Nanomedicine-Challenge and Perspectives Riehemann, Kristina; Schneider, Stefan W.; Luger, Thomas A. ...
Angewandte Chemie,
01/2009, Volume:
48, Issue:
5
Journal Article
Peer reviewed
Open access
The application of nanotechnology concepts to medicine joins two large cross‐disciplinary fields with an unprecedented societal and economical potential arising from the natural combination of ...specific achievements in the respective fields. The common basis evolves from the molecular‐scale properties relevant to the two fields. Local probes and molecular imaging techniques allow surface and interface properties to be characterized on a nanometer scale at predefined locations, while chemical approaches offer the opportunity to elaborate and address surfaces, for example, for targeted drug delivery, enhanced biocompatibility, and neuroprosthetic purposes. However, concerns arise in this cross‐disciplinary area about toxicological aspects and ethical implications. This Review gives an overview of selected recent developments and applications of nanomedicine.
Future of nanomedicine: Multiple functions can be integrated into nanoparticle systems for drug delivery. The schematic representation of a third‐generation nanovector illustrates this: On the outside are recognition units to interact with target cells and biological barriers, while inside are drug‐loaded nanoparticles, which leave the vector at the correct moment and release their load.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Pulsed dye lasers (PDL) are currently the first-line treatment of port-wine birthmarks (PWB). Due to high maintenance costs and instable technology, alternative methods are needed.
To compare ...clinical outcomes of a variable-sequenced, long-pulsed 532-nm potassium titanyl-phosphate (KTP) laser and PDL on treating PWB.
A prospective, randomized, split-side study. Patients were treated with a KTP laser and PDL with 1 to 5 sessions at intervals of 6-8 weeks. A follow-up visit was scheduled 6 weeks post-treatment. Efficacy was evaluated through colorimetric analysis, area reduction measurements and clinical evaluations by two blinded investigators based on photo documentation. Subjects provided rating of pain intensity during treatment, post-treatment reactions and satisfaction. Safety was measured by adverse events. Maintenance issues of the laser systems were documented.
A total of 35 patients (mean age 42.1 years) were enrolled. 63% were female. Patients received 2.4 (SD 1.4; 1-5) treatment sessions. Colorimetric analysis indicated a comparable clearance effect in PWB of both KTP laser and PDL. Independent investigators rated clinical appearance to be significantly improved compared to baseline. No significant difference was observed between both laser systems. Regarding post-treatment reactions, the KTP laser caused less swelling, purpura and crusts. 96% would recommend both treatment modalities. Patients were satisfied with both laser systems. During the study, PDL systems malfunctioned for 6.6 months in total. For the KTP laser, we did not observe any system failures.
Our data indicate that the KTP laser of the latest generation with large-spot sizes, subpulse technology and cryogen cooling has a comparable efficacy to the PDL in treating PWB. In addition, KTP laser is associated with greater tolerability, fewer technical failures and lower repair costs. Further prospective studies are required to determine the true effectiveness of the KTP laser in PWB treatment. This study was preregistered in Clinicaltrials.gov (NCT05771298).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The ability of a researcher to re‐identify (re‐ID) an individual animal upon re‐encounter is fundamental for addressing a broad range of questions in the study of ecosystem function, community and ...population dynamics and behavioural ecology. Tagging animals during mark and recapture studies is the most common method for reliable animal re‐ID; however, camera traps are a desirable alternative, requiring less labour, much less intrusion and prolonged and continuous monitoring into an environment. Despite these advantages, the analyses of camera traps and video for re‐ID by humans are criticized for their biases related to human judgement and inconsistencies between analyses.
In this review, we describe a brief history of camera traps for re‐ID, present a collection of computer vision feature engineering methodologies previously used for animal re‐ID, provide an introduction to the underlying mechanisms of deep learning relevant to animal re‐ID, highlight the success of deep learning methods for human re‐ID, describe the few ecological studies currently utilizing deep learning for camera trap analyses and our predictions for near future methodologies based on the rapid development of deep learning methods.
For decades, ecologists with expertise in computer vision have successfully utilized feature engineering to extract meaningful features from camera trap images to improve the statistical rigor of individual comparisons and remove human bias from their camera trap analyses. Recent years have witnessed the emergence of deep learning systems which have demonstrated the accurate re‐ID of humans based on image and video data with near perfect accuracy. Despite this success, ecologists have yet to utilize these approaches for animal re‐ID.
By utilizing novel deep learning methods for object detection and similarity comparisons, ecologists can extract animals from an image/video data and train deep learning classifiers to re‐ID animal individuals beyond the capabilities of a human observer. This methodology will allow ecologists with camera/video trap data to reidentify individuals that exit and re‐enter the camera frame. Our expectation is that this is just the beginning of a major trend that could stand to revolutionize the analysis of camera trap data and, ultimately, our approach to animal ecology.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Although, drugs are required in the various skin compartments such as viable epidermis, dermis, or hair follicles, to efficiently treat skin diseases, drug delivery into and across the skin is still ...challenging. An improved understanding of skin barrier physiology is mandatory to optimize drug penetration and permeation. The various barriers of the skin have to be known in detail, which means methods are needed to measure their functionality and outside-in or inside-out passage of molecules through the various barriers. In this review, we summarize our current knowledge about mechanical barriers, i.e., stratum corneum and tight junctions, in interfollicular epidermis, hair follicles and glands. Furthermore, we discuss the barrier properties of the basement membrane and dermal blood vessels. Barrier alterations found in skin of patients with atopic dermatitis are described. Finally, we critically compare the up-to-date applicability of several physical, biochemical and microscopic methods such as transepidermal water loss, impedance spectroscopy, Raman spectroscopy, immunohistochemical stainings, optical coherence microscopy and multiphoton microscopy to distinctly address the different barriers and to measure permeation through these barriers in vitro and in vivo.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ecological camera traps are increasingly used by wildlife biologists to unobtrusively monitor an ecosystems animal population. However, manual inspection of the images produced is expensive, ...laborious, and time‐consuming. The success of deep learning systems using camera trap images has been previously explored in preliminary stages. These studies, however, are lacking in their practicality. They are primarily focused on extremely large datasets, often millions of images, and there is little to no focus on performance when tasked with species identification in new locations not seen during training. Our goal was to test the capabilities of deep learning systems trained on camera trap images using modestly sized training data, compare performance when considering unseen background locations, and quantify the gradient of lower bound performance to provide a guideline of data requirements in correspondence to performance expectations. We use a dataset provided by Parks Canada containing 47,279 images collected from 36 unique geographic locations across multiple environments. Images represent 55 animal species and human activity with high‐class imbalance. We trained, tested, and compared the capabilities of six deep learning computer vision networks using transfer learning and image augmentation: DenseNet201, Inception‐ResNet‐V3, InceptionV3, NASNetMobile, MobileNetV2, and Xception. We compare overall performance on “trained” locations where DenseNet201 performed best with 95.6% top‐1 accuracy showing promise for deep learning methods for smaller scale research efforts. Using trained locations, classifications with <500 images had low and highly variable recall of 0.750 ± 0.329, while classifications with over 1,000 images had a high and stable recall of 0.971 ± 0.0137. Models tasked with classifying species from untrained locations were less accurate, with DenseNet201 performing best with 68.7% top‐1 accuracy. Finally, we provide an open repository where ecologists can insert their image data to train and test custom species detection models for their desired ecological domain.
Here, we present the capabilities of deep learning computer vision system for species identification from camera trap images. We compare when background locations are found within the training data, while also excluded. In addition, we also provide guidelines for the number of images required for ecologists when considering their ecosystem of interest.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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Chitosan (Ch) polysaccharide was mixed with phospholipids (P) to generate electrospun hybrid nanofibers intended to be used as platforms for transdermal drug delivery. Ch/P nanofibers ...exibithed average diameters ranging from 248±94nm to 600±201nm, depending on the amount of phospholipids used. Fourier Transformed Infra-Red (FTIR) spectroscopy and Dynamic Light Scattering (DLS) data suggested the occurrence of electrostatic interactions between amine groups of chitosan with the phospholipid counterparts. The nanofibers were shown to be stable for at least 7days in Phosphate Buffer Saline (PBS) solution. Cytotoxicity studies (WST-1 and LDH assays) demonstrated that the hybrid nanofibers have suitable biocompatibility. Fluorescence microscopy, also suggested that L929 cells seeded on top of the CH/P hybrid have similar metabolic activity comparatively to the cells seeded on tissue culture plate (control). The release of curcumin, diclofenac and vitamin B12, as model drugs, from Ch/P hybrid nanofibers was investigated, demonstrating their potential utilization as a transdermal drug delivery system.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The degree to which episodic and semantic memory processes contribute to retrospective self-reports have been shown to depend on the length of reporting period. Robinson and Clore (2002) argued that ...when the amount of accessible detail decreases due to longer reporting periods, an episodic retrieval strategy is abandoned in favor of a semantic retrieval strategy. The current study further examines this shift between retrieval strategies by conceptually replicating the model of Robinson and Clore (2002) for both emotions and symptoms and by attempting to estimate the exact moment of the theorized shift.
A sample of 469 adults reported the extent to which they experienced 8 states (excited, happy, calm, sad, anxious, angry, pain, stress) over 12 time frames (right now to in general). A series of curvilinear and piecewise linear multilevel growth models were used to examine the pattern of response times and response levels (i.e., rated intensity on a 1-5 scale) across the different time frames.
Replicating previous results, both response times and response levels increased with longer time frames. In contrast to prior work, no consistent evidence was found for a change in response patterns that would suggest a shift in retrieval strategies (i.e., a flattening or decrease of the slope for longer time frames). The relationship between the time frames and response times/levels was similar for emotions and symptoms.
Although the current study showed a pronounced effect of time frame on response times and response levels, it did not replicate prior work that suggested a shift from episodic to semantic memory as time frame duration increased. This indicates that even for longer time frames individuals might attempt to retrieve episodic information to provide a response. We suggest that studies relying on self-report should use the same well-defined time frames across all self-reported measures.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Clinical data suggest that thrombosis limits efficacy of ICIs (e.g. anti-PD-1).•Coagulation suppresses ICIs via platelets, leukocytes and the complement system.•Molecular mechanisms ...of CAT envision future therapeutic targets to support ICIs.•ICIs combined with anticoagulant LMWHs may improve clinical outcome.
Advances in understanding the molecular mechanisms of tumor progression have achieved impressive progress in the treatment of cancer and so-called immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. Indeed, antibody-based drugs blocking immune escape of tumor cells by modulation of T cell responses are increasingly utilized for a wide range of tumor entities. Nonetheless, response rates remain limited, and the development of secondary resistance is a common problem. In addition, by increasing the immune response a variety of severe side effects are provoked. Next to autoimmune responses, activation of the complement system and skin toxicity, an increased incidence for thrombotic complications has been observed associated with an increased mortality rate. Based on this, it can be postulated that the interplay of coagulation with inflammation in the tumor microenvironment is relevant for each step in the tumor life cycle. This review focuses on the coagulation as central player fostering mechanisms associated with tumor progression. Thus, a better understanding of the molecular pathways involved in the complex interaction of circulating tumor cells, the plasmatic coagulation and immune cells may help to improve therapeutic concepts reducing mortality and morbidity associated with cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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