Search Results (52)

Brain stem cavernomas are exceedingly rare in pediatric populations, with limited literature addressing their natural history, treatment guidelines, and counseling. We report the case of a 5-year-old girl presenting with acute neurological symptoms, including diplopia, gait ataxia, headache, and altered consciousness. Initial imaging revealed obstructive hydrocephalus caused by a hemorrhagic lesion near the pineal region. After emergency external ventricular drainage (EVD), most symptoms resolved except for diplopia. A subsequent MRI suggested a space-occupying hemorrhagic cyst in the tectal lamina, leading to endoscopic third ventriculostomy (ETV). During ETV, a large hemorrhagic mass at the aqueduct entrance was identified but not removed due to its fragility. Following ETV, the patient improved rapidly and was discharged. However, she was readmitted with recurrent symptoms and altered consciousness. An emergency MRI indicated a progressive hemorrhagic mass lesion compressing the midbrain, necessitating surgical intervention. The patient underwent suboccipital craniotomy using a telovelar approach. The intraoperative findings included cavernoma-like tissue within the aqueduct, which was successfully resected. Histopathology confirmed hemorrhagic and angiomatous tissue, excluding a primary brain tumor. Postoperatively, the patient showed significant, progressive neurological improvement, with mild internuclear strabism, trunk ataxia, and fatigue at the last follow-up. Six months later, a follow-up MRI and cerebral angiography showed no cavernoma remnants but identified a midbrain deep venous anomaly. This case underscores the feasibility of the microsurgical resection of midbrain cavernomas in symptomatic pediatric patients, highlighting the importance of the thorough assessment of atypical hemorrhagic midbrain lesions to exclude rare vascular malformations from differential diagnoses. Full article

Background: Endovascular treatment of venous disease is introducing new therapeutic options in neuroradiology. These procedures are technically challenging and require extensive physician training. Currently, training is mainly conducted on animal models, which presents drawbacks such as ethical concerns and anatomical differences from human vascular architecture. There is no training model that simulates treating intracranial venous disease using original instruments in a real angiography suite. Methods: This work presents the development of a venous system model for endovascular training simulations for integration into the existing Hamburg ANatomical NEurointerventional Simulator (HANNES) for arterial interventions. Results: The manufacturing process established at HANNES and the material used for the arterial vascular models were successfully transferred to the larger 3D-printed vein models. The application test was conducted in a real angiography suite with original instruments by an experienced neurointerventional physician to evaluate the system in terms of geometric mapping, flow, haptics and probing. Conclusion: This newly developed model provides a first approach to simulate an endovascular intervention in the venous system within the HANNES environment. Future expansions might include specific treatment simulations for conditions such as arteriovenous malformations, dural arteriovenous fistulas, sinus vein thrombosis and hydrocephalus. Full article

Thyroid eye disease (TED) is a common extrathyroidal manifestation of hyperthyroidism, typically associated with Graves’ disease (GD). This condition can cause severe functional limitations as well as significant aesthetic concerns. Treatment for TED patients aims to restore functionality and address aesthetic concerns. Surgical TED treatment is usually performed by orbital wall resection, which effectively decompresses intraorbital tissues and corrects the orbital/ocular disorders. Several different scenarios of surgical TED treatment including one-, two-, and three-wall resections are known. More recently, a new minimally invasive technique, the so-called lateral valgization (LAVA) of the orbital wall, was reported to show promising results comparable to conventional wall resection techniques. Due to the relatively limited data on TED treatment, only a few quantitative investigations of alternative TED surgery scenarios exist. In this feasibility study, we estimate the soft tissue outcome of LAVA treatment using computational simulation. Our experimental results show that the amount of intraorbital tissue released into the extraorbital space by LAVA treatment is comparable with the outcome of two-wall resection. Our computational simulation confirms previously reported isolated clinical findings suggesting that the minimally invasive LAVA approach represents an attractive alternative to conventional wall resection approaches for surgical TED treatment. Full article

Background: Advancements in genomic technologies are rapidly evolving, with the potential to transform laboratory diagnostics by enabling high-throughput analysis of complex biological data, such as microbiome data. Large Language Models (LLMs) have shown significant promise in extracting actionable insights from vast datasets, but their application in generating microbiome findings reports with clinical interpretations and lifestyle recommendations has not been explored yet. Methods: This article introduces an innovative framework that utilizes LLMs to automate the generation of findings reports in the context of microbiome diagnostics. The proposed model integrates LLMs within an event-driven, workflow-based architecture, designed to enhance scalability and adaptability in clinical laboratory environments. Special focus is given to aligning the model with clinical standards and regulatory guidelines such as the In-Vitro Diagnostic Regulation (IVDR) and the guidelines published by the High-Level Expert Group on Artificial Intelligence (HLEG AI). The implementation of this model was demonstrated through a prototype called “MicroFlow”. Results: The implementation of MicroFlow indicates the viability of automating findings report generation using LLMs. Initial evaluation by laboratory expert users indicated that the integration of LLMs is promising, with the generated reports being plausible and useful, although further testing on real-world data is necessary to assess the model’s accuracy and reliability. Conclusions: This work presents a potential approach for using LLMs to support the generation of findings reports in microbiome diagnostics. While the initial results seem promising, further evaluation and refinement are needed to ensure the model’s effectiveness and adherence to clinical standards. Future efforts will focus on improvements based on feedback from laboratory experts and comprehensive testing on real patient data. Full article

This paper presents a real-time implementation of a hybrid connected component labeling method for processing the Shack–Hartmann wavefront sensor’s images for an adaptive optics (AO) system. The output image of a wavefront sensor is an image of spots. During the sensor’s operation, it can happen that highly distorted wavefronts (WF) may cause the spots to shift outside of their sub-aperture, which may lead to the reduction of the AO system performance. This article explains the benefits of high-performance computing and parallel processing of a field programmable gate array (FPGA). The objective is to calculate the centroids of these spots. A hybrid labeling method was investigated to fulfill this purpose. First, this method was implemented using a forward and backward scan with a respective mask for each scan. Additionally, a relabeling process is applied after labeling each line, and it is carried out in both directions. After labeling, several processing units were implemented in parallel to calculate centroids. Each unit is responsible for calculating the centroid of one label. The system runs in real time with a latency of one frame, which means the output image is a fusion of a current frame and the centroids of the previous frame. Forward and backward labeling requires a large amount of memory, which is the reason for limiting the investigation to forward labeling only. The forward labeling was successfully implemented, and the centroids were detected under minimum spot distortion conditions. This forward labeling implementation also runs in real time with significant latency reduction to calculate the centroids, which leads to minimizing the overall AO system latency, enabling faster computation and correction in addition to reducing the memory usage to 1% when compared to the forward and backward labeling usage of 81% as an advantage for the hardware implementation. Full article

Significant efforts are being made across academia and industry to better characterize lithium ion battery cells as reliance on the technology for applications ranging from green energy storage to electric mobility increases. The measurement of short-term and long-term volume expansion in lithium-ion battery cells is relevant for several reasons. For instance, expansion provides information about the quality and homogeneity of battery cells during charge and discharge cycles. Expansion also provides information about aging over the cell’s lifetime. Expansion measurements are useful for the evaluation of new materials and the improvement of end-of-line quality tests during cell production. These measurements may also indicate the safety of battery cells by aiding in predicting the state of charge and the state of health over the lifetime of the cell. Expansion measurements can also assess inhomogeneities on the electrodes, in addition to defects such as gas accumulation and lithium plating. In this review, we first establish the mechanisms through which reversible and irreversible volume expansion occur. We then explore the current state-of-the-art for both contact and noncontact measurements of volume expansion. This review compiles the existing literature on four approaches to contact measurement and eight noncontact measurement approaches. Finally, we discuss the different considerations when selecting an appropriate measurement technique. Full article

Manual labeling and categorization are extremely time-consuming and, thus, costly. AI and ML-supported information systems can bridge this gap and support labor-intensive digital activities. Since it requires categorization, coding-based analysis, such as qualitative content analysis, reaches its limits with large amounts of data and could benefit from AI and ML-based support. Empirical social research, its application domain, benefits from Big Data’s ability to create more extensive human behavior and development models. A range of applications are available for statistical analysis to serve this purpose. This paper aims to implement an information system that supports researchers in empirical social research in performing AI-supported qualitative content analysis. AI2VIS4BigData is a reference model that standardizes use cases and artifacts for Big Data information systems that integrate AI and ML for user empowerment. Thus, this work’s concepts and implementations try to achieve an AI2VIS4BigData-compliant information system that supports social researchers in categorizing text data and creating insightful dashboards. Thereby, the text categorization is based on an existing ML component. Furthermore, it presents two evaluations that were conducted for these concepts and implementations: a qualitative cognitive walkthrough assessing the system’s usability and a quantitative user study with 18 participants revealed that though the users perceive AI support as more efficient, they need more time to reflect on the recommendations. The research revealed that AI support increased the correctness of the users’ categorizations but also slowed down their decision-making. The assumption that this is due to the UI design and additional information for processing requires follow-up research. Full article

Synaptopodin-2 (SYNPO2) is a protein associated with the Z-disc in striated muscle cells. It interacts with α-actinin and filamin C, playing a role in Z-disc maintenance under stress by chaperone-assisted selective autophagy (CASA). In smooth muscle cells, SYNPO2 is a component of dense bodies. Furthermore, it has been proposed to play a role in tumor cell proliferation and metastasis in many different kinds of cancers. Alternative transcription start sites and alternative splicing predict the expression of six putative SYNPO2 isoforms differing by extended amino- and/or carboxy-termini. Our analyses at mRNA and protein levels revealed differential expression of SYNPO2 isoforms in cardiac, skeletal and smooth muscle cells. We identified synemin, an intermediate filament protein, as a novel binding partner of the PDZ-domain in the amino-terminal extension of the isoforms mainly expressed in cardiac and smooth muscle cells, and demonstrated colocalization of SYNPO2 and synemin in both cell types. A carboxy-terminal extension, mainly expressed in smooth muscle cells, is sufficient for association with dense bodies and interacts with α-actinin. SYNPO2 therefore represents an additional and novel link between intermediate filaments and the Z-discs in cardiomyocytes and dense bodies in smooth muscle cells, respectively. In pathological skeletal muscle samples, we identified SYNPO2 in the central and intermediate zones of target fibers of patients with neurogenic muscular atrophy, and in nemaline bodies. Our findings help to understand distinct functions of individual SYNPO2 isoforms in different muscle tissues, but also in tumor pathology. Full article

Background: Sex-specific differences in heart disease outcomes are influenced by the levels of the steroid hormones, estrogen and testosterone. While the roles of estrogen receptors in cardiac disease are well-studied in animals and humans, respective research on androgen receptors (AR) is limited. Here we investigate AR protein and mRNA expression in human myocardium of various cardiac diseases. Methods: AR expression was analyzed by western blotting in myocardium from human non-failing hearts (NF, n = 6) and patients with aortic stenosis (AS, n = 6), hypertrophic cardiomyopathy (HCM, n = 7), dilated cardiomyopathy (DCM, n = 7), and ischemic cardiomyopathy (ICM, n = 7). Using an AR45-specific antibody, a subsequent western blot assessed samples from male and female patients with HCM (n = 10) and DCM (n = 10). The same sample set was probed for full-length AR and AR45 mRNA expression. Immunohistochemistry (IHC) localized AR in myocardium from HCM and AS hearts. Results: Full-length AR was notably enriched in AS and HCM hearts compared to ICM, DCM, and NF. Similarly, AR45 was more abundant in HCM than in DCM. In contrast to the pattern observed for AR protein, full-length AR mRNA levels were lower in HCM compared to DCM, with no discernible difference for the AR45 isoform. Although gender differences in AR expression were not detected in western blots or qRT-PCR, IHC showed stronger nuclear AR signals in males than in females. Conclusions: Our findings indicate disease-specific regulation of AR mRNA and/or AR protein in cardiac hypertrophy, underscoring a potential role in this cardiac pathology. Full article

Duchenne muscular dystrophy (DMD) is a severe progressive muscle disease that mainly affects boys due to X-linked recessive inheritance. In most affected individuals, MLPA or sequencing-based techniques detect deletions, duplications, or point mutations in the dystrophin-encoding DMD gene. However, in a small subset of patients clinically diagnosed with DMD, the molecular cause is not identified with these routine methods. Evaluation of the 60 DMD patients in our center revealed three cases without a known genetic cause. DNA samples of these patients were analyzed using whole-exome sequencing (WES) and, if unconclusive, optical genome mapping (OGM). WES led to a diagnosis in two cases: one patient was found to carry a splice mutation in the DMD gene that had not been identified during previous Sanger sequencing. In the second patient, we detected two variants in the fukutin gene (FKTN) that were presumed to be disease-causing. In the third patient, WES was unremarkable, but OGM identified an inversion disrupting the DMD gene (~1.28 Mb) that was subsequently confirmed with long-read sequencing. These results highlight the importance of reanalyzing unsolved cases using WES and demonstrate that OGM is a useful method for identifying large structural variants in cases with unremarkable exome sequencing. Full article

Genomics-based diagnostic data (GBDD) are becoming increasingly important for laboratory diagnostics. Due to the large quantity of data and their heterogeneity, GBDD poses a big data challenge. Current analysis tools for GBDD are primarily designed for research and do not meet the requirements of laboratory diagnostics for automation, reliability, transparency, reproducibility, robustness, and accessibility. This makes it difficult for laboratories to use these tools in tests that need to be validated according to regulatory frameworks and to execute tests in a time- and cost-efficient manner. In order to better address these requirements, we propose an event-driven workflow-based architecture as the basis for a processing platform that is highly scalable using container technologies and microservices. A prototype implementation of this approach, called GenomicInsights, has been developed and evaluated to demonstrate its feasibility and suitability for laboratory diagnostics. Full article

BICD2 variants have been linked to neurodegenerative disorders like spinal muscular atrophy with lower extremity predominance (SMALED2) or hereditary spastic paraplegia (HSP). Recently, mutations in BICD2 were implicated in myopathies. Here, we present one patient with a known and six patients with novel BICD2 missense variants, further characterizing the molecular landscape of this heterogenous neurological disorder. A total of seven patients were genotyped and phenotyped. Skeletal muscle biopsies were analyzed by histology, electron microscopy, and protein profiling to define pathological hallmarks and pathogenicity markers with consecutive validation using fluorescence microscopy. Clinical and MRI-features revealed a typical pattern of distal paresis of the lower extremities as characteristic features of a BICD2-associated disorder. Histological evaluation showed myopathic features of varying severity including fiber size variation, lipofibromatosis, and fiber splittings. Proteomic analysis with subsequent fluorescence analysis revealed an altered abundance and localization of thrombospondin-4 and biglycan. Our combined clinical, histopathological, and proteomic approaches provide new insights into the pathophysiology of BICD2-associated disorders, confirming a primary muscle cell vulnerability. In this context, biglycan and thrombospondin-4 have been identified, may serve as tissue pathogenicity markers, and might be linked to perturbed protein secretion based on an impaired vesicular transportation. Full article

As organs of photosynthesis, leaves are of vital importance for plants and a source of inspiration for biomimetic developments. Leaves are composed of interconnected functional elements that evolved in concert under high selective pressure, directed toward strategies for improving productivity with limited resources. In this paper, selected basic components of the leaf are described together with biomimetic examples derived from them. The epidermis (the “skin” of leaves) protects the leaf from uncontrolled desiccation and carries functional surface structures such as wax crystals and hairs. The epidermis is pierced by micropore apparatuses, stomata, which allow for regulated gas exchange. Photosynthesis takes place in the internal leaf tissue, while the venation system supplies the leaf with water and nutrients and exports the products of photosynthesis. Identifying the selective forces as well as functional limitations of the single components requires understanding the leaf as an integrated system that was shaped by evolution to maximize carbon gain from limited resource availability. These economic aspects of leaf function manifest themselves as trade-off solutions. Biomimetics is expected to benefit from a more holistic perspective on adaptive strategies and functional contexts of leaf structures. Full article

CSF protein levels are altered in neurological disorders, such as hydrocephalus of different etiologies. In this retrospective observational study, we analyzed cerebrospinal fluid (CSF) samples in hydrocephalic diseases such as aqueductal stenosis (AQS, n = 27), normal pressure hydrocephalus (NPH, n = 24), hydrocephalus communicans (commHC, n = 25) and idiopathic intracranial hypertension (IIH)/pseudotumor cerebri (PC, n = 7) in comparison with neurological patients without hydrocephalic configuration (control, n = 95). CSF was obtained through CSF diversion procedures and lumbar punction and analyzed for protein concentrations according to the institution’s laboratory standards. We found significantly decreased CSF protein levels in patients suffering from AQS (0.13 mg/dL [0.1–0.16 mg/dL] p = 2.28 × 10⁻⁸) and from PC (0.18 mg/dL [0.12–0.24 mg/dL] p = 0.01) compared with controls (0.34 mg/dL [0.33–0.35 mg/dL]). Protein levels were not altered in patients suffering from commHC and NPH compared with neurologically healthy individuals. We propose that a decrease in CSF protein levels is part of an active counterregulatory mechanism to lower CSF volume and, subsequently, intracranial pressure in specific diseases. Research regarding said mechanism and more specific proteomic research on a cellular level must still be performed to prove this hypothesis. Differences in protein levels between different diseases point to different etiologies and mechanisms in different hydrocephalic pathologies. Full article

Si_1−xGe_x nanowires (NWs) were prepared by gold-supported chemical vapor deposition (CVD) using a single-source precursor with preformed Si–Ge bonds. Besides the tamed reactivity of the precursor, the approach reduces the process parameters associated with the control of decomposition characteristics and the dosing of individual precursors. The group IV alloy NWs are single crystalline with a constant diameter along their axis. During the wire growth by low pressure CVD, an Au-containing surface layer on the NWs forms by surface diffusion from the substrate, which can be removed by a combination of oxidation and etching. The electrical properties of the Si_1−xGe_x/Au core-shell NWs are compared to the Si_1−xGe_x NWs after Au removal. Core–shell NWs show signatures of metal-like behavior, while the purely semiconducting NWs reveal typical signatures of intrinsic Si_1−xGe_x. The synthesized materials should be of high interest for applications in nano- and quantum-electronics. Full article