Publications by authors named "Tobias Schmidt"

196 Publications

Deep learning boosts sensitivity of mass spectrometry-based immunopeptidomics.

Nat Commun 2021 06 7;12(1):3346. Epub 2021 Jun 7.

Chair of Proteomics and Bioanalytics, Technical University of Munich (TUM), Freising, Germany.

Characterizing the human leukocyte antigen (HLA) bound ligandome by mass spectrometry (MS) holds great promise for developing vaccines and drugs for immune-oncology. Still, the identification of non-tryptic peptides presents substantial computational challenges. To address these, we synthesized and analyzed >300,000 peptides by multi-modal LC-MS/MS within the ProteomeTools project representing HLA class I & II ligands and products of the proteases AspN and LysN. The resulting data enabled training of a single model using the deep learning framework Prosit, allowing the accurate prediction of fragment ion spectra for tryptic and non-tryptic peptides. Applying Prosit demonstrates that the identification of HLA peptides can be improved up to 7-fold, that 87% of the proposed proteasomally spliced HLA peptides may be incorrect and that dozens of additional immunogenic neo-epitopes can be identified from patient tumors in published data. Together, the provided peptides, spectra and computational tools substantially expand the analytical depth of immunopeptidomics workflows.
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http://dx.doi.org/10.1038/s41467-021-23713-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184761PMC
June 2021

Fascial treatment versus manual therapy (HVLA) in patients with chronic neck pain: A randomized controlled trial.

J Back Musculoskelet Rehabil 2021 Jun 4. Epub 2021 Jun 4.

Department of General Practice, University Medical Center Göttingen, Göttingen, Germany.

Background: Chronic neck pain (CNP) is a common health problem in western industrialized nations. In recent years, the fascial tissue has attracted the attention of therapists, and a treatment of the fasciae promises to be a meaningful approach in the therapy of patients with CNP.

Objective: The aim of this study was to investigate the effectiveness of a fascial treatment (FT) compared to manual therapy (MT) and to no intervention (control group, CG) in patients with CNP.

Methods: Sixty participants with CNP were randomized into three groups. Primary outcome parameters were pain intensity as measured by the visual analogue scale (VAS), and severity of illness as measured by the Neck Pain and Disability Scale (NPAD). Secondary outcome parameter was the range of motion (ROM) of the cervical spine.

Results: Repeated measures t-tests demonstrated significant decreases with medium to large effect sizes for the FT (VAS: dR⁢M= 1.14; NPAD: dR⁢M= 0.51) and for the MT (VAS: dR⁢M= 1.15; NPAD: dR⁢M= 0.72).

Conclusion: Our results confirmed the effectiveness of MT on pain and severity of illness in the treatment of patients suffering from CNP. Furthermore, the results demonstrated the effectiveness and clinical relevance of FT for this population.
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http://dx.doi.org/10.3233/BMR-191731DOI Listing
June 2021

Urea-Creatinine Ratio (UCR) After Aneurysmal Subarachnoid Hemorrhage: Association of Protein Catabolism with Complication Rate and Outcome.

World Neurosurg 2021 May 18. Epub 2021 May 18.

Department of Neurosurgery, RWTH Aachen University, Aachen, Germany.

Objective: The urea-creatinine ratio (UCR) has been proposed as potential biomarker for critical illness-associated catabolism. Its role in the context of aneurysmal subarachnoid hemorrhage (aSAH) remains to be elucidated, which was the aim of the present study.

Methods: We enrolled 66 patients with aSAH with normal renal function and 36 patients undergoing elective cardiac surgery as a control group for the effects of surgery. In patients with aSAH, the predictive or diagnostic value of early (day 0-2) and critical (day 5-7) UCRs was assessed with regard to delayed cerebral ischemia (DCI), DCI-related infarction, and clinical outcome after 12 months.

Results: Preoperatively, UCR was similar both groups. Within 2 days postoperatively, UCRs increased significantly in patients in the elective cardiac surgery group (P < 0.001) but decreased back to baseline on day 5-7 (P = 0.245), whereas UCRs in patients with aSAH increased to significantly greater levels on day 5-7 (P = 0.028). Greater early or critical UCRs were associated with poor clinical outcomes (P = 0.015) or DCI (P = 0.011), DCI-related infarction (P = 0.006), and poor clinical outcomes (P < 0.001) respectively. In multivariate analysis, there was an independent association between greater early UCRs and poor clinical outcomes (P = 0.026).

Conclusions: In this exploratory study of UCR in the context of aSAH, greater early values were predictive for a poor clinical outcome after 12 months, whereas greater critical values were associated with DCI, DCI-related infarctions, and poor clinical outcomes. The clinical implications as well as the pathophysiologic relevance of protein catabolism should be explored further in the context of aSAH.
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http://dx.doi.org/10.1016/j.wneu.2021.05.025DOI Listing
May 2021

Universal Spectrum Explorer: A Standalone (Web-)Application for Cross-Resource Spectrum Comparison.

J Proteome Res 2021 06 10;20(6):3388-3394. Epub 2021 May 10.

Chair of Proteomics and Bioanalytics, Technical University of Munich, Freising 85354, Germany.

Here, we present the Universal Spectrum Explorer (USE), a web-based tool based on IPSA for cross-resource (peptide) spectrum visualization and comparison (https://www.proteomicsdb.org/use/). Mass spectra under investigation can be either provided manually by the user (table format) or automatically retrieved from online repositories supporting access to spectral data via the universal spectrum identifier (USI), or requested from other resources and services implementing a newly designed REST interface. As a proof of principle, we implemented such an interface in ProteomicsDB thereby allowing the retrieval of spectra acquired within the ProteomeTools project or real-time prediction of tandem mass spectra from the deep learning framework Prosit. Annotated mirror spectrum plots can be exported from the USE as editable scalable high-quality vector graphics. The USE was designed and implemented with minimal external dependencies allowing local usage and integration into other web sites (https://github.com/kusterlab/universal_spectrum_explorer).
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http://dx.doi.org/10.1021/acs.jproteome.1c00096DOI Listing
June 2021

Ca Microdomains, Calcineurin and the Regulation of Gene Transcription.

Cells 2021 Apr 12;10(4). Epub 2021 Apr 12.

Department of Medical Biochemistry and Molecular Biology, Saarland University Medical Faculty, D-66421 Homburg, Germany.

Ca ions function as second messengers regulating many intracellular events, including neurotransmitter release, exocytosis, muscle contraction, metabolism and gene transcription. Cells of a multicellular organism express a variety of cell-surface receptors and channels that trigger an increase of the intracellular Ca concentration upon stimulation. The elevated Ca concentration is not uniformly distributed within the cytoplasm but is organized in subcellular microdomains with high and low concentrations of Ca at different locations in the cell. Ca ions are stored and released by intracellular organelles that change the concentration and distribution of Ca ions. A major function of the rise in intracellular Ca is the change of the genetic expression pattern of the cell via the activation of Ca-responsive transcription factors. It has been proposed that Ca-responsive transcription factors are differently affected by a rise in cytoplasmic versus nuclear Ca. Moreover, it has been suggested that the mode of entry determines whether an influx of Ca leads to the stimulation of gene transcription. A rise in cytoplasmic Ca induces an intracellular signaling cascade, involving the activation of the Ca/calmodulin-dependent protein phosphatase calcineurin and various protein kinases (protein kinase C, extracellular signal-regulated protein kinase, Ca/calmodulin-dependent protein kinases). In this review article, we discuss the concept of gene regulation via elevated Ca concentration in the cytoplasm and the nucleus, the role of Ca entry and the role of enzymes as signal transducers. We give particular emphasis to the regulation of gene transcription by calcineurin, linking protein dephosphorylation with Ca signaling and gene expression.
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http://dx.doi.org/10.3390/cells10040875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068893PMC
April 2021

Transcatheter valve-in-valve-in-valve replacement in tricuspid position in a patient with pre-existing permanent dual-chamber pacemaker.

Clin Res Cardiol 2021 Apr 28. Epub 2021 Apr 28.

Department of Internal Medicine II, University Hospital of Schleswig-Holstein, Campus Lübeck, Germany.

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http://dx.doi.org/10.1007/s00392-021-01842-xDOI Listing
April 2021

[Impact of the COVID-19 lockdown on emergency medical service operations].

Notf Rett Med 2021 Apr 22:1-6. Epub 2021 Apr 22.

Institut für Allgemeinmedizin, Universitätsmedizin Göttingen, Humboldtallee 38, 37073 Göttingen, Deutschland.

Background: As a response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, extensive contact restrictions were imposed by law in Germany as in other European countries. The present study intends to clarify the effect of these restrictions on emergency medical service (EMS) operations.

Materials And Methods: Retrospective chart review of EMS operation protocols over the first 6 months of 2020 ( = 6668 rescue missions) in four rescue stations in eastern Lower Saxony (Germany). Description and statistical comparison of operations 6 weeks before the restrictions with an equally long period after the order of the restrictions ("lockdown").

Results: During the 6 weeks after the lockdown the frequency of rescue operations decreased by 17.7%. In particular, there was a 40.6% ( = 91) decrease of emergency cases with respiratory diseases, mainly due to a decline of pneumonia and exacerbated chronic-obstructive pulmonary disease (COPD). At the same time, patients' mean age increased with fewer patients under 65 years. There were no changes in the frequency of psychiatric disorders, deceased or injured patients, or refusal of treatment and transport. A total of 67 patients with suspected or confirmed SARS-CoV‑2 infection (1.0%) were observed during this period.

Discussion: EMS experienced a reduction of operations as a result of contact restrictions, although not as pronounced as was recently described for emergency rooms. This supports the hypothesis that the reduction is particularly evident in less severe cases and in younger patients. The reduction in pneumonia and COPD cases is striking. On the one hand, this could indicate that contact restrictions reduce the incidence of other respiratory infections and their impact on chronic respiratory disorders, but it could also mean that patients try to avoid hospital treatment.
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http://dx.doi.org/10.1007/s10049-021-00873-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060906PMC
April 2021

Synovial fluid neutrophils in oligoarticular juvenile idiopathic arthritis have an altered phenotype and impaired effector functions.

Arthritis Res Ther 2021 04 9;23(1):109. Epub 2021 Apr 9.

Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.

Background: Neutrophils are the most prevalent immune cells in the synovial fluid in inflamed joints of children with oligoarticular juvenile idiopathic arthritis (JIA). Despite this, little is known about neutrophil function at the site of inflammation in JIA and how local neutrophils contribute to disease pathogenesis. This study aimed to characterize the phenotype and function of synovial fluid neutrophils in oligoarticular JIA.

Methods: Neutrophils obtained from paired blood and synovial fluid from patients with active oligoarticular JIA were investigated phenotypically (n = 17) and functionally (phagocytosis and oxidative burst, n = 13) by flow cytometry. In a subset of patients (n = 6), blood samples were also obtained during inactive disease at a follow-up visit. The presence of CD206-expressing neutrophils was investigated in synovial biopsies from four patients by immunofluorescence.

Results: Neutrophils in synovial fluid had an activated phenotype, characterized by increased CD66b and CD11b levels, and most neutrophils had a CD16 CD62Laged phenotype. A large proportion of the synovial fluid neutrophils expressed CD206, a mannose receptor not commonly expressed by neutrophils but by monocytes, macrophages, and dendritic cells. CD206-expressing neutrophils were also found in synovial tissue biopsies. The synovial fluid neutrophil phenotype was not dependent on transmigration alone. Functionally, synovial fluid neutrophils had reduced phagocytic capacity and a trend towards impaired oxidative burst compared to blood neutrophils. In addition, the effector functions of the synovial fluid neutrophils correlated negatively with the proportion of CD206 neutrophils.

Conclusions: Neutrophils in the inflamed joint in oligoarticular JIA were altered, both regarding phenotype and function. Neutrophils in the synovial fluid were activated, had an aged phenotype, had gained monocyte-like features, and had impaired phagocytic capacity. The impairment in phagocytosis and oxidative burst was associated with the phenotype shift. We speculate that these neutrophil alterations might play a role in the sustained joint inflammation seen in JIA.
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http://dx.doi.org/10.1186/s13075-021-02483-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034063PMC
April 2021

Cortical volume reductions as a sign of secondary cerebral and cerebellar impairment in patients with degenerative cervical myelopathy.

Neuroimage Clin 2021 Mar 13;30:102624. Epub 2021 Mar 13.

Department of Neurosurgery, RWTH Aachen University, Pauwelsstraße 30, 52074 Aachen, Germany. Electronic address:

This study investigated supra- and infratentorial structural gray and white matter (GM, WM) alterations in patients with degenerative cervical myelopathy (DCM) as an indicator of secondary harm due to chronic cervical cord compression and micro trauma. With MRI-based anatomical assessment and subsequent voxel-based morphometry analyses, pre- and postoperative volume alterations in the primary motor cortex (MI), the primary somatosensory cortex (SI), the supplementary motor area (SMA), and the cerebellum were analyzed in 43 DCM patients and 20 controls. We assessed disease-related symptom severity by the modified Japanese Orthopaedic Association scale (mJOA). The study also explored symptom severity-based brain volume alterations as well as their association with clinical status. Patients had lower mJOA scores (p = .000) and lower GM volume than controls in SI (p = .016) and cerebellar regions (p = .001). Symptom severity-based subgroup analyses revealed volume reductions in almost all investigated GM ROIs (MI: p = .001; CB: p = .040; SMA: p = .007) in patients with severe clinical symptoms as well as atrophy already present in patients with moderate symptom severity. Clinical symptoms in DCM were associated with cortical and cerebellar volume reduction. GM volume alterations may serve as an indicator of both disease severity and ongoing disease progression in DCM, and should be considered in further patient care and treatment monitoring.
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http://dx.doi.org/10.1016/j.nicl.2021.102624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025145PMC
March 2021

Comparison of Self-Expanding RDV Perceval S versus TAVI ACURATE neo/TF.

Thorac Cardiovasc Surg 2021 Mar 24. Epub 2021 Mar 24.

Department of Cardiothoracic Surgery, Heart Center, University Hospital of Cologne, Cologne, Germany.

Background:  Rapid deployment aortic valve replacement (RDAVR) and transcatheter aortic valve implantation (TAVI) have emerged as increasingly used alternatives to conventional aortic valve replacement to treat patients at higher surgical risk. Therefore, in this single-center study, we retrospectively compared clinical outcomes and hemodynamic performance of two self-expanding biological prostheses, the sutureless and rapid deployment valve (RDV) Perceval-S (PER) and the transcatheter heart valve (THV) ACURATE /TF (NEO) in a 1:1 propensity-score-matching (PSM) patient cohort.

Methods:  A total of 332 consecutive patients with symptomatic aortic valve stenosis underwent either singular RDAVR with PER (119) or TAVI with NEO (213) at our institutions between 2012 and 2017. To compare the unequal patient groups, a 1:1 PSM for preoperative data and comorbidities was conducted. Afterward, 59 patient pairs were compared with regard to relevant hemodynamic parameter, relevant paravalvular leak (PVL), permanent postoperative pacemaker (PPM) implantation rate, and clinical postoperative outcomes.

Results:  Postoperative clinical short-term outcomes presented with slightly higher rates for 30-day all-cause mortality (PER = 5.1% vs. NEO = 1.7%,  = 0.619) and major adverse cardiocerebral event in PER due to cerebrovascular events (transient ischemic attack [TIA]-PER = 3.4% vs. TIA-NEO = 1.7%,  = 0.496 and Stroke-PER = 1.7% vs. Stroke-NEO = 0.0%,  = 1). Moreover, we show comparable PPM rates (PER = 10.2% vs. NEO = 8.5%,  = 0.752). However, higher numbers of PVL (mild-PER = 0.0% vs. NEO = 55.9%,  = 0.001; moderate or higher-PER = 0.0% vs. NEO = 6.8%,  = 0.119) after TAVI with NEO were observed.

Conclusion:  Both self-expanding bioprostheses, the RDV-PER and THV-NEO provide a feasible option in elderly and patients with elevated perioperative risk. However, the discussed PER collective showed more postoperative short-term complications with regard to 30-day all-cause mortality and cerebrovascular events, whereas the NEO showed higher rates of PVL.
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http://dx.doi.org/10.1055/s-0040-1722692DOI Listing
March 2021

Is there a benefit of ICD treatment in patients with persistent severely reduced systolic left ventricular function after TAVI?

Clin Res Cardiol 2021 Mar 23. Epub 2021 Mar 23.

Department of Cardiology, Heart Center, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.

Background: In patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) and heart failure with severely reduced ejection fraction, prediction of postprocedural left ventricular ejection fraction (LVEF) improvement is challenging. Decision-making and timing for implantable cardioverter defibrillator (ICD) treatment are difficult and benefit is still unclear in this patient population.

Objective: Aims of the study were to analyse long-term overall mortality in TAVI-patients with a preprocedural LVEF ≤ 35% regarding LVEF improvement and effect of ICD therapy.

Methods And Results: Retrospective analysis of a high-risk TAVI-population suffering from severe AS and heart failure with a LVEF ≤ 35%. Out of 1485 TAVI-patients treated at this center between January 2013 and April 2018, 120 patients revealed a preprocedural LVEF ≤ 35% and had sufficient follow-up. 36.7% (44/120) of the patients suffered from persistent reduced LVEF without a postprocedural increase above 35% within 1 year after TAVI or before death, respectively. Overall mortality was neither significantly reduced by LVEF recovery above 35% (p = 0.31) nor by additional ICD treatment in patients with persistent LVEF ≤ 35% (p = 0.33).

Conclusion: In high-risk TAVI-patients suffering from heart failure with LVEF ≤ 35%, LVEF improvement to more than 35% did not reduce overall mortality. Patients with postprocedural persistent LVEF reduction did not seem to benefit from ICD treatment. Effects of LVEF improvement and ICD treatment on mortality are masked by the competing risk of death from relevant comorbidities.
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http://dx.doi.org/10.1007/s00392-021-01826-xDOI Listing
March 2021

Outcome of aortic stenosis according to invasive cardiac damage staging after transcatheter aortic valve replacement.

Clin Res Cardiol 2021 May 20;110(5):699-710. Epub 2021 Mar 20.

Department of Cardiology, Asklepios Klinik St. Georg, Hamburg, Germany.

Background: In recent studies, a 5-stage cardiac damage classification in severe aortic stenosis (AS) based on echocardiographic parameters has shown to provide predictive value regarding clinical outcome. The objective of this study was to investigate the prognostic impact of a cardiac damage classification based on invasive hemodynamics in patients with AS undergoing transcatheter aortic valve replacement (TAVR).

Methods: A total of 1400 patients with symptomatic AS and full invasive hemodynamic assessment before TAVR were included. Patients were categorized according to their cardiac damage stage into five groups that are defined as: stage 0, no cardiac damage; stage 1, left ventricular damage; stage 2, left atrial and/or mitral valve damage; stage 3, pulmonary vasculature and/or tricuspid valve damage; stage 4, right ventricular damage.

Results: 9.9% patients were classified as stage 0, 23.6% as stage 1, the majority of patients as stage 2 (33.5%), 23.1% as stage 3 and 10% as stage 4. One- and 4-year mortality were 10.1%/29.5% in stage 0, 16.1%/60.6% in stage 1, 17.3%/39.4% in stage 2, 22%/54.6% in stage 3, 27.1%/62.2% in stage 4 (p = 0.001/p < 0.001). The extent of cardiac damage was independently associated with increased mortality after TAVR (HR 1.16 per each increment in stage, 95% confidence interval 1.03-1.18; p = 0.018).

Conclusions: Cardiac damage staging in severe AS patients based on invasive hemodynamics appears to show strong association between the extent of cardiac damage and post-TAVR mortality. This staging classification provides predictive value and may improve risk stratification, therapy management and decision-making in patients with AS. Invasive Staging Classification of Cardiac Damage in Severe Symptomatic Aortic Stenosis has an Impact on Outcome after TAVR. (Top) Invasive staging criteria for cardiac damage in five stages using left ventricular end-diastolic pressure (LVEDP) for stage 1 (red), post-capillary wedge pressure (PCWP) for stage 2 (green), systolic pulmonary artery pressure (SPAP) for stage 3 (purple) and right atrial pressure (RAP) for stage 4 (yellow). The cake chart shows the distribution of the different stage in the whole cohort. (Bottom) Survival Analyses According to Stage of Cardiac Damage after Transcatheter Aortic Valve Replacement using Invasive Criteria. Kaplan-Meier plots comparing overall (left) and cardiovascular (right) 4-year survival showing with the more advancing stage a higher mortality rate.
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http://dx.doi.org/10.1007/s00392-021-01835-wDOI Listing
May 2021

Meta-Analysis of Stroke and Mortality Rates in Patients Undergoing Valve-in-Valve Transcatheter Aortic Valve Replacement.

J Am Heart Assoc 2021 Mar 8;10(6):e019512. Epub 2021 Mar 8.

Department III of Internal Medicine University Hospital of Cologne Cologne Germany.

Background During the past decade, the use of transcatheter aortic valve replacement (TAVR) was extended beyond treatment-naïve patients and implemented for treatment of degenerated surgical bioprosthetic valves. Selection criteria for either valve-in-valve (viv) TAVR or redo surgical aortic valve replacement are not well established, and decision making on the operative approach still remains challenging for the interdisciplinary heart team. Methods and Results This review was intended to analyze all studies on viv-TAVR focusing on short- and mid-term stroke and mortality rates compared with redo surgical aortic valve replacement or native TAVR procedures. A structured literature search and review process led to 1667 potentially relevant studies on July 1, 2020. Finally, 23 studies fulfilled the inclusion criteria for qualitative analysis. All references were case series either with or without propensity score matching and registry analyses. Quantitative synthesis of data from 8509 patients revealed that viv-TAVR is associated with mean 30-day stroke and mortality rates of 2.2% and 4.2%, respectively. Pooled data analysis showed no significant differences in 30-day stroke rate, 30-day mortality, and 1-year mortality between viv-TAVR and comparator treatment (native TAVR [n=11 804 patients] or redo surgical aortic valve replacement [n=498 patients]). Conclusions This review is the first one comparing the risk for stroke and mortality rates in viv-TAVR procedures with native TAVR approach and contributes substantial data for the clinical routine. Moreover, this systematic review is the most comprehensive analysis on ischemic cerebrovascular events and early mortality in patients undergoing viv-TAVR. In this era with increasing numbers of bioprosthetic valves used in younger patients, viv-TAVR is a suitable option for the treatment of degenerated bioprostheses.
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http://dx.doi.org/10.1161/JAHA.120.019512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174195PMC
March 2021

Intraoperative Computed Tomography-Assisted Spinal Navigation in Dorsal Cervical Instrumentation: A Prospective Study on Accuracy Regarding Different Pathologies and Screw Types.

World Neurosurg 2021 May 9;149:e378-e385. Epub 2021 Feb 9.

Department of Neurosurgery, RWTH Aachen University, Aachen, Germany.

Background: Intraoperative computed tomography (iCT) navigated dorsal instrumentation has been successfully introduced as a new clinical standard. The proximity of vital anatomic structures makes cervical spine instrumentation an especially delicate task. Therefore, navigated approaches might prove to be beneficial. In this study, the accuracy of conventional instrumentation was compared with iCT navigated dorsal cervical spine instrumentation with focus on cervical pedicle screws (CPSs) versus lateral mass screws (LMSs) and pathologies.

Methods: We analyzed a prospective consecutive series of patients undergoing cervical dorsal instrumentation with iCT and spinal navigation and retrospectively analyzed a cohort that received conventional cervical instrumentation with C-arm fluoroscopy (control group). Accuracy was assessed with a modified Gertzbein-Robbins classification. Underlying pathologies were taken into account regarding accuracy in different entities.

Results: Fifty-nine patients were treated using iCT (357 screws: 238 CPSs, 119 LMSs), and 98 patients underwent conventional instrumentation (632 screws: 69 CPSs, 563 LMSs). We achieved an initial accuracy of 93.28% (n = 220 screws) in the iCT group and 80.9% (n = 511 screws) in the control group (P < 0.001). Significant differences were found regarding the accuracy of CPS placement in cases of degenerative disorders (iCT vs. control; 94% vs. 63%; P < 0.001) and trauma (iCT vs. control; 88% vs. 72%; P < 0.05). iCT yielded favorable precision rates in regard to LMS placement (iCT vs. control; 94.2% vs. 82%; P < 0.05).

Conclusions: Accuracy of iCT navigated instrumentation was significantly higher than conventional instrumentation. An overall tendency toward the use of CPSs with iCT navigation is evident, increasing the mechanical properties of the construct. iCT appears to be especially beneficial in elective surgery cases of degenerative spinal disorders.
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http://dx.doi.org/10.1016/j.wneu.2021.02.014DOI Listing
May 2021

Spurring low-carbon electrosynthesis through energy and innovation policy.

Authors:
Tobias S Schmidt

iScience 2021 Feb 9;24(2):102045. Epub 2021 Jan 9.

Energy Politics Group - Swiss Federal Institute of Technology, ETH Zurich, Haldeneggsteig 4, 8092 Zurich, Switzerland.

Reaching the climate targets set in the Paris Agreement on climate change requires decarbonizing all parts of the global economy. The electrification of industry processes-and more specifically, electrosynthesis (ES)-is an important decarbonization mechanism. To tap into this mechanism's potential and accelerate the decarbonization of these processes, I argue that public policy needs to perform two tasks. First, energy policy needs to enable the provision of CO emissions-free baseload electricity. Second, innovation policy needs to accelerate cost reductions for ES. Here, I discuss why this is the case, what the challenges are, how policy makers can address them, and how political ambition can be increased.
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http://dx.doi.org/10.1016/j.isci.2021.102045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843494PMC
February 2021

Risk profile of decompressive hemicraniectomy for malignant stroke after revascularization treatment.

J Neurol Sci 2021 01 16;420:117275. Epub 2020 Dec 16.

Department of Neurosurgery, RWTH Aachen University, Aachen, Germany. Electronic address:

Objective: Revascularization by pharmacological and/or endovascular treatment is an effective therapy for acute ischemic stroke caused by artery occlusion. In the context of malignant middle cerebral artery infarction (MMI), decompressive hemicraniectomy (DHC) can be life-saving. However, its effectiveness and safety after revascularization have not been thoroughly assessed. This retrospective study aimed to determine the risk profile of pre-surgical revascularization treatment (RT) for subsequent DHC.

Methods: A total of 152 consecutive patients treated by DHC after MMI were identified between 2012 and 2015. After elimination of cases with previous stroke and cases pre-treated with antiplatelets or anticoagulants (increased postoperative bleeding), twenty-four out of fifty patients (n = 24/50, 48%) received pre-surgical revascularization treatment by intravenous thrombolysis (TL), mechanical thrombectomy (MT) or a combination of both. Demographic data was compared alongside perioperative, postoperative complications (intra-/extracerebral hemorrhage, revision surgery due to hemorrhage or infection, and overall mortality) and economic parameters.

Results: Comparing patients with and without prior RT, there was no statistically significant difference in duration of surgery (RT: 83 [57-116] min vs. no-RT: 96 [69-119] min, p = 0.308), intraoperative blood loss (RT: 300 [225-375] ml vs. no-RT: 300 [250-400] ml, p = 0.763), intraoperative transfusion requirement (RT: 12.5% vs. no-RT: 26.9%, p = 0.294), or need for volume substitution (RT: 1300 [1200-1400] ml vs. no-RT: 1200 [1100-1400] ml, p = 0.359). The rate of postoperative complications was also comparable in both groups, including intra-/extracerebral hemorrhage, revision due to hemorrhage or infections, and mortality (p = 0.814, p = 0.520, p = 0.697, and p = 0.769). Health economic parameters were not affected (ventilation time: RT: 309 [12-527] hrs. vs. no-RT: 444 [171-605] hrs., p = 0.120, length of stay: RT: 23 [13-32] days vs. no-RT: 28 [19-41], p = 0.156, and stay costs: RT: 27768 [13044-60,248] € vs. no-RT: 35422 [21225-49,585] €, p = 0.312).

Conclusion: DHC for patients with MMI who previously received revascularization therapy appears to be safe and not associated with a higher complication rate or increased health economic burden.
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http://dx.doi.org/10.1016/j.jns.2020.117275DOI Listing
January 2021

The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA interaction.

Nucleic Acids Res 2021 01;49(1):458-478

Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.

The mammalian target of rapamycin (mTOR) is a critical regulator of cell growth, integrating multiple signalling cues and pathways. Key among the downstream activities of mTOR is the control of the protein synthesis machinery. This is achieved, in part, via the co-ordinated regulation of mRNAs that contain a terminal oligopyrimidine tract (TOP) at their 5'ends, although the mechanisms by which this occurs downstream of mTOR signalling are still unclear. We used RNA-binding protein (RBP) capture to identify changes in the protein-RNA interaction landscape following mTOR inhibition. Upon mTOR inhibition, the binding of LARP1 to a number of mRNAs, including TOP-containing mRNAs, increased. Importantly, non-TOP-containing mRNAs bound by LARP1 are in a translationally-repressed state, even under control conditions. The mRNA interactome of the LARP1-associated protein PABPC1 was found to have a high degree of overlap with that of LARP1 and our data show that PABPC1 is required for the association of LARP1 with its specific mRNA targets. Finally, we demonstrate that mRNAs, including those encoding proteins critical for cell growth and survival, are translationally repressed when bound by both LARP1 and PABPC1.
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http://dx.doi.org/10.1093/nar/gkaa1189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797073PMC
January 2021

Treatment of Delayed Cerebral Ischemia in Good-Grade Subarachnoid Hemorrhage: Any Role for Invasive Neuromonitoring?

Neurocrit Care 2020 Dec 10. Epub 2020 Dec 10.

Department of Neurosurgery, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074, Aachen, Germany.

Background: Good-grade aneurysmal subarachnoid hemorrhage (Hunt and Hess 1-2) is generally associated with a favorable prognosis. Nonetheless, patients may still experience secondary deterioration due to delayed cerebral ischemia (DCI), contributing to poor outcome. In those patients, neurological assessment is challenging and invasive neuromonitoring (INM) may help guide DCI treatment.

Methods: An observational analysis of 135 good-grade SAH patients referred to a single tertiary care center between 2010 and 2018 was performed. In total, 54 good-grade SAH patients with secondary deterioration evading further neurological assessment, were prospectively enrolled for this analysis. The cohort was separated into two groups: before and after introduction of INM in 2014 (pre-INM: n = 28; post-INM: n = 26). INM included either parenchymal oxygen saturation measurement (pO), cerebral microdialysis or both. Episodes of DCI (pO < 10 mmHg or lactate/pyruvate > 40) were treated via induced hypertension or in refractory cases by endovascular means. The primary outcome was defined as the extended Glasgow outcome scale after 12 months. In addition, we recorded the amount of imaging studies performed and the occurrence of silent and overall DCI-related infarction.

Results: Secondary deterioration, impeding neurological assessment, occurred in 54 (40.0%) of all good-grade SAH patients. In those patients, a comparable rate of favorable outcome at 12 months was observed before and after the introduction of INM (pre-INM 14 (50.0%) vs. post-INM 16, (61.6%); p = 0.253). A significant increase in good recovery (pre-INM 6 (50.0%) vs. post-INM 14, (61.6%); p = 0.014) was observed alongside a reduction in the incidence of silent infarctions (pre-INM 8 (28.6%) vs. post-INM 2 (7.7%); p = 0.048) and of overall DCI-related infarction (pre-INM 12 (42.8%) vs. post-INM 4 (23.1%); p = 0.027). The number of CT investigations performed during the DCI time frame decreased from 9.8 ± 5.2 scans in the pre-INM group to 6.1 ± 4.0 (p = 0.003) in the post-INM group.

Conclusions: A considerable number of patients with good-grade SAH experiences secondary deterioration rendering them neurologically not assessable. In our cohort, the introduction of INM to guide DCI treatment in patients with secondary deterioration increased the rate of good recovery after 12 months. Additionally, a significant reduction of CT scans and infarction load was recorded, which may have an underestimated impact on quality of life and more subtle neuropsychological deficits common after SAH.
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http://dx.doi.org/10.1007/s12028-020-01169-xDOI Listing
December 2020

Identification of MLH2/hPMS1 dominant mutations that prevent DNA mismatch repair function.

Commun Biol 2020 12 10;3(1):751. Epub 2020 Dec 10.

DNA Repair Mechanisms and Cancer, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany.

Inactivating mutations affecting key mismatch repair (MMR) components lead to microsatellite instability (MSI) and cancer. However, a number of patients with MSI-tumors do not present alterations in classical MMR genes. Here we discovered that specific missense mutations in the MutL homolog MLH2, which is dispensable for MMR, confer a dominant mutator phenotype in S. cerevisiae. MLH2 mutations elevated frameshift mutation rates, and caused accumulation of long-lasting nuclear MMR foci. Both aspects of this phenotype were suppressed by mutations predicted to prevent the binding of Mlh2 to DNA. Genetic analysis revealed that mlh2 dominant mutations interfere with both Exonuclease 1 (Exo1)-dependent and Exo1-independent MMR. Lastly, we demonstrate that a homolog mutation in human hPMS1 results in a dominant mutator phenotype. Our data support a model in which yeast Mlh1-Mlh2 or hMLH1-hPMS1 mutant complexes act as roadblocks on DNA preventing MMR, unraveling a novel mechanism that can account for MSI in human cancer.
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http://dx.doi.org/10.1038/s42003-020-01481-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730388PMC
December 2020

Genotype-Phenotype Associations in 72 Adults with Suspected ALPL-Associated Hypophosphatasia.

Calcif Tissue Int 2021 03 15;108(3):288-301. Epub 2020 Nov 15.

Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestrasse 59, 22529, Hamburg, Germany.

Hypophosphatasia (HPP) is a rare inborn error of metabolism due to a decreased activity of tissue nonspecific alkaline phosphatase (TNSALP). As the onset and severity of HPP are heterogenous, it can be challenging to determine the pathogenicity of detected rare ALPL variants in symptomatic patients. We aimed to characterize patients with rare ALPL variants to propose which patients can be diagnosed with adult HPP. We included 72 patients with (1) clinical symptoms of adult HPP or positive family history and (2) low TNSALP activity and/or high pyridoxal 5'-phosphate (PLP) levels, who underwent ALPL gene sequencing. The patients were analyzed and divided into three groups depending on ALPL variant pathogenicity according to the classification of the American College of Medical Genetics and Genomics (ACMG). Reported pathogenic (n = 34 patients), rare (n = 17) and common (n = 21) ALPL variants only were found. Muscular complaints were the most frequent symptoms (> 80%), followed by bone affection (> 50%). Tooth involvement was significantly more common in patients with pathogenic or rare ALPL variants. Seven rare variants could be classified as likely pathogenic (ACMG class 4) of which five have not yet been described. Inconclusive genetic findings and less specific symptoms make diagnosis difficult in cases where adult HPP is not obvious. As not every pathogenic or rare ALPL variant leads to a manifestation of HPP, only patients with bone complications and at least one additional complication concerning teeth, muscle, central nervous and mental system, repeated low TNSALP activity and high PLP levels should be diagnosed as adult HPP if rare ALPL gene variants of ACMG class 4 or higher support the diagnosis.
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http://dx.doi.org/10.1007/s00223-020-00771-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881968PMC
March 2021

Extensive 5'-surveillance guards against non-canonical NAD-caps of nuclear mRNAs in yeast.

Nat Commun 2020 11 2;11(1):5508. Epub 2020 Nov 2.

Institute of Pharmacy and Molecular Biotechnology (IPMB), Heidelberg University, 69120, Heidelberg, Germany.

The ubiquitous redox coenzyme nicotinamide adenine dinucleotide (NAD) acts as a non-canonical cap structure on prokaryotic and eukaryotic ribonucleic acids. Here we find that in budding yeast, NAD-RNAs are abundant (>1400 species), short (<170 nt), and mostly correspond to mRNA 5'-ends. The modification percentage of transcripts is low (<5%). NAD incorporation occurs mainly during transcription initiation by RNA polymerase II, which uses distinct promoters with a YAAG core motif for this purpose. Most NAD-RNAs are 3'-truncated. At least three decapping enzymes, Rai1, Dxo1, and Npy1, guard against NAD-RNA at different cellular locations, targeting overlapping transcript populations. NAD-mRNAs are not translatable in vitro. Our work indicates that in budding yeast, most of the NAD incorporation into RNA seems to be disadvantageous to the cell, which has evolved a diverse surveillance machinery to prematurely terminate, decap and reject NAD-RNAs.
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http://dx.doi.org/10.1038/s41467-020-19326-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606564PMC
November 2020

Mismatch between circulating cytokines and spontaneous cytokine production by leukocytes in hyperinflammatory COVID-19.

J Leukoc Biol 2021 01 13;109(1):115-120. Epub 2020 Aug 13.

Skåne University Hospital, Lund and Malmö, Sweden.

The disease COVID-19 has developed into a worldwide pandemic. Hyperinflammation and high levels of several cytokines, for example, IL-6, are observed in severe COVID-19 cases. However, little is known about the cellular origin of these cytokines. Here, we investigated whether circulating leukocytes from patients with COVID-19 had spontaneous cytokine production. Patients with hyperinflammatory COVID-19 (n = 6) and sepsis (n = 3) were included at Skåne University Hospital, Sweden. Healthy controls were also recruited (n = 5). Cytokines were measured in COVID-19 and sepsis patients using an Immulite immunoassay system. PBMCs were cultured with brefeldin A to allow cytokine accumulation. In parallel, LPS was used as an activator. Cells were analyzed for cytokines and surface markers by flow cytometry. High levels of IL-6 and measurable levels of IL-8 and TNF, but not IL-1β, were observed in COVID-19 patients. Monocytes from COVID-19 patients had spontaneous production of IL-1β and IL-8 (P = 0.0043), but not of TNF and IL-6, compared to controls. No spontaneous cytokine production was seen in lymphocytes from either patients or controls. Activation with LPS resulted in massive cytokine production by monocytes from COVID-19 patients and healthy controls, but not from sepsis patients. Finally, monocytes from COVID-19 patients produced more IL-1β than from healthy controls (P = 0.0087) when activated. In conclusion, monocytes contribute partly to the ongoing hyperinflammation by production of IL-1β and IL-8. Additionally, they are responsive to further activation. This data supports the notion of IL-1β blockade in treatment of COVID-19. However, the source of the high levels of IL-6 remains to be determined.
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http://dx.doi.org/10.1002/JLB.5COVBCR0720-310RRDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436862PMC
January 2021

Children with oligoarticular juvenile idiopathic arthritis have skewed synovial monocyte polarization pattern with functional impairment-a distinct inflammatory pattern for oligoarticular juvenile arthritis.

Arthritis Res Ther 2020 08 12;22(1):186. Epub 2020 Aug 12.

Department of Pediatrics, Clinical Sciences Lund, Lund University, BMC B13, Klinikgatan 26, 22185, Lund, Sweden.

Background: Juvenile idiopathic arthritis (JIA) is an umbrella term of inflammatory joint diseases in children. Oligoarthritis is the most common form in the Western world, representing roughly 60% of all patients. Monocytes and macrophages play an important role in adult arthritides, but their role in oligoarticular JIA is less studied. Polarization highly influences monocytes' and macrophages' effector functions, broadly separated into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Here, we set out to investigate the polarization pattern and functional aspects of synovial monocytes in oligoarticular juvenile idiopathic arthritis (JIA).

Methods: Paired synovial fluid, blood samples (n = 13), and synovial biopsies (n = 3) were collected from patients with untreated oligoarticular JIA. Monocytes were analyzed for polarization markers by flow cytometry and qPCR. Effector function was analyzed by a phagocytosis assay. Polarization of healthy monocytes was investigated by stimulation with synovial fluid in vitro. Monocyte/macrophage distribution, polarization, and mRNA expression were investigated in biopsies by immunohistochemistry, immunofluorescence, and in situ hybridization.

Results: Children with oligoarticular JIA have polarized synovial fluid monocytes of a specific M1(IFNγ)/M2(IL-4)-like pattern. This was evidenced by increased surface expression of CD40 (p < 0.001), CD86 (p < 0.001), and CD206 (p < 0.001), but not CD163, as compared to paired circulating monocytes. Additionally, polarization was extensively explored at the mRNA level and synovial fluid monocytes differentially expressed classical markers of M1(IFNγ)/M2(IL-4) polarization compared to circulating monocytes. Synovial fluid monocytes were functionally affected, as assessed by reduced capacity to phagocytose (p < 0.01). Synovial fluid induced M2 markers (CD16 and CD206), but not M1 (CD40) or CD86 in healthy monocytes and did not induce cytokine production. Single and co-expression of surface CD40 and CD206, as well as mRNA expression of IL-10 and TNF, was observed in monocytes/macrophages in synovial biopsies.

Conclusion: Children with untreated oligoarticular JIA have similar and distinct synovial fluid monocyte polarization pattern of mixed pro- and anti-inflammatory features. This pattern was not exclusively a result of the synovial fluid milieu as monocytes/macrophages in the synovial membrane show similar patterns. Our study highlights a distinct polarization pattern in oligoarticular JIA, which could be utilized for future treatment strategies.
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http://dx.doi.org/10.1186/s13075-020-02279-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425414PMC
August 2020

12(S)-HETE mediates diabetes-induced endothelial dysfunction by activating intracellular endothelial cell TRPV1.

J Clin Invest 2020 09;130(9):4999-5010

Department of Anesthesiology, Intensive Care and Pain Medicine, and.

Patients with diabetes develop endothelial dysfunction shortly after diabetes onset that progresses to vascular disease underlying the majority of diabetes-associated comorbidities. Increased lipid peroxidation, mitochondrial calcium overload, and mitochondrial dysfunction are characteristics of dysfunctional endothelial cells in diabetic patients. We here identified that targeting the lipid peroxidation product 12(S)-hydroxyeicosatetraenoic acid-induced [12(S)-HETE-induced] activation of the intracellularly located cation channel transient receptor potential vanilloid 1 (TRPV1) in endothelial cells is a means to causally control early-stage vascular disease in type I diabetic mice. Mice with an inducible, endothelium-specific 12/15-lipoxygenase (12/15Lo) knockout were protected similarly to TRPV1-knockout mice from type 1 diabetes-induced endothelial dysfunction and impaired vascular regeneration following arterial injury. Both 12(S)-HETE in concentrations found in diabetic patients and TRPV1 agonists triggered mitochondrial calcium influx and mitochondrial dysfunction in endothelial cells, and 12(S)-HETE effects were absent in endothelial cells from TRPV1-knockout mice. As a therapeutic consequence, we found that a peptide targeting 12(S)-HETE-induced TRPV1 interaction at the TRPV1 TRP box ameliorated diabetes-induced endothelial dysfunction and augmented vascular regeneration in diabetic mice. Our findings suggest that pharmacological targeting of increased endothelial lipid peroxidation can attenuate diabetes-induced comorbidities related to vascular disease.
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http://dx.doi.org/10.1172/JCI136621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456227PMC
September 2020

Sex-Based Differences in Tensiomyography as Assessed in the Lower Erector Spinae of Healthy Participants: An Observational Study.

Sports Health 2020 Jul/Aug;12(4):341-346. Epub 2020 Jun 8.

Department of Physical Therapy, Faculty of Health Sciences, University of Malaga, Malaga, Spain.

Background: Although there is mounting evidence on sex-linked differences in paraspinal muscle function, it is unknown whether sex-based variations in mechanical and contractile characteristics of the lumbar erector spinae (LES) can be monitored noninvasively in healthy participants at rest using tensiomyography (TMG).

Hypothesis: Sex-specific effects in muscle displacement (Dm) and velocity of muscle deformation (Vd) will be observed via TMG assessed in the LES.

Study Design: Observational study.

Level Of Evidence: Level 3.

Methods: LES response was measured in a relaxed state in 40 healthy adults (20 females). Possible differences between the conditions were investigated using mixed-model analyses of variance. Two-stage hierarchical linear regression analyses were performed to predict the outcome of TMG Dm and Vd based on participant sex.

Results: There were significant main effects of sex with large effect sizes for both TMG parameters, resulting from lower mean values in women compared with men (Dm, < 0.01; Vd, < 0.01). In contrast, neither the main effect of side (left vs right LES) nor the interaction between the side and sex reached significance (all > 0.3). Introducing the sex variable in stage 2 of the regression analyses significantly improved the prediction of the TMG parameters (all ≥ 0.18; all < 0.01; all ≥ 0.29).

Conclusion: Sex-based differences in muscle stiffness and contractile characteristics could be observed by TMG on LES muscles in healthy individuals at rest. The data suggest that these disparities are not exclusively attributable to anthropometric measures but may be linked to intrinsic sex-based differences in skeletal muscle characteristics.

Clinical Relevance: We recommend implementing TMG in a clinical setting using the obtained results as a basis to factor for the patient's biological sex when assessing effects of therapeutic/exercise regimens aiming at the optimization of myofascial tissue regeneration and performance.
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http://dx.doi.org/10.1177/1941738120917932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787569PMC
July 2020

Effects of Osteopathic Manipulative Treatment on Musicians: A Systematic Review.

Med Probl Perform Art 2020 Jun;35(2):110-115

Berlin Center for Musicians' Medicine, Institute for Social Medicine, Epidemiology and Health Economics, Charité Universitätsmedizin Berlin, Luisenstraße 57, 10117 Berlin, Germany. Tel +49 30 450 529 007.

Background: Professional musicians frequently suffer from musculoskeletal complaints and disorders (MCD), which can be treated by osteopathic manipulative treatment (OMT). The aim of this systematic review was to evaluate the effectiveness and efficacy of OMT in adult musicians.

Methods: A systematic literature search included the electronic databases PubMed/MEDLINE, Medpilot, EBSCOhost, BioMedCentral, OSTMED-Dr, osteopathic-research.com, PEDro, hand searches, and contact to European osteopathic academies. Interventional and observational studies published between January 1999 and January 2019, of professional or amateur musicians who were either healthy or had MCD treated by OMT, were included. The quality of the randomized controlled trials (RCTs) was assessed by the Physiotherapy Evidence Database (PEDro) Scale ranging between 0 and 10 points.

Results: Only 5 studies were identified investigating OMT in musicians, including 1 RCT (cross-over design), 3 clinical controlled trials, and 1 case report. The internal validity of the RCT was assessed as 6 points. OMT was reported to have a positive impact on healthy singers, improving phonation time, voice quality, and voice range. It also improved the cervical range of motion in violinists. No adverse events were observed, although only the cross-over RCT reported partly an assessment of adverse events.

Conclusions: The evidence for OMT in adult musicians is very limited. Prospective controlled clinical trials investigating OMT in musicians are required.
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http://dx.doi.org/10.21091/mppa.2020.2017DOI Listing
June 2020

Invasive neuromonitoring with an extended definition of delayed cerebral ischemia is associated with improved outcome after poor-grade subarachnoid hemorrhage.

J Neurosurg 2020 May 15:1-8. Epub 2020 May 15.

Departments of1Neurosurgery.

Objective: The current definition of delayed cerebral ischemia (DCI) is based on clinical characteristics precluding its use in patients with poor-grade subarachnoid hemorrhage (SAH). Additional concepts to evaluate the unconscious patient are required. Invasive neuromonitoring (INM) may allow timely detection of metabolic and oxygenation crises before irreversible damage has occurred.

Methods: The authors present a cohort analysis of all consecutive SAH patients referred to a single tertiary care center between 2010 and 2018. The cohort (n = 190) was split into two groups: one before (n = 96) and one after (n = 94) the introduction of INM in 2014. A total of 55 poor-grade SAH patients were prospectively monitored using parenchymal oxygen saturation measurement and cerebral microdialysis. The primary outcome was the Glasgow Outcome Scale-Extended (GOSE) score after 12 months.

Results: With neuromonitoring, the first DCI event was detected earlier (mean 2.2 days, p = 0.002). The overall rate of DCI-related infarctions decreased significantly (from 44.8% to 22.3%; p = 0.001) after the introduction of invasive monitoring. After 12 months, a higher rate of favorable outcome was observed in the post-INM group, compared to the pre-INM group (53.8% vs 39.8%), with a significant difference in the GOSE score distribution (OR 4.86, 95% CI -1.17 to -0.07, p = 0.028).

Conclusions: In this cohort analysis of poor-grade SAH patients, the introduction of INM and the extension of the classic DCI definition toward a functional dimension resulted in an earlier detection and treatment of DCI events. This led to an overall decrease in DCI-related infarctions and an improvement in outcome.
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http://dx.doi.org/10.3171/2020.3.JNS20375DOI Listing
May 2020

Navigating the Clean Energy Transition in the COVID-19 Crisis.

Joule 2020 Jun 29;4(6):1137-1141. Epub 2020 Apr 29.

Department of Humanities, Social and Political Sciences, Energy Politics Group, ETH Zurich, 8092 Zurich, Switzerland.

Bjarne Steffen is a senior researcher at ETH Zurich's Energy Politics Group. His research addresses policies related to energy innovation and the role of finance in the energy transition. He previously worked at MIT's Center for Energy and Environmental Policy Research, the World Economic Forum, and a strategy consultancy. Bjarne holds a Master's in economics from the University of Mannheim and a PhD in energy economics from the University of Duisburg-Essen. Florian Egli is a PhD candidate at ETH Zurich's Energy Politics Group. His research focuses on the role of finance in the energy transition and climate finance more generally. He is a World Economic Forum Global Shaper, is associated with the think tank foraus as its former vice president, and held a Mercator Fellowship on International Affairs in 2015 and 2016. Florian holds a Master's in International Economics from the Graduate Institute of International and Development Studies (IHEID) in Geneva. Michael Pahle is head of the working group "Climate and Energy Policy" at the Potsdam-Institute for Climate Impact Research. His research focuses on carbon pricing and power market design. He holds a Master's in Physics from Potsdam University and a PhD in economics from TU Berlin. Tobias S. Schmidt is Assistant Professor and the head of ETH Zurich's Energy Politics Group, an interdisciplinary group analyzing the interaction of energy policy and its underlying politics with technological change in the energy sector. His research covers both developed and developing countries. Tobias holds a Bachelor's and Master's of Science in electrical engineering (energy focus) from the Technical University Munich and a PhD from ETH Zurich in management, technology, and economics.
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http://dx.doi.org/10.1016/j.joule.2020.04.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189842PMC
June 2020

Generating high quality libraries for DIA MS with empirically corrected peptide predictions.

Nat Commun 2020 03 25;11(1):1548. Epub 2020 Mar 25.

Technical University of Munich, Freising, Germany.

Data-independent acquisition approaches typically rely on experiment-specific spectrum libraries, requiring offline fractionation and tens to hundreds of injections. We demonstrate a library generation workflow that leverages fragmentation and retention time prediction to build libraries containing every peptide in a proteome, and then refines those libraries with empirical data. Our method specifically enables rapid, experiment-specific library generation for non-model organisms, which we demonstrate using the malaria parasite Plasmodium falciparum, and non-canonical databases, which we show by detecting missense variants in HeLa.
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http://dx.doi.org/10.1038/s41467-020-15346-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096433PMC
March 2020