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  • 1
    Online Resource
    Online Resource
    MDPI AG ; 2022
    In:  Applied Sciences Vol. 12, No. 13 ( 2022-07-05), p. 6816-
    In: Applied Sciences, MDPI AG, Vol. 12, No. 13 ( 2022-07-05), p. 6816-
    Abstract: In the face of emerging technological achievements, cyber security remains a significant issue. Despite the new possibilities that arise with such development, these do not come without a drawback. Attackers make use of the new possibilities to take advantage of possible security defects in new systems. Advanced-persistent-threat (APT) attacks represent sophisticated attacks that are executed in multiple steps. In particular, network systems represent a common target for APT attacks where known or yet undiscovered vulnerabilities are exploited. For this reason, intrusion detection systems (IDS) are applied to identify malicious behavioural patterns in existing network datasets. In recent times, machine-learning (ML) algorithms are used to distinguish between benign and anomalous activity in such datasets. The application of such methods, especially autoencoders, has received attention for achieving good detection results for APT attacks. This paper builds on this fact and applies several autoencoder-based methods for the detection of such attack patterns in two datasets created by combining two publicly available benchmark datasets. In addition to that, statistical analysis is used to determine features to supplement the anomaly detection process. An anomaly detector is implemented and evaluated on a combination of both datasets, including two experiment instances–APT-attack detection in an independent test dataset and in a zero-day-attack test dataset. The conducted experiments provide promising results on the plausibility of features and the performance of applied algorithms. Finally, a discussion is provided with suggestions of improvements in the anomaly detector.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704225-X
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  • 2
    In: Cancers, MDPI AG, Vol. 12, No. 6 ( 2020-06-17), p. 1604-
    Abstract: Reliable entity subtyping is paramount for therapy stratification in lung cancer. Morphological evaluation remains the basis for entity subtyping and directs the application of additional methods such as immunohistochemistry (IHC). The decision of whether to perform IHC for subtyping is subjective, and access to IHC is not available worldwide. Thus, the application of additional methods to support morphological entity subtyping is desirable. Therefore, the ability of convolutional neuronal networks (CNNs) to classify the most common lung cancer subtypes, pulmonary adenocarcinoma (ADC), pulmonary squamous cell carcinoma (SqCC), and small-cell lung cancer (SCLC), was evaluated. A cohort of 80 ADC, 80 SqCC, 80 SCLC, and 30 skeletal muscle specimens was assembled; slides were scanned; tumor areas were annotated; image patches were extracted; and cases were randomly assigned to a training, validation or test set. Multiple CNN architectures (VGG16, InceptionV3, and InceptionResNetV2) were trained and optimized to classify the four entities. A quality control (QC) metric was established. An optimized InceptionV3 CNN architecture yielded the highest classification accuracy and was used for the classification of the test set. Image patch and patient-based CNN classification results were 95% and 100% in the test set after the application of strict QC. Misclassified cases mainly included ADC and SqCC. The QC metric identified cases that needed further IHC for definite entity subtyping. The study highlights the potential and limitations of CNN image classification models for tumor differentiation.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 3
    In: Cancers, MDPI AG, Vol. 12, No. 9 ( 2020-09-21), p. 2704-
    Abstract: Subtyping of non-small cell lung cancer (NSCLC) is paramount for therapy stratification. In this study, we analyzed the largest NSCLC cohort by mass spectrometry imaging (MSI) to date. We sought to test different classification algorithms and to validate results obtained in smaller patient cohorts. Tissue microarrays (TMAs) from including adenocarcinoma (ADC, n = 499) and squamous cell carcinoma (SqCC, n = 440), were analyzed. Linear discriminant analysis, support vector machine, and random forest (RF) were applied using samples randomly assigned for training (66%) and validation (33%). The m/z species most relevant for the classification were identified by on-tissue tandem mass spectrometry and validated by immunohistochemistry (IHC). Measurements from multiple TMAs were comparable using standardized protocols. RF yielded the best classification results. The classification accuracy decreased after including less than six of the most relevant m/z species. The sensitivity and specificity of MSI in the validation cohort were 92.9% and 89.3%, comparable to IHC. The most important protein for the discrimination of both tumors was cytokeratin 5. We investigated the largest NSCLC cohort by MSI to date and found that the classification of NSCLC into ADC and SqCC is possible with high accuracy using a limited set of m/z species.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 4
    In: Cancers, MDPI AG, Vol. 15, No. 9 ( 2023-04-25), p. 2444-
    Abstract: A common severe neurotoxic side effect of breast cancer (BC) therapy is chemotherapy-induced peripheral neuropathy (CIPN) and intervention is highly needed for the detection, prevention, and treatment of CIPN at an early stage. As the eye is susceptible to neurotoxic stimuli, the present study aims to determine whether CIPN signs in paclitaxel-treated BC patients correlate with ocular changes by applying advanced non-invasive biophotonic in vivo imaging. Patients (n = 14, 10 controls) underwent monitoring sessions after diagnosis, during, and after therapy (T0-T3). Monitoring sessions included general anamnesis, assessment of their quality of life, neurological scores, ophthalmological status, macular optical coherence tomography (OCT), and imaging of their subbasal nerve plexus (SNP) by large-area confocal laser-scanning microscopy (CLSM). At T0, no significant differences were detected between patients and controls. During treatment, patients’ scores significantly changed while the greatest differences were found between T0 and T3. None of the patients developed severe CIPN but retinal thickenings could be detected. CLSM revealed large SNP mosaics with identical areas while corneal nerves remained stable. The study represents the first longitudinal study combining oncological examinations with advanced biophotonic imaging techniques, demonstrating a powerful tool for the objective assessment of the severity of neurotoxic events with ocular structures acting as potential biomarkers.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 5
    In: Medicina, MDPI AG, Vol. 59, No. 6 ( 2023-05-23), p. 1003-
    Abstract: Background and Objectives: Immune checkpoint inhibitors (ICIs) have enriched tumor therapy, improving overall survival. Immunotherapy adverse events (irAEs) occur in up to 50% of patients and also affect the peripheral nervous system. The exact pathomechanism is unclear; however, an autoimmune process is implicated. Thus, the clinical evaluation of irAEs in the peripheral nervous system is still demanding. We retrospectively analyzed nerve ultrasound (NU) data of polyneuropathies (PNPs) secondary to checkpoint inhibitors. Materials and Methods: NU data of patients with PNP symptoms secondary to ICI therapy were retrospectively analyzed using the Ultrasound Pattern Sum Score (UPSS) as a quantitative marker. Our findings were compared with a propensity score match analysis (1:1 ratio) to NU findings in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and chemotherapy-associated PNP patients. Results: In total, 10 patients were included (4 female, mean age 66 ± 10.5, IQR 60–77), where NU was performed in 80%. The UPSS obtained ranged from 0 to 5 (mean 2 ± 1.6, IQR 1–2.5). The morphological changes seen in the NUs resembled sonographic changes seen in chemotherapy-associated PNP (n = 10, mean UPSS 1 ± 1, IQR 0–2) with little to no nerve swelling. In contrast, CIDP patients had a significantly higher UPSS (n = 10, mean UPSS 11 ± 4, IQR 8–13, p 〈 0.0001). Conclusions: Although an autoimmune process is hypothesized to cause peripheral neurological irAEs, NU showed no increased swelling as seen in CIDP. The nerve swelling observed was mild and comparable to ultrasound findings seen in chemotherapy-associated PNP.
    Type of Medium: Online Resource
    ISSN: 1648-9144
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2088820-X
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  • 6
    In: Cancers, MDPI AG, Vol. 14, No. 6 ( 2022-03-08), p. 1371-
    Abstract: Diffuse large B cell lymphomas (DLBCL) are the most common neoplasia of the lymphatic system. Circulating cell-free DNA released from tumor cells (ctDNA) has been studied in many tumor entities and successfully used to monitor treatment and follow up. Studies of ctDNA in DLBCL so far have mainly focused on tracking mutations in peripheral blood initially detected by next-generation sequencing (NGS) of tumor tissue from one lymphoma manifestation site. This approach, however, cannot capture the mutational heterogeneity of different tumor sites in its entirety. In this case report, we present repetitive targeted next-generation sequencing combined with digital PCR out of peripheral blood of a patient with DLBCL relapse. By combining both detection methods, we were able to detect a new dominant clone of ctDNA correlating with the development of secondary therapy-related acute myeloid leukemia (t-AML) during the course of observation. Conclusively, our case report reinforces the diagnostic importance of ctDNA in DLBCL as well as the importance of repeated ctDNA sequencing combined with focused digital PCR assays to display the dynamic mutational landscape during the clinical course.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 7
    In: Cancers, MDPI AG, Vol. 13, No. 9 ( 2021-04-23), p. 2046-
    Abstract: The programmed death-ligand 1 (PD-L1) plays a crucial role in immunomodulatory treatment concepts for end-stage non-small cell lung cancer (NSCLC). To date, its prognostic significance in patients with curative surgical treatment but regional nodal metastases, reflecting tumor spread beyond the primary site, is unclear. We evaluated the prognostic impact of PD-L1 expression in a surgical cohort of 277 consecutive patients with pN1 NSCLC on a tissue microarray. Patients with PD-L1 staining (clone SP263) on 〉 1% of tumor cells were defined as PD-L1 positive. Tumor-specific survival (TSS) of the entire cohort was 64% at five years. Low tumor stage (p 〈 0.0001) and adjuvant therapy (p = 0.036) were identified as independent positive prognostic factors in multivariate analysis for TSS. PD-L1 negative patients had a significantly better survival following adjuvant chemotherapy than PD-L1 positive patients. The benefit of adjuvant therapy diminished in patients with PD-L1 expression in more than 10% of tumor cells. Stratification towards histologic subtype identified PD-L1 as a significant positive predictive factor for TSS after adjuvant therapy in patients with adenocarcinoma, but not squamous cell carcinoma. Routine PD-L1 assessment in curative intent treatment may help to identify patients with a better prognosis. Further research is needed to elucidate the predictive value of PD-L1 in an adjuvant setting.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 8
    In: Diagnostics, MDPI AG, Vol. 11, No. 5 ( 2021-05-02), p. 826-
    Abstract: Purpose: To retrospectively evaluate the technical and clinical outcome of patients with symptomatic postoperative fluid collections following liver resection treated with CT-guided drainage (CTD). Methods: 143 suitable patients were examined between 2004 and 2017. Technical success was defined as (a) sufficient drainage of the fluid collection and (b) the non-occurrence of peri-interventional complications requiring surgical treatment with minor or prolonged hospitalization. Clinical success was defined as (a) decreasing or normalization of specific blood parameters within 30 days after intervention and (b) no surgical revision in addition to intervention required. C-reactive protein (CRP), leukocytes and Total Serum Bilirubin (TSB) were assessed. Dose length product (DLP) for the intervention parts was determined. Results: Technical success was achieved in 99.5% of 189 performed interventions. Clinical success was reached in 74% for CRP, in 86.7% for Leukocytes and in 62.1% for TSB. The median of successful decrease was 6.0 days for CRP, 3.5 days for Leukocytes and 5.5 days for TSB. In 90.2%, no surgical revision was necessary. Total DLP was significantly lower in the second half of the observation period (median 536.0 mGy*cm between years 2011 and 2017 vs. median 745.5 mGy*cm between years 2004 and 2010). Conclusions: Technical success rate of CTD was very high, and clinical success rate was fair to good. Reduction of the radiation dose reflects developments of CT technology and increased experience of the interventional radiologists.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662336-5
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  • 9
    In: Toxins, MDPI AG, Vol. 8, No. 3 ( 2016-03-17), p. 78-
    Type of Medium: Online Resource
    ISSN: 2072-6651
    Language: English
    Publisher: MDPI AG
    Publication Date: 2016
    detail.hit.zdb_id: 2518395-3
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