Automatic tractography and segmentation using finsler geometry based on higher-order tensor fields.

BACKGROUND AND OBJECTIVE: We focus on three-dimensional higher-order tensorial (HOT) images using Finsler geometry. In biomedical image analysis, these images are widely used, and they are based on the diffusion profiles inside the voxels. The diffusion information is stored in the so-called diffusion tensor D. Our objective is to present new methods revealing the architecture of neural fibers in presence of crossings and high curvatures. After tracking the fibers, we achieve direct 3D image segmentation to analyse the brain's white matter structures. METHODS: To deal with the construction of the underlying fibers, the inverse of the second-order diffusion tensor D, understood as the metric tensor D-1, is commonly used in DTI modality. For crossing and highly curved fibers, higher order tensors are more relevant, but it is challenging to find an analogue of such an inverse in the HOT case. We employ an innovative approach to metrics based on higher order tensors to track the fibers properly. We propose to feed the tracked fibers as the internal initial contours in an efficient version of 3D segmentation. RESULTS: We propose a brand-new approach to the inversion of a diffusion HOT, and an effective way of fiber tracking in the Finsler setting, based on innovative classification of the individual voxels. Thus, we can handle complex structures with high curvatures and crossings, even in the presence of noise. Based on our novel tractography approach, we also introduce a new segmentation method. We feed the detected fibers as the initial position of the contour surfaces to segment the image using a relevant active contour method (i.e., initiating the segmentation from inside the structures). CONCLUSIONS: This is a pilot work, enhancing methods for fiber tracking and segmentation. The implemented algorithms were successfully tested on both synthetic and real data. The new features make our algorithms robust and fast, and they allow distinguishing individual objects in complex structures, even under noise.

Coumarin-Based Sulfonamide Derivatives as Potential DPP-IV Inhibitors: Pre-ADME Analysis, Toxicity Profile, Computational Analysis, and In Vitro Enzyme Assay.

Recent research on dipeptidyl peptidase-IV (DPP-IV) inhibitors has made it feasible to treat type 2 diabetes mellitus (T2DM) with minimal side effects. Therefore, in the present investigation, we aimed to discover and develop some coumarin-based sulphonamides as potential DPP-IV inhibitors in light of the fact that molecular hybridization of many bioactive pharmacophores frequently results in synergistic activity. Each of the proposed derivatives was subjected to an in silico virtual screening, and those that met all of the criteria and had a higher binding affinity with the DPP-IV enzyme were then subjected to wet lab synthesis, followed by an in vitro biological evaluation. The results of the pre-ADME and pre-tox predictions indicated that compounds 6e, 6f, 6h, and 6m to 6q were inferior and violated the most drug-like criteria. It was observed that 6a, 6b, 6c, 6d, 6i, 6j, 6r, 6s, and 6t displayed less binding free energy (PDB ID: 5Y7H) than the reference inhibitor and demonstrated drug-likeness properties, hence being selected for wet lab synthesis and the structures being confirmed by spectral analysis. In the in vitro enzyme assay, the standard drug Sitagliptin had an IC50 of 0.018 µM in the experiment which is the most potent. All the tested compounds also displayed significant inhibition of the DPP-IV enzyme, but 6i and 6j demonstrated 10.98 and 10.14 µM IC50 values, respectively, i.e., the most potent among the synthesized compounds. Based on our findings, we concluded that coumarin-based sulphonamide derivatives have significant DPP-IV binding ability and exhibit optimal enzyme inhibition in an in vitro enzyme assay.

The Effect of Primary Aldosteronism on Carotid Artery Texture in Ultrasound Images.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension. Early diagnoses of PA are essential to avoid the long-term negative effects of elevated aldosterone concentration on the cardiovascular and renal system. In this work, we study the texture of the carotid artery vessel wall from longitudinal ultrasound images in order to automatically distinguish between PA and essential hypertension (EH). The texture is characterized using 140 Haralick and 10 wavelet features evaluated in a region of interest in the vessel wall, followed by the XGBoost classifier. Carotid ultrasound studies were carried out on 33 patients aged 42-72 years with PA, 52 patients with EH, and 33 normotensive controls. For the most clinically relevant task of distinguishing PA and EH classes, we achieved a classification accuracy of 73% as assessed by a leave-one-out procedure. This result is promising even compared to the 57% prediction accuracy using clinical characteristics alone or 63% accuracy using a combination of clinical characteristics and intima-media thickness (IMT) parameters. If the accuracy is improved and the method incorporated into standard clinical procedures, this could eventually lead to an improvement in the early diagnosis of PA and consequently improve the clinical outcome for these patients in future.

Management of Scaphoid Nonunion (SNU) With Ilizarov Ring Fixator Using Two Olive Wire Compression Without Bone Grafting: A Case Series.

BACKGROUND: The scaphoid is the most commonly fractured bone among the carpal bones seen in orthopedic practice. The majority have good favorable prognosis, but some develop nonunion of fracture despite optimal treatment, which can lead to further complications if left untreated. It is recommended that displaced scaphoid nonunions (SNUs) should be reduced and fixed to prevent degenerative changes from occurring, even if they are asymptomatic. Many treatments have been described, from a percutaneous fixation with a k-wire or screw to open reduction and internal fixation with or without bone grafting, but none of them is the gold standard. AIM: To evaluate the outcome of an SNU treated with an Ilizarov fixator using two olive wires without bone graft. METHODS: Eleven cases of non-union scaphoid fractures were considered in the study which was presented to the Department of Orthopedics of Kalinga Institute of Medical Sciences during the period of March 2015 to March 2018. This study has been approved by the scientific and ethical committees. The anatomical location of the fracture was graded according to the MAYO classification. An Ilizarov frame was applied with two cross olive wires for achieving compression at the fracture area and maintained for six weeks. A final outcome was assessed using the scaphoid outcome score. RESULTS: One out of 11 patients operated on during the study period was lost in follow-up, so 10 patients were considered for analysis of the results. There were nine male patients and one female patient. The majority were right-sided and dominant-handed, with varied occupations. The average duration of nonunion, when presented, was 10.7 months (a range of 6-20 months). The average follow-up was 43.6 months (range 27-60 months). Union was achieved in an average of 12.9 weeks (range 10-18 weeks). All the patients returned to their pre-injury activity level in a mean of 17.1 weeks (range 13-23 weeks). Grip strength improved from a mean of 29.5 kg preoperatively to 39.4 kg postoperatively. At the final follow-up, the mean scaphoid outcome score was 9.1. An excellent outcome was obtained in five cases (50%), a good outcome in three cases (30%), a fair outcome in one case (10%), and in one case (10%), a poor outcome. CONCLUSION: With our technique of Ilizarov fixation and compression with two cross olive wires, SNU can be treated safely even without opening the non-union site and even without bone grafting. Since we excluded SNU patients with humpback deformity, carpal instability, carpal collapse, or avascular necrosis (AVN), our results might not be directly comparable to those of other SNU series in the literature. These would have predisposed to a poor outcome. Since we did not assign the patients at random, it is challenging to compare the Ilizarov technique to other widely used SNU treatments and determine whether it is more effective. However, the study's results are encouraging and show that the Ilizarov method using two olive wires for compression.

Characterization of drug effects on cell cultures from phase-contrast microscopy images.

In this work, we classify chemotherapeutic agents (topoisomerase inhibitors) based on their effect on U-2 OS cells. We use phase-contrast microscopy images, which are faster and easier to obtain than fluorescence images and support live cell imaging. We use a convolutional neural network (CNN) trained end-to-end directly on the input images without requiring for manual segmentations or any other auxiliary data. Our method can distinguish between tested cytotoxic drugs with an accuracy of 98%, provided that their mechanism of action differs, outperforming previous work. The results are even better when substance-specific concentrations are used. We show the benefit of sharing the extracted features over all classes (drugs). Finally, a 2D visualization of these features reveals clusters, which correspond well to known class labels, suggesting the possible use of our methodology for drug discovery application in analyzing new, unseen drugs.

Geodesic fiber tracking in white matter using activation function.

BACKGROUND AND OBJECTIVE: The geodesic ray-tracing method has shown its effectiveness for the reconstruction of fibers in white matter structure. Based on reasonable metrics on the spaces of the diffusion tensors, it can provide multiple solutions and get robust to noise and curvatures of fibers. The choice of the metric on the spaces of diffusion tensors has a significant impact on the outcome of this method. Our objective is to suggest metrics and modifications of the algorithms leading to more satisfactory results in the construction of white matter tracts as geodesics. METHODS: Starting with the DTI modality, we propose to rescale the initially chosen metric on the space of diffusion tensors to increase the geodetic cost in the isotropic regions. This change should be conformal in order to preserve the angles between crossing fibers. We also suggest to enhance the methods to be more robust to noise and to employ the fourth order tensor data in order to handle the fiber crossings properly. RESULTS: We propose a way to choose the appropriate conformal class of metrics where the metric gets scaled according to tensor anisotropy. We use the logistic functions, which are commonly used in statistics as cumulative distribution functions. To prevent deviation of geodesics from the actual paths, we propose a hybrid ray-tracing approach. Furthermore, we suggest how to employ diagonal projections of 4th order tensors to perform fiber tracking in crossing regions. CONCLUSIONS: The algorithms based on the newly suggested methods were succesfuly implemented, their performance was tested on both synthetic and real data, and compared to some of the previously known approaches.

Methylene-bearing sulfur-containing cyanopyrimidine derivatives for treatment of cancer: Part-II.

In continuation of our previous work on anticancer and anti-inflammatory agents, a series of 22 novel methylene-bearing sulfur-containing cyanopyrimidine derivatives was synthesized by Biginelli condensation reaction, which was followed by nucleophilic substitution of the chloro group with secondary or tertiary amines. Structural confirmation of these derivatives was attained through different spectral techniques. Then, anticancer evaluation of these compounds was done at the National Cancer Institute. Compounds 4g, 4j, 4k, and 4v demonstrated appreciable results against different cell lines. Among the synthesized compounds, 4g (NSC: 795475) exhibited a growth inhibition (GI) of 81.34% against the NCI-H460 lung cancer cell line, 72.64% against the ACHN renal cancer cell line, and 112.17% against the OVCAR-4 ovarian cancer cell line. Compound 4j (NSC: 795746) was active against U-251 CNS cancer, OVCAR-4 ovarian cancer, and 786-0 and ACHN renal cancer cell lines, with GI of 78.84%, 150.38%, 75.64%, and 86.45%, respectively. The literature supporting the association between cancer and underlying inflammation prompted us to evaluate the four compounds, 4g, 4j, 4k, and 4v, with appreciable anticancer activity for their in vitro anti-inflammatory activity. Cyclooxygenase (COX)-2 inhibition studies were also performed to study the molecular target. To validate the target study, molecular docking studies in the ligand-binding domain of COX-2 (PDB ID: 1CX2) were also performed. Compounds 4g, 4j, and 4k did not show cytotoxicity on RAW 264.7 cells up to 10 µM concentration; however, compound 4v showed cytotoxic effects at 10 µM concentration.

Revealing quinquennial anticancer journey of morpholine: A SAR based review.

Morpholine, a six-membered heterocycle containing one nitrogen and one oxygen atom, is a moiety of great significance. It forms an important intermediate in many industrial and organic syntheses. Morpholine containing drugs are of high therapeutic value. Its wide array of pharmacological activity includes anti-diabetic, anti-emetic, growth stimulant, anti-depressant, bronchodilator and anticancer. Multi-drug resistance in cancer cases have emerged in the last few years and have led to the failure of many chemotherapeutic drugs. Newer treatment methods and drugs are being developed to overcome this problem. Target based drug discovery is an effective method to develop novel anticancer drugs. To develop newer drugs, previously reported work needs to be studied. Keeping this in mind, last five year's literature on morpholine used as anticancer agents has been reviewed and summarized in the paper herein.