370 results on '"Ghosh, SS"'
Search Results
2. Nanocrystalline Powder Cores for High-Power High-Frequency Power Electronics Applications
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Jiang, C, Li, X, Ghosh, SS, Zhao, H, Shen, Y, Long, T, Jiang, C [0000-0001-5374-364X], Li, X [0000-0002-8087-8301], Ghosh, SS [0000-0002-1779-309X], Zhao, H [0000-0003-2384-1606], Shen, Y [0000-0002-4583-7811], Long, T [0000-0003-4401-102X], and Apollo - University of Cambridge Repository
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Metals ,toroidal inductor ,nanocry-stalline powder core ,Powders ,Air gaps ,soft magnetic composites ,Soft magnetic materials ,high-frequency magnetics ,Permeability ,Magnetic flux ,Magnetic cores ,Core loss - Abstract
Soft magnetic composites (SMCs) based magnetic cores are attractive in high frequency inductor design. The desired overall core permeability of SMC core can be achieved by adjusting the powder size, addition of insulation material and phosphoric acid, and pressure during the preparation process to reduce the air gap loss and ease the inductor design. The nanocrystalline alloy (Fe-Cu-Nb-Si-B) is an emerging SMC with high saturation flux density and low hysteresis loss, showing potential suitability for SMC based magnetic cores. To date, nanocrystalline alloys are mostly used in form of laminated ribbon for magnetic cores and nanocrystalline powder SMCs have been seldom used in practice. Also, neither experimental validation nor comparison with other commercialized and commonly used SMC cores has been reported. In this paper, the structure and manufacturing process of nanocrystalline powder cores are introduced. The calculation of core loss is defined for the nanocrystalline powder core. The characteristics and performance of the nanocrystalline powder toroidal core are compared with those of existing commercial SMC cores such as Fe-Si powder (X flux), Fe-Ni powder (High flux), Fe-Si-Al powder (Kool Mµ), FeNi-Mo powder (MPP). Experimental results are conducted at frequencies from 100 kHz to 600 kHz to verify the loss calculation and feasibility of this new nanocrystalline powder core.
- Published
- 2020
3. Brainhack: Developing a culture of open, inclusive, community-driven neuroscience
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Gau, R, Noble, S, Heuer, K, Bottenhorn, KL, Bilgin, IP, Yang, YF, Huntenburg, JM, Bayer, JMM, Bethlehem, RAI, Rhoads, SA, Vogelbacher, C, Borghesani, V, Levitis, E, Wang, HT, Van Den Bossche, S, Kobeleva, X, Legarreta, JH, Guay, S, Atay, SM, Varoquaux, GP, Huijser, DC, Sandström, MS, Herholz, P, Nastase, SA, Badhwar, AP, Dumas, G, Schwab, S, Moia, S, Dayan, M, Bassil, Y, Brooks, PP, Mancini, M, Shine, JM, O'Connor, D, Xie, X, Poggiali, D, Friedrich, P, Heinsfeld, AS, Riedl, L, Toro, R, Caballero-Gaudes, C, Eklund, A, Garner, KG, Nolan, CR, Demeter, DV, Barrios, FA, Merchant, JS, McDevitt, EA, Oostenveld, R, Craddock, RC, Rokem, A, Doyle, A, Ghosh, SS, Nikolaidis, A, Stanley, OW, Uruñuela, E, Anousheh, N, Arnatkeviciute, A, Auzias, G, Bachar, D, Bannier, E, Basanisi, R, Basavaraj, A, Bedini, M, Bellec, P, Benn, RA, Berluti, K, Bollmann, S, Bradley, C, Brown, J, Buchweitz, A, Callahan, P, Chan, MY, Chandio, BQ, Cheng, T, Chopra, S, Chung, AW, Close, TG, Combrisson, E, Cona, G, Constable, RT, Cury, C, Dadi, K, Damasceno, PF, Das, S, De Vico Fallani, F, DeStasio, K, Dickie, EW, Dorfschmidt, L, Duff, EP, DuPre, E, Dziura, S, Esper, NB, Esteban, O, Fadnavis, S, Flandin, G, Flannery, JE, Flournoy, J, Forkel, SJ, Gau, R, Noble, S, Heuer, K, Bottenhorn, KL, Bilgin, IP, Yang, YF, Huntenburg, JM, Bayer, JMM, Bethlehem, RAI, Rhoads, SA, Vogelbacher, C, Borghesani, V, Levitis, E, Wang, HT, Van Den Bossche, S, Kobeleva, X, Legarreta, JH, Guay, S, Atay, SM, Varoquaux, GP, Huijser, DC, Sandström, MS, Herholz, P, Nastase, SA, Badhwar, AP, Dumas, G, Schwab, S, Moia, S, Dayan, M, Bassil, Y, Brooks, PP, Mancini, M, Shine, JM, O'Connor, D, Xie, X, Poggiali, D, Friedrich, P, Heinsfeld, AS, Riedl, L, Toro, R, Caballero-Gaudes, C, Eklund, A, Garner, KG, Nolan, CR, Demeter, DV, Barrios, FA, Merchant, JS, McDevitt, EA, Oostenveld, R, Craddock, RC, Rokem, A, Doyle, A, Ghosh, SS, Nikolaidis, A, Stanley, OW, Uruñuela, E, Anousheh, N, Arnatkeviciute, A, Auzias, G, Bachar, D, Bannier, E, Basanisi, R, Basavaraj, A, Bedini, M, Bellec, P, Benn, RA, Berluti, K, Bollmann, S, Bradley, C, Brown, J, Buchweitz, A, Callahan, P, Chan, MY, Chandio, BQ, Cheng, T, Chopra, S, Chung, AW, Close, TG, Combrisson, E, Cona, G, Constable, RT, Cury, C, Dadi, K, Damasceno, PF, Das, S, De Vico Fallani, F, DeStasio, K, Dickie, EW, Dorfschmidt, L, Duff, EP, DuPre, E, Dziura, S, Esper, NB, Esteban, O, Fadnavis, S, Flandin, G, Flannery, JE, Flournoy, J, and Forkel, SJ
- Published
- 2021
4. A Standards Organization for Open and FAIR Neuroscience: the International Neuroinformatics Coordinating Facility
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Abrams, MB, Bjaalie, JG, Das, S, Egan, GF, Ghosh, SS, Goscinski, WJ, Grethe, JS, Kotaleski, JH, Ho, ETW, Kennedy, DN, Lanyon, LJ, Leergaard, TB, Mayberg, HS, Milanesi, L, Moucek, R, Poline, JB, Roy, PK, Strother, SC, Tang, TB, Tiesinga, P, Wachtler, T, Wojcik, DK, Martone, ME, Abrams, MB, Bjaalie, JG, Das, S, Egan, GF, Ghosh, SS, Goscinski, WJ, Grethe, JS, Kotaleski, JH, Ho, ETW, Kennedy, DN, Lanyon, LJ, Leergaard, TB, Mayberg, HS, Milanesi, L, Moucek, R, Poline, JB, Roy, PK, Strother, SC, Tang, TB, Tiesinga, P, Wachtler, T, Wojcik, DK, and Martone, ME
- Abstract
There is great need for coordination around standards and best practices in neuroscience to support efforts to make neuroscience a data-centric discipline. Major brain initiatives launched around the world are poised to generate huge stores of neuroscience data. At the same time, neuroscience, like many domains in biomedicine, is confronting the issues of transparency, rigor, and reproducibility. Widely used, validated standards and best practices are key to addressing the challenges in both big and small data science, as they are essential for integrating diverse data and for developing a robust, effective, and sustainable infrastructure to support open and reproducible neuroscience. However, developing community standards and gaining their adoption is difficult. The current landscape is characterized both by a lack of robust, validated standards and a plethora of overlapping, underdeveloped, untested and underutilized standards and best practices. The International Neuroinformatics Coordinating Facility (INCF), an independent organization dedicated to promoting data sharing through the coordination of infrastructure and standards, has recently implemented a formal procedure for evaluating and endorsing community standards and best practices in support of the FAIR principles. By formally serving as a standards organization dedicated to open and FAIR neuroscience, INCF helps evaluate, promulgate, and coordinate standards and best practices across neuroscience. Here, we provide an overview of the process and discuss how neuroscience can benefit from having a dedicated standards body.
- Published
- 2021
5. A non-immunogenic adenoviral vector, coexpressing CTLA4Ig and bilirubin-uridine-diphosphoglucuronateglucuronosyltransferase permits long-term, repeatable transgene expression in the Gunn rat model of Crigler–Najjar syndrome
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Thummala, NR, Ghosh, SS, Lee, SW, Reddy, B, Davidson, A, Horwitz, MS, Roy Chowdhury, J, and Roy Chowdhury, N
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- 2002
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6. A Pilot Study Comparing Uric Acid and Biomarkers of Renal Injury and Inflammation in Pediatric Sickle Cell Disease at Vaso-Occlusive Crisis and Steady State
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Kaspar, CDW, primary, Ghosh, SS, additional, Lo, M, additional, McClish, D, additional, Sisler, I, additional, Newlin, J, additional, Feig, DI, additional, and Smith, W, additional
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- 2019
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7. Benefits of the CI-CCS converter
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Nathan, KS, Ghosh, SS, Tripathi, PR, Siwakoti, YP, Flack, TJ, Li, X, and Long, T
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- 2019
8. Dual polarity DC–DC converter integrated grid-tied single-phase transformer less inverter for solar application
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Ghosh, SS, Nathan, KS, Siwakoti, YP, Long, T, Ghosh, SS, Nathan, KS, Siwakoti, YP, and Long, T
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- 2019
9. MetaSearch: Phenotypic Search across public MRI data
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Ghosh, SS, Nichols, B Nolan, Heuer, K, Sterling, A, and Toro, R
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interactive search ,public neuroimaging data - Abstract
Growing number of human brain imaging datasets shared online that have related metadata, such as disease diagnostics, age, sex and other phenotypic, demographic or imaging information. The 1000 Functional Connectomes Project (FCP) and International Neuroimaging Data-sharing Initiative (INDI) are great examples of openly available brain imaging datasets with corresponding metadata. However, these data have diverse directory structures and file formats that make cross-dataset queries a time intensive project. With MetaSearch, we propose a Web platform that allows finding resources, filtering information by a user's needs, and enables social, distributed curation of scientific data. It is provided by the Open Neuroimaging Laboratory as a companion to BrainBox, a brain MRI curation and annotation tool., http://openneu.ro/metasearch/
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- 2017
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10. BIDS apps: Improving ease of use, accessibility, and reproducibility of neuroimaging data analysis methods
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Schneidman, D, Gorgolewski, KJ, Alfaro-Almagro, F, Auer, T, Bellec, P, Capota, M, Chakravarty, MM, Churchill, NW, Cohen, AL, Craddock, RC, Devenyi, GA, Eklund, A, Esteban, O, Flandin, G, Ghosh, SS, Guntupalli, JS, Jenkinson, M, Keshavan, A, Kiar, G, Liem, F, Raamana, PR, Raffelt, D, Steele, CJ, Quirion, P-O, Smith, RE, Strother, SC, Varoquaux, G, Wang, Y, Yarkoni, T, Poldrack, RA, Schneidman, D, Gorgolewski, KJ, Alfaro-Almagro, F, Auer, T, Bellec, P, Capota, M, Chakravarty, MM, Churchill, NW, Cohen, AL, Craddock, RC, Devenyi, GA, Eklund, A, Esteban, O, Flandin, G, Ghosh, SS, Guntupalli, JS, Jenkinson, M, Keshavan, A, Kiar, G, Liem, F, Raamana, PR, Raffelt, D, Steele, CJ, Quirion, P-O, Smith, RE, Strother, SC, Varoquaux, G, Wang, Y, Yarkoni, T, and Poldrack, RA
- Abstract
The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and described in compliance with the Brain Imaging Data Structure (BIDS). The portability of these applications (BIDS Apps) is achieved by using container technologies that encapsulate all binary and other dependencies in one convenient package. BIDS Apps run on all three major operating systems with no need for complex setup and configuration and thanks to the comprehensiveness of the BIDS standard they require little manual user input. Previous containerized data processing solutions were limited to single user environments and not compatible with most multi-tenant High Performance Computing systems. BIDS Apps overcome this limitation by taking advantage of the Singularity container technology. As a proof of concept, this work is accompanied by 22 ready to use BIDS Apps, packaging a diverse set of commonly used neuroimaging algorithms.
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- 2017
11. A Python-based software package for pipelined, batch analysis of fMRI data
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Ghosh, SS, primary, Whitfield-Gabrieli, S, additional, and Nieto-Castanon, A, additional
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- 2009
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12. Incorporating hemodynamic response functions to improve analysis models for sparse-acquisition experiments
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Ghosh, SS, primary, Kovelman, I, additional, Lymberis, J, additional, and Gabrieli, JD, additional
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- 2009
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13. An evaluation of volume- and surface-based nonlinear registration of human brain MRI data
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Klein, A, primary, Ghosh, SS, additional, and Parsey, RV, additional
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- 2009
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14. Hdl Mediated Cholesterol Efflux from Mesangial Cells: The Role of Map Kinase
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Ghosh, SS, primary, Gibson, BV, additional, Gehr, TW, additional, Ghosh, S, additional, and Sica, DA, additional
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- 2001
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15. Exploring potential molecular targets and therapeutic efficacy of beauvericin in triple-negative breast cancer cells.
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Patra A, Ghosh SS, and Saini GK
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- Humans, Molecular Docking Simulation, Drug Screening Assays, Antitumor, Apoptosis drug effects, Multidrug Resistance-Associated Proteins antagonists & inhibitors, Multidrug Resistance-Associated Proteins metabolism, Cell Line, Tumor, Reactive Oxygen Species metabolism, Molecular Structure, Dose-Response Relationship, Drug, Histone Deacetylase 1 antagonists & inhibitors, Histone Deacetylase 1 metabolism, Structure-Activity Relationship, Depsipeptides pharmacology, Depsipeptides chemistry, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms pathology, Triple Negative Breast Neoplasms metabolism, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Cell Proliferation drug effects, Cell Survival drug effects
- Abstract
Triple negative breast cancer (TNBC) presents a significant global health concern due to its aggressive nature, high mortality rate and limited treatment options, highlighting the urgent need for targeted therapies. Beauvericin, a bioactive fungal secondary metabolite, possess significant anticancer potential, although its molecular targets in cancer cells remain unexplored. This study has investigated possible molecular targets of beauvericin and its therapeutic insights in TNBC cells. In silico studies using molecular docking and MD simulation predicted the molecular targets of beauvericin. The identified targets included MRP-1 (ABCC1), HDAC-1, HDAC-2, LCK and SYK with average binding energy of -90.1, -44.3, -72.1, -105 and -60.8 KJ/mol, respectively, implying its multifaceted roles in reversing drug resistance, inhibiting epigenetic modulators and oncogenic tyrosine kinases. Beauvericin has significantly reduced the viability of MDA-MB-231 and MDA-MB-468 cells, with IC
50 concentrations of 4.4 and 3.9 µM, while concurrently elevating the intracellular ROS by 9.0 and 7.9 folds, respectively. Subsequent reduction of mitochondrial transmembrane potential in TNBC cells, has confirmed the induction of oxidative stress, leading to apoptotic cell death, as observed by flow cytometric analyses. Beauvericin has also arrested cell cycle at G1-phase and impaired the spheroid formation and clonal expansion abilities of TNBC cells. The viability of spheroids was reduced upon beauvericin treatment, exhibiting IC50 concentrations of 10.3 and 6.2 µM in MDA-MB-468 and MDA-MB-231 cells, respectively. In conclusion, beauvericin has demonstrated promising therapeutic potential against TNBC cells through possible inhibition of MRP-1 (ABCC1), HDAC-1, HDAC-2, LCK and SYK., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Siddhartha Sankar Ghosh reports financial support was provided by India Ministry of Science & Technology Department of Biotechnology. Siddhartha Sankar Ghosh reports financial support was provided by Indian Council of Medical Research. If there are other authors, they 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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16. Gliotoxin triggers cell death through multifaceted targeting of cancer-inducing genes in breast cancer therapy.
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Nambiar SS, Ghosh SS, and Saini GK
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- Humans, Female, Molecular Dynamics Simulation, Molecular Docking Simulation, Cell Death drug effects, Cell Survival drug effects, Drug Screening Assays, Antitumor, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Molecular Structure, Structure-Activity Relationship, Cell Line, Tumor, Gliotoxin pharmacology, Gliotoxin chemistry, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Breast Neoplasms pathology, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry
- Abstract
Fungal secondary metabolites have a long history of contributing to pharmaceuticals, notably in the development of antibiotics and immunosuppressants. Harnessing their potent bioactivities, these compounds are now being explored for cancer therapy, by targeting and disrupting the genes that induce cancer progression. The current study explores the anticancer potential of gliotoxin, a fungal secondary metabolite, which encompasses a multi-faceted approach integrating computational predictions, molecular dynamics simulations, and comprehensive experimental validations. In-silico studies have identified potential gliotoxin targets, including MAPK1, NFKB1, HIF1A, TDP1, TRIM24, and CTSD which are involved in critical pathways in cancer such as the NF-κB signaling pathway, MAPK/ERK signaling pathway, hypoxia signaling pathway, Wnt/β-catenin pathway, and other essential cellular processes. The gene expression analysis results indicated all the identified targets are overexpressed in various breast cancer subtypes. Subsequent molecular docking and dynamics simulations have revealed stable binding of gliotoxin with TDP1 and HIF1A. Cell viability assays exhibited a dose-dependent decreasing pattern with its remarkable IC
50 values of 0.32, 0.14, and 0.53 μM for MDA-MB-231, MDA-MB-468, and MCF-7 cells, respectively. Likewise, in 3D tumor spheroids, gliotoxin exhibited a notable decrease in viability indicating its effectiveness against solid tumors. Furthermore, gene expression studies using Real-time PCR revealed a reduction of expression of cancer-inducing genes, MAPK1, HIF1A, TDP1, and TRIM24 upon gliotoxin treatment. These findings collectively underscore the promising anticancer potential of gliotoxin through multi-targeting cancer-promoting genes, positioning it as a promising therapeutic option for breast cancer., 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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17. Detecting suicide risk among U.S. servicemembers and veterans: a deep learning approach using social media data.
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Zuromski KL, Low DM, Jones NC, Kuzma R, Kessler D, Zhou L, Kastman EK, Epstein J, Madden C, Ghosh SS, Gowel D, and Nock MK
- Abstract
Background: Military Servicemembers and Veterans are at elevated risk for suicide, but rarely self-identify to their leaders or clinicians regarding their experience of suicidal thoughts. We developed an algorithm to identify posts containing suicide-related content on a military-specific social media platform., Methods: Publicly-shared social media posts ( n = 8449) from a military-specific social media platform were reviewed and labeled by our team for the presence/absence of suicidal thoughts and behaviors and used to train several machine learning models to identify such posts., Results: The best performing model was a deep learning (RoBERTa) model that incorporated post text and metadata and detected the presence of suicidal posts with relatively high sensitivity (0.85), specificity (0.96), precision (0.64), F1 score (0.73), and an area under the precision-recall curve of 0.84. Compared to non-suicidal posts, suicidal posts were more likely to contain explicit mentions of suicide, descriptions of risk factors (e.g. depression, PTSD) and help-seeking, and first-person singular pronouns., Conclusions: Our results demonstrate the feasibility and potential promise of using social media posts to identify at-risk Servicemembers and Veterans. Future work will use this approach to deliver targeted interventions to social media users at risk for suicide.
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- 2024
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18. Beauvericin Reverses Epithelial-to-Mesenchymal Transition in Triple-Negative Breast Cancer Cells through Regulation of Notch Signaling and Autophagy.
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Patra A, Arora A, Ghosh SS, and Kaur Saini G
- Abstract
Metastasis stands as a prime contributor to triple-negative breast cancer (TNBC) associated mortality worldwide, presenting heightened severity and significant challenges due to limited treatment options. Addressing TNBC metastasis necessitates innovative approaches and novel therapeutics to specifically target its propensity for dissemination to distant organs. Targeted therapies capable of reversing epithelial-to-mesenchymal transition (EMT) play a crucial role in suppressing metastasis and enhancing the treatment response. Beauvericin, a promising fungal secondary metabolite, exhibits significant potential in diminishing the viability of EMT-induced TNBC cells by triggering intracellular oxidative stress, as evidenced by an enhanced reactive oxygen species level and reduced mitochondrial transmembrane potential. In monolayer cultures, it has exhibited an IC
50 of 2.3 μM in both MDA-MB-468 and MDA-MB-231 cells, while in 3D spheroids, the IC50 values are 9.7 and 7.1 μM, respectively. Beauvericin has also reduced the migratory capability of MDA-MB-468 and MDA-MB-231 cells by 1.5- and 1.7-fold, respectively. Both qRT-PCR and Western blot analysis have shown significant upregulation in the expression of epithelial marker (E-cadherin) and downregulation in the expression of mesenchymal markers (N-cadherin, vimentin, Snail, Slug, and β-catenin), following treatment, indicating reversal of EMT. Furthermore, beauvericin has suppressed the Notch signaling pathway by substantially downregulating Notch-1, Notch-3, Hes-1, and cyclinD3 expression and induced autophagy as observed by elevated expression of autophagy markers LC3 and Beclin-1. In conclusion, beauvericin has successfully downregulated TNBC cell survival by inducing oxidative stress and suppressed their migratory potential by reversing EMT through the inhibition of Notch signaling and activation of autophagy., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)- Published
- 2024
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19. Year-Long Cannabis Use for Medical Symptoms and Brain Activation During Cognitive Processes.
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Burdinski DCL, Kodibagkar A, Potter K, Schuster RM, Evins AE, Ghosh SS, and Gilman JM
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- Humans, Female, Male, Adult, Middle Aged, Cohort Studies, Young Adult, Anxiety, Sleep Initiation and Maintenance Disorders, Depression, Pain physiopathology, Boston epidemiology, Reward, Adolescent, Medical Marijuana therapeutic use, Cognition drug effects, Cognition physiology, Brain diagnostic imaging, Brain physiopathology, Brain drug effects, Memory, Short-Term drug effects, Memory, Short-Term physiology
- Abstract
Importance: Cannabis is increasingly being used to treat medical symptoms, but the effects on brain function in those using cannabis for these symptoms are not known., Objective: To test whether 1 year of cannabis use for medical symptoms after obtaining a medical cannabis card was associated with increased brain activation during working memory, reward, and inhibitory control tasks, areas of cognition affected by cannabis., Design, Setting, and Participants: This cohort study was conducted from July 2017 to July 2020 among participants from the greater Boston area who were recruited as part of a clinical trial of individuals seeking medical cannabis cards for anxiety, depression, pain, or insomnia symptoms. Participants were aged between 18 and 65 years. Exclusion criteria were daily cannabis use and cannabis use disorder at baseline. Data analysis was conducted from August 2021 to April 2024., Main Outcomes and Measures: Outcomes were whole brain functional activation during tasks involving working memory, reward, and inhibitory control at baseline and after 1 year of medical cannabis card ownership., Results: Imaging was collected from participants before and 1 year after obtaining medical cannabis cards, with 57 participants at baseline (38 female [66.7%]; 6 [10.5%] Black and 45 [78.9%] White participants; 1 [1.8%] Hispanic participant; median [IQR] age, 34.0 [24.0-51.0] years) and 54 participants at 1 year (37 female [68.5%]; 4 [7.4%] Black and 48 [88.9%] White participants; 1 [1.9%] Hispanic participant, median [IQR] age, 36.5 [25.0-51.0] years). Imaging was also collected in 32 healthy control participants at baseline (22 female [68.8%]; 2 [6.2%] Black and 27 [84.4%] White participants; 3 [9.4%] Hispanic participants; median [IQR] age, 33.0 [24.8-38.2] years). In all groups and at both time points, functional imaging revealed canonical activations of the probed cognitive processes. No statistically significant difference in brain activation between the 2 time points (baseline and 1 year) in those with medical cannabis cards and no associations between changes in cannabis use frequency and brain activation after 1 year were found., Conclusions and Relevance: In this cohort study of adults obtaining medical cannabis cards for medical symptoms, no significant association between brain activation in the areas of cognition of working memory, reward, and inhibitory control and 1 year of cannabis use was observed. The results warrant further studies that probe the association of cannabis at higher doses, with greater frequency, in younger age groups, and with larger, more diverse cohorts.
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- 2024
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20. Resting-State Functional Connectivity of the Amygdala in Autism: A Preregistered Large-Scale Study.
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Kliemann D, Galdi P, Van De Water AL, Egger B, Jarecka D, Adolphs R, and Ghosh SS
- Abstract
Objective: Three leading neurobiological hypotheses about autism spectrum disorder (ASD) propose underconnectivity between brain regions, atypical function of the amygdala, and generally higher variability between individuals with ASD than between neurotypical individuals. Past work has often failed to generalize, because of small sample sizes, unquantified data quality, and analytic flexibility. This study addressed these limitations while testing the above three hypotheses, applied to amygdala functional connectivity., Methods: In a comprehensive preregistered study, the three hypotheses were tested in a subset (N=488 after exclusions; N=212 with ASD) of the Autism Brain Imaging Data Exchange data sets. The authors analyzed resting-state functional connectivity (FC) from functional MRI data from two anatomically defined amygdala subdivisions, in three hypotheses with respect to magnitude, pattern similarity, and variability, across different anatomical scales ranging from whole brain to specific regions and networks., Results: A Bayesian approach to hypothesis evaluation produced inconsistent evidence in ASD for atypical amygdala FC magnitude, strong evidence that the multivariate pattern of FC was typical, and no consistent evidence of increased interindividual variability in FC. The results strongly depended on analytic choices, including preprocessing pipeline for the neuroimaging data, anatomical specificity, and subject exclusions., Conclusions: A preregistered set of analyses found no reliable evidence for atypical functional connectivity of the amygdala in autism, contrary to leading hypotheses. Future studies should test an expanded set of hypotheses across multiple processing pipelines, collect deeper data per individual, and include a greater diversity of participants to ensure robust generalizability of findings on amygdala FC in ASD., Competing Interests: The authors report no financial relationships with commercial interests.
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- 2024
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21. SAHA potentiates the activity of repurposed drug promethazine loaded PLGA nanoparticles in triple-negative breast cancer cells.
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Choudhury K, Sen P, and Ghosh SS
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- Humans, Cell Line, Tumor, Female, Reactive Oxygen Species metabolism, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Cell Proliferation drug effects, Histone Deacetylase Inhibitors pharmacology, Histone Deacetylase Inhibitors chemistry, Drug Synergism, Drug Carriers chemistry, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms pathology, Triple Negative Breast Neoplasms metabolism, Polylactic Acid-Polyglycolic Acid Copolymer chemistry, Vorinostat pharmacology, Vorinostat chemistry, Nanoparticles chemistry, Promethazine pharmacology, Drug Repositioning, Epithelial-Mesenchymal Transition drug effects, Apoptosis drug effects
- Abstract
Triple-negative breast cancer (TNBC) is considered the most aggressive form of breast cancer owing to the negative expression of targetable bioreceptors. Epithelial to mesenchymal transition (EMT) associated with metastatic abilities is its critical feature. As an attempt to target TNBC, nanotechnology was utilised to augment the effects of drug repurposing. Concerning that, a combination therapeutic module was structured with one of the aspects being a repurposed antihistamine, promethazine hydrochloride loaded PLGA nanoparticles. The as-synthesized nanoparticles were 217 nm in size and fluoresced at 522 nm, rendering them suitable for theranostic applications too. The second feature of the module was a common histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), used as a form of pre-treatment. Experimental studies demonstrated efficient cellular internalisation and significant innate anti-proliferative potential. The use of SAHA sensitised the cells to the drug loaded nanoparticle treatment. Mechanistic studies showed increase in ROS generation, mitochondrial dysfunction followed by apoptosis. Investigations into protein expression also revealed reduction of mesenchymal proteins like vimentin by 1.90 fold; while increase in epithelial marker like E-Cadherin by 1.42 fold, thus indicating an altered EMT dynamics. Further findings also provided better insight into the benefits of SAHA potentiated targeting of tumor spheroids that mimic solid tumors of TNBC. Thus, this study paves the avenue to a more rational translational validation of combining nanotherapeutics with drug repurposing., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)
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- 2024
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22. Epigenetic Modulations in Breast Cancer: An Emerging Paradigm in Therapeutic Implications.
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Sarkar S, Venkatesh D, Kandasamy T, and Ghosh SS
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- Humans, Female, Drug Resistance, Neoplasm genetics, Gene Expression Regulation, Neoplastic, Histones metabolism, Antineoplastic Agents therapeutic use, Antineoplastic Agents pharmacology, Histone Deacetylase Inhibitors therapeutic use, Breast Neoplasms genetics, Breast Neoplasms drug therapy, Breast Neoplasms therapy, Breast Neoplasms pathology, Breast Neoplasms metabolism, Epigenesis, Genetic, DNA Methylation, Epithelial-Mesenchymal Transition genetics
- Abstract
Breast cancer, a heterogeneous and intricate disease, ranks among the leading causes of mortality in women. Restricted therapeutic choices, drug resistance, recurrence, and metastasis are the predominant conditions that lead to mortality. Accumulating evidence has shown breast cancer initiation and progression happen through a multifaceted and intricate process that involves numerous genetic and epigenetic alterations. The modulation of gene expression through epigenetic modifications, encompassing DNA methylation, histone alterations, and non-coding RNA regulation, has emerged as a fascinating field that represents a new avenue for breast cancer therapy. This review emphasizes various aberrant epigenetic regulations implicated in the onset and advancement of breast cancer. The critical epigenetic modifications closely associated with estrogen signaling, epithelial-to-mesenchymal transition (EMT), cancer stemness, and drug resistance have been discussed extensively. Moreover, it highlights current epi-drugs, including DNA modifying agents, histone acetyltransferase inhibitors, histone deacetylase inhibitors, histone methyltransferase inhibitors, and histone demethyltransferase inhibitors used for breast cancer treatment. Nonetheless, we described current investigations pertaining to combination therapy employing epi-drugs and future challenges., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)
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- 2024
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23. The Human Connectome Project of adolescent anxiety and depression dataset.
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Hubbard NA, Bauer CCC, Siless V, Auerbach RP, Elam JS, Frosch IR, Henin A, Hofmann SG, Hodge MR, Jones R, Lenzini P, Lo N, Park AT, Pizzagalli DA, Vaz-DeSouza F, Gabrieli JDE, Whitfield-Gabrieli S, Yendiki A, and Ghosh SS
- Subjects
- Humans, Adolescent, Male, Female, Anxiety Disorders, Depressive Disorder, Magnetic Resonance Imaging, Brain diagnostic imaging, Connectome, Depression, Anxiety
- Abstract
This article describes primary data and resources available from the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) study, a novel arm of the Human Connectome Project (HCP). Data were collected from 215 adolescents (14-17 years old), 152 of whom had current diagnoses of anxiety and/or depressive disorders at study intake. Data include cross-sectional structural (T1- and T2-weighted), functional (resting state and three tasks), and diffusion-weighted magnetic resonance images. Both unprocessed and HCP minimally-preprocessed imaging data are available within the data release packages. Adolescent and parent clinical interview data, as well as cognitive and neuropsychological data are also included within these packages. Release packages additionally provide data collected from self-report measures assessing key features of adolescent psychopathology, including: anxious and depressive symptom dimensions, behavioral inhibition/activation, exposure to stressful life events, and risk behaviors. Finally, the release packages include 6- and 12-month longitudinal data acquired from clinical measures. Data are publicly accessible through the National Institute of Mental Health Data Archive (ID: #2505)., (© 2024. The Author(s).)
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- 2024
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24. L-Proline-catalysed synthesis of chromeno[2,3- b ]chromene from 4-hydroxy-2 H -chromene-2-thione and an anti-proliferative study.
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Mandal A, Singh S, Arora A, Nambiar SS, Ghosh SS, and Khan AT
- Abstract
The reactivity of 4-hydroxy-2 H -chromene-2-thione is investigated with aryl aldehydes and 5,5-dimethylcylohexane-1,3-dione (dimedone) in the presence of 20 mol% L-proline in toluene at 90 °C. Instead of the expected linear product with a sulphur atom in the ring provided by 4-hydroxydithiocoumarin or an angular product obtained from 4-hydroxycoumarin, the hitherto unreported products, 12-aryl substituted chromeno[2,3- b ]chromenes (4), were obtained in good to excellent yields. The reaction proceeds through a three-component reaction via Knoevenagel condensation between dimedone with an aromatic aldehyde followed by Michael addition with 4-hydroxy-2 H -chromene-2-thione. In addition, a molecular docking study of all the derivatives was performed and among them, four compounds exhibited anti-proliferative activity and elevated ROS generation in breast cancer (MCF7) cell lines.
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- 2024
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25. Concurrent inhibition of IR, ITGB1, and CD36 perturbated the interconnected network of energy metabolism and epithelial-to-mesenchymal transition in breast cancer cells.
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Kandasamy T, Sarkar S, Sen P, Venkatesh D, and Ghosh SS
- Subjects
- Humans, Female, MCF-7 Cells, Imidazoles pharmacology, Pyridazines pharmacology, Cell Proliferation drug effects, Cell Line, Tumor, Apoptosis drug effects, Signal Transduction drug effects, Gene Expression Regulation, Neoplastic drug effects, Epithelial-Mesenchymal Transition drug effects, Integrin beta1 metabolism, CD36 Antigens metabolism, Breast Neoplasms metabolism, Breast Neoplasms pathology, Breast Neoplasms drug therapy, Energy Metabolism drug effects
- Abstract
Altered energy metabolism is an emerging hallmark of cancer and plays a pivotal in cell survival, proliferation, and biosynthesis. In a rapidly proliferating cancer, energy metabolism acts in synergism with epithelial-to-mesenchymal transition (EMT), enabling cancer stemness, dissemination, and metastasis. In this study, an interconnected functional network governing energy metabolism and EMT signaling pathways was targeted through the concurrent inhibition of IR, ITGB1, and CD36 activity. A novel multicomponent MD simulation approach was employed to portray the simultaneous inhibition of IR, ITGB1, and CD36 by a 2:1 combination of Pimozide and Ponatinib. Further, in-vitro studies revealed the synergistic anticancer efficacy of drugs against monolayer as well as tumor spheroids of breast cancer cell lines (MCF-7 and MDA-MB-231). In addition, the combination therapy exerted approximately 40% of the apoptotic population and more than 1.5- to 3-fold reduction in the expression of ITGB1, IR, p-IR, IRS-1, and p-AKT in MCF-7 and MDA-MB-231 cell lines. Moreover, the reduction in fatty acid uptake, lipid droplet accumulation, cancer stemness, and migration properties were also observed. Thus, targeting IR, ITGB1, and CD36 in the interconnected network with the combination of Pimozide and Ponatinib represents a promising therapeutic approach for breast cancer., (© 2024 Wiley Periodicals LLC.)
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- 2024
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26. Integrated platform for multiscale molecular imaging and phenotyping of the human brain.
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Park J, Wang J, Guan W, Gjesteby LA, Pollack D, Kamentsky L, Evans NB, Stirman J, Gu X, Zhao C, Marx S, Kim ME, Choi SW, Snyder M, Chavez D, Su-Arcaro C, Tian Y, Park CS, Zhang Q, Yun DH, Moukheiber M, Feng G, Yang XW, Keene CD, Hof PR, Ghosh SS, Frosch MP, Brattain LJ, and Chung K
- Subjects
- Humans, Phenotype, Hydrogels chemistry, Connectome, Alzheimer Disease diagnostic imaging, Brain diagnostic imaging, Molecular Imaging methods
- Abstract
Understanding cellular architectures and their connectivity is essential for interrogating system function and dysfunction. However, we lack technologies for mapping the multiscale details of individual cells and their connectivity in the human organ-scale system. We developed a platform that simultaneously extracts spatial, molecular, morphological, and connectivity information of individual cells from the same human brain. The platform includes three core elements: a vibrating microtome for ultraprecision slicing of large-scale tissues without losing cellular connectivity (MEGAtome), a polymer hydrogel-based tissue processing technology for multiplexed multiscale imaging of human organ-scale tissues (mELAST), and a computational pipeline for reconstructing three-dimensional connectivity across multiple brain slabs (UNSLICE). We applied this platform for analyzing human Alzheimer's disease pathology at multiple scales and demonstrating scalable neural connectivity mapping in the human brain.
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- 2024
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27. Identifying bias in models that detect vocal fold paralysis from audio recordings using explainable machine learning and clinician ratings.
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Low DM, Rao V, Randolph G, Song PC, and Ghosh SS
- Abstract
Detecting voice disorders from voice recordings could allow for frequent, remote, and low-cost screening before costly clinical visits and a more invasive laryngoscopy examination. Our goals were to detect unilateral vocal fold paralysis (UVFP) from voice recordings using machine learning, to identify which acoustic variables were important for prediction to increase trust, and to determine model performance relative to clinician performance. Patients with confirmed UVFP through endoscopic examination (N = 77) and controls with normal voices matched for age and sex (N = 77) were included. Voice samples were elicited by reading the Rainbow Passage and sustaining phonation of the vowel "a". Four machine learning models of differing complexity were used. SHapley Additive exPlanations (SHAP) was used to identify important features. The highest median bootstrapped ROC AUC score was 0.87 and beat clinician's performance (range: 0.74-0.81) based on the recordings. Recording durations were different between UVFP recordings and controls due to how that data was originally processed when storing, which we can show can classify both groups. And counterintuitively, many UVFP recordings had higher intensity than controls, when UVFP patients tend to have weaker voices, revealing a dataset-specific bias which we mitigate in an additional analysis. We demonstrate that recording biases in audio duration and intensity created dataset-specific differences between patients and controls, which models used to improve classification. Furthermore, clinician's ratings provide further evidence that patients were over-projecting their voices and being recorded at a higher amplitude signal than controls. Interestingly, after matching audio duration and removing variables associated with intensity in order to mitigate the biases, the models were able to achieve a similar high performance. We provide a set of recommendations to avoid bias when building and evaluating machine learning models for screening in laryngology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Low 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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28. Sulphur-atom positional engineering in perylenimide: structure-property relationships and H-aggregation directed type-I photodynamic therapy.
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Khatun MN, Nandy S, Roy H, Ghosh SS, Kumar S, and Iyer PK
- Abstract
An innovative design strategy of placing sulfur (S)-atoms within the pendant functional groups and at carbonyl positions in conventional perylenimide (PNI-O) has been demonstrated to investigate the condensed state structure-property relationship and potential photodynamic therapy (PDT) application. Incorporation of simply S-atoms at the peri -functionalized perylenimide (RPNI-O) leads to an aggregation-induced enhanced emission luminogen (AIEEgen), 2-hexyl-8-(thianthren-1-yl)-1 H -benzo[5,10]anthra[2,1,9-def]isoquinoline-1,3(2 H )-dione (API), which achieves a remarkable photoluminescence quantum yield ( Φ
PL ) of 0.85 in aqueous environments and established novel AIE mechanisms. Additionally, substitution of the S-atom at the carbonyl position in RPNI-O leads to thioperylenimides (RPNI-S): 2-hexyl-8-phenyl-1 H -benzo[5,10]anthra[2,1,9-def]isoquinoline-1,3(2 H )-dithione (PPIS), 8-([2,2'-bithiophen]-5-yl)-2-hexyl-1 H -benzo[5,10]anthra[2,1,9-def]isoquinoline-1,3(2 H )-dithione (THPIS), and 2-hexyl-8-(thianthren-1-yl)-1 H -benzo[5,10]anthra[2,1,9-def]isoquinoline-1,3(2 H )-dithion (APIS), with distinct photophysical properties (enlarged spin-orbit coupling (SOC) and ΦPL ≈ 0.00), and developed diverse potent photosensitizers (PSs). The present work provides a novel SOC enhancement mechanism via pronounced H-aggregation. Surprisingly, the lowest singlet oxygen quantum yield ( ΦΔ ) and theoretical calculation suggest the specific type-I PDT for RPNI-S. Interestingly, RPNI-S efficiently produces superoxide (O2 ˙- ) due to its remarkably lower Gibbs free energy (Δ G ) values (THPIS: -40.83 kcal mol-1 ). The non-toxic and heavy-atom free very specific thio-based PPIS and THPIS PSs showed selective and efficient PDT under normoxia, as a rare example., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)- Published
- 2024
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29. Neurodesk: an accessible, flexible and portable data analysis environment for reproducible neuroimaging.
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Renton AI, Dao TT, Johnstone T, Civier O, Sullivan RP, White DJ, Lyons P, Slade BM, Abbott DF, Amos TJ, Bollmann S, Botting A, Campbell MEJ, Chang J, Close TG, Dörig M, Eckstein K, Egan GF, Evas S, Flandin G, Garner KG, Garrido MI, Ghosh SS, Grignard M, Halchenko YO, Hannan AJ, Heinsfeld AS, Huber L, Hughes ME, Kaczmarzyk JR, Kasper L, Kuhlmann L, Lou K, Mantilla-Ramos YJ, Mattingley JB, Meier ML, Morris J, Narayanan A, Pestilli F, Puce A, Ribeiro FL, Rogasch NC, Rorden C, Schira MM, Shaw TB, Sowman PF, Spitz G, Stewart AW, Ye X, Zhu JD, Narayanan A, and Bollmann S
- Subjects
- Humans, User-Computer Interface, Reproducibility of Results, Brain diagnostic imaging, Neuroimaging methods, Software
- Abstract
Neuroimaging research requires purpose-built analysis software, which is challenging to install and may produce different results across computing environments. The community-oriented, open-source Neurodesk platform ( https://www.neurodesk.org/ ) harnesses a comprehensive and growing suite of neuroimaging software containers. Neurodesk includes a browser-accessible virtual desktop, command-line interface and computational notebook compatibility, allowing for accessible, flexible, portable and fully reproducible neuroimaging analysis on personal workstations, high-performance computers and the cloud., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
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- 2024
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30. Single-cell transcriptomics reveals the intra-tumoral heterogeneity and SQSTM1/P62 and Wnt/β-catenin mediated epithelial to mesenchymal transition and stemness of triple-negative breast cancer.
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Shome R, Sen P, Sarkar S, and Ghosh SS
- Subjects
- Female, Humans, beta Catenin metabolism, beta Catenin genetics, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Mesenchymal Stem Cells metabolism, Mesenchymal Stem Cells pathology, Transcriptome genetics, Tumor Microenvironment genetics, Epithelial-Mesenchymal Transition, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Sequestosome-1 Protein metabolism, Sequestosome-1 Protein genetics, Single-Cell Analysis methods, Triple Negative Breast Neoplasms genetics, Triple Negative Breast Neoplasms pathology, Triple Negative Breast Neoplasms metabolism, Wnt Signaling Pathway genetics
- Abstract
Triple-negative breast cancer (TNBC) is characterized by the complex tumor microenvironment (TME) consisting of an abundance of mesenchymal stem cells (MSCs), which is known to facilitate epithelial-to-mesenchymal transition (EMT). The development of single-cell genomics is a powerful method for defining the intricate genetic landscapes of malignancies. In this study, we have employed single-cell RNA sequencing (scRNA-seq) to dissect the intra-tumoral heterogeneity and analyze the single-cell transcriptomic landscape to detect rare consequential cell subpopulations of significance. The scRNA-seq analysis of TNBC and Normal patient derived samples revealed that EMT markers and transcription factors were most upregulated in MSC population. Further, exploration of gene expression analysis among TNBC and Normal patient-derived MSCs ascertained the role of SQSTM1/P62 and Wnt/β-catenin in TNBC progression. Wnt/β-catenin and Wnt/PCP signaling pathways are prominent contributors of EMT, stemness, and cancer stem cell (CSC) properties of TNBC. SQSTM1/P62 cooperates with the components of the Wnt/PCP signaling pathway and is critically involved at the interface of autophagy and EMT. Moreover, siRNA targeting SQSTM1/P62 and inhibitor of Wnt/β-catenin (FH535) in conjunction was used to explore molecular modification of EMT and stemness markers. Although SQSTM1/P62 is not crucial for cell survival, cytotoxicity assay revealed synergistic interaction between the siRNA/inhibitor. Modulation of these important pathways helped in reduction of expression of genes and proteins contributing to CSC properties. Gene and protein expression analysis revealed the induction of EMT to MET. Moreover, co-treatment resulted in inactivation of non-canonical Wnt VANGL2-JNK signaling axis. The synergistic impact of inhibition of SQSTM1/P62 and Wnt/β-catenin signaling facilitates the development of a potential therapeutic regimen for TNBC., 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 Inc. All rights reserved.)
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- 2024
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31. The past, present, and future of the brain imaging data structure (BIDS).
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Poldrack RA, Markiewicz CJ, Appelhoff S, Ashar YK, Auer T, Baillet S, Bansal S, Beltrachini L, Benar CG, Bertazzoli G, Bhogawar S, Blair RW, Bortoletto M, Boudreau M, Brooks TL, Calhoun VD, Castelli FM, Clement P, Cohen AL, Cohen-Adad J, D'Ambrosio S, de Hollander G, de la Iglesia-Vayá M, de la Vega A, Delorme A, Devinsky O, Draschkow D, Duff EP, DuPre E, Earl E, Esteban O, Feingold FW, Flandin G, Galassi A, Gallitto G, Ganz M, Gau R, Gholam J, Ghosh SS, Giacomel A, Gillman AG, Gleeson P, Gramfort A, Guay S, Guidali G, Halchenko YO, Handwerker DA, Hardcastle N, Herholz P, Hermes D, Honey CJ, Innis RB, Ioanas HI, Jahn A, Karakuzu A, Keator DB, Kiar G, Kincses B, Laird AR, Lau JC, Lazari A, Legarreta JH, Li A, Li X, Love BC, Lu H, Marcantoni E, Maumet C, Mazzamuto G, Meisler SL, Mikkelsen M, Mutsaerts H, Nichols TE, Nikolaidis A, Nilsonne G, Niso G, Norgaard M, Okell TW, Oostenveld R, Ort E, Park PJ, Pawlik M, Pernet CR, Pestilli F, Petr J, Phillips C, Poline JB, Pollonini L, Raamana PR, Ritter P, Rizzo G, Robbins KA, Rockhill AP, Rogers C, Rokem A, Rorden C, Routier A, Saborit-Torres JM, Salo T, Schirner M, Smith RE, Spisak T, Sprenger J, Swann NC, Szinte M, Takerkart S, Thirion B, Thomas AG, Torabian S, Varoquaux G, Voytek B, Welzel J, Wilson M, Yarkoni T, and Gorgolewski KJ
- Abstract
The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS., Competing Interests: Gaia Rizzo is an employee of Invicro. No other authors have competing interests to declare., (© 2024 Massachusetts Institute of Technology. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)
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- 2024
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32. Corrigendum to: "Endoscopic duodenal mucosal resurfacing improves glycaemic and hepatic indices in type 2 diabetes: 6-month multicentre results" [JHEP Reports 5 (2019) 101041].
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van Baar ACG, Beuers U, Wong K, Haidry R, Costamagna G, Hadefi A, Deviere J, Ghosh SS, Lopez-Talavera JC, Rodriguez L, Galvao Neto MP, Sanyal A, and Bergman JJGHM
- Abstract
[This corrects the article DOI: 10.1016/j.jhepr.2019.10.006.]., (© 2024 The Author(s).)
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- 2024
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33. In vitro anticancer effects of recombinant anisoplin through activation of SAPK/JNK and downregulation of NFκB.
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Patra A, Kandasamy T, Ghosh SS, and Saini GK
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- Humans, Female, Down-Regulation, Apoptosis, MAP Kinase Signaling System, JNK Mitogen-Activated Protein Kinases metabolism, NF-kappa B metabolism, Breast Neoplasms
- Abstract
Emerging chemotherapeutic resistance is considered as one of the major obstacles in breast cancer therapy. Fungal ribotoxins possess promising therapeutic potential against cancer owing to their ribosome-targeted protein synthesis inhibitory action. Though the entomopathogenic ribotoxin anisoplin was characterized in the earlier study, its therapeutic efficacy against cancer cells remained unexplored. In the current study, recombinant anisoplin has been successfully produced in Escherichia coli BL21(DE3) expression system and further purified and validated by in silico, biophysical and functional characterizations. Recombinant anisoplin significantly reduced the viability of MCF-7 breast cancer cells in a dose-dependent manner. It exhibited an IC
50 value of 4 μM with concurrent 3.5 fold elevation in the intracellular reactive oxygen species. Anisoplin also resulted in depolarization of the mitochondrial membrane and subsequently induced apoptosis, as evident from flow cytometric analyses. In addition, MCF-7 cells significantly lost their self-renewal capability for clonal expansion and regeneration upon treatment. Immunoblotting experiments further confirmed activation of downstream JNK-dependent MAP kinase signaling pathway due to ribotoxic stress response generated by anisoplin through upregulation of phospho-SAPK/JNK expression. This upregulation was further correlated with the NFκB expression profile, leading to cell death, highlighting therapeutic potential of the recombinant anisoplin., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Siddhartha Sankar Ghosh reports financial support was provided by Department of Biotechnology, Ministry of Science and Technology, Govt. of India., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2024
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34. Targeting AR-positive breast cancer cells via drug repurposing approach.
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Dutta P, Sen P, Kandasamy T, and Ghosh SS
- Subjects
- Humans, Female, Molecular Docking Simulation, Drug Repositioning, Cell Line, Tumor, Cell Proliferation, Adapalene pharmacology, Adapalene therapeutic use, Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms metabolism
- Abstract
Androgen Receptor (AR) is overexpressed in almost all the molecular subtypes of breast cancer. Besides aiding the tumorigenic environment of cancer by abnormal cell proliferation, AR also takes part in promoting cancer signaling pathways, thereby promoting aggressiveness. In this study, AR was selected as the target protein in breast cancer cells. Following this, a library of 1293 FDA-approved drugs was screened via molecular docking, MD simulation, and MMPBSA binding energy. Amongst the library of compounds, Adapalene exhibited the least binding energy of (-10.2 kCal/mol) in comparison to that of the chosen reference compound, Nilutamide (-8.6 kCal/mol). Furthermore, the in vitro efficacy of Adapalene was also determined in two different breast cancer cell lines such as MCF7 (AR-positive/ER-positive) and MDA-MB-231 (AR negative/TNBC). Initially, the cell viability assay (MTT) was performed, which endowed us with a lesser IC
50 value of Adapalene in comparison to Nilutamide in both cell lines. The IC50 of Adapalene was found to be 12 μM and 39.4 μM in MCF7 and MDA-MB-231 cells, respectively. Furthermore, Adapalene also induced cellular ROS and apoptosis by 3.5-fold and 26.58% in MCF7 cells. However, the overall effect of Adapalene was significantly lower in the case of MDA-MB-231 cell lines, which could be attributed to its inherent nature of the absence of hormone receptors. Conclusively, Adapalene possesses greater therapeutic efficacy in comparison to the control drug, thereby hinting towards the potential use of Adapalene in the treatment of AR-positive breast cancer., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2024
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35. Amyloid Targeting Red Emitting AIE Dots for Diagnostic and Therapeutic Application against Alzheimer's Disease.
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Ghosh P, Shokeen K, Mondal S, Kandasamy T, Kumar S, Ghosh SS, and Iyer PK
- Subjects
- Humans, Reactive Oxygen Species metabolism, Molecular Docking Simulation, Amyloid beta-Peptides metabolism, Metals metabolism, Alzheimer Disease metabolism
- Abstract
The emergence of neurodegenerative diseases is connected to several pathogenic factors, including metal ions, amyloidogenic proteins, and reactive oxygen species. Recent studies suggest that cytotoxicity is caused by the small, dynamic, and metastable nature of early stage oligomeric species. This work introduces a small molecule-based red-emitting probe with smart features such as increased reactivities against multiple targets, metal-free amyloid-β (Aβ), and metal-bound amyloid-β (Aβ), and most importantly, early stage oligomeric species which are associated with the most common and widespread type of dementia, Alzheimer's disease (AD). Theoretical analyses like molecular dynamics simulation and molecular docking were performed to confirm the reactivity of the molecule toward Aβ and found some excellent interactions between the molecule and the peptide. The in vitro and cellular studies demonstrated that this highly biocompatible molecule effectively reduces the structural damage to mitochondria while shielding cells from apoptosis, scavenges ROS (reactive oxygen species), and attenuates multifaceted amyloid toxicity.
- Published
- 2024
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36. Brainchop: Providing an Edge Ecosystem for Deployment of Neuroimaging Artificial Intelligence Models.
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Plis SM, Masoud M, Hu F, Hanayik T, Ghosh SS, Drake C, Newman-Norlund R, and Rorden C
- Abstract
Deep learning has proven highly effective in various medical imaging scenarios, yet the lack of an efficient distribution platform hinders developers from sharing models with end-users. Here, we describe brainchop, a fully functional web application that allows users to apply deep learning models developed with Python to local neuroimaging data from within their browser. While training artificial intelligence models is computationally expensive, applying existing models to neuroimaging data can be very fast; brainchop harnesses the end user's graphics card such that brain extraction, tissue segmentation, and regional parcellation require only seconds and avoids privacy issues that impact cloud-based solutions. The integrated visualization allows users to validate the inferences, and includes tools to annotate and edit the resulting segmentations. Our pure JavaScript implementation includes optimized helper functions for conforming volumes and filtering connected components with minimal dependencies. Brainchop provides a simple mechanism for distributing models for additional image processing tasks, including registration and identification of abnormal tissue, including tumors, lesions and hyperintensities. We discuss considerations for other AI model developers to leverage this open-source resource.
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- 2024
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37. An in-silico approach to understand the potential role of Wnt inhibitory factor-1 (WIF-1) in the inhibition of the Wnt signalling pathway.
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Sen P, Roy Acharyya S, Arora A, and Ghosh SS
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- Humans, Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, Molecular Docking Simulation, Repressor Proteins genetics, Repressor Proteins metabolism, Wnt Signaling Pathway, Neoplasms genetics
- Abstract
WIF1 (Wnt inhibitory factor 1) is a potent tumour suppressor gene which is epigenetically silenced in numerous malignancies. The associations of WIF1 protein with the Wnt pathway molecules have not been fully explored, despite their involvement in the downregulation of several malignancies. In the present study, a computational approach encompassing the expression, gene ontology analysis and pathway analysis is employed to obtain an insight into the role of the WIF1 protein. Moreover, the interaction of the WIF1 domain with the Wnt pathway molecules was carried out to ascertain the tumour-suppressive role of the domain, along with the determination of their plausible interactions. Initially, the protein-protein interaction network analysis endowed us with the Wnt ligands (such as Wnt1, Wnt3a, Wnt4, Wnt5a, Wnt8a and Wnt9a), along with the Frizzled receptors (Fzd1 and Fzd2) and the low-density lipoprotein complex (Lrp5/6) as the foremost interactors of the protein. Further, the expression analysis of the aforementioned genes and proteins was determined using The Cancer Genome Atlas to comprehend the significance of the signalling molecules in the major cancer subtypes. Moreover, the associations of the aforementioned macromolecular entities with the WIF1 domain were explored using the molecular docking studies, whereas the dynamics and stability of the assemblage were investigated using 100 ns molecular dynamics simulations. Therefore, providing us insights into the plausible roles of WIF1 in inhibiting the Wnt pathways in various malignancies.Communicated by Ramaswamy H. Sarma.
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- 2024
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38. Synthesis of 3-sulfenylindole derivatives from 4-hydroxy-2H-chromene-2-thione and indole using oxidative cross-dehydrogenative coupling reaction and anti-proliferative activity study of some of their sulfone derivatives.
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Xalxo A, Jyoti Goswami U, Sarkar S, Kandasamy T, Mehta K, Ghosh SS, Bharatam PV, and Khan AT
- Subjects
- Humans, Cell Line, Tumor, Drug Screening Assays, Antitumor, Molecular Structure, Oxidative Stress, Structure-Activity Relationship, Sulfones pharmacology, Benzopyrans chemistry, Antineoplastic Agents chemistry, Indoles chemistry, Thiones chemistry
- Abstract
The synthesis of hitherto unreported 3-sulfenylindole derivatives is achieved from 4-hydroxy-2H-chromene-2-thione (1) and indole (2) by employing an oxidative cross-dehydrogenative coupling reaction using a combination of 10 mol% of molecular iodine and 1 equivalent of TBHP in DMSO at room temperature. Then, the 3-sulfenylindole derivatives 3a, 3b, 3d, 3f, 3 h, and 3 k were converted into their corresponding sulfone derivatives because of lead likeness properties. Subsequently, a target prediction and docking study of six sulfone derivatives (5a-f) was performed, and four sulfones, namely 5a, 5d, 5e, and 5f, were selected for further in-vitro studies. The four sulfones mentioned above exhibited prominent anti-proliferative activity on breast cancer (MCF7) cell lines. In addition, this reaction was exergonic through quantum chemical analysis of the mechanistic steps. The salient features of this reaction are mild reaction conditions, good yields, and broad substrate scope., 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 © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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39. Effect of thermal annealing on an emissive layer containing a blend of a small molecule and polymer as host for application in OLEDs.
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Meer BB, Sharma D, Tak S, Bisen GG, Shirsat MD, Girija KG, and Ghosh SS
- Abstract
In order to improve the performance of OLEDs, a host-guest mixture was used as an emissive layer. To have better host properties, a mixture of different materials with suitable properties can also be used as a host. In this study, we used a mixture of a polymer and a small molecule as the host and studied the effect of thermal annealing on the emissive layer properties by using Ir(ppy)
3 as the emitter. UV-visible absorption, steady-state and time-resolved photoluminescence, scanning electron microscopy, atomic force microscopy, and optical microscopic studies were performed to study the film properties. Devices were fabricated and their current-voltage and luminance-voltage characteristics were studied. Charge-carrier mobility in the devices was studied by dark CELIV and transient electroluminescence methods. We show that, below the glass transition temperature of the polymer, the small molecules formed aggregates due to thermal annealing, which was beneficial for the device performance in the lower-temperature range, mainly due to the improved electron mobility. However, this aggregate formation was detrimental in the higher-temperature range, as it led to inefficient energy transfer due to the increased pure phase formation. At temperatures above the glass transition temperature of the polymer, the small molecules were seen to be distributed more uniformly into the polymer matrix. However, as a result of the degradation of the polymer property due to degradation of the primary chain of the phenyl ring of the polymer, this uniform distribution was not of any use and the device performance deteriorated., Competing Interests: The authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)- Published
- 2023
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40. Highly efficient color-tunable organic co-crystals unveiling polymorphism, isomerism, delayed fluorescence for optical waveguides and cell-imaging.
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Barman D, Annadhasan M, Bidkar AP, Rajamalli P, Barman D, Ghosh SS, Chandrasekar R, and Iyer PK
- Abstract
Photofunctional co-crystal engineering strategies based on donor-acceptor π-conjugated system facilitates expedient molecular packing, consistent morphology, and switchable optical properties, conferring synergic 'structure-property relationship' for optoelectronic and biological functions. In this work, a series of organic co-crystals were formulated using a twisted aromatic hydrocarbon (TAH) donor and three diverse planar acceptors, resulting in color-tunable solid and aggregated state emission via variable packing and through-space charge-transfer interactions. While, adjusting the strength of acceptors, a structural transformation into hybrid stacking modes ultimately results in color-specific polymorphs, a configurational cis-isomer with very high photoluminescence quantum yield. The cis-isomeric co-crystal exhibits triplet-harvesting thermally activated delayed fluorescence (TADF) characteristics, presenting a key discovery in hydrocarbon-based multicomponent systems. Further, 1D-microrod-shaped co-crystal acts as an efficient photon-transducing optical waveguides, and their excellent dispersibility in water endows efficient cellular internalization with bright cell imaging performances. These salient approaches may open more avenues for the design and applications of TAH based co-crystals., (© 2023. Springer Nature Limited.)
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- 2023
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41. In silico screening and identification of potential drug against p300 acetyltransferase activity in breast cancer via drug repurposing approach.
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Sarkar S, Kandasamy T, Shome R, and Ghosh SS
- Abstract
Emerging evidence portray the involvement of epigenomic reprogramming in the onset and progression of several malignancies, including breast cancer. Histone acetyltransferase (HAT) p300 is a critical epigenetic regulator that acts as a transcription co-activator and regulates various cellular processes. p300 is overexpressed in breast cancer and promotes cellular invasion and survival, making it a promising druggable target. In this study, the relevance of p300 in different cancer pathways was established. Virtual screening of the FDA-approved drug library was carried out using molecular docking, and the top 10 potential repurposed drugs were identified. Further, recalculation of binding free energy of drug-p300 complexes was carried out using molecular mechanics Poisson-Boltzmann and surface area (MM-PBSA) method after molecular dynamic simulation. Based on molecular dynamic simulation parameters and binding free energy analysis, two drugs, namely Netarsudil (-305.068 kJ/mol) and Imatinib (-260.457 kJ/mol), were identified as potential repurposed drugs to inhibit the activity of p300. In conclusion, these findings suggest, Netarsudil and Imatinib might be a potential repurposed drug to combat breast cancer via p300 inhibition.Communicated by Ramaswamy H. Sarma.
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- 2023
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42. γ-Secretase Inhibitor Potentiates the Activity of Suberoylanilide Hydroxamic Acid by Inhibiting Its Ability to Induce Epithelial to Mesenchymal Transition and Stemness via Notch Pathway Activation in Triple-Negative Breast Cancer Cells.
- Author
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Sen P and Ghosh SS
- Abstract
Histone deacetylase inhibitors, such as suberoylanilide hydroxamic acid (SAHA), possess great therapeutic value for triple-negative breast cancer patients. However, their inherent ability to induce epithelial to mesenchymal transition in various malignancies has been of greater concern. Herein, we hypothesize that SAHA facilitates epithelial to mesenchymal transition (EMT) via activation of the Notch pathway. From the literature survey, it is evident that histone deacetylase mediates the formation of the co-repressor complex upon interacting with the DNA binding domain, thereby inhibiting the transcription of the Notch downstream genes. Hence, we hypothesize that the use of SAHA facilitates the transcriptional activation of the Notch target genes, by disrupting the co-repressor complex and recruiting the coactivator complex, thereby facilitating EMT. In this study, we have observed that SAHA upregulates the expression profile of the Notch downstream proteins (such as Notch intracellular domain, Hes-1, c-Myc, etc.) and the Notch ligands (such as Jagged-1 and Jagged-2), thereby aberrantly activating the signaling pathway. Therefore, we have focused on combination therapy using a γ-secretase inhibitor LY411575 that would enhance the efficacy of SAHA by blocking the canonical Notch pathway mediated via its intracellular domain. It was observed that co-treatment significantly mediates apoptosis, generates cellular reactive oxygen species, depolarizes mitochondria, and diminishes the stemness properties. Besides, it also mediates autophagy-independent cell death and diminishes the expression of inflammatory cytokines, along with the downregulation in the expression of the Notch downstream genes and mesenchymal markers. Altogether, our study provides a mechanistic basis for combating EMT potentiated by SAHA, which could be utilized as a rational strategy for the treatment of solid tumors, especially triple-negative breast cancer., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)
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- 2023
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43. OME-Zarr: a cloud-optimized bioimaging file format with international community support.
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Moore J, Basurto-Lozada D, Besson S, Bogovic J, Bragantini J, Brown EM, Burel JM, Casas Moreno X, de Medeiros G, Diel EE, Gault D, Ghosh SS, Gold I, Halchenko YO, Hartley M, Horsfall D, Keller MS, Kittisopikul M, Kovacs G, Küpcü Yoldaş A, Kyoda K, le Tournoulx de la Villegeorges A, Li T, Liberali P, Lindner D, Linkert M, Lüthi J, Maitin-Shepard J, Manz T, Marconato L, McCormick M, Lange M, Mohamed K, Moore W, Norlin N, Ouyang W, Özdemir B, Palla G, Pape C, Pelkmans L, Pietzsch T, Preibisch S, Prete M, Rzepka N, Samee S, Schaub N, Sidky H, Solak AC, Stirling DR, Striebel J, Tischer C, Toloudis D, Virshup I, Walczysko P, Watson AM, Weisbart E, Wong F, Yamauchi KA, Bayraktar O, Cimini BA, Gehlenborg N, Haniffa M, Hotaling N, Onami S, Royer LA, Saalfeld S, Stegle O, Theis FJ, and Swedlow JR
- Subjects
- Humans, Community Support, Software, Microscopy
- Abstract
A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals and institutes across diverse modalities facing these problems have designed a format specification process (OME-NGFF) to address these needs. This paper brings together a wide range of those community members to describe the cloud-optimized format itself-OME-Zarr-along with tools and data resources available today to increase FAIR access and remove barriers in the scientific process. The current momentum offers an opportunity to unify a key component of the bioimaging domain-the file format that underlies so many personal, institutional, and global data management and analysis tasks., (© 2023. The Author(s).)
- Published
- 2023
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44. Understanding Deformation and Breakup Tendency of Shear-Thinning Viscoelastic Drops in Constricted Microchannels.
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Prasad NK, Ghosh SS, and Dalal A
- Abstract
The study of drop deformation in response to various stresses has long piqued the interest of several academics. The deformation behavior of cells, drug carriers, and even drug particles moving via microcapillaries inside the human body can be modeled using a viscoelastic drop model. A drop breakup study can also provide better design guidance for nanocarriers that can deliver on-demand burst drug releases at specific cancer sites. Thus, we attempted to investigate the deformation and breakup of a shear-thinning finitely extensible nonlinear elastic-peterlin (FENE-P) drop moving through the constricted microchannel. The computational simulation suggested that drop deformation and breakup can be manipulated by varying of parameters like channel confinement, Deborah number, solvent viscosity ratio, viscosity ratio, and capillary number. We attempted to find the critical capillary number for initiation of drop breakup. Observations from present study will give valuable insights into deformation and breakup patterns of drug carriers inside constricted microcapillaries. The simulations of the two-phase viscoelastic drop─Newtonian matrix system were performed on an open-source solver, Basilisk.
- Published
- 2023
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45. A reproducible and generalizable software workflow for analysis of large-scale neuroimaging data collections using BIDS Apps.
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Zhao C, Jarecka D, Covitz S, Chen Y, Eickhoff SB, Fair DA, Franco AR, Halchenko YO, Hendrickson TJ, Hoffstaedter F, Houghton A, Kiar G, Macdonald A, Mehta K, Milham MP, Salo T, Hanke M, Ghosh SS, Cieslak M, and Satterthwaite TD
- Abstract
Neuroimaging research faces a crisis of reproducibility. With massive sample sizes and greater data complexity, this problem becomes more acute. Software that operates on imaging data defined using the Brain Imaging Data Structure (BIDS) - BIDS Apps - have provided a substantial advance. However, even using BIDS Apps, a full audit trail of data processing is a necessary prerequisite for fully reproducible research. Obtaining a faithful record of the audit trail is challenging - especially for large datasets. Recently, the FAIRly big framework was introduced as a way to facilitate reproducible processing of large-scale data by leveraging DataLad - a version control system for data management. However, the current implementation of this framework was more of a proof of concept, and could not be immediately reused by other investigators for different use cases. Here we introduce the BIDS App Bootstrap (BABS), a user-friendly and generalizable Python package for reproducible image processing at scale. BABS facilitates the reproducible application of BIDS Apps to large-scale datasets. Leveraging DataLad and the FAIRly big framework, BABS tracks the full audit trail of data processing in a scalable way by automatically preparing all scripts necessary for data processing and version tracking on high performance computing (HPC) systems. Currently, BABS supports jobs submissions and audits on Sun Grid Engine (SGE) and Slurm HPCs with a parsimonious set of programs. To demonstrate its scalability, we applied BABS to data from the Healthy Brain Network (HBN; n=2,565). Taken together, BABS allows reproducible and scalable image processing and is broadly extensible via an open-source development model.
- Published
- 2023
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46. NIDM-Terms: community-based terminology management for improved neuroimaging dataset descriptions and query.
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Queder N, Tien VB, Abraham SA, Urchs SGW, Helmer KG, Chaplin D, van Erp TGM, Kennedy DN, Poline JB, Grethe JS, Ghosh SS, and Keator DB
- Abstract
The biomedical research community is motivated to share and reuse data from studies and projects by funding agencies and publishers. Effectively combining and reusing neuroimaging data from publicly available datasets, requires the capability to query across datasets in order to identify cohorts that match both neuroimaging and clinical/behavioral data criteria. Critical barriers to operationalizing such queries include, in part, the broad use of undefined study variables with limited or no annotations that make it difficult to understand the data available without significant interaction with the original authors. Using the Brain Imaging Data Structure (BIDS) to organize neuroimaging data has made querying across studies for specific image types possible at scale. However, in BIDS, beyond file naming and tightly controlled imaging directory structures, there are very few constraints on ancillary variable naming/meaning or experiment-specific metadata. In this work, we present NIDM-Terms, a set of user-friendly terminology management tools and associated software to better manage individual lab terminologies and help with annotating BIDS datasets. Using these tools to annotate BIDS data with a Neuroimaging Data Model (NIDM) semantic web representation, enables queries across datasets to identify cohorts with specific neuroimaging and clinical/behavioral measurements. This manuscript describes the overall informatics structures and demonstrates the use of tools to annotate BIDS datasets to perform integrated cross-cohort queries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Queder, Tien, Abraham, Urchs, Helmer, Chaplin, van Erp, Kennedy, Poline, Grethe, Ghosh and Keator.)
- Published
- 2023
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47. A guide to the BRAIN Initiative Cell Census Network data ecosystem.
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Hawrylycz M, Martone ME, Ascoli GA, Bjaalie JG, Dong HW, Ghosh SS, Gillis J, Hertzano R, Haynor DR, Hof PR, Kim Y, Lein E, Liu Y, Miller JA, Mitra PP, Mukamel E, Ng L, Osumi-Sutherland D, Peng H, Ray PL, Sanchez R, Regev A, Ropelewski A, Scheuermann RH, Tan SZK, Thompson CL, Tickle T, Tilgner H, Varghese M, Wester B, White O, Zeng H, Aevermann B, Allemang D, Ament S, Athey TL, Baker C, Baker KS, Baker PM, Bandrowski A, Banerjee S, Bishwakarma P, Carr A, Chen M, Choudhury R, Cool J, Creasy H, D'Orazi F, Degatano K, Dichter B, Ding SL, Dolbeare T, Ecker JR, Fang R, Fillion-Robin JC, Fliss TP, Gee J, Gillespie T, Gouwens N, Zhang GQ, Halchenko YO, Harris NL, Herb BR, Hintiryan H, Hood G, Horvath S, Huo B, Jarecka D, Jiang S, Khajouei F, Kiernan EA, Kir H, Kruse L, Lee C, Lelieveldt B, Li Y, Liu H, Liu L, Markuhar A, Mathews J, Mathews KL, Mezias C, Miller MI, Mollenkopf T, Mufti S, Mungall CJ, Orvis J, Puchades MA, Qu L, Receveur JP, Ren B, Sjoquist N, Staats B, Tward D, van Velthoven CTJ, Wang Q, Xie F, Xu H, Yao Z, Yun Z, Zhang YR, Zheng WJ, and Zingg B
- Subjects
- Animals, Humans, Mice, Ecosystem, Neurons, Brain, Neurosciences
- Abstract
Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also essential to manipulate cell types in controlled ways and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data-generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization. Emphasis of the BICCN is on the whole mouse brain with demonstration of prototype feasibility for human and nonhuman primate (NHP) brains. Here, we provide a guide to the cellular and spatial approaches employed by the BICCN, and to accessing and using these data and extensive resources, including the BRAIN Cell Data Center (BCDC), which serves to manage and integrate data across the ecosystem. We illustrate the power of the BICCN data ecosystem through vignettes highlighting several BICCN analysis and visualization tools. Finally, we present emerging standards that have been developed or adopted toward Findable, Accessible, Interoperable, and Reusable (FAIR) neuroscience. The combined BICCN ecosystem provides a comprehensive resource for the exploration and analysis of cell types in the brain., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AR is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas Therapeutics and, until 31 July 2020, was a scientific advisory board member of Thermo Fisher Scientific, Syros Pharmaceuticals, Asimov, and Neogene Therapeutics. From 1 August 2020, AR is an employee of Genentech and has equity in Roche. AR is a named inventor on multiple patents related to single cell and spatial genomics filed by or issued to the Broad Institute., (Copyright: © 2023 Hawrylycz 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.)
- Published
- 2023
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48. Designing of disruptor molecules to restrain the protein-protein interaction network of VANG1/SCRIB/NOS1AP using fragment-based drug discovery techniques.
- Author
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Acharyya SR, Sen P, Kandasamy T, and Ghosh SS
- Subjects
- Molecular Docking Simulation, Protein Binding, Proteins, Protein Interaction Maps, Drug Discovery methods
- Abstract
Governing protein-protein interaction networks are the cynosure of cell signaling and oncogenic networks. Multifarious processes when aligned with one another can result in a dysregulated output which can result in cancer progression. In the current research, one such network of proteins comprising VANG1/SCRIB/NOS1AP, which is responsible for cell migration, is targeted. The proteins are modeled using in-silico approaches, and the interaction is visualized utilizing protein-protein docking. Designing drugs for the convoluted protein network can serve as a challenging task that can be overcome by fragment-based drug designing, a recent game-changer in the computational drug discovery strategy for protein interaction networks. The model is exposed to the extraction of hotspots, also known as the restrained regions for small molecular hits. The hotspot regions are subjected to a library of generated fragments, which are then recombined and rejoined to develop small molecular disruptors of the macromolecular assemblage. Rapid screening methods using pharmacokinetic tools and 2D interaction studies resulted in four molecules that could serve the purpose of a disruptor. The final validation is executed by long-range simulations of 100 ns and exploring the stability of the complex using several parameters leading to the emergence of two novel molecules VNS003 and VNS005 that could be used as the disruptors of the protein assembly VANG1/SCRIB/NOS1AP. Also, the molecules were explored as single protein targets approbated via molecular docking and 100 ns molecular dynamics simulation. This concluded VNS003 as the most suitable inhibitor module capable of acting as a disruptor of a macromolecular assembly as well as acting on individual protein chains, thus leading to the primary hindrance in the formation of the protein interaction complex., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
- Published
- 2023
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49. The Intricate Notch Signaling Dynamics in Therapeutic Realms of Cancer.
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Sen P and Ghosh SS
- Abstract
The Notch pathway is remarkably simple without the interventions of secondary messengers. It possesses a unique receptor-ligand interaction that imparts signaling upon cleavage of the receptor followed by the nuclear localization of its cleaved intracellular domain. It is found that the transcriptional regulator of the Notch pathway lies at the intersection of multiple signaling pathways that enhance the aggressiveness of cancer. The preclinical and clinical evidence supports the pro-oncogenic function of Notch signaling in various tumor subtypes. Owing to its oncogenic role, the Notch signaling pathway assists in enhanced tumorigenesis by facilitating angiogenesis, drug resistance, epithelial to mesenchymal transition, etc., which is also attributed to the poor outcome in patients. Therefore, it is extremely vital to discover a suitable inhibitor to downregulate the signal-transducing ability of Notch. The Notch inhibitory agents, such as receptor decoys, protease (ADAM and γ-secretase) inhibitors, and monoclonal/bispecific antibodies, are being investigated as candidate therapeutic agents. Studies conducted by our group exemplify the promising results in ablating tumorigenic aggressiveness by inhibiting the constituents of the Notch pathway. This review deals with the detailed mechanism of the Notch pathways and their implications in various malignancies. It also bestows us with the recent therapeutic advances concerning Notch signaling in the context of monotherapy and combination therapy., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)
- Published
- 2023
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- View/download PDF
50. Neurodesk: An accessible, flexible, and portable data analysis environment for reproducible neuroimaging.
- Author
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Renton AI, Dao TT, Johnstone T, Civier O, Sullivan RP, White DJ, Lyons P, Slade BM, Abbott DF, Amos TJ, Bollmann S, Botting A, Campbell MEJ, Chang J, Close TG, Eckstein K, Egan GF, Evas S, Flandin G, Garner KG, Garrido MI, Ghosh SS, Grignard M, Hannan AJ, Huber R, Kaczmarzyk JR, Kasper L, Kuhlmann L, Lou K, Mantilla-Ramos YJ, Mattingley JB, Morris J, Narayanan A, Pestilli F, Puce A, Ribeiro FL, Rogasch NC, Rorden C, Schira M, Shaw TB, Sowman PF, Spitz G, Stewart A, Ye X, Zhu JD, Hughes ME, Narayanan A, and Bollmann S
- Abstract
Neuroimaging data analysis often requires purpose-built software, which can be challenging to install and may produce different results across computing environments. Beyond being a roadblock to neuroscientists, these issues of accessibility and portability can hamper the reproducibility of neuroimaging data analysis pipelines. Here, we introduce the Neurodesk platform, which harnesses software containers to support a comprehensive and growing suite of neuroimaging software (https://www.neurodesk.org/). Neurodesk includes a browser-accessible virtual desktop environment and a command line interface, mediating access to containerized neuroimaging software libraries on various computing platforms, including personal and high-performance computers, cloud computing and Jupyter Notebooks. This community-oriented, open-source platform enables a paradigm shift for neuroimaging data analysis, allowing for accessible, flexible, fully reproducible, and portable data analysis pipelines., Competing Interests: Competing interests The authors declare no financial conflicts of interest.
- Published
- 2023
- Full Text
- View/download PDF
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