BRENDA in 2019: a European ELIXIR core data resource

The BRENDA enzyme database (www.brenda-enzymes.org), recently appointed ELIXIR Core Data Resource, is the main enzyme and enzyme-ligand information system. The core database provides a comprehensive overview on enzymes. A collection of 4.3 million data for ∼84 000 enzymes manually evaluated and extracted from ∼140 000 primary literature references is combined with information obtained by text and data mining, data integration and prediction algorithms. Supplements comprise disease-related data, protein sequences, 3D structures, predicted enzyme locations and genome annotations. Major developments are a revised ligand summary page and the structure search now including a similarity and isomer search. BKMS-react, an integrated database containing known enzyme-catalyzed reactions, is supplemented with further reactions and improved access to pathway connections. In addition to existing enzyme word maps with graphical information of enzyme specific terms, plant word maps have been developed. They show a graphical overview of terms, e.g. enzyme or plant pathogen information, connected to specific plants. An organism summary page showing all relevant information, e.g. taxonomy and synonyms linked to enzyme data, was implemented. Based on a decision by the IUBMB enzyme task force the enzyme class EC 7 has been established for ‘translocases’, enzymes that catalyze a transport of ions or metabolites across cellular membranes

Business Continuity Management in Micro Enterprises: Perception, Strategies, and Use of ICT

Small and medium-sized enterprises (SMEs) represent 99% of enterprises in Germany and more than 95% in the European Union. Given the recent increase of natural disasters and man-made crises and emergencies, it seems an important economic goal to ascertain that SMEs are capable of maintaining their work, revenue and profit at an acceptable level. According to ISO 22301, business continuity management (BCM) is a holistic management process which identifies potential threats and their impact to an organization and serves as a framework to increase organizational resilience and response capabilities. Prior research identified that BCM is under-represented in SMEs and that their security level is partially in an uneconomical range. This article presents the analysis of interviews with 19 independent micro enterprises highlighting findings on their low crisis awareness, varying technical dependency, existing action strategies and communication strategies and proposing a categorization of micro enterprises as preventive technicians, data-intensive chains or pragmatic jumpers

Immune checkpoint expression on immune cells of HNSCC patients and modulation by chemo- and immunotherapy

Endogenous control mechanisms, including immune checkpoints and immunosuppressive cells, are exploited in the process of tumorigenesis to weaken the anti-tumor immune response. Cancer treatment by chemotherapy or immune checkpoint inhibition can lead to changes of checkpoint expression, which influences therapy success. Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) were isolated from head and neck squamous cell carcinoma (HNSCC) patients (n = 23) and compared to healthy donors (n = 23). Immune checkpoint expression (programmed cell death ligand 1 (PD-1), tumor necrosis factor receptor (TNFR)-related (GITR), CD137, tumor necrosis factor receptor superfamily member 4 (TNFRSF4) (OX40), t-cell immunoglobulin and mucin-domain containing-3 (TIM3), B- and T-lymphocyte attenuator (BTLA), lymphocyte-activation gene 3 (LAG3)) was determined on immune cells by flow cytometry. PD-L1 expression was detected on tumor tissue by immunohistochemistry. Immune cells were treated with immuno- and chemotherapeutics to investigate treatment-specific change in immune checkpoint expression, in vitro. Specific changes of immune checkpoint expression were identified on PBL and TIL of HNSCC patients compared to healthy donors. Various chemotherapeutics acted differently on the expression of immune checkpoints. Changes of checkpoint expression were significantly less pronounced on regulatory T cells compared to other lymphocyte populations. Nivolumab treatment significantly reduced the receptor PD-1 on all analyzed T cell populations, in vitro. The specific immune checkpoint expression patterns in HNSCC patients and the investigated effects of immunomodulatory agents may improve the development and efficacy of targeted immunotherapy

Circulating exosomes inhibit B cell proliferation and activity

(1) Background: Head and neck squamous cell carcinoma (HNSCC) is characterized by a distinctive suppression of the anti-tumor immunity, both locally in the tumor microenvironment (TME) and the periphery. Tumor-derived exosomes mediate this immune suppression by directly suppressing T effector function and by inducing differentiation of regulatory T cells. However, little is known about the effects of exosomes on B cells. (2) Methods: Peripheral B cells from healthy donors and HNSCC patients were isolated and checkpoint receptor expression was analyzed by flow cytometry. Circulating exosomes were isolated from the plasma of HNSCC patients (n = 21) and healthy individuals (n = 10) by mini size-exclusion chromatography. B cells from healthy individuals were co-cultured with isolated exosomes for up to 4 days. Proliferation, viability, surface expression of checkpoint receptors, and intracellular signaling were analyzed in B cells by flow cytometry. (3) Results: Expression of the checkpoint receptors PD-1 and LAG3 was increased on B cells from HNSCC patients. The protein concentration of circulating exosomes was increased in HNSCC patients as compared to healthy donors. Both exosomes from healthy individuals and HNSCC patients inhibited B cell proliferation and survival, in vitro. Surface expression of inhibitory and stimulatory checkpoint receptors on B cells was modulated in co-culture with exosomes. In addition, an inhibitory effect of exosomes on B cell receptor (BCR) signaling was demonstrated in B cells. (4) Conclusions: Plasma-derived exosomes show inhibitory effects on the function of healthy B cells. Interestingly, these inhibitory effects are similar between exosomes from healthy individuals and HNSCC patients, suggesting a physiological B cell inhibitory role of circulating exosomes

Prospective longitudinal study of immune checkpoint molecule (ICM) expression in immune cell subsets during curative conventional therapy of head and neck squamous cell carcinoma (HNSCC)

Programmed-death-1 (PD1) antibodies are approved for recurrent and metastatic head and neck squamous cell carcinoma. Multiple drugs targeting costimulatory and coinhibitory immune checkpoint molecules (ICM) have been discovered. However, it remains unknown how these ICM are affected by curative conventional therapy on different immune cell subsets during the course of treatment. In the prospective noninterventional clinical study titled “Immune Response Evaluation to Curative conventional Therapy” (NCT03053661), 22 patients were prospectively enrolled. Blood samples were drawn at defined time points throughout curative conventional treatment and follow-up. Immune cells (IC) from the different time points were assessed by multicolor flow cytometry. The following ICM were measured by flow cytometry: PD1, CTLA4, BTLA, CD137, CD27, GITR, OX40, LAG3 and TIM3. Dynamics of ICM expression were assessed using nonparametric paired samples tests. Significant changes were noted for PD1, BTLA and CD27 on multiple IC types during or after radiotherapy. Nonsignificant trends for increased expression of OX40 and GITR from baseline until the end of RT were observed on CD4 T cells and CD4+ CD39+ T cells. In patients with samples at recurrence of disease, a nonsignificant increase of TIM3 and LAG3 positive CD4+ CD39+ T cells was evident, accompanied by an increase of double positive cells for TIM3/LAG3. Potential future targets to be combined with RT in the conventional treatment and anti-PD1/PD-L could be BTLA agonists, or agonistic antibodies to costimulatory ICM like CD137, OX40 or GITR. The combination of cetuximab with CD27 agonistic antibodies enhancing ADCC or the targeting of TIM3/LAG3 may be another promising strategy

Replikationsstudien bestätigen das Phänomen der Offenohrigkeit im frühen Grundschulalter

Gembris H, Heye A, Jeske L. Replikationsstudien bestätigen das Phänomen der Offenohrigkeit im frühen Grundschulalter. In: Auhagen W, Bullerjahn C, von Georgi R, eds. Offenohrigkeit. Ein Postulat im Fokus. Musikpsychologie. Jahrbuch der Deutschen Gesellschaft für Musikpsychologie. Vol 24. Göttingen: Hogrefe; 2014: 100-132

Artificial intelligence in Emergency Medical Services dispatching:assessing the potential impact of an automatic speech recognition software on stroke detection taking the Capital Region of Denmark as case in point

BACKGROUND AND PURPOSE: Stroke recognition at the Emergency Medical Services (EMS) impacts the stroke treatment and thus the related health outcome. At the EMS Copenhagen 66.2% of strokes are detected by the Emergency Medical Dispatcher (EMD) and in Denmark approximately 50% of stroke patients arrive at the hospital within the time-to-treatment. An automatic speech recognition software (ASR) can increase the recognition of Out-of-Hospital cardiac arrest (OHCA) at the EMS by 16%. This research aims to analyse the potential impact an ASR could have on stroke recognition at the EMS Copenhagen and the related treatment. METHODS: Stroke patient data (n = 9049) from the years 2016-2018 were analysed retrospectively, regarding correlations between stroke detection at the EMS and stroke specific, as well as personal characteristics such as stroke type, sex, age, weekday, time of day, year, EMS number contacted, and treatment. The possible increase in stroke detection through an ASR and the effect on stroke treatment was calculated based on the impact of an existing ASR to detect OHCA from CORTI AI. RESULTS: The Chi-Square test with the respective post-hoc test identified a negative correlation between stroke detection and females, the 1813-Medical Helpline, as well as weekends, and a positive correlation between stroke detection and treatment and thrombolysis. While the association analysis showed a moderate correlation between stroke detection and treatment the correlation to the other treatment options was weak or very weak. A potential increase in stroke detection to 61.19% with an ASR and hence an increase of thrombolysis by 5% in stroke patients calling within time-to-treatment was predicted. CONCLUSIONS: An ASR can potentially improve stroke recognition by EMDs and subsequent stroke treatment at the EMS Copenhagen. Based on the analysis results improvement of stroke recognition is particularly relevant for females, younger stroke patients, calls received through the 1813-Medical Helpline, and on weekends. TRIAL REGISTRATION: This study was registered at the Danish Data Protection Agency (PVH-2014-002) and the Danish Patient Safety Authority (R-21013122)