Refine
Has Fulltext
- yes (21)
Is part of the Bibliography
- yes (21)
Year of publication
Document Type
- Journal article (18)
- Working Paper (2)
- Preprint (1)
Keywords
- sarcopenia (3)
- State-of-the-Art (2)
- Systematischer Überblick (2)
- exercise (2)
- expression (2)
- microbial spectrum (2)
- AVHRR (1)
- Alignment (1)
- Applied physics (1)
- Atacama (1)
- B7-H1 (1)
- Beschaffung (1)
- Biomedical engineering (1)
- Bone Mineral Density (1)
- CD10 (1)
- CT (1)
- Chile (1)
- Crohn's disease (1)
- Doppelquantenkohärenz (1)
- EU-RHAB registry (1)
- Earth Observation (1)
- Effizienz (1)
- Einkauf (1)
- Empirische Forschung (1)
- Europe (1)
- Fluoreszenz (1)
- Imaging techniques (1)
- InSAR (1)
- KIF (1)
- KIF11 (1)
- Literatur Review (1)
- Literature Review (1)
- Meta-Analyse (1)
- Molekülzustand (1)
- NCH93 (1)
- Optische Spektroskopie (1)
- Outcomes (1)
- PC-1 blockade (1)
- PD-1 (1)
- PD-L1 (1)
- PEComa (1)
- Procurement (1)
- Purchasing (1)
- ROI (1)
- RTPS1 (1)
- RTPS2 (1)
- Sentinel-1 (1)
- Skin (1)
- Sourcing (1)
- Supply Chain (1)
- Supply Management (1)
- Supply chain management (1)
- Systematischer (Literatur) Review (1)
- TIMELINE (1)
- Tertiärstudie (1)
- X-ray (1)
- Zweidimensionale Spektroskopie (1)
- adults (1)
- aging (1)
- albumins (1)
- anorectal abscess (1)
- antibiotic resistance (1)
- atypical teratoid rhabdoid tumors (1)
- automatic processing (1)
- bone QCT (1)
- bone mineral density (1)
- brain metastases (1)
- breast cancer (1)
- cancer (1)
- cardiovascular (1)
- cell lung cancer (1)
- climate related trends (1)
- coherence (1)
- community-dwelling (1)
- computed tomography (1)
- cutaneous PEComa (1)
- drug metabolism (1)
- elektronisch angeregte Zustände (1)
- enzyme metabolism (1)
- extracranial malignant rhabdoid tumor (1)
- fistulizing Crohn’s Disease (1)
- genetics (1)
- geomorphology (1)
- germline mutation (1)
- harmonization (1)
- heptaocytes (1)
- holotomography (1)
- human heptocytes (1)
- immunoresistance (1)
- immunosurveillance (1)
- individual drug responses (1)
- induction (1)
- intraabdominal abscess (1)
- kinesin (1)
- melanoma (1)
- men (1)
- meningioma (1)
- mesenchymal stem cells (1)
- metabolic risk (1)
- metabolic syndrome (1)
- mouse xenografts (1)
- multiscalar holotomography (1)
- obesity (1)
- older people (1)
- oncology (1)
- oragnoids (1)
- osteopenia (1)
- osteoporosis (1)
- ovarian tumor (1)
- overview (1)
- penetrating ileitis (1)
- perfusion culture (1)
- perianal fistulas (1)
- perivascular epitheloid cell tumour (1)
- personalized medicine (1)
- precision-cut tumor slices (1)
- preclinical model (1)
- primary cells (1)
- reconstruction (1)
- region of interest (1)
- resistance exercise (1)
- risk factors (1)
- safety (1)
- survival (1)
- time series analysis (1)
- tumor microenvironment (1)
- tumor-infiltrating lymphocytes (1)
- whole-body electromyostimulation (1)
Institute
- Lehrstuhl für Orthopädie (4)
- Betriebswirtschaftliches Institut (2)
- Institut für Geographie und Geologie (2)
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (2)
- Theodor-Boveri-Institut für Biowissenschaften (2)
- Fakultät für Physik und Astronomie (1)
- Frauenklinik und Poliklinik (1)
- Institut für Humangenetik (1)
- Institut für Physikalische und Theoretische Chemie (1)
- Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik) (1)
Sonstige beteiligte Institutionen
Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.
Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
Kinesins play an important role in many physiological functions including intracellular vesicle transport and mitosis. The emerging role of kinesins in different cancers led us to investigate the expression and functional role of kinesins in meningioma. Therefore, we re-analyzed our previous microarray dataset of benign, atypical, and anaplastic meningiomas (n = 62) and got evidence for differential expression of five kinesins (KIFC1, KIF4A, KIF11, KIF14 and KIF20A). Further validation in an extended study sample (n = 208) revealed a significant upregulation of these genes in WHO°I to °III meningiomas (WHO°I n = 61, WHO°II n = 88, and WHO°III n = 59), which was most pronounced in clinically more aggressive tumors of the same WHO grade. Immunohistochemical staining confirmed a WHO grade-associated upregulated protein expression in meningioma tissues. Furthermore, high mRNA expression levels of KIFC1, KIF11, KIF14 and KIF20A were associated with shorter progression-free survival. On a functional level, knockdown of kinesins in Ben-Men-1 cells and in the newly established anaplastic meningioma cell line NCH93 resulted in a significantly inhibited tumor cell proliferation upon siRNA-mediated downregulation of KIF11 in both cell lines by up to 95% and 71%, respectively. Taken together, in this study we were able to identify the prognostic and functional role of several kinesin family members of which KIF11 exhibits the most promising properties as a novel prognostic marker and therapeutic target, which may offer new treatment options for aggressive meningiomas.
Background:
Sarcopenic obesity (SO) is characterized by a combination of low muscle and high fat mass with an additive negative effect of both conditions on cardiometabolic risk. The aim of the study was to determine the effect of whole-body electromyostimulation (WB-EMS) on the metabolic syndrome (MetS) in community-dwelling women aged ≥70 years with SO.
Methods:
The study was conducted in an ambulatory university setting. Seventy-five community-dwelling women aged ≥70 years with SO living in Northern Bavaria, Germany, were randomly allocated to either 6 months of WB-EMS application with (WB-EMS&P) or without (WB-EMS) dietary supplementation (150 kcal/day, 56% protein) or a non-training control group (CG). WB-EMS included one session of 20 min (85 Hz, 350 µs, 4 s of strain–4 s of rest) per week with moderate-to-high intensity. The primary study endpoint was the MetS Z-score with the components waist circumference (WC), mean arterial pressure (MAP), triglycerides, fasting plasma glucose, and high-density lipoprotein cholesterol (HDL-C); secondary study endpoints were changes in these determining variables.
Results:
MetS Z-score decreased in both groups; however, changes compared with the CG were significant (P=0.001) in the WB-EMS&P group only. On analyzing the components of the MetS, significant positive effects for both WB-EMS groups (P≤0.038) were identified for MAP, while the WB-EMS group significantly differed for WC (P=0.036), and the WB-EMS&P group significantly differed for HDL-C (P=0.006) from the CG. No significant differences were observed between the WB-EMS groups.
Conclusion:
The study clearly confirms the favorable effect of WB-EMS application on the MetS in community-dwelling women aged ≥70 years with SO. However, protein-enriched supplements did not increase effects of WB-EMS alone. In summary, we considered this novel technology an effective and safe method to prevent cardiometabolic risk factors and diseases in older women unable or unwilling to exercise conventionally.
We demonstrate two-quantum (2Q) coherent two-dimensional (2D)electronic spectroscopy using a shot-to-shot-modulated pulse shaper and fluorescence detection. Broadband collinear excitation is realized with the supercontinuum output of an argon-filled hollow-core fiber, enabling us to excite multiple transitions simultaneously in the visible range. The 2Q contribution is extracted via a three-pulse sequence with 16-fold phase cycling and simulated employing cresyl violet as a model system. Furthermore, we report the first experimental realization of one-quantum−two-quantum (1Q-2Q) 2D spectroscopy, offering less congested spectra as compared with the 2Q implementation. We avoid scattering artifacts and nonresonant solvent contributions by using fluorescence as the observable. This allows us to extract quantitative information about doubly excited states that agree with literature expectations. The high sensitivity and background-free nature of fluorescence detection allow for a general applicability of this method to many other systems.
Das vorliegende Working Paper untersucht die Performancewirkung eines multi-dimensionalen Strategie-Alignments in der Beschaffung. Hierfür wird zunächst ein Systematischer Literatur Review durchgeführt und der Wissenstand im Forschungsfeld erhoben. Die systematische Klassifikation, Analyse, Bewertung und Synthese der identifizierten 29 empirischen Studien erfolgt dabei auf der Grundlage eines konzeptionellen Frameworks und zugehöriger Inhaltskategorien sowie weiterer methodischer Vergleichsgrößen. Die Ergebnisse dieser Untersuchung zeigen nachdrücklich auf, dass eine Abstimmung, Harmonisierung und Verbindung von Beschaffungsstrategien (1) mit den übergeordneten Unternehmenszielen und -strategien, (2) anderen funktionalen Teilbereichen, sowie (3) der Lieferantenbasis (unter Berücksichtigung der kontextbezogenen Anforderungen und Gegebenheiten) zu signifikant positiven Performance-Effekten beiträgt. Insofern sollten die Empfehlungen dieser Untersuchung für ein holistisches Strategie-Alignment im Einkauf herangezogen werden. Neben der Ableitung von Implikationen für die Unternehmenspraxis wird eine Forschungsagenda für interessierte Wissenschaftler erarbeitet, indem inhaltliche Wissenslücken und methodische Verbesserungspotenziale auf Basis des Bezugsrahmens und einschlägiger Referenztexte definiert sowie zukünftige Forschungsbedarfe aufgezeigt werden. Darauf aufbauend wird die zentrale (bis dato unbeantwortete) Forschungsfrage eines integrativen Strategie-Alignment-Index durch die Operationalisierung der zugehörigen Konstrukte sowie der Formulierung entsprechender Hypothesen als Grundlage für die Durchführung einer empirischen Studie adressiert.
Earth Observation satellite data allows for the monitoring of the surface of our planet at predefined intervals covering large areas. However, there is only one medium resolution sensor family in orbit that enables an observation time span of 40 and more years at a daily repeat interval. This is the AVHRR sensor family. If we want to investigate the long-term impacts of climate change on our environment, we can only do so based on data that remains available for several decades. If we then want to investigate processes with respect to climate change, we need very high temporal resolution enabling the generation of long-term time series and the derivation of related statistical parameters such as mean, variability, anomalies, and trends. The challenges to generating a well calibrated and harmonized 40-year-long time series based on AVHRR sensor data flown on 14 different platforms are enormous. However, only extremely thorough pre-processing and harmonization ensures that trends found in the data are real trends and not sensor-related (or other) artefacts. The generation of European-wide time series as a basis for the derivation of a multitude of parameters is therefore an extremely challenging task, the details of which are presented in this paper.
In this study we used differentiated adult human upcyte (R) cells for the in vitro generation of liver organoids. Upcyte (R) cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte (R) process). Proliferating upcyte (R) cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte (R) cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel\(^{TM}\), they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.
The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts.
We here present the case of a 67-year-old woman with a history of a slowly progressive, polypous nodule on her left wrist. The lesion was excised, and the histological analysis revealed a clear cell tumour that was relatively sharply demarked from the surrounding tissue extending into the subcutaneous tissue. The tumour showed a characteristic trabecular pattern in which the tumour cells were arranged around numerous vessels. The neoplastic cells had a predominantly epithelioid shape, granular eosinophilic to clear cytoplasm and prominent centrally located nucleoli. The histological differential diagnosis included a metastatic clear-cell renal cell carcinoma and a primary cutaneous perivascular epithelioid cell tumour (PEComa). Immunohistochemically, the tumour cells revealed homogenous expression of HMB-45, MiTF and CD10, whereas MART-1 and S100 were negative. Antibodies against actin marked the trabecularly arranged vessels, and the neoplastic cells yielded a patchy positivity against actin and desmin. Additional immunohistochemical stains against pan-cytokeratin, CAIX, PAX-8 and EMA were negative. Based on the morphologic and immunophenotypic findings, the histological diagnosis of a CD10-positive cutaneous PEComa was made.
Diese Arbeit untersucht Literatur Reviews (LRs) im Forschungsfeld des Supply Chain Managements (SCM). Hierfür werden zunächst die methodischen und terminologischen Grundlagen der Analyse erarbeitet sowie taxonomische und thematische Klassifikati-onsschemata vergleichend gegenübergestellt. Anschließend werden der LR-Prozess dieser Untersuchung und ausgewählte Evaluationsdimensionen definiert. Auf diesen grundlegenden Vorarbeiten aufbauend werden LRs des SCM identifiziert, klassifiziert und umfassend bewertet. Die Forschungsergebnisse zeigen, dass es narrativen LRs teil-weise an methodischer Genauigkeit mangelt und infolgedessen die Technik des syste-matischen LR zunehmend an Bedeutung gewinnt. Darüber hinaus dient diese Arbeit als Bewertungsraster zur Evaluation der methodischen Güte von LRs, als Leitlinie zur Er-stellung von systematischen LRs und als State-of-the-Art der Sekundärforschung im SCM.
The present study aimed to evaluate the effect of high intensity dynamic resistance exercise (HIT-DRT) and whey protein supplementation (WPS) on bone mineral density (BMD) and sarcopenia parameters in osteosarcopenic men. Men ≥ 72 years with osteosarcopenia (n = 43) were randomly assigned to a HIT-RT (HIT-RT: n = 21) or a non-training control group (n = 22). Supervised HIT-RT twice/week was applied for 18 months, while the control group maintained their habitual lifestyle. Supplying WPS, total protein intake amounted to 1.5–1.6 (HIT-RT) and 1.2 g/kg/body mass/d (control). Both groups were supplied with calcium and vitamin D. Primary study outcomes were BMD and the sarcopenia Z-score. After adjusting for multiplicity, we observed significant positive effects for sarcopenia Z-score (standardized mean difference (SMD): 1.40), BMD at lumbar spine (SMD: 0.72) and total hip (SMD: 0.72). In detail, effect sizes for skeletal muscle mass changes were very pronounced (1.97, p < 0.001), while effects for functional sarcopenia parameters were moderate (0.87, p = 0.008; handgrip strength) or low (0.39, p = 0.209; gait velocity). Apart from one man who reported short periods of temporary worsening of existing joint pain, no HIT-RT/WPS-related adverse effects or injuries were reported. We consider HIT-RT supported by whey protein supplementation as a feasible, attractive, safe and highly effective option to fight osteosarcopenia in older men.
Holotomography is an extension of computed tomography where samples with low X-ray absorption can be investigated with higher contrast. In order to achieve this, the imaging system must yield an optical resolution of a few micrometers or less, which reduces the measurement area (field of view = FOV) to a few mm at most. If the sample size, however, exceeds the field of view (called local tomography or region of interest = ROI CT), filter problems arise during the CT reconstruction and phase retrieval in holotomography. In this paper, we will first investigate the practical impact of these filter problems and discuss approximate solutions. Secondly, we will investigate the effectiveness of a technique we call “multiscalar holotomography”, where, in addition to the ROI CT, a lower resolution non-ROI CT measurement is recorded. This is used to avoid the filter problems while simultaneously reconstructing a larger part of the sample, albeit with a lower resolution in the additional area.
Magnetic Particle Imaging (MPI) is a promising new tomographic modality for fast as well as three-dimensional visualization of magnetic material. For anatomical or structural information an additional imaging modality such as computed tomography (CT) is required. In this paper, the first hybrid MPI-CT scanner for multimodal imaging providing simultaneous data acquisition is presented.
Microbial spectrum and antibiotic resistance in patients suffering from penetrating Crohn's disease
(2022)
Intraabdominal abscess formation occurs in up to 30% of patients suffering from Crohn's disease (CD). While international guidelines recommend a step-up approach with a combination of empiric antibiotic therapy and percutaneous drainage to delay or even avoid surgery, evidence about microbial spectrum in penetrating ileitis is sparse. We retrospectively assessed outcomes of 46 patients with terminal penetrating Ileitis where microbial diagnostics have been performed and compared microbial spectrum and antibiotic resistance profile of CD patients with patients suffering from diverticulitis with intraabdominal abscess formation. In both groups, the most frequently isolated pathogen was the gram-negative bacterium E. coli belonging to the family of Enterobacterales. However, overall Enterobacterales were significantly more often verifiable in the control group than in CD patients. Furthermore, microbial analysis showed significant differences regarding isolation of anaerobic pathogens with decreased frequency in patients with CD. Subgroup analysis of CD patients to evaluate a potential influence of immunosuppressive therapy on microbial spectrum only revealed that Enterobacterales was less frequently detected in patients treated with steroids. Immunosuppressive therapy did not show any impact on all other groups of pathogens and did not change antibiotic resistance profile of CD patients. In conclusion, we were able to demonstrate that the microbial spectrum of CD patients does differ only for some pathogen species without increased rate of antibiotic resistance. However, the empiric antibiotic therapy for CD-associated intra-abdominal abscess remains challenging since different points such as local epidemiological and microbiological data, individual patient risk factors, severity of infection, and therapy algorithm including non-surgical and surgical therapy options should be considered before therapeutical decisions are made.
Dynamic resistance exercise (DRT) might be the most promising agent for fighting sarcopenia in older people. However, the positive effect of DRT on osteopenia/osteoporosis in men has still to be confirmed. To evaluate the effect of low‐volume/high‐intensity (HIT)‐DRT on bone mineral density (BMD) and skeletal muscle mass index (SMI) in men with osteosarcopenia, we initiated the Franconian Osteopenia and Sarcopenia Trial (FrOST). Forty‐three sedentary community‐dwelling older men (aged 73 to 91 years) with osteopenia/osteoporosis and SMI‐based sarcopenia were randomly assigned to a HIT‐RT exercise group (EG; n = 21) or a control group (CG; n = 22). HIT‐RT provided a progressive, periodized single‐set DRT on machines with high intensity, effort, and velocity twice a week, while CG maintained their lifestyle. Both groups were adequately supplemented with whey protein, vitamin D, and calcium. Primary study endpoint was integral lumbar spine (LS) BMD as determined by quantitative computed tomography. Core secondary study endpoint was SMI as determined by dual‐energy X‐ray absorptiometry. Additional study endpoints were BMD at the total hip and maximum isokinetic hip−/leg‐extensor strength (leg press). After 12 months of exercise, LS‐BMD was maintained in the EG and decreased significantly in the CG, resulting in significant between‐group differences (p < 0.001; standardized mean difference [SMD] = 0.90). In parallel, SMI increased significantly in the EG and decreased significantly in the CG (p < 0.001; SMD = 1.95). Total hip BMD changes did not differ significantly between the groups (p = 0.064; SMD = 0.65), whereas changes in maximum hip−/leg‐extensor strength were much more prominent (p < 0.001; SMD = 1.92) in the EG. Considering dropout (n = 2), attendance rate (95%), and unintended side effects/injuries (n = 0), we believe our HIT‐RT protocol to be feasible, attractive, and safe. In summary, we conclude that our combined low‐threshold HIT‐RT/protein/vitamin D/calcium intervention was feasible, safe, and effective for tackling sarcopenia and osteopenia/osteoporosis in older men with osteosarcopenia.
This study investigates synthetic aperture radar (SAR) time series of the Sentinel-1 mission acquired over the Atacama Desert, Chile, between March 2015 and December 2018. The contribution analyzes temporal and spatial variations of Sentinel-1 interferometric SAR (InSAR) coherence and exemplarily illustrates factors that are responsible for observed signal differences. The analyses are based on long temporal baselines (365–1090 days) and temporally dense time series constructed with short temporal baselines (12–24 days). Results are compared to multispectral data of Sentinel-2, morphometric features of the digital elevation model (DEM) TanDEM-X WorldDEM™, and to a detailed governmental geographic information system (GIS) dataset of the local hydrography. Sentinel-1 datasets are suited for generating extensive, nearly seamless InSAR coherence mosaics covering the entire Atacama Desert (>450 × 1100 km) at a spatial resolution of 20 × 20 meter per pixel. Temporal baselines over several years lead only to very minor decorrelation, indicating a very high signal stability of C-Band in this region, especially in the hyperarid uplands between the Coastal Cordillera and the Central Depression. Signal decorrelation was associated with certain types of surface cover (e.g., water or aeolian deposits) or with actual surface dynamics (e.g., anthropogenic disturbance (mining) or fluvial activity and overland flow). Strong rainfall events and fluvial activity in the periods 2015 to 2016 and 2017 to 2018 caused spatial patterns with significant signal decorrelation; observed linear coherence anomalies matched the reference channel network and indicated actual episodic and sporadic discharge events. In the period 2015–2016, area-wide loss of coherence appeared as strip-like patterns of more than 80 km length that matched the prevailing wind direction. These anomalies, and others observed in that period and in the period 2017–2018, were interpreted to be caused by overland flow of high magnitude, as their spatial location matched well with documented heavy rainfall events that showed cumulative precipitation amounts of more than 20 mm.
Introduction: Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors, genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were analyzed (2005–2020). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH, and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK). Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27% (26/97) at diagnosis. A germline mutation (GLM) was detected in 55% (47/86). DNA methylation subgrouping was available in 50% (31 / 62) with ATRT or SYN; for eMRT, methylation-based subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were 23.5 ± 4.6% and 19 ± 4.1%, respectively. Male sex (11 ± 5% vs. 35.8 ± 7.4%), M+ stage (6.1 ± 5.4% vs. 36.2 ± 7.4%), presence of SYN (7.1 ± 6.9% vs. 26.6 ± 5.3%) and GLM (7.7 ± 4.2% vs. 45.7 ± 8.6%) were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model, clinical factors that favorably influence the prognosis were female sex, localized stage, absence of a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option.
In contrast to postmenopausal women, evidence for a favorable effect of exercise on Bone Mineral Density (BMD) is still limited for men. This might be due to the paucity of studies, but also to the great variety of participants and study characteristics that may dilute study results. The aim of the present systematic review and meta-analysis was to evaluate the effect of exercise on BMD changes with rational eligibility criteria. A comprehensive search of six electronic databases up to 15 March 2021 was conducted. Briefly, controlled trials ≥6 months that determined changes in areal BMD in men >18 years old, with no apparent diseases or pharmacological therapy that relevantly affect bone metabolism, were included. BMD changes (standardized mean differences: SMD) of the lumbar spine (LS) and femoral neck (FN) were considered as outcomes. Twelve studies with 16 exercise and 12 control groups were identified. The pooled estimate of random-effect analysis was SMD = 0.38, 95%-CI: 0.14–0.61 and SMD = 0.25, 95%-CI: 0.00–0.49, for LS and FN, respectively. Heterogeneity between the trials was low–moderate. Funnel plots and rank and regression correlation tests indicate evidence for small study publication bias for LS but not FN-BMD. Subgroup analyses that focus on study length, type of exercise and methodologic quality revealed no significant difference between each of the three categories. In summary, we provided further evidence for a low but significant effect of exercise on BMD in men. However, we are currently unable to give even rough exercise recommendations for male cohorts.
Perianal fistulizing Crohn’s Disease (CD) with abscess formation represents an aggressive phenotype in Inflammatory Bowel Disease (IBD) with increased morbidity. Treatment is multidisciplinary and includes antibiotics, but knowledge about the microbial spectrum is rare often resulting in inadequate antimicrobial therapy. In this single center retrospective study, all patients who were operated due to perianal abscess formation were retrospectively analyzed and the microbial spectrum evaluated. Patients were divided into a CD and non-CD group with further subgroup analysis. 138 patients were finally included in the analysis with 62 patients suffering from CD. Relevant differences were detected for the microbial spectrum with anaerobic bacteria being significantly more often isolated from non-CD patients. In a subgroup-analysis of CD patients only, medical therapy had a relevant effect on the microbial spectrum since Streptococcus groups and Enterobacterales were significantly more often isolated in patients treated with steroids compared to those being treated by antibodies. In conclusion, the microbial spectrum of patients suffering from CD varies significantly from non-CD patients and immunosuppressive medication has a relevant effect on isolated pathogens. Based on that, adaption of antibiotic treatment might be discussed in the future.