Miracle-dz/UniFAR-FTUs huggingface dataset:
Local Anesthetic-Induced Central Nervous System Toxicity during Interscalene Brachial Plexus Block: A Case Series Study of Three Patients

Local anesthetics are commonly administered by nuchal infiltration to provide a temporary interscalene brachial plexus block (ISB) in a surgical setting. Although less commonly reported, local anesthetics can induce central nervous system toxicity. In this case study, we present three patients with acute central nervous system toxicity induced by local anesthetics applied during ISB with emphasis on neurological symptoms, key neuroradiological findings and functional outcome. Medical history, clinical and imaging findings, and outcome of three patients with local anesthetic-induced toxic left hemisphere syndrome during left ISB were analyzed. All patients were admitted to our neurological intensive care unit between November 2016 and September 2019. All three patients presented in poor clinical condition with impaired consciousness and left hemisphere syndrome. Electroencephalography revealed slow wave activity in the affected hemisphere of all patients. Seizure activity with progression to status epilepticus was observed in one patient. In two out of three patients, cortical FLAIR hyperintensities and restricted diffusion in the territory of the left internal carotid artery were observed in magnetic resonance imaging. Assessment of neurological severity scores revealed spontaneous partial reversibility of neurological symptoms. Local anesthetic-induced CNS toxicity during ISB can lead to severe neurological impairment and anatomically variable cerebral lesions.
INVESTIGATION OF THE ROLE OF OXIDATIVE DNA DAMAGE IN AFLATOXIN B1-INDUCED PULMONARY CARCINOGENESIS

ii CO-AUTHORSHIP iv ACKNOWLEDGEMENTS v TABLE OF CONTENTS vi LIST OF FIGURES x LIST OF TABLES xii LIST OF ABBREVIATIONS xiii CHAPTER 1 1 GENERAL INTRODUCTION 1 1.1 STATEMENT OF RESEARCH PROBLEM 1 1.2 CHEMICAL CARCINOGENESIS 2 1.2.1 Lung Cancer 2 1.2. 2 Cell types in the lung 5 1.2. 3 Molecular alterations in human lung cancer 8 1.2. 4 Modelling lung cancer in the mouse 10 1.2. 5 Role of the K-ras protooncogene in lung cancer 12 1.3 REACTIVE OXYGEN SPECIES AND CARCINOGENESIS 13 1.3. 1 Formation and mutagenicity of specific DNA lesions 16 1.3. 1.1 8-hydroxy-2’-deoxyguanosine (8-OHdG) 17 1.3. 1.2 Cytosine oxidation 21 1.3. 2 Antioxidant defense mechanisms 23 1.3. 2.1 Catalase 26 1.3. 3 Base excision repair 28 1.3. 4 Oxidative DNA damage and carcinogenesis 33 1.4 AFLATOXINS 37 1.4. 1 Occurrence and sources of aflatoxins 37 1.4. 2 Biotransformation of aflatoxin B1 37 1.4. 3 Carcinogenicity of AFB1 41 vii 1.4. 4 AFB1-DNA adduct repair 43 1.4. 5 Species/Tissue Susceptibility to AFB1 43 1.4. 6 K-ras activation due to AFB1 exposure 44 1.4. 7 AFB1-induced oxidative DNA damage 45 1.5 RESEARCH HYPOTHESES AND OBJECTIVES 47 CHAPTER 2 51 ELEVATION OF 8-HYDROXYDEOXYGUANOSINE IN DNA FROM ISOLATED MOUSE LUNG CELLS FOLLOWING IN VIVO TREATMENT WITH AFLATOXIN B1 51 2.
Patient and Therapist Perspectives on Treatment for Adults with PTSD from Childhood Trauma

This study aimed to explore patients’ and therapists’ experiences with trauma-focused treatments in patients with posttraumatic stress disorder from childhood trauma (Ch-PTSD). Semi-structured interviews were conducted with patients (n = 44) and therapists (n = 16) from an international multicentre randomised clinical trial comparing two trauma-focused treatments (IREM), imagery rescripting and eye movement and desensitisation (EMDR). Thematic analysis was used to identify key themes within the data. Patients and therapists commented about the process of therapy. The themes that emerged from these comments included the importance of the patients’ willingness to engage and commit to the treatment process; the importance and difficulty of the trauma work, observations of how the trauma focused therapy produced changes in insight, and sense of self and empowerment for the future. In addition, therapists made suggestions for optimising the therapist role in the trauma-focused treatment. This included the importance of having confidence in their own ability, confronting their own and their client’s avoidance and the necessity and difficulties of adhering to the treatment protocols. These reported experiences add further support to the idea that trauma-focused treatments, without a stabilisation phase, can be tolerated and deepens our understanding of how to make this palatable for individuals with Ch-PTSD.
Trabectedin for Patients with Advanced Soft Tissue Sarcoma: A Non-Interventional, Retrospective, Multicenter Study of the Italian Sarcoma Group

Simple Summary Active therapeutic options in advanced soft tissue sarcoma (STS), able to induce durable objective responses, are scarce beyond first-line chemotherapy. Thus, new strategies and optimal sequencing in the treatment algorithm for sarcoma represents an utmost clinical challenge. This non-interventional, retrospective, multicenter study of the Italian sarcoma group aimed to provide insights of the real-world efficacy, toxicity, and management of patients with advanced STS treated with trabectedin in clinical practice across Italy. Our findings on 512 pretreated metastatic patients with multiple sarcoma histologies in terms of time-to-event outcomes (median progression-free survival of 5.1 months and median overall survival of 21.6 months) confirm the activity of this regimen in a real-life setting with a manageable and well-characterized safety profile. Our study has corroborated that in real-life clinical practice, trabectedin is mostly given as a second-line treatment to patients with a good performance status and high-grade, metastatic leiomyosarcoma and liposarcoma. Abstract The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft tissue sarcoma, pretreated with ≥1 anthracycline-based treatment, and treated with trabectedin every three weeks. Primary endpoint was to describe real-life use of trabectedin across Italy. Secondary endpoints included objective response rate (ORR) and safety. Overall, 512 patients from 20 Italian centers were evaluated. Leiomyosarcoma (37.7%)/liposarcoma (30.3%) were the most prevalent histological types (abbreviated as L-sarcoma). Patients received a median of four trabectedin cycles (range: 1–40), mostly as a second-line treatment (~60% of patients). The ORR was 13.7% superior (p < 0.0001) in patients with L-sarcoma compared with patients with non-L-sarcoma (16.6% vs. 9.0%). Median progression-free survival (PFS) was 5.1 months, whereas median overall survival (OS) was 21.6 months. Significantly better PFS and OS were observed in patients with L-sarcoma, those with objective responses and/or disease stabilization, treated in an early line and treated with reduced dose. Bone marrow toxicity (61.4%) and transaminase increases (21.9%) were the most common grade 3/4 adverse events. The results of this real-life study suggest that trabectedin is an active treatment, which is mostly given as a second-line treatment to patients with a good performance status and high-grade, metastatic L-sarcoma (clinical trial information: NCT02793050).
Detection of Dental Caries and Cracks with Quantitative Light-Induced Fluorescence in Comparison to Radiographic and Visual Examination: A Retrospective Case Study

The aim of this study was to present an optimal diagnostic protocol by comparing and analyzing a conventional examination and the quantitative light-induced fluorescence (QLF) technique. Selected were 297 teeth of 153 patients to take QLF images and bitewing radiographs. Occlusal dental caries, proximal dental caries and cracks were evaluated and scored using QLF, X-ray and/or visual criteria. The sensitivity, specificity, and area under the curve (AUC) of a receiver operating characteristic analysis were calculated. Two fluorescence parameters (|ΔFmax| and ΔRmax) were utilized to evaluate the fluorescence pattern according to the severity of lesions based on QLF or X-ray criteria. QLF showed higher scores for detecting occlusal dental caries and cracks than the conventional method. ΔRmax increased more clearly than ΔFmax did with occlusal dental caries. The |ΔFmax| values of occlusal dental caries, proximal dental caries and cracks showed good AUC levels (0.84, 0.81 and 0.83, respectively). The ΔRmax of occlusal dental caries showed the highest AUC (0.91) and the ΔRmax of proximal dental caries showed a fail level (0.59) compared to bitewing radiographs. The QLF image could visualize and estimate the degree of occlusal dental caries or cracks. Consequently, the QLF technique may be an adjunct tool to conventional methods for the detection of occlusal caries and peripheral cracks.
A Comparative Study of Window Size and Channel Arrangement on EEG-Emotion Recognition Using Deep CNN

Emotion recognition based on electroencephalograms has become an active research area. Yet, identifying emotions using only brainwaves is still very challenging, especially the subject-independent task. Numerous studies have tried to propose methods to recognize emotions, including machine learning techniques like convolutional neural network (CNN). Since CNN has shown its potential in generalization to unseen subjects, manipulating CNN hyperparameters like the window size and electrode order might be beneficial. To our knowledge, this is the first work that extensively observed the parameter selection effect on the CNN. The temporal information in distinct window sizes was found to significantly affect the recognition performance, and CNN was found to be more responsive to changing window sizes than the support vector machine. Classifying the arousal achieved the best performance with a window size of ten seconds, obtaining 56.85% accuracy and a Matthews correlation coefficient (MCC) of 0.1369. Valence recognition had the best performance with a window length of eight seconds at 73.34% accuracy and an MCC value of 0.4669. Spatial information from varying the electrode orders had a small effect on the classification. Overall, valence results had a much more superior performance than arousal results, which were, perhaps, influenced by features related to brain activity asymmetry between the left and right hemispheres.
Pulmonary fate and consequences of transferrin-functionalized gold nanoparticles

Surface functionalization of nanoparticles (NPs) may alter their biological interactions such as uptake by alveolar macrophages (AMs). Pulmonary delivery of gold NPs (Au NPs) has theranostic potential due to their optoelectronic properties, minimal alveoli to blood translocation, and possibility of specific cell targeting. Here, we examined whether coating Au NPs with transferrin alters their protein corona, uptake by macrophages, and pulmonary translocation. Methods: Rats were intratracheally instilled with transferrin-coated Au NPs (Tf-Au NPs) or polyethylene glycol-coated Au NPs (PEG-Au NPs). AMs were collected and processed for quantitation of Au cell uptake using ICP-MS and electron microscopy. Au retention in the lungs and other organs was also determined. The uptake of fluorescently labeled Tf-Au NPs and PEG-Au NPs by monocyte-derived human macrophages was also evaluated in vitro. Results: We showed that Tf-Au NPs were endocytosed by AMs and were retained in the lungs to a greater extent than PEG-Au NPs. Both Au NPs acquired similar protein coronas after incubation in rat broncho-alveolar lavage fluid (BALf). The translocation of Au from both NPs to other organs was less than 0.5% of the instilled dose. Transferrin coating enhanced the uptake of Au NPs by primary monocyte-derived human macrophages. Conclusions: We report that coating of NP surface with transferrin can target them to rat AMs and human monocyte-derived macrophages. NP functionalization with transferrin may enhance NP-based therapeutic strategies for lung diseases.
Screening and verification of hub genes involved in osteoarthritis using bioinformatics

Osteoarthritis (OA) is one of the most common causes of disability and its development is associated with numerous factors. A major challenge in the treatment of OA is the lack of early diagnosis. In the present study, a bioinformatics method was employed to filter key genes that may be responsible for the pathogenesis of OA. From the Gene Expression Omnibus database, the datasets GSE55457, GSE12021 and GSE55325 were downloaded, which comprised 59 samples. Of these, 30 samples were from patients diagnosed with osteoarthritis and 29 were normal. Differentially expressed genes (DEGs) were obtained by downloading and analyzing the original data using bioinformatics. The Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed using the Database for Annotation, Visualization and Integrated Discovery online database. Protein-protein interaction network analysis was performed using the Search Tool for the Retrieval of Interacting Genes/proteins online database. BSCL2 lipid droplet biogenesis associated, seipin, FOS-like 2, activator protein-1 transcription factor subunit (FOSL2), cyclin-dependent kinase inhibitor 1A (CDKN1A) and kinectin 1 (KTN1) genes were identified as key genes by using Cytoscape software. Functional enrichment revealed that the DEGs were mainly accumulated in the ErbB, MAPK and PI3K-Akt pathways. Reverse transcription-quantitative PCR analysis confirmed a significant reduction in the expression levels of FOSL2, CDKN1A and KTN1 in OA samples. These genes have the potential to become novel diagnostic and therapeutic targets for OA.
Silencing CDCA8 Suppresses Hepatocellular Carcinoma Growth and Stemness via Restoration of ATF3 Tumor Suppressor and Inactivation of AKT/β–Catenin Signaling

Simple Summary Although the overexpression of CDCA8 is frequently observed in hepatocellular carcinoma (HCC) tissues, the functions of CDCA8 during HCC development remain to be clarified. The aim of our study was to investigate if targeting CDCA8 could affect liver tumor phenotypes in vitro and in vivo and to identify underlying molecular mechanisms to exert its therapeutic effect. We found that silencing of CDCA8 by siRNA inhibits the growth of parental cancer cell culture and mice tumors and suppresses stemness of CD133+ cancer stem cell population through the common responses of the upregulation of the tumor suppressive ATF3/GADD34 functional pathway and inactivation of the Akt/β–catenin signaling axis. These findings suggest CDCA8 as a novel therapeutic target for both primary HCC treatment and the prevention of metastasis or recurrence providing mode of action performed by a CDCA8 inhibitor. Abstract Big data analysis has revealed the upregulation of cell division cycle associated 8 (CDCA8) in human hepatocellular carcinoma (HCC) and its poorer survival outcome. However, the functions of CDCA8 during HCC development remain unknown. Here, we demonstrate in vitro that CDCA8 silencing inhibits HCC cell growth and long-term colony formation and migration through the accumulation of the G2/M phase cell population. Conversely, CDCA8 overexpression increases the ability to undergo long-term colony formation and migration. RNA sequencing and bioinformatic analysis revealed that CDCA8 knockdown led to the same directional regulation in 50 genes (25 down- and 25 upregulated). It was affirmed based on protein levels that CDCA8 silencing downregulates the levels of cyclin B1 and p-cdc2 and explains how it could induce G2/M arrest. The same condition increased the protein levels of tumor-suppressive ATF3 and GADD34 and inactivated AKT/β–catenin signaling, which plays an important role in cell growth and stemness, reflecting a reduction in sphere-forming capacity. Importantly, it was demonstrated that the extent of CDCA8 expression is much greater in CD133+ cancer stem cells than in CD133− cancer cells, and that CDCA8 knockdown decreases levels of CD133, p-Akt and β-catenin and increases levels of ATF3 and GADD34 in the CD133+ cancer stem cell (CSC) population. These molecular changes led to the inhibition of cell growth and sphere formation in the CD133+ cell population. Targeting CDCA8 also effectively suppressed tumor growth in a murine xenograft model, showing consistent molecular alterations in tumors injected with CDCA8siRNA. Taken together, these findings indicate that silencing CDCA8 suppresses HCC growth and stemness via restoring the ATF3 tumor suppressor and inactivating oncogenic AKT/β–catenin signaling, and that targeting CDCA8 may be the next molecular strategy for both primary HCC treatment and the prevention of metastasis or recurrence.
Exploring Obscurin and SPEG Kinase Biology

Three members of the obscurin protein family that contain tandem kinase domains with important signaling functions for cardiac and striated muscles are the giant protein obscurin, its obscurin-associated kinase splice isoform, and the striated muscle enriched protein kinase (SPEG). While there is increasing evidence for the specific roles that each individual kinase domain plays in cross-striated muscles, their biology and regulation remains enigmatic. Our present study focuses on kinase domain 1 and the adjacent low sequence complexity inter-kinase domain linker in obscurin and SPEG. Using Phos-tag gels, we show that the linker in obscurin contains several phosphorylation sites, while the same region in SPEG remained unphosphorylated. Our homology modeling, mutational analysis and molecular docking demonstrate that kinase 1 in obscurin harbors all key amino acids important for its catalytic function and that actions of this domain result in autophosphorylation of the protein. Our bioinformatics analyses also assign a list of putative substrates for kinase domain 1 in obscurin and SPEG, based on the known and our newly proposed phosphorylation sites in muscle proteins, including obscurin itself.
On the Analysis of PM/FM Noise Radar Waveforms Considering Modulating Signals with Varied Stochastic Properties

Noise Radar technology is the general term used to describe radar systems that employ realizations of a given stochastic process as transmit waveforms. Originally, carriers modulated in amplitude by a Gaussian random signal, derived from a hardware noise source, were taken into consideration, justifying the adopted nomenclature. With the advances made in hardware as well as the rise of the software defined noise radar concept, waveform design emerges as an important research area related to such systems. The possibility of generating signals with varied stochastic properties increased the potential in achieving systems with enhanced performances. The characterization of random phase and frequency modulated waveforms (more suitable for several applications) has then gained considerable notoriety within the radar community as well. Several optimization algorithms have been proposed in order to conveniently shape both the autocorrelation function of the random samples that comprise the transmit signal, as well as their power spectrum density. Nevertheless, little attention has been driven to properly characterize the stochastic properties of those signals through closed form expressions, jeopardizing the effectiveness of the aforementioned algorithms as well as their reproducibility. Within this context, this paper investigates the performance of several random phase and frequency modulated waveforms, varying the stochastic properties of their modulating signals.
Determination of oxalate in beer by zone electrophoresis on a chip with conductivity detection

The use of a poly(methylmethacrylate) capillary electrophoresis chip, provided with a high sample load capacity separation system (a 8500 nL separation channel combined with a 500 nL sample injection channel) and a pair of on-chip conductivity detectors, for zone electrophoresis (ZE) determination of oxalate in beer was studied. Hydrodynamic and electroosmotic flows of the solution in the separation compartment of the chip were suppressed and electrophoresis was a dominant transport process in the separations performed on the chip. A low pH of the carrier electrolyte (3.8), implemented by aspartic acid and bis-tris propane, provided an adequate selectivity in the separation of oxalate from anionic beer constituents and, at the same time, also a sufficient sensitivity in its conductivity detection. Under our working conditions, this anion could be detected at a 0.5 μmol/L concentration also in samples containing chloride (a major anionic constituent of beer) at a 1800 higher concentration. Such a favorable analyte/matrix concentration ratio made possible accurate and reproducible [typically, 2-5% relative standard deviation (RSD) values of the peak areas of the analyte in dependence on its concentration in the sample] determination of oxalate in 500 nL volumes of 20-50-fold diluted beer samples. Short analysis times (about 200 s), minimum sample preparation, and reproducible migration times of this analyte (0.5-1.0% RSD values) were characteristic for ZE on the chip.
Automatic Subsidence Troughs Detection in SAR Interferograms Using Circlet Transform

This article presents the results of automatic detection of subsidence troughs in synthetic aperture radar (SAR) interferograms. The detection of subsidence troughs is based on the circlet transform, which is able to detect features with circular shapes. Compared to other methods of detecting circles, the circular transform takes into account the finite data frequency. Moreover, the search shape is not limited to a circle but identified on the basis of a certain width. This is especially important in the case of detection of subsidence troughs whose shapes may not be similar to circles or ellipses but to their fragments. The transformation works directly on the image gradient; it does not require further binary segmentation or edge detection as in the case of other methods, e.g., the Hough transform. The entire processing process can be automated to save time and increase reliability compared to traditional methods. The proposed automatic detection method was tested on a differential interferogram that was generated based on Sentinel-1A SAR images of the Upper Silesian Coal Basin area. The test carried out showed that the proposed method is 20% more effective in detecting troughs that than the method using Hough transform.
A studyforrest extension, an annotation of spoken language in the German dubbed movie “Forrest Gump” and its audio-description

Here we present an annotation of speech in the audio-visual movie “Forrest Gump” and its audio-description for a visually impaired audience, as an addition to a large public functional brain imaging dataset ( studyforrest.org). The annotation provides information about the exact timing of each of the more than 2500 spoken sentences, 16,000 words (including 202 non-speech vocalizations), 66,000 phonemes, and their corresponding speaker. Additionally, for every word, we provide lemmatization, a simple part-of-speech-tagging (15 grammatical categories), a detailed part-of-speech tagging (43 grammatical categories), syntactic dependencies, and a semantic analysis based on word embedding which represents each word in a 300-dimensional semantic space. To validate the dataset’s quality, we build a model of hemodynamic brain activity based on information drawn from the annotation. Results suggest that the annotation’s content and quality enable independent researchers to create models of brain activity correlating with a variety of linguistic aspects under conditions of near-real-life complexity.