Miracle-dz/UniFAR-FTUs huggingface dataset:
Brain tumor detection and multi‐classification using advanced deep learning techniques

A brain tumor is an uncontrolled development of brain cells in brain cancer if not detected at an early stage. Early brain tumor diagnosis plays a crucial role in treatment planning and patients' survival rate. There are distinct forms, properties, and therapies of brain tumors. Therefore, manual brain tumor detection is complicated, time‐consuming, and vulnerable to error. Hence, automated computer‐assisted diagnosis at high precision is currently in demand. This article presents segmentation through Unet architecture with ResNet50 as a backbone on the Figshare data set and achieved a level of 0.9504 of the intersection over union (IoU). The preprocessing and data augmentation concept were introduced to enhance the classification rate. The multi‐classification of brain tumors is performed using evolutionary algorithms and reinforcement learning through transfer learning. Other deep learning methods such as ResNet50, DenseNet201, MobileNet V2, and InceptionV3 are also applied. Results thus obtained exhibited that the proposed research framework performed better than reported in state of the art. Different CNN, models applied for tumor classification such as MobileNet V2, Inception V3, ResNet50, DenseNet201, NASNet and attained accuracy 91.8, 92.8, 92.9, 93.1, 99.6%, respectively. However, NASNet exhibited the highest accuracy.
Stochastic Dynamics of Einstein Matter-Radiation Model with Spikes

Motivated by the Einstein classical description of the matter-radiation dynamics we revise a dynamical system producing spikes of the photon emission. Then we study the corresponding stochastic model, which takes into account the randomness of spontaneous and stimulated atomic transitions supporting by a pumping. Our model reduces to Markovian density dependent processes for the inversion coefficient and the photon specific value driven by small but fast jumps. We analyse the model in three limits: the many-component, the mean-field, and the one-component. In the last case it is a positive recurrent Markov chain with sound spikes.
Fast Valuation of Options under Parameter Uncertainty

Option valuation is typically done under the assumption of perfect knowledge about latent states (such as stochastic volatility) and parameters, an assumption that is rather dubious from a statistical point of view! This needs to be accounted for without introducing arbitrage. Fourier based methods for computing (vanilla) option values are nowadays the bread and butter in many risk management systems in the financial industry. We introduce a correction for the (parameter and state) uncertainty that previously had to be computed using Monte Carlo methods or deterministic quadrature into the Fourier based framework. We find that these new Fourier methods are retaining all the good properties we have gotten used to, being fast, accurate and applicable to a wide range of models. (Less)
Self-Assembly of Janus Type Amphiphilic Dendrimers from Dissipative Particle Dynamics Simulation

The self-assembly of Janus type amphiphilic dendrimers has been studied extensively through experiments and computer simulations, while most of the simulations assume that Janus molecules are connected by covalent bonds, disregarding the noncovalent interaction which evokes the particular dynamic self-assembly regulation. This paper investigates the dynamic self-assembly behavior of Janus type amphiphilic dendrimers through the dissipative particle dynamics (DPD) method. A series of coarse-grained models of Janus type amphiphilic dendrimers with different hydrophobic-hydrophilic ratios were constructed to simulate the static self-assembly, and then the dynamic self-assembly was carried out through introducing a chemical bonding reaction to simulate the non-covalent interaction between the two different parts of Janus type dendrimers. The control of reaction rate was accomplished by modifying the reaction probability to adjust the dynamic self-assembly process. The results indicate that the introduction of non-covalent interaction changes the self-assembly behavior of some models and generates different dynamic self-assembly structures. It can also be deduced that the reaction rate exerts influence on the structure of dynamic self-assembly.
Human Body Measurement by Digital Photogrammetry System

We have developed an automatic system of all around 3D measurement comprised of special digital cameras and projector in a unit, which can measure human body all around with high precision. It has a calibration box which we use, prior to photographing, to determine the exterior orientation parameters of the cameras so that 3D measurement can be performed automatically as soon as the photographing unit is set up against an object. For stereo-matching we created a robust matching system and integrated it into an all-automatic system.
Analysis of the TCGA Dataset Reveals that Subsites of Laryngeal Squamous Cell Carcinoma Are Molecularly Distinct

Simple Summary Squamous cell carcinomas from different parts of the larynx have distinct presentations and prognoses, but the molecular basis for this discrepancy has yet to be characterized. We aimed to determine whether different types of mutations at the DNA, mRNA, and protein levels exist to explain the differential prognoses observed. We found that cancers of the supraglottis had higher overall and smoking-associated genome mutations. Further, supraglottic cancers had a significantly poorer prognosis when other clinical variables and mutational status were controlled for. Different protein pathways were enriched in each subsite: muscle-related in the glottis and neural in the supraglottis. Specific cancer-related proteins were also differentially abundant between the supraglottis and glottis. Our findings may partially explain therapeutic response differences, but further study is required for validation. Abstract Laryngeal squamous cell carcinoma (LSCC) from different subsites have distinct presentations and prognosis. In this study, we carried out a multiomic comparison of LSCC subsites. The Cancer Genome Atlas (TCGA) LSCC cohort was analyzed in the R statistical environment for differences between supraglottic and glottic cancers in single nucleotide variations (SNVs), copy number alterations (CNAs), mRNA abundance, protein abundance, pathway overrepresentation, tumor microenvironment (TME), hypoxia status, and patient outcome. Supraglottic cancers had significantly higher overall and smoking-associated SNV mutational load. Pathway analysis revealed upregulation of muscle related pathways in glottic cancer and neural pathways in supraglottic cancer. Proteins involved in cancer relevant signaling pathways including PI3K/Akt/mTOR, the cell cycle, and PDL1 were differentially abundant between subsites. Glottic and supraglottic tumors have different molecular profiles, which may partially account for differences in presentation and response to therapy.
Integrated Omics Analysis of Non-Small-Cell Lung Cancer Cells Harboring the EGFR C797S Mutation Reveals the Potential of AXL as a Novel Therapeutic Target in TKI-Resistant Lung Cancer

Simple Summary In this study, we employed CRISPR/Cas9 editing technology to introduce the EGFR C797S mutation into an NSCLC cell line harboring EGFR L858R/T790M to establish a cellular model for the investigation of the resistance mechanism associated with the acquired C797S mutation and to explore strategies to battle this type of TKI resistance. Transcriptome and proteome analyses revealed that the differentially expressed genes/proteins in the cells harboring the EGFR C797S mutation are associated with elevated expression of AXL. Furthermore, we presented evidence that inhibition of AXL is effective in slowing the growth of NSCLC cells harboring EGFR C797S. Our findings suggest that AXL inhibition could be a second-line or a potential adjuvant treatment for NSCLC harboring the EGFR C797S mutation. Abstract Oncogenic mutations of epidermal growth factor receptor (EGFR) are responsive to targeted tyrosine kinase inhibitor (TKI) treatment in non-small-cell lung cancer (NSCLC). However, NSCLC patients harboring activating EGFR mutations inevitably develop resistance to TKIs. The acquired EGFR C797S mutation is a known mechanism that confers resistance to third-generation EGFR TKIs such as AZD9291. In this work, we employed CRISPR/Cas9 genome-editing technology to knock-in the EGFR C797S mutation into an NSCLC cell line harboring EGFR L858R/T790M. The established cell model was used to investigate the biology and treatment strategy of acquired EGFR C797S mutations. Transcriptome and proteome analyses revealed that the differentially expressed genes/proteins in the cells harboring the EGFR C797S mutation are associated with a mesenchymal-like cell state with elevated expression of AXL receptor tyrosine kinase. Furthermore, we presented evidence that inhibition of AXL is effective in slowing the growth of NSCLC cells harboring EGFR C797S. Our findings suggest that AXL inhibition could be a second-line or a potential adjuvant treatment for NSCLC harboring the EGFR C797S mutation.
The Extreme Ends of the Treatment Response Spectrum to Botulinum Toxin in Cervical Dystonia

Background: The response to BoNT is not uniform; a broad spectrum of responses and side-effects usually occurs. This study aimed to show special cervical dystonia cases with therapy response very different to normal treatment course which indicate the extreme ends of therapy spectrum. Patients: Clinical data and course of treatment of five long-term treated patients with cervical dystonia out of therapy response norms are presented: a patient who was supersensitive to standard dose and has required dose adjustment to lower dose of BoNT; one patient who worsened under a standard dose, but responded excellently to twice the standard dose; one insensitive patient who responded poorly for years to a dose well above the standard dose, but responded when dose was further increased; and two patients with a totally different response pattern to BoNT/A preparation 1, but the development of a neutralizing antibody induced secondary treatment failure in both cases and a totally different response after switch to BoNT/A preparation 2. Conclusions: These five patients indicate that the response of a patient to a BoNT preparation may be unexpected. Therefore, cautious onset of BoNT therapy is recommended as well as consequent dose adjustment later on and even switch to another BoNT/A preparation when a patient has already developed NABs against BoNT/A.
Good Visual Outcomes After Pituitary Tumor Surgery Are Associated With Increased Visual Cortex Functional Connectivity

Supplemental Digital Content is Available in the Text. Background: Patients presenting with visual impairment secondary to pituitary macroadenomas often experience variable recovery after surgery. Several factors may impact visual outcomes including the extent of neuroaxonal damage in the afferent visual pathway and cortical plasticity. Optical coherence tomography (OCT) measures of retinal structure and resting-state functional MRI (rsfMRI) can be used to evaluate the impact of neuroaxonal injury and cortical adaptive processes, respectively. The purpose of this study was to determine whether rsfMRI patterns of functional connectivity (FC) distinguish patients with good vs poor visual outcomes after surgical decompression of pituitary adenomas. Methods: In this retrospective cohort study, we compared FC patterns between patients who manifested good (GO) vs poor (PO) visual outcomes after pituitary tumor surgery. Patients (n = 21) underwent postoperative rsfMRI a minimum of 1 year after tumor surgery. Seed-based connectivity of the visual cortex (primary [V1], prestriate [V2], and extrastriate [V5]) was compared between GO and PO patients and between patients and healthy controls (HCs) (n = 19). Demographics, visual function, and OCT data were compared preoperatively and postoperatively between patient groups. The threshold for GO was visual field mean deviation equal or less than −5.00 dB and/or visual acuity equal to or better than 20/40. Results: Increased postoperative FC of the visual system was noted for GO relative to PO patients. Specifically, good visual outcomes were associated with increased connectivity of right V5 to the bilateral frontal cortices. Compared with HCs, GO patients showed increased connectivity of V1 and left V2 to sensorimotor cortex, increased connectivity of right and left V2 to medial prefrontal cortex, and increased connectivity of right V5 the right temporal and frontal cortices. Conclusions: Increased visual cortex connectivity is associated with good visual outcomes in patients with pituitary tumor, at late phase of recovery. Our findings suggest that rsfMRI does distinguish GO and PO patients after pituitary tumor surgery. This imaging modality may have a future role in characterizing the impact of cortical adaptation on visual recovery.
Down-Regulated CK 8 Expression in Human Intervertebral Disc Degeneration

As an intermediate filament protein, cytokeratin 8 (CK8) exerts multiple cellular functions. Moreover, it has been identified as a marker of notochord cells, which play essential roles in human nucleus pulposus (NP). However, the distribution of CK8 positive cells in human NP and their relationship with intervertebral disc degeneration (IDD) have not been clarified until now. Here, we found the percentage of CK8 positive cells in IDD (25.7±4.14%) was significantly lower than that in normal and scoliosis NP (51.9±9.73% and 47.8±5.51%, respectively, p<0.05). Western blotting and qRT-PCR results confirmed the down-regulation of CK8 expression in IDD on both of protein and mRNA levels. Furthermore, approximately 37.4% of cell clusters were CK8 positive in IDD. Taken together, this is the first study to show a down-regulated CK8 expression and the percentage of CK8 positive cell clusters in IDD based upon multiple lines of evidence. Consequently, CK8 positive cells might be considered as a potential option in the development of cellular treatment strategies for NP repair.
Decrease in Myelin-Associated Lipids Precedes Neuronal Loss and Glial Activation in the CNS of the Sandhoff Mouse as Determined by Metabolomics

Sandhoff disease (SD) is a lysosomal disease caused by mutations in the gene coding for the β subunit of β-hexosaminidase, leading to deficiency in the enzymes β-hexosaminidase (HEX) A and B. SD is characterised by an accumulation of gangliosides and related glycolipids, mainly in the central nervous system, and progressive neurodegeneration. The underlying cellular mechanisms leading to neurodegeneration and the contribution of inflammation in SD remain undefined. The aim of the present study was to measure global changes in metabolism over time that might reveal novel molecular pathways of disease. We used liquid chromatography-mass spectrometry and 1H Nuclear Magnetic Resonance spectroscopy to profile intact lipids and aqueous metabolites, respectively. We examined spinal cord and cerebrum from healthy and Hexb−/− mice, a mouse model of SD, at ages one, two, three and four months. We report decreased concentrations in lipids typical of the myelin sheath, galactosylceramides and plasmalogen-phosphatidylethanolamines, suggesting that reduced synthesis of myelin lipids is an early event in the development of disease pathology. Reduction in neuronal density is progressive, as demonstrated by decreased concentrations of N-acetylaspartate and amino acid neurotransmitters. Finally, microglial activation, indicated by increased amounts of myo-inositol correlates closely with the late symptomatic phases of the disease.
Cross-talk between the calcium channel TRPV4 and reactive oxygen species interlocks adhesive and degradative functions of invadosomes

Vellino et al. investigated the fine tuning between adhesive and extracellular matrix degradative functions of invadosomes. They characterized the importance of the calcium channel TRPV4 in this coupling through its unique ability to sense ROS and regulate the activities of β1-integrins and a new Ask1–MYO1C functional complex.
Contribution of Th17 cells to tissue injury in hypertension

Purpose of review Hypertension has been demonstrated to be a chief contributor to morbidity and mortality throughout the world. Although the cause of hypertension is multifactorial, emerging evidence, obtained in experimental studies, as well as observational studies in humans, points to the role of inflammation and immunity. Many aspects of immune function have now been implicated in hypertension and end-organ injury; this review will focus upon the recently-described role of Th17 cells in this pathophysiological response. Recent findings Studies in animal models and human genetic studies point to a role in the adaptive immune system as playing a contributory role in hypertension and renal tissue damage. Th17 cells, which produce the cytokine IL17, are strongly pro-inflammatory cells, which may contribute to tissue damage if expressed in chronic disease conditions. The activity of these cells may be enhanced by physiological factors associated with hypertension such as dietary salt or Ang II. This activity may culminate in the increased sodium retaining activity and exacerbation of inflammation and renal fibrosis via multiple cellular mechanisms. Summary Th17 cells are a distinct component of the adaptive immune system that may strongly enhance pathways leading to increased sodium reabsorption, elevated vascular tone and end-organ damage. Moreover, this pathway may lend itself towards specific targeting for treatment of kidney disease and hypertension.
Structural and biochemical characterization of MepR , a multidrug binding transcription regulator of the Staphylococcus aureus multidrug efflux pump

MepR is a multidrug binding transcription regulator that represses expression of the Staphylococcus aureus multidrug efflux pump gene, mepA, as well as its own gene. MepR is induced by multiple cationic toxins, which are also substrates of MepA. In order to understand the gene regulatory and drug-binding mechanisms of MepR, we carried out biochemical, in vivo and structural studies. The 2.40 Å resolution structure of drug-free MepR reveals the most open MarR family protein conformation to date, which will require a huge conformational change to bind cognate DNA. DNA-binding data show that MepR uses a dual regulatory binding mode as the repressor binds the mepA operator as a dimer of dimers, but binds the mepR operator as a single dimer. Alignment of the six half sites reveals the consensus MepR binding site, 5’-GTTAGAT-3’. ‘Drug’ binding studies show that MepR binds to ethidium and DAPI with comparable affinities (Kd = 2.6 and 4.5 kM, respectively), but with significantly lower affinity to the larger rhodamine 6G (Kd = 62.6 kM). Mapping clinically relevant or in vitro selected MepR mutants onto the MepR structure suggests that their defective repressor phenotypes are due to structural and allosteric defects.
Morphological, immunohistochemical, and genetic analyses of bronchiolar adenoma and its putative variants

We collected 26 cases of bronchiolar adenoma (BA) and its variants, and performed a comprehensive characterization using a combination of morphological, immunohistochemical, and genetic assessments. Of these 26, 13 were classic bilayered cases, including 10 proximal and 3 distal‐type BAs. Of note, we also identified 13 cases that lacked a continuous basal cell layer. In five cases, the adenomas were partially classic bilayered, leaving a single layer of columnar or cuboidal epithelial cells in some areas of the lesion (BA with monolayered cell lesions). In the other eight cases, the glandular or papillary structures were entirely composed of monolayered columnar or cuboidal epithelial cells, which were morphologically identical to the luminal epithelial cells of classic BA (monolayered BA‐like lesions). Immunohistochemical analysis revealed thyroid transcription factor 1 expression by ciliated columnar epithelial cells, basal cells, and nonciliated columnar and cuboidal epithelial cells. Basal cells also expressed p40 and p63. Twenty‐five cases underwent next‐generation sequencing using a 422‐cancer‐gene panel (GeneseeqPrime). Oncogenic driver mutations were detected in 23 cases, including 13 (52%) with EGFR mutations, 4 (16%) with KRAS G12D/V mutations, 3 (12%) with BRAF V600E mutations, 2 (8%) with ERBB2 exon 20 insertions, and 1 (4%) with a RET fusion. EGFR exon 20 insertions were present in 100% of BAs with monolayered cell lesions, 37.5% of monolayered BA‐like lesions, and 8% of classic BA (Fisher's exact test, p = 0.002, false discovery rate = 0.014). Collectively, our study revealed a gradual morphological transition between BA and its variants. The genetic composition of BAs with monolayered structures differed significantly from those of classic BAs or lung adenocarcinoma.
Shareholder Protection, Stock Markets and Cross-Border Mergers

This paper is the first one that uses a panel data of different types of shareholder protection in order to examine (i) the effect of such laws on stock market development and (ii) the convergence of shareholder protection laws through cross-border mergers and acquisitions. We find significant results for enabling laws but less so for paternalistic ones.
Bacteriophage Treatment: Critical Evaluation of Its Application on World Health Organization Priority Pathogens

Bacteriophages represent an effective, natural, and safe strategy against bacterial infections. Multiple studies have assessed phage therapy’s efficacy and safety as an alternative approach to combat the emergence of multi drug-resistant pathogens. This systematic review critically evaluates and summarizes published articles on phages as a treatment option for Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis infection models. It also illustrates appropriate phage selection criteria, as well as recommendations for successful therapy. Published studies included in this review were identified through EMBASE, PubMed, and Web of Science databases and were published in the years between 2010 to 2020. Among 1082 identified articles, 29 studies were selected using specific inclusion and exclusion criteria and evaluated. Most studies (93.1%) showed high efficacy and safety for the tested phages, and a few studies also examined the effect of phage therapy combined with antibiotics (17.2%) and resistance development (27.6%). Further clinical studies, phage host identification, and regulatory processes are required to evaluate phage therapy’s safety and efficacy and advance their clinical use.