Computational methods for the analysis of functional 4D-CT chest images.

Medical imaging is an important emerging technology that has been intensively used in the last few decades for disease diagnosis and monitoring as well as for the assessment of treatment effectiveness. Medical images provide a very large amount of valuable information that is too huge to be exploited by radiologists and physicians. Therefore, the design of computer-aided diagnostic (CAD) system, which can be used as an assistive tool for the medical community, is of a great importance. This dissertation deals with the development of a complete CAD system for lung cancer patients, which remains the leading cause of cancer-related death in the USA. In 2014, there were approximately 224,210 new cases of lung cancer and 159,260 related deaths. The process begins with the detection of lung cancer which is detected through the diagnosis of lung nodules (a manifestation of lung cancer). These nodules are approximately spherical regions of primarily high density tissue that are visible in computed tomography (CT) images of the lung. The treatment of these lung cancer nodules is complex, nearly 70% of lung cancer patients require radiation therapy as part of their treatment. Radiation-induced lung injury is a limiting toxicity that may decrease cure rates and increase morbidity and mortality treatment. By finding ways to accurately detect, at early stage, and hence prevent lung injury, it will have significant positive consequences for lung cancer patients. The ultimate goal of this dissertation is to develop a clinically usable CAD system that can improve the sensitivity and specificity of early detection of radiation-induced lung injury based on the hypotheses that radiated lung tissues may get affected and suffer decrease of their functionality as a side effect of radiation therapy treatment. These hypotheses have been validated by demonstrating that automatic segmentation of the lung regions and registration of consecutive respiratory phases to estimate their elasticity, ventilation, and texture features to provide discriminatory descriptors that can be used for early detection of radiation-induced lung injury. The proposed methodologies will lead to novel indexes for distinguishing normal/healthy and injured lung tissues in clinical decision-making. To achieve this goal, a CAD system for accurate detection of radiation-induced lung injury that requires three basic components has been developed. These components are the lung fields segmentation, lung registration, and features extraction and tissue classification. This dissertation starts with an exploration of the available medical imaging modalities to present the importance of medical imaging in today’s clinical applications. Secondly, the methodologies, challenges, and limitations of recent CAD systems for lung cancer detection are covered. This is followed by introducing an accurate segmentation methodology of the lung parenchyma with the focus of pathological lungs to extract the volume of interest (VOI) to be analyzed for potential existence of lung injuries stemmed from the radiation therapy. After the segmentation of the VOI, a lung registration framework is introduced to perform a crucial and important step that ensures the co-alignment of the intra-patient scans. This step eliminates the effects of orientation differences, motion, breathing, heart beats, and differences in scanning parameters to be able to accurately extract the functionality features for the lung fields. The developed registration framework also helps in the evaluation and gated control of the radiotherapy through the motion estimation analysis before and after the therapy dose. Finally, the radiation-induced lung injury is introduced, which combines the previous two medical image processing and analysis steps with the features estimation and classification step. This framework estimates and combines both texture and functional features. The texture features are modeled using the novel 7th-order Markov Gibbs random field (MGRF) model that has the ability to accurately models the texture of healthy and injured lung tissues through simultaneously accounting for both vertical and horizontal relative dependencies between voxel-wise signals. While the functionality features calculations are based on the calculated deformation fields, obtained from the 4D-CT lung registration, that maps lung voxels between successive CT scans in the respiratory cycle. These functionality features describe the ventilation, the air flow rate, of the lung tissues using the Jacobian of the deformation field and the tissues’ elasticity using the strain components calculated from the gradient of the deformation field. Finally, these features are combined in the classification model to detect the injured parts of the lung at an early stage and enables an earlier intervention

Fabrication and Characterization of Effective Biochar Biosorbent Derived from Agricultural Waste to Remove Cationic Dyes from Wastewater

The main aim of this work is to treat sugarcane bagasse agricultural waste and prepare an efficient, promising, and eco-friendly adsorbent material. Biochar is an example of such a material, and it is an extremely versatile and eco-friendly biosorbent to treat wastewater. Crystal violet (CV)-dye and methylene blue (MB)-dye species are examples of serious organic pollutants. Herein, biochar was prepared firstly from sugarcane bagasse (SCB), and then a biochar biosorbent was synthesized through pyrolysis and surface activation with NaOH. SEM, TEM, FTIR, Raman, surface area, XRD, and EDX were used to characterize the investigated materials. The reuse of such waste materials is considered eco-friendly in nature. After that, the adsorption of MB and CV-species from synthetically prepared wastewater using treated biochar was investigated under various conditions. To demonstrate the study’s effectiveness, it was attempted to achieve optimum effectiveness at an optimum level by working with time, adsorbent dose, dye concentration, NaCl, pH, and temperature. The number of adsorbed dyes reduced as the dye concentrations increased and marginally decreased with NaCl but increased with the adsorbent dosage, pH, and temperature of the solution increased. Furthermore, it climbed for around 15 min before reaching equilibrium, indicating that all pores were almost full. Under the optimum condition, the removal perecentages of both MB and CV-dyes were ≥98%. The obtained equilibrium data was represented by Langmuir and Freundlich isotherm models. Additionally, the thermodynamic parameters were examined at various temperatures. The results illustrated that the Langmuir isotherm was utilized to explain the experimental adsorption processes with maximum adsorption capacities of MB and CV-dyes were 114.42 and 99.50 mgg$_{−1}$, respectively. The kinetic data were estimated by pseudo-first and pseudo-second-order equations. The best correlation coefficients of the investigated adsorption processes were described by the pseudo-second-order kinetic model. Finally, the data obtained were compared with some works published during the last four years

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Borophene and Pristine Graphene 2D Sheets as Potential Surfaces for the Adsorption of Electron-Rich and Electron-Deficient π-Systems: A Comparative DFT Study

The versatility of striped borophene (sB), β12 borophene (β12), and pristine graphene (GN) to adsorb π-systems was comparatively assessed using benzene (BNZ) and hexafluorobenzene (HFB) as electron-rich and electron-deficient aromatic π-systems, respectively. Using the density functional theory (DFT) method, the adsorption process of the π-systems on the investigated 2D sheets in the parallel configuration was observed to have proceeded more favorably than those in the vertical configuration. According to the observations of the Bader charge transfer analysis, the π-system∙∙∙sB complexes were generally recorded with the largest contributions of charge transfer, followed by the π-system∙∙∙β12 and ∙∙∙GN complexes. The band structures of the pure sheets signaled the metallic and semiconductor characters of the sB/β12 and GN surfaces, respectively. In the parallel configuration, the adsorption of both BNZ and HFB showed more valence and conduction bands compared to the adsorption in the vertical configuration, revealing the prominent preferentiality of the anterior configuration. The density-of-states (DOSs) results also affirmed that the adsorption process of the BNZ and HFB on the surface of the investigated 2D sheets increased their electrical properties. In all instances, the sB and β12 surfaces demonstrated higher adsorptivity towards the BNZ and HFB than the GN analog. The findings of this work could make a significant contribution to the deep understanding of the adsorption behavior of aromatic π-systems toward 2D nanomaterials, leading, in turn, to their development of a wide range of applications

Identification of a Cucumber Mosaic Virus from <i>Cucurbita pepo</i> on New Reclamation Land in Egypt and the Changes Induced in Pumpkin Plants

In 2020, the leaves and fruit of 50 pumpkin plants with suspected cucumber mosaic virus (CMV) symptoms of leaf mosaic, vein yellowing, and mild leaf curling were collected from Sharq El-Owainat (Al Wadi El-Gaded governorate), a new reclamation land in Egypt. This study was aimed at deciphering and characterizing the causal agent of the leaf yellowing disease associated with pumpkin plants in Egypt. The causal agent was identified by serological, cytological, and molecular means. The serological identification by DAS–ELISA confirmed the presence of CMV in 20% of the plants. The cytological identification by electron microscopy revealed typical cucumovirus isometric particles of 28–30 nm diameter in the cytoplasm of the leaf parenchyma, epidermal cells, the integument, and the nucleus. Molecular characterization by one-step reverse transcriptase-PCR yielded the required size of amplicon (678 bp) for CMV. Additionally, mechanical sap inoculation was used to determine the host range and symptomatology of the isolated CMV in seventeen different plant species belonging to six different plant families. CMV replicated, moved systemically, and induced a range of symptoms in sixteen plant species. The isolated CMV was transmitted to pumpkin plants at a 16.4% rate by seeds. CMV-infected pumpkin plant leaves were characterized by a substantially low concentration of photosynthetic pigments, a high level of reducing sugars, relatively low protein levels, and a significant increase in total phenol contents, implying their potential role as antiviral agents. Ultrathin sections of infected cells revealed histological changes and cytological abnormalities in comparison to healthy plants. This is the first identification of CMV on new reclamation land in Egypt, pinpointing its swift spread, which could pose a major constraint to pumpkin production in Egypt

Type I&ndash;IV Halogen&#8943;Halogen Interactions: A Comparative Theoretical Study in Halobenzene&#8943;Halobenzene Homodimers

In the current study, unexplored type IV halogen&#8943;halogen interaction was thoroughly elucidated, for the first time, and compared to the well-established types I&ndash;III interactions by means of the second-order M&oslash;ller&ndash;Plesset (MP2) method. For this aim, the halobenzene&#8943;halobenzene homodimers (where halogen = Cl, Br, and I) were designed into four different types, parodying the considered interactions. From the energetic perspective, the preference of scouted homodimers was ascribed to type II interactions (i.e., highest binding energy), whereas the lowest binding energies were discerned in type III interactions. Generally, binding energies of the studied interactions were observed to decline with the decrease in the &sigma;-hole size in the order, C6H5I&#8943;IC6H5 &gt; C6H5Br&#8943;BrC6H5 &gt; C6H5Cl&#8943;ClC6H5 homodimers and the reverse was noticed in the case of type IV interactions. Such peculiar observations were relevant to the ample contributions of negative-belt&#8943;negative-belt interactions within the C6H5Cl&#8943;ClC6H5 homodimer. Further, type IV torsional trans &rarr; cis interconversion of C6H5X&#8943;XC6H5 homodimers was investigated to quantify the &pi;&#8943;&pi; contributions into the total binding energies. Evidently, the energetic features illustrated the amelioration of the considered homodimers (i.e., more negative binding energy) along the prolonged scope of torsional trans &rarr; cis interconversion. In turn, these findings outlined the efficiency of the cis configuration over the trans analog. Generally, symmetry-adapted perturbation theory-based energy decomposition analysis (SAPT-EDA) demonstrated the predominance of all the scouted homodimers by the dispersion forces. The obtained results would be beneficial for the omnipresent studies relevant to the applications of halogen bonds in the fields of materials science and crystal engineering

External Electric Field Effect on the Strength of &sigma;-Hole Interactions: A Theoretical Perspective in Like&#8943;Like Carbon-Containing Complexes

For the first time, &sigma;-hole interactions within like&#8943;like carbon-containing complexes were investigated, in both the absence and presence of the external electric field (EEF). The effects of the directionality and strength of the utilized EEF were thoroughly unveiled in the (F-C-F3)2, (F-C-H3)2, and (H-C-F3)2 complexes. In the absence of the EEF, favorable interaction energies, with negative values, are denoted for the (F-C-F3)2 and (H-C-F3)2 complexes, whereas the (F-C-H3)2 complex exhibits unfavorable interactions. Remarkably, the strength of the applied EEF exhibits a prominent role in turning the repulsive forces within the latter complex into attractive ones. The symmetrical nature of the considered like&#8943;like carbon-containing complexes eradicated the effect of directionality of the EEF. The quantum theory of atoms in molecules (QTAIM), and the noncovalent interaction (NCI) index, ensured the occurrence of the attractive forces, and also outlined the substantial contributions of the three coplanar atoms to the total strength of the studied complexes. Symmetry-adapted perturbation theory (SAPT) results show the dispersion-driven nature of the interactions

Chetomin, a SARS-CoV-2 3C-like Protease (3CL^pro) Inhibitor: <i>In Silico</i> Screening, Enzyme Docking, Molecular Dynamics and Pharmacokinetics Analysis

The emergence of the Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 6 million deaths. The 3C-like protease (3CLpro) enzyme of the SARS-CoV-2 virus is an attractive druggable target for exploring therapeutic drug candidates to combat COVID-19 due to its key function in viral replication. Marine natural products (MNPs) have attracted considerable attention as alternative sources of antiviral drug candidates. In looking for potential 3CLpro inhibitors, the MNP database (>14,000 molecules) was virtually screened against 3CLpro with the assistance of molecular docking computations. The performance of AutoDock and OEDocking software in anticipating the ligand-3CLpro binding mode was first validated according to the available experimental data. Based on the docking scores, the most potent MNPs were further subjected to molecular dynamics (MD) simulations, and the binding affinities of those molecules were computed using the MM-GBSA approach. According to MM-GBSA//200 ns MD simulations, chetomin (UMHMNP1403367) exhibited a higher binding affinity against 3CLpro than XF7, with ΔGbinding values of −55.5 and −43.7 kcal/mol, respectively. The steadiness and tightness of chetomin with 3CLpro were evaluated, revealing the high stabilization of chetomin (UMHMNP1403367) inside the binding pocket of 3CLpro throughout 200 ns MD simulations. The physicochemical and pharmacokinetic features of chetomin were also predicted, and the oral bioavailability of chetomin was demonstrated. Furthermore, the potentiality of chetomin analogues –namely, chetomin A-D– as 3CLpro inhibitors was investigated. These results warrant further in vivo and in vitro assays of chetomin (UMHMNP1403367) as a promising anti-COVID-19 drug candidate

Exploring Toxins for Hunting SARS-CoV-2 Main Protease Inhibitors: Molecular Docking, Molecular Dynamics, Pharmacokinetic Properties, and Reactome Study

The main protease (Mpro) is a potential druggable target in SARS-CoV-2 replication. Herein, an in silico study was conducted to mine for Mpro inhibitors from toxin sources. A toxin and toxin-target database (T3DB) was virtually screened for inhibitor activity towards the Mpro enzyme utilizing molecular docking calculations. Promising toxins were subsequently characterized using a combination of molecular dynamics (MD) simulations and molecular mechanics-generalized Born surface area (MM-GBSA) binding energy estimations. According to the MM-GBSA binding energies over 200 ns MD simulations, three toxins&mdash;namely philanthotoxin (T3D2489), azaspiracid (T3D2672), and taziprinone (T3D2378)&mdash;demonstrated higher binding affinities against SARS-CoV-2 Mpro than the co-crystalized inhibitor XF7 with MM-GBSA binding energies of &minus;58.9, &minus;55.9, &minus;50.1, and &minus;43.7 kcal/mol, respectively. The molecular network analyses showed that philanthotoxin provides a ligand lead using the STRING database, which includes the biochemical top 20 signaling genes CTSB, CTSL, and CTSK. Ultimately, pathway enrichment analysis (PEA) and Reactome mining results revealed that philanthotoxin could prevent severe lung injury in COVID-19 patients through the remodeling of interleukins (IL-4 and IL-13) and the matrix metalloproteinases (MMPs). These findings have identified that philanthotoxin&mdash;a venom of the Egyptian solitary wasp&mdash;holds promise as a potential Mpro inhibitor and warrants further in vitro/in vivo validation