The Clinical Relevance of Circulating Tumor Cells in Early Breast Cancer

Circulating tumor cells (CTCs) are considered to be evading cancer cells that have been shed or actively invaded from the primary tumor into the blood circulation or lymphatic system and which may finally extravasate to found metastases. CTCs as “liquid biopsy” hold great promise to be a powerful non-invasive real-time measurable biomarker for predicting clinical outcomes and cancer treatment response. Several studies evaluated the role of CTC presence and count in the neoadjuvant and adjuvant setting of early breast cancer (EBC) and revealed their significant prognostic value. In this chapter, we highlight the clinical relevance of CTCs in early breast cancer (EBC) and state the urgency for further research in this field to definitely translate this marker from bench to bedside

Flexibilisierung von Arbeitszeiten und Arbeitsformen in Bibliotheken

Die vorliegende, von Studierenden der Fachhochschule für Bibliothekswesen in Frankfurt am Main erstellte Projektarbeit befaßt sich mit Fragen, Aspekten und Möglichkeiten der Flexibilisierung von Arbeitszeiten und Arbeitsformen in Bibliotheken. Im ersten Teil der Arbeit werden die wichtigsten Arbeitsteilzeitmodelle vorgestellt und deren Vorteile für Arbeitgeber und nehmer herausgearbeitet. Anschließend erfolgt eine durch Graphiken und Tabellen veranschaulichte Untersuchung von drei ausgewählte Universitätsbibliotheken (Gießen, Marburg, Mainz) in bezug auf bereits existierende Arbeitszeitflexibilisierung. Ein Ausblick geht der Frage nach, ob die dargestellten Teilzeitmodelle für Bibliotheken notwendig und ausreichend sind. Der zweite Themenkomplex befaßt sich mit der Telearbeit als einer innovativen Arbeitsform in Bibliotheken. Ausgehend von einer Begriffsbestimung werden verschiedene Formen der Telearbeit sowie deren Vor und Nachteile geschildert. Es wird erläutert, welche Bedingungen an den Telearbeiter und seinen Arbeitsplatz geknüpft sind, welche rechtlichen Voraussetzungen erfüllt werden müssen, welche finanziellen Aspekte eine Rolle spielen und welche Anwendungsmöglichkeiten für Telearbeit in Bibliotheken bestehen. An drei konkreten Beispielen wird dann geschildert, wie Telearbeit in Bibliotheken bereits verwirklicht wurde. Abschließend wird der Frage nachgegangen, welche Perspektiven der Einsatz von Telearbeit in Bibliotheken hat. Der dritte Abschnitt der Ausarbeitung stellt das bibliothekarische Call Center als neue Form einer benutzerorientierten Einrichtung vor. Zielsetzungen und Dienstleistungsformen des Call Centers werden ebenso abgehandelt wie Aspekte der Planung, Einrichtung und Arbeitsplatzergonomie sowie des Einsatzes von Telearbeit. Anhand des Beispiels der Zentral und Landesbibliothek Berlin wird schließlich dokumentiert, wie sich ein bibliothekarisches Call Center in der Praxis bereits bewährt hat

Flavonoids from Ericameria nauseosa inhibiting PI3K/AKT pathway in human melanoma cells.

The PI3K/AKT and MAPK/ERK pathways are frequently mutated in metastatic melanoma. In a screen of over 2500 plant extracts, the dichloromethane extract of Ericameria nauseosa significantly inhibited oncogenic activity of AKT in MM121224 human melanoma cells. This extract was analyzed by analytical HPLC, and the column effluent was fractionated and tested for activity to generate the so-called HPLC-based activity profile. Compounds eluting within active time-windows of the chromatogram were subsequently isolated in a larger scale to afford 11 flavones (1-11), four flavanones (12-15), two diterpenes (16, 17), and a seco-caryophyllene (18). All isolated compounds were tested for activity, whereby only flavonoids were found active. Of these, flavones were shown to be more active than the flavanones. The most potent flavone was compound 9, that was displaying an IC50 of 14.7 ± 1.4 µM on AKT activity in MM121224 cells. The terpenoids (16-18) were found to be inactive in the assay. Both diterpenes, a grindelic acid derivative (16) and an ent-neo-clerodane (17) were identified as new natural products. Their absolute configuration was established by ECD. Compound 17 is the first description of a clerodane type diterpene in the genus Ericameria

HCMV-infection in a human arterial organ culture model: effects on cell proliferation and neointimal hyperplasia

<p>Abstract</p> <p>Background</p> <p>The impact of infections with the human cytomegalovirus (HCMV) for the development of atherosclerosis and restenosis is still unclear. Both a clear correlation and no correlation at all have been reported in clinical, mostly serological studies. In our study we employed a human non-injury ex vivo organ culture model to investigate the effect of an in vitro permissive HCMV-infection on cell proliferation and neointimal hyperplasia for a period of 56 days.</p> <p>Results</p> <p>During routine-nephrectomies parts of renal arteries from 71 patients were obtained and prepared as human organ cultures. Cell free HCMV infection was performed with the fibroblast adapted HCMV strain AD169, the endotheliotropic strain TB40E, and a clinical isolate (AN 365). After 3, 7, 14, 21, 28, 35, and 56 days in culture staining of HCMV-antigens was carried out and reactive cell proliferation and neointimal thickening were analysed. Successful HCMV-infection was accomplished with all three virus strains studied. During the first 21 days in organ culture no cell proliferation or neointimal hyperplasia was detected. At day 35 and day 56 moderate cell proliferation and neointimal hyperplasia was found both in HCMV-infected segments and mock infected controls. Neointimal hyperplasia in productively HCMV-infected segments was lower than in non infected at day 35 and day 56, but relatively higher after infection with the endotheliotropic TB40E in comparison with the two other strains.</p> <p>Conclusion</p> <p>The data do not support the hypothesis that HCMV-infection triggers restenosis via a stimulatory effect on cell proliferation and neointimal hyperplasia in comparison to non infected controls. Interestingly however, even after lytic infection, a virus strain specific difference was observed.</p

Catecholamine responses to virtual combat: implications for post-traumatic stress and dimensions of functioning

PTSD symptoms can result in functional impairment among service members (SMs), even in those without a clinical diagnosis. The variability in outcomes may be related to underlying catecholamine mechanisms. Individuals with PTSD tend to have elevated basal catecholamine levels, though less is known regarding catecholamine responses to trauma-related stimuli. We assessed whether catecholamine responses to a virtual combat environment impact the relationship between PTSD symptom clusters and elements of functioning. Eighty-seven clinically healthy SMs, within 2 months after deployment to Iraq or Afghanistan, completed self-report measures, viewed virtual-reality (VR) combat sequences, and had sequential blood draws. Norepinephrine responses to VR combat exposure moderated the relationship between avoidance symptoms and scales of functioning including physical functioning, physical-role functioning, and vitality. Among those with high levels of avoidance, norepinephrine change was inversely associated with functional status, whereas a positive correlation was observed for those with low levels of avoidance. Our findings represent a novel use of a virtual environment to display combat-related stimuli to returning SMs to elucidate mind-body connections inherent in their responses. The insight gained improves our understanding of post-deployment symptoms and quality of life in SMs and may facilitate enhancements in treatment. Further research is needed to validate these findings in other populations and to define the implications for treatment effectiveness

Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: A retrospective study by the I-BFM study group

To study the prognostic relevance of rare genetic aberrations in acute myeloid leukemia (AML), such as t(16:21), international collaboration is required. Two different types of t(16:21) translocations can be distinguished: t(16:21)(p11;q22), resulting in the FUS-ERG fusion gene; and t(16:21)(q24;q22), resulting in RUNX1-core binding factor (CBFA2T3). We collected data on clinical and biological characteristics of 54 pediatric AML cases with t(16:21) rearrangements from 14 international collaborative study groups participating in the international Berlin-Frankfurt-Miinster (I-BFM) AML study group. The AML-BFM cohort diagnosed between 1997 and 2013 was used as a reference cohort. RUNX1-CBFA2T3 (n = 23) had significantly lower median white blood cell count (12.5 x 10(9)/L, P = .03) compared with the reference cohort. FUS-ERG rearranged AML (n = 31) had no predominant French-American-British (FAB) type, whereas 76% of RUNX1-CBFA2T3 had an M1/M2 FAB type (M1, M2), significantly different from the reference cohort (P = .004). Four-year event-free survival (EFS) of patients with FUS-ERG was 7% (standard error [SE] = 5%), significantly lower compared with the reference cohort (51%, SE = 1%, P < .001). Four-year EFS of RUNX1-CBFA2T3 was 77% (SE = 8%, P = .06), significantly higher compared with the reference cohort. Cumulative incidence of relapse was 74% (SE = 8%) in FUS-ERG, 0% (SE = 0%) in RUNX1-CBFA2T3, compared with 32% (SE = 1%) in the reference cohort (P < .001). Multivariate analysis identified both FUS-ERG and RUNX1-CBFA2T3 as independent risk factors with hazard ratios of 1.9 (P < .0001) and 0.3 (P = .025), respectively. These results describe 2 clinically relevant distinct subtypes of pediatric AML. Similarly to other core-binding factor AMLs, patients with RUNX1-CBFA2T3 rearranged AML may benefit from stratification in the standard risk treatment, whereas patients with FUS-ERG rearranged AML should be considered high-risk

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Integration of Ecosystem Services and Habitats into the Biodiversity Atlas Austria

The Biodiversity Atlas Austria (“Biodiversitäts-Atlas Österreich”) is a data portal to explore Austria’s biodiversity. It is based on the open-source infrastructure of the Atlas of Living Australia (ALA) and was launched with support of the Living Atlas (LA) community in late 2019 by the Biodiversity Hub of the University of Continuing Education Krems funded by the Government of Lower Austria. At present, it stores more than 8.5 million species occurrence records from various data partners and institutions and is available in both English and German. The Atlas is running on two virtual machines with 4 TB storage and is hosting many of the ALA-developed tools and services such as collectory, biocache, biodiversity information explorer, regions, spatial portal, sensitive data service, lists, images, and dashboard.In the project “ÖKOLEITA” (2021-2023), two new tools were developed within the existing LA infrastructure and will be launched in late 2023 to allow users to deal with ecosystem services and habitat data.The “ecosys”-tool will allow management, visualization, and analysis  of ecosystem services by uploading different (raster or vector) TIFF files containing mapped ecosystem services to the geoserver. Users will be able to inspect various ecosystem services at a specific geolocation or compare different geolocations or a transect on their respective ecosystem service potential. The ecosystem service values are presented on the one hand as pictograms, where the value is transformed into quintiles, orienting on the work by Schreder et al. (2018), and as bar chart showing the true values.The “habitat” tool will store and manage datasets of habitat mappings (shapefiles) and allow users to spatially explore those various habitat mappings on a map. Users will be able to search for specific habitats across all datasets or a specific one and get all occurrences of this habitat type returned. Through linkage to the biocache, a click on a specific area reveals the list of species found within that habitat recording, as well as all the species occurrences within that area stored in the database. A “habitat backbone” of the most used habitat classifications in Austria will allow dealing with habitat mappings that use different classifications.Both tools are integrated into the Living Atlases infrastructure and communicate with the other tools and services of the Biodiversity Atlas Austria (Fig. 1). They share a common administration back-end but have different front-ends, where the users can explore the ecosystem services and habitats spatially and in connection with species occurrence records and other contextual information

Magnetic resonance imaging findings of high-grade ductal carcinoma in situ of the male breast: A case report

Ductal carcinoma in situ in men is incredibly rare and detection by conventional mammography and ultrasound is often challenging. We report an unusual case of a 50-year-old male, with no family history of breast cancer, who presented with an 8-year history of left-sided breast pain and recurrent bloody nipple discharge without any significant suspicious imaging features in mammography and targeted high-resolution ultrasound. Breast magnetic resonance imaging was performed as an adjunct modality. Magnetic resonance imaging findings revealed a suspicious retroareolar non-mass abnormality of segmental, linear and dendritic pattern, which was highly suspicious for a ductal carcinoma in situ. Stereotactic guided biopsy and subsequent mastectomy were consistent with pure high-grade ductal carcinoma in situ of the left breast. Overall, this case highlights the challenges in diagnosing ductal carcinoma in situ in men and demonstrates the importance for further investigating clinical suspicions of the male breast

A Dimerosesquiterpene and Sesquiterpene Lactones from Artemisia argyi Inhibiting Oncogenic PI3K/AKT Signaling in Melanoma Cells.

A library of more than 2500 plant extracts was screened for activity on oncogenic signaling in melanoma cells. The ethyl acetate extract from the aerial parts of Artemisia argyi displayed pronounced inhibition of the PI3K/AKT pathway. Active compounds were tracked with the aid of HPLC-based activity profiling, and altogether 21 active compounds were isolated, including one novel dimerosequiterpenoid (1), one new disesquiterpenoid (2), three new guaianolides (3-5), 12 known sesquiterpenoids (6-17), and four known flavonoids (19-22). A new eudesmanolide derivative (13b) was isolated as an artifact formed by methanolysis. Compound 1 is the first adduct comprising a sesquiterpene lactone and a methyl jasmonate moiety. The absolute configurations of compounds 1 and 3-18 were established by comparison of their experimental and calculated ECD spectra. The absolute configuration for 2 was determined by X-ray diffraction analysis. Guaianolide 8 was the most potent sesquiterpene lactone, inhibiting the PI3K/AKT pathway with an IC50 value of 8.9 ± 0.9 μM