595 results on '"H. Joshi"'
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2. Solubilisation & purification of membrane proteins using benzylamine-modified SMA polymers.
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Akram A, Hadasha W, Kuyler GC, Smith MP, Bailey-Dallaway S, Preedy A, Browne C, Broadbent L, Hill A, Javaid T, Nazar H, Samra N, Naveed A, Tregunna H, Joshi H, Akhtar N, Javed A, Bowater J, Ravenhill J, Hajdu P, Ali Y, Tailor Y, Mumtaz S, Hamza M, Gill K, Gillett J, Patton F, Arshid H, Zaheer M, Qureshi H, Edwards I, Patel S, Azadi A, Pollock N, Kitchen P, Klumperman B, and Rothnie AJ more...
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- Polymers chemistry, Animals, Polystyrenes chemistry, Lipid Bilayers chemistry, Polymerization, Membrane Proteins chemistry, Membrane Proteins isolation & purification, Maleates chemistry, Solubility, Benzylamines chemistry, Benzylamines isolation & purification
- Abstract
Extraction of proteins from the membrane using styrene maleic acid co-polymers (SMA), forming SMA lipid particles (SMALPs), has allowed for the first time the purification of membrane proteins with their lipid bilayer environment. To date, SMA2000 has been the most effective polymer used for this purpose, with a 2:1 ratio of styrene:maleic acid, and styrene and maleic acid moieties spread statistically throughout the chain. However, SMA2000 is a highly polydisperse polymer that contains an array of different polymer lengths and sequences. RAFT polymerisation offers much better control over the polymer length; however, homogeneous distribution of styrene and maleic acid throughout the polymer is difficult to achieve. Instead, here RAFT polymerisation was used to produce a 1:1 styrene:maleic anhydride polymer, which was then modified with benzylamine. This mimics the 2:1 hydrophobic:hydrophilic nature of SMA2000, while controlling the length and obtaining a homogeneous distribution of the hydrophobic moieties (styrene and N-benzylmaleimide). SMA-benzylamine (SMA-BA) polymers of three different lengths (2, 4, and 7 kDa) were all able to solubilise purified lipids, cellular membranes, and a range of specific proteins. However, the larger 7 kDa polymer solubilised membranes more slowly and less efficiently than the shorter polymers. This also affected the yield of purified protein obtained by affinity purification with this polymer. The smallest 2 kDa polymer solubilised membranes the fastest but appeared to offer less stability to the extracted proteins. The SMA-BA polymers were more sensitive to Mg
2+ ions than SMA2000. SMA-BA 4 kDa was otherwise comparable to SMA2000 and even gave a higher degree of purity., Competing Interests: Declaration of competing interest The authors have no conflicting interests to declare that are relevant to the content of this article. GCK and BK are directors of Nanosene (Pty) Ltd., a company that commercializes amphiphilic copolymers for the isolation of membrane proteins. 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. Published by Elsevier B.V.) more...- Published
- 2025
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3. Microstructural mapping of neural pathways in Alzheimer's disease using macrostructure-informed normative tractometry.
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Feng Y, Chandio BQ, Villalon-Reina JE, Thomopoulos SI, Nir TM, Benavidez S, Laltoo E, Chattopadhyay T, Joshi H, Venkatasubramanian G, John JP, Jahanshad N, Reid RI, Jack CR, Weiner MW, and Thompson PM more...
- Abstract
Introduction: Diffusion-weighted magnetic resonance imaging (dMRI) is sensitive to the microstructural properties of brain tissues and shows great promise in detecting the effects of degenerative diseases. However, many approaches analyze single measures averaged over regions of interest without considering the underlying fiber geometry., Methods: We propose a novel macrostructure-informed normative tractometry (MINT) framework to investigate how white matter (WM) microstructure and macrostructure are jointly altered in mild cognitive impairment (MCI) and dementia. We compared MINT-derived metrics with univariate diffusion tensor imaging (DTI) metrics to examine how fiber geometry may impact the interpretation of microstructure., Results: In two multisite cohorts from North America and India, we find consistent patterns of microstructural and macrostructural anomalies implicated in MCI and dementia; we also rank diffusion metrics' sensitivity to dementia., Discussion: We show that MINT, by jointly modeling tract shape and microstructure, has the potential to disentangle and better interpret the effects of degenerative disease on the brain's neural pathways., Highlights: Changes in diffusion tensor imaging metrics may be due to macroscopic changes. Normative models encode normal variability of diffusion metrics in healthy controls. Variational autoencoder applied on tractography can learn patterns of fiber geometry. WM microstructure and macrostructure are modeled with multivariate methods. Transfer learning uses pretraining and fine-tuning for increased efficiency., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.) more...
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- 2024
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4. Dynamic analysis of fractal-fractional cancer model under chemotherapy drug with generalized Mittag-Leffler kernel.
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Joshi H, Yavuz M, Taylan O, and Alkabaa A
- Abstract
Background and Objective: Cancer's complex and multifaceted nature makes it challenging to identify unique molecular and pathophysiological signatures, thereby hindering the development of effective therapies. This paper presents a novel fractal-fractional cancer model to study the complex interplay among stem cells, effectors cells, and tumor cells in the presence and absence of chemotherapy. The cancer model with effective treatment through chemotherapy drugs is considered and discussed in detail., Methods: The numerical method for the fractal-fractional cancer model with a generalized Mittag-Leffler kernel is presented. The Routh-Hurwitz stability criteria are applied to confirm the local asymptotically stability of an endemic equilibrium point of the cancer model without treatment and with effective treatment under some conditions. The existence and uniqueness criteria of the fractal-fractional cancer model are derived. Furthermore, the stability analysis of the fractal-fractional cancer model is performed., Results: The temporal concentration pattern of stem cells, effectors cells, tumor cells, and chemotherapy drugs are procured. The usage of chemotherapy drugs kills the tumor cells or decreases their density over time and as a consequence takes a longer time to reach to equilibrium point. The decay rate of stem cells and tumor cells plays a crucial role in cancer dynamics. The notable role of fractal dimensions along with fractional order is observed in capturing the cancer cell concentration., Conclusion: A dynamic analysis of the fractal-fractional cancer model is demonstrated to examine the impact of chemotherapy drugs with a generalized Mittag-Leffler kernel. The model possesses three equilibrium points among them two correspond to the cancer model without treatment namely the tumor-free equilibrium point and endemic equilibrium point. One additional endemic equilibrium point exists in the case of effective treatment through chemotherapy drugs. The Routh-Hurwitz stability criteria are applied to confirm the local asymptotically stability of an endemic equilibrium point of the cancer model with and without treatment under some conditions. The chemotherapy drug plays a crucial role in controlling the growth of tumor cells. The fractal-fractional operator provided robustness to study cancer dynamics by the inclusion of memory and heterogeneity., 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 B.V. All rights reserved.) more...
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- 2024
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5. A Catalytic, Enantioselective Sulfamate Tethered Aza -Michael Cyclization.
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Joshi H, Manna A, Nagamalla S, Thomas AA, and Sathyamoorthi S
- Abstract
We show the first examples of enantioselective cyclization reactions of tethered sulfamates onto pendant α,β-unsaturated esters, ketones, and thioesters. This reaction is promoted by a new chiral bifunctional guanidine catalyst and is operationally very simple. A variety of primary sulfamates and sulfamides were examined, and in many cases, products were delivered in excellent yields and enantiomeric ratios. With secondary sulfamates, kinetic resolutions were possible. The product oxathiazinanes are very useful chiral synthons. more...
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- 2024
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6. Role of the Quantum Interactions in H 2 Adsorption on Late Transition Metal Chelated Linkers of Covalent Organic Frameworks.
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Joshi H and Pakhira S
- Abstract
Transition metal (Tm) chelation is an effective strategy to achieve optimal binding enthalpy (▵H) of H
2 -adsorption in the linkers of covalent organic frameworks (COFs). The first principle-based DFT method has been implemented to determine the H2 adsorption in nine organic linkers chelated with transition metal atoms from Cr to Zn. The obtained range of binding enthalpy for single H2 adsorbed on the pure and chelated complexes is -7 to -20 kJ/mol, which is required for onboard H2 storage. The Linker-3 chelated with Ni (II) metal exhibits the most favorable binding enthalpy of approximately -18.72 kJ/mol for the single adsorbed H2 molecule, which falls within the physisorption range. Some of the complexes have shown the binding enthalpy range between physisorption and chemisorption, i. e., in that case, H2 binds via Kubas interactions. However, physisorption-based complexes are preferable to others because physisorption is a reversible process with rapid kinetics. This study reveals that the dispersion, polarization, and electrostatic interactions mainly contribute to the binding enthalpy of H2 adsorption. Molecular surface potential analysis verifies the origin of induced dipole moment in the H2 molecule, which enhances the hydrogen adsorption in transition metal chelated COFs., (© 2024 Wiley-VCH GmbH.) more...- Published
- 2024
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7. Plant growth-promoting Bacillus amyloliquefaciens orchestrate homeostasis under nutrient deficiency exacerbated drought and salinity stress in Oryza sativa L. seedlings.
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Bisht N, Singh T, Ansari MM, Joshi H, Mishra SK, and Chauhan PS
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- Droughts, Homeostasis, Salt Stress, Gene Expression Regulation, Plant, Salinity, Nutrients metabolism, Stress, Physiological, Oryza microbiology, Oryza genetics, Oryza physiology, Oryza growth & development, Oryza metabolism, Bacillus amyloliquefaciens physiology, Seedlings microbiology, Seedlings growth & development, Seedlings physiology, Seedlings genetics
- Abstract
Main Conclusion: Nutrient deficiency intensifies drought and salinity stress on rice growth. Bacillus amyloliquefaciens inoculation provides resilience through modulation in metabolic and gene regulation to enhance growth, nutrient uptake, and stress tolerance. Soil nutrient deficiencies amplify the detrimental effects of abiotic stresses, such as drought and salinity, creating substantial challenges for overall plant health and crop productivity. Traditional methods for developing stress-resistant varieties are often slow and labor-intensive. Previously, we demonstrated that plant growth-promoting rhizobacteria Bacillus amyloliquefaciens strain SN13 effectively alleviates stress induced by sub-optimum nutrient conditions in rice. In this study, we evaluated the effectiveness of SN13 in reducing the compounded impacts of drought and salinity under varying nutrient regimes in rice seedlings. The results demonstrated that PGPR inoculation not only improved the growth parameters, nutrient content, and physio-biochemical characteristics under nutrient-limited conditions, but also reduced the oxidative stress markers. The altered expression of stress-related and transcription factor genes (USP, DEF, CYP450, GST, MYB, and bZIP) revealed the regulatory effect of PGPR in enhancing stress tolerance through these genes. GC-MS-based untargeted metabolomic analysis revealed that PGPR significantly influenced various metabolic pathways, including galactose metabolism, fructose and mannose metabolism, and fatty acid biosynthesis pathways, suggesting that PGPR affects both energy production and stress-protective mechanisms, facilitating better growth and survival of rice seedlings., Competing Interests: Declarations. Conflict of interest: The authors state that they do not have any known financial interests or personal relationships that could have been perceived as having an impact on the research presented in this article., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) more...
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- 2024
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8. Deformed mandibular posterior border.
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Bansal N, Chaudhary Z, Sharma P, Augustine J, Dar JI, and Joshi H
- Abstract
Competing Interests: Informed Consent The authors have obtained written informed consent from the patient for publication of extraoral photographs.
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- 2024
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9. Elucidation of PGPR-responsive OsNAM2 regulates salt tolerance in Arabidopsis by AFP2 and SUS protein interaction.
- Author
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Joshi H, Harter K, Rohr L, Mishra SK, and Chauhan PS
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- Plant Roots microbiology, Plant Roots growth & development, Plant Roots metabolism, Plant Roots genetics, Plant Proteins genetics, Plant Proteins metabolism, Plants, Genetically Modified genetics, Seedlings growth & development, Seedlings genetics, Signal Transduction, Sodium Chloride metabolism, Germination, Salt Stress, Abscisic Acid metabolism, Proline metabolism, Arabidopsis genetics, Arabidopsis metabolism, Arabidopsis physiology, Salt Tolerance genetics, Gene Expression Regulation, Plant, Bacillus amyloliquefaciens genetics, Bacillus amyloliquefaciens metabolism, Bacillus amyloliquefaciens physiology
- Abstract
This study investigates the molecular mechanisms underlying salt stress responses in plants, focusing on the regulatory roles of OsNAM2, a gene influenced by the plant growth-promoting rhizobacterium Bacillus amyloliquefaciens (SN13). The study examines how SN13-modulated OsNAM2 enhances salt tolerance in Arabidopsis through physiological, biochemical, and molecular analyses. Overexpression of OsNAM2, especially with SN13 inoculation, improves germination, seedling growth, root length, and biomass under high NaCl concentrations compared to wild-type plants, indicating a synergistic effect. OsNAM2 overexpression enhances relative water content, reduces electrolyte leakage and malondialdehyde accumulation, and increases proline content, suggesting better membrane integrity and stress endurance. Furthermore, SN13 and OsNAM2 overexpression modulates essential metabolic genes involved in glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle, facilitating metabolic adjustments crucial for salt stress adaptation. The interaction of OsNAM2 with SUS, facilitated by SN13, suggests enhanced sucrose metabolism efficiency, providing substrates for protective responses. Additionally, OsNAM2 plays a regulatory role in the ABA signaling pathway through significant protein-protein interactions like with AFP2. This study highlights the intricate interplay between SN13-responsive OsNAM2 and key signaling pathways, suggesting strategies for enhancing crop salt tolerance through targeted genetic and microbial interventions., (Copyright © 2024 Elsevier GmbH. All rights reserved.) more...
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- 2024
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10. Host defense peptides at the crossroad of endothelial cell physiology: Insight into mechanistic and pharmacological implications.
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Garg VK, Joshi H, Sharma AK, Yadav K, and Yadav V
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- Humans, Animals, Signal Transduction drug effects, Antimicrobial Peptides pharmacology, Antimicrobial Peptides metabolism, Antimicrobial Peptides chemistry, Apoptosis drug effects, Endothelial Cells drug effects, Endothelial Cells metabolism
- Abstract
Antimicrobial peptides (AMPs), particularly host defense peptides (HDPs), have gained recognition for their role in host defense mechanisms, but they have also shown potential as a promising anticancer, antiviral, antiparasitic, antifungal and immunomodulatory agent. Research studies in recent years have shown HDPs play a crucial role in endothelial cell function and biology. The function of endothelial cells is impacted by HDPs' complex interplay between cytoprotective and cytotoxic actions as they are known to modulate barrier integrity, inflammatory response and angiogenesis. This biphasic response varies and depends on the peptide structure, its concentration, and the microenvironment. These effects are mediated through key signaling pathways, including MAPK, NF-κB, and PI3K/Akt, which controls responses such as cell proliferation, apoptosis, and migration. In the present review, we have discussed the significance of the intriguing relationship between HDPs and endothelial cell physiology which suggests it potential as a therapeutic agents for the treating wounds, cardiovascular diseases, and inflammation-related endothelial damage., Competing Interests: Declaration of Competing Interest Authors declare no conflict of Interest., (Copyright © 2024. Published by Elsevier Inc.) more...
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- 2024
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11. Competition-driven phenotypic plasticity in Iron acquisition and aromatic utilization confers a fitness advantage to Pseudomonas putida in an Iron-limited rhizospheric environment.
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Joshi H and Khan A
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- Gene Expression Regulation, Bacterial, Soil Microbiology, Phenotype, Bacterial Proteins genetics, Bacterial Proteins metabolism, Plant Roots microbiology, Pseudomonas putida genetics, Pseudomonas putida metabolism, Pseudomonas putida growth & development, Rhizosphere, Iron metabolism, Siderophores metabolism, Oligopeptides metabolism
- Abstract
Iron scarcity poses a critical challenge for rhizospheric bacteria like Pseudomonas putida in the competitive rhizosphere. Despite its dependence on iron for essential functions such as root colonization, motility, and aromatic compound utilization, P. putida exhibits limited capability for heterologous siderophore utilization and primarily relies on the secretion of a single siderophore, pyoverdine. This study investigates the mechanisms by which P. putida acquires iron in an iron-limited, aromatic-rich, rhizosphere-like environment. Our findings demonstrate that P. putida exhibits significant phenotypic plasticity, dynamically modulating pyoverdine secretion in response to competitive pressures and substrate availability. This adaptive strategy optimizes energy expenditure and iron acquisition, providing a competitive advantage. Comparative gene expression analysis supports these observations, revealing the molecular underpinnings of this plasticity. Enhanced pyoverdine production driven by competition compensates for the bacterium's limited siderophore repertoire and facilitates rapid aromatic compound utilization, conferring a distinct fitness advantage in iron-deprived conditions. This study elucidates the complex interplay between competition, iron uptake, and aromatic compound utilization that underpins the rhizospheric success of P. putida., (© 2024. The Author(s).) more...
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- 2024
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12. Exploration of One-Pot, Tandem Sulfamoylation and aza -Michael Cyclization Reactions for the Syntheses of Oxathiazinane Dioxide Heterocycles.
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Nirpal AK, Joshi H, Kelley SP, and Sathyamoorthi S
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We show the first examples of one-pot tandem sulfamoylation/ aza -Michael reactions for the preparation of oxathiazinane dioxide heterocycles from linear alkenyl alcohol precursors. Our optimized protocols are tolerant of a variety of functional groups and provide products that are amenable for further transformations. The reactions scale well, and no special precautions are required to exclude air or ambient moisture. more...
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- 2024
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13. Correction: "Luck of the draw really": a qualitative exploration of Australian trainee doctors' experiences of mandatory research.
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Brandenburg C, Hilder J, Noble C, Liang R, Forrest K, Joshi H, Keijzers G, Mickan S, Pearson D, Scott IA, Veysey E, and Stehlik P
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- 2024
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14. Bacillus australimaris protect Gloriosa superba L. against Alternaria alternata infestation.
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Semwal P, Mishra SK, Majhi B, Mishra A, Joshi H, Misra S, Misra A, Srivastava S, and Chauhan PS
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- Chitinases metabolism, Peptide Hydrolases metabolism, Antifungal Agents pharmacology, Antifungal Agents metabolism, Plant Leaves microbiology, Ascomycota drug effects, Ascomycota metabolism, Fungicides, Industrial pharmacology, Alternaria drug effects, Alternaria growth & development, Plant Diseases microbiology, Plant Diseases prevention & control, Endophytes metabolism, Endophytes physiology, Bacillus metabolism
- Abstract
Gloriosa superba L., a medicinally important plant, is often affected by leaf blight disease caused by Alternaria alternata, which compromises its productivity. This study explores the protective effects of Bacillus australimaris endophyte (NBRI GS34), demonstrating that its inoculation not only inhibits the disease but also promotes plant growth and increases the concentrations of bioactive metabolites. Co-culturing NBRI GS34 with A. alternata significantly boosts protease (30-50%) and chitinase (6-28%) activities, evidencing a synergistic interaction. Scanning electron microscopy and GC-MS analysis confirm NBRI GS34's antagonistic action and reveal antifungal compounds like undecanoic acid and benzene carboxylic acid in treatments. Greenhouse experiments show a 78% reduction in disease incidence with NBRI GS34 treatment, enhancing vegetative growth and upregulating defense-related genes. Additionally, HPLC analysis reveals increased gloriosine and colchicine concentrations by 52% and 33%, respectively. These findings suggest NBRI GS34 could serve as a sustainable fungicide alternative, enhancing the production of medically valuable compounds and highlighting its potential pharmaceutical applications., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.) more...
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- 2024
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15. Descriptive analysis of 1,048 presentations in the first five years of a zero-suicide framework in a child and youth mental health service in Australia.
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Branjerdporn G, McCosker LK, Jackson D, Gillespie KM, McDowell S, Chand S, Joshi H, Pisani AR, Stapelberg NJC, Welch M, Turner K, and Woerwag-Mehta S
- Abstract
Introduction: Suicide in children is a significant and unacceptable global phenomenon. This paper provides a descriptive overview of the children presenting in the first five years (2016-2021) of the implementation of the Zero Suicide Framework (ZSF) and Suicide Prevention Pathway (SPP) at a Child and Youth Mental Health Service in Queensland, Australia., Methods: Basic demographic variables (sex, age, socioeconomic status), and changes in presentations over time, are presented for 1,048 children. Completeness of selected SPP components relating to care planning and universal interventions are examined as an indicator of fidelity to the SPP model of care. The paper then focuses on the cohort of children who received care through the SPP in 2020, describing their demographic characteristics and baseline clinical scores., Result: There was an increase in admissions each year and children presented with a diverse range of clinical needs. The SPP greatly increased the provision of first line interventions for patients., Discussion: A standardized approach to suicide prevention improves consistency in management. These findings may inform the use of the ZSF/SPP in child mental health settings globally., Competing Interests: AP is the founder of SafeSide Prevention/SafeSide Australia which licensed educational materials from University of Rochester. SafeSide receives fees for education, consultation, and leadership services for healthcare organizations and government. The University of Rochester receives royalties from SafeSide and declares this financial interest. A conflict of interest management plan is in place at the University of Rochester and routinely communicated and monitored per University guidelines. AP receives book royalties from Cambridge University Press. The remaining 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 © 2024 Branjerdporn, McCosker, Jackson, Gillespie, McDowell, Chand, Joshi, Pisani, Stapelberg, Welch, Turner and Woerwag-Mehta.) more...
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- 2024
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16. Intramolecular Silanoxy-Michael Reactions with Pendant Nitroalkenes: Racemic and Enantioselective.
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Joshi H and Sathyamoorthi S
- Abstract
We present the first racemic and scalemic examples of di- tert -butyl silanoxy-Michael additions. Our operationally simple protocol is selective for nitro-olefins and simply involves stirring the substrate with an appropriate hydrogen-bond donor catalyst without any special precautions to exclude air or moisture. For each substrate examined, we have developed complementary protocols that optimize yield and enantioselectivity. Our reactions scale well, and the products are valuable intermediates for further transformations, including for the preparation of enantioenriched vicinal amino alcohols. more...
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- 2024
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17. Computational Insights Into the Mechanism of EGCG's Binding and Inhibition of the TDP-43 Aggregation.
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Meshram VD, Balaji R, Saravanan P, Subbamanda Y, Deeksha W, Bajpai A, Joshi H, Bhargava A, and Patel BK
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- Humans, Binding Sites, Thermodynamics, Protein Aggregates drug effects, Protein Domains, Catechin analogs & derivatives, Catechin chemistry, Catechin pharmacology, Catechin metabolism, DNA-Binding Proteins metabolism, DNA-Binding Proteins chemistry, DNA-Binding Proteins antagonists & inhibitors, Molecular Dynamics Simulation, Molecular Docking Simulation, Protein Binding
- Abstract
Misfolding and aggregation of TAR DNA-binding protein, TDP-43, is linked to devastating proteinopathies such as ALS. Therefore, targeting TDP-43's aggregation is significant for therapeutics. Recently, green tea polyphenol, EGCG, was observed to promote non-toxic TDP-43 oligomer formation disallowing TDP-43 aggregation. Here, we investigated if the anti-aggregation effect of EGCG is mediated via EGCG's binding to TDP-43. In silico molecular docking and molecular dynamics (MD) simulation suggest a strong binding of EGCG with TDP-43's aggregation-prone C-terminal domain (CTD). Three replicas, each having 800 ns MD simulation of the EGCG-TDP-43-CTD complex, yielded a high negative binding free energy (ΔG) inferring a stable complex formation. Simulation snapshots show that EGCG forms close and long-lasting contacts with TDP-43's Phe-313 and Ala-341 residues, which were previously identified for monomer recruitment in CTD's aggregation. Notably, stable physical interactions between TDP-43 and EGCG were also detected in vitro using TTC staining and isothermal titration calorimetry which revealed a high-affinity binding site of EGCG on TDP-43 (K
d , 7.8 μM; ΔG, -6.9 kcal/mol). Additionally, TDP-43 co-incubated with EGCG was non-cytotoxic when added to HEK293 cells. In summary, EGCG's binding to TDP-43 and blocking of residues important for aggregation can be a possible mechanism of its anti-aggregation effects on TDP-43., (© 2024 John Wiley & Sons Ltd.) more...- Published
- 2024
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18. Development and preliminary validation of a diagnostic prediction model to optimise outpatient management of patients with urolithiasis using urinary stones and intervention quality of life (USIQoL) measure.
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Jarvis RC, Pallmann P, Clements C, and Joshi H
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- Humans, Female, Male, Prospective Studies, Middle Aged, Adult, Urolithiasis psychology, Urolithiasis therapy, Surveys and Questionnaires, Aged, Outpatients psychology, Ambulatory Care, Psychometrics, Reproducibility of Results, Triage, Quality of Life
- Abstract
Purpose: Patients with urinary calculi undergo resource-intensive follow-up. Application of a PROM, Urinary Stones and Intervention Quality of Life (USIQoL), can potentially optimise current practices if it matches the outcomes of traditional follow-up. Our objective was to develop, and conduct, a preliminary validation of the USIQoL based prediction model to aid triage., Methods: We performed a two phase prospective cohort study. The 1st phase included development of the USIQoL-based decision model using multicentre data. The 2nd phase involved prospective single-blind external validation for the outpatient application. The aim was to evaluate correlations between the USIQoL scores and key predictors; clinical outcomes and global health ratings (EuroQoL EQ-5D). We used statistical analysis to validate USIQoL cut-off scores to aid triage and the decision to intervene., Results: Of 503 patients invited, 91% (n = 455, Development [305] and Validation [150]; M = 308, F = 147) participated. The relationship between USIQoL domain scores and clinical outcomes was consistently significant (estimated odds: PPH 1.24, p < 0.001, 95% CI 1.13-1.36; PSH 1.22, p < 0.001, 95% CI 1.12-1.33). The ROC values for the model were ≥ 0.75. The optimum domain cut-off scores were derived with rising scores implying increased need to intervene. The model demonstrated satisfactory sensitivity (0.81-0.89) and specificity (0.36-0.47)., Conclusions: The study demonstrates satisfactory correlation between the USIQoL and clinical outcomes making this model a valid aid for triage and optimising outpatient management with the cut-off scores able to identify high risk patients who need active treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.) more...
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- 2024
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19. Nickel Complexes Bearing Quinoline Derived NNS Donor Ligands as Catalytic Activators for N-Alkylation of Anilines with Alcohols.
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Tanwar D, Mahala S, Ahluwalia D, Bhuvanesh N, Joshi H, and Kumar U
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Herein, we have reported a new series of NNS-donor ligands coordinated Ni(II) complexes and utilized them as catalytic activator to synthesize N-alkylated amines and 1,2-disubstituted benzimidazoles. The reaction of thiophenol/4-chlorothiophenol/4-methylthiophenol/4-methoxythiophenol with 2-bromo-N-quinolin-8-yl-acetamide in presence of sodium hydroxide in ethanol at 80 °C gave [C
9 H6 N-NH-C(O)-CH2 -S-Ar] [Ar=C6 H5 (L1); C6 H4 Cl-4 (L2); C6 H4 Me-4 (L3) and C6 H4 -OMe-4 (L4)], respectively. The corresponding reaction of L1-L4 with Ni(OAc)2 in methanol at 80 °C for 3 hours resulted in octahedral nickel complexes [(L1-H)2 Ni] (C1), [(L2-H)2 Ni] (C2), [(L3-H)2 Ni] (C3), and [(L4-H)2 Ni] (C4), respectively. All compounds have been characterized by micro and spectroscopic analysis. The molecular structure of complexes C1-C3 has also been determined by single crystal X-ray diffraction data. The utility of complexes C1-C4 were evaluated for the N-alkylation of aniline with benzyl alcohols, and for 1,2-disubstituted benzimidazoles synthesis. The obtained results indicate that complex C1 showed better catalytic activity in both N-alkylation of amines with benzyl alcohols [catalyst loading: 2.0 mol %; Yield up to 92 %], and for 1,2-disubstituted benzimidazoles derivatives [catalyst loading: 2.0 mol %; Yield up to 94 %)]. The mechanistic studies suggested that the reaction works through hydrogen borrowing from benzyl alcohol and its subsequent utilization for in situ reduction of imine. The experimentally observed catalytic reactivity patterns of complexes C1-C4 have found in good agreement with the HOMO-LUMO energy gaps obtained by DFT analysis of corresponding complexes., (© 2024 Wiley-VCH GmbH.) more...- Published
- 2024
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20. PerR: A Peroxide Sensor Eliciting Metal Ion-dependent Regulation in Various Bacteria.
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Kandari D and Joshi H
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Bacteria have to thrive in difficult conditions wherein their competitors generate partially reduced forms of oxygen, like hydrogen peroxide and superoxides. These oxidative stress molecules can also arise from within via the autoxidation of redox enzymes. To adapt to such conditions, bacteria express detox enzymes as well as repair proteins. Transcription factors regulate these defenses, and PerR is one of them. PerR is a Fur family transcriptional regulator that senses peroxide stress. Metal-bound PerR (either Mn
2+ or Fe2+ ) can repress transcription of its regulon, but only the Fe2+ -bound form of PerR can sense H2 O2 . This review describes different aspects of PerR and its varied roles, specifically in bacterial pathogens. Despite having roles beyond sensing peroxides, it is an underrated regulator that needs to be explored more deeply in pathogens., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.) more...- Published
- 2024
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21. "Luck of the draw really": a qualitative exploration of Australian trainee doctors' experiences of mandatory research.
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Brandenburg C, Hilder J, Noble C, Liang R, Forrest K, Joshi H, Keijzers G, Mickan S, Pearson D, Scott IA, Veysey E, and Stehlik P
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- Humans, Australia, Female, Male, Attitude of Health Personnel, Interviews as Topic, Adult, Physicians psychology, Qualitative Research, Biomedical Research
- Abstract
Background: Many medical trainees, prior to achieving specialist status, are required to complete a mandatory research project, the usefulness of which has been debated. The aim of this study was to gain an in-depth understanding of trainees' experiences and satisfaction of conducting such research projects in Australia., Methods: A qualitative descriptive approach was used. Semi-structured interviews with trainees were undertaken between May 2021 and June 2022. Australian medical trainees who had completed a research project as part of specialty training within the past five years were invited to participate. The purposive sample was drawn from participants in a survey on the same topic who had indicated interest in participating in an interview. Interviews explored trainees' overall experience of and satisfaction with conducting research projects, as well as their perceptions of research training, support, barriers, enablers, and perceived benefits. Interviews were transcribed verbatim and thematically analysed., Results: Sixteen medical doctors from seven medical colleges were interviewed. Trainee experience and satisfaction was highly variable between participants and was shaped by four factors: 1) trainees entered their specialty training with their own perspectives on the value and purpose of the research project, informed by their previous experiences with research and perceived importance of research in their planned career path; 2) in conducting the project, enablers including protected time, supervisor support and institutional structures, were vital to shaping their experience; 3) trainees' access to these enablers was variable, mediated by a combination of luck, and the trainees' own drive and research skill; and 4) project outcomes, in terms of research merit, learning, career benefits and impacts on patient care., Conclusions: Trainee experiences of doing research were mixed, with positive experiences often attributed to chance rather than an intentionally structured learning experience. We believe alternatives to mandatory trainee research projects must be explored, including recognising other forms of research learning activities, and directing scarce resources to supporting the few trainees who plan to pursue clinician researcher careers., (© 2024. The Author(s).) more...
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- 2024
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22. Comparison of Explainable AI Models for MRI-based Alzheimer's Disease Classification.
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Chattopadhyay T, Joshy NA, Jagad C, Gleave EJ, Thomopoulos SI, Feng Y, Villalón-Reina JE, Laltoo E, Joshi H, Venkatasubramanian G, John JP, Ver Steeg G, Ambite JL, and Thompson PM
- Abstract
Deep learning models based on convolutional neural networks (CNNs) have been used to classify Alzheimer's disease or infer dementia severity from 3D T1-weighted brain MRI scans. Here, we examine the value of adding occlusion sensitivity analysis (OSA) and gradient-weighted class activation mapping (Grad-CAM) to these models to make the results more interpretable. Much research in this area focuses on specific datasets such as the Alzheimer's Disease Neuroimaging Initiative (ADNI) or National Alzheimer's Coordinating Center (NACC), which assess people of North American, predominantly European ancestry, so we examine how well models trained on these data generalize to a new population dataset from India (NIMHANS cohort). We also evaluate the benefit of using a combined dataset to train the CNN models. Our experiments show feature localization consistent with knowledge of AD from other methods. OSA and Grad-CAM resolve features at different scales to help interpret diagnostic inferences made by CNNs. more...
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- 2024
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23. Generation of antigen-specific memory CD4 T cells by heterologous immunization enhances the magnitude of the germinal center response upon influenza infection.
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Sircy LM, Ramstead AG, Gibbs LC, Joshi H, Baessler A, Mena I, García-Sastre A, Emerson LL, Fairfax KC, Williams MA, and Hale JS
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- Animals, Mice, Antibodies, Viral immunology, Mice, Inbred C57BL, B-Lymphocytes immunology, Immunologic Memory, Memory T Cells immunology, Immunization methods, Female, Antigens, Viral immunology, Germinal Center immunology, Orthomyxoviridae Infections immunology, Orthomyxoviridae Infections prevention & control, Influenza Vaccines immunology, Influenza Vaccines administration & dosage, CD4-Positive T-Lymphocytes immunology
- Abstract
Current influenza vaccine strategies have yet to overcome significant obstacles, including rapid antigenic drift of seasonal influenza viruses, in generating efficacious long-term humoral immunity. Due to the necessity of germinal center formation in generating long-lived high affinity antibodies, the germinal center has increasingly become a target for the development of novel or improvement of less-efficacious vaccines. However, there remains a major gap in current influenza research to effectively target T follicular helper cells during vaccination to alter the germinal center reaction. In this study, we used a heterologous infection or immunization priming strategy to seed an antigen-specific memory CD4+ T cell pool prior to influenza infection in mice to evaluate the effect of recalled memory T follicular helper cells in increased help to influenza-specific primary B cells and enhanced generation of neutralizing antibodies. We found that heterologous priming with intranasal infection with acute lymphocytic choriomeningitis virus (LCMV) or intramuscular immunization with adjuvanted recombinant LCMV glycoprotein induced increased antigen-specific effector CD4+ T and B cellular responses following infection with a recombinant influenza strain that expresses LCMV glycoprotein. Heterologously primed mice had increased expansion of secondary Th1 and Tfh cell subsets, including increased CD4+ TRM cells in the lung. However, the early enhancement of the germinal center cellular response following influenza infection did not impact influenza-specific antibody generation or B cell repertoires compared to primary influenza infection. Overall, our study suggests that while heterologous infection or immunization priming of CD4+ T cells is able to enhance the early germinal center reaction, further studies to understand how to target the germinal center and CD4+ T cells specifically to increase long-lived antiviral humoral immunity are needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sircy 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.) more...
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- 2024
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24. Machine learning reveals the rules governing the efficacy of mesenchymal stromal cells in septic preclinical models.
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Gakhar D, Joshi H, Makkar D, Taneja N, Arora A, and Rakha A
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- Humans, Animals, Machine Learning, Mesenchymal Stem Cells metabolism, Mesenchymal Stem Cells cytology, Sepsis therapy, Mesenchymal Stem Cell Transplantation methods
- Abstract
Background: Mesenchymal Stromal Cells (MSCs) are the preferred candidates for therapeutics as they possess multi-directional differentiation potential, exhibit potent immunomodulatory activity, are anti-inflammatory, and can function like antimicrobials. These capabilities have therefore encouraged scientists to undertake numerous preclinical as well as a few clinical trials to access the translational potential of MSCs in disease therapeutics. In spite of these efforts, the efficacy of MSCs has not been consistent-as is reflected in the large variation in the values of outcome measures like survival rates. Survival rate is a resultant of complex cascading interactions that not only depends upon upstream experimental factors like dosage, time of infusion, type of transplant, etc.; but is also dictated, post-infusion, by intrinsic host specific attributes like inflammatory microniche including proinflammatory cytokines and alarmins released by the damaged host cells. These complex interdependencies make a researcher's task of designing MSC transfusion experiments challenging., Methods: In order to identify the rules and associated attributes that influence the final outcome (survival rates) of MSC transfusion experiments, we decided to apply machine learning techniques on manually curated data collected from available literature. As sepsis is a multi-faceted condition that involves highly dysregulated immune response, inflammatory environment and microbial invasion, sepsis can be an efficient model to verify the therapeutic effects of MSCs. We therefore decided to implement rule-based classification models on data obtained from studies involving interventions of MSCs in sepsis preclinical models., Results: The rules from the generated graph models indicated that survival rates, post-MSC-infusion, are influenced by factors like source, dosage, time of infusion, pre-Interleukin-6 (IL-6)/ Tumour Necrosis Factor- alpha (TNF-α levels, etc. CONCLUSION: This approach provides important information for optimization of MSCs based treatment strategies that may help the researchers design their experiments., (© 2024. The Author(s).) more...
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- 2024
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25. Heterogeneity in Methods of Estimating Kidney Function for Cancer Clinical Trial Eligibility.
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Karol AB, Paredes R, Fujiwara Y, Argulian A, Joshi H, Abramson M, and Galsky MD
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- Humans, Eligibility Determination, Patient Selection, Kidney Function Tests methods, Kidney Function Tests statistics & numerical data, Glomerular Filtration Rate, Female, Male, Middle Aged, Aged, Neoplasms, Clinical Trials as Topic
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- 2024
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26. Predictors of Mortality in Adults With Calcium Channel Blocker Toxicity Receiving Extra Corporeal Membrane Oxygenation Support: An Extracorporeal Life Support Organization Registry Analysis.
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Subramanian R, Roebuck A, Joshi H, and Drouin M
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Calcium channel blocker (CCB) toxicity presents a significant mortality risk, highlighting the need for effective treatment strategies such as extracorporeal membrane oxygenation (ECMO). This study analyzes Extracorporeal Life Support Organization (ELSO) registry data to determine the mortality rate in adults treated with ECMO for CCB toxicity and identifies clinical predictors of mortality. A retrospective analysis of the ELSO registry from January 2016 to April 2023 was conducted, focusing on adults diagnosed with CCB toxicity (ICD-10 T46.1) who received ECMO. Data collected included patient demographics, ECMO details (mode, duration, type), pre-ECMO clinical indicators (pH, lactate levels, cardiac arrest incidence), and in-hospital mortality. The analysis employed descriptive statistics to profile the patient population, with independent t-tests and chi-square tests comparing survivors to nonsurvivors. Logistic regression identified mortality predictors, integrating multiple imputations to remedy missing data, thus ensuring the analysis's integrity. The mortality rate for ECMO-treated CCB toxicity was 40.6%. Severe acidosis and the need for pre-ECMO renal replacement therapy were identified as key predictors of mortality. Further research is needed to determine if early ECMO initiation before a significant pH drop improves outcomes., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.) more...
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- 2024
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27. Potential anxiolytic therapeutics from Hybanthus enneaspermus (L.) F. Muell. - mitigate anxiety by plausibly modulating the GABA A -Cl - channel.
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Fernandes E Mendonça LM, Joshi AB, Bhandarkar A, Shaikh S, Fernandes S, Joshi H, and Joshi S
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- Animals, Rats, Male, Molecular Docking Simulation, Receptors, GABA-A metabolism, Receptors, GABA-A drug effects, Brain drug effects, Brain metabolism, Maze Learning drug effects, Anti-Anxiety Agents pharmacology, Anti-Anxiety Agents isolation & purification, Anti-Anxiety Agents therapeutic use, Anti-Anxiety Agents chemistry, Plant Extracts pharmacology, Plant Extracts isolation & purification, Plant Extracts therapeutic use, Plant Extracts chemistry, Anxiety drug therapy, Anxiety metabolism, Rats, Wistar
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Anxiety is a commonly prevailing psychological disorder that requires effective treatment, wherein phytopharmaceuticals and nutraceuticals could offer a desirable therapeutic profile. Hybanthus enneaspermus (L.) F. Muell. is a powerful medicinal herb, reportedly effective against several ailments, including psychological disorders. The current research envisaged evaluating the anxiolytic potential of the ethanolic extract of Hybanthus enneaspermus (EEHE) and its toluene insoluble biofraction (ITHE) employing experimental and computational approaches. Elevated Plus Maze, Light and Dark Transition, Mirror Chamber, Hole board and Open field tests were used as screening models to assess the antianxiety potential of 100, 200 and 400 mg/kg body weight of EEHE and ITHE in rats subjected to social isolation, using Diazepam as standard. The brains of rats exhibiting significant anxiolytic activity were dissected for histopathological and biochemical studies. Antioxidant enzymes like catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase; and neurotransmitters viz. monoamines (serotonin, noradrenaline, dopamine), Gamma-aminobutyric acid (GABA), and glutamate were quantified in the different regions of rats' brain (cortex, hippocampus, pons, medulla oblongata, cerebellum). Chromatographic techniques were used to isolate phytoconstituents from the fraction exhibiting significant activity that were characterized by spectroscopic methods and subjected to in silico molecular docking. ITHE at 400 mg/kg body weight significantly mitigated anxiety in all the screening models (p < 0.05), reduced the inflammatory vacuoles and necrosis (p < 0.05) and potentiated the antioxidant enzymes (p < 0.05). It enhanced the monoamines and GABA levels while attenuating glutamate levels (p < 0.01) in the brain. Three significant flavonoids viz. Quercitrin, Rutin and Hesperidin were isolated from ITHE. In silico docking studies of these flavonoids revealed that the compounds exhibited substantial binding to the GABA
A receptor. ITHE displayed a promising pharmacological profile in combating anxiety and modulating oxidative stress, attributing its therapeutic virtues to the flavonoids present., 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.) more...- Published
- 2024
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28. Optimizing outcomes in paraesophageal hernia repair: a novel critical view.
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Saleh Z, Verchio V, Ghanem YK, Lou J, Hundley E, Rouhi AD, Joshi H, Moccia MC, Scalia DM, Lenart AM, Ladd ZA, Minakata K, and Shersher DD
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- Humans, Female, Retrospective Studies, Male, Middle Aged, Aged, Treatment Outcome, Laparoscopy methods, Robotic Surgical Procedures methods, Postoperative Complications epidemiology, Postoperative Complications etiology, Postoperative Complications prevention & control, Esophagus surgery, Hernia, Hiatal surgery, Herniorrhaphy methods, Recurrence
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Background: The recurrence rate of paraesophageal hernia repair (PEHR) is high with reported rates of recurrence varying between 25 and 42%. We present a novel approach to PEHR that involves the visualization of a critical view to decrease recurrence rate. Our study aims to investigate the outcomes of PEHR following the implementation of a critical view., Methods: This is a single-center retrospective study that examines operative outcomes in patients who underwent PEHR with a critical view in comparison to patients who underwent standard repair. The critical view is defined as full dissection of the posterior mediastinum with complete mobilization of the esophagus to the level of the inferior pulmonary vein, visualization of the left crus of the diaphragm as well as the left gastric artery while the distal esophagus is retracted to expose the spleen in the background. Bivariate chi-squared analysis and multivariable logistic and linear regressions were used for statistical analysis., Results: A total of 297 patients underwent PEHR between 2015 and 2023, including 207 with critical view and 90 with standard repair which represents the historic control. Type III hernias were most common (48%) followed by type I (36%), type IV (13%), and type II (2.0%). Robotic-assisted repair was most common (65%), followed by laparoscopic (22%) and open repair (14%). Fundoplications performed included Dor (59%), Nissen (14%), Belsey (5%), and Toupet (2%). Patients who underwent PEHR with critical view had lower hernia recurrence rates compared to standard (9.7% vs 20%, P < .01) and lower reoperation rates (0.5% vs 10%, P < .001). There were no differences in postoperative complications on unadjusted bivariate analysis; however, adjusted outcomes revealed a lower odds of postoperative complications in patients with critical view (AOR .13, 95% CI .05-.31, P < .001)., Conclusion: We present dissection of a novel critical view during repair of all types of paraesophageal hernia that results in reproducible, consistent, and durable postoperative outcomes, including a significant reduction in recurrence and reoperation., (© 2024. The Author(s).) more...
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- 2024
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29. Endoscopic repair of duodenal perforations, a scoping review.
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Williams J, Joshi H, Schwartz M, Kalola A, Mercado A, Saracco B, Adams A, Chaaya A, Baik D, Elfant A, and Hong YK
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- Humans, Duodenal Diseases surgery, Duodenal Diseases etiology, Duodenoscopy methods, Iatrogenic Disease, Intestinal Perforation surgery, Intestinal Perforation etiology, Duodenum injuries, Duodenum surgery
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Background: There is a discrepancy in the surgical and endoscopic literature for managing duodenal perforations. Although often managed conservatively, surgical repair is the standard treatment for duodenal perforations. This contrasts with the gastroenterology literature, which now recommends endoscopic repair of duodenal perforations, which are more frequently iatrogenic from the growing field of advanced endoscopic procedures. This study aims to provide a scoping review to summarize the current literature content and quality on endoscopic repair of duodenal perforations., Methods: The protocol for performing this scoping review was outlined by the Joanna Briggs Institute. All studies that reported primary outcomes of patients who had undergone endoscopic repair of duodenal perforations before February 2022, regardless of perforation etiology or repair type were reviewed, with studies after 1999 meeting inclusion criteria. The study excluded articles that did not report clinical outcomes of endoscopic repair, articles that did not describe where in the gastrointestinal tract the endoscopic repair occurred, pediatric patients, and animal studies., Results: 7606 abstracts were screened, with 474 full articles reviewed and 152 studies met inclusion criteria. 560 patients had duodenal perforations repaired endoscopically, with a technical success rate of 90.4% and a survival rate of 86.7%. Most of these perforations (74.5%) were iatrogenic from endoscopic procedures or surgery. Only one randomized control trial (RCT) was found, and 53% of studies were case reports., Conclusion: These results suggest that endoscopic repair could emerge as a viable first-line treatment for duodenal perforation and highlight the need for more high-quality research in this topic., (© 2024. The Author(s).) more...
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- 2024
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30. Designing Cobalt(II) Complex for Chemoselective Synthesis of 2-Aryl-3-Formyl Indoles from Amino Alcohols and Alcohols † .
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Mahala S, Gupta N, Singh S, Sharma AK, Bhuvanesh N, and Joshi H
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An air-stable, inexpensive, and isolable cobalt(II) complex (C1) of N-((1-methyl-1H-imidazol-2-yl)methyl)-2-(phenylselanyl)ethan amine (L1) was synthesized and characterized. The complex was used to catalyze a one-pot cascade reaction between 2-(2-aminophenyl)ethanols and benzyl alcohol derivatives. Interestingly, 2-aryl-3-formylindole derivatives were formed instead of N-alkylated or C-3 alkylated indoles. A broad substrate scope can be activated using this protocol with only 5.0 mol % catalyst loading to achieve up to 87 % yield of 2-aryl-3-formylindole derivatives. The mechanistic studies suggested that the reaction proceeds through tandem imine formation followed by cyclization., (© 2024 Wiley-VCH GmbH.) more...
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- 2024
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31. Strengthening primary health care through community health workers in South Asia.
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Shrestha P, Afsana K, Weerasinghe MC, Perry HB, Joshi H, Rana N, Memon ZA, Khaled N, Malhotra S, Bhardwaj S, Kafle S, Inagaki Y, Schimdt A, Hodgins S, Neupane D, and Rao KD
- Abstract
The growing health challenges in South Asia require further adaptations of community health worker (CHW) programs as a key element of primary health care (PHC). This paper provides a comparative analysis of CHW programs in five countries (Bangladesh, India, Nepal, Pakistan, and Sri Lanka), examines successes and challenges, and suggests reforms to better ensure highly performing CHW programs. To examine CHW programs in the region, we conducted a narrative review of the peer-reviewed and grey literatures, as well as eliciting opinions from experts. Common roles of CHWs include health education, community mobilization, and community-based services, particularly related to reproductive, maternal, neonatal, and child health. Some countries utilize CHWs for non-communicable diseases and other emerging health issues. To maximize the potential contribution of CHWs to achieving Universal Health Coverage, we recommend future research and policy focus on strengthening existing health systems to support the expansion of CHWs roles and better integrating of CHWs into national PHC systems. This is Paper 4 in the Series on Primary Health Care in South Asia, addressing areas that have the potential to revitalize health systems in South Asian countries., Funding: The authors received financial support from the Department of Health Systems Development, WHO South-East Asia Regional Office (WHO SEAR)., Competing Interests: The authors declare no conflict of interest in writing this manuscript., (© 2024 The Authors.) more...
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- 2024
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32. Spinal cord injury in high-risk complex adult spinal deformity surgery: review of incidence and outcomes from the Scoli-RISK-1 study.
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Jiang F, Joshi H, Badhiwala JH, Wilson JRF, Lenke LG, Shaffrey CI, Cheung KMC, Carreon LY, Dekutoski MB, Schwab FJ, Boachie-Adjei O, Kebaish KM, Ames CP, Berven SH, Qiu Y, Matsuyama Y, Dahl BT, Mehdian H, Pellisé F, Lewis SJ, and Fehlings MG more...
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- Humans, Male, Female, Middle Aged, Adult, Incidence, Postoperative Complications epidemiology, Aged, Treatment Outcome, Cohort Studies, Prospective Studies, Spinal Cord Injuries epidemiology, Spinal Cord Injuries complications, Spinal Cord Injuries surgery
- Abstract
Study Design: Clinical case series., Objective: To describe the cause, treatment and outcome of 6 cases of perioperative spinal cord injury (SCI) in high-risk adult deformity surgery., Setting: Adult spinal deformity patients were enrolled in the multi-center Scoli-RISK-1 cohort study., Methods: A total of 272 patients who underwent complex adult deformity surgery were enrolled in the prospective, multi-center Scoli-RISK-1 cohort study. Clinical follow up data were available up to a maximum of 2 years after index surgery. Cases of perioperative SCI were identified and an extensive case review was performed., Results: Six individuals with SCI were identified from the Scoli-RISK-1 database (2.2%). Two cases occurred intraoperatively and four cases occurred postoperatively. The first case was an incomplete SCI due to a direct intraoperative insult and was treated postoperatively with Riluzole. The second SCI case was caused by a compression injury due to overcorrection of the deformity. Three cases of incomplete SCI occurred; one case of postoperative hematoma, one case of proximal junctional kyphosis (PJK) and one case of adjacent segment disc herniation. All cases of post-operative incomplete SCI were managed with revision decompression and resulted in excellent clinical recovery. One case of incomplete SCI resulted from infection and PJK. The patient's treatment was complicated by a delay in revision and the patient suffered persistent neurological deficits up to six weeks following the onset of SCI., Conclusion: Despite the low incidence in high-risk adult deformity surgeries, perioperative SCI can result in devastating consequences. Thus, appropriate postoperative care, follow up and timely management of SCI are essential., (© 2024. The Author(s).) more...
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- 2024
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33. Tailoring Phage Nanosomes for Enhanced Theranostic Properties of Near Infrared Dyes.
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Sankaranarayanan SA, Yadav DN, Yadav S, Srivastava A, Pramatha SR, Kotagiri VR, Joshi H, and Rengan AK
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- Humans, Theranostic Nanomedicine methods, Coloring Agents chemistry, Coloring Agents pharmacology, Indoles chemistry, Indoles pharmacology, Mitoxantrone chemistry, Mitoxantrone pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Molecular Dynamics Simulation, Indocyanine Green chemistry, Indocyanine Green pharmacology, Infrared Rays
- Abstract
Near-infrared (NIR) phototherapies offer noninvasive, cost-effective solutions for treating tumors and microbial infections. However, organic NIR dyes commonly used suffer from solubility and stability issues requiring frequent dosing. We address this challenge by exploring the bacteriophage-mediated enhancement of NIR dye properties. Upon encapsulation within phage nanosomes, IR780 and Indocyanine green (ICG), with similar optical properties but distinct water solubility and exhibit enhanced UV-vis absorbance and photothermal transduction efficacy compared to liposomes. Experimental characterization corroborated with all-atom molecular dynamics simulations imprints the nanoscale structure, solubility, dynamics, and binding of these NIR dye molecules to the membrane and protein molecules present in Phage capsid. These NIR dye-loaded phage nanosomes, coencapsulated with mitoxantrone, demonstrate enhanced anticancer activity, and when combined with amphotericin B, these dye molecules exhibit superior photothermal effects against fungal infections. Our findings present a simple and efficient approach for tuning the photothermal performance of existing NIR dyes through a rational design for enhanced therapeutic outcomes. more...
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- 2024
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34. Open-label, phase II study of talimogene laherparepvec plus pembrolizumab for the treatment of advanced melanoma that progressed on prior anti-PD-1 therapy: MASTERKEY-115.
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Robert C, Gastman B, Gogas H, Rutkowski P, Long GV, Chaney MF, Joshi H, Lin YL, Snyder W, and Chesney JA
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- Humans, Male, Middle Aged, Female, Aged, Adult, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors adverse effects, Programmed Cell Death 1 Receptor antagonists & inhibitors, Aged, 80 and over, Skin Neoplasms drug therapy, Skin Neoplasms pathology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Oncolytic Virotherapy methods, Antineoplastic Agents, Immunological therapeutic use, Antineoplastic Agents, Immunological adverse effects, Disease Progression, Melanoma drug therapy, Melanoma pathology, Melanoma mortality, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Biological Products therapeutic use, Biological Products adverse effects, Biological Products administration & dosage, Herpesvirus 1, Human
- Abstract
Background: Treatment options for immunotherapy-refractory melanoma are an unmet need. The MASTERKEY-115 phase II, open-label, multicenter trial evaluated talimogene laherparepvec (T-VEC) plus pembrolizumab in advanced melanoma that progressed on prior programmed cell death protein-1 (PD-1) inhibitors., Methods: Cohorts 1 and 2 comprised patients (unresectable/metastatic melanoma) who had primary or acquired resistance, respectively, and disease progression within 12 weeks of their last anti-PD-1 dose. Cohorts 3 and 4 comprised patients (resectable disease) who underwent complete surgery, received adjuvant anti-PD-1, and experienced recurrence. Cohort 3 were disease-free for < 6 months and cohort 4 for ≥ 6 months after starting the adjuvant anti-PD-1 therapy and before confirmed recurrence. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included complete response rate (CRR), disease control rate (DCR) and progression-free survival (PFS) per RECIST v1.1 and irRC-RECIST, and safety., Results: Of the 72 enrolled patients, 71 were treated. The ORR (95% CI) was 0%, 6.7% (0.2-32.0), 40.0% (16.3-67.7), and 46.7% (21.3-73.4) in cohorts 1-4, respectively; iORR was 3.8% (0.1-19.6), 6.7% (0.2-32.0), 53.3% (26.6-78.7), and 46.7% (21.3-73.4). iCRR was 0%, 0%, 13.3%, and 13.3%. Median iPFS (months) was 5.5, 8.2, not estimable [NE], and NE for cohorts 1-4, respectively; iDCR was 50.0%, 40.0%, 73.3%, and 86.7%. Treatment-related adverse events (TRAEs), grade ≥ 3 TRAEs, serious AEs, and fatal AEs occurred in 54 (76.1%), 9 (12.7%), 24 (33.8%), and 10 (14.1%) patients, respectively., Conclusion: T-VEC-pembrolizumab demonstrated antitumor activity and tolerability in PD-1-refractory melanoma, specifically in patients with disease recurrence on or after adjuvant anti-PD-1., Trial Registration: ClinicalTrials.gov identifier - NCT04068181., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Caroline Robert: Consulting or advisory role: Bristol-Myers Squibb (BMS), Roche, Novartis, Pierre Fabre, MSD, Sanofi, AstraZeneca, Pfizer, Sunpharma; Scientific co-founder of Ribonexus. Brian Gastman: Consulting or advisory role: Quest Imaging, Castle Biosciences; Speakers' Bureau: Castle Biosciences; Stock and other ownership interests: Castle Biosciences; Research funding: Alkermes, NeoImmuneTech, Merck, Instil Bio. Helen Gogas: Advisory board: BMS, MSD, Pierre Fabre, Sanofi; Invited Speaker: BMS, MSD, Novartis, Pierre Fabre, Sanofi; Local PI: Amgen, Bayer, BMS, Iovance, MSD, Replimune; Research Grant: BMS, Lilly, Pfizer, Pierre Fabre; Steering Committee Member: Amgen, Replimune. Piotr Rutkowski: Consulting or advisory role: BMS, MSD, Novartis, Pierre Fabre, Sanofi, Merck, Philogen, Blueprint Medicine; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, Sanofi, Merck, Astra Zeneca, Philogen, Blueprint Medicine. Georgina V. Long: Consulting fees and advisory boards: Agenus, Amgen, Array Biopharma, AstraZeneca, Bayer, BioNTech, Boehringer Ingelheim, BMS, Evaxion, Hexal AG (Sandoz Company), Highlight Therapeutics S.L., IOBiotech, Immunocore, Innovent Biologics USA, Merck Sharpe & Dohme, Novartis, PHMR Ltd, Pierre Fabre, Regeneron, Scancell; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BMS, Pierre Fabre. Marya F. Chaney: Employee: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Stock Ownership: Merck & Co., Inc., Rahway, NJ, USA. Harshada Joshi: Employee: Parexel. Yu-Lin Lin: Employee/stock ownership: Amgen. Wendy Snyder: Employee/stock ownership: Amgen. Jason A. Chesney: Research funding: Amgen., (Copyright © 2024. Published by Elsevier Ltd.) more...
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- 2024
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35. Compact Linnik-type hyperspectral quantitative phase microscope for advanced classification of cellular components.
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Joshi H, Singh BP, Butola A, Surya V, Mishra D, Agarwal K, and Mehta DS
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- Humans, Image Processing, Computer-Assisted methods, Hyperspectral Imaging methods, Principal Component Analysis, Cheek, Microscopy instrumentation
- Abstract
Hyperspectral quantitative phase microscopy (HS-QPM) involves the acquisition of phase images across narrow spectral bands, which enables wavelength-dependent study of different biological samples. In the present work, a compact Linnik-type HS-QPM system is developed to reduce the instability and complexity associated with conventional HS-QPM techniques. The use of a single objective lens for both reference and sample arms makes the setup compact. The capabilities of the system are demonstrated by evaluating the HS phase map of both industrial and biological specimens. Phase maps of exfoliated cheek cells at different wavelengths are stacked to form a HS phase cube, adding spectral dimensionality to spatial phase distribution. Analysis of wavelength response of different cellular components are performed using principal component analysis to identify dominant spectral features present in the HS phase dataset. Findings of the study emphasize on the efficiency and effectiveness of HS-QPM for advancing cellular characterization in biomedical research and clinical applications., (© 2024 Wiley‐VCH GmbH.) more...
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- 2024
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36. Luteolin: A promising modulator of apoptosis and survival signaling in liver cancer.
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Rath P, Chauhan A, Ranjan A, Aggarwal D, Rani I, Choudhary R, Shahwan M, Ramniwas S, Joshi H, Haque S, Mathkor DM, and Tuli HS
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- Humans, Autophagy drug effects, Animals, Antineoplastic Agents therapeutic use, Antineoplastic Agents pharmacology, Luteolin pharmacology, Luteolin therapeutic use, Apoptosis drug effects, Liver Neoplasms drug therapy, Liver Neoplasms pathology, Liver Neoplasms metabolism, Signal Transduction drug effects
- Abstract
Due to the increasing incidence of cancer and the difficulties in determining the safety profile of existing therapeutic approaches, cancer research has recently become heavily involved in the search for new therapeutic approaches. The therapeutic significance of natural substances, especially flavonoids, against the onset and progression of cancer has been emphasized in traditional food-based medicine. Interestingly, the flavone luteolin possesses biological effects that have been linked to its anti-inflammatory, antioxidant, and anticancer effects. Luteolin interacts with several downstream chemicals and signaling pathways, including those involved in apoptosis, autophagy, cell cycle progression, and angiogenesis, to exert its anticancer effects on various cancerous cells. A complete understanding of both intrinsic and extrinsic apoptotic pathways, autophagy, and, most critically, the nanodelivery of luteolin in liver cancer is provided in the current review., Competing Interests: Declaration of Competing Interest The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript., (Copyright © 2024 Elsevier GmbH. All rights reserved.) more...
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- 2024
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37. Refining clinically relevant parameters for mis-splicing risk in shortened introns with donor-to-branchpoint space constraint.
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Zhang KY, Joshi H, Marchant RG, Bryen SJ, Dawes R, Yuen M, Cooper ST, and Evesson FJ
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- Humans, RNA Splicing, beta-Thalassemia genetics, beta-Thalassemia diagnosis, RNA Splice Sites, Sequence Deletion, Spliceosomes genetics, Spliceosomes metabolism, Introns, beta-Globins genetics
- Abstract
Intronic deletions that critically shorten donor-to-branchpoint (D-BP) distance of a precursor mRNA impose biophysical space constraint on assembly of the U1/U2 spliceosomal complex, leading to canonical splicing failure. Here we use a series of β-globin (HBB) gene constructs with intron 1 deletions to define D-BP lengths that present low/no risk of mis-splicing and lengths which are critically short and likely elicit clinically relevant mis-splicing. We extend our previous observation in EMD intron 5 of 46 nt as the minimal productive D-BP length, demonstrating spliceosome assembly constraint persists at D-BP lengths of 47-56 nt. We exploit the common HBB exon 1 β-thalassemia variant that strengthens a cryptic donor (NM_000518.5(HBB):c.79G > A) to provide a simple barometer for the earliest signs of space constraint, via cryptic donor activation. For clinical evaluation of intronic deletions, we assert D-BP lengths > 60 nt present low mis-splicing risk while space constraint increases exponentially with D-BP lengths < 55 nt, with critical risk and profound splicing abnormalities with D-BP lengths < 50 nt., (© 2024. The Author(s).) more...
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- 2024
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38. Exploring the link between eustress and adolescent health in India: An empirical study.
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Saini R, Arora A, Joshi H, and Gaurav AK
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Background: Modern psychological research challenges the conventional view of stress as solely detrimental by introducing the concept of eustress versus distress, emphasizing the potentially positive aspects of stress. In the context of India, limited studies have investigated the distinct effects of eustress and distress on adolescents, a group prone to stress-related health issues. This study aims to bridge this gap by examining the correlation between eustress and both mental and physical well-being among adolescents attending government schools in two districts of Haryana, India., Materials and Methods: A non-experimental quantitative research approach was adopted to achieve this objective. The study involved a sample of 400 adolescent students, equally split between genders, aged 15 to 18 years, enrolled in grades 10 to 12. Participants were selected through systematic random sampling from two districts in Haryana. The assessment tools employed in the study included the Post Graduate Institute Health Questionnaire and the Eustress Scale, which were utilized to evaluate the participants' mental, physical, and eustress levels., Results: In our study involving Indian adolescents, we discovered a substantial positive correlation (r = 0.563, P < 0.01) between eustress and mental health, underlining the valuable role of positive stress in enhancing psychological well-being. Notably, male participants exhibited significantly higher eustress scores (mean = 26.63) than their female counterparts (mean = 22.82, P < 0.01), indicating gender-specific variations in stress responses. Furthermore, our findings emphasized the influence of cultural nuances inherent to the Indian context on how adolescents perceived and experienced eustress. These outcomes emphasize the urgency of culturally sensitive interventions to promote adolescents' well-being., Conclusion: This investigation contributes valuable insights into the nexus between eustress and adolescent health in the Indian context. The study accentuates the potential advantages of leveraging eustress to foster positive development by underlining the differential influence of eustress and distress on adolescent health. Future research endeavors and policy formulation could delve into the mechanisms underpinning eustress and distress, thus guiding strategies to enhance adolescents' health and overall well-being., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Education and Health Promotion.) more...
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- 2024
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39. Revisiting Race, Ethnicity, and Disparities in Rheumatology Educational Materials: An Update Since 2020.
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Zickuhr L, Roberts E, Daugherty T, Rana A, Joshi H, Pollard B, Yu J, Jones HA, and Goglin S
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- Humans, Ethnicity, Racial Groups, Race Factors, Rheumatology education, Teaching Materials
- Abstract
Objective: In 2020, one study by Strait and colleagues raised awareness that the clinical images in rheumatology educational materials underrepresent people with skin of color (P-SOC). Since then, publishers of rheumatology educational materials have focused on addressing this shortcoming. This study investigates the change in representation of P-SOC following the review of Strait et al. METHODS: We used the methods of the aforementioned study to collect images from commonly referenced rheumatology educational materials and categorized the skin tones within them as "light" or "dark." We calculated the proportional change in images depicting dark skin tones between 2020 and 2022 from the American College of Rheumatology (ACR) Image Library, the 10th edition of Kelley's Textbook of Rheumatology, and New England Journal of Medicine (NEJM) as well as between 2020 and 2024 from rheumatology articles within UpToDate. We compared results using one-sided Z-tests., Results: Overall, the proportion of images depicting dark skin tones increased 40.6% (P < 0.0001). The 10th edition of Kelley's Textbook of Rheumatology most significantly increased inclusion of P-SOC (90.1%; P = 0.0039), with ACR Image Library, UpToDate, and NEJM also enhancing representation (41.9%, P < 0.0001; 31.0%, P = 0.0083; 28.2%, P = 0.3046, respectively)., Conclusion: This study assesses the progress of rheumatology educational materials toward equitable representation of P-SOC. It demonstrates that awareness coupled with focused efforts from educational publishers can enhance the proportion of images depicting dark skin tones, thereby enriching the quality of foundational knowledge relayed to rheumatology providers with the goal of improving health experiences and outcomes for P-SOC with rheumatic diseases., (© 2024 American College of Rheumatology.) more...
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- 2024
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40. A current review on P2X7 receptor antagonist patents in the treatment of neuroinflammatory disorders: a patent review on antagonists.
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Soni S, Lukhey MS, Thawkar BS, Chintamaneni M, Kaur G, Joshi H, Ramniwas S, and Tuli HS
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- Humans, Animals, Patents as Topic, Receptors, Purinergic P2X7 metabolism, Purinergic P2X Receptor Antagonists therapeutic use, Purinergic P2X Receptor Antagonists pharmacology, Neuroinflammatory Diseases drug therapy
- Abstract
Chronic inflammation is defined by an activated microglial state linked to all neurological disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (a motor neuron disease that affects the brain and spinal cord). P2X7 receptors (P2X7R) are ATP-activated ion-gated channels present on microglial surfaces. Prolonged ATP release under pathological settings results in sustained P2X7R activation, which leads to inflammasome development and cytokine release. P2X7R and its enabling roles have recently been linked to neurodegenerative diseases, making it a potential research subject. This research provides an overview of current patents for chemicals, biologics, and medicinal applications. The World Intellectual Property Organization (WIPO), European Patent Office (EPO, Espacenet), and the United States Patent and Trademark Office (USPTO) databases were searched for patents using the keywords "P2X7R and Neuroinflammation." During the study period from 2015 to 2021, 103 patents were examined. The countries that protected these innovations were the United States, PCT (Patent Cooperation Treaty states), Europe, Canada, Australia, and India. Janssen Pharmaceutica NV had the most applications, followed by Acetelion Pharmaceuticals LTD., Renovis Inc., Kelly Michael G, Kincaid Jhon, Merck Patent GMBH, H Lundbeck A/S, and many more. The P2X7R is a possible diagnostic and therapeutic target for cancer, pain disorders, and inflammation. For P2X7 R, several compounds have been discovered and are presently the subject of clinical trial investigations. This study featured patents for P2X7R antagonists, which help treat conditions including neuroinflammation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) more...
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- 2024
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41. Utilization of Truenat chips in defining XDR, pre-XDR and MDR in tuberculous meningitis.
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Sharma K, Sharma M, Shree R, Singla N, Joshi H, Modi T, Goyal M, Sharma A, Sharma N, and Modi M
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- Humans, Phenotype, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant microbiology, Predictive Value of Tests, Rifampin pharmacology, Molecular Diagnostic Techniques methods, Diarylquinolines therapeutic use, Diarylquinolines pharmacology, Isoniazid pharmacology, Tuberculosis, Meningeal microbiology, Tuberculosis, Meningeal diagnosis, Tuberculosis, Meningeal drug therapy, Tuberculosis, Meningeal cerebrospinal fluid, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis isolation & purification, Microbial Sensitivity Tests, Antitubercular Agents pharmacology, Antitubercular Agents therapeutic use, Drug Resistance, Multiple, Bacterial genetics, Extensively Drug-Resistant Tuberculosis microbiology, Extensively Drug-Resistant Tuberculosis drug therapy, Extensively Drug-Resistant Tuberculosis diagnosis
- Abstract
Setting and Objective: To develop and evaluate newer molecular tests that identify drug resistance according to contemporary definitions in Tuberculous meningitis (TBM), the most severe form of EPTB., Design: 93 cerebrospinal fluid (CSF) specimens [41 culture-positive and 52 culture-negative], were subjected to Truenat MTB Plus assay along with chips for rifampicin, isoniazid, fluoroquinolones and bedaquiline resistance. The performance was compared against phenotypic drug susceptibility testing (pDST), Line probe assay (LPA) and gene sequencing., Results: Against pDST, Truenat chips had a sensitivity and specificity of 100%; 94.47%, 100%; 94.47%, 100%; 97.14% and 100%; 100%, respectively for rifampicin, isoniazid, fluoroquinolones and bedaquiline. Against LPA, all Truenat chips detected resistant isolates with 100% sensitivity; but 2 cases each of false-rifampicin and false-isoniazid resistance and 1 case of false-fluoroquinolone resistance was reported. Truenat drug chips gave indeterminate results in ∼25% cases, which were excluded. All cases reported indeterminate were found to be susceptible by pDST/LPA., Conclusion: The strategic drug resistance chips of Truenat Plus assay can contribute greatly to TB elimination by providing rapid and reliable detection of drug resistance pattern in TBM. Cases reported indeterminate require confirmation by other phenotypic and genotypic methods., Competing Interests: Declaration of competing interest The authors confirm that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.) more...
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- 2024
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42. Novel nucleus-localized GRAM protein encoding OsGRAM57 gene enhances salt tolerance through ABA-dependent pathway and modulated carbohydrate metabolism.
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Joshi H, Tiwari S, Berendzen K, Mishra SK, Prasad V, Harter K, and Chauhan PS
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- Cell Nucleus metabolism, Plant Proteins genetics, Plant Proteins metabolism, Stress, Physiological genetics, Plant Growth Regulators metabolism, Plant Growth Regulators pharmacology, Abscisic Acid metabolism, Abscisic Acid pharmacology, Salt Tolerance genetics, Gene Expression Regulation, Plant, Arabidopsis genetics, Arabidopsis metabolism, Carbohydrate Metabolism genetics, Signal Transduction
- Abstract
GRAM (Glucosyltransferases-like GTPase activators and Myotubularin) domain-encoding proteins play pivotal roles in plant growth and responses to biotic stresses. Yet, their influence on abiotic stress responses has remained enigmatic. This study unveils a novel nucleus-localized OsGRAM57, a GRAM protein-encoding gene and its profound regulatory functions in enhancing salt stress tolerance using Arabidopsis thaliana as a model plant. OsGRAM57-OEX (OsGRAM57-OEX) lines displayed significant enhancement in salt tolerance, modulated physiological, biochemical, K
+ /Na+ ratios, and enzymatic indices as compared to their wild-type (WT). Furthermore, OsGRAM57-OEX seedlings demonstrate increased levels of endogenous abscisic acid (ABA) and other phytohormones, while metabolic profiling revealed enhanced carbohydrate metabolism. Delving into the ABA signaling pathway, OsGRAM57 emerged as a central regulator, orchestrating the expression of genes crucial for salt stress responses, carbohydrate metabolism, and ABA signaling. The observed interactions with target genes and transactivation assays provided additional support for OsGRAM57's pivotal role. These findings underscore OsGRAM57's positive influence on the ABA pathway and affirm its capacity to enhance salt tolerance through an ABA-dependent pathway and fine-tuned carbohydrate metabolism. In summary, this new study reveals the previously undiscovered regulatory roles of OsGRAM57 in Arabidopsis abiotic stress responses, offering promising ways for strengthening plant resilience in the face of adverse environmental conditions., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.) more...- Published
- 2024
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43. The contribution of household income to rectal cancer patient characteristics, treatment, and outcomes from 2010 to 2020.
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Moccia MC, Waters JP, Dibato J, Ghanem YK, Joshi H, Saleh ZB, Toma H, Giugliano DN, and McClane SJ
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Background: There is a paucity of recent literature investigating the sole effect of income level on the treatment and survival of patients with rectal cancer., Methods: We analyzed all cases of rectal cancer in the Rectal Cancer PUF of the NCDB from 2010 to 2020. We utilized the Median Income Quartiles 2016-2020 to define our income levels. The two lower quartiles were combined to create a lower income group, with the upper two quartiles creating the higher income group. The total cohort included 201,329 patients, with 116,843 and 84,486 in the higher and lower income groups, respectively., Results: Lower income patients were more often black (17 % vs 6 %), lived farther from the nearest hospital (33.5 miles vs 25.7 miles) despite being more likely to live in urban areas (25 % vs 7 %), and had lower levels of private insurance (36 % vs 49 %). They underwent more APRs (17 % vs 14 %) and had a 13 % higher chance of undergoing an open operation (OR 1.13, CI 1.09-1.17). Higher income patients had a 12 % reduction in 90-day (OR 0.88, 95 % CI 0.82-0.96) and overall mortality (OR 0.88, 95 % CI 0.86-0.89)., Conclusions: Clinicians should be aware that lower income patients are often faced with unique challenges that may impact care delivery., Competing Interests: 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 article., (© 2024 The Authors. Published by Elsevier Ltd.) more...
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- 2024
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44. Health literacy among patients with non-communicable diseases at a tertiary level hospital in Nepal- A cross sectional study.
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Joshi H, Kalauni BR, Bhusal K, Bhandari R, Subedi A, and Bhandari B
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- Humans, Female, Male, Nepal epidemiology, Middle Aged, Cross-Sectional Studies, Adult, Surveys and Questionnaires, Aged, Health Literacy statistics & numerical data, Noncommunicable Diseases epidemiology, Tertiary Care Centers
- Abstract
Health literacy (HL) is crucial in achieving the Sustainable Development Goal of reducing one-third of premature mortality by 2030 from Non-Communicable Diseases (NCDs) and improving Universal Health Coverage. Low health literacy is linked to poor health outcomes, and evidence shows that levels of limited HL are high, even among highly educated individuals. This study aims to assess HL levels and related factors among patients with NCDs at Tribhuvan University Teaching Hospital (TUTH) in Nepal. A cross-sectional survey was conducted at TUTH among 303 patients with NCDs with Cardiovascular Diseases, Chronic Obstructive Pulmonary Disease, Diabetes Mellitus, Hypertension, Epilepsy, Asthma and Cancer who came for follow-up from December 2022 to February 2023. Data was collected via face-to-face interviews by the trained enumerators using a structured Health Literacy Questionnaire (HLQ) containing 44 items (divided into nine domains). Multivariate logistic regression analysis was performed using SPSS version 26, with statistical significance at 0.05, to determine the associated factors of HL. The mean ±SD age of the respondents was 47.4±16.18 years. More than half of the respondents were female (56.1%). The patients had higher HL in all HL domains except 'Navigating the healthcare system'. Educational status was significantly associated with six out of nine HL domains. Co-morbidity, attendance at health-related seminars, regular physical activity, and social connectedness were associated with at least one of the domains of HL. This study identified the important factors of HL, such as socio-demographic and medical factors among patients with NCDs. This highlights the need for a comprehensive approach to address identified gaps in HL, considering its multifaceted and composite nature and promoting interventions to improve HL in high-risk populations., Competing Interests: The authors have declared that no competing interest exist., (Copyright: © 2024 Joshi 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.) more...
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- 2024
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45. Cardiovascular Toxicity Associated With Androgen Receptor Axis-Targeted Agents in Patients With Prostate Cancer: A Meta-analysis of Randomized Controlled Trials.
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Zhou S, Alerasool P, Kishi N, Joshi H, Sahni G, and Tsao CK
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- Humans, Male, Cardiovascular Diseases chemically induced, Androgen Receptor Antagonists adverse effects, Androgen Receptor Antagonists therapeutic use, Androgen Receptor Antagonists administration & dosage, Receptors, Androgen metabolism, Phenylthiohydantoin adverse effects, Phenylthiohydantoin therapeutic use, Phenylthiohydantoin administration & dosage, Benzamides adverse effects, Clinical Trials, Phase III as Topic, Nitriles adverse effects, Thiohydantoins adverse effects, Thiohydantoins administration & dosage, Thiohydantoins therapeutic use, Androstenes adverse effects, Androstenes therapeutic use, Androstenes administration & dosage, Randomized Controlled Trials as Topic, Prostatic Neoplasms drug therapy
- Abstract
Introduction: Second-generation androgen receptor axis-targeting (ARAT) agents have become a standard treatment for patients with advanced prostate cancer (PC), however much remains unknown about the potential cardiovascular toxicities., Patients and Methods: We performed a systematic search of PubMed, Embase, Web of Science, and Cochrane library for randomized controlled trials of patients receiving ARAT agents for PC from inception to March 2023. The odds ratios (ORs) of all-grade and high-grade cardiovascular adverse events (CVAEs) for patients treated with and without ARAT agents were pooled for meta-analysis. Subgroup analyses based on PC type and treatment regimen were conducted., Results: A total of 15 double-blind placebo-controlled phase 3 trials comprising 15,842 patients were included. In addition to hot flush and hypertension of any degree of severity, inclusion of ARAT agents was associated with a significantly higher risk of acute myocardial infarction (OR: 1.96, 95% CI: 1.05-3.68, P = .04), myocardial infarction (OR: 2.44, 95% CI: 1.27-4.66, P = .007) and angina pectoris (OR: 2.00, 95% CI: 1.00-4.02, P = .05). With regard to individual ARAT agents, enzalutamide was associated with a significantly higher risk of acute myocardial infarction (OR: 3.11, 95% CI: 1.17-8.28, P = .02), coronary artery disease (OR: 8.33, 95% CI: 1.54-44.95, P = .01), and high-grade hypertension (OR: 4.94, 95% CI: 1.11-22.06, P = .04), while abiraterone and apalutamide were associated with a significantly higher risk of angina pectoris (OR: 5.48, 95% CI: 1.23-24.33, P = .03) and myocardial infarction (OR: 7.00, 95% CI: 1.60-30.62, P = .01), respectively., Conclusion: The inclusion of ARAT agents was associated with a significantly higher risk of several CVAEs. Clinicians should remain vigilant, both in pre-treatment screening and monitoring for clinical symptoms and signs, when considering ARAT agent particularly for patients with pre-existing risk factors., Competing Interests: Disclosure None of the authors disclose any potential conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.) more...
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- 2024
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46. A unique case of appendiceal diverticulum presenting with positive faecal immunochemical test.
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Saqib IU, Noor N, and Joshi H
- Abstract
Appendiceal diverticulum is a rare condition that usually presents with symptoms similar to acute appendicitis. Although imaging can be used to aid the diagnosis of this condition, it is usually confirmed postoperatively on the basis of histology. Because of an increased risk of appendiceal neoplasms, the usual management is prophylactic appendicectomy. We report the case of a 70-year-old lady with no symptoms referred from her GP surgery for a positive faecal immunochemical test as part of the bowel screening programme. Colonoscopy showed a mass at the appendiceal orifice with normal histology. She underwent an appendicectomy with a small cuff of caecal resection. The lesion was ~8 cm at its maximum dimension and showed appendiceal diverticulum. Appendiceal diverticulum is an important differential diagnosis to consider in patients with atypical history of acute appendicitis or positive faecal immunochemical test with no other symptoms., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.) more...
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- 2024
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47. The implementation of a zero-suicide framework in a child and youth mental health service in Australia: processes and learnings.
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Branjerdporn G, McCosker LK, Jackson D, McDowell S, Williams P, Chand S, Joshi H, Pisani AR, Stapelberg C, Welch M, Turner K, and Woerwag-Mehta S
- Abstract
Suicide in children is a significant and growing problem. The "zero suicide" framework (ZSF) is one approach to suicide prevention used in health services for adults and children. This paper reports on the introduction of the first suicide prevention pathway (SPP) based on ZSF at a Child and Youth Mental Health Service (CYMHS) in Australia. It begins by describing the adaptations made to elements of the SPP originally designed for adults to meet the needs of children. Lessons learned in applying the SPP in the service are then discussed. The aim is to inform and improve practice in the use of zero suicide approaches in child and youth mental health settings in Australia and worldwide., Competing Interests: AP is the equity owner of SafeSide Prevention / SafeSide Australia which licensed educational materials from University of Rochester. SafeSide receives fees for education, consultation, and leadership services for healthcare organisations and government. The University of Rochester receives royalties from SafeSide and declares this financial interest. A conflict of interest management plan is in place at the University of Rochester and routinely communicated and monitored per University guidelines. AP receives book royalties from Cambridge University Press. The remaining 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 © 2024 Branjerdporn, McCosker, Jackson, McDowell, Williams, Chand, Joshi, Pisani, Stapelberg, Welch, Turner and Woerwag-Mehta.) more...
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- 2024
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48. Physiotherapists' Adoption and Perceptions of Tele-Rehabilitation for Cardiorespiratory Care in Response to COVID-19.
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Schertzer K, Belitzky J, Conboy C, Joshi H, Harvey K, Hondal GS, Miller E, Mathur S, and Wickerson L
- Abstract
Purpose: The use of tele-rehabilitation as a mode for physiotherapy services was widely implemented following the onset of the coronavirus disease 2019 (COVID-19) pandemic. This study explored the perceived value and experiences of physiotherapists relating to tele-rehabilitation for cardiorespiratory care., Method: Semi-structured interviews were conducted with physiotherapists who provided tele-rehabilitation to adults with cardiorespiratory conditions between March 11 and December 31, 2020. Interviews were analyzed using conventional content analysis., Results: Seven participants were interviewed; six practising solely in pulmonary rehabilitation and one practising in both pulmonary and cardiac rehabilitation. Three major themes emerged: (1) the pandemic presented unique challenges to implementing tele-rehabilitation while exacerbating previous challenges inherent with virtual care, (2) tele-rehabilitation use during the pandemic was deemed as equally effective in quality of care and patient adherence when compared to in-person services, and (3) tele-rehabilitation had significant value during the pandemic and has potential as an alternative delivery model post pandemic., Conclusion: Despite the inherent challenges, tele-rehabilitation was endorsed by participants as a suitable and effective alternative to care delivery and holds promise as a post-pandemic delivery model. Further evaluation is needed to support and optimize tele-rehabilitation use in physiotherapy practice., Competing Interests: Competing Interests: The authors have no conflicts of interest to declare., (© Canadian Physiotherapy Association, 2024.) more...
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- 2024
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49. Brain Age Analysis and Dementia Classification using Convolutional Neural Networks trained on Diffusion MRI: Tests in Indian and North American Cohorts.
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Chattopadhyay T, Joshy NA, Ozarkar SS, Buwa KS, Feng Y, Laltoo E, Thomopoulos SI, Villalon-Reina JE, Joshi H, Venkatasubramanian G, John JP, and Thompson PM
- Abstract
Deep learning models based on convolutional neural networks (CNNs) have been used to classify Alzheimer's disease or infer dementia severity from T1-weighted brain MRI scans. Here, we examine the value of adding diffusion-weighted MRI (dMRI) as an input to these models. Much research in this area focuses on specific datasets such as the Alzheimer's Disease Neuroimaging Initiative (ADNI), which assesses people of North American, largely European ancestry, so we examine how models trained on ADNI, generalize to a new population dataset from India (the NIMHANS cohort). We first benchmark our models by predicting 'brain age' - the task of predicting a person's chronological age from their MRI scan and proceed to AD classification. We also evaluate the benefit of using a 3D CycleGAN approach to harmonize the imaging datasets before training the CNN models. Our experiments show that classification performance improves after harmonization in most cases, as well as better performance for dMRI as input. more...
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- 2024
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50. Dr. Google to Dr. ChatGPT: assessing the content and quality of artificial intelligence-generated medical information on appendicitis.
- Author
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Ghanem YK, Rouhi AD, Al-Houssan A, Saleh Z, Moccia MC, Joshi H, Dumon KR, Hong Y, Spitz F, Joshi AR, and Kwiatt M
- Subjects
- Humans, Comprehension, Internet, Consumer Health Information standards, Patient Education as Topic methods, Appendicitis, Artificial Intelligence
- Abstract
Introduction: Generative artificial intelligence (AI) chatbots have recently been posited as potential sources of online medical information for patients making medical decisions. Existing online patient-oriented medical information has repeatedly been shown to be of variable quality and difficult readability. Therefore, we sought to evaluate the content and quality of AI-generated medical information on acute appendicitis., Methods: A modified DISCERN assessment tool, comprising 16 distinct criteria each scored on a 5-point Likert scale (score range 16-80), was used to assess AI-generated content. Readability was determined using the Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level (FKGL) scores. Four popular chatbots, ChatGPT-3.5 and ChatGPT-4, Bard, and Claude-2, were prompted to generate medical information about appendicitis. Three investigators independently scored the generated texts blinded to the identity of the AI platforms., Results: ChatGPT-3.5, ChatGPT-4, Bard, and Claude-2 had overall mean (SD) quality scores of 60.7 (1.2), 62.0 (1.0), 62.3 (1.2), and 51.3 (2.3), respectively, on a scale of 16-80. Inter-rater reliability was 0.81, 0.75, 0.81, and 0.72, respectively, indicating substantial agreement. Claude-2 demonstrated a significantly lower mean quality score compared to ChatGPT-4 (p = 0.001), ChatGPT-3.5 (p = 0.005), and Bard (p = 0.001). Bard was the only AI platform that listed verifiable sources, while Claude-2 provided fabricated sources. All chatbots except for Claude-2 advised readers to consult a physician if experiencing symptoms. Regarding readability, FKGL and FRE scores of ChatGPT-3.5, ChatGPT-4, Bard, and Claude-2 were 14.6 and 23.8, 11.9 and 33.9, 8.6 and 52.8, 11.0 and 36.6, respectively, indicating difficulty readability at a college reading skill level., Conclusion: AI-generated medical information on appendicitis scored favorably upon quality assessment, but most either fabricated sources or did not provide any altogether. Additionally, overall readability far exceeded recommended levels for the public. Generative AI platforms demonstrate measured potential for patient education and engagement about appendicitis., (© 2024. The Author(s).) more...
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- 2024
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