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Einblicke ... / Tourismusverband Sächsische Schweiz: Tourismusnachrichten aus der Sächsischen Schweiz
No full text1x1 der Schule: Fragen und Antworten zum Schulalltag
No full textFragen und Antworten zum Schulalltag. In diesem Notizbüchlein, dem „1×1 der Schule“, sind die Fragen gesammelt und beantwortet, die im Ministerium immer wieder gestellt werden. Natürlich hoffen wir, dass auch Ihre Frage dabei ist. Wenn nicht, wenden Sie sich einfach an unsere Bürgerbeauftragte.
Redaktionsschluss: 30.04.202
Lung lineage induction through small molecules and partial cell reprogramming for lung organoid generation: Mimicking the pulmonary niche in vitro
No full textPrematurity-associated pulmonary complications pose significant challenges to both affected newborns and the healthcare system. To better understand the underlying causes of immature lungs and find effective treatments, there is a need for new in vitro and in vivo models. An accurate in vitro lung model should closely resemble the distal lung in terms of cell composition, structure, and function. Unfortunately, current lung models are not sufficient for studying the mechanisms of late lung maturation and developmental stages of pulmonary embryology.
To address this need, research has turned to lung organoids as a promising tool. These 3D cell culture models, made up of various self-organizing progenitor or stem cells, closely replicate the structure of the corresponding organ and can be used to study lung maturation and disease processes. So far, organoids were derived from isolated organ progenitor cells or induced Pluripotent Stem Cells (iPSCs), and Embryonic Stem Cells (ESCs). However, logistical and ethical barriers currently hamper access to the corresponding tissue and prevent widespread implementation. To overcome these challenges, this study developed a lung model from progenitor and stem cells obtained from the placenta and umbilical cord. These tissues are an accessible and innovative source of stem cells, as they are usually discarded postnatally and do not raise ethical concerns. Epithelial progenitor cells (EpiPCs) were isolated from the amniotic epithelium, which already expresses lung progenitor cell markers, and endothelial cells (HUVECs) were isolated from the umbilical vein, while mesenchymal stem cells (hWJ-MSCs) were isolated from the Wharton's jelly. Subsequently, by co-culturing EpiPCs—without any prior induction toward lung lineage—with HUVECs, we were able to generate primitive human Lung Organoids (phLOs).
To induce lung lineage in these phLOs, biophysical and biochemical cues were utilized to mimic the pulmonary niche. This included ALI-cell culture conditions, induced cell aggregation, and the use of an extracellular matrix. These techniques facilitated the more effective spreading of phLOs, leading to the formation of cell aggregates with sufficient space for further three-dimensional growth. As a result, a more uniform cell distribution, enhanced reproducibility, and alveolar-like growth could be observed, which further encouraged the development of lung lineages.
Long-term culture of phLOs (phLOsDIV120) was also performed to test if lung-related gene expression (αENaC, βENaC, γENaC, SFTPB, SFTPC, CFTR) and alveolar-like growth patterns were enhanced over time. The findings indicated that lung-related gene expression increased significantly until DIV46 while no significant increase was observed after DIV120. In the long-term culture of phLOsDIV120 two growth patterns were observed: a cystic growth pattern with grape-like formations and delineated luminal structures and a branched growth pattern with condensed antler-like structures with an opaque appearance.
Inducing lung lineage properties was found to be crucial not only for the final construct of phLOs but also, more importantly, for the initial cell populations. The closer these starting cells are to the in vivo lung environment, the more accurate the resulting lung model will be. Consequently, this study distinguishes between primitive hLOs (phLOs) and optimized hLOs. Unlike phLOs, optimized hLOs are derived from a starting cell population that has been induced towards lung lineage. The starting cells used to generate optimized hLOs include EpiPCs that have been manipulated with small molecules, as well hWJ-MSCs that have been manipulated through partial reprogramming.
Lung lineage induction in EpiPCs involved mimicking the steps of lung development in vitro by activating signaling cascades including FGF, WNT, and SHH pathways through the use of small molecules. The addition of these small molecules to the EpiPCs culture medium aimed to increase the number of EpiPCs, while also inducing distal lung cell characteristics, primarily the induction of the lung fate transcription factor TTF-1 and the expression of lung-related genes such as CFTR, NKX2.1, SFTPB, SFTPC, and ENaC α/β/γ. The functions of ENaC and CFTR are important in maintaining fluid homeostasis in the lung and its adaptation to air breathing. AT2 cells synthesize and secrete surfactant, which prevents alveolar collapse during exhalation. NKX2.1 plays a crucial role in lung embryology, as its presence determines the respiratory lineage of endodermal cells. TTF-1 is the transcription factor of NKX2.1 and thus plays a vital role as a lineage-survival factor in lung development.
All small molecules tested, including A83-01, CHIR99021, SAG, and FGF2, demonstrated a tendency to enhance the yield of EpiPC cells. However, only the application of the small molecule FGF2, as well as the combination of the SHH-Activator SAG and FGF2, led to a significant increase in the EpiPC cell count. While the WNT-Activator caused a notable decrease in TTF-1 expression, no significant effects on TTF-1 expression were observed from the other small molecules.
All cultured EpiPCs exposed to small molecules exhibited the expression of lung-related genes, including αENaC, βENaC, γENaC, SFTPB, SFTPC, and CFTR. The SHH activator SAG significantly increased the expression of βENaC, while the WNT activator CHIR99021 significantly decreased the expression of αENaC. Additionally, the small molecule FGF2 notably reduced the expression of NKX2.1.
HWJ-MSCs show great promise as an alternative cell population to EpiPCs that can be used to generate optimized hLOs. These cells offer high plasticity and are easily manipulable and isolated. To induce lung lineage, hWJ-MSCs require a process called mesenchymal-epithelial transition (MET), as the distal lung mainly comprises epithelial cells. MET can be induced through partial cell reprogramming, which involves introducing a cocktail of four pluripotency genes, namely NANOG, OCT4, KLF4, and SOX2 (NOKS), that are known to be sufficient for reprogramming somatic cells into pluripotent cells. During the initial stage of cell reprogramming, an alteration in the cell's expression pattern occurs, leading to epithelialization of the cells and paving the way for further lung lineage induction. To induce pluripotency gene expression and MET, retroviral transduction and mRNA transfection of hWJ-MSCs were utilized.
Partially reprogrammed hWJ-MSCsNOKS showed significant expression of the pluripotency gene NANOG. However, there was no expression observed for the pluripotency genes OCT4 and SOX2, nor for the stem cell marker CXCR4. Half of the partially reprogrammed hWJ-MSCsNOKS successfully expressed the epithelial marker E-Cadherin, but EpCAM expression was absent.
Successful cell reprogramming was demonstrated by changes in cell morphology characterized by the formation of tightly packed cell colonies resembling iPSCs, along with the loss of adherence.
Both mRNA transfection and retroviral transduction led to the hWJ-MSCsNOKS adopting a rounded morphology and forming compact colonies with distinct borders and well-defined edges. These morphological changes indicated the epithelialization of the hWJ-MSCsNOKS and were interpreted as MET. Consequently, both gene transfer methods in this work effectively induced MET.
After dramatic changes of the partially reprogrammed hWJ-MSCsNOKS in the sense of MET were observed, further lung lineage induction was conducted. hWJ-MSCsNOKS were additionally transfected with lung fate transcription factor TTF-1 mRNA and exposed to cell culture conditions promoting lung cell differentiation. Ultimately, it was shown that after additional transfection most partially reprogrammed hWJ-MSCsNOKS expressed the lung fate marker TTF-1, which is a crucial step for lung lineage induction.
The objective of this work was to create a distal lung model that mimics the in vivo cell niche, promoting the study of fetal lung development, its perturbations, and therapeutic solutions. To achieve this, placental and umbilical cord progenitor and stem cells, representing a novel approach to generating hLOs were utilized. These cells were manipulated to exhibit lung lineage characteristics, resulting in an optimized distal lung model. Thereby this study aimed to contribute to future translational medicine applications, overcoming the limitations of current approaches to modeling human alveoli
Taming Airbnb locally: Analysing regulations in Amsterdam, Berlin and London
No full textEuropean cities have responded differently to the growing number of short-term
rentals (such as
Airbnb) and proposed a variety of regulations, although little is known about their efficiency. This
paper contributes to filling the gap by analyzing both policy documents and spatial distributions
of Airbnb listings between 2015 and 2020 using Amsterdam, Berlin, and London as case studies.
We also compare the results with those of nine other European capitals. Our results show that
cities follow highly individualized approaches. According to the strictness of each regulation,
we see different intensities in the growth (and drop) of Airbnb listings, the share of multi-hosts,
and the share of apartments withdrawn from the regular housing market. There is also
a spatial dispersion of listings from the center to the periphery. Our numbers insinuate that
dynamically changing regulations force hosts to adapt continuously–which
tames an uncontrolled
proliferation, but more research is necessary
Nasschemische Bottom-up Synthese von Graphen-Nanostreifen mit atompräzisen Nanoporen
No full textDie Inkorporation von Nanoporen in Graphen-Nanostrukturen wurde als effiziente Methode zur Anpassung der Bandlücke und elektronischen Struktur dieser Materialien demonstriert. Allerdings ist die atomgenaue Einbettung uniformer Nanoporen in Graphen-Nanostreifen (GNS, engl. GNR) auf atomarer Ebene durch Mangel an effizienten Synthesestrategien bislang unterentwickelt. Wir berichten hier vom ersten lösungschemisch dargestellten, vollständig durch Scholl-Reaktion konjugierten porösen GNS (pGNS), welchen wir durch das atomgenau dargestellte Polyphenylen P1 mit vorinstallierten hexagonalen Makrozyklen zugänglich machen konnten. pGNS enthält periodische Poren im sub-Nanometerbereich (0.6 nm) mit einem Abstand von 1.7 nm zueinander. Um unsere Synthesestrategie zu untermauern, wurden zwei poröse Modellverbindungen (1 a, 1b) mit einer zu pGNS identischen Pore erfolgreich dargestellt. Die chemische Struktur und photophysikalischen Eigenschaften von pGNS wurden durch verschiedene spektroskopische Methoden untersucht. Die eingebetteten periodischen Nanoporen vermindern die π-Konjugation und damit die Interaktion zwischen den Nanostreifen, verglichen mit nicht porösen GNS von ähnlicher Breite. pGNS zeigt demzufolge eine erhöhte Bandlücke und eine verbesserte nasschemische Prozessierbarkeit
Machine learning-based prediction of side effects due to chemoradiotherapy using imaging features of patients with head and neck cancer
No full textFor patients with tumours in the head and neck region, the most debilitating side effects of chemoradiotherapy are xerostomia and dysphagia. Precise prediction of toxicity is essential for strategies aimed at mitigating side effects and enhancing patient outcomes. However, current clinical models rely on dosimetric parameters and baseline risk factors, which do not fully capture the variability in side effect occurrence and severity among patients. Radiomics hypothesises that imaging data contains valuable information about tissue characteristics. Therefore, incorporating additional imaging features analysed using machine learning algorithms may improve the prediction of chemoradiotherapy-induced side effects in head and neck tumour patients. A retrospective investigation was undertaken on 173 patients with locoregionally advanced head and neck squamous cell carcinoma. Employing a radiomic framework, involving the extraction and analysis quantitative image features derived from computed tomography
scans using machine learning algorithms, predictive risk models for multiple endpoints of xerostomia and dysphagia were developed. To ensure the reliability of the clinical risk models, three different feature selection methods and two learning algorithms were evaluated and internally validated. This study demonstrates that integrating imaging features can enhance the predictive capacity of normal tissue complication probability models based on dosimetric and clinical parameters, particularly for acute and late xerostomia. The signature mainly consists of texture-based and dose-based features of the contralateral parotid gland for acute xerostomia and of texture-based features of the submandibular gland for late xerostomia. Conversely, for dysphagia, the inclusion of imaging features did not improve prediction models. The significant features in the predictive model for acute dysphagia were age, alcohol consumption, and a dose-volume parameter of the ipsilateral submandibular gland. Moreover,
a comparison between established dose parameters and results from our patient cohort confirmed a statistically significant correlation between the mean dose of the parotids gland for acute xerostomia. Additionally, two texture-based features of the contralateral parotid gland described by van Dijk et al. (van Dijk et al., 2017) exhibited significant correlation or demonstrated a statistical trend with acute and late xerostomia. These findings underscore the potential benefits of incorporating imaging features, especially of texture-based features, describing tissue heterogeneity, in prediction models for chemoradiotherapy induced side effects. Further investigation and comprehensive validation are essential to comprehend the underlying pathomechanisms driving changes in imaging features, and to assess its full utility in clinical applications.Für Patienten mit Tumoren im Kopf- und Halsbereich sind Mundtrockenheit (Xerostomie) und Schluckstörungen (Dysphagie) die schwerwiegendsten Nebenwirkungen einer kurativen Radiochemotherapie. Eine präzise Vorhersage dieser Nebenwirkungen ist entscheidend für Strategien zur Verbesserung der Therapieergebnisse. Aktuelle klinische Modelle, die hauptsächlich auf dosimetrischen Parametern und Risikofaktoren der Patienten basieren, können die Variabilität im Auftreten und der Ausprägung von Nebenwirkungen nicht vollständig erfassen. Ein neuartiger Ansatz, Radiomics, beschreibt die quantitative Analyse von medizinischer Bildgebung unter der Annahme, dass diese wertvolle Informationen über Gewebecharakteristika enthalten. Die Integration dieser Bildparameter könnte die Vorhersage von Nebenwirkungen, hervorgerufen durch eine Radiochemotherapie, verbessern. An 173 Patienten mit lokal fortgeschrittenem Plattenepithelkarzinom im Kopf- und Halsbereich wurde eine retrospektive Analyse durchgeführt. Dabei wurden mittels maschineller Lernalgorithmen quantitative Bildmerkmale aus Computertomographie-Scans extrahiert und analysiert, um prädiktive Risikomodelle für verschiedene Aspekte von Xerostomie und Dysphagie zu entwickeln. Zur Sicherstellung der Zuverlässigkeit der klinischen Risikomodelle wurden drei verschiedene Methoden zur Merkmalsauswahl und zwei Lernalgorithmen evaluiert und intern validiert. In dieser Studie konnte gezeigt werden, dass die Integration von Bildmerkmalen die Vorhersagekapazität von Modellen zur Bewertung von Nebenwirkungen, basierend auf dosimetrischen und klinischen Parametern, verbessern kann. Für den Endpunkt der akuten Xerostomie wurden textur- und dosisbasierten Merkmalen der kontralateralen Parotis gewählt,
während für späte Xerostomie texturbasierte Merkmale der Unterkieferspeicheldrüsen selektiert wurden. Im Gegensatz dazu führte die Einbeziehung von Bildmerkmalen nicht zu einer Verbesserung der Vorhersagemodelle für Dysphagie. Als signifikante Faktoren für akute Dysphagie wurden Alter, Alkoholkonsum und ein Dosis-Volumen-Parameter der ipsilateralen Unterkieferspeicheldrüse identifiziert. Ein Vergleich zwischen etablierten Dosisparametern und den Ergebnissen unserer Patientenkohorte bestätigte eine statistisch signifikante Korrelation zwischen der mittleren Dosis der Parotis und akuter Xerostomie. Zudem konnte eine signifikante Korrelation sowie ein statistischer Trend für zwei bereits beschriebene texturbasierte Merkmale der kontralateralen Parotis für Xerostomie nachgewiesen werden.
Diese Ergebnisse unterstreichen die potenziellen Vorteile der Integration von Bildparametern in Vorhersagemodelle für Nebenwirkungen. Weitere Untersuchungen und umfassende Validierung sind erforderlich, um die zugrunde liegenden biologischen Prozesse zu verstehen sowie ihre klinischen Anwendungen zu bewerten
Diagnostik und Therapie der sternalen Wundinfektion nach kardiochirurgischen Eingriffen
No full textDie Sternale Wundinfektion beschreibt eine seltene aber schwerwiegende infektiöse Entzündung des Sternums und des umliegenden Weichteilgewebes. Das Ziel dieser Studie war es, die Haupterreger und ihr Resistenzspektrum der sternalen Wundinfektion zu identifizieren und diagnostische sowie therapeutische Handlungsstrategien zu etablieren. Dabei soll die Notwendigkeit von oberflächlichen Wundabstrichen sowie Gewebeproben und mögliche Risikofaktoren für das Entstehen der sternalen Wundinfektionen nach kardiochirurgischen Eingriffen diskutiert werden. Effektive Präventionsmaßnamen, um das Langzeitüberleben der Patient*innen positiv zu beeinflussen, sollen identifiziert werden.:Inhaltsverzeichnis
ABKÜRZUNGSVERZEICHNIS
TABELLENVERZEICHNIS
ABBILDUNGSVERZEICHNIS
EINLEITUNG
DEFINITION UND KLASSIFIKATION DER STERNALEN WUNDINFEKTION
EPIDEMIOLOGIE UND ÄTIOLOGIE
RISIKOFAKTOREN
PRÄVENTION DIAGNOSTIK
SYMPTOME UND KLINIK
KLINISCHE CHEMIE
BILDGEBUNG
MIKROBIOLOGISCHE UND HISTOPATHOLOGISCHE DIAGNOSTIK
ERREGERSPEKTRUM
STAPHYLOCOCCUS EPIDERMIDIS
STAPHYLOCOCCUS AUREUS
ENTEROKOKKEN
GRAM-NEGATIVE BAKTERIEN
THERAPIE DER STERNALEN WUNDINFEKTION
ANATOMIE
ANTIBIOTISCHE THERAPIE
CHIRURGISCHES DEBRIDEMENT
VAKUUM-ASSISTED-CLOSURE THERAPIE (VAC-THERAPIE)
LAPPENPLASTIKEN
FRAGESTELLUNG UND ZIELSETZUNG
MATERIAL UND METHODEN
STUDIENDESIGN UND AUSWAHL DER PATIENT*INNEN
DATENERHEBUNG
STATISTISCHE AUSWERTUNG
ERGEBNISSE
DESKRIPTIVE STATISTIK
ALLGEMEINE PATIENT*INNENDATEN
RISIKOFAKTOREN UND KOMORBIDITÄTEN
BILDGEBENDE DIAGNOSTIK UND LABORCHEMISCHE PARAMETER
MIKROBIOLOGISCHE DIAGNOSTIK
ANTIBIOTISCHE THERAPIE
OPERATIONSBEZOGENE DATEN
UNSERE THERAPEUTISCHE STRATEGIE
ANALYTISCHE STATISTIK
DISKUSSION
EINLEITUNG, ALLGEMEINE DATEN DER PATIENT*INNEN UND RISIKOFAKTOREN
ÄTIOLOGIE UND PRÄVENTION
DIAGNOSTIK
BILDGEBENDE DIAGNOSTIK UND LABORCHEMISCHE PARAMETER
MIKROBIOLOGISCHE ABSTRICHE, GEWEBEPROBEN UND ERREGERSPEKTRUM
THERAPIE
OPERATIONSBEZOGENE DATEN
ANTIBIOTISCHE THERAPIE
LIMITATIONEN
SCHLUSSFOLGERUNGEN ZUSAMMENFASSUNG
SUMMARY
PUBLIKATIONEN
DANKSAGUNG
LITERATURVERZEICHNI