Medical Image Retrieval Using Pretrained Embeddings

A wide range of imaging techniques and data formats available for medical images make accurate retrieval from image databases challenging. Efficient retrieval systems are crucial in advancing medical research, enabling large-scale studies and innovative diagnostic tools. Thus, addressing the challenges of medical image retrieval is essential for the continued enhancement of healthcare and research. In this study, we evaluated the feasibility of employing four state-of-the-art pretrained models for medical image retrieval at modality, body region, and organ levels and compared the results of two similarity indexing approaches. Since the employed networks take 2D images, we analyzed the impacts of weighting and sampling strategies to incorporate 3D information during retrieval of 3D volumes. We showed that medical image retrieval is feasible using pretrained networks without any additional training or fine-tuning steps. Using pretrained embeddings, we achieved a recall of 1 for various tasks at modality, body region, and organ level.Comment: 8 pages, 3 figures, 4 table

Defined Geldrop Cultures Maintain Neural Precursor Cells

Distinct micro-environmental properties have been reported to be essential for maintenance of neural precursor cells (NPCs) within the adult brain. Due to high complexity and technical limitations, the natural niche can barely be studied systematically in vivo. By reconstituting selected environmental properties (adhesiveness, proteolytic degradability, and elasticity) in geldrop cultures, we show that NPCs can be maintained stably at high density over an extended period of time (up to 8 days). In both conventional systems, neurospheres and monolayer cultures, they would expand and (in the case of neurospheres) differentiate rapidly. Further, we report a critical dualism between matrix adhesiveness and degradability. Only if both features are functional NPCs stay proliferative. Lastly, Rho-associated protein kinase was identified as part of a pivotal intracellular signaling cascade controlling cell morphology in response to environmental cues inside geldrop cultures. Our findings demonstrate that simple manipulations of the microenvironment in vitro result in an important preservation of stemness features in the cultured precursor cells

Detection of liver dysfunction using a wearable electronic nose system based on semiconductor metal oxide sensors

The purpose of this exploratory study was to determine whether liver dysfunction can be generally classified using a wearable electronic nose based on semiconductor metal oxide (MOx) gas sensors, and whether the extent of this dysfunction can be quantified. MOx gas sensors are attractive because of their simplicity, high sensitivity, low cost, and stability. A total of 30 participants were enrolled, 10 of them being healthy controls, 10 with compensated cirrhosis, and 10 with decompensated cirrhosis. We used three sensor modules with a total of nine different MOx layers to detect reducible, easily oxidizable, and highly oxidizable gases. The complex data analysis in the time and non-linear dynamics domains is based on the extraction of 10 features from the sensor time series of the extracted breathing gas measurement cycles. The sensitivity, specificity, and accuracy for distinguishing compensated and decompensated cirrhosis patients from healthy controls was 1.00. Patients with compensated and decompensated cirrhosis could be separated with a sensitivity of 0.90 (correctly classified decompensated cirrhosis), a specificity of 1.00 (correctly classified compensated cirrhosis), and an accuracy of 0.95. Our wearable, non-invasive system provides a promising tool to detect liver dysfunctions on a functional basis. Therefore, it could provide valuable support in preoperative examinations or for initial diagnosis by the general practitioner, as it provides non-invasive, rapid, and cost-effective analysis results

Increased MCL1 dependency leads to new applications of BH3-mimetics in drug-resistant neuroblastoma.

Neuroblastoma is a paediatric cancer that is characterised by poor prognosis for chemoresistant disease, highlighting the need for better treatment options. Here, we asked whether BH3-mimetics inhibiting BCL2 proteins may eliminate chemoresistant neuroblastoma cells. We utilised cisplatin-adapted neuroblastoma cell lines as well as patient tissues before and after relapse to study alterations of BCL2 proteins upon chemoresistance. In a direct comparison of cisplatin-resistant cells we identified a prominent loss of sensitivity to BCL2/BCL-X inhibitors that is associated with an increase in MCL1 dependency and high expression of MCL1 in patient tumour tissues. Screening of FDA-approved anti-cancer drugs in chemoresistant cells identified therapeutics that may be beneficial in combination with the clinically tested BH3-mimetic ABT263, but no synergistic drug interactions with the selective MCL1 inhibitor S63845. Further exploration of potential treatment options for chemoresistant neuroblastoma identified immunotherapy based on NK cells as highly promising, since NK cells are able to efficiently kill both parental and chemoresistant cells. These data highlight that the application of BH3-mimetics may differ between first line treatment and relapsed disease. Combination of NK cell-based immunotherapy with BH3-mimetics may further increase killing of chemoresistant neuroblastoma, outlining a new treatment strategy for relapsed neuroblastoma. [Abstract copyright: © 2023. The Author(s).

bZIP-Type transcription factors CREB and OASIS bind and stimulate the promoter of the mammalian transcription factor GCMa/Gcm1 in trophoblast cells

One of the master regulators of placental cell fusion in mammals leading to multi-nucleated syncytiotrophoblasts is the transcription factor GCMa. Recently, we proved that the cAMP-driven protein kinase A signaling pathway is fundamental for up-regulation of GCMa transcript levels and protein stability. Here, we show that Transducer of Regulated CREB activity (TORC1), the human co-activator of cAMP response element-binding protein (CREB), but not a dominant-negative CREB mutant, significantly up-regulates the GCMa promoter. We identified potential cAMP response element (CRE)-binding sites within the GCMa promoter upstream of the transcriptional start site. Only the CRE site at -1337 interacted strongly with CREB in promoter mapping experiments. The characterization of GCMa promoter mutants and additional bZIP-type family members demonstrated that also old astrocyte specifically-induced substance (OASIS) is able to stimulate GCMa transcription. Knockdown of endogenous CREB or OASIS in BeWo cells decreased endogenous GCMa mRNA level and activity. Overexpression of TORC1 or OASIS in choriocarcinoma cells led to placental cell fusion, accompanied by placental expression of gap junction forming protein connexin-43. Further, we show that CREB expression is replaced by OASIS expression around E12.5 suggesting that a sequential order of bZIP-type family members ensures a high rate of GCMa transcription throughout placentation

A co-culture model of the hippocampal neurogenic niche reveals differential effects of astrocytes, endothelial cells and pericytes on proliferation and differentiation of adult murine precursor cells

The niche concept of stem cell biology proposes a functional unit between the precursor cells and their local microenvironment, to which several cell types might contribute by cell–cell contacts, extracellular matrix, and humoral factors. We here established three co-culture models (with cell types separated by membrane) for both adherent monolayers and neurospheres to address the potential influence of different niche cell types in the neurogenic zone of the adult hippocampus of mice. Astrocytes and endothelial cells enhanced precursor cell proliferation and neurosphere formation. Endothelial factors also led to a prolonged increase in proliferation after growth factor withdrawal, which otherwise induces differentiation. All niche cell types enhanced cell survival in monolayer cultures, endothelial cells also stimulated neuronal differentiation. A parallel trend elicited by astrocytes did not reach conventional statistical significance. Pericytes had variable effects here. We did not observe changes in differentiation in neurosphere co-cultures. In summary, our data indicate that in precursor cell culture protocols survival could be improved by adding as yet unknown factors physiologically contributed by astrocytes and endothelial cells. Our findings also underscore the complexity of the niche and the differential impact of factors from the different sources on distinct aspects of neuronal development. With the help of the models presented here, identification of these factors and their specific biological activity can now be initiated