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result(s) for
"Mahajan, Mayank"
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Hydrogen bonding template enables remote meta-C–H alkenylation of nitroarenes with electron-deficient alkenes
2024
Regioselective distal C−H functionalization of nitroarenes by overriding proximal C−H activation has remained an unsolved challenge. Herein, we present a palladium-catalyzed
meta
-C−H alkenylation of nitroarene substrate, achieved through leveraging the non-covalent hydrogen bonding interactions. Urea-based templates comprising an elongated biphenyl linker designed in such a way that it interacts with nitro group via strong hydrogen bonding interaction, while a cyano based directing group is attached along the template to coordinate with the palladium center, thereby facilitating the activation of the remote
meta
-C−H bond of nitrobenzene. Computational mechanistic investigation and the analysis of non-covalent interaction deciphers the crucial role of H-bonding in regulating the regioselectivity.
Regioselective distal C-H functionalization of nitroarenes by overriding proximal C-H activation has remained an unsolved challenge. Herein, the authors present a palladium-catalyzed meta-C-H alkenylation of nitroarene substrate, achieved through leveraging the noncovalent hydrogen bonding interactions.
Journal Article
The Correlation of the Neutrophil-to-Lymphocyte Ratio With Microvascular Complications in Patients With Diabetes Mellitus
by
Vidyapati
,
Marandi, Sujeet
,
Mahajan, Mayank
in
Chi-square test
,
Diabetes
,
Diabetic nephropathy
2023
BackgroundHigh neutrophil-to-lymphocyte ratio (NLR) may be used as a reliable measure of vascular complications and an indicator of poor outcomes in cases of diabetes mellitus (DM).MethodsA prospective analytical cross-sectional observational study was conducted at the Rajendra Institute of Medical Sciences (RIMS), Ranchi, Jharkhand, India. A total of 100 patients with DM who met the inclusion and exclusion criteria were included in the study. A pre-tested and semi-structured questionnaire was given to the patients. IBM SPSS software version 26 (IBM Corp., Armonk, NY, USA) and MedCalc trial version 20.114 (MedCalc Software Ltd., Ostend, Belgium) were used for data analysis. Logistic regression analysis was performed to determine the association of the NLR with microvascular complications.ResultsIn our study, the male-to-female ratio was 1.78:1 (male: 64 (n)%, female: 36 (n)%). The mean age of our study population was 56.28 ± 13.24 years. Of 58 patients with microvascular complications, 34 had a high NLR, and 24 patients had a normal NLR. Of 42 patients without microvascular complications, only 14 had a high NLR, and the remaining 28 patients had a normal NLR (p = 0.012). Logistic regression was performed to analyze the association between the NLR and microvascular complications, which demonstrated a significant association (odds ratio (OR): 2.833, 95% confidence interval (CI): 1.238-6.481; p = 0.013).ConclusionsOur study demonstrated the higher odds of having microvascular complications among diabetics with a high NLR compared with non-diabetics. Therefore, the NLR may be used as a measure of microvascular complications in the diabetic population.
Journal Article
Demographics and clinical profile of patients with ocular Calotropis poisoning in India
2021
Purpose:
To describe the clinical profile of patients with ocular Calotropis poisoning presenting to a multitier ophthalmology hospital network in India.
Methods:
This cross-sectional hospital-based study included 2,047,360 new patients presenting between August 2010 and March 2020. Patients with a clinical diagnosis of Calotropis poisoning in at least one eye were included. The data were collected using an electronic medical record system. Descriptive statistics using mean ± standard deviation and median with inter-quartile range (IQR) were used to elucidate the demographic data. Chi-square test was done for univariate analysis.
Results:
Overall, 362 (0.018%) new patients were diagnosed with ocular Calotropis poisoning during the study period. The mean age of the patients was 44.10 ± 18.61 years. The incidence rates were 0.013% in children and 0.018% in adults. Males were 57.46% and 87.29% had unilateral affliction. A significant number of patients presented from the rural geography (59.67%) and were from the higher socioeconomic class (72.65%). About a fourth of the patients were homemakers (23.48%) followed by agriculture workers (18.23%). Of the 408 affected eyes, 49.26% had mild visual impairment (<20/70) followed by moderate visual impairment (>20/70 to ≤ 20/200) in 23.28%. The most common clinical signs were conjunctival congestion (61.03%), descemet membrane folds (57.35%), stromal edema (30.39%), and corneal epithelial defect (24.51%).
Conclusion:
Calotropis poisoning in individuals seeking eye care in India is very rare. It is commonly unilateral and occurs more in the rural geography. It is common in middle-aged males and may affect vision due to involvement of the cornea.
Journal Article
Peritoneal Tuberculosis With Raised Cancer Antigen 125 (CA-125) in a Post-partum Woman: A Case Report
2023
Peritoneal tuberculosis is a common cause of ascites in areas endemic to
. The presentation of tuberculous ascites can mimic ovarian malignancy when it is associated with elevated cancer antigen 125 (CA-125) levels. We hereby discuss a case of a four months post-partum female patient who presented with gradual abdominal distension and was diagnosed with peritoneal tuberculosis after proper evaluation. She was started on anti-tubercular therapy and the treatment was successful. This case report highlights the importance of considering peritoneal tuberculosis as a differential diagnosis in cases of ascites with raised serum CA-125 levels in a
endemic region.
Journal Article
Effectiveness of Topical Sucralfate in the Management of Diabetic Foot Ulcers: An Open-Labeled Randomized Study
2023
Diabetic foot ulcer (DFU) is a major cause of lower limb amputations. Many treatment recommendations have been proposed. This study was conducted to evaluate the effectiveness of topical sucralfate when combined with mupirocin ointment, in the treatment of diabetic foot ulcer in comparison to topical mupirocin alone, in terms of healing rates.
This open-labeled randomized study was conducted on 108 patients to evaluate the effectiveness of topical sucralfate and mupirocin combination, compared to topical mupirocin alone. The patients were administered the same parenteral antibiotic, and wounds were subjected to daily dressing. The healing rates (determined by the percentage reduction in wound area) in the two groups were calculated. The mean healing rates in both groups were expressed in percentage and compared using the Student's t-test.
A total of 108 patients were included in the study. Male-to-female ratio was 3:1. The incidence of diabetic foot was the highest (50.9%) in the age group of 50-59 years. The mean age of the study population was 51 years. The incidence of diabetic foot ulcers was highest in the months of July-August (42%). A total of 71.2% patients had random blood sugar levels between 150-200 mg/dL, and 72.2% patients had diabetes for five to 10 years. The mean±standard deviation (SD) of the healing rates in the sucralfate and mupirocin combination group and the control group were 16.2±7.3% and 14.5±6.6%, respectively. Comparison of the means by Student's t-test failed to show a statistical difference in healing rates between the two groups (p=0.201).
We concluded that the addition of topical sucralfate does not show any obvious benefits in terms of healing rates in diabetic foot ulcers as compared to mupirocin alone.
Journal Article
Leveraging sequences missing from the human genome to diagnose cancer
2025
Background
Cancer diagnosis using cell-free DNA (cfDNA) has the potential to improve treatment and survival but has several technical limitations.
Methods
In this study, we developed a prediction model based on neomers, DNA sequences 13–17 nucleotides in length that are predominantly absent from the genomes of healthy individuals and are created by tumor-associated mutations.
Results
We show that neomer-based classifiers can accurately detect cancer, including early stages, and distinguish subtypes and features. Analysis of 2577 cancer genomes from 21 cancer types shows that neomers can distinguish tumor types with higher accuracy than state-of-the-art methods. Generation and analysis of 465 cfDNA whole-genome sequences demonstrates that neomers can precisely detect lung and ovarian cancer, including early stages, with an area under the curve ranging from 0.89 to 0.94. By testing various promoters or over 9000 candidate enhancer sequences with massively parallel reporter assays, we show that neomers can identify cancer-associated mutations that alter regulatory activity.
Conclusions
Combined, our results identify a sensitive, specific, and simple cancer diagnostic tool that can also identify cancer-associated mutations in gene regulatory elements.
Plain language summary
DNA fragments circulating in the blood are often present in people with cancer. Current tests using DNA fragments circulating in the blood have limitations in detecting cancer. We developed a cancer diagnostic approach that uses neomers, short DNA sequences that are mostly absent in healthy individuals but are present in tumors as a consequence of changes in the DNA (DNA mutations) in cancer cells. We show that this approach can accurately detect lung and ovarian cancers from DNA fragments extracted from blood and identify changes in the DNA associated with cancer. Our diagnostic tool could be used to improve cancer detection and identify how changes in the DNA affect development of cancer.
Georgakopoulos-Soares, Yizhar-Barnea, Mouratidis et al. identify neomers, short (16 base pair) DNA sequences that are absent in the genomes of healthy individuals but appear in tumors due to mutations. They show that neomers can accurately detect cancer from cell-free DNA and that neomers found in gene regulatory elements can alter regulatory activity.
Journal Article
Diagnostic Accuracy of Cerebrospinal Fluid (CSF) Adenosine Deaminase (ADA) for Tuberculous Meningitis (TBM) in Adults: A Systematic Review and Meta-Analysis
2023
Tuberculous meningitis is the most serious complication of tuberculosis. Early diagnosis is crucial to start relevant treatment to prevent death and disability. Electronic databases PubMed, Google Scholar, and Cochrane Library were used to find relevant articles from January 1980 to June 2022. The random-effect model in terms of pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence interval was adopted to derive the diagnostic efficacy of cerebrospinal fluid (CSF) adenosine deaminase (ADA) for the diagnosis of tuberculous meningitis (TBM) in adult patients. A total of 22 studies (20 prospective and two retrospective data) have been included in this meta-analysis, having 1927 participants. We perceived acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROCs), and diagnostic odds ratio (DOR) of 0.85 (95% CI: 0.77-0.90), 0.90 (95% CI: 0.85-0.93), 0.94 (95% CI: 0.91-0.96) and 48 (95% CI: 26-86), respectively, for CSF-ADA for differentiating TBM from non-TBM in adult patients. To ascertain the certainty of evidence for CSF-ADA as a diagnostic marker for TBM, Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) analysis was used. CSF-ADA is an auspicious diagnostic test with a high degree of specificity and acceptable sensitivity for the diagnosis of tuberculous meningitis, however, with very low certainty of evidence.
Journal Article
Paralogization and New Protein Architectures in Planctomycetes Bacteria with Complex Cell Structures
2020
Bacteria of the phylum Planctomycetes have a unique cell plan with an elaborate intracellular membrane system, thereby resembling eukaryotic cells. The origin and evolution of these remarkable features is debated. To study the evolutionary genomics of bacteria with complex cell architectures, we have resequenced the 9.2-Mb genome of the model organism Gemmata obscuriglobus and sequenced the 10-Mb genome of G. massiliana Soil9, the 7.9-Mb genome of CJuql4, and the 6.7-Mb genome of Tuwongella immobilis, all of which belong to the family Gemmataceae. A gene flux analysis of the Planctomycetes revealed a massive emergence of novel protein families at multiple nodes within the Gemmataceae. The expanded protein families have unique multidomain architectures composed of domains that are characteristic of prokaryotes, such as the sigma factor domain of extracytoplasmic sigma factors, and domains that have proliferated in eukaryotes, such as the WD40, leucine-rich repeat, tetratricopeptide repeat and Ser/Thr kinase domains. Proteins with identifiable domains in the Gemmataceae have longer lengths and linkers than proteins in most other bacteria, and the analyses suggest that these traits were ancestrally present in the Planctomycetales. A broad comparison of protein length distribution profiles revealed an overlap between the longest proteins in prokaryotes and the shortest proteins in eukaryotes. We conclude that the many similarities between proteins in the Planctomycetales and the eukaryotes are due to convergent evolution and that there is no strict boundary between prokaryotes and eukaryotes with regard to features such as gene paralogy, protein length, and protein domain composition patterns.
Journal Article
Impact of Plateletpheresis on the Hemoglobin, Hematocrit, and Total Red Blood Cell Count: An Updated Meta-Analysis
2024
Plateletpheresis has become a pivotal part of transfusion medicine. With the increasing demand for plateletpheresis, donor safety is an area of concern because plateletpheresis alters donor hematological parameters. For a better understanding of plateletpheresis, a systemic review is needed to study more evidence-based aspects of plateletpheresis. Electronic databases PubMed, Google Scholar, and Cochrane Library were used to find articles from January 1, 1980, to May 23, 2024. The random effect model was used to meta-analyze the effect of plateletpheresis on hematocrit, hemoglobin, and red blood cell (RBC) count. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. A total of 24 studies were found; the effect of plateletpheresis on hemoglobin, hematocrit, and RBC count was studied in the following respective numbers of donors: 3,374, 3,374, and 690. A decrease of hemoglobin, hematocrit, and RBC count was observed after plateletpheresis having a weighted mean difference (WMD) of 0.50 (95%CI = -0.72 to -0.27), WMD of -1.36 (95%CI = -2.05 to -0.66), and WMD of -0.18 (95%CI = -0.23 to -0.12), respectively. Plateletpheresis shows a decrease in the value of hematological parameters such as hemoglobin, hematocrit, and erythrocyte count due to blood loss in the kits employed in the procedure; cell lysis was also seen because of exposure of erythrocytes to stress or change in osmotic pressure. Thus, strict criteria for donation must be developed for better safety of the donors. Improved automated cell separators for plateletpheresis should be made available in blood banks to ensure good quality hematologic products. Our findings suggest that the duration of the procedure should be decreased.
Journal Article
Evolution of Cellular Complexity and Other Remarkable Features in Gemmataceae: Complex Bacterial Lineages Defy Prokaryotic Trends
2019
Bacteria of the family Gemmataceae belong the phylum Planctomycetes and are remarkable because of their complex cellular architectures, previously considered to be traits exclusive to eukaryotes. This thesis provides clues to the atypical cell envelope, the enhanced radiotolerance and the amazing cellular complexity of these bacteria.A comparative genomics study of these bacteria revealed massive duplications and new combinations of structural domains that are highly abundant in eukaryotes but rare in bacteria. These domains are known to facilitate signalling and protein interactions. The proteins of these bacteria also contain long regions with no predicted domains. On average, eukaryotic proteins are longer and more disordered than prokaryotic proteins. Intriguingly, the length and fraction of disordered regions in proteins of some bacteria are higher than in many other prokaryotes, and these bacteria also have complex lifestyles. Many bacteria in the Planctomycetes, including the Gemmataceae, are among these few bacteria. This suggests that there is no sharp boundary between prokaryotes and eukaryotes with respect to protein length and domain composition patterns, as previously thought.A bioinformatics analysis revealed the loss of genes for the peptidoglycan cell wall in some lineages of the Planctomycetes. Loss of the gene for the FtsZ protein, the major cell division protein in bacteria, may have facilitated the evolution of budding in the Planctomycetales and led to the gradual loss of the cell wall and cell division gene cluster. These changes may have enabled the expansion of the inner membrane and triggered adaptive changes in conserved membrane proteins and transport systems. The loss of the peptidoglycan cell wall may also explain the altered cell morphology. A subcellular proteomics study showed that the DNA replication and repair proteins are associated with the cell envelope, which supports the cell factory model of DNA replication.T. immobilis, which has the simplest genome of all members of the Gemmataceae, was found to be naturally competent and most suitable for transformation experiments. T. immobilis was transformed to produce mutants in which the gene for DdrA, a double stranded break DNA repair protein, has been inactivated. The DdrA-null mutant showed a major loss in radiotolerance.
Dissertation