR coefficients and the error variance-covariance matrices, greatly reducing estimation uncertainty in large dimensions while maintaining computational tractability. We illustrate our approach by means of two applications. The first application uses synthetic data to investigate the properties of the model across different data-generating processes, and the second application analyzes the predictive gains from sparsification in a forecasting exercise for U.S. data.
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http://dx.doi.org/10.1002/jae.2807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048898PMC
January 2021

Dynamic shrinkage in time-varying parameter stochastic volatility in mean models.

J Appl Econ (Chichester Engl) 2021 Mar 6;36(2):262-270. Epub 2021 Jan 6.

Department of Economics Salzburg Centre of European Union Studies University of Salzburg Mönchsberg 2A Salzburg 5020 Austria.

Successful forecasting models strike a balance between parsimony and flexibility. This is often achieved by employing suitable shrinkage priors that penalize model complexity but also reward model fit. In this article, we modify the stochastic volatility in mean (SVM) model by introducing state-of-the-art shrinkage techniques that allow for time variation in the degree of shrinkage. Using a real-time inflation forecast exercise, we show that employing more flexible prior distributions on several key parameters sometimes improves forecast performance for the United States, the United Kingdom, and the euro area (EA). Comparing in-sample results reveals that our proposed model yields qualitatively similar insights to the original version of the model.
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http://dx.doi.org/10.1002/jae.2804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048439PMC
March 2021

Debottlenecking a Pulp Mill by Producing Biofuels from Black Liquor in Three Steps.

ChemSusChem 2021 Jun 6;14(11):2414-2425. Epub 2021 May 6.

Department of Organic Chemistry, Stockholm University, 10691, Stockholm, Sweden.

By extracting lignin, pulp production can be increased without heavy investments in a new recovery boiler, the typical bottleneck of a pulp mill. The extraction is performed by using 0.20 and 0.15 weight equivalents of CO and H SO respectively. Herein, we describe lignin esterification with fatty acids using benign reagents to generate a lignin ester mixable with gas oils. The esterification is accomplished by activating the fatty acid and lignin with acetic anhydride which can be regenerated from the acetic acid recycled in this reaction. The resulting mass balance ratio is fatty acid/lignin/acetic acid (2 : 1 : 0.1). This lignin ester can be hydroprocessed to generate hydrocarbons in gasoline, aviation, and diesel range. A 300-hour continuous production of fuel was accomplished. By recirculating reagents from both the esterification step and applying a water gas shift reaction on off-gases from the hydroprocessing, a favorable overall mass balance is realized.
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http://dx.doi.org/10.1002/cssc.202100496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251813PMC
June 2021

Sensitive Immunopeptidomics by Leveraging Available Large-Scale Multi-HLA Spectral Libraries, Data-Independent Acquisition, and MS/MS Prediction.

Mol Cell Proteomics 2021 Apr 9;20:100080. Epub 2021 Apr 9.

Department of Oncology, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital and the University of Lausanne, Lausanne, Switzerland. Electronic address:

Mass spectrometry (MS) is the state-of-the-art methodology for capturing the breadth and depth of the immunopeptidome across human leukocyte antigen (HLA) allotypes and cell types. The majority of studies in the immunopeptidomics field are discovery driven. Hence, data-dependent tandem MS (MS/MS) acquisition (DDA) is widely used, as it generates high-quality references of peptide fingerprints. However, DDA suffers from the stochastic selection of abundant ions that impairs sensitivity and reproducibility. In contrast, in data-independent acquisition (DIA), the systematic fragmentation and acquisition of all fragment ions within given isolation m/z windows yield a comprehensive map for a given sample. However, many DIA approaches commonly require generating comprehensive DDA-based spectrum libraries, which can become impractical for studying noncanonical and personalized neoantigens. Because the amount of HLA peptides eluted from biological samples such as small tissue biopsies is typically not sufficient for acquiring both meaningful DDA data necessary for generating comprehensive spectral libraries and DIA MS measurements, the implementation of DIA in the immunopeptidomics translational research domain has remained limited. We implemented a DIA immunopeptidomics workflow and assessed its sensitivity and accuracy by matching DIA data against libraries with growing complexity-from sample-specific libraries to libraries combining 2 to 40 different immunopeptidomics samples. Analyzing DIA immunopeptidomics data against a complex multi-HLA spectral library resulted in a two-fold increase in peptide identification compared with sample-specific library and in a three-fold increase compared with DDA measurements, yet with no detrimental effect on the specificity. Furthermore, we demonstrated the implementation of DIA for sensitive personalized neoantigen discovery through the analysis of DIA data with predicted MS/MS spectra of clinically relevant HLA ligands. We conclude that a comprehensive multi-HLA library for DIA approach in combination with MS/MS prediction is highly advantageous for clinical immunopeptidomics, especially when low amounts of biological samples are available.
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http://dx.doi.org/10.1016/j.mcpro.2021.100080DOI Listing
April 2021

Measuring the effectiveness of US monetary policy during the COVID-19 recession.

Scott J Polit Econ 2021 Feb 22. Epub 2021 Feb 22.

University of Salzburg Salzburg Austria.

The COVID-19 recession that started in March 2020 led to an unprecedented decline in economic activity across the globe. To fight this recession, policy makers in central banks engaged in expansionary monetary policy. This paper asks whether the measures adopted by the US Federal Reserve (Fed) have been effective in boosting real activity and calming financial markets. To measure these effects at high frequencies, we propose a novel mixed frequency vector autoregressive (MF-VAR) model. This model allows us to combine weekly and monthly information within a unified framework. Our model combines a set of macroeconomic aggregates such as industrial production, unemployment rates, and inflation with high-frequency information from financial markets such as stock prices, interest rate spreads, and weekly information on the Fed's balance sheet size. The latter set of high-frequency time series is used to dynamically interpolate the monthly time series to obtain weekly macroeconomic measures. We use this setup to simulate counterfactuals in absence of monetary stimulus. The results show that the monetary expansion caused higher output growth and stock market returns, more favorable long-term financing conditions and a depreciation of the US dollar compared with a no-policy benchmark scenario.
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http://dx.doi.org/10.1111/sjpe.12275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014274PMC
February 2021

Personalized cancer vaccine strategy elicits polyfunctional T cells and demonstrates clinical benefits in ovarian cancer.

NPJ Vaccines 2021 Mar 15;6(1):36. Epub 2021 Mar 15.

Department of Oncology, Lausanne University Hospital (CHUV), Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland.

T cells are important for controlling ovarian cancer (OC). We previously demonstrated that combinatorial use of a personalized whole-tumor lysate-pulsed dendritic cell vaccine (OCDC), bevacizumab (Bev), and cyclophosphamide (Cy) elicited neoantigen-specific T cells and prolonged OC survival. Here, we hypothesize that adding acetylsalicylic acid (ASA) and low-dose interleukin (IL)-2 would increase the vaccine efficacy in a recurrent advanced OC phase I trial (NCT01132014). By adding ASA and low-dose IL-2 to the OCDC-Bev-Cy combinatorial regimen, we elicited vaccine-specific T-cell responses that positively correlated with patients' prolonged time-to-progression and overall survival. In the ID8 ovarian model, animals receiving the same regimen showed prolonged survival, increased tumor-infiltrating perforin-producing T cells, increased neoantigen-specific CD8 T cells, and reduced endothelial Fas ligand expression and tumor-infiltrating T-regulatory cells. This combinatorial strategy was efficacious and also highlighted the predictive value of the ID8 model for future ovarian trial development.
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http://dx.doi.org/10.1038/s41541-021-00297-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960755PMC
March 2021

Prediction of neo-epitope immunogenicity reveals TCR recognition determinants and provides insight into immunoediting.

Cell Rep Med 2021 Feb 6;2(2):100194. Epub 2021 Feb 6.

Department of Oncology, Ludwig Institute for Cancer Research Lausanne, University of Lausanne, Lausanne, Switzerland.

CD8+ T cell recognition of peptide epitopes plays a central role in immune responses against pathogens and tumors. However, the rules that govern which peptides are truly recognized by existing T cell receptors (TCRs) remain poorly understood, precluding accurate predictions of neo-epitopes for cancer immunotherapy. Here, we capitalize on recent (neo-)epitope data to train a predictor of immunogenic epitopes (PRIME), which captures molecular properties of both antigen presentation and TCR recognition. PRIME not only improves prioritization of neo-epitopes but also correlates with T cell potency and unravels biophysical determinants of TCR recognition that we experimentally validate. Analysis of cancer genomics data reveals that recurrent mutations tend to be less frequent in patients where they are predicted to be immunogenic, providing further evidence for immunoediting in human cancer. PRIME will facilitate identification of pathogen epitopes in infectious diseases and neo-epitopes in cancer immunotherapy.
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http://dx.doi.org/10.1016/j.xcrm.2021.100194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897774PMC
February 2021

CIITA-Transduced Glioblastoma Cells Uncover a Rich Repertoire of Clinically Relevant Tumor-Associated HLA-II Antigens.

Mol Cell Proteomics 2021 Jan 6;20:100032. Epub 2021 Jan 6.

Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland; Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. Electronic address:

CD4+ T cell responses are crucial for inducing and maintaining effective anticancer immunity, and the identification of human leukocyte antigen class II (HLA-II) cancer-specific epitopes is key to the development of potent cancer immunotherapies. In many tumor types, and especially in glioblastoma (GBM), HLA-II complexes are hardly ever naturally expressed. Hence, little is known about immunogenic HLA-II epitopes in GBM. With stable expression of the class II major histocompatibility complex transactivator (CIITA) coupled to a detailed and sensitive mass spectrometry-based immunopeptidomics analysis, we here uncovered a remarkable breadth of the HLA-ligandome in HROG02, HROG17, and RA GBM cell lines. The effect of CIITA expression on the induction of the HLA-II presentation machinery was striking in each of the three cell lines, and it was significantly higher compared with interferon gamma (IFNɣ) treatment. In total, we identified 16,123 unique HLA-I peptides and 32,690 unique HLA-II peptides. In order to genuinely define the identified peptides as true HLA ligands, we carefully characterized their association with the different HLA allotypes. In addition, we identified 138 and 279 HLA-I and HLA-II ligands, respectively, most of which are novel in GBM, derived from known GBM-associated tumor antigens that have been used as source proteins for a variety of GBM vaccines. Our data further indicate that CIITA-expressing GBM cells acquired an antigen presenting cell-like phenotype as we found that they directly present external proteins as HLA-II ligands. Not only that CIITA-expressing GBM cells are attractive models for antigen discovery endeavors, but also such engineered cells have great therapeutic potential through massive presentation of a diverse antigenic repertoire.
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http://dx.doi.org/10.1074/mcp.RA120.002201DOI Listing
January 2021

Spec2Vec: Improved mass spectral similarity scoring through learning of structural relationships.

PLoS Comput Biol 2021 02 16;17(2):e1008724. Epub 2021 Feb 16.

Bioinformatics Group, Wageningen University, Wageningen, the Netherlands.

Spectral similarity is used as a proxy for structural similarity in many tandem mass spectrometry (MS/MS) based metabolomics analyses such as library matching and molecular networking. Although weaknesses in the relationship between spectral similarity scores and the true structural similarities have been described, little development of alternative scores has been undertaken. Here, we introduce Spec2Vec, a novel spectral similarity score inspired by a natural language processing algorithm-Word2Vec. Spec2Vec learns fragmental relationships within a large set of spectral data to derive abstract spectral embeddings that can be used to assess spectral similarities. Using data derived from GNPS MS/MS libraries including spectra for nearly 13,000 unique molecules, we show how Spec2Vec scores correlate better with structural similarity than cosine-based scores. We demonstrate the advantages of Spec2Vec in library matching and molecular networking. Spec2Vec is computationally more scalable allowing structural analogue searches in large databases within seconds.
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http://dx.doi.org/10.1371/journal.pcbi.1008724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909622PMC
February 2021

Comparison of different CT metal artifact reduction strategies for standard titanium and carbon-fiber reinforced polymer implants in sheep cadavers.

BMC Med Imaging 2021 02 15;21(1):29. Epub 2021 Feb 15.

Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Faculty of Medicine, University of Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.

Background: CT artifacts induced by orthopedic implants can limit image quality and diagnostic yield. As a number of different strategies to reduce artifact extent exist, the aim of this study was to systematically compare ex vivo the impact of different CT metal artifact reduction (MAR) strategies on spine implants made of either standard titanium or carbon-fiber-reinforced-polyetheretherketone (CFR-PEEK).

Methods: Spine surgeons fluoroscopically-guided prepared six sheep spine cadavers with pedicle screws and rods of either titanium or CFR-PEEK. Samples were subjected to single- and dual-energy (DE) CT-imaging. Different tube voltages (80, DE mixed, 120 and tin-filtered 150 kVp) at comparable radiation dose and iterative reconstruction versus monoenergetic extrapolation (ME) techniques were compared. Also, the influence of image reconstruction kernels (soft vs. bone tissue) was investigated. Qualitative (Likert scores) and quantitative parameters (attenuation changes induced by implant artifact, implant diameter and image noise) were evaluated by two independent radiologists. Artifact degree of different MAR-strategies and implant materials were compared by multiple ANOVA analysis.

Results: CFR-PEEK implants induced markedly less artifacts than standard titanium implants (p < .001). This effect was substantially larger than any other tested MAR technique. Reconstruction algorithms had small impact in CFR-PEEK implants and differed significantly in MAR efficiency (p < .001) with best MAR performance for DECT ME 130 keV (bone kernel). Significant differences in image noise between reconstruction kernels were seen (p < .001) with minor impact on artifact degree.

Conclusions: CFR-PEEK spine implants induce significantly less artifacts than standard titanium compositions with higher MAR efficiency than any alternate scanning or image reconstruction strategy. DECT ME 130 keV image reconstructions showed least metal artifacts. Reconstruction kernels primarily modulate image noise with minor impact on artifact degree.
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http://dx.doi.org/10.1186/s12880-021-00554-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885519PMC
February 2021

HS sensing for breath analysis with Au functionalized ZnO nanowires.

Nanotechnology 2021 May;32(20):205505

Institute of Quantum Matter/Semiconductor Physics Group, Ulm University, D-89069 Ulm, Germany.

This work presents a HS selective resistive gas sensor design based on a chemical field effect transistor (ChemFET) with open gate formed by hundreds of high temperature chemical vapour deposition (CVD) grown zinc oxide nanowires (ZnO NW). The sensing ability of pristine ZnO NWs and surface functionalized ZnO NWs for HS is analysed systematically. ZnO NWs are functionalized by deposition of discontinuous gold (Au) nanoparticle films of different thicknesses of catalyst layer ranging from 1 to 10 nm and are compared in their gas sensing properties. All experiments were performed in a temperature stabilized small volume compartment with adjustable gas mixture at room temperature. The results allow for a well-founded understanding of signal-to-noise ratio, enhanced response, and improved limit of detection due to the Au functionalisation. Comprehension and controlled application of the beneficial effects of Au catalyst on ZnO NWs allow for the detection of very low HS concentrations down to 10 ppb, and a theoretically estimated 500 ppt in synthetic air at room temperature.
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http://dx.doi.org/10.1088/1361-6528/abe004DOI Listing
May 2021

Impact of the coronavirus disease 2019 (COVID-19) pandemic on the care of patients with acute and chronic aortic conditions.

Eur J Cardiothorac Surg 2021 05;59(5):1096-1102

Division of Cardiac Surgery, University of Brescia Medical School, Brescia, Italy.

Objectives: To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on acute and elective thoracic and abdominal aortic procedures.

Methods: Forty departments shared their data on acute and elective thoracic and abdominal aortic procedures between January and May 2020 and January and May 2019 in Europe, Asia and the USA. Admission rates as well as delay from onset of symptoms to referral were compared.

Results: No differences in the number of acute thoracic and abdominal aortic procedures were observed between 2020 and the reference period in 2019 [incidence rates ratio (IRR): 0.96, confidence interval (CI) 0.89-1.04; P = 0.39]. Also, no difference in the time interval from acute onset of symptoms to referral was recorded (<12 h 32% vs > 12 h 68% in 2020, < 12 h 34% vs > 12 h 66% in 2019 P = 0.29). Conversely, a decline of 35% in elective procedures was seen (IRR: 0.81, CI 0.76-0.87; P < 0.001) with substantial differences between countries and the most pronounced decline in Italy (-40%, P < 0.001). Interestingly, in Switzerland, an increase in the number of elective cases was observed (+35%, P = 0.02).

Conclusions: There was no change in the number of acute thoracic and abdominal aortic cases and procedures during the initial wave of the COVID-19 pandemic, whereas the case load of elective operations and procedures decreased significantly. Patients with acute aortic syndromes presented despite COVID-19 and were managed according to current guidelines. Further analysis is required to prove that deferral of elective cases had no impact on premature mortality.
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http://dx.doi.org/10.1093/ejcts/ezaa452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799089PMC
May 2021

Country-Level Relationships of the Human Intake of N and P, Animal and Vegetable Food, and Alcoholic Beverages with Cancer and Life Expectancy.

Int J Environ Res Public Health 2020 10 3;17(19). Epub 2020 Oct 3.

CSIC, Global Ecology Unit CREAF-CSIC-UAB, 08193 Cerdanyola del Vallès, Spain.

Background: The quantity, quality, and type (e.g., animal and vegetable) of human food have been correlated with human health, although with some contradictory or neutral results. We aimed to shed light on this association by using the integrated data at country level.

Methods: We correlated elemental (nitrogen (N) and phosphorus (P)) compositions and stoichiometries (N:P ratios), molecular (proteins) and energetic traits (kilocalories) of food of animal (terrestrial or aquatic) and vegetable origin, and alcoholic beverages with cancer prevalence and mortality and life expectancy (LE) at birth at the country level. We used the official databases of United Nations (UN), Food and Agriculture Organization of the United Nations (FAO), Organization for Economic Co-operation and Development (OECD), World Bank, World Health Organization (WHO), U.S. Department of Agriculture, U.S. Department of Health, and Eurobarometer, while also considering other possibly involved variables such as income, mean age, or human development index of each country.

Results: The per capita intakes of N, P, protein, and total intake from terrestrial animals, and especially alcohol were significantly and positively associated with prevalence and mortality from total, colon, lung, breast, and prostate cancers. In contrast, high per capita intakes of vegetable N, P, N:P, protein, and total plant intake exhibited negative relationships with cancer prevalence and mortality. However, a high LE at birth, especially in underdeveloped countries was more strongly correlated with a higher intake of food, independent of its animal or vegetable origin, than with other variables, such as higher income or the human development index.

Conclusions: Our analyses, thus, yielded four generally consistent conclusions. First, the excessive intake of terrestrial animal food, especially the levels of protein, N, and P, is associated with higher prevalence of cancer, whereas equivalent intake from vegetables is associated with lower prevalence. Second, no consistent relationship was found for food N:P ratio and cancer prevalence. Third, the consumption of alcoholic beverages correlates with prevalence and mortality by malignant neoplasms. Fourth, in underdeveloped countries, reducing famine has a greater positive impact on health and LE than a healthier diet.
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http://dx.doi.org/10.3390/ijerph17197240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579602PMC
October 2020

A multi-country dynamic factor model with stochastic volatility for euro area business cycle analysis.

J Forecast 2020 Sep 25;39(6):911-926. Epub 2020 Feb 25.

Austrian Institute of Economic Research (WIFO) Vienna Austria.

This paper develops a dynamic factor model that uses euro area country-specific information on output and inflation to estimate an area-wide measure of the output gap. Our model assumes that output and inflation can be decomposed into country-specific stochastic trends and a common cyclical component. Comovement in the trends is introduced by imposing a factor structure on the shocks to the latent states. We moreover introduce flexible stochastic volatility specifications to control for heteroscedasticity in the measurement errors and innovations to the latent states. Carefully specified shrinkage priors allow for pushing the model towards a homoscedastic specification, if supported by the data. Our measure of the output gap closely tracks other commonly adopted measures, with small differences in magnitudes and timing. To assess whether the model-based output gap helps in forecasting inflation, we perform an out-of-sample forecasting exercise. The findings indicate that our approach yields superior inflation forecasts, both in terms of point and density predictions.
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http://dx.doi.org/10.1002/for.2667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507863PMC
September 2020

Differentiation of Crystals Associated With Arthropathies by Spectral Photon-Counting Radiography: A Proof-of-Concept Study.

Invest Radiol 2021 Mar;56(3):147-152

From the Institute of Diagnostic and Interventional Radiology, University Hospital Zurich and Faculty of Medicine, University of Zurich, Zurich.

Objectives: The aims of this study were to test whether spectral photon-counting radiography (SPCR) is able to identify and distinguish different crystals associated with arthropathies in vitro and to validate findings in a gouty human third toe ex vivo.

Materials And Methods: Industry-standard calibration rods of calcium pyrophosphate, calcium hydroxyapatite (HA), and monosodium urate (MSU) were scanned with SPCR in an experimental setup. Each material was available at 3 different concentrations, and a dedicated photon-counting detector was used for SPCR, whereas validation scans were obtained on a clinical dual-energy computed tomography (DECT) scanner. Regions of interest were placed on SPCR images and consecutive DECT images to measure x-ray attenuation characteristics, including effective atomic numbers (Zeff). Statistical tests were performed for differentiation of Zeff between concentrations, materials, and imaging modalities. In addition, a third toe from a patient with chronic gouty arthritis was scanned with SPCR and DECT for differentiation of MSU from HA.

Results: In both SPCR and DECT, significant differences in attenuation and Zeff values were found for different concentrations among (P < 0.001) and between different materials (P < 0.001). Overall, quantitative measurements of Zeff did not differ significantly between SPCR- and DECT-derived measurements (P = 0.054-0.412). In the human cadaver toe, gouty bone erosions were visible on standard grayscale radiographic images; however, spectral image decomposition revealed the nature and extent of MSU deposits and was able to separate it from bone HA by Zeff.

Conclusions: Identification and differentiation of different crystals related to arthropathies are possible with SPCR at comparable diagnostic accuracy to DECT. Further research is needed to assess diagnostic accuracy and clinical usability in vivo.
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http://dx.doi.org/10.1097/RLI.0000000000000717DOI Listing
March 2021

Rapid tumor vaccine using Toll-like receptor-activated ovarian cancer ascites monocytes.

J Immunother Cancer 2020 08;8(2)

Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland

Background: Novel therapeutic strategies in ovarian cancer (OC) are needed as the survival rate remains dismally low. Although dendritic cell-based cancer vaccines are effective in eliciting therapeutic responses, their complex and costly manufacturing process hampers their full clinical utility outside specialized clinics. Here, we describe a novel approach of generating a rapid and effective cancer vaccine using ascites-derived monocytes for treating OC.

Methods: Using the ID8 mouse ovarian tumor model and OC patient samples, we isolated ascites monocytes and evaluated them with flow cytometry, Luminex cytokine and chemokine array analysis, ex vivo cocultures with T cells, in vivo tumor challenge and T cell transfer experiments, RNA-sequencing and mass spectrometry.

Results: We demonstrated the feasibility of isolating ascites monocytes and restoring their ability to function as bona fide antigen-presenting cells (APCs) with Toll-like receptor (TLR) 4 lipopolysaccharide and TLR9 CpG-oligonucleotides, and a blocking antibody to interleukin-10 receptor (IL-10R Ab) in the ID8 model. The ascites monocytes were laden with tumor antigens at a steady state in vivo. After a short 48 hours activation, they upregulated maturation markers (CD80, CD86 and MHC class I) and demonstrated strong ex vivo T cell stimulatory potential and effectively suppressed tumor and malignant ascites in vivo. They also induced protective long-term T cell memory responses. To evaluate the translational potential of this approach, we isolated ascites monocytes from stage III/IV chemotherapy-naïve OC patients. Similarly, the human ascites monocytes presented tumor-associated antigens (TAAs), including MUC1, ERBB2, mesothelin, MAGE, PRAME, GPC3, PMEL and TP53 at a steady state. After a 48-hour treatment with TLR4 and IL-10R Ab, they efficiently stimulated oligoclonal tumor-associated lymphocytes (TALs) with strong reactivity against TAAs. Importantly, the activated ascites monocytes retained their ability to activate TALs in the presence of ascitic fluid.

Conclusions: Ascites monocytes are naturally loaded with tumor antigen and can perform as potent APCs following short ex vivo activation. This novel ascites APC vaccine can be rapidly prepared in 48 hours with a straightforward and affordable manufacturing process, and would be an attractive therapeutic vaccine for OC.
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http://dx.doi.org/10.1136/jitc-2020-000875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430560PMC
August 2020

MRI in the assessment of adipose tissues and muscle composition: how to use it.

Quant Imaging Med Surg 2020 Aug;10(8):1636-1649

Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland.

Body composition analysis based on the characterization of different tissue compartments is currently experiencing increasing attention by a broad range of medical disciplines for both clinical and research questions. However, body composition profiling (BCP) can be performed utilizing different modalities, which all come along with several technical and diagnostic strengths and limitations, respectively. Magnetic resonance imaging (MRI) demonstrates good soft tissue resolution, high contrast between fat and water, and is free from ionizing radiation. This review article represents an overview of imaging techniques for body composition assessment, focussing on qualitative and quantitative methods of assessing adipose tissue and muscles in MRI.
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http://dx.doi.org/10.21037/qims.2020.02.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378099PMC
August 2020

Impact of Surface Chemistry and Doping Concentrations on Biofunctionalization of GaN/Ga‒In‒N Quantum Wells.

Sensors (Basel) 2020 Jul 28;20(15). Epub 2020 Jul 28.

Institute of Functional Nanosystems, Ulm University, Albert-Einstein-Allee 45, D-89081 Ulm, Germany.

The development of sensitive biosensors, such as gallium nitride (GaN)-based quantum wells, transistors, etc., often makes it necessary to functionalize GaN surfaces with small molecules or even biomolecules, such as proteins. As a first step in surface functionalization, we have investigated silane adsorption, as well as the formation of very thin silane layers. In the next step, the immobilization of the tetrameric protein streptavidin (as well as the attachment of chemically modified iron transport protein ferritin (ferritin-biotin-rhodamine complex)) was realized on these films. The degree of functionalization of the GaN surfaces was determined by fluorescence measurements with fluorescent-labeled proteins; silane film thickness and surface roughness were estimated, and also other surface sensitive techniques were applied. The formation of a monolayer consisting of adsorbed organosilanes was accomplished on Mg-doped GaN surfaces, and also functionalization with proteins was achieved. We found that very high Mg doping reduced the amount of surface functionalized proteins. Most likely, this finding was a consequence of the lower concentration of ionizable Mg atoms in highly Mg-doped layers as a consequence of self-compensation effects. In summary, we could demonstrate the necessity of Mg doping for achieving reasonable bio-functionalization of GaN surfaces.
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http://dx.doi.org/10.3390/s20154179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435836PMC
July 2020
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