Abid Qureshi - Academia.edu (original) (raw)
Papers by Abid Qureshi
Stroke, 2020
Introduction: Perfusion imaging can identify patients who respond favorably to endovascular thera... more Introduction: Perfusion imaging can identify patients who respond favorably to endovascular therapy (EVT) in the anterior circulation; no data are available for the posterior circulation. We evaluated perfusion patterns, assessed with RAPID software, in a consecutive cohort of patients with basilar artery occlusion treated with EVT and assessed the association between reperfusion and favorable clinical outcome based on the perfusion profile. Hypothesis: We hypothesized that patients with limited regions of severe hypoperfusion (Tmax > 10s) would have a favorable response (mRS 0-2) to reperfusion (mTICI 2b-3) while patients with multiple critical brain regions severely hypoperfused would have poor outcome (mRS 4-6) despite reperfusion. Methods: From a multicenter cohort of perfusion imaging in posterior circulation stroke, we included patients with basilar artery occlusion and EVT. We pre-specified a Critical Area Perfusion Score (CAPS, 0 - 8 points) to identify severe hypoperfusi...
Additional file 1. Supporting information including Table S1. Performance of QSAR predictive mode... more Additional file 1. Supporting information including Table S1. Performance of QSAR predictive models on three times randomly picked ~ 10% independent/validation data. These models were developed using remaining ~ 90% data during training/testing respectively for each of the six datasets; Table S2. Details of statistical parameters used for the development of IC50 based QSAR models; Table S3. Details of statistical parameters used for the development of percent inhibition based QSAR models; Table S4. Details of chemical descriptors used in the development of IC50 based QSAR models; Table S5. Details of chemical descriptors used in the development of percent inhibition based QSAR models; Table S6. Details of slopes k (predicted vs. observed inhibition) and k' (observed vs. predicted inhibition) of the regression lines for the QSAR models; Table S7. Details of Y-randomization test performed on the QSAR models; Figure S1. Chemical space analysis of QSAR studies (Table 5) for Protease...
Stroke, 2020
Introduction: The vascular territory of an occluded large intracranial vessel can be reliably ide... more Introduction: The vascular territory of an occluded large intracranial vessel can be reliably identified by CT or MR perfusion imaging. Furthermore, prior studies have shown that perfusion imaging can reliably predict the specific vessel that is occluded in anterior circulation large vessel strokes. We evaluated whether perfusion imaging can predict the specific vessel occlusion (vertebral, basilar, or posterior cerebral) in posterior circulation strokes. Hypothesis: We hypothesized that the occluded vessel could be inferred from the perfusion imaging results in >80% of patients with an acute stroke due to large vessel occlusion in the posterior circulation using the simultaneous CTA or MRA as the gold standard. Furthermore, the inter-rater agreement between a vascular neurologist and a neuroradiologist would be > 90%. Agreement Coefficients (AC1) were determined. Methods: From a multicenter cohort of consecutive patients with posterior circulation stroke, we included patients...
Helicobacter pylori (H. pylori ) are a widespread kind of bacteria which flourish in the digestiv... more Helicobacter pylori (H. pylori ) are a widespread kind of bacteria which flourish in the digestive tract and have a propensity to damage the stomach lining. The microbe infects around 60% of the adults globally. H. pylori infections are responsible for most of stomach and small intestine ulcers. Using Bioinformatics approaches, we have identified certain proteins that possess the resistance, essentiality and virulence factors for this pathogen. Computational tools and servers were used for the identification of MHC class I, II and B cell epitopes. The set of chosen epitopes were also filtered as per their immunogenic and toxicity potentials. Designed vaccine construct was docked against multiple HLA targets employing virtual modeling. Therefore the designated vaccine constructs may be developed to control the infection caused by H. pylori .
Handbook of Research on Advancements in Cancer Therapeutics, 2021
Cancer is the second biggest killer worldwide. It has been estimated that specific lifestyle and ... more Cancer is the second biggest killer worldwide. It has been estimated that specific lifestyle and dietary measures can prevent 30–40% of all cancers. Consumption of nutrient sparse foods, such as refined flour products and concentrated sugars, consumption of red meat, low fibre intake, and disproportion of omega 3 and omega 6 fatty acids, contributes to cancer risks. Microbiological and chemical food contaminants as well as conventional and industrial food processing methods may further increase the carcinogenicity of diets while protective agents in a cancer prevention diet include folic acid, selenium, vitamin D, vitamin B-12, chlorophyll, and antioxidants such as the carotenoids, kryptoxanthin, lycopene, and lutein. Diet can also influence the gut microbes that may have positive or adverse effects on cancer risk. The authors summarize cancer prevention by functional foods and discuss the role of different dietary factors such as promoter or inhibitor in pathogenesis of different s...
Journal of the American College of Cardiology, 2020
Background: Use of direct oral anticoagulants (DOACs) for the treatment of left ventricular (LV) ... more Background: Use of direct oral anticoagulants (DOACs) for the treatment of left ventricular (LV) thrombus has gained considerable interest. Objective: We aimed to evaluate if DOACs are effective in the treatment of LV thrombus compared with warfarin. Methods: We evaluated the medical records of patients diagnosed with a new LV thrombus at a tertiary medical center. The primary outcome was the composite of thrombus persistence, stroke, or systemic embolism. We adjusted for potential confounders using multiple logistic regression. The safety outcome was the composite of hemorrhagic stroke or bleeding requiring blood transfusion. Results: A total of 129 patients were treated with warfarin and 22, with a DOAC. In unadjusted analysis, 54.3% of patients treated with warfarin met criteria for the efficacy outcome as compared with 40.9% of patients treated with a DOAC (P = 0.25). In adjusted analysis, no difference between groups was observed (odds ratio = 0.39; 95% CI = 0.14-1.06; P = 0.07 for DOAC vs warfarin). In all, 3.9% of patients treated with warfarin met safety criteria as compared with 4.5% of patients treated with a DOAC. A total of 8 patients in the warfarin group had a stroke or systemic embolism as compared with 0 patients in the DOAC group (P = 0.37). Conclusion and Relevance: Our data suggest that DOACs may be reasonable alternatives for treatment of LV thrombus. When added to the totality of available studies, this study demonstrates that the effectiveness of DOACs in LV thrombus remains uncertain. Randomized clinical trials are needed.
Journal of Clinical Oncology, 2015
8568 Background: DLBCL is a heterogeneous disease. Gene expression profile (GEP) based distinctio... more 8568 Background: DLBCL is a heterogeneous disease. Gene expression profile (GEP) based distinction into ABC and GCB sub-types, provides basis for risk stratification in DLBCL patients. GEP is an in...
Reviews in Medical Virology, 2018
Viral diseases like influenza, AIDS, hepatitis, and Ebola cause severe epidemics worldwide. Along... more Viral diseases like influenza, AIDS, hepatitis, and Ebola cause severe epidemics worldwide. Along with their resistant strains, new pathogenic viruses continue to be discovered so creating an ongoing need for new antiviral treatments. RNA interference is a cellular gene-silencing phenomenon in which sequence-specific degradation of target mRNA is achieved by means of complementary short interfering RNA (siRNA) molecules. Short interfering RNA technology affords a potential tractable strategy to combat viral pathogenesis because siRNAs are specific, easy to design, and can be directed against multiple strains of a virus by targeting their conserved gene regions. In this review, we briefly summarize the current status of siRNA therapy for representative examples from different virus families. In addition, other aspects like their design, delivery, medical significance, bioinformatics resources, and limitations are also discussed.
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2018
Hepatitis C virus plays a significant role in the development of hepatocellular carcinoma (HCC) g... more Hepatitis C virus plays a significant role in the development of hepatocellular carcinoma (HCC) globally. The pathogenic mechanisms of hepatocellular carcinoma with HCV infection are generally linked with inflammation, cytokines, fibrosis, cellular signaling pathways, and liver cell proliferation modulating pathways. HCV encoded proteins (Core, NS3, NS4, NS5A) interact with a broad range of hepatocytes derived factors to modulate an array of activities such as cell signaling, DNA repair, transcription and translational regulation, cell propagation, apoptosis, membrane topology. These four viral proteins are also implicated to show a strong conversion potential in tissue culture. Furthermore, Core and NS5A also trigger the accretion of the β-catenin pathway as a common target to contribute viral induced transformation. There is a strong association between HCV variants within Core, NS4, and NS5A and host single nucleotide polymorphisms (SNPs) with the HCC pathogenesis. Identification...
Journal of cheminformatics, Jan 9, 2018
A number of anti-retroviral drugs are being used for treating Human Immunodeficiency Virus (HIV) ... more A number of anti-retroviral drugs are being used for treating Human Immunodeficiency Virus (HIV) infection. Due to emergence of drug resistant strains, there is a constant quest to discover more effective anti-HIV compounds. In this endeavor, computational tools have proven useful in accelerating drug discovery. Although methods were published to design a class of compounds against a specific HIV protein, but an integrated web server for the same is lacking. Therefore, we have developed support vector machine based regression models using experimentally validated data from ChEMBL repository. Quantitative structure activity relationship based features were selected for predicting inhibition activity of a compound against HIV proteins namely protease (PR), reverse transcriptase (RT) and integrase (IN). The models presented a maximum Pearson correlation coefficient of 0.78, 0.76, 0.74 and 0.76, 0.68, 0.72 during tenfold cross-validation on ICand percent inhibition datasets of PR, RT, I...
The Journal of Bone and Joint Surgery-American Volume, 2003
The best method of reconstructing osteoarticular defects to maintain joint stability and prevent ... more The best method of reconstructing osteoarticular defects to maintain joint stability and prevent early degenerative joint disease has yet to be resolved. Buckwalter broadly divided the treatment strategies into two types 1 : those that stimulate repair or regeneration of articular cartilage and those that involve transplantation of an articular surface. However, these methods do not provide the osseous support that may be needed when bone loss has occurred in the epiphysis. We report the case of a three-year-old patient in whom massive osteoarticular bone loss from the medial tibial plateau of the left leg, due to a lawn-mower injury, was treated with the Ilizarov technique of distraction histogenesis. To our knowledge, this is the first time that this method has been utilized to repair an osteochondral defect. Our patient was informed that data concerning the case would be submitted for publication. A three-year-old boy sustained an injury to the left leg from a lawn mower. He sustained soft-tissue and bone loss on the medial aspect of the proximal part of the left tibia and knee. The medial tibial plateau, including the articular cartilage, was missing, and there was a fracture through the remaining proximal tibial physis. A gastrocnemius-muscle pedicle graft and a split-thickness skin graft were used to cover the soft-tissue defect. The detached patellar tendon was sutured back in the region of the tibial tubercle. Six months after the initial injury, a nonunion of the proximal tibial physeal fracture ( Fig. 1 ) was treated with open reduction and iliac-crest bone grafting and screw fixation. The bone healed in three months ( Fig. 2 ) but with medial instability at the knee joint, which was controlled with a hinged knee-ankle-foot orthosis. The knee had an extension lag of 20° secondary to quadriceps weakness. Fig. 1: Anteroposterior and lateral radiographs of …
G3 (Bethesda, Md.), Sep 10, 2017
Allele-specific siRNAs (ASP-siRNAs) have emerged as promising therapeutic molecules owing to thei... more Allele-specific siRNAs (ASP-siRNAs) have emerged as promising therapeutic molecules owing to their selectivity to inhibit the mutant allele or associated single nucleotide polymorphisms (SNPs) sparing the expression of the wild-type counterpart. Thus, a dedicated bioinformatics platform encompassing updated ASP-siRNAs and an algorithm for the prediction of their inhibitory efficacy will be helpful in tackling currently intractable genetic disorders. In the present study, we have developed the ASPsiRNA resource (http://crdd.osdd.net/servers/aspsirna/) covering three components viz (i) ASPsiDb (ii) ASPsiPred and (iii) analysis tools like ASP-siOffTar. ASPsiDb is a manually curated database harboring 4543 (including 422 chemically modified) ASP-siRNAs targeting 78 unique genes involved in 51 different diseases. It furnishes comprehensive information from experimental studies on ASP-siRNAs along with multidimensional genetic and clinical information for numerous mutations. ASPsiPred is ...
Chemical biology & drug design, Jan 4, 2016
Viral infections constantly jeopardize the global public health due to lack of effective antivira... more Viral infections constantly jeopardize the global public health due to lack of effective antiviral therapeutics. Therefore, there is an imperative need to speed up the drug discovery process to identify novel and efficient drug candidates. In the present study, we have developed Quantitative structure-activity relationship (QSAR) based models for predicting Antiviral compounds (AVCs) against deadly viruses like Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), Hepatitis B virus (HBV), Human herpesvirus (HHV) and 26 others using publicly available experimental data from the ChEMBL bioactivity database. Support Vector Machine (SVM) models achieved a maximum Pearson Correlation Coefficient of 0.72, 0.74, 0.66, 0.68 and 0.71 in regression mode and a maximum Matthew's correlation coefficient 0.91, 0.93, 0.70, 0.89 and 0.71 respectively in classification mode during 10-fold cross-validation. Furthermore, similar performance was observed on the independent validation sets. W...
Scientific Reports, 2016
Small interfering RNA (siRNA) technology has vast potential for functional genomics and developme... more Small interfering RNA (siRNA) technology has vast potential for functional genomics and development of therapeutics. However, it faces many obstacles predominantly instability of siRNAs due to nuclease digestion and subsequently biologically short half-life. Chemical modifications in siRNAs provide means to overcome these shortcomings and improve their stability and potency. Despite enormous utility bioinformatics resource of these chemically modified siRNAs (cm-siRNAs) is lacking. Therefore, we have developed siRNAmod, a specialized databank for chemically modified siRNAs. Currently, our repository contains a total of 4894 chemically modified-siRNA sequences, comprising 128 unique chemical modifications on different positions with various permutations and combinations. It incorporates important information on siRNA sequence, chemical modification, their number and respective position, structure, simplified molecular input line entry system canonical (SMILES), efficacy of modified siRNA, target gene, cell line, experimental methods, reference etc. It is developed and hosted using Linux Apache MySQL PHP (LAMP) software bundle. Standard user-friendly browse, search facility and analysis tools are also integrated. It would assist in understanding the effect of chemical modifications and further development of stable and efficacious siRNAs for research as well as therapeutics. siRNAmod is freely available at: http://crdd.osdd.net/servers/sirnamod. RNA interference (RNAi) phenomenon was described by A. Fire and coworkers in Caenorhabditis elegans 1. They injected double stranded RNA that potentially and specifically interfere with the endogenous gene at mRNA level leading to its silencing 1. RNA silencing pathway utilizes dicer to process long double stranded RNA (dsRNA) to 19-21 nucleotide small interfering RNAs (siRNAs) with 2-nucleotide unphosphorylated 3′ overhangs 2. RNA induced silencing complex (RISC) incorporates siRNA antisense strand, resulting in cleavage of cognate mRNA target 3 as shown in Fig. 1. siRNAs are explored extensively in gene silencing experiments and therapeutics development 4. However, their therapeutic usage is hampered due to many factors e.g. susceptibility to ribonucleases digestion, short biological half-life, lack of proper delivery vehicle, cellular uptake, immune-stimulatory effect, non-specific gene targeting and toxicity 5,6. These limitations are due to the inherent physicochemical properties of siRNAs that includes short and stiff structure, high charge density (poly-anionic), hydrophilic and liability to nuclease cleavage 5,6. To mitigate these restraints, chemical modifications in siRNAs have been substantially investigated 7. Synthetic oligonucleotides were used in the late 1970's for gene inhibition known as antisense technology 8. Modified nucleoside phosphoramidites are used in solid phase chemical synthesis of siRNA which allow site-specific incorporation of chemically modified nucleotide moiety at specific positions within the siRNA 9. Chemical modifications on siRNA are categorized based on component of nucleotide modified as ribose, base or phosphate and change in properties like biological activity, thermodynamic stability and nuclease resistance 7. Chemical modifications on sugar moiety e.g. locked nucleic acids (LNA), unlocked nucleic acids (UNA) 10,11 , 2′-deoxy, 2′-O-methyl 12 , 2′-fluoro, 2′-methoxyethyl, 2′-aminoethyl, were tested for RNAi activity 13,14. In LNA, methylene bridge is created between 2′-oxygen and 4′-carbon to increase the RNAi activity favorably 15,16 and also improves nuclease resistance 17. UNA are open ring derivatives of ribose without C-2′ and C-3′ carbon-carbon bond but structurally mimic the RNA when incorporated into duplex 18. Ribose 2′-OH and phosphorothioate modification increases stability of siRNA 19,20. Besides the 2′-OH was not found to be essential for RNAi activity 21. However, fluorine modification at 2′-OH on different nucleotide positions of siRNA maintains silencing
NeuroImage, Jan 15, 2015
Imaging biomarkers derived from magnetic resonance imaging (MRI) data are used to quantify normal... more Imaging biomarkers derived from magnetic resonance imaging (MRI) data are used to quantify normal development, disease, and the effects of disease-modifying therapies. However, motion during image acquisition introduces image artifacts that, in turn, affect derived markers. A systematic effect can be problematic since factors of interest like age, disease, and treatment are often correlated with both a structural change and the amount of head motion in the scanner, confounding the ability to distinguish biology from artifact. Here we evaluate the effect of head motion during image acquisition on morphometric estimates of structures in the human brain using several popular image analysis software packages (FreeSurfer 5.3, VBM8 SPM, and FSL Siena 5.0.7). Within-session repeated T1-weighted MRIs were collected on 12 healthy volunteers while performing different motion tasks, including two still scans. We show that volume and thickness estimates of the cortical gray matter are biased by...
Applied immunohistochemistry & molecular morphology : AIMM / official publication of the Society for Applied Immunohistochemistry, Jan 21, 2015
MicroRNA (MIR) signatures are critical to pathobiology and prognosis of acute myeloid leukemia (A... more MicroRNA (MIR) signatures are critical to pathobiology and prognosis of acute myeloid leukemia (AML). MIR223 is expressed at low levels in progenitor cells, whereas high expression is induced by granulocytic differentiation. Novel-targeted therapies through epigenetic manipulation of MIR223 regulators are being explored in AML but correlative data between established clinical prognostic markers and MIR223 expression in AML is lacking. MIR223 has inverse relationship with LMO2 protein expression and our group has recently reported a close association between LMO2 protein expression and chromosomal findings in AML patients. In this study, we examined the expression of MIR223 in a large cohort of AML patients and correlated it with LMO2 protein expression, cytogenetic data, degree of differentiation [French-American and British (FAB)/World Health Organization classifications], and overall survival. MIR223 expression was upregulated in only a subset of patients (37%). Suppression of MIR...
Bangladesh Journal of Child Health, 2014
The term pheochromocytoma (in Greek, phios means dusky, chroma means color, and cytoma means tumo... more The term pheochromocytoma (in Greek, phios means dusky, chroma means color, and cytoma means tumor) refers to the color of the tumor cells acquired when stained with chromium salts. Roux performed the first surgical resection of a pheochromocytoma in Lausanne, Switzerland in 1926. Later the same year, Charles Mayo performed the first surgical resection in the United States 1-2. Pheochromocytoma, a rare tumor found in children and adults, is a catecholamine-secreting tumor. It arises from the chromaffin cells of the sympathetic nervous system (adrenal medulla and sympathetic chain); however, the tumor may develop anywhere in the body. Tumors have been reported to have been found in the neck, mediastinum, retro-peritoneal and pelvic sites and virtually every other site of the body 3,4. Common locations for extra-adrenal pheochromocytomas include the organ of Zuckerkandl (close to origin of the inferior mesenteric artery), bladder wall, heart, mediastinum, carotid and glomus jugular bodies 1-2,5-6 .
Database : the journal of biological databases and curation, 2014
Viral microRNAs (miRNAs) regulate gene expression of viral and/or host genes to benefit the virus... more Viral microRNAs (miRNAs) regulate gene expression of viral and/or host genes to benefit the virus. Hence, miRNAs play a key role in host-virus interactions and pathogenesis of viral diseases. Lately, miRNAs have also shown potential as important targets for the development of novel antiviral therapeutics. Although several miRNA and their target repositories are available for human and other organisms in literature, but a dedicated resource on viral miRNAs and their targets are lacking. Therefore, we have developed a comprehensive viral miRNA resource harboring information of 9133 entries in three subdatabases. This includes 1308 experimentally validated miRNA sequences with their isomiRs encoded by 44 viruses in viral miRNA ' VIRMIRNA:…
Stroke, 2020
Introduction: Perfusion imaging can identify patients who respond favorably to endovascular thera... more Introduction: Perfusion imaging can identify patients who respond favorably to endovascular therapy (EVT) in the anterior circulation; no data are available for the posterior circulation. We evaluated perfusion patterns, assessed with RAPID software, in a consecutive cohort of patients with basilar artery occlusion treated with EVT and assessed the association between reperfusion and favorable clinical outcome based on the perfusion profile. Hypothesis: We hypothesized that patients with limited regions of severe hypoperfusion (Tmax > 10s) would have a favorable response (mRS 0-2) to reperfusion (mTICI 2b-3) while patients with multiple critical brain regions severely hypoperfused would have poor outcome (mRS 4-6) despite reperfusion. Methods: From a multicenter cohort of perfusion imaging in posterior circulation stroke, we included patients with basilar artery occlusion and EVT. We pre-specified a Critical Area Perfusion Score (CAPS, 0 - 8 points) to identify severe hypoperfusi...
Additional file 1. Supporting information including Table S1. Performance of QSAR predictive mode... more Additional file 1. Supporting information including Table S1. Performance of QSAR predictive models on three times randomly picked ~ 10% independent/validation data. These models were developed using remaining ~ 90% data during training/testing respectively for each of the six datasets; Table S2. Details of statistical parameters used for the development of IC50 based QSAR models; Table S3. Details of statistical parameters used for the development of percent inhibition based QSAR models; Table S4. Details of chemical descriptors used in the development of IC50 based QSAR models; Table S5. Details of chemical descriptors used in the development of percent inhibition based QSAR models; Table S6. Details of slopes k (predicted vs. observed inhibition) and k' (observed vs. predicted inhibition) of the regression lines for the QSAR models; Table S7. Details of Y-randomization test performed on the QSAR models; Figure S1. Chemical space analysis of QSAR studies (Table 5) for Protease...
Stroke, 2020
Introduction: The vascular territory of an occluded large intracranial vessel can be reliably ide... more Introduction: The vascular territory of an occluded large intracranial vessel can be reliably identified by CT or MR perfusion imaging. Furthermore, prior studies have shown that perfusion imaging can reliably predict the specific vessel that is occluded in anterior circulation large vessel strokes. We evaluated whether perfusion imaging can predict the specific vessel occlusion (vertebral, basilar, or posterior cerebral) in posterior circulation strokes. Hypothesis: We hypothesized that the occluded vessel could be inferred from the perfusion imaging results in >80% of patients with an acute stroke due to large vessel occlusion in the posterior circulation using the simultaneous CTA or MRA as the gold standard. Furthermore, the inter-rater agreement between a vascular neurologist and a neuroradiologist would be > 90%. Agreement Coefficients (AC1) were determined. Methods: From a multicenter cohort of consecutive patients with posterior circulation stroke, we included patients...
Helicobacter pylori (H. pylori ) are a widespread kind of bacteria which flourish in the digestiv... more Helicobacter pylori (H. pylori ) are a widespread kind of bacteria which flourish in the digestive tract and have a propensity to damage the stomach lining. The microbe infects around 60% of the adults globally. H. pylori infections are responsible for most of stomach and small intestine ulcers. Using Bioinformatics approaches, we have identified certain proteins that possess the resistance, essentiality and virulence factors for this pathogen. Computational tools and servers were used for the identification of MHC class I, II and B cell epitopes. The set of chosen epitopes were also filtered as per their immunogenic and toxicity potentials. Designed vaccine construct was docked against multiple HLA targets employing virtual modeling. Therefore the designated vaccine constructs may be developed to control the infection caused by H. pylori .
Handbook of Research on Advancements in Cancer Therapeutics, 2021
Cancer is the second biggest killer worldwide. It has been estimated that specific lifestyle and ... more Cancer is the second biggest killer worldwide. It has been estimated that specific lifestyle and dietary measures can prevent 30–40% of all cancers. Consumption of nutrient sparse foods, such as refined flour products and concentrated sugars, consumption of red meat, low fibre intake, and disproportion of omega 3 and omega 6 fatty acids, contributes to cancer risks. Microbiological and chemical food contaminants as well as conventional and industrial food processing methods may further increase the carcinogenicity of diets while protective agents in a cancer prevention diet include folic acid, selenium, vitamin D, vitamin B-12, chlorophyll, and antioxidants such as the carotenoids, kryptoxanthin, lycopene, and lutein. Diet can also influence the gut microbes that may have positive or adverse effects on cancer risk. The authors summarize cancer prevention by functional foods and discuss the role of different dietary factors such as promoter or inhibitor in pathogenesis of different s...
Journal of the American College of Cardiology, 2020
Background: Use of direct oral anticoagulants (DOACs) for the treatment of left ventricular (LV) ... more Background: Use of direct oral anticoagulants (DOACs) for the treatment of left ventricular (LV) thrombus has gained considerable interest. Objective: We aimed to evaluate if DOACs are effective in the treatment of LV thrombus compared with warfarin. Methods: We evaluated the medical records of patients diagnosed with a new LV thrombus at a tertiary medical center. The primary outcome was the composite of thrombus persistence, stroke, or systemic embolism. We adjusted for potential confounders using multiple logistic regression. The safety outcome was the composite of hemorrhagic stroke or bleeding requiring blood transfusion. Results: A total of 129 patients were treated with warfarin and 22, with a DOAC. In unadjusted analysis, 54.3% of patients treated with warfarin met criteria for the efficacy outcome as compared with 40.9% of patients treated with a DOAC (P = 0.25). In adjusted analysis, no difference between groups was observed (odds ratio = 0.39; 95% CI = 0.14-1.06; P = 0.07 for DOAC vs warfarin). In all, 3.9% of patients treated with warfarin met safety criteria as compared with 4.5% of patients treated with a DOAC. A total of 8 patients in the warfarin group had a stroke or systemic embolism as compared with 0 patients in the DOAC group (P = 0.37). Conclusion and Relevance: Our data suggest that DOACs may be reasonable alternatives for treatment of LV thrombus. When added to the totality of available studies, this study demonstrates that the effectiveness of DOACs in LV thrombus remains uncertain. Randomized clinical trials are needed.
Journal of Clinical Oncology, 2015
8568 Background: DLBCL is a heterogeneous disease. Gene expression profile (GEP) based distinctio... more 8568 Background: DLBCL is a heterogeneous disease. Gene expression profile (GEP) based distinction into ABC and GCB sub-types, provides basis for risk stratification in DLBCL patients. GEP is an in...
Reviews in Medical Virology, 2018
Viral diseases like influenza, AIDS, hepatitis, and Ebola cause severe epidemics worldwide. Along... more Viral diseases like influenza, AIDS, hepatitis, and Ebola cause severe epidemics worldwide. Along with their resistant strains, new pathogenic viruses continue to be discovered so creating an ongoing need for new antiviral treatments. RNA interference is a cellular gene-silencing phenomenon in which sequence-specific degradation of target mRNA is achieved by means of complementary short interfering RNA (siRNA) molecules. Short interfering RNA technology affords a potential tractable strategy to combat viral pathogenesis because siRNAs are specific, easy to design, and can be directed against multiple strains of a virus by targeting their conserved gene regions. In this review, we briefly summarize the current status of siRNA therapy for representative examples from different virus families. In addition, other aspects like their design, delivery, medical significance, bioinformatics resources, and limitations are also discussed.
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 2018
Hepatitis C virus plays a significant role in the development of hepatocellular carcinoma (HCC) g... more Hepatitis C virus plays a significant role in the development of hepatocellular carcinoma (HCC) globally. The pathogenic mechanisms of hepatocellular carcinoma with HCV infection are generally linked with inflammation, cytokines, fibrosis, cellular signaling pathways, and liver cell proliferation modulating pathways. HCV encoded proteins (Core, NS3, NS4, NS5A) interact with a broad range of hepatocytes derived factors to modulate an array of activities such as cell signaling, DNA repair, transcription and translational regulation, cell propagation, apoptosis, membrane topology. These four viral proteins are also implicated to show a strong conversion potential in tissue culture. Furthermore, Core and NS5A also trigger the accretion of the β-catenin pathway as a common target to contribute viral induced transformation. There is a strong association between HCV variants within Core, NS4, and NS5A and host single nucleotide polymorphisms (SNPs) with the HCC pathogenesis. Identification...
Journal of cheminformatics, Jan 9, 2018
A number of anti-retroviral drugs are being used for treating Human Immunodeficiency Virus (HIV) ... more A number of anti-retroviral drugs are being used for treating Human Immunodeficiency Virus (HIV) infection. Due to emergence of drug resistant strains, there is a constant quest to discover more effective anti-HIV compounds. In this endeavor, computational tools have proven useful in accelerating drug discovery. Although methods were published to design a class of compounds against a specific HIV protein, but an integrated web server for the same is lacking. Therefore, we have developed support vector machine based regression models using experimentally validated data from ChEMBL repository. Quantitative structure activity relationship based features were selected for predicting inhibition activity of a compound against HIV proteins namely protease (PR), reverse transcriptase (RT) and integrase (IN). The models presented a maximum Pearson correlation coefficient of 0.78, 0.76, 0.74 and 0.76, 0.68, 0.72 during tenfold cross-validation on ICand percent inhibition datasets of PR, RT, I...
The Journal of Bone and Joint Surgery-American Volume, 2003
The best method of reconstructing osteoarticular defects to maintain joint stability and prevent ... more The best method of reconstructing osteoarticular defects to maintain joint stability and prevent early degenerative joint disease has yet to be resolved. Buckwalter broadly divided the treatment strategies into two types 1 : those that stimulate repair or regeneration of articular cartilage and those that involve transplantation of an articular surface. However, these methods do not provide the osseous support that may be needed when bone loss has occurred in the epiphysis. We report the case of a three-year-old patient in whom massive osteoarticular bone loss from the medial tibial plateau of the left leg, due to a lawn-mower injury, was treated with the Ilizarov technique of distraction histogenesis. To our knowledge, this is the first time that this method has been utilized to repair an osteochondral defect. Our patient was informed that data concerning the case would be submitted for publication. A three-year-old boy sustained an injury to the left leg from a lawn mower. He sustained soft-tissue and bone loss on the medial aspect of the proximal part of the left tibia and knee. The medial tibial plateau, including the articular cartilage, was missing, and there was a fracture through the remaining proximal tibial physis. A gastrocnemius-muscle pedicle graft and a split-thickness skin graft were used to cover the soft-tissue defect. The detached patellar tendon was sutured back in the region of the tibial tubercle. Six months after the initial injury, a nonunion of the proximal tibial physeal fracture ( Fig. 1 ) was treated with open reduction and iliac-crest bone grafting and screw fixation. The bone healed in three months ( Fig. 2 ) but with medial instability at the knee joint, which was controlled with a hinged knee-ankle-foot orthosis. The knee had an extension lag of 20° secondary to quadriceps weakness. Fig. 1: Anteroposterior and lateral radiographs of …
G3 (Bethesda, Md.), Sep 10, 2017
Allele-specific siRNAs (ASP-siRNAs) have emerged as promising therapeutic molecules owing to thei... more Allele-specific siRNAs (ASP-siRNAs) have emerged as promising therapeutic molecules owing to their selectivity to inhibit the mutant allele or associated single nucleotide polymorphisms (SNPs) sparing the expression of the wild-type counterpart. Thus, a dedicated bioinformatics platform encompassing updated ASP-siRNAs and an algorithm for the prediction of their inhibitory efficacy will be helpful in tackling currently intractable genetic disorders. In the present study, we have developed the ASPsiRNA resource (http://crdd.osdd.net/servers/aspsirna/) covering three components viz (i) ASPsiDb (ii) ASPsiPred and (iii) analysis tools like ASP-siOffTar. ASPsiDb is a manually curated database harboring 4543 (including 422 chemically modified) ASP-siRNAs targeting 78 unique genes involved in 51 different diseases. It furnishes comprehensive information from experimental studies on ASP-siRNAs along with multidimensional genetic and clinical information for numerous mutations. ASPsiPred is ...
Chemical biology & drug design, Jan 4, 2016
Viral infections constantly jeopardize the global public health due to lack of effective antivira... more Viral infections constantly jeopardize the global public health due to lack of effective antiviral therapeutics. Therefore, there is an imperative need to speed up the drug discovery process to identify novel and efficient drug candidates. In the present study, we have developed Quantitative structure-activity relationship (QSAR) based models for predicting Antiviral compounds (AVCs) against deadly viruses like Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), Hepatitis B virus (HBV), Human herpesvirus (HHV) and 26 others using publicly available experimental data from the ChEMBL bioactivity database. Support Vector Machine (SVM) models achieved a maximum Pearson Correlation Coefficient of 0.72, 0.74, 0.66, 0.68 and 0.71 in regression mode and a maximum Matthew's correlation coefficient 0.91, 0.93, 0.70, 0.89 and 0.71 respectively in classification mode during 10-fold cross-validation. Furthermore, similar performance was observed on the independent validation sets. W...
Scientific Reports, 2016
Small interfering RNA (siRNA) technology has vast potential for functional genomics and developme... more Small interfering RNA (siRNA) technology has vast potential for functional genomics and development of therapeutics. However, it faces many obstacles predominantly instability of siRNAs due to nuclease digestion and subsequently biologically short half-life. Chemical modifications in siRNAs provide means to overcome these shortcomings and improve their stability and potency. Despite enormous utility bioinformatics resource of these chemically modified siRNAs (cm-siRNAs) is lacking. Therefore, we have developed siRNAmod, a specialized databank for chemically modified siRNAs. Currently, our repository contains a total of 4894 chemically modified-siRNA sequences, comprising 128 unique chemical modifications on different positions with various permutations and combinations. It incorporates important information on siRNA sequence, chemical modification, their number and respective position, structure, simplified molecular input line entry system canonical (SMILES), efficacy of modified siRNA, target gene, cell line, experimental methods, reference etc. It is developed and hosted using Linux Apache MySQL PHP (LAMP) software bundle. Standard user-friendly browse, search facility and analysis tools are also integrated. It would assist in understanding the effect of chemical modifications and further development of stable and efficacious siRNAs for research as well as therapeutics. siRNAmod is freely available at: http://crdd.osdd.net/servers/sirnamod. RNA interference (RNAi) phenomenon was described by A. Fire and coworkers in Caenorhabditis elegans 1. They injected double stranded RNA that potentially and specifically interfere with the endogenous gene at mRNA level leading to its silencing 1. RNA silencing pathway utilizes dicer to process long double stranded RNA (dsRNA) to 19-21 nucleotide small interfering RNAs (siRNAs) with 2-nucleotide unphosphorylated 3′ overhangs 2. RNA induced silencing complex (RISC) incorporates siRNA antisense strand, resulting in cleavage of cognate mRNA target 3 as shown in Fig. 1. siRNAs are explored extensively in gene silencing experiments and therapeutics development 4. However, their therapeutic usage is hampered due to many factors e.g. susceptibility to ribonucleases digestion, short biological half-life, lack of proper delivery vehicle, cellular uptake, immune-stimulatory effect, non-specific gene targeting and toxicity 5,6. These limitations are due to the inherent physicochemical properties of siRNAs that includes short and stiff structure, high charge density (poly-anionic), hydrophilic and liability to nuclease cleavage 5,6. To mitigate these restraints, chemical modifications in siRNAs have been substantially investigated 7. Synthetic oligonucleotides were used in the late 1970's for gene inhibition known as antisense technology 8. Modified nucleoside phosphoramidites are used in solid phase chemical synthesis of siRNA which allow site-specific incorporation of chemically modified nucleotide moiety at specific positions within the siRNA 9. Chemical modifications on siRNA are categorized based on component of nucleotide modified as ribose, base or phosphate and change in properties like biological activity, thermodynamic stability and nuclease resistance 7. Chemical modifications on sugar moiety e.g. locked nucleic acids (LNA), unlocked nucleic acids (UNA) 10,11 , 2′-deoxy, 2′-O-methyl 12 , 2′-fluoro, 2′-methoxyethyl, 2′-aminoethyl, were tested for RNAi activity 13,14. In LNA, methylene bridge is created between 2′-oxygen and 4′-carbon to increase the RNAi activity favorably 15,16 and also improves nuclease resistance 17. UNA are open ring derivatives of ribose without C-2′ and C-3′ carbon-carbon bond but structurally mimic the RNA when incorporated into duplex 18. Ribose 2′-OH and phosphorothioate modification increases stability of siRNA 19,20. Besides the 2′-OH was not found to be essential for RNAi activity 21. However, fluorine modification at 2′-OH on different nucleotide positions of siRNA maintains silencing
NeuroImage, Jan 15, 2015
Imaging biomarkers derived from magnetic resonance imaging (MRI) data are used to quantify normal... more Imaging biomarkers derived from magnetic resonance imaging (MRI) data are used to quantify normal development, disease, and the effects of disease-modifying therapies. However, motion during image acquisition introduces image artifacts that, in turn, affect derived markers. A systematic effect can be problematic since factors of interest like age, disease, and treatment are often correlated with both a structural change and the amount of head motion in the scanner, confounding the ability to distinguish biology from artifact. Here we evaluate the effect of head motion during image acquisition on morphometric estimates of structures in the human brain using several popular image analysis software packages (FreeSurfer 5.3, VBM8 SPM, and FSL Siena 5.0.7). Within-session repeated T1-weighted MRIs were collected on 12 healthy volunteers while performing different motion tasks, including two still scans. We show that volume and thickness estimates of the cortical gray matter are biased by...
Applied immunohistochemistry & molecular morphology : AIMM / official publication of the Society for Applied Immunohistochemistry, Jan 21, 2015
MicroRNA (MIR) signatures are critical to pathobiology and prognosis of acute myeloid leukemia (A... more MicroRNA (MIR) signatures are critical to pathobiology and prognosis of acute myeloid leukemia (AML). MIR223 is expressed at low levels in progenitor cells, whereas high expression is induced by granulocytic differentiation. Novel-targeted therapies through epigenetic manipulation of MIR223 regulators are being explored in AML but correlative data between established clinical prognostic markers and MIR223 expression in AML is lacking. MIR223 has inverse relationship with LMO2 protein expression and our group has recently reported a close association between LMO2 protein expression and chromosomal findings in AML patients. In this study, we examined the expression of MIR223 in a large cohort of AML patients and correlated it with LMO2 protein expression, cytogenetic data, degree of differentiation [French-American and British (FAB)/World Health Organization classifications], and overall survival. MIR223 expression was upregulated in only a subset of patients (37%). Suppression of MIR...
Bangladesh Journal of Child Health, 2014
The term pheochromocytoma (in Greek, phios means dusky, chroma means color, and cytoma means tumo... more The term pheochromocytoma (in Greek, phios means dusky, chroma means color, and cytoma means tumor) refers to the color of the tumor cells acquired when stained with chromium salts. Roux performed the first surgical resection of a pheochromocytoma in Lausanne, Switzerland in 1926. Later the same year, Charles Mayo performed the first surgical resection in the United States 1-2. Pheochromocytoma, a rare tumor found in children and adults, is a catecholamine-secreting tumor. It arises from the chromaffin cells of the sympathetic nervous system (adrenal medulla and sympathetic chain); however, the tumor may develop anywhere in the body. Tumors have been reported to have been found in the neck, mediastinum, retro-peritoneal and pelvic sites and virtually every other site of the body 3,4. Common locations for extra-adrenal pheochromocytomas include the organ of Zuckerkandl (close to origin of the inferior mesenteric artery), bladder wall, heart, mediastinum, carotid and glomus jugular bodies 1-2,5-6 .
Database : the journal of biological databases and curation, 2014
Viral microRNAs (miRNAs) regulate gene expression of viral and/or host genes to benefit the virus... more Viral microRNAs (miRNAs) regulate gene expression of viral and/or host genes to benefit the virus. Hence, miRNAs play a key role in host-virus interactions and pathogenesis of viral diseases. Lately, miRNAs have also shown potential as important targets for the development of novel antiviral therapeutics. Although several miRNA and their target repositories are available for human and other organisms in literature, but a dedicated resource on viral miRNAs and their targets are lacking. Therefore, we have developed a comprehensive viral miRNA resource harboring information of 9133 entries in three subdatabases. This includes 1308 experimentally validated miRNA sequences with their isomiRs encoded by 44 viruses in viral miRNA ' VIRMIRNA:…