4,017 results on '"SK Gupta"'
Search Results
202. Clinical and molecular correlates of the Index of Severity for Eosinophilic Esophagitis.
- Author
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Sato H, Dellon ES, Aceves SS, Arva NC, Chehade M, Collins MH, Davis CM, Falk GW, Furuta GT, Gonsalves NP, Gupta SK, Hirano I, Hiremath G, Katzka DA, Khoury P, Leung J, Menard-Katcher P, Pesek R, Peterson KA, Pletneva MA, Spergel JM, Wechsler JB, Yang GY, Rothenberg ME, and Shoda T
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- Humans, Male, Female, Child, Adult, Adolescent, Child, Preschool, Middle Aged, Prospective Studies, Young Adult, Eosinophilic Esophagitis diagnosis, Severity of Illness Index
- Abstract
Background: The Index of Severity for Eosinophilic Esophagitis (I-SEE) is a new expert-defined clinical tool that classifies disease severity of eosinophilic esophagitis (EoE)., Objective: We aimed to determine whether I-SEE is associated with patient characteristics, molecular features of EoE, or both., Methods: We analyzed a prospective cohort of patients with EoE from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Associations between I-SEE and clinical and molecular features (assessed by an EoE diagnostic panel [EDP]) were assessed., Results: In 318 patients with chronic EoE (209 adults, 109 children), median total I-SEE score was 7.0, with a higher symptoms and complications score in children than adults (4.0 vs 1.0; P < .001) and higher inflammatory and fibrostenotic features scores in adults than children (3.0 vs 1.0 and 3.0 vs 0, respectively; both P < .001). Total I-SEE score had a bimodal distribution with the inactive to moderate categories and severe category. EDP score correlated with total I-SEE score (r = -0.352, P < .001) and both inflammatory and fibrostenotic features scores (r = -0.665, P < .001; r = -0.446, P < .001, respectively), but not with symptoms and complications scores (r = 0.047, P = .408). Molecular severity increased from inactive to mild and moderate, but not severe, categories. Longitudinal changes of modified I-SEE scores and inflammatory and fibrostenotic features scores reflected histologic and molecular activity., Conclusions: I-SEE score is associated with select clinical features across severity categories and with EoE molecular features for nonsevere categories, warranting further validation., Competing Interests: Disclosure statement Supported by National Institutes of Health (NIH) grant K99/R00 AI158660 (to T.S.) and the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR, U54 AI117804), which is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences (NCATS), and is cofunded by the National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NCATS, and in part by the Intramural Research Program of NIAID. CEGIR is also supported by patient advocacy groups, including the American Partnership for Eosinophilic Disorders (APFED), Campaign Urging Research for Eosinophilic Disease (CURED), and Eosinophilic Family Coalition (EFC). As a member of the RDCRN, CEGIR is also supported by its Data Management and Coordinating Center (DMCC) (U2CTR002818). Funding support for the DMCC is provided by NCATS and the National Institute of Neurological Disorders and Stroke (NINDS). This project was supported in part by NIH P30 DK078392 (Gene Expression Core, Pathology Research Core, and Confocal Imaging Core) of the Digestive Diseases Research Core Center in Cincinnati. Disclosure of potential conflict of interest: E. S. Dellon is consultant for Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/ Bristol Meyers Squibb (BMS), Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio. E. S. Dellon has received research funding from Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, and Shire/Takeda; and has received educational grants from Allakos, Holoclara, and Invea. S. S. Aceves is disease state awareness speaker and consultant for Sanofi/Regeneron, consultant for Ferring Pharma; has research funding from Implicit Biosciences and BMS; and is a coinventor of oral viscous budesonide UCSD patent, Takeda license. M. Chehade served as consultant for Regeneron, Adare/Ellodi, AstraZeneca, Sanofi, BMS, Allakos, Shire/Takeda, Phathom, Recludix Pharma, Nexstone Immunology; and received research funding from Regeneron, Allakos, AstraZeneca, Adare/Ellodi, BMS, Danone, and Shire/Takeda. M. H. Collins is consultant for Allakos, Arena Pharmaceuticals, AstraZeneca, BMS, Calypso Biotech, EsoCap Biotech, GlaxoSmithKline, Receptos/Celgene, Regeneron Pharmaceuticals, Robarts Clinical Trials/Alimentiv, Sanofi, and Shire/Takeda. C. M. Davis receives research funding from the NIH/NIAID (U01AI126614, UM2AI130836, U54AI117804), DBV Technologies, Aimmune Therapeutics, Regeneron Pharmaceuticals, Takeda, and Allergenis. G. W. Falk is consultant for Ellodi, Sanofi/Regeneron, BMS/Celgene, Takeda, Ubiquity Bio, and Phathom Pharmaceuticals; and receives research funding from Arena/Pfizer, Ellodi, Sanofi/Regeneron, BMS/Celgene, Takeda, Allakos, Nexteos, and Celldex Therapeutics. G. T. Furuta receives research funding from Pfizer/Arena; is consultant for Sanofi/Regeneron and BMS; and is chief medical officer for EnteroTrack. N. P. Gonsalves is consultant for Allakos, AstraZeneca, BMS, and Sanofi/Regeneron; is speaker for Sanofi/Regeneron; and receives publication royalties from UpToDate. S. K. Gupta is consultant/data safety monitoring board member of Adare, BMS, QOL, Takeda, MedScape, PVI, ViaSkin, and UpToDate; and receives research funding from Allakos, Ellodi, and AstraZeneca. I. Hirano has received research funding from Ellodi/Adare, Allakos, Pfizer/Arena Pharmaceuticals, AstraZeneca, Meritage Pharma, Receptos/Celgene, Sanofi, Regeneron, and Shire/Takeda; and is is consultant for Ellodi/Adare, Allakos, AstraZeneca, BMS/Receptos/Celgene, Calyx/Parexel, EsoCap Biotech, Gossamer Bio, Lilly, Meritage Pharma, Pfizer/Arena Pharmaceuticals, Phathom, Sanofi/Regeneron, and Shire/Takeda. K. A. Peterson is consultant/advisory for AGA, Alladapt, AstraZeneca, Allakos, BMS, Ellodi, Invea, Lucid, Nexstone, WebMD, Peerview, Regeneron, Revolo, Takeda, and WebMD; receives research funding from AstraZeneca, Allakos, Regeneron-Sanofi, Revolo, Adare, Ellodi, BMS, and Celldex; is speaker for AGA, Regeneron, Peerview, Takeda, Allakos, and WebMD; has grant support (unrestricted) from Allakos; and has equity in Nexeos Bio. M. A. Pletneva is consultant for Allakos and Sanofi/Regeneron. J. M. Spergel is consultant for Novartis, Regeneron, and Sanofi; and receives grant support from Regeneron and Sanofi. J. B. Wechsler is speaker for Sanofi/Regeneron; and consultant for Sanofi/Regeneron, Celldex, Celgene/Receptos/BMS, Allakos, Ellodi, and AstraZeneca. M. E. Rothenberg is consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Allakos, Celldex, Nextstone One, BMS, AstraZeneca, Ellodi Pharma, Glaxo Smith Kline, Sanofi/Regeneron, Revolo Biotherapeutics, and Guidepoint; has equity interest in the first 6 listed; receives royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust), and UpToDate; and is an inventor of patents owned by Cincinnati Children’s Hospital Medical Center. T. Shoda is a coinventor of patents owned by Cincinnati Children’s Hospital Medical Center. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)
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- 2024
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203. Infusion of active compound into sliced button mushrooms through vacuum impregnation to improve functionality: Comparing response surface methodology and artificial neural network.
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Wagh MD, Alam MS, Roy T, and Gupta SK
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- Vacuum, Food Handling methods, Nutritive Value, Temperature, Hydrogen-Ion Concentration, Neural Networks, Computer, Ascorbic Acid analysis, Agaricus chemistry
- Abstract
The present study explores the infusion of active compounds (ascorbic acid and calcium lactate) into sliced button mushrooms (Agaricus bisporus) to increase the nutritional value and reduce the browning effect of sliced mushrooms using the vacuum impregnation (VI) technique. The aim was to functionalize the vacuum-infused sliced mushrooms and evaluate the physicochemical properties of button mushrooms for diversifying food use. The central composite design was implemented to determine the optimized condition for the process with four independent factors, that is, immersion time (IT) 30-90 min, solution temperature (ST) 35-55°C, solution concentration (SC) 4%-12%, and vacuum pressure (VP) 50-170 mbar. The optimum VI processes obtained were ST-40°C, SC-8%, VP-140 mbar, and IT-65 min with a desirability function of 0.77. Statistically, two models (response surface methodology [RSM] and artificial neural network [ANN]) were employed to compare the better performance for the prediction of VI operational process parameters. The RSM model showed a better prediction of VI process parameters than the ANN model, with a higher R
2 value (0.9228 vs. 0.8160) and lower root mean square error value (1.4004 vs. 2.1751), χ2 (2.4491 vs. 5.2762), mean absolute error (1.1177 vs. 1.1611), and absolute average deviation (4.3532 vs. 5.6746) for water loss. A similar pattern was observed for solute gain, ascorbic acid, titratable acidity, color change, firmness, and pH. Therefore, the VI process was found to be an effective method for enhancing the nutritional properties of sliced mushrooms. These findings concluded that the RSM model is more efficient for better prediction with good accuracy of the VI process than the ANN model., (© 2024 Institute of Food Technologists.)- Published
- 2024
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204. A pre-B acute lymphoblastic leukemia cell line model reveals the mechanism of thalidomide therapy-related B-cell leukemogenesis.
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Ramani M, Singh RK, Shrivastva S, Ribeyron L, Gupta SK, and Roy A
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- Humans, Cell Line, Tumor, Lenalidomide pharmacology, Trans-Activators metabolism, Trans-Activators genetics, Gene Expression Regulation, Leukemic drug effects, Proto-Oncogene Proteins, Ikaros Transcription Factor metabolism, Ikaros Transcription Factor genetics, Thalidomide pharmacology, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
Lenalidomide, a thalidomide derivative, is prescribed as maintenance therapy for multiple myeloma (MM). Patients with MM receiving lenalidomide were found to develop a distinct therapy-related B cell acute lymphoblastic leukemia (B-ALL). However, the molecular mechanism by which lenalidomide drives B-ALL is unknown. We show that thalidomide treatment of B cell lines increased CD34 expression and fibronectin adhesion. This resembled the effects of Ikzf1 loss of function mutations in B-ALL. IKZF1 is a transcription factor that can act as both a transcriptional activator and a repressor depending upon the target loci. In our experiments, thalidomide-induced degradation of IKZF1 increased the expression of its transcriptional repression targets Itga5 and CD34 explaining the increased adhesion and stemness. Strikingly, withdrawal of thalidomide lead to the mis-localization of IKZF1 to the cytoplasm. Moreover, chromatin immunoprecipitation data showed a long-term effect of thalidomide treatment on IKZF1 target loci. This included decreased chromatin occupancy at early B cell factor 1 (EBF1) and Spi1 (PU.1). Consequently, B-cell lineage specifying transcription factors including Pax5, Spi1 and EBF1 were downregulated even after 7 days of thalidomide withdrawal. Our study thus provides a molecular mechanism of thalidomide-induced B-ALL whereby thalidomide alters the chromatin occupancy of IKZF1 at key B-cell lineage transcription factors leading to a persistent block in B-cell differentiation., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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205. Bystander Effects, Pharmacokinetics, and Linker-Payload Stability of EGFR-Targeting Antibody-Drug Conjugates Losatuxizumab Vedotin and Depatux-M in Glioblastoma Models.
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Jain S, Griffith JI, Porath KA, Rathi S, Le J, Pasa TI, Decker PA, Gupta SK, Hu Z, Carlson BL, Bakken K, Burgenske DM, Feldsien TM, Lefebvre DR, Vaubel RA, Eckel-Passow JE, Reilly EB, Elmquist WF, and Sarkaria JN
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- Animals, Humans, Mice, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Cell Line, Tumor, Female, Glioblastoma drug therapy, Glioblastoma pathology, Glioblastoma metabolism, Immunoconjugates pharmacokinetics, Immunoconjugates pharmacology, Immunoconjugates administration & dosage, ErbB Receptors antagonists & inhibitors, Xenograft Model Antitumor Assays, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized pharmacokinetics, Bystander Effect
- Abstract
Purpose: Antibody-drug conjugates (ADC) are targeted therapies with robust efficacy in solid cancers, and there is intense interest in using EGFR-specific ADCs to target EGFR-amplified glioblastoma (GBM). Given GBM's molecular heterogeneity, the bystander activity of ADCs may be important for determining treatment efficacy. In this study, the activity and toxicity of two EGFR-targeted ADCs with similar auristatin toxins, Losatuxizumab vedotin (ABBV-221) and Depatuxizumab mafodotin (Depatux-M), were compared in GBM patient-derived xenografts (PDX) and normal murine brain following direct infusion by convection-enhanced delivery (CED)., Experimental Design: EGFRviii-amplified and non-amplified GBM PDXs were used to determine in vitro cytotoxicity, in vivo efficacy, and bystander activities of ABBV-221 and Depatux-M. Nontumor-bearing mice were used to evaluate the pharmacokinetics (PK) and toxicity of ADCs using LC-MS/MS and immunohistochemistry., Results: CED improved intracranial efficacy of Depatux-M and ABBV-221 in three EGFRviii-amplified GBM PDX models (Median survival: 125 to >300 days vs. 20-49 days with isotype control AB095). Both ADCs had comparable in vitro and in vivo efficacy. However, neuronal toxicity and CD68+ microglia/macrophage infiltration were significantly higher in brains infused with ABBV-221 with the cell-permeable monomethyl auristatin E (MMAE), compared with Depatux-M with the cell-impermeant monomethyl auristatin F. CED infusion of ABBV-221 into the brain or incubation of ABBV-221 with normal brain homogenate resulted in a significant release of MMAE, consistent with linker instability in the brain microenvironment., Conclusions: EGFR-targeting ADCs are promising therapeutic options for GBM when delivered intratumorally by CED. However, the linker and payload for the ADC must be carefully considered to maximize the therapeutic window., (©2024 The Authors; Published by the American Association for Cancer Research.)
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- 2024
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206. Microglial mediators in autoimmune Uveitis: Bridging neuroprotection and neurotoxicity.
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Sharma M, Pal P, and Gupta SK
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- Humans, Animals, Microglia immunology, Uveitis immunology, Autoimmune Diseases immunology, Neuroprotection
- Abstract
Autoimmune uveitis, a severe inflammatory condition of the eye, poses significant challenges due to its complex pathophysiology and the critical balance between protective and detrimental immune responses. Central to this balance are microglia, the resident immune cells of the central nervous system, whose roles in autoimmune uveitis are multifaceted and dynamic. This review article delves into the dual nature of microglial functions, oscillating between neuroprotective and neurotoxic outcomes in the context of autoimmune uveitis. Initially, we explore the fundamental aspects of microglia, including their activation states and basic functions, setting the stage for a deeper understanding of their involvement in autoimmune uveitis. The review then navigates through the intricate mechanisms by which microglia contribute to disease onset and progression, highlighting both their protective actions in immune regulation and tissue repair, and their shift towards a pro-inflammatory, neurotoxic profile. Special emphasis is placed on the detailed pathways and cellular interactions underpinning these dual roles. Additionally, the review examines the potential of microglial markers as diagnostic and prognostic indicators, offering insights into their clinical relevance. The article culminates in discussing future research directions, and the ongoing challenges in translating these findings into effective clinical applications. By providing a comprehensive overview of microglial mechanisms in autoimmune uveitis, this review underscores the critical balance of microglial activities and its implications for disease management and therapy development., Competing Interests: Declaration of generative AI and AI assisted technologies in the writing process During the preparation of this work the author(s) used Microsoft Copilot in order to improve the language and readability. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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207. Exploring the Efficacy of Large Language Models in Summarizing Mental Health Counseling Sessions: Benchmark Study.
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Adhikary PK, Srivastava A, Kumar S, Singh SM, Manuja P, Gopinath JK, Krishnan V, Gupta SK, Deb KS, and Chakraborty T
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- Humans, Adult, Mental Disorders therapy, Female, Benchmarking, Counseling methods
- Abstract
Background: Comprehensive session summaries enable effective continuity in mental health counseling, facilitating informed therapy planning. However, manual summarization presents a significant challenge, diverting experts' attention from the core counseling process. Leveraging advances in automatic summarization to streamline the summarization process addresses this issue because this enables mental health professionals to access concise summaries of lengthy therapy sessions, thereby increasing their efficiency. However, existing approaches often overlook the nuanced intricacies inherent in counseling interactions., Objective: This study evaluates the effectiveness of state-of-the-art large language models (LLMs) in selectively summarizing various components of therapy sessions through aspect-based summarization, aiming to benchmark their performance., Methods: We first created Mental Health Counseling-Component-Guided Dialogue Summaries, a benchmarking data set that consists of 191 counseling sessions with summaries focused on 3 distinct counseling components (also known as counseling aspects). Next, we assessed the capabilities of 11 state-of-the-art LLMs in addressing the task of counseling-component-guided summarization. The generated summaries were evaluated quantitatively using standard summarization metrics and verified qualitatively by mental health professionals., Results: Our findings demonstrated the superior performance of task-specific LLMs such as MentalLlama, Mistral, and MentalBART evaluated using standard quantitative metrics such as Recall-Oriented Understudy for Gisting Evaluation (ROUGE)-1, ROUGE-2, ROUGE-L, and Bidirectional Encoder Representations from Transformers Score across all aspects of the counseling components. Furthermore, expert evaluation revealed that Mistral superseded both MentalLlama and MentalBART across 6 parameters: affective attitude, burden, ethicality, coherence, opportunity costs, and perceived effectiveness. However, these models exhibit a common weakness in terms of room for improvement in the opportunity costs and perceived effectiveness metrics., Conclusions: While LLMs fine-tuned specifically on mental health domain data display better performance based on automatic evaluation scores, expert assessments indicate that these models are not yet reliable for clinical application. Further refinement and validation are necessary before their implementation in practice., (©Prottay Kumar Adhikary, Aseem Srivastava, Shivani Kumar, Salam Michael Singh, Puneet Manuja, Jini K Gopinath, Vijay Krishnan, Swati Kedia Gupta, Koushik Sinha Deb, Tanmoy Chakraborty. Originally published in JMIR Mental Health (https://mental.jmir.org), 23.07.2024.)
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- 2024
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208. Autocombustion Route Derived Zinc Ferrite Nanoparticles as Chemiresistive Sensor for Detection of Alcohol Vapors.
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Bhagat B, Gupta SK, Mandal D, Bandyopadhyay R, and Mukherjee K
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Prolonged exposure to alcohol vapors can have detrimental effects on human health, potentially leading to eye irritation, dizziness, and in some cases, damage to the nervous system. The present article aims to provide a comprehensive understanding on the synthesis and characterization of zinc ferrite (ZnFe
2 O4 ) nanoparticles, as well as their interactions with a range of alcohol vapors, including methanol, ethanol, n-propanol, and isopropanol. These alcohols differ in their molecular weight, boiling points, diffusivity, and other properties. The study reveals the semiconducting ZnFe2 O4 nanoparticulate sensor's capability for reversible, repeatable, and sensitive detection of alcohol vapors. The sensor exhibits the highest response to ethanol within operating temperature range (225-300 °C). An attempt is made to establish a correlation between the properties of the target analytes and the observed sensing signals. Additionally, the response conductance transients of ZnFe2 O4 under the exposure to the studied alcohol vapors are modeled based on the Langmuir-Hinshelwood adsorption mechanism. The characteristic time constants obtained from this modeling are justified with respect to the properties of the analytes., (© 2024 Wiley-VCH GmbH.)- Published
- 2024
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209. The Role of Branched Chain Ketoacid Dehydrogenase Kinase (BCKDK) in Skeletal Muscle Biology and Pathogenesis.
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Fernicola J, Vyavahare S, Gupta SK, Kalwaghe A, Kosmac K, Davis A, Nicholson M, Isales CM, Shinde R, and Fulzele S
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- Humans, Animals, Aging metabolism, Aging genetics, Muscular Diseases metabolism, Muscular Diseases pathology, Muscular Diseases genetics, 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) metabolism, 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) genetics, Protein Kinases, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Amino Acids, Branched-Chain metabolism
- Abstract
Muscle wasting can be caused by nutrition deficiency and inefficient metabolism of amino acids, including Branched Chain Amino Acids (BCAAs). Branched Chain Amino Acids are a major contributor to the metabolic needs of healthy muscle and account for over a tenth of lean muscle mass. Branched chain alpha-ketoacid dehydrogenase (BCKD) is the rate limiting enzyme of BCAA metabolism. Inhibition of BCKD is achieved through a reversible phosphorylation event by Branched Chain a-ketoacid dehydrogenase kinase (BCKDK). Our study set out to determine the importance of BCKDK in the maintenance of skeletal muscle. We used the Gene Expression Omnibus Database to understand the role of BCKDK in skeletal muscle pathogenesis, including aging, muscular disease, and interrupted muscle metabolism. We found BCKDK expression levels were consistently decreased in pathologic conditions. These results were most consistent when exploring muscular disease followed by aging. Based on our findings, we hypothesize that decreased BCKDK expression alters BCAA catabolism and impacts loss of normal muscle integrity and function. Further research could offer valuable insights into potential therapeutic strategies for addressing muscle-related disorders.
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- 2024
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210. Enhancing sports image data classification in federated learning through genetic algorithm-based optimization of base architecture.
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Fu S, Huang J, Hazra D, Dwivedi AK, Gupta SK, Shivahare BD, and Garg D
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- Humans, Deep Learning, Neural Networks, Computer, Algorithms, Sports
- Abstract
Nowadays, federated learning is one of the most prominent choices for making decisions. A significant benefit of federated learning is that, unlike deep learning, it is not necessary to share data samples with the model owner. The weight of the global model in traditional federated learning is created by averaging the weights of all clients or sites. In the proposed work, a novel method has been discussed to generate an optimized base model without hampering its performance, which is based on a genetic algorithm. Chromosome representation, crossover, and mutation-all the intermediate operations of the genetic algorithm have been illustrated with useful examples. After applying the genetic algorithm, there is a significant improvement in inference time and a huge reduction in storage space. Therefore, the model can be easily deployed on resource-constrained devices. For the experimental work, sports data has been used in balanced and unbalanced scenarios with various numbers of clients in a federated learning environment. In addition, we have used four famous deep learning architectures, such as AlexNet, VGG19, ResNet50, and EfficientNetB3, as the base model. We have achieved 92.34% accuracy with 9 clients in the balanced data set by using EfficientNetB3 as the base model using a GA-based approach. Moreover, after applying the genetic algorithm to optimize EfficientNetB3, there is an improvement in inference time and storage space by 20% and 2.35%, respectively., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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211. Extreme arterial tortuosity with ascending aortic aneurysm in a child with suspected Cutis Laxa syndrome.
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Singh D, Pandey NN, Gupta SK, and Jagia P
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- 2024
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212. Community perspective and healthcare assessment in malaria endemic states of India: a cross-sectional study protocol.
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B M S, H C V, Singhal R, Singh K, N SN, Tripathi PK, Singh P, Eapen A, Singh SP, Sinha DP, Malla WA, Gupta SK, Yadav CP, Singh P, Aggarwal CS, P Choudhary V, Sharma R, Jain T, Sharma A, Anvikar AR, Goel A, and Rahi M
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- Humans, India epidemiology, Cross-Sectional Studies, Research Design, Antimalarials therapeutic use, Health Knowledge, Attitudes, Practice, Delivery of Health Care, Malaria epidemiology, Malaria prevention & control, Endemic Diseases
- Abstract
Introduction: India's contribution to the malaria burden was highest in South-East Asia Region in 2021, accounting for 79% of the estimated malaria cases and 83% of malaria-related deaths. Intensified Malaria Control Programme supported by Global Funds to Fight against AIDS, Tuberculosis and Malaria has deployed crucial interventions to reduce the overall burden of malaria in India. Evaluation of utilisation of malaria elimination interventions by the community and assessment of the healthcare system is underway in eleven high malaria endemic states in India. Health system preparedness for malaria elimination, logistics, and supply chain management of diagnostic kits and anti-malarial drugs in addition to the knowledge, attitude and practice of the healthcare workers is also being assessed., Methods and Analysis: The study is being undertaken in 11 malaria endemic states with a variable annual parasite incidence of malaria. In total, 47 districts (administrative unit of malaria control operations) covering 37 976 households are to be interviewed and assessed. We present here the protocol following which the study is being undertaken at the behest and approval of Ministry of Health and Family Welfare in India., Ethics and Dissemination: No patients were involved in the study. Study findings will be shared with Institutional ethics board of National Institute for Malaria Research New Delhi (NIMR) in a timely, comprehensive, accurate, unbiased, unambiguous and transparent manner and to the National Vector-borne Disease (Malaria) Control Programme officers and the Community public who participated. Important findings will be communicated through community outreach meetings which are existing in the Health system. Results will be informed to study participants via local fieldwork supervised by District Malaria Officers. Also findings will be published in reputed journals based on Indian Council of Medical Research (ICMR) publication policy.The ICMR-NIMR ethics committee approved the study via letter No. NIMR/ECM/2023/Feb/14 dated 24 April 2023 for version 5. All standard ethical practices will be followed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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213. Pulsed Field vs Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation: Recurrent Atrial Arrhythmia Burden.
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Reddy VY, Mansour M, Calkins H, d'Avila A, Chinitz L, Woods C, Gupta SK, Kim J, Eldadah ZA, Pickett RA, Winterfield J, Su WW, Waks JW, Schneider CW, Richards E, Albrecht EM, Sutton BS, and Gerstenfeld EP
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- Humans, Male, Female, Middle Aged, Aged, Quality of Life, Treatment Outcome, Atrial Fibrillation surgery, Atrial Fibrillation therapy, Atrial Fibrillation physiopathology, Catheter Ablation methods, Recurrence
- Abstract
Background: The ADVENT randomized trial revealed no significant difference in 1-year freedom from atrial arrhythmias (AA) between thermal (radiofrequency/cryoballoon) and pulsed field ablation (PFA). However, recent studies indicate that the postablation AA burden is a better predictor of clinical outcomes than the dichotomous endpoint of 30-second AA recurrence., Objectives: The goal of this study was to determine: 1) the impact of postablation AA burden on outcomes; and 2) the effect of ablation modality on AA burden., Methods: In ADVENT, symptomatic drug-refractory patients with paroxysmal atrial fibrillation underwent PFA or thermal ablation. Postablation transtelephonic electrocardiogram monitor recordings were collected weekly or for symptoms, and 72-hour Holters were at 6 and 12 months. AA burden was calculated from percentage AA on Holters and transtelephonic electrocardiogram monitors. Quality-of-life assessments were at baseline and 12 months., Results: From 593 randomized patients (299 PFA, 294 thermal), using aggregate PFA/thermal data, an AA burden exceeding 0.1% was associated with a significantly reduced quality of life and an increase in clinical interventions: redo ablation, cardioversion, and hospitalization. There were more patients with residual AA burden <0.1% with PFA than thermal ablation (OR: 1.5; 95% CI: 1.0-2.3; P = 0.04). Evaluation of outcomes by baseline demographics revealed that patients with prior failed class I/III antiarrhythmic drugs had less residual AA burden after PFA compared to thermal ablation (OR: 2.5; 95% CI: 1.4-4.3; P = 0.002); patients receiving only class II/IV antiarrhythmic drugs pre-ablation had no difference in AA burden between ablation groups., Conclusions: Compared with thermal ablation, PFA more often resulted in an AA burden less than the clinically significant threshold of 0.1% burden. (The FARAPULSE ADVENT PIVOTAL Trial PFA System vs SOC Ablation for Paroxysmal Atrial Fibrillation [ADVENT]; NCT04612244)., Competing Interests: Funding Support and Author Disclosures This study was funded by Boston Scientific. Dr Reddy has been a consultant to and received equity from Farapulse (now divested); has received grant support from and served as a consultant to Boston Scientific; has served as a consultant for and has equity in Ablacon, Acutus Medical, Affera-Medtronic, Anumana, Apama Medical-Boston Scientific, APN Health, Append Medical, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, Cardiofocus, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Laminar Medical, LuxMed, Medlumics, Neutrace, Nuvera-Biosense Webster, Oracle Health, Pulse Biosciences, Restore Medical, Sirona Medical, SoundCath, and Valcare, unrelated to this manuscript; has served as a consultant for Abbott, Adagio Medical, AtriAN, Biosense Webster, BioTel Heart, Biotronik, Cairdac, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Novo Nordisk, and Philips, unrelated to this work; and has equity in Atraverse, DRS Vascular, Manual Surgical Sciences, Newpace, Nyra Medical, Surecor, and Vizaramed, unrelated to this work. Dr Mansour has been a consultant for Boston Scientific, Biosense Webster, Abbott, Medtronic, Siemens, and SentreHeart/Atricure; and has equity in EPD-Philips (divested) and NewPace Ltd. Dr Calkins has been a consultant to and received honoraria from Boston Scientific. Dr d’Avila has received an honorarium and grant support from Biosense, Biotronik, and Abbott. Dr Waks was previously on the advisory board for HeartcoR solutions; and performs current core lab work for HeartcoR solutions, both unrelated to this trial. Dr Chinitz has been a consultant to and received speaker honoraria from Biosense Webster, Abbott, Medtronic, and Biotronik. Dr Woods has received equity in Inheart and Solopace; has intellectual property with EnsoETM and SoloPace; and has been a consultant to Abbott and Atricure. Dr Gupta has been a consultant for Medtronic and Boston Scientific. Dr Kim has been a consultant for Boston Scientific and Biosense Webster. Dr Pickett has been a consultant for Boston Scientific and Medtronic. Dr Winterfield has been a consultant for Biosense Webster, Abbott, Boston Scientific, and Thermedical. Dr Su has been a consultant to and received research support from Boston Scientific Inc. Mr Schneider, Ms Richards, Dr Albrecht, and Dr Sutton are employes of Boston Scientific. Dr Gerstenfeld has been a consultant to Boston Scientific, Biosense Webster, and Adagio Medical; has received lecture honoraria from Boston Scientific, Medtronic, Biosense Webster, Adagio Medical, and Abbott; and has received research grants from Abbott, Biosense Webster, and Adagio Medical. Dr Eldadah has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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214. Role of [18F]FDG - PET/CT Scan in Cervical Tuberculosis.
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Kumar S, Singh P, Gupta SK, Verma AK, and Kumar S
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Background: Distribution and quantification of extra-pulmonary tuberculosis and elicitation of response antitubercular therapy via F18-Fluorodeoxyglucose Positron Emission-based Tomography/ Computed Tomography(F18-FDG PET/CT)., Materials and Methods: This was a prospective Pilot study. In this study 30 patients of age between 15 to 36 years(mean 26.8±6.13years) were included. PET/CT scan was performed at the time of presentation(baseline) and after 2 months of anti-tubercular therapy to evaluate bacterial activity in different levels of cervical lymph nodes and changes in various parameters of lymph nodes such as size, conglomeration and abscess formation were included in the evaluation., Result: In this study, 18 patients were of 18 to 30 years(60.0%), 3 patients were below 18 years(10.0%) and 9 patients above 30 years(30%). The female proportion was higher in our study population(53.3%). Node-positive status, conglomeration, and abscess were evaluated clinically. Maximum percentages were found in level II and level V groups. While minimum percentage was found in level I and level VI. We also found that in all patients of tubercular cervical lymphadenopathy, tubercular bacterial activity was found at some distant sites also the common sites were the lung(56.7%), mediastinum(53.3%), abdomen(36.7%) and bone(23.3%). The response of antitubercular therapy by F18 - FDG PET/CT scan after 2 months of treatment was checked. There was a significant change in standardized uptake value(SUV-max) pre-treatment and post-treatment at all distant sites except the bony site., Conclusion: F18-FDG PET/CT scan is a non-invasive tool in monitoring the response of antitubercular chemotherapy in patients of extrapulmonary and multiorgan lymphadenopathy., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Nuclear Medicine.)
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- 2024
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215. Pulmonary stenosis-related proteinuria misdiagnosed as nephrotic syndrome.
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Faisal NV, Kadiyani L, and Gupta SK
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Competing Interests: There are no conflicts of interest.
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- 2024
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216. Evaluation and comparison of sonographic difficult airway assessment parameters with clinical airway predictors.
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Anushaprasath U, Kumar M, Kamal M, Bhatia P, Kaloria N, Paliwal B, Gupta SK, Mohammed S, and Sharma A
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Background and Aims: None of the clinical difficult airway predictors are 100% sensitive and specific. Ultrasound is being used for airway assessment, but there is still no established parameters or model to predict difficult laryngoscopy. This observational study was planned to determine the predictive ability of clinical and sonography-based airway assessment parameters for difficult laryngoscopy and intubation., Material and Methods: A total of 130 patients of 18-60 years of age undergoing elective intubation were included. The distribution of Cormack-Lehane (CL) grade and intubation difficulty scale (IDS) was correlated with the clinical and sonographic screening parameters for difficult airways., Results: The prevalence of difficult laryngoscopy and difficult intubation in our study was 17.6% and 11.5%, respectively. Mallampati grade (MMG), upper lip bite test (ULBT), neck circumference, hyomental distance ratio (HMDR), tongue thickness (TT), skin to epiglottis/epiglottis to vocal cord distance (SED/E-VC), and mandibular condylar mobility (MCM) had significant association with the difficult laryngoscopy and MMG, neck circumference, SED, SED/E-VC; MCM had significant association with the difficult intubation. The combination of these predictors showed better diagnostic ability for difficult airways. Model 1 based on ultrasound parameters showed an area under the curve (AUC) of 0.848 (CI- 0.748-0.947, P value < 0.0001) and model 2 based on combined clinical and ultrasound parameters showed an AUC of 0.755 (95% CI- 0.631-0.879, P value < 0.0001)., Conclusions: Ultrasound-based airway predictors can help in predicting difficult laryngoscopy and intubation along with the clinical parameters. Individual sonographic predictors have moderately satisfactory diagnostic profiles. The models based on combined tests have better diagnostic value., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Anaesthesiology Clinical Pharmacology.)
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- 2024
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217. Hourglass-Shaped Homo- and Heteronuclear Nonanuclear Lanthanide Clusters: Structures, Magnetism, Photoluminescence, and Theoretical Analysis.
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Pandey P, Chauhan D, Walawalkar MG, Gupta SK, Meyer F, Rajaraman G, and Murugavel R
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Synthesis of nonameric cationic clusters [Dy
9 (acac)16 (μ3 -OH)8 (μ4 -OH)2 ]OH·6H2 O ( 1 ), [Dy8 Tb (acac)16 (μ3 -OH)8 (μ4 -OH)2 ]OH·2H2 O ( 2 ), and [Gd9 (acac)16 (μ3 -OH)8 (μ4 -OH)2 ]OH·6H2 O ( 3 ) (acac = acetylacetonate) is reported. The emission spectrum of 1 shows Dy(III) ion characteristic bands assignable to the4 F9/2 →6 HJ ( J = 15/2 to 9/2) transitions. Emission due to both Dy(III) and Tb(III) ions is observed for 2 in the visible range, with Tb(III) specific bands appearing due to the5 D4 →7 FJ ( J = 6, 4, and 3) transitions. Cluster 3 exhibits a significant magnetocaloric effect (MCE), with -Δ Sm values increasing with decrease in temperature and increase in field, reaching -Δ Sm max = 20.98 J kg-1 K-1 at 2 K and 9 T. Isotropic magnetic coupling constants ( Js ) in 3 derived from density functional theory (DFT) calculations reveal that the exchange interactions are antiferromagnetic and weak. Compound 3 possesses S = 7/2 ground state arising from the central Gd(III) ion along with several nested excited states due to competing antiferromagnetic interactions that yield reasonably large MCE values. Utilizing computed exchange coupling interactions, we have performed ab initio CASSCF/RASSI-SO/POL_ANISO calculations on antiferromagnetic 1 and 2 to estimate the exchange interactions using the Lines model. For 2 , Dy(III)···Tb(III) exchange interactions were extracted for the first time and were found to be weakly antiferromagnetically coupled.- Published
- 2024
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218. Dual Drainage Total Anomalous Pulmonary Venous Connection With Infracardiac and Supracardiac Drainage.
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Faisal NV, Akhtar S, Pandey NN, and Gupta SK
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- Humans, Pulmonary Veins abnormalities, Pulmonary Veins surgery, Scimitar Syndrome surgery
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Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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219. Comparative Analysis of P-selectin Levels in Psoriasis, Vitiligo, and Nonskin Disease in a Tertiary Care Hospital: A Case-Control Study.
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Kumar J, Tiwari S, Suvirya S, Verma N, Chaudhary M, and Gupta SK
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- Humans, Male, Female, Case-Control Studies, Adult, Middle Aged, Tertiary Care Centers, Young Adult, Biomarkers blood, Psoriasis blood, Vitiligo blood, P-Selectin blood, Severity of Illness Index
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Introduction: The role and function of P-selectin levels in various inflammatory and immune-mediated diseases have been established. Whether they have an association with inflammatory skin diseases such as vitiligo and psoriasis needs to be established., Objective: The objective of this study was to assess P-selectin levels in psoriasis and vitiligo and to compare them with matched controls without skin disease., Materials and Methods: The study included a total of 90 subjects with age- and sex-matched - 30 each in psoriasis, vitiligo and 30 controls without skin disease. Psoriasis and vitiligo severity was assessed using the Psoriasis Area and Severity Index and the Vitiligo Area Scoring Index scores. P-selectin levels were assessed and compared among the groups. P-selectin levels were also compared with the severity of psoriasis and vitiligo. Chi-square and analysis of variance tests were used to compare the data., Results: The mean age of subjects was 36.28 ± 11.80 years. Majority of the subjects were males (65.6%). The three groups were matched for age, sex, and other demographics. The mean P-selectin levels were 610.43 ± 134.19, 292.52 ± 60.99, and 158.97 ± 34.76 ng/ml, respectively, in the psoriasis, vitiligo, and control groups, respectively (P < 0.001). No significant association of P-selectin levels was observed with psoriasis severity; however, with increasing vitiligo severity, there was a significant increase in P-selectin levels (P < 0.001)., Conclusion: Patients with skin diseases have raised P-selectin levels. Within skin diseases, inflammatory diseases such as psoriasis have higher P-selectin levels as compared to autoimmune diseases such as vitiligo. A significant association of P-selectin levels was observed with vitiligo severity but not with psoriasis severity., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)
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- 2024
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220. Stature estimation from the scapula measurements using 3D-volume rendering technique by regression equations in the Northern Indian population.
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Raj K KV, Gokul G, Yadav A, Gupta SK, Tyagi S, and Srinivasamurthy A
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- Humans, Male, Female, India, Adult, Middle Aged, Regression Analysis, Aged, Young Adult, Cadaver, Aged, 80 and over, Scapula anatomy & histology, Scapula diagnostic imaging, Body Height, Forensic Anthropology methods, Imaging, Three-Dimensional, Multidetector Computed Tomography
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The present study assessed the correlation between the stature and scapular measurements from both sides in order to develop population-specific regression equations to estimate the stature from measurements of the scapula in a contemporary Northern Indian population individually for the left and right sides. A total of 597 cadavers underwent postmortem multidetector computed tomography and subsequent medicolegal autopsy in our department between August 2021 and August 2022. Two hundred samples (100 males and 100 females) were randomly collected based on inclusion and exclusion criteria. Six linear anthropometric measurements of the scapula from either side were measured using the 3D volume-rendered technique by an electronic cursor. Each anthropometric measurement showed a significant difference between males and females ( p < 0.05). Regression analysis was applied to match the taken measurements against stature. The accuracy to predict stature ranged from 3.99 to 4.94 cm for males and from 4.49 to 5.27 cm for females, respectively. Left-sided measurements were better predictors of stature than the right side in both genders. The results of this study indicate that scapular measurements could be useful to estimate the stature of Northern Indian individuals, particularly in scenarios of disaster victim identification lacking long bones, which are considered to be better predictors to date., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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221. Advances in Alzheimer's disease: A multifaceted review of potential therapies and diagnostic techniques for early detection.
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Sharma M, Pal P, and Gupta SK
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- Humans, Animals, Cholinesterase Inhibitors therapeutic use, Cholinesterase Inhibitors pharmacology, Alzheimer Disease diagnosis, Alzheimer Disease drug therapy, Alzheimer Disease metabolism, Alzheimer Disease therapy, Alzheimer Disease genetics, Early Diagnosis
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Alzheimer's disease (AD) remains one of the most formidable neurological disorders, affecting millions globally. This review provides a holistic overview of the therapeutic strategies, both conventional and novel, aimed at mitigating the impact of AD. Initially, we delve into the conventional approach, emphasizing the role of Acetylcholinesterase (AChE) inhibition, which has been a cornerstone in AD management. As our understanding of AD evolves, several novel potential approaches emerge. We discuss the promising roles of Butyrylcholinesterase (BChE) inhibition, Tau Protein inhibitors, COX-2 inhibition, PPAR-γ agonism, and FAHH inhibition, among others. The potential of the endocannabinoids (eCB) system, cholesterol-lowering drugs, metal chelators, and MMPs inhibitors are also explored, culminating in the exploration of the pivotal role of microRNA in AD progression. Parallel to these therapeutic insights, we shed light on the novel tools and methodologies revolutionizing AD research. From the quantitative analysis of gene expression by qRTPCR to the evaluation of mitochondrial function using induced pluripotent stem cells (iPSCs), the advances in diagnostic and research tools offer renewed hope. Moreover, we explore the current landscape of clinical trials, highlighting the leading drug interventions and their respective stages of development. This comprehensive review concludes with a look into the future perspectives, capturing the potential breakthroughs and innovations on the horizon. Through a synthesis of current knowledge and emerging research, this article aims to provide a consolidated resource for clinicians, researchers, and academicians in the realm of Alzheimer's disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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222. Rheological and dielectric behavior of sodium carboxymethyl cellulose (NaCMC)/Ca 2+ and esterified NaCMC/Ca 2+ hydrogels: Correlating microstructure and dynamics with properties.
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Gupta SK, Deshpande AP, and Kumar R
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Polyelectrolyte-based conductive hydrogels are being extensively explored for applications in energy storage and as electrode materials for batteries. We synthesized ionically crosslinked sodium carboxymethyl cellulose (NaCMC), esterified NaCMC, and Ca
2+ doped esterified NaCMC hydrogels. This work aims to understand the effect of Ca2+ ions on the NaCMC and esterified NaCMC. FTIR, SEM, Rheology and EIS studies were performed to understand the structure and dynamics of hydrogels. Results confirmed that Ca2+ ions have an important role in determining the rheological and dielectric response of hydrogels. Power law behavior was observed in their rheological response with exponent (n) of 0.81 for G' and 0.76 for G″ of ionically crosslinked NaCMC, 5.38 for G' and 4.70 for G″ of esterified NaCMC, whereas, negative exponents -1.44 for G' and -1.10 for G″ of Ca2+ ion doped esterified NaCMC. Ionically crosslinked NaCMC hydrogels have relaxation times (τ) in the range of 8.9 × 10-5 s-2.8 × 10-5 s may be due to the formation of temporary dipoles by electrostatic bridge formations with dc conductivity of (0.1 S/cm-5 S/cm), whereas, esterified NaCMC showed relaxation times (10-3 s-8.9 × 10-5 s) with increasing ester crosslinks and dc conductivity of (0.05 S/cm-0.8 S/cm). Interestingly, Ca2+ ion doped esterified hydrogels showed multiple dielectric relaxations on Ca2+ ion addition with different relaxation times may be due to change in ionic environment. The understanding obtained from this work may be useful for designing tuneable hydrogels with optimum electrical and mechanical properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)- Published
- 2024
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223. Transcatheter pulmonary valve implantation with custom-made 35-mm Myval™ transcatheter heart valve.
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Ramakrishnan S, Faisal NV, Kadiyani L, Gupta SK, and Sivaprakasam MC
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Transcatheter pulmonary valve implantation (TPVI) is the standard of care in patients with repaired tetralogy of Fallot (rTOF) presenting with right ventricular outflow tract (RVOT) dysfunction. However, the feasibility of TPVI is limited by the high cost and nonavailability of larger-sized valves for dilated native RVOT of rTOF patients. We report the first successful TPVI with a custom-made 35 mm balloon-expandable valve (Myval™) in a 30-year-old rTOF patient with severe pulmonary regurgitation and RV dysfunction., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Annals of Pediatric Cardiology.)
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- 2024
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224. ATM inhibition exploits checkpoint defects and ATM-dependent double strand break repair in TP53-mutant glioblastoma.
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Laverty DJ, Gupta SK, Bradshaw GA, Hunter AS, Carlson BL, Calmo NM, Chen J, Tian S, Sarkaria JN, and Nagel ZD
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- Humans, Cell Line, Tumor, Mutation, Drug Resistance, Neoplasm genetics, Drug Resistance, Neoplasm drug effects, DNA Repair drug effects, Brain Neoplasms genetics, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Brain Neoplasms metabolism, Animals, DNA End-Joining Repair drug effects, Mice, Phosphorylation drug effects, Ataxia Telangiectasia Mutated Proteins metabolism, Ataxia Telangiectasia Mutated Proteins antagonists & inhibitors, Ataxia Telangiectasia Mutated Proteins genetics, Glioblastoma genetics, Glioblastoma drug therapy, Glioblastoma metabolism, Glioblastoma pathology, Tumor Suppressor Protein p53 metabolism, Tumor Suppressor Protein p53 genetics, DNA Breaks, Double-Stranded drug effects, Temozolomide pharmacology
- Abstract
Determining the balance between DNA double strand break repair (DSBR) pathways is essential for understanding treatment response in cancer. We report a method for simultaneously measuring non-homologous end joining (NHEJ), homologous recombination (HR), and microhomology-mediated end joining (MMEJ). Using this method, we show that patient-derived glioblastoma (GBM) samples with acquired temozolomide (TMZ) resistance display elevated HR and MMEJ activity, suggesting that these pathways contribute to treatment resistance. We screen clinically relevant small molecules for DSBR inhibition with the aim of identifying improved GBM combination therapy regimens. We identify the ATM kinase inhibitor, AZD1390, as a potent dual HR/MMEJ inhibitor that suppresses radiation-induced phosphorylation of DSBR proteins, blocks DSB end resection, and enhances the cytotoxic effects of TMZ in treatment-naïve and treatment-resistant GBMs with TP53 mutation. We further show that a combination of G2/M checkpoint deficiency and reliance upon ATM-dependent DSBR renders TP53 mutant GBMs hypersensitive to TMZ/AZD1390 and radiation/AZD1390 combinations. This report identifies ATM-dependent HR and MMEJ as targetable resistance mechanisms in TP53-mutant GBM and establishes an approach for simultaneously measuring multiple DSBR pathways in treatment selection and oncology research., (© 2024. The Author(s).)
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- 2024
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225. Electrocatalytic OER behavior of the Bi-Fe-O system: an understanding from the perspective of the presence of oxygen vacancies.
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Jyoti S, Vijay A, Terranova U, Gupta SK, Sudarshan K, and Vaidya S
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This study aims to understand and correlate the role of the nature and relative concentration of oxygen vacancies with the trend observed in the OER with the Bi-Fe-O system. To understand this, we first investigated the system of oxides using X-ray photoelectron spectroscopy (XPS) and electron paramagnetic resonance (EPR), which revealed the presence of oxygen vacancies in the system. Density functional theory (DFT) was employed to investigate the relative concentration of these vacancies by calculating their formation energies. Positron annihilation lifetime spectroscopy (PALS) was carried out to understand the nature of these oxygen vacancies. We observed that the presence of a higher concentration of monovacancies created due to the absence of oxygen from the structure of Bi
2 Fe4 O9 was mainly responsible for the high performance of the oxide towards the OER compared to that of the other oxides viz -BiFeO3 and Bi25 FeO40 of the Bi-Fe-O system.- Published
- 2024
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226. Identification and Analysis of Atrial-Bronchial-Abdominal Disharmony in Patients with Isomeric Atrial Appendages.
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Vidiyala P, Pandey NN, Gupta SK, Sreelal TV, Verma M, Kumar S, Ramakrishnan S, and Jagia P
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Ideally, the morphology of atrial appendages should solely be used to identify and differentiate patients with isomeric right and left atrial appendages. However, in clinical practice, the segregation is often indirectly based on the arrangement of thoraco-abdominal structures. The correlation between thoraco-abdominal arrangement and atrial appendages, however, is imperfect. In this study, we sought to clarify the cardiovascular malformations in patients with isomeric atrial appendages with an emphasis on atrial-thoracic-abdominal disharmony. A retrospective review of all patients who underwent cardiac CT angiography between January 2014 and June 2023 and identified to have isomeric atrial appendages was performed. Of the 366 cases (median age: 2 years [interquartile range: 11 months-7 years]), 247 (67.5%) patients had isomeric right atrial appendages while 119 (32.5%) patients had isomeric left atrial appendages. In 316 (86.3%) patients, the thoraco-abdominal arrangement was as per atrial appendage morphology while the remaining 50 (13.6%) patients had disharmonious patterns. Compared to isomeric left atrial appendages, the disharmonious pattern was more frequent with isomeric right atrial appendages (5.9% vs. 17.4%; p 0.003). Irrespective of the type of isomerism, disharmony was mostly confined to the level of the abdomen. Not all patients with isomeric atrial appendages have a harmonious thoraco-abdominal arrangement. The atrial-bronchial-abdominal disharmony is more frequent with isomeric right atrial appendages and is mostly present at the level of the abdomen. A detailed sequential segmental analysis with an independent description of each organ system is, therefore, essential for the complete evaluation of patients with isomeric atrial appendages., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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227. Malaria Vector Bionomics: Countrywide Surveillance Study on Implications for Malaria Elimination in India.
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Rahi M, Mishra AK, Chand G, Baharia RK, Hazara RK, Singh SP, Khan S, Sreehari U, Kamaraju D, Kumar G, Gupta SK, Sharma A, Raghavendra K, Gunasekaran K, Singh OP, and Subbarao SK
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- India epidemiology, Animals, Humans, Disease Eradication methods, Insecticides, Insecticide Resistance, Ecology, Mosquito Vectors, Malaria prevention & control, Malaria epidemiology, Anopheles drug effects
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Background: The biological characteristics of mosquito vectors vary, impacting their response to control measures. Thus, having up-to-date information on vector bionomics is essential to maintain the effectiveness of existing control strategies and tools, particularly as India aims for malaria elimination by 2030., Objective: This study aims to assess the proportions of vector species resting indoors and outdoors, determine their preference for host biting/feeding, identify transmission sites, and evaluate the susceptibility of vectors to insecticides used in public health programs., Methods: Mosquito collections were conducted in 13 districts across 8 Indian states from 2017 to 2020 using various methods to estimate their densities. Following morphological identification in the field, sibling species of Anopheles mosquitoes were identified molecularly using polymerase chain reaction (PCR)-specific alleles. Plasmodium falciparum and Plasmodium vivax infections in the vectors were detected using enzyme-linked immunosorbent assay (ELISA) and PCR assays. In addition, we assessed the insecticide susceptibility status of primary malaria vectors following the World Health Organization (WHO) protocol., Results: Anopheles culicifacies, a primary malaria vector, was collected (with a man-hour density ranging from 3.1 to 15.9) from all states of India except those in the northeastern region. Anopheles fluviatilis, another primary vector, was collected from the states of Madhya Pradesh, Maharashtra, Karnataka, and Odisha. In Haryana and Karnataka, An. culicifacies sibling species A predominated, whereas species C and E were predominant in Madhya Pradesh and Maharashtra. An. culicifacies displayed mainly endophilic behavior across all states, except in Madhya Pradesh, where the proportion of semigravid and gravid mosquitoes was nearly half of that of unfed mosquitoes. The human blood index of An. culicifacies ranged from 0.001 to 0.220 across all study sites. The sporozoite rate of An. culicifacies ranged from 0.06 to 4.24, except in Madhya Pradesh, where none of the vector mosquitoes were found to be infected with the Plasmodium parasite. In the study area, An. culicifacies exhibited resistance to DDT (dichlorodiphenyltrichloroethane; with <39% mortality). Moreover, it showed resistance to malathion (with mortality rates ranging from 49% to 78%) in all districts except Angul in Odisha and Palwal in Haryana. In addition, resistance to deltamethrin was observed in districts of Maharashtra, Gujarat, Haryana, and Karnataka., Conclusions: Our study offers vital insights into the prevalence, resting behavior, and sibling species composition of malaria vectors in India. It is evident from our findings that resistance development in An. culicifacies, the primary vector, to synthetic pyrethroids is on the rise in the country. Furthermore, the results of our study suggest a potential change in the resting behavior of An. culicifacies in Madhya Pradesh, although further studies are required to confirm this shift definitively. These findings are essential for the development of effective vector control strategies in India, aligning with the goal of malaria elimination by 2030., (©Manju Rahi, AK Mishra, Gyan Chand, RK Baharia, RK Hazara, SP Singh, Siraj Khan, U Sreehari, Divya Kamaraju, Gaurav Kumar, Sanjeev Kumar Gupta, Amit Sharma, K Raghavendra, K Gunasekaran, Om P Singh, Sarala K Subbarao. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 17.06.2024.)
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228. Genome analysis of Salmonella enterica serovar enteritis strains isolated from poultry and humans in Burkina Faso.
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Kagambèga A, Ramadan H, Dione M, Bouda SC, Hiott LM, McMillan EA, Sharma P, Gupta SK, Barro N, Jackson CR, and Frye JG
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Whole-genome sequencing (WGS) was used to characterize four Salmonella enterica Enteritidis isolates from poultry ( n=2 ) and human ( n=2 ) from Ouagadougou, Burkina Faso. Antimicrobial resistance genes, chromosomal mutations, and mobile genetic elements were identified by analysis of WGS data using sequence homology., Competing Interests: The authors declare no conflict of interest.
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- 2024
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229. Dynamin-1 is a potential mediator in Cancer-Related Cognitive Impairment.
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Ng DQ, Hudson C, Nguyen T, Gupta SK, Koh YQ, Acharya MM, and Chan A
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Dynamin-1 (DNM1) consolidates memory through synaptic transmission and modulation and has been explored as a therapeutic target in Alzheimer's disease. Through a two-prong approach, this study examined its role in cancer-related cognitive impairment (CRCI) pathogenesis using human and animal models. The human study recruited newly diagnosed, chemotherapy-naïve adolescent and young adult cancer and non-cancer controls to complete a cognitive instrument (FACT-Cog) and blood draws for up to three time points. Concurrently, a syngeneic young-adult WT (C57BL/6 female) mouse model of breast cancer was developed to study DNM1 expression in the brain. Samples from eighty-six participants with 30 adolescent and young adult (AYA) cancer and 56 non-cancer participants were analyzed. DNM1 levels were significantly lower among cancer participants compared to non-cancer prior to treatment. While receiving cancer treatment, cognitively impaired patients were found with a significant downregulation of DNM1, but not among those without impairment. In murine breast cancer-bearing mice receiving chemotherapy, we consistently found a significant decline in DNM1 immunoreactivity in the hippocampal CA1 and CA3 subregions. Observed in both human and animal studies, the downregulation of DNM1 is linked with the onset of CRCI. Future research should explore the potential of DNM1 in CRCI pathogenesis and therapeutics development.
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- 2024
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230. Data from collection and analysis of RNA sequencing data from pearl millet.
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Kambara K, Gupta SK, Takano T, and Tsugama D
- Abstract
Pearl millet ( Pennisetum glaucum , also known as Cenchrus americanus ) is a cereal crop that has a C4 photosynthesis system and that can grow and develop seeds even under stressed conditions including drought-stressed, high temperature-stressed and nutrient-poor conditions. In previous studies, transcriptomes of pearl millet were studied by RNA sequencing (RNA-Seq) to understand mechanisms regulating its development and tolerance to such stressed conditions. Here, RNA-Seq reads from 565 pearl millet samples from 25 projects in the NCBI (National Center for Biotechnology Information) BioProject database were collected and mapped to the pearl millet reference genome to obtain read counts and transcripts per million (TPM) for each pearl millet gene. The count and TPM data for all the 565 samples as well as the attributes of those samples and projects were deposited in the figshare repository (https://doi.org/10.6084/m9.figshare.24902100)., (© 2024 The Author(s).)
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- 2024
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231. Unveiling the genetic structure of pig population in a Himalayan state Uttarakhand through microsatellite and mitochondrial DNA analyses.
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Sahu K, Gopi GV, and Gupta SK
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- Animals, India, Genetics, Population, Female, Genotype, Microsatellite Repeats, DNA, Mitochondrial analysis, DNA, Mitochondrial genetics, Genetic Variation, Sus scrofa genetics, Haplotypes
- Abstract
This study traced the maternal lineage of the domestic swine populations using mitochondrial DNA control region markers and genetic diversity using microsatellite markers in Uttarakhand, an Indian state situated at the foothills of the world's youngest (geo-dynamically sensitive) mountain system, "the Himalayas". Analysis of 68 maternally unrelated individuals revealed 20 haplotypes. The maternal signature of the Pacific, Southeast Asian, European, and ubiquitously distributed Chinese haplotypes was present in Uttarakhand's domestic pig population. The D3 haplotype reported in wild pigs from North India was also identified in 47 domestic samples. A unique gene pool, UKD (Uttarakhand Domestic), as another lineage specific to this region has been proposed. Genotypes were analyzed, using 13 sets of microsatellite markers. The observed (Ho) and expected (He) heterozygosities were 0.83 ± 0.02 and 0.84 ± 0.01, respectively. The average polymorphic information content value of 0.83 ± 0.01 indicated the high informativeness of the marker. The overall mean F
IS value for all the microsatellite markers was low (F = 0.04, P < 0.01). Seven loci deviated from Hardy-Weinberg equilibrium (HWE) at a significant level (p < 0.05). Two clusters were identified, indicating overlapping populations. These results suggested that though belonging to different maternal lineages, the traditional management practices in Uttarakhand have allowed for genetic mixing and the sharing of genetic material among pig populations. It could contribute to increased genetic diversity but might also result in the loss of distinct genetic characteristics or breed purity of the local breeds if not carefully managed., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)- Published
- 2024
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232. Modulating the effective ionic radii of trivalent dopants in ceria using a combination of dopants to improve catalytic efficiency for the oxygen evolution reaction.
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Das D, Prakash J, Bandyopadhyay A, Balhara A, Goutam UK, Acharya R, Gupta SK, and Sudarshan K
- Abstract
Aliovalent doping in ceria and defect engineering are important aspects in tuning the properties of ceria for advanced technological applications, especially in the emerging field of electrocatalytic water-splitting for harvesting renewable energy. However, the ambiguity regarding the choice of dopants/co-dopants and ways to deal with the size difference between dopants and lattice hosts remains a long-standing problem. In this study, ceria was aliovalently codoped with Sc
3+ and La3+ while keeping the total concentration of dopants constant; the ionic radius of the former is smaller and that of the latter is larger than Ce4+ . Variations in the relative amounts of these dopants helped to modulate the effective ionic radii and match that of the host. A systematic study on the role of these aliovalent dopants in defect evolution in ceria and in modulating the Ce3+ fraction using powder XRD, Rietveld refinement, positron annihilation lifetime spectroscopy, X-ray photoelectron spectroscopy, Eu3+ photoluminescence, and Raman spectroscopy is presented here. The evolved defects and their dependence on subtle factors other than charge compensation are further correlated with their electrocatalytic activity towards oxygen evolution reaction (OER) in alkaline medium. The catalyst with an optimum defect density, maximum Ce3+ fraction at the surface and the least effective ionic radius difference between the dopants and the host demonstrated the best performance towards the OER. This study demonstrates how effective ionic radius modulation in defect-engineered ceria through a judicious choice of codopants can enhance the catalytic property of ceria and provides immensely helpful information for designing ceria-based heterogeneous catalysts with desired functionalities., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)- Published
- 2024
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233. Phenotyping and a genome-wide association study of elite lines of pearl millet.
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Kambara K, Gupta SK, Takano T, and Tsugama D
- Abstract
Pearl millet ( Pennisetum glaucum (L.) R. BR.) is a cereal crop mainly grown in India and sub-Saharan Africa. In pearl millet, genes and genomic regions associated with traits are largely unknown. Pearl millet parental lines bred at the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) are useful for the production and breeding of pearl millet. However, the phenotypic diversity of these lines has not been fully evaluated. In this study, 16 traits of 107 of those parental lines were assessed with field trials in Japan, and a genome-wide association study (GWAS) was performed using these phenotypic data to identify the genomic regions and genes associated with those traits. The GWAS revealed genomic regions associated with culm height and pigmentation of the shoot basal part (PS). The genomic region associated with PS contained a homolog of PHENYLALANINE AMMONIA LYASE 2 ( PAL2 ), a gene involved in anthocyanin accumulation in Arabidopsis thaliana . The PAL2 homolog can be a candidate for a gene involved in regulating PS in pearl millet. These results provide a better understanding of the phenotypic diversity of pearl millet and its genetic background., (Copyright © 2024 by JAPANESE SOCIETY OF BREEDING.)
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- 2024
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234. Regulatory roles of microRNAs in modulating mitochondrial dynamics, amyloid beta fibrillation, microglial activation, and cholinergic signaling: Implications for alzheimer's disease pathogenesis.
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Sharma M, Tanwar AK, Purohit PK, Pal P, Kumar D, Vaidya S, Prajapati SK, Kumar A, Dhama N, Kumar S, and Gupta SK
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- Humans, Animals, Signal Transduction physiology, Alzheimer Disease metabolism, Alzheimer Disease genetics, MicroRNAs metabolism, MicroRNAs genetics, Amyloid beta-Peptides metabolism, Mitochondrial Dynamics physiology, Microglia metabolism
- Abstract
Alzheimer's Disease (AD) remains a formidable challenge due to its complex pathology, notably involving mitochondrial dysfunction and dysregulated microRNA (miRNA) signaling. This study delves into the underexplored realm of miRNAs' impact on mitochondrial dynamics and their interplay with amyloid-beta (Aβ) aggregation and tau pathology in AD. Addressing identified gaps, our research utilizes advanced molecular techniques and AD models, alongside patient miRNA profiles, to uncover miRNAs pivotal in mitochondrial regulation. We illuminate novel miRNAs influencing mitochondrial dynamics, Aβ, and tau, offering insights into their mechanistic roles in AD progression. Our findings not only enhance understanding of AD's molecular underpinnings but also spotlight miRNAs as promising therapeutic targets. By elucidating miRNAs' roles in mitochondrial dysfunction and their interactions with hallmark AD pathologies, our work proposes innovative strategies for AD therapy, aiming to mitigate disease progression through targeted miRNA modulation. This contribution marks a significant step toward novel AD treatments, emphasizing the potential of miRNAs in addressing this complex disease., Competing Interests: Declaration of Competing Interest All author(s) declare no conflict of interest., (Published by Elsevier Ltd.)
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- 2024
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235. Benzimidazole-derived carbohydrazones as dual monoamine oxidases and acetylcholinesterase inhibitors: design, synthesis, and evaluation.
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Kumar S, Jaiswal S, Gupta SK, and Ayyannan SR
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- Structure-Activity Relationship, Humans, Molecular Dynamics Simulation, Molecular Structure, Binding Sites, Monoamine Oxidase Inhibitors chemistry, Monoamine Oxidase Inhibitors pharmacology, Monoamine Oxidase Inhibitors chemical synthesis, Cholinesterase Inhibitors chemistry, Cholinesterase Inhibitors pharmacology, Cholinesterase Inhibitors chemical synthesis, Benzimidazoles chemistry, Benzimidazoles pharmacology, Benzimidazoles chemical synthesis, Molecular Docking Simulation, Acetylcholinesterase chemistry, Acetylcholinesterase metabolism, Monoamine Oxidase metabolism, Monoamine Oxidase chemistry, Drug Design, Hydrazones chemistry, Hydrazones pharmacology, Hydrazones chemical synthesis
- Abstract
A series of novel benzimidazole-derived carbohydrazones was designed, synthesized and evaluated for their dual inhibition potential against monoamine oxidases (MAOs) and acetylcholinesterase (AChE) using multitarget-directed ligand approach (MTDL). The investigated compounds have exhibited moderate to excellent in vitro MAOs/AChE inhibitory activity at micromolar to nanomolar concentrations. Compound 12 , 2-(1 H -Benzo[d]imidazol-1-yl)- N' -[1-(4-hydroxyphenyl) ethylidene]acetohydrazide has emerged as a lead dual MAO-AChE inhibitor by exhibiting superior multi-target activity profile against MAO-A (IC
50 = 0.067 ± 0.018 µM), MAO-B (IC50 = 0.029 ± 0.005 µM) and AChE (IC50 = 1.37 ± 0.026 µM). SAR studies suggest that the site A (hydrophobic ring) and site C (semicarbazone linker) modifications attempted on the semicarbazone-based MTDL resulted in a significant enhancement in the MAO-A/B inhibitory potential and a drastic decrease in the AChE inhibitory activity. Further, molecular docking and dynamics simulation experiments disclosed the possible molecular interactions of inhibitors inside the active site of respective enzymes. Also, computational prediction of drug-likeness and ADME parameters of test compounds revealed their drug-like characteristics.Communicated by Ramaswamy H. Sarma.- Published
- 2024
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236. Role of plant neurotransmitters in salt stress: A critical review.
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Malakar P, Gupta SK, and Chattopadhyay D
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- Plants metabolism, Salt Tolerance, Neurotransmitter Agents metabolism, Plant Physiological Phenomena, Salt Stress, Signal Transduction
- Abstract
Neurotransmitters are naturally found in many plants, but the molecular processes that govern their actions still need to be better understood. Acetylcholine, γ-Aminobutyric acid, histamine, melatonin, serotonin, and glutamate are the most common neurotransmitters in animals, and they all play a part in the development and information processing. It is worth noting that all these chemicals have been found in plants. Although much emphasis has been placed on understanding how neurotransmitters regulate mood and behaviour in humans, little is known about how they regulate plant growth and development. In this article, the information was reviewed and updated considering current thinking on neurotransmitter signaling in plants' metabolism, growth, development, salt tolerance, and the associated avenues for underlying research. The goal of this study is to advance neurotransmitter signaling research in plant biology, especially in the area of salt stress physiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
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- 2024
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237. Pattern of Medical Device Adverse Events in a Tertiary Care Hospital in Northern India: An Ambispective Study.
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Saifuddin PK, Prakash A, Samujh R, Gupta SK, Suri V, Kumar RM, Sharma S, and Medhi B
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- Humans, India epidemiology, Male, Adult, Female, Prospective Studies, Retrospective Studies, Young Adult, Middle Aged, Equipment and Supplies adverse effects, Tertiary Care Centers statistics & numerical data
- Abstract
Background: Knowledge about the pattern of adverse events caused by medical devices (MDs) is limited in India. We aimed to assess the pattern of MD adverse events (MDAEs) in a tertiary hospital in Northern India., Materials and Methods: This descriptive study was conducted ambispectively at various clinical departments of PGIMER, Chandigarh. We followed the guidelines edged by the Materiovigilance Program of India (MvPI) to conduct this study. The prospective study (PS) was done from January to December 2020, with a concurrent retrospective study (RS) proceeding to 3 years to learn more about the reporting culture, demographics, notification status, risk class of defective devices, and the type of adverse events., Results: We received 224 MDAE in the PS and identified 413 MDAE in the RS. Reporting of adverse events to the national MvPI was negligible in the RS. In the PS, nurses reported the majority of MDAEs (65%), followed by doctors (30%). The occurrence of MDAE was higher in males (PS; 52%, RS; 57%) and age groups between 21 and 30 years (PS; 19.1%, RS; 23.2%) in both studies. MDAEs were frequent in low- to moderate-risk devices (class B: 66%) in the PS, while it was documented only for high-risk devices (class C: 51% and class D: 49%) in the RS. Most of the serious adverse events (SAEs) were reported among moderate to high-risk devices, and an increased frequency of SAE (60.4%) was observed among nonnotified MDs. The overall incidence of near-miss events was 14%., Conclusion: Knowledge of MDAEs and reporting of defective devices to regulatory authorities is essential to prevent further incidence. Adverse events caused by MDs are ubiquitous irrespective of their risk classification, notification status, and patient demographic factors. Accelerated reporting of MDAE by all cadre of healthcare professionals is urgently required to safeguard the health of Indians., (© Journal of the Association of Physicians of India 2024.)
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- 2024
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238. Unique among high passes: Phylogenetic inferences from DNA barcoding of the butter fl y fauna of Ladakh Trans-Himalaya, India.
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Ali M, Dey R, Das M, Kumar V, Chandra K, Uniyal VP, and Gupta SK
- Abstract
The butterfly assemblage of Ladakh Trans-Himalaya demands a thorough analysis of their population genetic structure owing to their typical biogeographic affinity and their adaptability to extreme cold-desert climates. No such effort has been taken till date, and in this backdrop, we created a barcode reference library of 60 specimens representing 23 species. Barcodes were generated from freshly collected leg samples using the Sanger sequencing method, followed by phylogenetic clade analyses and divergence calculation. Our data represents 22% of Ladakh's Rhopaloceran fauna with the novel barcode submission for six species, including one Schedule II species, Paralasa mani . Contrary to the 3% threshold rule, the interspecific divergence between two species pairs of typical mountain genus Hyponephele and Karanasa was found to be 2.3% and 2.2%, respectively. The addition of conspecific global barcodes revealed that most species showed little increase in divergence value, while a two-fold increase was noted in a few species. Bayesian clade clustering outcomes largely aligned with current morphological classifications, forming monophyletic clades of conspecific barcodes, with only minor exceptions observed for the taxonomically complicated genus Polyommatus and misidentified records of Aulocera in the database. We also observed variations within the same phylogenetic clades forming nested lineages, which may be attributed to the taxonomic intricacies present at the subspecies level globally, mostly among Eurasian species. Overall, our effort not only substantiated the effectiveness of DNA Barcoding for the identification and conservation of this climatically vulnerable assemblage but also highlighted the significance of deciphering the unique genetic composition among this geographically isolated population of Ladakh butterflies., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest or competing interests associated with the research presented in this paper.
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- 2024
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239. Decreased Ocular Perfusion Pressure Associated With Reverse Ophthalmic Artery Flow on Transcranial Doppler Ultrasonography.
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Murillo BA, Cheng AM, Tsai J, and Gupta SK
- Abstract
Innovative applications of clinical ocular diagnostic tools are emerging to help identify systemic disorders that extend beyond ocular diseases. Ophthalmodynamometry (ODM) is a screening tool that non-invasively determines mean central retinal artery pressure (MCRAP) and ocular perfusion pressure (OPP). Decreased OPP and MCRAP on Falck Medical Multifunctional Device (FMD, Falck Medical, Inc., Mystic, CT), along with reverse ophthalmic artery flow (ROAF) on transcranial Doppler ultrasonography (TCD), indicate increased collateral brain perfusion and possible stenosis of the ophthalmic artery or internal carotid artery (ICA). In this case report, we describe the case of a 78-year-old female with ROAF, reduced MCRAP, and OPP in the right eye, confirmed by carotid duplex of 50-79% right ICA stenosis. Early application of ODM and TCD allowed for prompt diagnosis and management with a vascular specialist., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Murillo et al.)
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- 2024
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240. The Role of Aryl Hydrocarbon Receptor in Bone Biology.
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Vyavahare S, Ahluwalia P, Gupta SK, Kolhe R, Hill WD, Hamrick M, Isales CM, and Fulzele S
- Abstract
Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is crucial in maintaining the skeletal system. Our study focuses on encapsulating the role of AhR in bone biology and identifying novel signaling pathways in musculoskeletal pathologies using the GEO dataset. The GEO2R analysis identified 8 genes (CYP1C1, SULT6B1, CYB5A, EDN1, CXCR4B, CTGFA, TIPARP, and CXXC5A) involved in the AhR pathway, which play a pivotal role in bone remodeling. The AhR knockout in hematopoietic stem cells showed alteration in several novel bone-related transcriptomes (eg, Defb14, ZNF 51, and Chrm5). Gene Ontology Enrichment Analysis demonstrated 54 different biological processes associated with bone homeostasis. Mainly, these processes include bone morphogenesis, bone development, bone trabeculae formation, bone resorption, bone maturation, bone mineralization, and bone marrow development. Employing Functional Annotation and Clustering through DAVID, we further uncovered the involvement of the xenobiotic metabolic process, p450 pathway, oxidation-reduction, and nitric oxide biosynthesis process in the AhR signaling pathway. The conflicting evidence of current research of AhR signaling on bone (positive and negative effects) homeostasis may be due to variations in ligand binding affinity, binding sites, half-life, chemical structure, and other unknown factors. In summary, our study provides a comprehensive understanding of the underlying mechanisms of the AhR pathway in bone biology., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)
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- 2024
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241. Influence of climatic factors on the life stages of Aedes mosquitoes and vectorial transmission: A review.
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Prasad P, Gupta SK, Mahto KK, Kumar G, Rani A, Velan I, Arya DK, and Singh H
- Abstract
Background Objectives: Aedes aegypti and Aedes albopictus are two sympatric mosquito species that compete with each other for resources when their breeding habitats overlap. This study examines what happens when sympatric Aedes aegypti and Aedes albopictus mosquitoes' mate with each other and other species by looking at insemination rates, fecundity, and hatchability rate., Methods: We performed controlled mating experiments in laboratory setting, assessing both conspecific and interspecific crosses. We measured insemination rates, egg numbers, and hatching success to examine the reproductive interference dynamics between these two distinct mosquito species., Results: In the context of conspecific mating, it was observed that both female Ae. aegypti and Ae. albopictus exhibited high insemination rates, with percentages of 98% and 94%, respectively. However, interspecific mating exhibited interesting asymmetries: Ae. albopictus males achieved a notable insemination success rate of 28% when mating with Ae. aegypti females, while Ae. aegypti males achieved only 8% insemination success with Ae. albopictus females. Additionally, females that mated with interspecific males had reduced production of viable eggs compared to conspecific mating. Most notably, interspecific mating resulted in the production of infertile eggs, while conspecific mating led to successful hatching., Interpretation Conclusion: The study reveals that, Ae. aegypti and Ae. albopictus can asymmetrically interfere with each other's reproduction, causing a 'satyr' effect. This understanding of interspecific competition and reproductive interference in these mosquito species could impact their coexistence in shared breeding habitats., (Copyright © 2024 Copyright: © 2024 Journal of Vector Borne Diseases.)
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- 2024
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242. PermDroid a framework developed using proposed feature selection approach and machine learning techniques for Android malware detection.
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Mahindru A, Arora H, Kumar A, Gupta SK, Mahajan S, Kadry S, and Kim J
- Abstract
The challenge of developing an Android malware detection framework that can identify malware in real-world apps is difficult for academicians and researchers. The vulnerability lies in the permission model of Android. Therefore, it has attracted the attention of various researchers to develop an Android malware detection model using permission or a set of permissions. Academicians and researchers have used all extracted features in previous studies, resulting in overburdening while creating malware detection models. But, the effectiveness of the machine learning model depends on the relevant features, which help in reducing the value of misclassification errors and have excellent discriminative power. A feature selection framework is proposed in this research paper that helps in selecting the relevant features. In the first stage of the proposed framework, t-test, and univariate logistic regression are implemented on our collected feature data set to classify their capacity for detecting malware. Multivariate linear regression stepwise forward selection and correlation analysis are implemented in the second stage to evaluate the correctness of the features selected in the first stage. Furthermore, the resulting features are used as input in the development of malware detection models using three ensemble methods and a neural network with six different machine-learning algorithms. The developed models' performance is compared using two performance parameters: F-measure and Accuracy. The experiment is performed by using half a million different Android apps. The empirical findings reveal that malware detection model developed using features selected by implementing proposed feature selection framework achieved higher detection rate as compared to the model developed using all extracted features data set. Further, when compared to previously developed frameworks or methodologies, the experimental results indicates that model developed in this study achieved an accuracy of 98.8%., (© 2024. The Author(s).)
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- 2024
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243. A Hospital-Based Cross-Sectional Study on the Histopathology of Upper Gastrointestinal Tract Endoscopic Biopsy in Dyspeptic Patients.
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Mahto SK, Murmu SK, Kumar A, Paswan MK, Gupta SK, N V, and Ashu T
- Abstract
Background Dyspepsia is one of the most common GI complaints encountered in clinical practice. Histopathological assessment of endoscopic gastric mucosa biopsy is crucial to delineate the exact cause of dyspepsia to guide patients' management. Objectives The aim of this study was to determine the histopathological spectrum of upper gastrointestinal (GI) tract endoscopic biopsies and to study the age and sex distribution of the predominant upper GI lesions. Methods A cross-sectional study was conducted in the Department of Pathology, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India, from January 2022 to December 2023. All endoscopic mucosal biopsies of the esophagus, stomach, and duodenum (first and second parts) lesions were examined under a microscope for histopathological findings. Results Out of 250 endoscopic biopsies studied, there were 76 cases of esophageal biopsies, 149 cases of gastric biopsies, and 25 cases of duodenal biopsies. The male-to-female ratio was 1.2:1. Non-neoplastic lesions were more common than neoplastic lesions. The most common lesions encountered were esophagitis in the esophagus, gastritis in the stomach, and duodenitis in the duodenum. Conclusion The main organic cause of dyspepsia in our setting was chronic gastritis. We conclude that endoscopy of the upper GI tract and histopathological examination help in the earlier detection of both benign and malignant lesions. This aids in better timely management of the patients and improves the overall treatment provided resulting in a better prognosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Mahto et al.)
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- 2024
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244. Differential Distribution of the DNA-PKcs Inhibitor Peposertib Selectively Radiosensitizes Patient-derived Melanoma Brain Metastasis Xenografts.
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Ji J, Dragojevic S, Callaghan CM, Smith EJ, Talele S, Zhang W, Connors MA, Mladek AC, Hu Z, Bakken KK, Sarkaria PP, Carlson BL, Burgenske DM, Decker PA, Rashid MA, Jang MH, Gupta SK, Eckel-Passow JE, Elmquist WF, and Sarkaria JN
- Subjects
- Animals, Humans, Mice, Cell Line, Tumor, Sulfones pharmacology, Female, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors pharmacokinetics, Protein Kinase Inhibitors therapeutic use, Brain Neoplasms secondary, Brain Neoplasms drug therapy, Brain Neoplasms radiotherapy, DNA-Activated Protein Kinase antagonists & inhibitors, Radiation-Sensitizing Agents pharmacology, Radiation-Sensitizing Agents pharmacokinetics, Radiation-Sensitizing Agents therapeutic use, Melanoma drug therapy, Melanoma pathology, Xenograft Model Antitumor Assays
- Abstract
Radioresistance of melanoma brain metastases limits the clinical utility of conventionally fractionated brain radiation in this disease, and strategies to improve radiation response could have significant clinical impact. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is critical for repair of radiation-induced DNA damage, and inhibitors of this kinase can have potent effects on radiation sensitivity. In this study, the radiosensitizing effects of the DNA-PKcs inhibitor peposertib were evaluated in patient-derived xenografts of melanoma brain metastases (M12, M15, M27). In clonogenic survival assays, peposertib augmented radiation-induced killing of M12 cells at concentrations ≥100 nmol/L, and a minimum of 16 hours exposure allowed maximal sensitization. This information was integrated with pharmacokinetic modeling to define an optimal dosing regimen for peposertib of 125 mpk dosed just prior to and 7 hours after irradiation. Using this drug dosing regimen in combination with 2.5 Gy × 5 fractions of radiation, significant prolongation in median survival was observed in M12-eGFP (104%; P = 0.0015) and M15 (50%; P = 0.03), while more limited effects were seen in M27 (16%, P = 0.04). These data support the concept of developing peposertib as a radiosensitizer for brain metastases and provide a paradigm for integrating in vitro and pharmacokinetic data to define an optimal radiosensitizing regimen for potent DNA repair inhibitors., (©2024 The Authors; Published by the American Association for Cancer Research.)
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- 2024
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245. Brachytherapy at the nanoscale with protein functionalized and intrinsically radiolabeled [ 169 Yb]Yb 2 O 3 nanoseeds.
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Ghosh S, Patra S, Younis MH, Chakraborty A, Guleria A, Gupta SK, Singh K, Rakhshit S, Chakraborty S, Cai W, and Chakravarty R
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- Animals, Mice, Tissue Distribution, Nanoparticles chemistry, Isotope Labeling, Single Photon Emission Computed Tomography Computed Tomography, Mice, Inbred C57BL, Gum Arabic chemistry, Female, Glycoproteins chemistry, Cell Line, Tumor, Radioisotopes chemistry, Radioisotopes therapeutic use, Brachytherapy methods, Ytterbium chemistry
- Abstract
Purpose: Classical brachytherapy of solid malignant tumors is an invasive procedure which often results in an uneven dose distribution, while requiring surgical removal of sealed radioactive seed sources after a certain period of time. To circumvent these issues, we report the synthesis of intrinsically radiolabeled and gum Arabic glycoprotein functionalized [
169 Yb]Yb2 O3 nanoseeds as a novel nanoscale brachytherapy agent, which could directly be administered via intratumoral injection for tumor therapy., Methods:169 Yb (T½ = 32 days) was produced by neutron irradiation of enriched (15.2% in168 Yb) Yb2 O3 target in a nuclear reactor, radiochemically converted to [169 Yb]YbCl3 and used for nanoparticle (NP) synthesis. Intrinsically radiolabeled NP were synthesized by controlled hydrolysis of Yb3+ ions in gum Arabic glycoprotein medium. In vivo SPECT/CT imaging, autoradiography, and biodistribution studies were performed after intratumoral injection of radiolabeled NP in B16F10 tumor bearing C57BL/6 mice. Systematic tumor regression studies and histopathological analyses were performed to demonstrate therapeutic efficacy in the same mice model., Results: The nanoformulation was a clear solution having high colloidal and radiochemical stability. Uniform distribution and retention of the radiolabeled nanoformulation in the tumor mass were observed via SPECT/CT imaging and autoradiography studies. In a tumor regression study, tumor growth was significantly arrested with different doses of radiolabeled NP compared to the control and the best treatment effect was observed with ~ 27.8 MBq dose. In histopathological analysis, loss of mitotic cells was apparent in tumor tissue of treated groups, whereas no significant damage in kidney, lungs, and liver tissue morphology was observed., Conclusions: These results hold promise for nanoscale brachytherapy to become a clinically practical treatment modality for unresectable solid cancers., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2024
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246. Preclinical evaluation of engineered L-asparaginase variants to improve the treatment of Acute Lymphoblastic Leukemia.
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Sengupta S, Biswas M, Gandhi KA, Gupta SK, Gera PB, Gota V, and Sonawane A
- Abstract
Introduction: Escherichia coli l-asparaginase (EcA), an integral part of multi-agent chemotherapy protocols of acute lymphoblastic leukemia (ALL), is constrained by safety concerns and the development of anti-asparaginase antibodies. Novel variants with better pharmacological properties are desirable., Methods: Thousands of novel EcA variants were constructed using protein engineering approach. After preliminary screening, two mutants, KHY-17 and KHYW-17 were selected for further development. The variants were characterized for asparaginase activity, glutaminase activity, cytotoxicity and antigenicity in vitro. Immunogenicity, pharmacokinetics, safety and efficacy were tested in vivo. Binding of the variants to pre-existing antibodies in primary and relapsed ALL patients' samples was evaluated., Results: Both variants showed similar asparaginase activity but approximately 24-fold reduced glutaminase activity compared to wild-type EcA (WT). Cytotoxicity against Reh cells was significantly higher with the mutants, although not toxic to human PBMCs than WT. The mutants showed approximately 3-fold lower IgG and IgM production compared to WT. Pharmacokinetic study in BALB/c mice showed longer half-life of the mutants (KHY-17- 267.28±9.74; KHYW-17- 167.41±14.4) compared to WT (103.24±18). Single and repeat-doses showed no toxicity up to 2000 IU/kg and 1600 IU/kg respectively. Efficacy in ALL xenograft mouse model showed 80-90 % reduction of leukemic cells with mutants compared to 40 % with WT. Consequently, survival was 90 % in each mutant group compared to 10 % with WT. KHYW-17 showed over 2-fold lower binding to pre-existing anti-asparaginase antibodies from ALL patients treated with l-asparaginase., Conclusion: EcA variants demonstrated better pharmacological properties compared to WT that makes them good candidates for further development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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247. Pharmacologic Management of Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Diseases.
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Dellon ES and Gupta SK
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- Humans, Adrenal Cortex Hormones therapeutic use, Immunosuppressive Agents, Eosinophilia diagnosis, Eosinophilia drug therapy, Esophagitis drug therapy, Enteritis diagnosis, Enteritis drug therapy, Enteritis etiology
- Abstract
Data for pharmacologic treatments for non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal diseases (EGIDs) are limited. Nevertheless, because of the increasing understanding of EGID pathogenesis, a number of medications are used to treat EGIDs, though all are currently off-label. Initial therapy generally starts with corticosteroids, and "topical" delivery is preferred over systemic due to long-term side effects. A number of other small molecules could potentially be used, ranging from allergy medications to immunosuppressants. Biologics are also being used and investigated for EGIDs and represent promising targeted therapies. Multiple therapeutic targets have also been identified, many of which overlap with EoE targets., Competing Interests: Disclosure E.S. Dellon: Research funding: Adare/Ellodi, Allakos, ARENA, United States/Pfizer, AstraZeneca, United Kingdom, Eupraxia, Canada, GSK, Meritage, Miraca, Nutricia, United States, Celgene, United States/Receptos/BMS, Regeneron, United States, Revolo, Shire/Takeda. Consultant: Abbott, Abbvie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, Upstream Bio; Educational grant: Allakos, Aqilion, Holoclara, Invea. S.K. Gupta: Research funding: Adare/Ellodi, Allakos, Regeneron, Shire/Takeda. Consultant: Adare/Ellodi, Allakos, Celgene/Receptos/BMS, PeerViewRegeneron, Shire/Takeda., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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248. Fetal ductal constriction: An ominous but treatable entity!
- Author
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Kadiyani L, Rana A, Dadhwal V, and Gupta SK
- Abstract
Competing Interests: There are no conflicts of interest.
- Published
- 2024
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249. Interventional management of an unusual cause of cyanosis in repaired tetralogy of Fallot.
- Author
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Kadiyani L, Gupta SK, and Ramakrishnan S
- Abstract
Arterial desaturation following surgical repair of tetralogy of Fallot (TOF) is rare. In most instances, it results from residual right ventricular outflow tract obstruction, causing right-to-left shunt across residual interatrial or interventricular communication. In this report, we present an unusual scenario of arterial desaturation due to a recanalized left cardinal vein in a child with repaired TOF. We also discuss stepwise evaluation that led to successful identification and occlusion of the abnormal venous channel by percutaneous device closure., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Annals of Pediatric Cardiology.)
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- 2024
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250. Effect of Antibiotic Prophylaxis on Infection Rates in Pediatric Supracondylar Humerus Fractures Treated with Closed Reduction and Percutaneous Pinning: A Prospective Double-Blinded Randomized Controlled Trial.
- Author
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Gupta SK, Esposito ER, Phillips R, Schwab PE, Leary EV, and Hoernschemeyer DG
- Subjects
- Child, Humans, Anti-Bacterial Agents therapeutic use, Antibiotic Prophylaxis, Bone Nails adverse effects, Cefazolin therapeutic use, Prospective Studies, Retrospective Studies, Treatment Outcome, Double-Blind Method, Arthritis, Infectious etiology, Humeral Fractures surgery, Osteomyelitis etiology
- Abstract
Background: Supracondylar humerus fractures (SCHFs) are the most common elbow fracture in the pediatric population. In the case of displaced fractures, closed reduction and percutaneous Kirschner wire pinning (CRPP) is commonly performed. Infection rates are between 0 and 7%; however, retrospective studies have shown no benefit of preoperative antibiotics. There continues to be notable variability in antibiotic usage based on surgeon preference and local institutional policy. We conducted a double-blinded, randomized controlled trial to evaluate whether antibiotic prophylaxis reduces the risk of infection in pediatric SCHF patients treated with CRPP., Methods: Pediatric patients with displaced SCHF who presented to a pediatric hospital were enrolled and randomized into two groups. Group I received one dose of prophylactic antibiotics (25 mg/kg cefazolin IV up to 1g or clindamycin 10 mg/kg up to 600 mg/kg IV in the case of cefazolin allergy). Group II received placebo (10-mL prefilled syringe of normal saline). All patients underwent CRPP and casting followed by pin removal 3 to 6 weeks after the initial procedure. The presence of pin-site infection, erythema, drainage, septic arthritis, and osteomyelitis was recorded., Results: One hundred sixty patients were enrolled in the study. Eighty-two patients were randomized to receive antibiotics, and 78 patients were randomized to placebo. No difference was seen in the rate of infection between the treatment groups (1.2% in the antibiotic group versus 1.3% in the placebo group; P = 1.00). Presence of purulent drainage (0.0% versus 1.3%; P = 0.49), septic arthritis (0.0% versus 0.0%; P = 1.00), and osteomyelitis (1.2% versus 0.0%; P = 1.00) was similar in both groups. No difference in the need for additional antibiotics (1.2% versus 1.3%; P = 1.00) or additional surgery (1.2% versus 0.0%; P = 1.00) was found between groups., Discussion: The use of antibiotic prophylaxis did not affect the risk of infection in pediatric patients who underwent CRPP for displaced SCHF., Clinical Trial Registration: ClinicalTrials.gov: NCT03261830., Level of Evidence: Therapeutic Level I., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)
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- 2024
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