TY - JOUR A1 - Litovkin, Kirill A1 - Van Eynde, Aleyde A1 - Joniau, Steven A1 - Lerut, Evelyne A1 - Laenen, Annouschka A1 - Gevaert, Thomas A1 - Gevaert, Olivier A1 - Spahn, Martin A1 - Kneitz, Burkhard A1 - Gramme, Pierre A1 - Helleputte, Thibault A1 - Isebaert, Sofie A1 - Haustermans, Karin A1 - Bollen, Mathieu T1 - DNA Methylation-Guided Prediction of Clinical Failure in High-Risk Prostate Cancer JF - PLoS ONE N2 - Background Prostate cancer (PCa) is a very heterogeneous disease with respect to clinical outcome. This study explored differential DNA methylation in a priori selected genes to diagnose PCa and predict clinical failure (CF) in high-risk patients. Methods A quantitative multiplex, methylation-specific PCR assay was developed to assess promoter methylation of the APC, CCND2, GSTP1, PTGS2 and RARB genes in formalin-fixed, paraffin-embedded tissue samples from 42 patients with benign prostatic hyperplasia and radical prostatectomy specimens of patients with high-risk PCa, encompassing training and validation cohorts of 147 and 71 patients, respectively. Log-rank tests, univariate and multivariate Cox models were used to investigate the prognostic value of the DNA methylation. Results Hypermethylation of APC, CCND2, GSTP1, PTGS2 and RARB was highly cancer-specific. However, only GSTP1 methylation was significantly associated with CF in both independent high-risk PCa cohorts. Importantly, trichotomization into low, moderate and high GSTP1 methylation level subgroups was highly predictive for CF. Patients with either a low or high GSTP1 methylation level, as compared to the moderate methylation groups, were at a higher risk for CF in both the training (Hazard ratio [HR], 3.65; 95% CI, 1.65 to 8.07) and validation sets (HR, 4.27; 95% CI, 1.03 to 17.72) as well as in the combined cohort ( HR, 2.74; 95% CI, 1.42 to 5.27) in multivariate analysis. Conclusions Classification of primary high-risk tumors into three subtypes based on DNA methylation can be combined with clinico-pathological parameters for a more informative risk-stratification of these PCa patients. KW - CpG island hypermethylation KW - radical prostatectomy KW - promoter methylation KW - receptor beta KW - gene KW - GSTP1 KW - biomarkers KW - diagnosis KW - recurrence KW - reveals Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151705 VL - 10 IS - 6 ER - TY - JOUR A1 - Lichthardt, Sven A1 - Kerscher, Alexander A1 - Dietz, Ulrich A. A1 - Jurowich, Christian A1 - Kunzmann, Volker A1 - von Rahden, Burkhard H. A. A1 - Germer, Christoph-Thomas A1 - Wiegering, Armin T1 - Original article: role of adjuvant chemotherapy in a perioperative chemotherapy regimen for gastric cancer JF - BMC Cancer N2 - Background Multimodal treatment strategies – perioperative chemotherapy (CTx) and radical surgery – are currently accepted as treatment standard for locally advanced gastric cancer. However, the role of adjuvant postoperative CTx (postCTx) in addition to neoadjuvant preoperative CTx (preCTx) in this setting remains controversial. Methods Between 4/2006 and 12/2013, 116 patients with locally advanced gastric cancer were treated with preCTx. 72 patients (62 %), in whom complete tumor resection (R0, subtotal/total gastrectomy with D2-lymphadenectomy) was achieved, were divided into two groups, one of which receiving adjuvant therapy (n = 52) and one without (n = 20). These groups were analyzed with regard to survival and exclusion criteria for adjuvant therapy. Results Postoperative complications, as well as their severity grade, did not correlate with fewer postCTx cycles administered (p = n.s.). Long-term survival was shorter in patients receiving postCTx in comparison to patients without postCTx, but did not show statistical significance. In per protocol analysis by excluding two patients with perioperative death, a shorter 3-year survival rate was observed in patients receiving postCTx compared to patients without postCTx (3-year survival: 71.2 % postCTx group vs. 90.0 % non-postCTx group; p = 0.038). Conclusion These results appear contradicting to the anticipated outcome. While speculative, they question the value of post-CTx. Prospectively randomized studies are needed to elucidate the role of postCTx. KW - gastric cancer KW - chemotherapy KW - neoadjuvant KW - multimodal KW - complication KW - adjuvant KW - risk factor KW - survival Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147743 VL - 16 IS - 650 ER - TY - JOUR A1 - Seyfried, Florian A1 - von Rahden, Burkhard H. A1 - Miras, Alexander D. A1 - Gasser, Martin A1 - Maeder, Uwe A1 - Kunzmann, Volker A1 - Germer, Christoph-Thomas A1 - Pelz, Jörg O. W. A1 - Kerscher, Alexander G. T1 - Incidence, time course and independent risk factors for metachronous peritoneal carcinomatosis of gastric origin – a longitudinal experience from a prospectively collected database of 1108 patients JF - BMC Cancer N2 - Background Comprehensive evidence on the incidence, time course and independent risk factors of metachronous peritoneal carcinomatosis (metaPC) in gastric cancer patients treated with curative intent in the context of available systemic combination chemotherapies is lacking. Methods Data from a prospectively collected single-institutional Center Cancer Registry with 1108 consecutive patients with gastric adenocarcinoma (GC), clinical, histological and survival data were analyzed for independent risk factors and prognosis with focus on the development of metaPC. Findings were then stratified to the time periods of treatment with surgery alone, 5-Fluorouracil-only and contemporary combined systemic perioperative chemotherapy strategies, respectively. Results Despite R0 D2 gastrectomy (n = 560), 49.6% (±5.4%) of the patients were diagnosed with tumour recurrence and 15.5% (±1.8%) developed metaPC after a median time of 17.7 (15.1-20.3) months after surgery resulting in a tumour related mortality of 100% with a median survival of 3.0 months (2.1 – 4.0). Independent risk factors for the development of metaPC were serosa positive T-category, nodal positive-status, signet cell and undifferentiated gradings (G3/G4). Contemporary systemic combination chemotherapy did not improve the incidence and prognosis of metaPC (p = 0.54). Conclusions Despite significant improvements in the overall survival for the complete cohort with gastric cancer over time, those patients with metaPC did not experience the same benefits. The lack of change in the incidence, and persistent poor prognosis of metaPC after curative surgery expose the need for further prevention and/or improved treatment options for this devastating condition. KW - recurrence survival KW - metachronous KW - peritoneal carcinomatosis KW - gastric cancer KW - risk factors KW - perioperative chemotherapy Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125014 VL - 15 IS - 73 ER - TY - JOUR A1 - Hailer, Amelie A1 - Grunewald, Thomas G. P. A1 - Orth, Martin A1 - Reiss, Cora A1 - Kneitz, Burkhard A1 - Spahn, Martin A1 - Butt, Elke T1 - Loss of tumor suppressor mir-203 mediates overexpression of LIM and SH3 Protein 1 (LASP1) in high-risk prostate cancer thereby increasing cell proliferation and migration JF - Oncotarget N2 - Several studies have linked overexpression of the LIM and SH3 domain protein 1 (LASP1) to progression of breast, colon, liver, and bladder cancer. However, its expression pattern and role in human prostate cancer (PCa) remained largely undefined. Analysis of published microarray data revealed a significant overexpression of LASP1 in PCa metastases compared to parental primary tumors and normal prostate epithelial cells. Subsequent gene-set enrichment analysis comparing LASP1-high and -low PCa identified an association of LASP1 with genes involved in locomotory behavior and chemokine signaling. These bioinformatic predictions were confirmed in vitro as the inducible short hairpin RNA-mediated LASP1 knockdown impaired migration and proliferation in LNCaP prostate cancer cells. By immunohistochemical staining and semi-quantitative image analysis of whole tissue sections we found an enhanced expression of LASP1 in primary PCa and lymph node metastases over benign prostatic hyperplasia. Strong cytosolic and nuclear LASP1 immunoreactivity correlated with PSA progression. Conversely, qRT-PCR analyses for mir-203, which is a known translational suppressor of LASP1 in matched RNA samples revealed an inverse correlation of LASP1 protein and mir-203 expression. Collectively, our results suggest that loss of mir-203 expression and thus uncontrolled LASP1 overexpression might drive progression of PCa. KW - mir-203 KW - PSA KW - LNCaP KW - LASP1 KW - prostate cancer Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120540 SN - 1949-2553 VL - 5 IS - 12 ER - TY - THES A1 - Thomas, Burkhard T1 - Prothetischer temporärer Kiefergelenksersatz - Eine retrospektive Langzeituntersuchung einer seltenen Indikation - T1 - Temporary prothetic replacement of the temporomandibular joint- A retrospective study of a rare indication - N2 - Bei 23 Patienten wurden 27 Kiefergelenke mit einer Metall-Kiefergelenkendoprothese reseziert. Bei vier dieser Patienten erfolgte die Rekonstruktion beidseitig. Zum Vergleich wurden in dieser Untersuchung sowohl 3 Patienten herangezogen, denen im gleichen Zeitraum ein Kiefergelenk reseziert worden war, ohne es durch eine Kiefergelenkendoprothese zu rekonstruieren als auch 4 der oben genannten 23 Patienten, welche nach Kiefergelenkresektion zum einen bestimmten Zeitraum mit als auch ohne Rekonstruktion durch eine metallische Kiefergelenkendoprothese lebten. An Hand der stationären und ambulanten Krankengeschichten, der röntgenologischen Verlaufsdokumentation sowie klinischer Nachunter¬suchungen wurden funktionelle und ästhetische Kurzzeit- und Langzeit¬ergebnisse ermittelt. Diesen wurden in der Literatur beschriebene, auf dem Einsatz aktueller Kiefergelenkendoprothesen basierende Ergebnisse gegenübergestellt und diskutiert. Hieraus ergaben sich folgende wesentliche Aussagen: 1. Auch die 27 hier verwendeten metallischen Kiefergelenkendoprothesen erreichen nicht die Funktionsqualität des natürlichen Kiefergelenkes. 2. Diese Kiefergelenkendoprothesen können als langfristiger Ersatz des Kiefergelenkes dienen wie die Kontrolluntersuchungen nach durch¬schnittlich 4 Jahren und 9 Monaten zeigen. 3. Wie bei anderen Prothesen auch sind bei Einsatz der metallischen Kiefergelenkendoprothesen die maximale Mundöffnung, Laterotrusion und Protrusion im Vergleich zum gesunden Patienten und im Vergleich zum Patienten mit alleiniger Kiefergelenkresektion vermindert, jedoch funktionell unbedeutend. 4. Bei Einsatz dieser Endoprothesen verfügen die Patienten über eine größere Kaukraft und bessere Gesichtssymmetrie als Patienten nach einer Resektion ohne Rekonstruktion des Kiefergelenkes. 5. Wird zusätzlich zur metallischen Kiefergelenkendoprothese ein freies Knochentransplantat vom Becken oder der 10. Rippe transplantiert, so verringert sich die Gesichtsasymmetrie im Vergleich zur alleinigen Verwendung einer metallischen Prothese. 6. Die beidseitige Versorgung mit einer metallischen Kiefergelenkendoprothese zeigt gleiche funktionelle und ästhetische Ergebnisse wie der einseitige Ersatz. 7. Patienten mit metallischen Kiefergelenkendoprothesen fühlen sich subjektiv im geringeren Maße im Alltag eingeschränkt als nach Resektion ohne Gelenkersatz und zeigen geringere Beschwerden bei längerem Sprechen. 8. Mittels intensiver, funktioneller Rehabilitationsmaßnahmen kann das postoperative Ergebnis deutlich verbessert werden. 9. Operativ bedingte Komplikationen können bei gezielter und schonender Präparation vermieden werden. 10. Ästhetische Beeinträchtigungen durch Narben treten nicht auf. 11. Myoarthropathische Veränderungen im kontralateralen Gelenk treten bei Patienten mit alleiniger Gelenkresektion häufiger und ausgeprägter auf als bei Patienten mit metallischer Endoprothese. 12. Die Rekonstruktion der Gelenkkapsel mit Hilfe eines aus dem M. temporalis gebildeten Muskel-Fascien-Lappens verhindert bei gleich¬zeitigem Einsatz einer metallischen Endoprothese eine Reankylosierung und eine Penetration des künstlichen Condylus in die Fossa temporalis. 13. Bei Tumorpatienten mit metallischer Kiefergelenkendoprothese kann problemlos eine Radiatio angewendet werden. Beurteilungsprobleme zeigen sich allerdings bei der Tumornachsorge wegen der metallischen Artefakte in der bildgebenden Diagnostik. N2 - 27 temporomandibular joints (TMJ) from 23 patients were reconstructed with metallic condylar head prostheses (4 patients underwent a reconstruction of both TMJ). They were compared with four other patients whom the TMJ-endoprosthesis later had to be removed, including three patients who underwent condylar resection without substitution. The resected region / endoprosthesis, facial and masticatory muscles, the dental system and the contralateral joints were clinically and radiographically monitored after the operations. The functional and aesthetic long term results were compared with other results from the current literature. 1. The 27 TMJ-endoprostheses did not achieve the total functional quality of a normal TMJ. 2. The endoprostheses worked in some cases as a long term joint replacement. 3. Max. mandibular opening and lateral and protrusive excursions were only slightly reduced in comparison with patients who underwent condylar resection without substitution. 4. Patients with TMJ endoprostheses reported less trouble with eating and speaking for a longer time – and endoprostheses preserved a better facial symmetry. 5. The best facial symmetry was preserved in two patients who underwent an additional graft from their own pelvis or rib. 6. Bilateral condylar prostheses exhibited the same functional and aesthetic results as unilateral arthroplasty. 7. Patients with metallic condylar head prostheses felt subjectively less handicapped in daily life. 8. The functioning of the TMJ-endoprosthesis could be improved through measures of functional rehabilitation and physiotherapy. 9. Complications caused by the operation could be prevented by careful preparation. 10. In all cases there were no impairments through scars. 11. Myarthropathic changes in contralateral joints were more frequent in patients with condylar resection without substitution. 12. The reconstruction of the TMJ-capsule by a muscle flap of the M. temporalis could prevent penetration of the metallic condyle in the Fossa temporalis. 13. In tumor patients with metallic TMJ-endoprostheses ray treatments could be applied unproblematically but there were problems in the findings of the tumor aftercare because of artefacts. KW - Kiefergelenk KW - Kiefergelenksersatz KW - Kiefergelenkendoprothese KW - Kiefergelenkresektion KW - Kiefergelenkrekonstruktion KW - Temporomandibular Joint prostheses KW - TMJ-endoprostheses Y1 - 2007 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-25860 ER - TY - JOUR A1 - Schütz, Burkhard A1 - Jurastow, Innokentij A1 - Bader, Sandra A1 - Ringer, Cornelia A1 - Engelhardt, Jakob von A1 - Chubanov, Vladimir A1 - Gudermann, Thomas A1 - Diener, Martin A1 - Kummer, Wolfgang A1 - Krasteva-Christ, Gabriela A1 - Weihe, Eberhard T1 - Chemical coding and chemosensory properties of cholinergic brush cells in the mouse gastrointestinal and biliary tract JF - Frontiers in Physiology N2 - The mouse gastro-intestinal and biliary tract mucosal epithelia harbor choline acetyltransferase (ChAT)-positive brush cells with taste cell-like traits. With the aid of two transgenic mouse lines that express green fluorescent protein (EGFP) under the control of the ChAT promoter (EGFP\(^{ChAT}\)) and by using in situ hybridization and immunohistochemistry we found that EGFP\(^{ChAT}\) cells were clustered in the epithelium lining the gastric groove. EGFP\(^{ChAT}\) cells were numerous in the gall bladder and bile duct, and found scattered as solitary cells along the small and large intestine. While all EGFP\(^{ChAT}\) cells were also ChAT-positive, expression of the high-affinity choline transporter (ChT1) was never detected. Except for the proximal colon, EGFP\(^{ChAT}\) cells also lacked detectable expression of the vesicular acetylcholine transporter (VAChT). EGFP\(^{ChAT}\) cells were found to be separate from enteroendocrine cells, however they were all immunoreactive for cytokeratin 18 (CK18), transient receptor potential melastatin-like subtype 5 channel (TRPM5), and for cyclooxygenases 1 (COX1) and 2 (COX2). The ex vivo stimulation of colonic EGFP\(^{ChAT}\) cells with the bitter substance denatonium resulted in a strong increase in intracellular calcium, while in other epithelial cells such an increase was significantly weaker and also timely delayed. Subsequent stimulation with cycloheximide was ineffective in both cell populations. Given their chemical coding and chemosensory properties, EGFP\(^{ChAT}\) brush cells thus may have integrative functions and participate in induction of protective reflexes and inflammatory events by utilizing ACh and prostaglandins for paracrine signaling. KW - vesicular acetylcholine transporter KW - nonneuronal acetylcholine KW - nervous system KW - functional characterization KW - cholinergic KW - taste receptor cells KW - enteroendocrine cells KW - gene locus KW - tuft cells KW - transgenic mice KW - expression KW - brush cell KW - ChAT KW - VAChT KW - ChT1 KW - intestine KW - gall bladder KW - bile duct Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143550 VL - 6 IS - 87 ER - TY - JOUR A1 - Porubsky, Stefan A1 - Popovic, Zoran V. A1 - Badve, Sunil A1 - Banz, Yara A1 - Berezowska, Sabina A1 - Borchert, Dietmar A1 - Brüggemann, Monika A1 - Gaiser, Timo A1 - Graeter, Thomas A1 - Hollaus, Peter A1 - Huettl, Katrin S. A1 - Kotrova, Michaela A1 - Kreft, Andreas A1 - Kugler, Christian A1 - Lötscher, Fabian A1 - Möller, Burkhard A1 - Ott, German A1 - Preissler, Gerhard A1 - Roessner, Eric A1 - Rosenwald, Andreas A1 - Ströbel, Philipp A1 - Marx, Alexander T1 - Thymic hyperplasia with lymphoepithelial sialadenitis (LESA)-like features: strong association with lymphomas and non-myasthenic autoimmune diseases JF - Cancers N2 - Thymic hyperplasia (TH) with lymphoepithelial sialadenitis (LESA)-like features (LESA-like TH) has been described as a tumor-like, benign proliferation of thymic epithelial cells and lymphoid follicles. We aimed to determine the frequency of lymphoma and autoimmunity in LESA-like TH and performed retrospective analysis of cases with LESA-like TH and/or thymic MALT-lymphoma. Among 36 patients (21 males) with LESA-like TH (age 52 years, 32–80; lesion diameter 7.0 cm, 1–14.5; median, range), five (14%) showed associated lymphomas, including four (11%) thymic MALT lymphomas and one (3%) diffuse large B-cell lymphoma. One additional case showed a clonal B-cell-receptor rearrangement without evidence of lymphoma. Twelve (33%) patients (7 women) suffered from partially overlapping autoimmune diseases: systemic lupus erythematosus (n = 4, 11%), rheumatoid arthritis (n = 3, 8%), myasthenia gravis (n = 2, 6%), asthma (n = 2, 6%), scleroderma, Sjögren syndrome, pure red cell aplasia, Grave’s disease and anti-IgLON5 syndrome (each n = 1, 3%). Among 11 primary thymic MALT lymphomas, remnants of LESA-like TH were found in two cases (18%). In summary, LESA-like TH shows a striking association with autoimmunity and predisposes to lymphomas. Thus, a hematologic and rheumatologic workup should become standard in patients diagnosed with LESA-like TH. Radiologists and clinicians should be aware of LESA-like TH as a differential diagnosis for mediastinal mass lesions in patients with autoimmune diseases. KW - autoimmune disease KW - imaging KW - LESA KW - lymphoma KW - myasthenia KW - pathology KW - surgery KW - thymus KW - thymic epithelial tumor KW - thymitis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223049 SN - 2072-6694 VL - 13 IS - 2 ER - TY - JOUR A1 - Moris, Lisa A1 - Van den Broeck, Thomas A1 - Tosco, Lorenzo A1 - Van Baelen, Anthony A1 - Gontero, Paolo A1 - Karnes, Robert Jeffrey A1 - Everaerts, Wouter A1 - Albersen, Maarten A1 - Bastian, Patrick J. A1 - Chlosta, Piotr A1 - Claessens, Frank A1 - Chun, Felix K. A1 - Graefen, Markus A1 - Gratzke, Christian A1 - Kneitz, Burkhard A1 - Marchioro, Giansilvio A1 - Salas, Rafael Sanchez A1 - Tombal, Bertrand A1 - Van Der Poel, Henk A1 - Walz, Jochen Christoph A1 - De Meerleer, Gert A1 - Bossi, Alberto A1 - Haustermans, Karin A1 - Montorsi, Francesco A1 - Van Poppel, Hendrik A1 - Spahn, Martin A1 - Briganti, Alberto A1 - Joniau, Steven T1 - Impact of lymph node burden on survival of high-risk prostate cancer patients following radical prostatectomy and pelvic lymph node dissection JF - Frontiers in Surgery N2 - Aim To determine the impact of the extent of lymph node invasion (LNI) on long-term oncological outcomes after radical prostatectomy (RP). Material and methods In this retrospective study, we examined the data of 1,249 high-risk, non-metastatic PCa patients treated with RP and pelvic lymph node dissection (PLND) between 1989 and 2011 at eight different tertiary institutions. We fitted univariate and multivariate Cox models to assess independent predictors of cancer-specific survival (CSS) and overall survival (OS). The number of positive lymph node (LN) was dichotomized according to the most informative cutoff predicting CSS. Kaplan–Meier curves assessed CSS and OS rates. Only patients with at least 10 LNs removed at PLND were included. This cutoff was chosen as a surrogate for a well performed PNLD. Results Mean age was 65 years (median: 66, IQR 60–70). Positive surgical margins were present in 53.7% (n = 671). Final Gleason score (GS) was 2–6 in 12.7% (n = 158), 7 in 52% (n = 649), and 8–10 in 35.4% (n = 442). The median number of LNs removed during PLND was 15 (IQR 12–17). Of all patients, 1,128 (90.3%) had 0–3 positive LNs, while 126 (9.7%) had ≥4 positive LNs. Patients with 0–3 positive LNs had significantly better CSS outcome at 10-year follow-up compared to patients with ≥4 positive LNs (87 vs. 50%; p < 0.0001). Similar results were obtained for OS, with a 72 vs. 37% (p < 0.0001) survival at 10 years for patients with 0–3 vs. ≥4 positive LNs, respectively. At multivariate analysis, final GS of 8–10, salvage ADT therapy, and ≥4 (vs. <4) positive LNs were predictors of worse CSS and OS. Pathological stage pT4 was an additional predictor of worse CSS. Conclusion Four or more positive LNs, pathological stage pT4, and final GS of 8–10 represent independent predictors for worse CSS in patients with high-risk PCa. Primary tumor biology remains a strong driver of tumor progression and patients having ≥4 positive LNs could be considered an enriched patient group in which novel treatment strategies should be studied. KW - high-risk prostate cancer KW - lymph node dissection KW - positive lymph node KW - prognosis KW - surgery Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195721 SN - 2296-875X VL - 3 ER - TY - JOUR A1 - Solger, Franziska A1 - Kunz, Tobias C. A1 - Fink, Julian A1 - Paprotka, Kerstin A1 - Pfister, Pauline A1 - Hagen, Franziska A1 - Schumacher, Fabian A1 - Kleuser, Burkhard A1 - Seibel, Jürgen A1 - Rudel, Thomas T1 - A Role of Sphingosine in the Intracellular Survival of Neisseria gonorrhoeae JF - Frontiers in Cellular and Infection Microbiology N2 - Obligate human pathogenic Neisseria gonorrhoeae are the second most frequent bacterial cause of sexually transmitted diseases. These bacteria invade different mucosal tissues and occasionally disseminate into the bloodstream. Invasion into epithelial cells requires the activation of host cell receptors by the formation of ceramide-rich platforms. Here, we investigated the role of sphingosine in the invasion and intracellular survival of gonococci. Sphingosine exhibited an anti-gonococcal activity in vitro. We used specific sphingosine analogs and click chemistry to visualize sphingosine in infected cells. Sphingosine localized to the membrane of intracellular gonococci. Inhibitor studies and the application of a sphingosine derivative indicated that increased sphingosine levels reduced the intracellular survival of gonococci. We demonstrate here, that sphingosine can target intracellular bacteria and may therefore exert a direct bactericidal effect inside cells. KW - sphingosine KW - sphingolipids KW - sphingosine kinases KW - invasion KW - survival KW - click chemistry Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204111 SN - 2235-2988 VL - 10 ER - TY - JOUR A1 - Pryss, Rüdiger A1 - Schlee, Winfried A1 - Hoppenstedt, Burkhard A1 - Reichert, Manfred A1 - Spiliopoulou, Myra A1 - Langguth, Berthold A1 - Breitmayer, Marius A1 - Probst, Thomas T1 - Applying Machine Learning to Daily-Life Data From the TrackYourTinnitus Mobile Health Crowdsensing Platform to Predict the Mobile Operating System Used With High Accuracy: Longitudinal Observational Study JF - Journal of Medical Internet Research N2 - Background: Tinnitus is often described as the phantom perception of a sound and is experienced by 5.1% to 42.7% of the population worldwide, at least once during their lifetime. The symptoms often reduce the patient's quality of life. The TrackYourTinnitus (TYT) mobile health (mHealth) crowdsensing platform was developed for two operating systems (OS)-Android and iOS-to help patients demystify the daily moment-to-moment variations of their tinnitus symptoms. In all platforms developed for more than one OS, it is important to investigate whether the crowdsensed data predicts the OS that was used in order to understand the degree to which the OS is a confounder that is necessary to consider. KW - crowdsensing KW - ecological momentary assessment KW - mHealth KW - machine learning KW - mobile operating system differences KW - tinnitus KW - mobile phone Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229517 VL - 22 IS - 6 ER - TY - JOUR A1 - Viljur, Mari‐Liis A1 - Abella, Scott R. A1 - Adámek, Martin A1 - Alencar, Janderson Batista Rodrigues A1 - Barber, Nicholas A. A1 - Beudert, Burkhard A1 - Burkle, Laura A. A1 - Cagnolo, Luciano A1 - Campos, Brent R. A1 - Chao, Anne A1 - Chergui, Brahim A1 - Choi, Chang‐Yong A1 - Cleary, Daniel F. R. A1 - Davis, Thomas Seth A1 - Dechnik‐Vázquez, Yanus A. A1 - Downing, William M. A1 - Fuentes‐Ramirez, Andrés A1 - Gandhi, Kamal J. K. A1 - Gehring, Catherine A1 - Georgiev, Kostadin B. A1 - Gimbutas, Mark A1 - Gongalsky, Konstantin B. A1 - Gorbunova, Anastasiya Y. A1 - Greenberg, Cathryn H. A1 - Hylander, Kristoffer A1 - Jules, Erik S. A1 - Korobushkin, Daniil I. A1 - Köster, Kajar A1 - Kurth, Valerie A1 - Lanham, Joseph Drew A1 - Lazarina, Maria A1 - Leverkus, Alexandro B. A1 - Lindenmayer, David A1 - Marra, Daniel Magnabosco A1 - Martín‐Pinto, Pablo A1 - Meave, Jorge A. A1 - Moretti, Marco A1 - Nam, Hyun‐Young A1 - Obrist, Martin K. A1 - Petanidou, Theodora A1 - Pons, Pere A1 - Potts, Simon G. A1 - Rapoport, Irina B. A1 - Rhoades, Paul R. A1 - Richter, Clark A1 - Saifutdinov, Ruslan A. A1 - Sanders, Nathan J. A1 - Santos, Xavier A1 - Steel, Zachary A1 - Tavella, Julia A1 - Wendenburg, Clara A1 - Wermelinger, Beat A1 - Zaitsev, Andrey S. A1 - Thorn, Simon T1 - The effect of natural disturbances on forest biodiversity: an ecological synthesis JF - Biological Reviews N2 - Disturbances alter biodiversity via their specific characteristics, including severity and extent in the landscape, which act at different temporal and spatial scales. Biodiversity response to disturbance also depends on the community characteristics and habitat requirements of species. Untangling the mechanistic interplay of these factors has guided disturbance ecology for decades, generating mixed scientific evidence of biodiversity responses to disturbance. Understanding the impact of natural disturbances on biodiversity is increasingly important due to human‐induced changes in natural disturbance regimes. In many areas, major natural forest disturbances, such as wildfires, windstorms, and insect outbreaks, are becoming more frequent, intense, severe, and widespread due to climate change and land‐use change. Conversely, the suppression of natural disturbances threatens disturbance‐dependent biota. Using a meta‐analytic approach, we analysed a global data set (with most sampling concentrated in temperate and boreal secondary forests) of species assemblages of 26 taxonomic groups, including plants, animals, and fungi collected from forests affected by wildfires, windstorms, and insect outbreaks. The overall effect of natural disturbances on α‐diversity did not differ significantly from zero, but some taxonomic groups responded positively to disturbance, while others tended to respond negatively. Disturbance was beneficial for taxonomic groups preferring conditions associated with open canopies (e.g. hymenopterans and hoverflies), whereas ground‐dwelling groups and/or groups typically associated with shady conditions (e.g. epigeic lichens and mycorrhizal fungi) were more likely to be negatively impacted by disturbance. Across all taxonomic groups, the highest α‐diversity in disturbed forest patches occurred under moderate disturbance severity, i.e. with approximately 55% of trees killed by disturbance. We further extended our meta‐analysis by applying a unified diversity concept based on Hill numbers to estimate α‐diversity changes in different taxonomic groups across a gradient of disturbance severity measured at the stand scale and incorporating other disturbance features. We found that disturbance severity negatively affected diversity for Hill number q = 0 but not for q = 1 and q = 2, indicating that diversity–disturbance relationships are shaped by species relative abundances. Our synthesis of α‐diversity was extended by a synthesis of disturbance‐induced change in species assemblages, and revealed that disturbance changes the β‐diversity of multiple taxonomic groups, including some groups that were not affected at the α‐diversity level (birds and woody plants). Finally, we used mixed rarefaction/extrapolation to estimate biodiversity change as a function of the proportion of forests that were disturbed, i.e. the disturbance extent measured at the landscape scale. The comparison of intact and naturally disturbed forests revealed that both types of forests provide habitat for unique species assemblages, whereas species diversity in the mixture of disturbed and undisturbed forests peaked at intermediate values of disturbance extent in the simulated landscape. Hence, the relationship between α‐diversity and disturbance severity in disturbed forest stands was strikingly similar to the relationship between species richness and disturbance extent in a landscape consisting of both disturbed and undisturbed forest habitats. This result suggests that both moderate disturbance severity and moderate disturbance extent support the highest levels of biodiversity in contemporary forest landscapes. KW - natural disturbance KW - diversity–disturbance relationship KW - disturbance severity KW - disturbance extent KW - intermediate disturbance hypothesis KW - forest communities KW - α‐diversity KW - β‐diversity Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287168 VL - 97 IS - 5 SP - 1930 EP - 1947 ER -