Miracle-dz/UniFAR-FTUs huggingface dataset:
Deep Learning-Based Tool for Automatic Feature Marking, Cropping, Visualization, and Classification of Chest Radiographs

The prime objective of this research is to develop an automatic tool 'Lung-Infection Visualizer' for marking the Region of Infection and cropping of the marked region in chest radiographs. The tool is also integrated with the feature extractor, feature visualization algorithm, and deep learning-based classifier. Thus, it facilitates the radiology experts where they can easily mark the infected region and visualize the region of infection. In this manuscript, the authors employ the template-based and Brute Force approach of feature mapping. Further, they applied the ResNet, Faster Recurrent Neural Network, XceptionNet, and VGG-16 deep learning-based classifiers for classifying the chest radiographs into bacterial pneumonia, viral pneumonia, COVID-19, and Normal classes. The authors also fine-tune the model parameters and hyperparameters for optimizing the performance of the deep learning-based models. The comparison in the performance proves that the VGG-16 model reports the highest accuracy of 90.07% and outperforms the other models on the dataset of 5,499 chest radiographs used for this research. The cropping tool is registered as Intellectual Property Rights in the name of authors with the registration number SW-14092/2021. And the title 'AutoCrop Tool'.
The Torque Teno Virus Titer in Saliva Reflects the Level of Circulating CD4+ T Lymphocytes and HIV in Individuals Undergoing Antiretroviral Maintenance Therapy

Introduction Torque teno virus (TTV) is a non-pathogenic virus present in body fluids. Its titer in the circulation increases in association with immune suppression, such as in HIV-infected individuals. We evaluated if the TTV titer in saliva from HIV-positive individuals undergoing antiretroviral therapy (ART) was related to the circulating CD4+ T lymphocyte concentration and the HIV titer. Methods Saliva was collected from 276 asymptomatic individuals undergoing ART, and an additional 48 individuals positive for AIDS-associated Kaposi's Sarcoma (AIDS-KS). The salivary TTV titer was measured by gene amplification analysis. The circulating CD4+ T lymphocyte and HIV levels were obtained by chart review. Results TTV was detectable in saliva from 80% of the asymptomatic subjects and 87% of those with AIDS-KS. In the asymptomatic group the median log10 TTV titer/ml was 3.3 in 200 males vs. 2.4 in 76 females (p < 0.0001). TTV titer/ml was 3.7 when HIV was acquired by intravenous drug usage, 3.2 when by sexual acquisition and 2.4 when blood transfusion acquired. The salivary TTV titer was inversely correlated with the circulating CD4+ T lymphocyte level (p < 0.0001) and positively correlated with the circulating HIV concentration (p = 0.0005). The median salivary TTV titer and circulating HIV titer were higher, and the CD4+ count was lower, in individuals positive for AIDS-KS than in the asymptomatic subjects (p < 0.0001). Conclusion The TTV titer in saliva is a potential biomarker for monitoring immune status in individuals undergoing ART.
Platelet-Derived Growth Factor-BB Inhibits Intervertebral Disc Degeneration via Suppressing Pyroptosis and Activating the MAPK Signaling Pathway

Platelet-derived growth factor-BB (PDGF-BB) is a cytokine involved in tissue repair and tumor progression. It has been found to have expression differences between normal and degenerative intervertebral discs. However, it is not clear whether PDGF-BB has a protective effect on intervertebral disc degeneration (IDD). In this experiment, we treated nucleus pulposus cells (NPCs) with IL-1β to simulate an inflammatory environment and found that the extracellular matrix (ECM) anabolic function of NPCs in an inflammatory state was inhibited. Moreover, the induction of IL-1β also enhanced the expression of NLRP3 and the cleavage of caspase-1 and IL-1β, which activated the pyroptosis of NPCs. In this study, we studied the effect of PDGF-BB on IL-1β-treated NPCs and found that PDGF-BB not only significantly promotes the ECM anabolism of NPCs, but also inhibits the occurrence of pyroptosis and the production of pyroptosis products of NPCs. Consistent with this, when we used imatinib to block the PDGF-BB receptor, the above-mentioned protective effect disappeared. In addition, we found that PDGF-BB can also promote the ECM anabolism of NPCs by regulating the ERK, JNK, PI3K/AKT signaling pathways, but not the P38 signaling pathway. In vivo studies, mice that blocked PDGF-BB receptors showed more severe histological manifestations of intervertebral disc degeneration. In summary, our results indicate that PDGF-BB participates in inhibiting the occurrence and development of IDD by inhibiting pyroptosis and regulating the MAPK signaling pathway.
Comparative Effectiveness and Safety of Low-Dose Oral Anticoagulants in Patients With Atrial Fibrillation

Aims: Observational studies of various dose levels of direct oral anticoagulants (DOACs) for patients with atrial fibrillation (AF) found that a high proportion of patients received a dose lower than the target dose tested in randomized controlled trials. There is a need to compare low-dose DOACs with warfarin or other DOACs on effectiveness and safety. Methods: Using administrative data from Quebec province, Canada, we built a cohort of new warfarin or DOAC users discharged from hospital between 2011 and 2017. We determined CHA2DS2-VASc and HAS-BLED scores, and comorbidities for 3-year prior cohort entry. The primary effectiveness endpoint was a composite of ischemic stroke/systemic embolism (SE), and secondary outcomes included a safety composite of major bleeding (MB) events and effectiveness composite (stroke/SE, death) at 1-year follow-up. We contrasted each low-dose DOAC with warfarin or other DOACs as references using inverse probability of treatment weighting to estimate marginal Cox hazard ratios (HRs). Results: The cohort comprised 22,969 patients (mean age: 80–86). We did not find a significant risk reduction for the stroke/SE primary effectiveness endpoint for DOACs vs. warfarin; however, we observed a significantly lower risk for low-dose dabigatran vs. warfarin (HR [95%CI]: 0.59 [0.42–0.81]) for effectiveness composite, mainly due to a lower death rate. The differences in effectiveness and safety composites between low-dose rivaroxaban vs. warfarin were not significant. However, low-dose apixaban had a better safety composite (HR: 0.68 [0.53–0.88]) vs. warfarin. Comparisons of dabigatran vs. apixaban showed a lower risk of stroke/SE (HR: 0.53 [0.30–0.93]) and a 2-fold higher risk of MB. The MB risk was higher for rivaroxaban than for apixaban (HR: 1.58 [1.09–2.29]). Conclusions: The results of this population-based study suggest that low-dose dabigatran has a better effective composite than warfarin. Compared with apixaban, low-dose dabigatran had a better effectiveness composite but a worse safety profile. Low-dose apixaban had a better safety composite than warfarin and other low-dose DOACs. Given that the comparative effectiveness and safety seem to vary from one DOAC to another, pharmacokinetic data for specific populations are now warranted.
Combined Anterior and Posterior Decompression With Fusion for Cervical Ossification of the Posterior Longitudinal Ligament

Objective: Cervical myelopathy caused by ossification of the posterior longitudinal ligament (OPLL) is not uncommon among Asian ethnic groups. Despite reports comparing the pros and cons of anterior- and posterior-only approaches, the optimal management remains debatable. This study aimed to evaluate the outcomes of patients who underwent a combined anterior and posterior approach, simultaneous circumferential decompression and fixation, for cervical OPLL. Method: The study retrospectively reviewed patients with OPLL and who underwent circumferential decompression and fixation, combined anterior corpectomy and posterior laminectomy. The clinical outcomes were evaluated by the Visual Analog Scale of neck and arm pain, the Japanese Orthopedic Association scores, Neck Disability Index, and Nurick scores at each time-point of evaluation. Radiological evaluations included plain and dynamic radiographs and computed tomography for every patient within 2 years post-operation. Subgroup analyses were further performed between the groups, with and without intra-operative cerebrospinal fluid (CSF) leakage. Results: A total of 41 patients completed the follow-up for more than 2 years (mean = 39.8 months) and were analyzed. Continuous-type OPLL was the most common (44%), followed by segmental (27%), mixed (22%), and localized types (7%) in the cohort. Myelopathy and all other functional outcomes improved significantly at 2 years post-operation (all p < 0.05). There were 13 (32%) patients who had intra-operative CSF leakage. At 2 years post-operation, there were no differences in the demographics, functional outcomes, and complication rates between the CSF-leakage and no-leakage groups. The CSF-leakage group had more patients with continuous-type OPLL than the no-leakage group (77 vs. 29%, p = 0.004 < 0.05). During the follow-up, there was no secondary or revision surgery for pseudomeningocele, pseudarthrosis, or other surgery-related complications. Conclusions: Simultaneous circumferential decompression and fixation combine the surgical benefits of sufficient decompression by the posterior approach and direct decompression of OPLL by the anterior approach. It is an effective surgical option for patients with cervical myelopathy caused by OPLL, given that myelopathy unanimously improved without neurological complications in this study. The fusion rates were high, and reoperation rates were low. Despite higher rates of CSF leakage, there were no related long-term sequelae, and minimal wound complications.
The Leading-Edge Structure Based on Geometric Bionics Affects the Transient Cavitating Flow and Vortex Evolution of Hydrofoils

A hydrofoil is a fundamental structure in fluid machinery, and it is widely applied to the fields of propellers, blades of axial flow pumps and underwater machinery. To reveal that the geometric structure of the leading-edge of a hydrofoil is the mechanism that affects the transient cavitating flow, we regard the three fish-type leading-edge structures of mackerel, sturgeon and small yellow croaker as the research objects and use high-precision non-contact 3D scanners to establish three bionic hydrofoils (Mac./Stu./Cro.). We use large eddy simulation to simulate the transient cavitating flow of hydrofoils numerically and compare and analyze their lift–drag characteristics, the transient behavior of unsteady cavitation and the vortex evolution. The numerical simulation results are in good agreement with the experimental results. The warping of leading-edge structure will cause a change in lift–drag characteristics, and the Cro. hydrofoil has a good lift-to-drag ratio. When the leading-edge structure is tilted upward (Cro. hydrofoil), the position of the attached cavity will move forward, which will accelerate the cavitation evolution and improve the velocity fluctuation of the trailing edge. When the leading-edge structure is tilted downward (Stu. hydrofoil), the change in the vortex stretching and dilatation terms will be complex, and the influence area of the vortex will widen.
Slovenian Validation of the Children’s Perceived Use of Self-Regulated Learning Inventory

The importance of self-regulated learning (SRL) has increased during the COVID-19 pandemic and measures for assessing students’ self-regulation skills and knowledge are greatly needed. We present the results of the first thorough adaptation of the Children’s Perceived use of Self-Regulated Learning Inventory (CP-SRLI). The inventory, consisting of 15 scales measuring nine components of SRL, was administered to a sample of 541 Slovenian ninth graders. Confirmatory factor analyses supported internal structure validity of most components, but two components required some structural modifications. Internal consistency coefficients were acceptable for the majority of scale scores and were highly comparable to the original ones. While metric invariance across gender was confirmed, the scalar invariance of some scales needs further examination. Meaningful correlations with relevant externally assessed and self-reported self-regulation and school performance variables indicated good criterion validity of the inventory. The Slovenian version of the CP-SRLI thus proved to be a sufficiently valid and reliable instrument for assessing pupils’ learning self-regulation.
Alcohol Promotes Exosome Biogenesis and Release via Modulating Rabs and miR-192 Expression in Human Hepatocytes

Exosomes are membrane vesicles released by various cell types into the extracellular space under different conditions including alcohol exposure. Exosomes are involved in intercellular communication and as mediators of various diseases. Alcohol use causes oxidative stress that promotes exosome secretion. Here, we elucidated the effects of alcohol on exosome biogenesis and secretion using human hepatocytes. We found that alcohol treatment induces the expression of genes involved in various steps of exosome formation. Expression of Rab proteins such as Rab1a, Rab5c, Rab6, Rab10, Rab11, Rab27a and Rab35 were increased at the mRNA level in primary human hepatocytes after alcohol treatment. Rab5, Rab6 and Rab11 showed significant induction in the livers of patients with alcohol-associated liver disease. Further, alcohol treatment also led to the induction of syntenin, vesicle-associated membrane proteins (VAMPs), and syntaxin that all play various roles in exosome biogenesis and secretion. VAMP3, VAMP5, VAPb, and syntaxin16 mRNA transcripts were increased in alcohol treated cells and in the livers of alcohol-associated liver disease (ALD) patients. Induction in these genes was associated with increases in exosome secretion in alcohol treated hepatocytes. We found that hepatocyte enriched miR-192 and miR-122 levels were significantly decreased in alcohol treated hepatocytes whereas their levels were increased in the cell-free supernatant. The primary transcripts of miR-192 and miR-122 were reduced in alcohol treated hepatocytes, suggesting alcohol partially affects these miRNAs at the transcriptional level. We found that miR-192 has putative binding sites for genes involved in exosome secretion. Inhibition of miR-192 in human hepatoma cells caused a significant increase in Rab27a, Rab35, syntaxin7 and syntaxin16 and a concurrent increase in exosome secretion, suggesting miR-192 regulates exosomes release in hepatocytes. Collectively, our results reveal that alcohol modulates Rabs, VAMPs and syntaxins directly and partly via miR-192 to induce exosome machinery and release.
Vascular Reactivity to Hypercapnia Is Impaired in the Cerebral and Retinal Vasculature in the Acute Phase After Experimental Subarachnoid Hemorrhage

Objective: Impaired cerebral blood flow (CBF) regulation, such as reduced reactivity to hypercapnia, contributes to the pathophysiology after aneurysmal subarachnoid hemorrhage (SAH), but temporal dynamics in the acute phase are unknown. Featuring comparable molecular regulation mechanisms, the retinal vessels participate in chronic and subacute stroke- and SAH-associated vessel alterations in patients and can be studied non-invasively. This study is aimed to characterize the temporal course of the cerebral and retinal vascular reactivity to hypercapnia in the acute phase after experimental SAH and compare the potential degree of impairment. Methods: Subarachnoid hemorrhage was induced by injecting 0.5 ml of heparinized autologous blood into the cisterna magna of male Wistar rats using two anesthesia protocols [isoflurane/fentanyl n = 25 (Sham + SAH): Iso—Group, ketamine/xylazine n = 32 (Sham + SAH): K/X—Group]. CBF (laser speckle contrast analysis) and physiological parameters were measured continuously for 6 h. At six predefined time points, hypercapnia was induced by hypoventilation controlled via blood gas analysis, and retinal vessel diameter (RVD) was determined non-invasively. Results: Cerebral reactivity and retinal reactivity in Sham groups were stable with only a slight attenuation after 2 h in RVD of the K/X—Group. In the SAH Iso—Group, cerebral and retinal CO2 reactivity compared to baseline was immediately impaired starting at 30 min after SAH (CBF p = 0.0090, RVD p = 0.0135) and lasting up to 4 h (p = 0.0136, resp. p = 0.0263). Similarly, in the K/X—Group, cerebral CO2 reactivity was disturbed early after SAH (30 min, p = 0.003) albeit showing a recovery to baseline after 2 h while retinal CO2 reactivity was impaired over the whole observation period (360 min, p = 0.0001) in the K/X—Group. After normalization to baseline, both vascular beds showed a parallel behavior regarding the temporal course and extent of impairment. Conclusion: This study provides a detailed temporal analysis of impaired cerebral vascular CO2 reactivity starting immediately after SAH and lasting up to 6 h. Importantly, the retinal vessels participate in these acute changes underscoring the promising role of the retina as a potential non-invasive screening tool after SAH. Further studies will be required to determine the correlation with functional outcomes.
The Arsenal of Bioactive Molecules in the Skin Secretion of Urodele Amphibians

Urodele amphibians (∼768 spp.), salamanders and newts, are a rich source of molecules with bioactive properties, especially those isolated from their skin secretions. These include pharmacological attributes, such as antimicrobial, antioxidant, vasoactive, immune system modulation, and dermal wound healing activities. Considering the high demand for new compounds to guide the discovery of new drugs to treat conventional and novel diseases, this review summarizes the characteristics of molecules identified in the skin of urodele amphibians. We describe urodele-derived peptides and alkaloids, with emphasis on their biological activities, which can be considered new scaffolds for the pharmaceutical industry. Although much more attention has been given to anurans, bioactive molecules produced by urodeles have the potential to be used for biotechnological purposes and stand as viable alternatives for the development of therapeutic agents.
Automated Application and Resource Management in the Cloud

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Automated Application and Resource Management in the Cloud Nikos Parlavantzas
S1-bZIP Transcription Factors Play Important Roles in the Regulation of Fruit Quality and Stress Response

Sugar metabolism not only determines fruit sweetness and quality but also acts as signaling molecules to substantially connect with other primary metabolic processes and, therefore, modulates plant growth and development, fruit ripening, and stress response. The basic region/leucine zipper motif (bZIP) transcription factor family is ubiquitous in eukaryotes and plays a diverse array of biological functions in plants. Among the bZIP family members, the smallest bZIP subgroup, S1-bZIP, is a unique one, due to the conserved upstream open reading frames (uORFs) in the 5′ leader region of their mRNA. The translated small peptides from these uORFs are suggested to mediate Sucrose-Induced Repression of Translation (SIRT), an important mechanism to maintain sucrose homeostasis in plants. Here, we review recent research on the evolution, sequence features, and biological functions of this bZIP subgroup. S1-bZIPs play important roles in fruit quality, abiotic and biotic stress responses, plant growth and development, and other metabolite biosynthesis by acting as signaling hubs through dimerization with the subgroup C-bZIPs and other cofactors like SnRK1 to coordinate the expression of downstream genes. Direction for further research and genetic engineering of S1-bZIPs in plants is suggested for the improvement of quality and safety traits of fruit.
Efficient Random Beacons with Adaptive Security for Ungrindable Blockchains

We describe and analyze a simple protocol for 𝑛 parties that implements a randomness beacon : a sequence of high entropy values, continuously emitted at regular intervals, with sub-linear communication per value. The algorithm can tolerate a (1 − 𝜖)∕2 fraction of the 𝑛 players to be controlled by an adaptive adversary that may deviate arbitrarily from the protocol. The randomness mechanism relies on verifiable random functions (VRF), modeled as random functions, and effectively stretches an initial 𝜆 -bit seed to an arbitrarily long public sequence so that (i) with overwhelming probability in 𝑘 —the security parameter—each beacon value has high min-entropyconditionedonthefullhistoryofthealgorithm, and(ii)thetotalworkandcommunicationrequired per value is 𝑂(𝑘) cryptographic operations. The protocol can be directly applied to provide a qualitative improvement in the security of several proof-of-stake blockchain algorithms, rendering them safe from “grinding” attacks.
Editorial: Classical and Modern Biotechnology Applied to the Treatment of Epilepsy and Anxiety Disorders

The classical and modern approaches applied to the search for new therapeutic options in neurological disorder management have rendered important theoretical and practical innovations, especially when considering the broad contribution of biotechnology advances (Maguire, 2019). Our research topic dealing with these issues was carefully assembled by reviews and original research articles written by invited eminent researchers from different countries in which neurological disorders are equally relevant and customarily represent a huge public health problem. This statement is essentially true when those disorders appear as comorbidities such as in the case of epileptic patients with anxiety and depression as examples of more common comorbidities. As supported by solid clinical evidence, it has been assumed that the improvement or worsening of symptoms elicited by depression and/or anxiety may produce respectively a positive or negative influence on the prognosis of epileptic condition and vice versa (Thapar et al., 2009). Several different contributing factors can modulate the neuropathology and prognosis underlying different neurological disorders per se. However, and despite the important molecular and cellular bases differences in those disorders, the sharing of specific pathophysiological mechanisms and neural pathways subserving epilepsy and simultaneously involved in the regulation of behavior and mood underlying anxiety or depression allows the use of combined therapeutic strategies for each specific case (Thapar et al., 2009; Dhir, 2010). The significant symptom relief and/or cure for the patients suffering from those neurological conditions separately or in comorbidities with psychiatric diseases is the golden goal for clinicians and pharmacologists, each time mostly aided by biotechnological advances (Maguire, 2019). The most imperative advances should be focused on avoidance of side effects elicited by the current arsenal of drugs, as well as in the shortness of time for the onset of their pharmacological action when applied for the treatment of those medical conditions. In addition, the increase of therapeutic compliance of patients and a satisfactory therapeutic response to the novel therapeutic strategies, especially when applied in therapy of refractory cases, are equally welcome (Beyenburg et al., 2005; Maguire, 2019). Based on this, new theoretical and practical therapeutic innovations, the earlier and more correct diagnosis, a more complete and clear nosological classification, and an advanced understanding of different Edited and reviewed by: Nicholas M. Barnes, University of Birmingham, United Kingdom