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Artificial Intelligence in Chest X-Ray Analysis in the Intensive Care Unit: A Retrospective Study
No full textRöntgen-Thorax-Aufnahmen im Liegen gehören auf Intensivstationen zu den am häufigsten durchgeführten bildgebenden Untersuchungen. Diese Arbeit untersucht den Effekt eines KI-basierten Systems auf die diagnostische Leistung und Befundungszeit von MedizinerInnen im intensivmedizinischen Kontext. In dieser Studie wurde ein CE-zertifiziertes KI-basiertes-System verwendet, dass speziell für die Analyse von Röntgen-Thorax-Aufnahmen trainiert wurde. Für diese monozentrische retrospektive Studie wurden insgesamt 520 Röntgen-Thorax-Aufnahmen von Erwachsenen auf der Intensivstation eines Universitätsklinikums eingeschlossen, bei denen zwischen April und Mai 2021 Röntgen-Thorax-Aufnahmen am Krankenbett durchgeführt wurden. Die Befundung erfolgte unter Zeiterfassung anhand einer strukturierten Vorlage. Insgesamt drei BefunderInnen unterschiedlicher Erfahrungsstufen bewerteten die Aufnahmen einmal mit und einmal ohne KI-Unterstützung auf das Vorliegen verschiedener Krankheitsmuster anhand einer semiquantitativen Wahrscheinlichkeitsskala (0 = sicher nicht vorhanden bis 5 = sicher vorhanden). Eingeschlossene Krankheitsmuster waren Konsolidierung, Pneumothorax, Atelektase, Fibrose, Pneumoperitoneum, Mediastinale Erweiterung, Knoten, Verkalkung, Kardiomegalie und Pleuraerguss. Anhand der AUC der ROC wurde die diagnostische Leistungsfähigkeit der BefunderInnen ohne und mit KI-Unterstützung bewertet. Als Referenzdiagnose diente die Beurteilung der Aufnahmen durch einen auf Röntgen-Thorax spezialisierten Facharzt für Radiologie unter Zuhilfenahme aller klinischen Befunde der PatientInnen. Es zeigt sich bei keinem der BefunderInnen eine signifikante Reduktion der Befundungszeit durch die Unterstützung des KI-basierten-Systems (p-Werte: Doktorandin 0,10; Intermediate 0,99; erfahrener Befunder 0,72). In Bezug auf die Befundungsqualität zeigt sich kein signifikanter Effekt durch den Einsatz des KI-basierten Systems. Die Ergebnisse der durchgeführten AUROC-Analysen liegen fast ausschließlich im nicht-signifikanten Bereich (p-Werte Doktorandin /Intermediate /erfahrener Befunder: Konsolidierung 0,12/0,01/0,48; Pneumothorax 0,13/0,24/0,57; Atelektase 0,045/0,33/0,93; Pleuraerguss 0,55/0,07/0,46; Fibrose -/0,60/0,026; Mediastinale Erweiterung 0,46/0,70/0,49; Verkalkung 0,71/0,69/0,41; Kardiomegalie 0,06/0,89/0,47). Der Einsatz eines KI-basierten Systems zur Unterstützung in der Befundung von Röntgen-Thorax-Aufnahmen im Liegen auf der Intensivstation führte weder zu einer diagnostischen noch zu einer zeitlichen Verbesserung im Vergleich zur Analyse ohne KI-Unterstützung.Supine chest radiographs are among the most frequently performed imaging studies in intensive care units. This study investigates the effect of an artificial intelligence (AI)-based system on the diagnostic performance and reporting time of clinicians in an intensive care setting. A CE-certified AI system specifically trained for the interpretation of chest radiographs was used. This single-center retrospective study included a total of 520 bedside chest radiographs from adult ICU patients at a university hospital, acquired between April and May 2021. Reporting was conducted with time tracking using a structured template. Three readers with varying levels of experience evaluated each radiograph twice—once with and once without AI support—assessing the presence of specific pathological findings using a semiquantitative probability scale (0 = definitely not present to 5 = definitely present). The assessed pathologies included consolidation, pneumothorax, atelectasis, fibrosis, pneumoperitoneum, mediastinal widening, nodules, calcifications, cardiomegaly, and pleural effusion. Diagnostic performance with and without AI support was evaluated using the area under the receiver operating characteristic curve (AUROC). The reference standard was established by a board-certified thoracic radiologist with access to all available clinical information. No statistically significant reduction in reporting time was observed for any of the readers with AI assistance (p-values: doctoral student 0.10; intermediate reader 0.99; senior reader 0.72). Likewise, no consistent or significant improvement in diagnostic accuracy was demonstrated with AI support. The results of the AUROC analyses were predominantly non-significant (p-values for docotral student/intermediate/experienced reader: consolidation 0.12/0.01/0.48; pneumothorax 0.13/0.24/0.57; atelectasis 0.045/0.33/0.93; pleural effusion 0.55/0.07/0.46; fibrosis –/0.60/0.026; mediastinal widening 0.46/0.70/0.49; calcifications 0.71/0.69/0.41; cardiomegaly 0.06/0.89/0.47).
The use of an AI-based system to support the interpretation of supine chest radiographs in the ICU setting did not lead to improvements in either diagnostic accuracy or reporting efficiency compared to unaided image interpretation.2026-06-2
Synthesis and Adhesion Properties of E-Cadherin Mimetic Peptides
No full textCell adhesion molecules (CAMs) are essential for various biological processes, including tissue homeostasis and wound healing. One such molecule, the calcium-dependent protein E-cadherin, is primarily expressed at adherens junctions which connect neighboring epithelial cells. The interaction between E-cadherin molecules occurs at the N-terminal region of the monomer, where the amino acid sequence histidine-alanine-valine (HAV) in the first extracellular (EC1) domain plays a key role in mediating these interactions.
To understand and mimic these E-cadherin-mediated cell-cell interactions, peptides containing the HAV-unit were synthesized using solid-phase peptide synthesis (SPPS). These HAV-peptides were then incorporated into solid-supported membranes through two distinct chemical strategies. One method involved complexing 1,2-dioleoyl-sn-glycero-3-[(N-(5-amino-1-carboxypentyl)iminodiacetic acid)succinyl] (nickel salt) (DOGS-NTA (Ni)) lipid with a polyhistidine-tagged HAV-peptide, while the other utilized in situ Michael addition to attach a terminal Cys-HAV-peptide to a maleimide lipid. Various lengths of HAV-peptides were synthesized to investigate their impact on adhesion properties. Binding of the HAV-peptides to the membrane was verified using Reflectometric Interference Spectroscopy (RIfS) and Attenuated Total Reflectance Infrared (ATR-IR) spectroscopy, which confirmed the successful HAV-peptide attachment to the membrane.
The molecular interactions between HAV-peptides and E-cadherin were investigated using Quartz Crystal Microbalance (QCM). HAV-peptides were immobilized on gold surfaces via Au-thiol coupling, and their binding to Fc-IgG-E-cadherin was studied. This allowed for a comparison of the frequency shifts induced by Fc-IgG-E-cadherin and the Fc-IgG fragment as control, enabling the calculation of the contribution from specific interactions.
Additionally, holographic Video Particle Tracking (hVPT) was employed to investi-gate the behavior of HAV-functionalized beads on cell surfaces. The trajectories of the beads were analyzed, revealing that the beads exhibited strongly confined motion in the presence of HAV-peptides. This confined movement of the beads indicated a specific interaction between the HAV-peptides and E-cadherin on the cell surface, supporting the hypothesis that HAV-peptides interact with E-cadherin.
To further validate the specificity of these interactions, Atomic Force Microscopy (AFM)-based colloidal probe technique (CPT) was used. From force-distance curves, the work of adhesion as well as the maximum adhesion forces could be quantified. The AFM measurements showed that the HAV-peptides significantly increased both the work of adhesion, and the maximum adhesion force compared to the absence of HAV-peptides, indicating that the presence of HAV-peptides promotes stronger adhesive interactions. Due to the complexity of the cell surface, experiments were conducted using polydimethylsiloxane (PDMS) coated with Fc-IgG-E-cadherin and micropatterned Fc-IgG-E-cadherin substrates. The experiments showed a similar trend, with both maximum adhesion force and work of adhesion showing increased values in the presence of HAV-peptides. Additionally, the known lengths of the Fc-IgG-E-cadherin molecules (24 nm for the dimeric form and 37 nm for the stretched form) were used to assign peak-to-peak distances in the force curves to the E-cadherin molecules. This study confirms that HAV-peptides enhance specific E-cadherin-mediated cell adhesion, thereby supporting their role in tissue interactions.2026-02-2
Pairing transcranial direct current stimulation and mindfulness meditation in the treatment of fibromyalgia
No full textThe lack of effective treatments for managing pain and associated symptoms in
fibromyalgia (FM) poses both a clinical challenge and an economic burden on the health
sector. Typical FM therapies include an array of pharmacological and non-pharmacological
interventions. Commonly used drugs have demonstrated only mild improvements in FM while
benefitting only a minority of patients. In this scenario, repeated anodal transcranial direct
current stimulation (tDCS) and mindfulness-based interventions have emerged as two promising
non-pharmacological treatments for pain relief and improvement of FM-associated symptoms.
However, the strength and durability of the therapeutic benefits of these methods vary across
studies. The combination of non-pharmacological therapies has been proposed as a way to
optimise and bolster the therapeutic effects of monomodal interventions. Although the
combination of tDCS and mindfulness meditation (MM) has shown synergistic effects in both
healthy individuals and patients with neuropsychiatric disorders and some chronic pain
conditions, it has not yet been investigated in patients with FM. The rationale behind exploring
this combination was to modulate the brain state via MM, with the goal of boosting the
neuroplastic effects of currently recommended conventional tDCS protocols for chronic pain.
In this dissertation, the current state of the literature on combining these two methods was
reviewed. A sham-controlled randomised pilot clinical study was conducted to test the
preliminary therapeutic efficacy and safety of a ten-day intervention concurrently applying
anodal tDCS targeting the left primary motor cortex (M1) and MM, administered as a clinicbased treatment, in patients with FM. Prior to the combined therapy, participants received a fiveday training in MM. Patients in the active tDCS group reported a larger clinically meaningful
improvement in quality of life following the combined intervention, compared to those receiving
sham tDCS paired with MM or treatment-as-usual. No differences in pain reduction and
improvements in sleep quality or psychological well-being were observed among the groups.
Building on these findings and addressing the limitations of the pilot study, we investigated the
therapeutic and mechanistic impact of a ten-day treatment combining anodal tDCS over the left
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M1 and MM on pain relief, quality of life, and associated symptoms in individuals with FM
trained in mindfulness. Participants in this trial completed a four-week brief mindfulness
intervention tailored for FM (BMIF) prior to randomisation. The combined treatment was
administered as an at-home intervention under remote supervision. To investigate the possible
underlying mechanisms, we measured changes in cortical excitability using transcranial
magnetic stimulation (TMS) of the left M1. Finally, we implemented a responder analysis
approach to decipher the effects of the BMIF and the add-on combination of tDCS and MM
with regard to emotion regulation (ER), which is one of the primary targets mediating
improvement in symptom burden and management in FM. Although patients showed
improvements in clinical symptoms, no superior therapeutic benefits were observed when
pairing MM with anodal tDCS, compared to the combination of MM with sham tDCS. Both
groups demonstrated substantial and acute pain relief and improvements in quality of life, sleep
quality, affect, and psychological well-being following the combined intervention. The lack of
group differences in TMS metrics failed to provide meaningful insights into the potential
synergistic mechanisms of tDCS and MM. Interestingly, clinical responders to the combined
intervention in the active tDCS group exhibited impaired ER compared to the sham group, even
suggesting potential antagonistic effects of pairing M1-tDCS with MM for ER. Moreover, the
reduction of the cortical excitability of the left M1, likely mediated by daily MM practice, might
block the mechanistic consequences of anodal tDCS of the left M1. On the other hand, the nonspecific main effect of time in clinical outcomes, alongside a large significant increase in
mindfulness over time, hints at a potential ‘mindfulness effect’, in line with previous studies
showing that longer MM practice results in greater therapeutic benefits in FM.
The introduction of the Medical Device Regulation in 2021 and the recent reclassification of
some of the non-invasive brain stimulation (NIBS) devices (for example, tDCS and TMS) to
the same risk level as invasive deep brain stimulation in the European Union have imposed a
considerable hindrance to the research and further development of tDCS. A multinational
participatory study including different stakeholders involved in the consumption, use,
manufacturing, and regulation of NIBS was conducted to address the clinical, academic, legal,
ethical, and social concerns surrounding NIBS. The different stakeholders’ perspectives were
analysed and compiled to draft a set of recommendations for the use and regulation of NIBS,
including tDCS in the European subcontinent. To improve the accessibility of tDCS to patients,
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the optimisation of currently available NIBS treatments via broader administration and further
development of home-based tDCS as well as personalisation of therapy have been suggested by
the stakeholders. Stricter regulation of tDCS for non-medical reasons and research focused on
higher effectiveness of tDCS, underlying mechanisms, and development of responders were
also proposed, among others.
Taken together, our work challenges the combination of M1-tDCS and MM as a strategy to
optimise tDCS treatment for pain relief and symptom improvement in patients with FM.
However, this dissertation highlights the pivotal role of clinical research regarding combined
interventions, whereby two therapies beneficial on their own might not necessarily be more
effective when combined. Future research should explore the additional effect of combining
MM and tDCS compared to tDCS and MM alone and delve deeper into the workings of the
combined intervention using more sophisticated neuroimaging tools, with the goal of
developing novel and individualised methods to optimise the currently available NIBS
technologies for the treatment of FM.2026-08-1
In-vivo-Diagnostik und Therapiemonitoring mittels 18F-FDG-Positronenemissionstomographie im Tg4-42 Alzheimer-Mausmodell
No full textIn this study, two groups of Alzheimer's model mice of the Tg4-42 type were injected intravenously with 18F-FDG at the
age of 7 months and 3 months. Subsequently, the 18F-FDG uptake of the brain was visualized by PET/MRI. Similarly, wild-type
animals of the C57Bl/6J type were examined as a control group for their 18F-FDG uptake at 7 months of age. 18F-FDG-PET is able to visualize the reduced glucose metabolism in vivo, which essentially depends on the number of neurons and the synaptic activity of the brain. In comparison, it could be shown that the older Tg4-42 mice exhibit a lower 18F-FDG uptake
in the entire brain as well as in almost all brain regions and thus a reduced glucose metabolism compared to wild-type animals. The young Tg4-42 mice showed no significant change over the entire brain. In the brain regions of the hypothalamus, the amygdala and the midbrain there was already a reduced glucose metabolism compared to the wild-type mice. Significant changes were also visible in the comparison of young to older Tg4-42 mice. The older Tg4-42 mice showed a significantly reduced 18F-FDG uptake in the whole brain and over all brain regions except the amygdala, in contrast to the young Tg4-42 mice. This demonstrated that 18F-FDG PET is able to visualize reduced age-dependent glucose metabolism in vivo, consistent with the results of Alzheimer's patients in the Tg4-42 mouse model. In the second step, one group of Tg4-42 mice was treated preventively at the age of 3 months (before the onset of neuronal loss) with tetrahydrocannabinol and another group at
the age of 3 months with cannabidiol for 42 days each. At the age of 7 months these groups were examined by 18F-FDG-PET/MRI. Compared to untreated Tg4-42 mice of the same age, mice treated with tetrahydrocannabinol showed a significant increase in glucose uptake in the brain areas of the hippocampus, hypothalamus and forebrain. The group treated with cannabidiol showed no significant change in glucose metabolism compared to the untreated control group.2026-04-1
Effects of environmental change on grassland birds in the Central-Asian flyway through the annual cycle
No full textLandnutzungsänderungen sind ein bedeutender Faktor für den Verlust der biologischen Vielfalt, aber ihre Auswirkungen wurden bisher vor allem in gemäßigten Regionen und Waldökosystemen untersucht. In dieser Arbeit habe ich die Abundanz, das Vorkommen und den Artenreichtum von Vögeln als Indikatoren für die Reaktion der biologischen Vielfalt auf Landnutzungsänderungen auf globaler Ebene verwendet. Insbesondere habe ich die Auswirkungen von Umweltveränderungen in Grasland und offenen Ökosystemen auf regionale Vögel und Zugvögel auf der zentralasiatischen Flugroute im Jahreszyklus untersucht. Alle drei kritischen Gebiete für Grasland-Zugvögel in der zentralasiatischen Flugroute - Brutgebiete, Zwischenlandeplätze und Überwinterungsgebiete - haben in den letzten drei Jahrzehnten erhebliche Veränderungen in der Landnutzung erfahren. In den drei Kapiteln (II, III und IV) wurden diese Veränderungen und ihre Auswirkungen auf die biologische Vielfalt der Vögel im Jahreszyklus untersucht. Das zweite Kapitel dieser Arbeit konzentrierte sich auf die Brutgebiete in der kasachischen Steppe. Durch die weit verbreitete Aufgabe von Ackerland und Viehzucht in Kasachstan nach der Auflösung der Sowjetunion wurde das Feuer bis Mitte der 90er Jahre zur dominierenden Störung. Zwischen 2001 und 2009 wurde in der kasachischen Steppe der Großteil der jährlichen Brände in Zentralasien gezählt. Für eine Region mit einem langen Erbe des nomadischen Hirtenwesens, welches sich vor mehr als 5000 Jahren entwickelt hat, sind der Wechsel des Störungsregimes von der Weidehaltung zur Feuerbekämpfung und die daraus resultierenden Auswirkungen auf die biologische Vielfalt in der Steppe kaum erforscht. In ähnlicher Weise wurden im dritten Kapitel der Arbeit die Arten-Lebensraum-Verbindungen in den Überwinterungsgebieten Westindiens analysiert, die größtenteils aus natürlichen und halbnatürlichen Savannen und anderen offenen Ökosystemen bestehen. Die meisten Savannen auf dem indischen Subkontinent, die offiziell als „Ödland“ eingestuft werden, werden regelmäßig für landwirtschaftliche und infrastrukturelle Entwicklungen sowie für Aufforstungen genutzt. In Westindien bestehen die Savannen aufgrund der Fragmentierung infolge dieser Landnutzungsänderung größtenteils aus Agrar-Savannen-Mosaiken. Der anhaltende Rückgang der Zugvogelpopulationen in Indien in den letzten zwei Jahrzehnten wird häufig auf diese Lebensraumfragmentierung zurückgeführt, aber es gibt nur wenige empirische Studien, die die spezifischen Ursachen für diesen Rückgang durch Landnutzungsänderungen aufzeigen. Im vierten Kapitel wurde schließlich die Veränderung der biologischen Vielfalt über den Jahreszyklus hinweg anhand einer Kombination aus Aufzeichnungen über die Abundanz von Vögeln und mehrjährigen Satelliten- und GPS-Tracking-Daten für eine Modellart - das Vorkommen des Kiebitzes (Vanellus gregarius) - untersucht. Unter Verwendung satellitengestützter Indikatoren für die Bodenbedeckung, die räumlich und zeitlich mit dem Datum und dem Ort des Auftretens der Vögel abgestimmt wurden, wurden im vierten Kapitel Vorhersagen über die ganzjährige Eignung des Lebensraums für die Modellart getroffen. Die Ergebnisse des zweiten Kapitels zeigten einen signifikanten Rückgang der gesamten biologischen Vielfalt der Vögel in den Brutgebieten nach einer Zunahme der Brandstörung, wobei die Nachwirkungen des Feuers erst nach mindestens acht Jahren nachweisbar waren. Die Ergebnisse des dritten Kapitels wiesen auf einen größeren Reichtum und eine höhere Abundanz (und damit eine bessere Anpassungsfähigkeit) der ansässigen Arten in fragmentierten Agrar-Savannen-Mosaiken hin, hatten jedoch negative Auswirkungen auf die paläarktischen Zugvogelarten, was deren Präferenz für kompositorisch einfache Landschaften analog zu Steppengrasland während der Wintersaison unterstreicht. Die Ergebnisse zeigten auch, dass in Landschaften mit einem höheren Anteil an einjährigen Kulturen in der Fruchtfolge insgesamt mehr Vögel vorkommen, während die Größe der Felder (Komplexität der Konfiguration) keine signifikanten Auswirkungen auf die Wintervogelbestände hatte. Die Ergebnisse des vierten Kapitels, die sich auf multitemporale Modelle stützen, deuten darauf hin, dass die Zahl der ganzjährig geeigneten Lebensräume für den Kiebitz in den letzten drei Jahrzehnten auf der zentralasiatischen Flugroute insgesamt zugenommen hat, wobei die Arten während des gesamten Jahreszyklus eine hohe Präferenz für Agrarlandschaften zeigen. Die Ergebnisse aus den Kapiteln II-IV bieten drei wichtige Erkenntnisse für die Erhaltung der biologischen Vielfalt. Erstens zeigen sie, dass die Hinterlassenschaften von Landnutzungsänderungen auch die Veränderung der Artenvielfalt beeinflussen können und daher bei der Bewertung des Zustands berücksichtigt werden sollten. Zweitens kann die landwirtschaftliche Flächennutzung einen wesentlichen Einfluss auf die biologische Vielfalt der Vögel haben, aber ihre Auswirkungen hängen stark von der landwirtschaftlichen Zusammensetzung ab und sind nicht immer negativ. Drittens können Big Data - satellitengestützte Fernerkundung der Umwelt oder des Vorkommens von Arten - komplexe Zusammenhänge zwischen Arten und Umwelt durch einen dynamischen, multitemporalen Modellierungsansatz untersuchen. Der interdisziplinäre Ansatz dieser Arbeit leistet einen Beitrag zur Vogelökologie, zur Wissenschaft der Analyse von Landnutzungsänderungen und zur Anwendungen von Satellitenfernerkundung für den Schutz der biologischen Vielfalt. Die ökologischen Erkenntnisse aus dieser Arbeit bieten politischen Entscheidungsträgern eine Grundlage für die Planung gemeinsamer Anstrengungen zum Schutz von Zugvögeln auf globaler Ebene, während Fernerkundungs- und Berechnungsmethoden die notwendigen Instrumente zur Identifizierung und Quantifizierung von Umwelt- und Landnutzungsänderungen liefern, die ihre Verbreitung beeinflussen.Land use change is a significant driver of biodiversity loss, but its impacts have been largely studied with a particular focus on temperate regions and forest ecosystems. In this thesis, I used bird abundance, occurrence, and species richness as indicators of biodiversity response to land use land cover change on globally relevant scales. Specifically, I disentangled the effects of environmental change in grasslands and open ecosystems on regional and migratory birds moving in the Central-Asian flyway through the annual cycle. All three critical areas for migratory grassland birds in the Central Asian Flyway – breeding grounds, stopover sites, and wintering grounds – have experienced considerable changes in land use over the last three decades. The three chapters (II, III and IV), addressed these changes and their impacts on bird biodiversity through the annual cycle. The second chapter of this thesis focused on breeding grounds in the Kazakh steppe. Widespread abandonment of cropland and livestock in Kazakhstan following the dissolution of the Soviet Union established fire as the dominant disturbance by the mid-90s. Between 2001 – 2009, the Kazakh steppe accounted for majority of the annual burning in Central Asia. For a region with a long legacy of nomadic pastoralism that evolved over 5000 years ago, the change in disturbance regime from grazer to fire control, and resulting impacts on biodiversity in the steppe are poorly explored. Similarly, the third chapter of the thesis analyzed species – habitat associations in the wintering grounds of western India that largely comprise natural and semi-natural savannas and other open ecosystems. Officially classified as ‘wastelands’, majority of the savannas on the Indian subcontinent are regularly earmarked for agricultural, infrastructural developments and afforestation. In western India, savannas largely exist as agriculture-savanna mosaics due to the fragmentation resulting from this land use change. Continued decline in migratory bird populations in India over the past two decades is often attributed to this habitat fragmentation but few empirical studies exist showing specific land use change drivers of this decline. Lastly, chapter four accounted for biodiversity response through the annual cycle by using combination of bird abundance records and multi-year, satellite and GPS tracking data for a model species – Social lapwing (Vanellus gregarius) occurrence. Using satellite based land cover indicators which were spatio-temporally matched with the date and location of bird occurrence, the fourth chapter predicted year-round habitat suitability for the model species. The results of the second chapter revealed a significant decline in overall bird biodiversity on the breeding grounds following an increase in fire disturbance with legacy effects of fire detectable after at least eight years. The results of the third chapter indicated a higher richness and abundance (and therefore better adaptability) of resident species in heterogeneous agriculture-savanna mosaics, but a negative impact on Palearctic migratory species underscoring their preference for compositionally simpler landscapes during the winter season, analogous to steppe grasslands. Results also showed a higher overall bird abundance in landscapes with a higher proportion of annual crops cultivated in rotation, while field size (configurational complexity) indicated no significant effects during the winter bird assemblage. The results of the fourth chapter, based on multi-temporal models suggested an overall increase in year-round suitable habitat for the Sociable lapwing over the past three decades in the Central-Asian flyway with species showing a high preference for agricultural landscapes through the annual cycle. The results from chapters II-IV offer three key insights for biodiversity conservation. First, they show that legacies of land use change can also drive biodiversity response, thus should be considered in status assessments. Second, agricultural land use can be a significant driver of bird biodiversity but its impact is highly dependent on the regional agricultural composition and is not always negative. Third, ‘big data’ from satellite remote sensing of the environment or species occurrence can address complex species – environment associations through a dynamic, multi-temporal modeling approach. The interdisciplinary manner of this work contributes to the fields of bird ecology, biogeography – in particular our understanding of land use land cover change, and applications of satellite remote sensing for biodiversity conservation. The ecological insights from the thesis provide a framework for policymakers to plan collaborative efforts for the conservation of migratory birds on a global scale, while remote sensing and computational methods provide necessary tools to identify and quantify environmental and land use change drivers that influence species distributions.2026-04-0
High-resolution morphometric analysis of synaptic vesicle formation
No full textSynaptic vesicle (SV) biogenesis plays an important role in neurotransmission, yet the intricacies of SV formation remain a significant scientific challenge. In this PhD thesis, I seek to address both technical and biological challenges associated with studying SV biogenesis through three main objectives:
First, I aimed to establish a multiplexing method that enables high-resolution visualization of multiple targets within the same sample. This objective required the development of advanced imaging techniques that can simultaneously resolve various SV components, thereby providing a comprehensive view of the molecular composition within neurons.
Second, I collected a high-resolution stimulated emission depletion (STED) microscopy dataset focused on several key SV proteins in developing neurons. The use of STED microscopy was critical here, as it surpasses the resolution limitations of traditional light microscopy and allows for the visualization of SV proteins at a nanoscale level within the complex environment of developing hippocampal neurons.
Third, I analyzed the distribution and nanocluster formations of different SV proteins across various organelles in the secretory pathway. By examining specific protein localization and clustering, I aimed to uncover the molecular mechanisms and spatial organization involved in SV biogenesis.
Together, these integrated approaches are designed to overcome existing limitations in SV research, providing unprecedented insights into the assembly and organization of synaptic vesicles. The high-resolution model developed from this research offers a novel perspective on SV formation, enhancing our understanding of synaptic function and potentially informing therapeutic
strategies for neurodevelopmental disorders. This work, therefore, makes a critical contribution to the field of neurobiology by advancing both methodological capabilities and biological knowledge of synaptic vesicle biogenesis in primary hippocampal neurons.2026-07-0
Effects of perturbed sumoylation and neddylation on synaptic transmission
No full textPost-translational modifications (PTMs) regulate a wide range of cellular processes. PTMs involving ubiquitin-like modifiers (UBLs) have been implicated in neurodevelopment and brain diseases. Recent evidence indicates that UBLs may also conjugate to synaptic protein targets suggesting that they can regulate synaptic function. In light of this, we focused on the two most studied UBLs to date, NEDD8 and SUMO, and examined whether they are involved in synaptic transmission. In the present study, we used conditional knock-out mouse lines for NEDD8 and SUMO2 and assessed the consequences of the ablation of these UBLs in excitatory hippocampal neurons. Our results revealed that NEDD8 deficiency alters gene expression, decreases dendritic arborization, alters the expression levels of synaptic proteins, and increases vesicle release probability. In parallel, we found that SUMO2 depletion resulted in decreased synapse number and dendritic arborization, altered high-voltage-activated Ca2+ channel activity, and reduced neurotransmitter release. Taken together, our work demonstrates that NEDD8 and SUMO2 are implicated in neuronal morphology and function, and that different UBLs can regulate neurotransmitter release via distinct mechanisms in young excitatory hippocampal neurons.2026-07-0
Transcriptomic Mechanisms in Post-mitotic and Excitable Cells in Inter-Organ Communication
No full textThe human body functions as an integrated network where organs communicate through complex molecular signals rather than as isolated systems. This inter-organ communication occurs through various mediators including proteins, metabolites, hormones, extracellular vesicles, and non-coding RNAs. Disruptions in these communication pathways contribute to the development of comorbidities, while enhancement of these pathways through interventions like exercise promotes systemic resilience. The heart-brain and muscle-brain axes represent critical examples of such inter-organ communication, with mounting evidence demonstrating how cardiac dysfunction impacts cognitive health and how skeletal muscle activity influences brain function through circulating factors.
Cardiovascular disease remains the leading cause of global mortality, accounting for approximately 34% of deaths worldwide. Heart failure patients exhibit 1.5 to 1.8 times higher risk of developing cognitive impairment and dementia, highlighting the existence of bidirectional communication pathways between heart and brain. This relationship manifests through multiple mechanisms including reduced cerebral perfusion, neuroinflammation, and systemic metabolic dysregulation. Similarly, physical exercise consistently improves cognitive function and decreases neurodegeneration risk through muscle-derived factors that cross the blood-brain barrier to enhance neuroplasticity and glial support functions.
Non-coding RNAs have emerged as critical regulators of these inter-organ communication pathways, functioning both as messengers and modulators of downstream effects. MicroRNAs (miRNAs), small non-coding RNAs typically 20-25 nucleotides in length, regulate gene expression post-transcriptionally by binding to complementary sequences in target mRNAs. Long non-coding RNAs (lncRNAs), defined as transcripts exceeding 200 nucleotides without protein-coding potential, exhibit diverse regulatory functions including transcriptional regulation, chromatin remodeling, and protein complex scaffolding. Both classes of non- coding RNAs display tissue and cell-type specificity, making them attractive therapeutic targets for modulating pathological processes in cardiac and neurological diseases while minimizing off-target effects.
In the first project the aim was to investigate the molecular basis of exercise-induced brain benefits. Therefore, I developed an in vitro model using electrically stimulated muscle cells to examine how muscle-derived factors directly influence brain cell function. The secretome from stimulated muscle cells significantly enhanced neuronal activity, increased mushroom spine density, and upregulated genes associated with synaptic plasticity in primary neurons.
In primary astrocytes, muscle-derived factors enhanced supportive functions, particularly glutamate uptake and phagocytic activity, despite minimal transcriptomic changes. Interestingly, microglia showed limited responses to the muscle secretome, suggesting cell type-specific mechanisms in the brain's response to peripheral signals. These findings demonstrate that muscle-derived factors alone, independent of systemic adaptations like increased cerebral blood flow, can directly enhance brain cell function.
In the second project we investigated cognitive impairment in the CaMKIIδC transgenic mouse model of heart failure. While 3-month-old transgenic mice exhibited significant memory impairments and extensive hippocampal transcriptional dysregulation, these deficits were largely resolved by 6 months of age. Through RNA sequencing and small RNA sequencing, we discovered a compensatory network of 27 microRNAs that reinstated normal expression of genes critical for hippocampal function.
This compensatory miRNA signature, centered around miR-181a-5p as a hub regulator and including members of the let-7 and miR-29 families, targeted 73% of reinstated transcripts, demonstrating the powerful role of miRNAs in buffering transcriptional fluctuations during disease progression. These findings challenge linear models of heart failure-induced cognitive decline and reveal endogenous resilience mechanisms that may represent novel therapeutic targets.
In my last project I characterized a cardiomyocyte-specific long non-coding RNA (CRMA) with complex roles in cardiac health and disease. CRMA is consistently deregulated across various cardiac pathologies, including dilated cardiomyopathy, ischemic cardiomyopathy, and heart failure with reduced ejection fraction.
Using iPSC-derived cardiomyocytes, I demonstrated that CRMA knockdown produced paradoxical effects: downregulating hypertrophic marker genes while simultaneously disrupting pathways essential for cardiomyocyte structural integrity. In an endothelin-1- induced hypertrophy model, CRMA depletion attenuated hypertrophic responses and selectively restored potassium currents without affecting sodium or calcium homeostasis. These findings suggest CRMA functions both in maintaining normal cardiomyocyte structure and in promoting pathological hypertrophic responses, highlighting the complex roles of lncRNAs in cardiac physiology and disease.
Collectively, these projects establish non-coding RNAs as critical mediators of inter-organ communication, functioning both as messengers between distant tissues and as regulators that coordinate complex cellular responses. The identification of a compensatory miRNA network in heart failure, the characterization of CRMA's dual role in cardiac health and disease, and the demonstration that muscle-derived factors directly modulate neuronal and astrocytic function advance our understanding of how organs communicate and coordinate responses to physiological and pathological stimuli.
This work provides insights into potential therapeutic strategies targeting inter-organ communication pathways, such as modulating specific miRNAs to enhance cognitive resilience in heart failure patients, targeting CRMA to attenuate pathological cardiac hypertrophy, and harnessing muscle-derived factors to promote brain health in individuals with limited exercise capacity.2026-05-2
Stabilized Optical Scanning Tunneling Microscopy: Probing Defect-Driven Phenomena in Correlated Electron Systems
No full textThis thesis presents the development and application of a stabilized optical scanning tunneling microscopy (STM) approach that enables controlled, localized optical excitation at the atomic scale. A key advancement is the implementation of grating-coupled plasmonic gold tips combined with active beam stabilization via image recognition, which suppress long-term thermal drift and pointing instabilities that have historically limited optical STM experiments. This method allows surface plasmon polaritons to be launched remotely and adiabatically focused to the tip apex, providing nanometer-scale excitation without far-field illumination of the junction.
The technique is applied to the correlated layered material 1T-TaS₂, a prototypical charge density wave (CDW) system exhibiting insulating, metallic, and metastable photo-induced states. Using low-temperature STM and scanning tunneling spectroscopy, we first identify a fully metallic anti-phase boundary embedded within the semiconducting commensurate CDW phase. Under controlled optical excitation, we observe the nucleation and manipulation of CDW domain structures and reveal a correlation between defect sites and the formation of domain wall networks. Additionally, we report the emergence of chiral domain configurations by optically quentching the sample system.2026-10-2
Changes in Surrogate Markers of Hepatic Steatosis During Metformin Therapy in Women with PCOS
No full textPCOS ist eine häufige Erkrankung unter Frauen im reproduktiven Alter, die neben der Hauptsymptomatik Hirsutismus, Problematik der Fruchtbarkeit und Adipositas mit einer Reihe Begleiterkrankungen einhergehen kann. Besonders oft werden bei betroffenen Patientinnen ein oder mehrere Komponenten des metabolischen Syndroms beobachtet, so zum Beispiel Diabetes mellitus, Insulinresistenz oder Dyslipidämie. Auch das kardiovaskuläre Risiko ist bei PCOS-Patientinnen erhöht. In den letzten Jahren konnte auch eine Assoziation von PCOS mit der nichtalkoholischen Fettleber beobachtet werden. Auch die MASLD wird mit dem metabolischen Syndrom assoziiert. Die Insulinresistenz, die bei PCOS-Patientinnen oftmals vorliegt, scheint in der Pathogenese der MASLD eine zentrale Rolle zu spielen.
Auch MASLD ist eine häufige Erkrankung, die ähnlich dem PCOS mit einem erhöhten Risiko auf metabolische und kardiovaskuläre Erkrankungen einhergeht. Für die Diagnostik einer MASLD stehen mehrere Optionen zur Verfügung, am häufigsten verwendet wird die Abdomensonographie. Doch auch Surrogat-Marker wie der HSI eignen sich zum Screening auf MASLD. Eine leitliniengerechte medikamentöse Therapie der MASLD steht aktuell nicht zur Verfügung. Metformin, welches als Insulin-Sensitizer auch in der PCOS-Therapie angewandt wird, scheint jedoch einen potenziell günstigen Einfluss auf die Leberverfettung zu haben.
In Zusammenschau dieser Tatsachen stellt sich nun die Frage, ob Metformin bei PCOS-Patientinnen einen Einfluss auf die Leberverfettung haben kann.
Um diese Fragestellung zu beantworten, wurde bei 82 PCOS-Patientinnen retrospektiv der HSI zu zwei Zeitpunkten bestimmt: Einmal vor und einmal im Verlauf von fünf bis zwölf Monaten einer Metformin-Therapie bzw. nach dem gleichen zeitlichen Intervall bei Patientinnen ohne Metformin-Therapie. Um zu differenzieren, ob bestimmte Patientinnen mehr oder weniger von einer Metformin-Therapie bzgl. einer MASLD profitieren, wurden die Patientinnen mit Metformin-Therapie weiter unterteilt nach eingangs bestimmten metabolischen Parametern. Genauer wurden die Patientinnen anhand ihres HSI in „MASLD wahrscheinlich“ und „MASLD unwahrscheinlich“, anhand ihres BMI in „schlank“, „übergewichtig“ und „stark übergewichtig“ und anhand ihres HOMA in „Insulinresistenz vorhanden“ bzw. „Insulinresistenz nicht vorhanden“ unterteilt.
In der statistischen Auswertung oben genannter Daten ergab sich eine (hoch-)signifikante Reduktion des HSI unter Metformin-Therapie bei schlanken Patientinnen mit einem BMI von <30 kg/m².
Aufgrund der kleinen Gruppengrößen sowie des retrospektiven Studiendesigns lassen sich diese Ergebnisse nicht ohne Vorbehalt auf die Gesamtpopulation übertragen. Dennoch lässt sich zusammenfassend festhalten, dass der Einfluss von Metformin auf die MASLD insbesondere bei PCOS-Patientinnen weiter untersucht werden sollte.Polycystic ovary syndrome (PCOS) is a common condition among women of reproductive age. In addition to its core manifestations—hirsutism, fertility problems, and obesity—it is frequently associated with a range of comorbidities. Many affected patients present with one or more components of the metabolic syndrome, such as diabetes mellitus, insulin resistance, or dyslipidemia. Cardiovascular risk is likewise increased in women with PCOS. In recent years, an association between PCOS and non-alcoholic fatty liver disease has also been observed. Metabolic dysfunction-associated steatotic liver disease (MASLD), like PCOS, is closely linked to the metabolic syndrome, with insulin resistance—commonly present in PCOS—playing a central role in its pathogenesis.
MASLD is itself a highly prevalent disease and, similar to PCOS, is associated with an elevated risk of metabolic and cardiovascular complications. Several diagnostic approaches are available, with abdominal ultrasonography being the most widely used. Surrogate markers such as the Hepatic Steatosis Index (HSI) are also suitable for MASLD screening. Currently, no guideline-recommended pharmacological therapy for MASLD exists. However, metformin—used as an insulin sensitizer in PCOS therapy—appears to have a potentially beneficial effect on hepatic steatosis.
Based on these observations, the question arises whether metformin can influence hepatic steatosis in women with PCOS.
To address this, the HSI was retrospectively evaluated in 82 PCOS patients at two time points: once before treatment and once after five to twelve months of metformin therapy, or after the same interval in patients who did not receive metformin. To determine whether specific subgroups might benefit more or less from metformin with respect to MASLD, patients receiving metformin were further stratified according to baseline metabolic parameters. More specifically, they were categorized by HSI (“MASLD likely” vs. “MASLD unlikely”), BMI (“normal weight,” “overweight,” “obese”), and HOMA-IR (“insulin resistance present” vs. “insulin resistance absent”).
Statistical analysis showed a (highly) significant reduction in HSI among normal-weight patients (BMI <30 kg/m²) receiving metformin.
Given the small sample sizes and the retrospective study design, these findings cannot be generalized without caution. Nonetheless, the results suggest that the effect of metformin on MASLD—particularly in PCOS patients—warrants further investigation.2026-02-1