Aberrant expression of CD markers in AML in patients attending RIMS, Ranchi - An observational study.

Introduction: Acute myeloid leukaemia (AML) is a tumour of hematopoietic progenitors caused by acquired oncogenic mutations that impede differentiation, leading to the accumulation of immature myeloid blasts in the marrow. Aberrant phenotype is a phenomenon in which lymphoid-associated and other myeloid lineage markers are expressed in myeloblasts or myeloid-associated markers are expressed in lymphoblasts. Materials and Methods: Diagnosed cases of AML were included in this study to study the aberrant expression using multiparametric flow cytometry. Results: Out of a sample size of 50, 30 cases expressed aberrant CD markers. Male: Female ratio was 0.76. Majority of cases belonged to the age group >60 years of age. CD 7 was overall the most common aberrant CD marker. Conclusion: Immunophenotyping has a significant role in diagnosis and predicting prognosis of hematopoietic malignancies in the absence of more advanced diagnostic tools like cytogenetics.

Design, Synthesis, Structural Investigation and Photo Induced Biological Investigations of Co(II), Ni(II) and Cu(II) Complexes Derived from N,O Donor Schiff Bases.

A series of chelated metal complexes, [Co(LI)2] (1), [Ni(LI)2] (2), [Cu(LI)2] (3) [Co(LII)2] (4), [Ni(LII)2] (5) and [Cu(LII)2] (6) were designed and synthesized from newly synthesized Schiff bases, LI = 2-((E)-(5-(4-fluorophenyl)isoxazol-3-ylimino)methyl)-5-methylphenol and LII = 2-((E)-(5-(4-fluorophenyl)isoxazol-3-ylimino)methyl)-4-chlorophenol. The synthesized compounds were characterized by elemental analysis, nuclear magnetic resonance spectroscopy (NMR), electronic spectroscopy (UV-Vis), infrared spectroscopy (FT-IR), magnetic susceptibility (µeff), electron spin resonance spectroscopy (ESR), Thermogravimetric analysis (TGA), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), and powder X-ray diffraction analysis (P-XRD). The spectral investigations have been clearly suggested 1:2 (metal: ligand) stoichiometric complexes with square planar geometrical arrangement around the metal ion. The thermal gravimmetric analysis (TGA) of these complexes indicates greater thermal stability and various steps involved in thermal decomposition of metal complexes. The binding ability between these metal complexes and calf thymus DNA (CT-DNA) was investigated by UV-Vis, fluorescence spectroscopy and viscometric experiments, which disclosed that, the complexes interacted to CT-DNA via an intercalation binding mode. The cleavage property of metal complexes against pBR322 DNA has been explored by gel electrophoresis technique mediated by UV-illumination and H2O2, showed momentous cleavage activity. Antioxidant activity of all complexes was determined by DPPH free radical scavenging experiment and showed prominent antioxidant activity. Further, the antibacterial and antifungal activities of all compounds were screened against bacterial and fungal strains via in-vitro disc diffusion method. These studies revealed that the complexes showed comparatively more antimicrobial activity than free ligands against tested microbial strains.

An Evaluation of Medical Students' Perceptions, Knowledge, and Attitudes About People With Disability After Attending the Learning Session on Disability Competency: A Cross-Sectional Study.

Background and objective The Medical Council of India [now replaced by the National Medical Commission (NMC)] has implemented a new competency-based curriculum for medical education. Eight competencies in the curriculum are related to the principles of disability-inclusive compassionate care. This study aimed to evaluate the knowledge, perceptions, and attitudes among undergraduate medical students about people with disability after attending learning sessions on disability competency. Materials and methods After they attended the learning session during the foundation course, participants were evaluated by using a questionnaire involving 26 questions, of which 17 were based on the Likert scale to assess general perceptions towards the person with a disability, while three questions aimed to assess attitudes, and six closed-ended questions tried to assess knowledge about disability. Results In the present study, 79.7% (n=157) of the students thought that people with disabilities faced problems getting involved in society, and 81.2% (n=160) felt that it was harder for them to make friends than others. The majority of the students disagreed with the idea that people with disabilities are a burden on society (n=149, 75.6%) or their families (n=119, 60.4%); 65% (n=128) of the students thought that people with disabilities are more determined than others to reach their goals and achieve more owing to their disability (n=104, 52.85%). A total of 161 (81.7%) students disagreed with the statement that people with disabilities should not be optimistic about their future. A comparison of the pre- and post-test data revealed that students' knowledge regarding disability increased and they gained a more positive attitude towards people with a disability after attending teaching and learning sessions (p<0.0001). Conclusion Our findings showed a significant improvement in the undergraduate medical students' understanding and empathy toward individuals with disabilities following sessions on disability competency. Teaching and learning sessions on disability competencies for newly admitted students in medical school can sensitize, orient, increase knowledge, and develop positive attitudes toward people with disabilities. Further studies on the topic are needed involving different phases of clinical teaching.

Evaluating the Diagnostic Potential of Serum Vascular Endothelial Growth Factor and Adiponectin in Diabetic Peripheral Neuropathy.

INTRODUCTION: Diabetic peripheral neuropathy (DPN) presents a formidable health challenge in type 2 diabetes mellitus (T2DM) patients. This study in eastern Uttar Pradesh aims to assess the roles of vascular endothelial growth factor (VEGF) and adiponectin in DPN, recognizing the crucial need for understanding its molecular underpinnings for enhanced diagnosis and management. METHODS: In a cross-sectional study analyzing clinical and biochemical data, 86 individuals aged 35 to 65 years were examined, including 43 with neuropathy and 43 without. Neuropathy assessment included the neuropathy symptom score (NSS), diabetes neuropathy examination (DNE) score, and nerve conduction studies. Levels of VEGF and adiponectin were correlated with motor nerve amplitude, NSS, and DNE scores. Receiver operating characteristic (ROC) curve analysis gauged diagnostic potential, and logistic regression assessed predictors for DPN. RESULTS: Patients with neuropathy exhibited significantly elevated VEGF levels compared to those without, while adiponectin showed no significant difference. VEGF demonstrated a negative correlation with motor nerve amplitude and a positive correlation with NSS and DNE scores. ROC analysis revealed strong diagnostic capability for VEGF (area under the curve: 0.807). NSS and DNE scores indicated good and moderate diagnostic accuracy, respectively. In logistic regression analysis, VEGF emerged as the sole significant predictor (odds ratio: 1.11, 95% CI (1.03, 1.20), p = 0.0092). CONCLUSION: Findings suggest VEGF's potential as a biomarker for diagnosing DPN in T2DM, associated with neuropathy severity. Adiponectin showed no significant association. The study underscores NSS and DNE scores' therapeutic relevance as valid neuropathy assessment tools.

Unveiling the healing properties of 2,3-dehydrosilychristin: a potential silymarin-derived flavonolignan from Vitex negundo.

The compound 2,3-dehydrosilychristin, a flavonolignan linked to silychristin and silymarin, remains intriguing due to its challenging isolation from silymarin. While silymarin has been the exclusive source of flavonolignans - silybin, silychristin and silydianin - 2,3-dehydrosilychristin is reported in this study from Vitex negundo Linn. leaves. 2,3-Dehydrosilychristin (7) and 14 other compounds were isolated through focused extraction. Its subsequent pharmacological evaluation demonstrated potent antioxidant and in-vitro anti-inflammatory effects, notably inhibiting cytokines TNF-α, IL-6, IL-8 and VEGF. In in-vivo assessments, 2,3-dehydrosilychristin (7) revealed remarkable hepatoprotective potential by reducing liver enzyme levels AST and ALT. These findings expand the potential of 2,3-dehydrosilychristin and suggest bioprospecting Vitex species as alternate sources of bioactive flavonolignans.

Semecarpus anacardium L.f. leaf extract exhibits activities against breast cancer and prolongs the survival of tumor-bearing mice.

Semecarpus anacardium L.f. has been commonly used in various traditional medicines from ancient times. The nuts have been described in Ayurveda medication systems to treat numerous clinical ailments. However, isolating phytochemical constituents from nuts remain challenging and exhibits cytotoxic effects on other cells. In this study, we have standardized procedures for isolating phytochemicals from the leaf extract. The ethyl acetate leaf extract selectively affects cancer cells in a dose-dependent manner (IC50: 0.57 µg/ml in MCF-7 cells) in various cancer cell lines and induces apoptosis in cancer cells. However, the non-malignant cells were relatively insensitive to the extract. Next, the incubation of the leaf extract induces cell cycle arrest and suppresses cancer cell migration in the cell culture model. Moreover, oral administration of extract significantly restored tumor growth in mice. Together, these observations suggest the anti-cancer activities of S. anacardium L.f. leaf potential for both in vitro and in vivo models.

Validation of the VirCapSeq-VERT system for differential diagnosis, detection, and surveillance of viral infections.

IMPORTANCE: Broad range assay for accurate and sensitive diagnostics.

Rapid eye movement sleep loss associated cytomorphometric changes and neurodegeneration.

Rapid eye movement sleep (REMS) is essential for leading normal healthy living at least in higher-order mammals, including humans. In this review, we briefly survey the available literature for evidence linking cytomorphometric changes in the brain due to loss of REMS. As a mechanism of action, we add evidence that REMS loss elevates noradrenaline (NA) levels in the brain, which affects neuronal cytomorphology. These changes may be a compensatory mechanism as the changes return to normal after the subjects recover from the loss of REMS or if during REMS deprivation, the subjects are treated with NA-adrenoceptor antagonist prazosin (PRZ). We had proposed earlier that one of the fundamental functions of REMS is to maintain the level of NA in the brain. We elaborate on this idea to propose that if REMS loss continues without recovery, the sustained level of NA breaks down neurophysiologically active compensatory mechanism/s starting with changes in the neuronal cytomorphology, followed by their degeneration, leading to acute and chronic pathological conditions. Identification of neuronal cytomorphological changes could prove to be of significance for predicting future neuronal (brain) damage as well as an indicator for REMS health. Although current brain imaging techniques may not enable us to visualize changes in neuronal cytomorphology, given the rapid technological progress including use of artificial intelligence, we are optimistic that it may be a reality soon. Finally, we propose that maintenance of optimum REMS must be considered a criterion for leading a healthy life.

Revisiting the Role of CD63 as Pro-Tumorigenic or Anti-Tumorigenic Tetraspanin in Cancers and its Theragnostic Implications.

Cluster of differentiation antigen 63 (CD63) belongs to a superfamily of proteins, usually defined as tetraspanins which are known to transverse the bilayer membranes four times. The expression of CD63 has been shown to get altered in several cancers, where it has been demonstrated to act as both a tumor promoter and tumor suppressor. The present review describes the mechanism of how CD63 promotes tumor formation in certain cancer types while inhibiting in some other specific cancers. Glycosylation, a post-translational process plays a significant role in regulating the expression and function of these membrane proteins. Being a crucial exosomal flag protein, CD63 has been found to get involved in endosomal cargo sorting as well as the production of extracellular vesicles. Increased expression of exosomal CD63 derived from advanced tumors has demonstrated its role in promoting metastasis. CD63 also regulates the characteristic and function of stem cells on which they get expressed. This particular tetraspanin has been discovered to participate in gene fusion to perform distinctive roles in certain specific cancer types like breast cancer and pigmented epithelioid melanocytoma. Furthermore, this review mentions twelve different microRNAs obtained from miRDB that might target CD63. A few theragnostic uses of this membrane protein are also discussed. Thereby, the review indicates that further studies on CD63 might prove it to be an effective therapeutic target in different cancers in the coming future.

Partial Activation of PPAR-γ by Synthesized Quercetin Derivatives Modulates TGF-ß1-Induced EMT in Lung Cancer Cells.

Non-small cell lung cancer (NSCLC) has a very low survival rate due to poor response to chemotherapy and late detection. Epithelial to mesenchymal transition (EMT) is regarded as a major contributor to drive metastasis during NSCLC progression. Towards this, transforming growth factor-beta 1 (TGF-ß1) is the key driver that endows cancer cells with increased aggressiveness. Recently, this group synthesized a series of Schiff base quercetin derivatives (QDs) and ascertained their effectiveness on EMT markers of A549 cell line. This study evidenced that the EMT process is counteracted via the partial activation of a nuclear hormone receptor, Peroxisome proliferator-activated receptor (PPAR)-γ through QDs. Here, that work is extended to investigate the interplay between PPAR-γ partial activation and TGF-ß1-induced EMT in human lung cancer A549 cells. The results reveal that TGF-ß1 plays a critical role in suppressing PPAR-γ, which is markedly reversed and increased by partial agonists: QUE2FH and QUESH at both protein and transcriptional levels. The partial agonists not only stimulate PPAR-γ in a balanced manner but also prevent the loss of E-cadherin and acquisition of TGF-ß1-induced mesenchymal markers (Snail, Slug, Vimentin, and Zeb-1). Subsequently, the effects are accompanied by attenuation of TGF-ß1-induced migratory ability of A549 cells.

Design, Synthesis, and Biological Evaluation of Novel Quercetin Derivatives as PPAR-γ Partial Agonists by Modulating Epithelial-Mesenchymal Transition in Lung Cancer Metastasis.

Epithelial-to-mesenchymal transition (EMT) is responsible for driving metastasis of multiple cancer types including lung cancer. Peroxisome proliferator-activated receptor (PPAR)-γ, a ligand-activated transcription factor, controls expression of variety of genes involved in EMT. Although several synthetic compounds act as potent full agonists for PPAR-γ, their long term application is restricted due to serious adverse effects. Therefore, partial agonists involving reduced and balanced PPAR-γ activity are more effective and valued. A previous study discerned the efficacy of quercetin and its derivatives to attain favorable stabilization with PPAR-γ. Here this work is extended by synthesizing five novel quercetin derivatives (QDs) namely thiosemicarbazone (QUETSC)) and hydrazones (quercetin isonicotinic acid hydrazone (QUEINH), quercetin nicotinic acid hydrazone (QUENH), quercetin 2-furoic hydrazone (QUE2FH), and quercetin salicyl hydrazone (QUESH)) and their effects are analyzed in modulating EMT in lung cancer cell lines via PPAR-γ partial activation. QDs-treated A549 cells diminish cell proliferation strongly at nanomolar concentration compared to NCI-H460 cells. Of the five screened derivatives, QUETSC, QUE2FH, and QUESH exhibit the property of partial activation as compared to the overexpressive level of rosiglitazone. Consistently, these QDs also suppress EMT process by markedly downregulating the levels of mesenchymal markers (Snail, Slug, and zinc finger E-box binding homeobox 1) and concomitant upregulation of epithelial marker (E-cadherin).

Complimentary effect of exogenous enzymes, essential amino acids and essential fatty acids supplemented de-oiled rice bran (DORB) based diets on hematology, liver and intestinal histoarchitecture in Labeo rohita.

A 60-day feeding trial was conducted to study the hematology, liver, and intestinal histoarchitecture of Labeo rohita fed with a combination of exogenous enzymes, essential amino acids, and essential fatty acids to DORB (De-oiled rice bran) based diets. Three treatments viz., T1 [DORB + phytase and xylanase (0.01% each)], T2 [DORB + phytase (0.01%) + xylanase (0.01%) + L-lysine(1.4%) + L-methionine (0.4%) + EPA and DHA (0.5%)] and T3 [DORB + phytase (0.01%), xylanase and cellulase (0.075%) + L-lysine (1.4%) +L-methionine (0.4%) + EPA and DHA (0.5%)] were used in the present study. Serum total protein, albumin content and A/G ratio varied significantly (p < 0.05) among groups. Globulin content did not vary significantly among groups (p ≥ 0.05). The Hb content, RBC and MCV count varied significantly (p < 0.05) whereas MCH, MCHC content, WBC and lymphocyte count did not vary significantly among groups (p > 0.05). The liver and intestine examination revealed no visible alteration and showed normal histo-architecture. Based on the finding it is concluded that DORB supplemented with exogenous enzymes, essential amino acids and essential fatty acids with phytase (0.01%), xylanase and cellulase (0.075%), L-lysine (1.4%), DL-methionine (0.4%) and EPA and DHA (0.5%) improves the health of L. rohita.

Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained debilitating fatigue, cognitive dysfunction, gastrointestinal disturbances, and orthostatic intolerance. Here, we report a multi-omic analysis of a geographically diverse cohort of 106 cases and 91 healthy controls that revealed differences in gut microbiome diversity, abundances, functional pathways, and interactions. Faecalibacterium prausnitzii and Eubacterium rectale, which are both recognized as abundant, health-promoting butyrate producers in the human gut, were reduced in ME/CFS. Functional metagenomics, qPCR, and metabolomics of fecal short-chain fatty acids confirmed a deficient microbial capacity for butyrate synthesis. Microbiome-based machine learning classifier models were robust to geographic variation and generalizable in a validation cohort. The abundance of Faecalibacterium prausnitzii was inversely associated with fatigue severity. These findings demonstrate the functional nature of gut dysbiosis and the underlying microbial network disturbance in ME/CFS, providing possible targets for disease classification and therapeutic trials.

Molecule generation toward target protein (SARS-CoV-2) using reinforcement learning-based graph neural network via knowledge graph.

AI-driven approaches are widely used in drug discovery, where candidate molecules are generated and tested on a target protein for binding affinity prediction. However, generating new compounds with desirable molecular properties such as Quantitative Estimate of Drug-likeness (QED) and Dopamine Receptor D2 activity (DRD2) while adhering to distinct chemical laws is challenging. To address these challenges, we proposed a graph-based deep learning framework to generate potential therapeutic drugs targeting the SARS-CoV-2 protein. Our proposed framework consists of two modules: a novel reinforcement learning (RL)-based graph generative module with knowledge graph (KG) and a graph early fusion approach (GEFA) for binding affinity prediction. The first module uses a gated graph neural network (GGNN) model under the RL environment for generating novel molecular compounds with desired properties and a custom-made KG for molecule screening. The second module uses GEFA to predict binding affinity scores between the generated compounds and target proteins. Experiments show how fine-tuning the GGNN model under the RL environment enhances the molecules with desired properties to generate 100 % valid and 100 % unique compounds using different scoring functions. Additionally, KG-based screening reduces the search space of generated candidate molecules by 96.64 % while retaining 95.38 % of promising binding molecules against SARS-CoV-2 protein, i.e., 3C-like protease (3CLpro). We achieved a binding affinity score of 8.185 from the top rank of generated compound. In addition, we compared top-ranked generated compounds to Indinavir on different parameters, including drug-likeness and medicinal chemistry, for qualitative analysis from a drug development perspective. Supplementary Information: The online version contains supplementary material available at 10.1007/s13721-023-00409-2.

Synthesis of Iron Nanoparticles Using Sargassum wightii Extract and Its Impact on Serum Biochemical Profile and Growth Response of Etroplus suratensis Juveniles.

The present study focuses on the green synthesis of iron nanoparticles using plant extracts as reducing, capping, and stabilizing agents. Aqueous seaweed extracts with the addition of iron solution were mixed using a magnetic stirrer which resulted in a color change indicating the formation of iron nanoparticles. The iron nanoparticles were successfully synthesized using Sargassum wightii extract. The synthesized iron nanoparticles were characterized by UV-Vis spectrophotometer, Fourier transform infrared spectroscopy (FTIR), and zeta potential techniques. The UV-Vis spectra showed a peak at 412 to 415 nm. Zeta potential revealed that the synthesized iron nanoparticles were negative and positive charges. FTIR spectroscopy analysis showed the presence of chemical bond and amide group likely to be responsible for the green synthesis of iron nanoparticles. The effect of nano-iron as a dietary iron source on the growth and serum biochemical profile of Etroplus suratensis fingerlings was evaluated. Iron nanoparticles were fed to E. suratensis fingerlings for 60 days with two levels 10 mg (T1) and 20 mg (T2) and a control group without iron nanoparticles. The highest WG% and SGR and lowest FCR were observed in the T2 group which is significantly different (p < 0.05) from other groups. The serum biochemical profile showed significantly increased activity on 20 mg/kg of nano-iron-supplemented diet. The findings of the present study concluded that supplementation of nano-iron at the 20 mg/kg level to the regular fish diet has a better impact not only on growth but also on the overall health of the fish.

Unraveling the Role of Tumor Necrosis Factor-Alpha in Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

Diabetic peripheral neuropathy (DPN) is a prevalent and debilitating complication of diabetes mellitus, leading to sensory abnormalities, decreased balance, and increased risk of foot problems. Although tumor necrosis factor-alpha (TNF-α) has emerged as a potential factor in the pathogenesis of DPN, its role remains contested. This study intends to thoroughly analyze the association between TNF-α and DPN by combining data from various global studies. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and included 23 articles investigating TNF-α levels in DPN patients for systematic review and 11 articles for meta-analysis. Data were extracted, and heterogeneity was examined. A random-effect model was chosen due to high heterogeneity. The major outcome measure across studies was serum TNF-α levels. The meta-analysis found a significant mean difference of 15.2464 (95% confidence interval = 4.4963; 25.9965) under the random-effect model due to the substantial heterogeneity (I2 = 98.1%) among included studies. The meta-analysis indicates a consistent elevation in TNF-α levels in individuals with DPN compared to those without neuropathy. This underlines the potential of TNF-α as a biomarker and contributor to diabetic neuropathy. Despite heterogeneity, the study's extensive scope and systematic approach enhance the trustworthiness and generalizability of the findings.

Repercussions of Caregiving on Caregivers of Stroke Survivors: A Cross-Sectional Study.

BACKGROUND: Stroke is one of the most common causes of disability. Stroke survivors may have a wide variety of sensorimotor, cognitive, perceptual, and behavioral dysfunctions. The majority of long-term care for stroke survivors in residential settings is provided by informal caregivers, such as family members. This study was conducted to assess the burden of caregiving on caregivers of stroke survivors. MATERIALS AND METHODS: This cross-sectional study was conducted by the Department of Physical Medicine and Rehabilitation in a tertiary care institute in Western India. Patients were evaluated for inclusion and exclusion criteria. Caregiver strain among caregivers was assessed using the Modified Caregiver Strain Index Questionnaire (MCSI). The Katz index was used to assess activities of daily living. RESULTS: The inclusion and exclusion criteria were fulfilled by 125 primary caregivers of stroke patients. Among stroke survivors, the majority were male (57.6%), and caregivers were wives of stroke survivors (28.8%). There was a significant statistical difference in the median of the modified caregiver strain index when the stroke survivor was male (p=0.034), fully dependent (p<0.001), and had a hemorrhagic stroke (p<0.001). There was no significant statistical difference in the median of the MCSI based on the sex of caregivers (p=0.928). There was a positive correlation between the age of the patient and MCSI (r=0.373, p<0.001). No correlation was found between the MCSI and age of caregivers (r=-0.108, p=0.230) and duration of stroke (r=-0.089, p=0.321). CONCLUSION: The findings in our study provide evidence that caregivers of stroke survivors experience significant levels of strain. It is desirable to recognize caregiver strain during the rehabilitation of stroke survivors and manage it appropriately.

PPAR-γ Partial Agonists in Disease-Fate Decision with Special Reference to Cancer.

Peroxisome proliferator-activated receptor-γ (PPAR-γ) has emerged as one of the most extensively studied transcription factors since its discovery in 1990, highlighting its importance in the etiology and treatment of numerous diseases involving various types of cancer, type 2 diabetes mellitus, autoimmune, dermatological and cardiovascular disorders. Ligands are regarded as the key determinant for the tissue-specific activation of PPAR-γ. However, the mechanism governing this process is merely a contradictory debate which is yet to be systematically researched. Either these receptors get weakly activated by endogenous or natural ligands or leads to a direct over-activation process by synthetic ligands, serving as complete full agonists. Therefore, fine-tuning on the action of PPAR-γ and more subtle modulation can be a rewarding approach which might open new avenues for the treatment of several diseases. In the recent era, researchers have sought to develop safer partial PPAR-γ agonists in order to dodge the toxicity induced by full agonists, akin to a balanced activation. With a particular reference to cancer, this review concentrates on the therapeutic role of partial agonists, especially in cancer treatment. Additionally, a timely examination of their efficacy on various other disease-fate decisions has been also discussed.

GAN for synthesizing CT from T2-weighted MRI data towards MR-guided radiation treatment.

OBJECTIVE: In medical domain, cross-modality image synthesis suffers from multiple issues , such as context-misalignment, image distortion, image blurriness, and loss of details. The fundamental objective behind this study is to address these issues in estimating synthetic Computed tomography (sCT) scans from T2-weighted Magnetic Resonance Imaging (MRI) scans to achieve MRI-guided Radiation Treatment (RT). MATERIALS AND METHODS: We proposed a conditional generative adversarial network (cGAN) with multiple residual blocks to estimate sCT from T2-weighted MRI scans using 367 paired brain MR-CT images dataset. Few state-of-the-art deep learning models were implemented to generate sCT including Pix2Pix model, U-Net model, autoencoder model and their results were compared, respectively. RESULTS: Results with paired MR-CT image dataset demonstrate that the proposed model with nine residual blocks in generator architecture results in the smallest mean absolute error (MAE) value of [Formula: see text], and mean squared error (MSE) value of [Formula: see text], and produces the largest Pearson correlation coefficient (PCC) value of [Formula: see text], SSIM value of [Formula: see text] and peak signal-to-noise ratio (PSNR) value of [Formula: see text], respectively. We qualitatively evaluated our result by visual comparisons of generated sCT to original CT of respective MRI input. DISCUSSION: The quantitative and qualitative comparison of this work demonstrates that deep learning-based cGAN model can be used to estimate sCT scan from a reference T2 weighted MRI scan. The overall accuracy of our proposed model outperforms different state-of-the-art deep learning-based models.

Generating novel molecule for target protein (SARS-CoV-2) using drug-target interaction based on graph neural network.

The transmittable spread of viral coronavirus (SARS-CoV-2) has resulted in a significant rise in global mortality. Due to lack of effective treatment, our aim is to generate a highly potent active molecule that can bind with the protein structure of SARS-CoV-2. Different machine learning and deep learning approaches have been proposed for molecule generation; however, most of these approaches represent the drug molecule and protein structure in 1D sequence, ignoring the fact that molecules are by nature in 3D structure, and because of this many critical properties are lost. In this work, a framework is proposed that takes account of both tertiary and sequential representations of molecules and proteins using Gated Graph Neural Network (GGNN), Knowledge graph, and Early Fusion approach. The generated molecules from GGNN are screened using Knowledge Graph to reduce the search space by discarding the non-binding molecules before being fed into the Early Fusion model. Further, the binding affinity score of the generated molecule is predicted using the early fusion approach. Experimental result shows that our framework generates valid and unique molecules with high accuracy while preserving the chemical properties. The use of a knowledge graph claims that the entire generated dataset of molecules was reduced by roughly 96% while retaining more than 85% of good binding desirable molecules and the rejection of more than 99% of fruitless molecules. Additionally, the framework was tested with two of the SARS-CoV-2 viral proteins: RNA-dependent-RNA polymerase (RdRp) and 3C-like protease (3CLpro).