Chancengleich vom Studium in den Beruf?

An der Humboldt-Universität zu Berlin am Institut für Erziehungswissenschaften, Abteilung Hochschulforschung wurde im Rahmen des Forschungsvorhabens „Chancengleich vom Studium in den Beruf?“ in dem Projektzeitraum vom 1. Januar 2020 bis 31. Oktober 2021 auf Grundlage von quantitativen Absolventenbefragungen und qualitativen Interviews mit Absolvent:innen und Expert:innen die Bedeutung des Migrationshintergrunds und der sozialen Herkunft beim Berufseinstieg nach dem Studium untersucht. Die Ergebnisse des Forschungsvorhabens bestätigen und spezifizieren bestehende Forschungserkenntnisse. So zeigen sich hinsichtlich des Einkommens und der Qualifikationsadäquanz der Beschäftigung wenig herkunfts- und migrationsspezifische Unterschiede, jedoch gestaltet sich der Einstieg in den Ar-beitsmarkt für Personen mit Migrationshintergrund schwieriger und ist von Phasen der Arbeitslosigkeit durchzogen. Hochschulinterne und -externe Beratungs- und Unterstützungsangebote für den Über-gang vom Studium in den Beruf werden von allen Absolvent:innen, unabhängig von Herkunft und Migrationshintergrund, selten in Anspruch genommen. Stattdessen werden Jobportale und Stellenanzeigen genutzt. In den Interviews wurde vereinzelt von Mentoringangeboten zum Austausch und zur Vernetzung berichtet, die als besonders hilfreich erlebt wurden und von denen sich der größte Gewinn erwartet wurde. Den eigenen Migrationshintergrund als Potential, d.h. damit verbundene Kompetenzen als Wettbewerbsvorteil auf dem Arbeitsmarkt, sehen die interviewten Absolvent:innen mit Migrationshintergrund nicht. Hingegen werden Auslandserfahrungen während des Studiums und erweiterte Englischkenntnisse von allen Absolvent:innen als erstrebenswert und vorteilhaft angesehen. Bestätigt werden anhand der quantitativen und qualitativen Daten auch andere Forschungen zur Aufstiegsorientierung der Absolvent:innen mit Migrationshintergrund. Herkunftsspezifische Unterschiede zu Studienbeginn und im Verlauf des Studiums stimmen ebenfalls mit dem aktuellen Kenntnisstand überein. Aus den Forschungsergebnissen lässt sich ableiten, dass es Potential zum Ausbau hochschulischer (zielgruppenspezifischer) Beratungsangebote für den Übergang in den Arbeitsmarkt gibt. Expert:innen berichten von diversen Herausforderungen in Bezug auf den Kenntnisstand zur Diversität der Studierenden und deren Bedarfen sowie der spezifischen Zielgruppenerreichung, aber auch hinsichtlich der bestehenden Strukturen an Hochschulen sowie der personellen und finanziellen Ausstat-tung von Career Service Einrichtungen. Zugleich zeigt sich, dass besonders die potentiellen Arbeitge-ber:innen in die Pflicht genommen werden müssen, diversitätssensible Bewerbungsprozesse zu gestalten

Chancengleich vom Studium in den Beruf?

An der Humboldt-Universität zu Berlin am Institut für Erziehungswissenschaften, Abteilung Hochschulforschung wurde im Rahmen des Forschungsvorhabens „Chancengleich vom Studium in den Beruf?“ in dem Projektzeitraum vom 1. Januar 2020 bis 31. Oktober 2021 auf Grundlage von quantitativen Absolventenbefragungen und qualitativen Interviews mit Absolvent:innen und Expert:innen die Bedeutung des Migrationshintergrunds und der sozialen Herkunft beim Berufseinstieg nach dem Studium untersucht. Die Ergebnisse des Forschungsvorhabens bestätigen und spezifizieren bestehende Forschungserkenntnisse. So zeigen sich hinsichtlich des Einkommens und der Qualifikationsadäquanz der Beschäftigung wenig herkunfts- und migrationsspezifische Unterschiede, jedoch gestaltet sich der Einstieg in den Ar-beitsmarkt für Personen mit Migrationshintergrund schwieriger und ist von Phasen der Arbeitslosigkeit durchzogen. Hochschulinterne und -externe Beratungs- und Unterstützungsangebote für den Über-gang vom Studium in den Beruf werden von allen Absolvent:innen, unabhängig von Herkunft und Migrationshintergrund, selten in Anspruch genommen. Stattdessen werden Jobportale und Stellenanzeigen genutzt. In den Interviews wurde vereinzelt von Mentoringangeboten zum Austausch und zur Vernetzung berichtet, die als besonders hilfreich erlebt wurden und von denen sich der größte Gewinn erwartet wurde. Den eigenen Migrationshintergrund als Potential, d.h. damit verbundene Kompetenzen als Wettbewerbsvorteil auf dem Arbeitsmarkt, sehen die interviewten Absolvent:innen mit Migrationshintergrund nicht. Hingegen werden Auslandserfahrungen während des Studiums und erweiterte Englischkenntnisse von allen Absolvent:innen als erstrebenswert und vorteilhaft angesehen. Bestätigt werden anhand der quantitativen und qualitativen Daten auch andere Forschungen zur Aufstiegsorientierung der Absolvent:innen mit Migrationshintergrund. Herkunftsspezifische Unterschiede zu Studienbeginn und im Verlauf des Studiums stimmen ebenfalls mit dem aktuellen Kenntnisstand überein. Aus den Forschungsergebnissen lässt sich ableiten, dass es Potential zum Ausbau hochschulischer (zielgruppenspezifischer) Beratungsangebote für den Übergang in den Arbeitsmarkt gibt. Expert:innen berichten von diversen Herausforderungen in Bezug auf den Kenntnisstand zur Diversität der Studierenden und deren Bedarfen sowie der spezifischen Zielgruppenerreichung, aber auch hinsichtlich der bestehenden Strukturen an Hochschulen sowie der personellen und finanziellen Ausstat-tung von Career Service Einrichtungen. Zugleich zeigt sich, dass besonders die potentiellen Arbeitge-ber:innen in die Pflicht genommen werden müssen, diversitätssensible Bewerbungsprozesse zu gestalten

The impact of histological annotations for accurate tissue classification using mass spectrometry imaging

Knowing the precise location of analytes in the tissue has the potential to provide information about the organs’ function and predict its behavior. It is especially powerful when used in diagnosis and prognosis prediction of pathologies, such as cancer. Spatial proteomics, in particular mass spectrometry imaging, together with machine learning approaches, has been proven to be a very helpful tool in answering some histopathology conundrums. To gain accurate information about the tissue, there is a need to build robust classification models. We have investigated the impact of histological annotation on the classification accuracy of different tumor tissues. Intrinsic tissue heterogeneity directly impacts the efficacy of the annotations, having a more pronounced effect on more heterogeneous tissues, as pancreatic ductal adenocarcinoma, where the impact is over 20% in accuracy. On the other hand, in more homogeneous samples, such as kidney tumors, histological annotations have a slenderer impact on the classification accuracy

Pharmacoproteomic characterisation of human colon and rectal cancer

Most molecular cancer therapies act on protein targets but data on the proteome status of patients and cellular models for proteome-guided pre-clinical drug sensitivity studies are only beginning to emerge. Here, we profiled the proteomes of 65 colorectal cancer (CRC) cell lines to a depth of > 10,000 proteins using mass spectrometry. Integration with proteomes of 90 CRC patients and matched transcriptomics data defined integrated CRC subtypes, highlighting cell lines representative of each tumour subtype. Modelling the responses of 52 CRC cell lines to 577 drugs as a function of proteome profiles enabled predicting drug sensitivity for cell lines and patients. Among many novel associations, MERTK was identified as a predictive marker for resistance towards MEK1/2 inhibitors and immunohistochemistry of 1,074 CRC tumours confirmed MERTK as a prognostic survival marker. We provide the proteomic and pharmacological data as a resource to the community to, for example, facilitate the design of innovative prospective clinical trials. © 2017 The Authors. Published under the terms of the CC BY 4.0 licens

Elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in gastric cancer: a distinct microsatellite instability type with potential clinical impact?

We investigated the clinical impact of elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in the context of neoadjuvant chemotherapy (CTx) in gastric/gastro-oesophageal adenocarcinomas. We analysed 583 resected tumours (272 without and 311 after CTx) and 142 tumour biopsies before CTx. If at least two or three of the five tetranucleotide repeat markers tested showed instability, the tumours were defined as EMAST (2+) or EMAST (3+), respectively. Expression of mismatch repair proteins including MSH3 was analysed using immunohistochemistry. Microsatellite instability (MSI) and Epstein-Barr virus (EBV) positivity were determined using standard assays. EMAST (2+) and (3+) were detected in 17.8 and 11.5% of the tumours, respectively. The frequency of EMAST (2+) or (3+) in MSI-high (MSI-H) tumours was 96.2 or 92.5%, respectively, demonstrating a high overlap with this molecular subtype, and the association of EMAST and MSI status was significant (each overall p < 0.001). EMAST (2+ or 3+) alone in MSI-H and EBV-negative tumours demonstrated only a statistically significant association of EMAST (2+) positivity and negative lymph node status (42.3% in EMAST (2+) and 28.8% in EMAST negative, p = 0.045). EMAST alone by neither definition was significantly associated with overall survival (OS) of the patients. The median OS for EMAST (2+) patients was 40.0 months (95% confidence interval [CI] 16.4-63.6) compared with 38.7 months (95% CI 26.3-51.1) for the EMAST-negative group (p = 0.880). The median OS for EMAST (3+) patients was 46.7 months (95% CI 18.2-75.2) and 38.7 months (95% CI 26.2-51.2) for the negative group (p = 0.879). No statistically significant association with response to neoadjuvant CTx was observed (p = 0.992 and p = 0.433 for EMAST (2+) and (3+), respectively). In conclusion, our results demonstrate a nearly complete intersection between MSI-H and EMAST and they indicate that EMAST alone is not a distinct instability type associated with noticeable clinico-pathological characteristics of gastric carcinoma patients

The BCL-2 family member BOK promotes KRAS-driven lung cancer progression in a p53-dependent manner.

A variety of cancer entities are driven by KRAS mutations, which remain difficult to target clinically. Survival pathways, such as resistance to cell death, may represent a promising treatment approach in KRAS mutated cancers. Based on the frequently observed genomic deletions of BCL-2-related ovarian killer (BOK) in cancer patients, we explored the function of BOK in a mutant KrasG12D-driven murine model of lung cancer. Using KrasG12D/+ Bok-/- mice, we observed an overall tumor-promoting function of BOK in vivo. Specifically, loss of BOK reduced proliferation both in cell lines in vitro as well as in KrasG12D-driven tumor lesions in vivo. During tumor development in vivo, loss of BOK resulted in a lower tumor burden, with fewer, smaller, and less advanced tumors. Using KrasG12D/+ Tp53Δ/Δ Bok-/- mice, we identified that this phenotype was entirely dependent on the presence of functional p53. Furthermore, analysis of a human dataset of untreated early-stage lung tumors did not identify any common deletion of the BOK locus, independently of the TP53 status or the histopathological classification. Taken together our data indicate that BOK supports tumor progression in Kras-driven lung cancer

Structure and content of the EU-IVDR: current status and implications for pathology

Background Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) was passed by the European Parliament and the Council of the European Union on 5 April 2017 and came into force on 26 May 2017. A new amending regulation, which introduces a phased implementation of the IVDR with new transitional provisions for certain in vitro diagnostic medical devices (IVDs) and a later date of application of some requirements for in-house devices for healthcare facilities, was adopted on 15 December 2021. The combined use of CE-certified IVDs (CE-IVDs), in-house IVDs (IH-IVDs), and research use only (RUO) devices are a cornerstone of diagnostics in pathology departments and crucial for optimal patient care. The IVDR not only regulates the manufacture and placement on the market of industrially manufactured IVDs, but also imposes conditions on the manufacture and use of IH-IVDs for internal use by healthcare facilities. Objectives Our work provides an overview of the background and structure of the IVDR and identifies core areas that need to be interpreted and fleshed out in the context of the legal framework as well as expert knowledge. Conclusions The gaps and ambiguities in the IVDR crucially require the expertise of professional societies, alliances, and individual stakeholders to successfully facilitate the implementation and use of the IVDR in pathology departments and to avoid aberrant developments

Levels of the Autophagy-Related 5 Protein Affect Progression and Metastasis of Pancreatic Tumors in Mice

[Background and Aims]: Cells in pancreatic ductal adenocarcinoma (PDAC) undergo autophagy, but its effects vary with tumor stage and genetic factors. We investigated the consequences of varying levels of the autophagy related 5 (Atg5) protein on pancreatic tumor formation and progression. [Methods]: We generated mice that express oncogenic Kras in primary pancreatic cancer cells and have homozygous disruption of Atg5 (A5;Kras) or heterozygous disruption of Atg5 (A5+/–;Kras), and compared them with mice with only oncogenic Kras (controls). Pancreata were analyzed by histology and immunohistochemistry. Primary tumor cells were isolated and used to perform transcriptome, metabolome, intracellular calcium, extracellular cathepsin activity, and cell migration and invasion analyses. The cells were injected into wild-type littermates, and orthotopic tumor growth and metastasis were monitored. Atg5 was knocked down in pancreatic cancer cell lines using small hairpin RNAs; cell migration and invasion were measured, and cells were injected into wild-type littermates. PDAC samples were obtained from independent cohorts of patients and protein levels were measured on immunoblot and immunohistochemistry; we tested the correlation of protein levels with metastasis and patient survival times. [Results]: A5+/–;Kras mice, with reduced Atg5 levels, developed more tumors and metastases, than control mice, whereas A5;Kras mice did not develop any tumors. Cultured A5+/–;Kras primary tumor cells were resistant to induction and inhibition of autophagy, had altered mitochondrial morphology, compromised mitochondrial function, changes in intracellular Ca2+ oscillations, and increased activity of extracellular cathepsin L and D. The tumors that formed in A5+/–;Kras mice contained greater numbers of type 2 macrophages than control mice, and primary A5+/–;Kras tumor cells had up-regulated expression of cytokines that regulate macrophage chemoattraction and differentiation into M2 macrophage. Knockdown of Atg5 in pancreatic cancer cell lines increased their migratory and invasive capabilities, and formation of metastases following injection into mice. In human PDAC samples, lower levels of ATG5 associated with tumor metastasis and shorter survival time. [Conclusions]: In mice that express oncogenic Kras in pancreatic cells, heterozygous disruption of Atg5 and reduced protein levels promotes tumor development, whereas homozygous disruption of Atg5 blocks tumorigenesis. Therapeutic strategies to alter autophagy in PDAC should consider the effects of ATG5 levels to avoid the expansion of resistant and highly aggressive cells.This study was supported in part by the Mildred-Scheel-Professur der Deutschen Krebshilfe 111464, DFG AL 1174/6-1 to H.A., DFG DI 2299/1-1 to K.N.D., DFG SFB1321 (S01) to K.S. and W.W., and the German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD e.V.) to J.A

Candidiasis caused by Candida kefyr in a neonate: Case report

<p>Abstract</p> <p>Background</p> <p>Systemic <it>Candidia </it>infections are of major concern in neonates, especially in those with risk factors such as longer use of broad spectrum antibiotics. Recent studies showed that also term babies with underlying gastrointestinal or urinary tract abnormalities are much more prone to systemic <it>Candida </it>infection. We report a very rare case of candidiasis caused by <it>Candida kefyr </it>in a term neonate.</p> <p>Case Presentation</p> <p>Renal agenesis on the left side was diagnosed antenatally and anal atresia postnatally. Moreover, a vesico-ureteral-reflux (VUR) grade V was detected by cystography. The first surgical procedure, creating a protective colostoma, was uneventful. Afterwards our patient developed urosepsis caused by <it>Enterococcus faecalis </it>and was treated with piperacillin. The child improved initially, but deteriorated again. A further urine analysis revealed <it>Candida kefyr </it>in a significant number. As antibiotic resistance data about this non-<it>albicans Candida </it>species are limited, we started liposomal amphotericin B (AMB), but later changed to fluconazole after receiving the antibiogram. Candiduria persisted and abdominal imaging showed a <it>Candida </it>pyelonephritis. Since high grade reflux was prevalent we instilled AMB into the child's bladder as a therapeutic approach. While undergoing surgery (creating a neo-rectum) a recto-vesical fistula could be shown and subsequently was resected. The child recovered completely under systemic fluconazole therapy over 3 months.</p> <p>Conclusions</p> <p>Candidiasis is still of major concern in neonates with accompanying risk factors. As clinicians are confronted with an increasing number of non-<it>albicans Candida </it>species, knowledge about these pathogens and their sensitivities is of major importance.</p

Who Is at Risk for Diagnostic Discrepancies? Comparison of Pre- and Postmortal Diagnoses in 1800 Patients of 3 Medical Decades in East and West Berlin

<div><h3>Background</h3><p>Autopsy rates in Western countries consistently decline to an average of <5%, although clinical autopsies represent a reasonable tool for quality control in hospitals, medically and economically. Comparing pre- and postmortal diagnoses, diagnostic discrepancies as uncovered by clinical autopsies supply crucial information on how to improve clinical treatment. The study aimed at analyzing current diagnostic discrepancy rates, investigating their influencing factors and identifying risk profiles of patients that could be affected by a diagnostic discrepancy.</p> <h3>Methods and Findings</h3><p>Of all adult autopsy cases of the Charité Institute of Pathology from the years 1988, 1993, 1998, 2003 and 2008, the pre- and postmortal diagnoses and all demographic data were analyzed retrospectively. Based on power analysis, 1,800 cases were randomly selected to perform discrepancy classification (class I-VI) according to modified Goldman criteria. The rate of discrepancies in major diagnoses (class I) was 10.7% (95% CI: 7.7%–14.7%) in 2008 representing a reduction by 15.1%. Subgroup analysis revealed several influencing factors to significantly correlate with the discrepancy rate. Cardiovascular diseases had the highest frequency among class-I-discrepancies. Comparing the 1988-data of East- and West-Berlin, no significant differences were found in diagnostic discrepancies despite an autopsy rate differing by nearly 50%. A risk profile analysis visualized by intuitive heatmaps revealed a significantly high discrepancy rate in patients treated in low or intermediate care units at community hospitals. In this collective, patients with genitourinary/renal or infectious diseases were at particularly high risk.</p> <h3>Conclusions</h3><p>This is the current largest and most comprehensive study on diagnostic discrepancies worldwide. Our well-powered analysis revealed a significant rate of class-I-discrepancies indicating that autopsies are still of value. The identified risk profiles may aid both pathologists and clinicians to identify patients at increased risk for a discrepant diagnosis and possibly suboptimal treatment intra vitam.</p> </div