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Article ; Online: The therapeutic potential of ketones in cardiometabolic disease: impact on heart and skeletal muscle.

Soni, Shubham / Tabatabaei Dakhili, Seyed Amirhossein / Ussher, John R / Dyck, Jason R B

American journal of physiology. Cell physiology

2024 Volume 326, Issue 2, Page(s) C551–C566

Abstract: β-Hydroxybutyrate (βOHB) is the major ketone in the body, and it is recognized as a metabolic energy source and an important signaling molecule. While ketone oxidation is essential in the brain during prolonged fasting/starvation, other organs such as ... ...

Abstract	β-Hydroxybutyrate (βOHB) is the major ketone in the body, and it is recognized as a metabolic energy source and an important signaling molecule. While ketone oxidation is essential in the brain during prolonged fasting/starvation, other organs such as skeletal muscle and the heart also use ketones as metabolic substrates. Additionally, βOHB-mediated molecular signaling events occur in heart and skeletal muscle cells, and via metabolism and/or signaling, ketones may contribute to optimal skeletal muscle health and cardiac function. Of importance, when the use of ketones for ATP production and/or as signaling molecules becomes disturbed in the presence of underlying obesity, type 2 diabetes, and/or cardiovascular diseases, these changes may contribute to cardiometabolic disease. As a result of these disturbances in cardiometabolic disease, multiple approaches have been used to elevate circulating ketones with the goal of optimizing either ketone metabolism or ketone-mediated signaling. These approaches have produced significant improvements in heart and skeletal muscle during cardiometabolic disease with a wide range of benefits that include improved metabolism, weight loss, better glycemic control, improved cardiac and vascular function, as well as reduced inflammation and oxidative stress. Herein, we present the evidence that indicates that ketone therapy could be used as an approach to help treat cardiometabolic diseases by targeting cardiac and skeletal muscles.
MeSH term(s)	Humans ; Ketones/therapeutic use ; Ketones/metabolism ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/metabolism ; Muscle, Skeletal/metabolism ; Myocardium/metabolism ; 3-Hydroxybutyric Acid/metabolism ; Heart Failure/metabolism
Chemical Substances	Ketones ; 3-Hydroxybutyric Acid (TZP1275679)
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00501.2023
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Article ; Online: The Multiple Effects of SGLT2 Inhibitors Suggest Potential Benefit in COVID-19 Patients.

Soni, Shubham / Dyck, Jason R B

The Canadian journal of cardiology

2020 Volume 36, Issue 10, Page(s) 1691.e3

MeSH term(s)	Anti-Inflammatory Agents/therapeutic use ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Humans ; Inflammation/drug therapy ; Inflammation/immunology ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; SARS-CoV-2 ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
Chemical Substances	Anti-Inflammatory Agents ; Sodium-Glucose Transporter 2 Inhibitors
Keywords	covid19
Language	English
Publishing date	2020-07-24
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	632813-1
ISSN	1916-7075 ; 0828-282X
ISSN (online)	1916-7075
ISSN	0828-282X
DOI	10.1016/j.cjca.2020.07.230
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Book ; Online: MILDSum

Datta, Debtanu / Soni, Shubham / Mukherjee, Rajdeep / Ghosh, Saptarshi

A Novel Benchmark Dataset for Multilingual Summarization of Indian Legal Case Judgments

2023

Abstract: Automatic summarization of legal case judgments is a practically important problem that has attracted substantial research efforts in many countries. In the context of the Indian judiciary, there is an additional complexity -- Indian legal case judgments ...

Abstract	Automatic summarization of legal case judgments is a practically important problem that has attracted substantial research efforts in many countries. In the context of the Indian judiciary, there is an additional complexity -- Indian legal case judgments are mostly written in complex English, but a significant portion of India's population lacks command of the English language. Hence, it is crucial to summarize the legal documents in Indian languages to ensure equitable access to justice. While prior research primarily focuses on summarizing legal case judgments in their source languages, this study presents a pioneering effort toward cross-lingual summarization of English legal documents into Hindi, the most frequently spoken Indian language. We construct the first high-quality legal corpus comprising of 3,122 case judgments from prominent Indian courts in English, along with their summaries in both English and Hindi, drafted by legal practitioners. We benchmark the performance of several diverse summarization approaches on our corpus and demonstrate the need for further research in cross-lingual summarization in the legal domain. Comment: Accepted at EMNLP 2023 (Main Conference)
Keywords	Computer Science - Computation and Language ; Computer Science - Artificial Intelligence
Publishing date	2023-10-28
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Improving Access to Justice for the Indian Population

Mahapatra, Sayan / Datta, Debtanu / Soni, Shubham / Goswami, Adrijit / Ghosh, Saptarshi

A Benchmark for Evaluating Translation of Legal Text to Indian Languages

2023

Abstract: Most legal text in the Indian judiciary is written in complex English due to historical reasons. However, only about 10% of the Indian population is comfortable in reading English. Hence legal text needs to be made available in various Indian languages, ... ...

Abstract	Most legal text in the Indian judiciary is written in complex English due to historical reasons. However, only about 10% of the Indian population is comfortable in reading English. Hence legal text needs to be made available in various Indian languages, possibly by translating the available legal text from English. Though there has been a lot of research on translation to and between Indian languages, to our knowledge, there has not been much prior work on such translation in the legal domain. In this work, we construct the first high-quality legal parallel corpus containing aligned text units in English and nine Indian languages, that includes several low-resource languages. We also benchmark the performance of a wide variety of Machine Translation (MT) systems over this corpus, including commercial MT systems, open-source MT systems and Large Language Models. Through a comprehensive survey by Law practitioners, we check how satisfied they are with the translations by some of these MT systems, and how well automatic MT evaluation metrics agree with the opinions of Law practitioners.
Keywords	Computer Science - Computation and Language ; Computer Science - Artificial Intelligence
Subject code	410
Publishing date	2023-10-15
Publishing country	us
Document type	Book ; Online
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Article: The Multiple Effects of SGLT2 Inhibitors Suggest Potential Benefit in COVID-19 Patients

Soni, Shubham / Dyck, Jason R B

Can J Cardiol

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #671639
Database	COVID19

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Article ; Online: The Multiple Effects of SGLT2 Inhibitors Suggest Potential Benefit in COVID-19 Patients

Soni, Shubham / Dyck, Jason R.B.

Canadian Journal of Cardiology

2020 Volume 36, Issue 10, Page(s) 1691.e3

Keywords	Cardiology and Cardiovascular Medicine ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	632813-1
ISSN	1916-7075 ; 0828-282X
ISSN (online)	1916-7075
ISSN	0828-282X
DOI	10.1016/j.cjca.2020.07.230
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Article ; Online: Ketone therapy for heart failure: current evidence for clinical use.

Takahara, Shingo / Soni, Shubham / Maayah, Zaid H / Ferdaoussi, Mourad / Dyck, Jason R B

Cardiovascular research

2021 Volume 118, Issue 4, Page(s) 977–987

Abstract: During conditions that result in depleted circulating glucose levels, ketone bodies synthesized in the liver are necessary fuel substrates for the brain. In other organs, such as the heart, the reliance on ketones for generating energy in the absence of ... ...

Abstract	During conditions that result in depleted circulating glucose levels, ketone bodies synthesized in the liver are necessary fuel substrates for the brain. In other organs, such as the heart, the reliance on ketones for generating energy in the absence of glucose is less important as the heart can utilize alternative fuel sources, such as fatty acids. However, during pathophysiological conditions, such as heart failure, cardiac defects in metabolic processes that normally allow for sufficient energy production from fatty acids and carbohydrates contribute to a decline in contractile function. As such, it has been proposed that the failing heart relies more on ketone bodies as an energy source than previously appreciated. Furthermore, it has been shown that ketone bodies function as signaling molecules that can suppress systemic and cardiac inflammation. Thus, it is possible that intentionally elevating circulating ketones may be beneficial as an adjunct treatment for heart failure. Although many approaches can be used for 'ketone therapy', each of these has their own advantages and disadvantages in the treatment of heart failure. Thus, we summarize current preclinical and clinical studies involving various types of ketone therapy in cardiac disease and discuss the advantages and disadvantages of each modality as possible treatments for heart failure.
MeSH term(s)	Fatty Acids/metabolism ; Glucose/metabolism ; Heart Failure/diagnosis ; Heart Failure/drug therapy ; Humans ; Ketone Bodies/metabolism ; Ketones/therapeutic use
Chemical Substances	Fatty Acids ; Ketone Bodies ; Ketones ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-03-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80340-6
ISSN	1755-3245 ; 0008-6363
ISSN (online)	1755-3245
ISSN	0008-6363
DOI	10.1093/cvr/cvab068
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Article ; Online: Exogenous ketone ester administration attenuates systemic inflammation and reduces organ damage in a lipopolysaccharide model of sepsis.

Soni, Shubham / Martens, Matthew D / Takahara, Shingo / Silver, Heidi L / Maayah, Zaid H / Ussher, John R / Ferdaoussi, Mourad / Dyck, Jason R B

Biochimica et biophysica acta. Molecular basis of disease

2022 Volume 1868, Issue 11, Page(s) 166507

Abstract: Aims: Sepsis is a life-threatening condition of organ dysfunction caused by dysregulated inflammation which predisposes patients to developing cardiovascular disease. The ketone β-hydroxybutyrate is reported to be cardioprotective in cardiovascular ... ...

Abstract	Aims: Sepsis is a life-threatening condition of organ dysfunction caused by dysregulated inflammation which predisposes patients to developing cardiovascular disease. The ketone β-hydroxybutyrate is reported to be cardioprotective in cardiovascular disease and this may be due to their signaling properties that contribute to reducing inflammation. While exogenous ketone esters (KE) increase blood ketone levels, it remains unknown whether KEs can reduce the enhanced inflammatory response and multi-organ dysfunction that is observed in sepsis. Thus, this study assesses whether a recently developed and clinically safe KE can effectively improve the inflammatory response and organ dysfunction in sepsis. Methods and results: To assess the anti-inflammatory effects of a KE, we utilized a model of lipopolysaccharide (LPS)-induced sepsis in which an enhanced inflammatory response results in multi-organ dysfunction. Oral administration of KE for three days prior to LPS-injection significantly protected mice against the profound systemic inflammation compared to their vehicle-treated counterparts. In assessing organ dysfunction, KE protected mice from sepsis-induced cardiac dysfunction as well as renal dysfunction and fibrosis. Furthermore, KE administration attenuated the sepsis-induced inflammation in the heart, kidney, and liver. Moreover, these protective effects occurred independent of changes to enzymes involved in ketone metabolism. Conclusion: These data show that the use of an exogenous KE attenuates the dysregulated systemic and organ inflammation as well as organ dysfunction in a model of severe inflammation. We postulate that this exogenous KE is an appealing and promising approach to capitalize on the protective anti-inflammatory effects of ketones in sepsis and/or other inflammatory responses.
MeSH term(s)	3-Hydroxybutyric Acid/therapeutic use ; Animals ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Cardiovascular Diseases ; Esters/pharmacology ; Esters/therapeutic use ; Inflammation/drug therapy ; Ketones/pharmacology ; Lipopolysaccharides/toxicity ; Mice ; Multiple Organ Failure/drug therapy ; Multiple Organ Failure/etiology ; Multiple Organ Failure/prevention & control ; Sepsis/chemically induced ; Sepsis/drug therapy ; Sepsis/metabolism
Chemical Substances	Anti-Inflammatory Agents ; Esters ; Ketones ; Lipopolysaccharides ; 3-Hydroxybutyric Acid (TZP1275679)
Language	English
Publishing date	2022-07-25
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2022.166507
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Article ; Online: Empagliflozin suppresses inflammation and protects against acute septic renal injury.

Maayah, Zaid H / Ferdaoussi, Mourad / Takahara, Shingo / Soni, Shubham / Dyck, Jason R B

Inflammopharmacology

2020 Volume 29, Issue 1, Page(s) 269–279

Abstract: Background: Sepsis-induced systemic inflammation response syndrome is the leading cause of morbidity and mortality among patients in intensive care units in North America. While sepsis is associated with multiple organ damage, acute renal injury ... ...

Abstract	Background: Sepsis-induced systemic inflammation response syndrome is the leading cause of morbidity and mortality among patients in intensive care units in North America. While sepsis is associated with multiple organ damage, acute renal injury represents a hallmark of sepsis. Since systemic and renal inflammation is known to play a vital role in morbidity and mortality associated with sepsis, identifying a potent anti-inflammatory agent may help minimize morbidity and mortality associated with acute septic kidney injury. Since recent work has suggested that empagliflozin, a renal sodium-glucose cotransporter 2 (SGLT2) inhibitor, may assist in the treatment of inflammatory diseases, our objective was to examine the effect of empagliflozin on acute sepsis-induced renal injury. Method: Mice were treated with three daily doses of empagliflozin or vehicle, with lipopolysaccharide (LPS) administered on the third day, at the same time as the third dose of empagliflozin or vehicle. In another cohort, mice were injected with a single dose of LPS 3 h before a dose of empagliflozin. Results: Our results show that empagliflozin improves survival in a mouse model of LPS-induced septic shock. We further demonstrate that the beneficial effects of empagliflozin are likely mediated via reducing LPS-induced acute renal injury. Moreover, our data indicate that empagliflozin significantly reduces systemic and renal inflammation to contribute to the improvements observed in an LPS-model of acute septic renal injury. Conclusion: Overall, the findings of this study suggest that empagliflozin could be repurposed to reduce morbidity and mortality in patients with acute septic renal injury. Trial registration: Not applicable.
MeSH term(s)	Acute Kidney Injury/etiology ; Acute Kidney Injury/prevention & control ; Animals ; Anti-Inflammatory Agents/administration & dosage ; Anti-Inflammatory Agents/pharmacology ; Benzhydryl Compounds/administration & dosage ; Benzhydryl Compounds/pharmacology ; Disease Models, Animal ; Glucosides/administration & dosage ; Glucosides/pharmacology ; Inflammation/drug therapy ; Inflammation/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Sepsis/complications ; Sepsis/drug therapy ; Shock, Septic/complications ; Shock, Septic/drug therapy ; Sodium-Glucose Transporter 2 Inhibitors/administration & dosage ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology
Chemical Substances	Anti-Inflammatory Agents ; Benzhydryl Compounds ; Glucosides ; Sodium-Glucose Transporter 2 Inhibitors ; empagliflozin (HDC1R2M35U)
Language	English
Publishing date	2020-06-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1080058-x
ISSN	1568-5608 ; 0925-4692
ISSN (online)	1568-5608
ISSN	0925-4692
DOI	10.1007/s10787-020-00732-4
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Article ; Online: Perinatal iron restriction is associated with changes in neonatal cardiac function and structure in a sex-dependent manner.

Noble, Ronan M N / Holody, Claudia D / Woodman, Andrew G / Nie, Chunpeng / Liu, Si Ning / Young, Daniel / Wiedemeyer, Alyssa / Soni, Shubham / Dyck, Jason R B / Graf, Daniel / Eckersley, Luke G / Dufour, Antoine / Bourque, Stephane L

Clinical science (London, England : 1979)

2023 Volume 137, Issue 15, Page(s) 1115–1130

Abstract: Iron deficiency (ID) is common during gestation and in early infancy and can alter developmental trajectories with lasting consequences on cardiovascular health. While the effects of ID and anemia on the mature heart are well documented, comparatively ... ...

Abstract	Iron deficiency (ID) is common during gestation and in early infancy and can alter developmental trajectories with lasting consequences on cardiovascular health. While the effects of ID and anemia on the mature heart are well documented, comparatively little is known about their effects and mechanisms on offspring cardiac development and function in the neonatal period. Female Sprague-Dawley rats were fed an iron-restricted or iron-replete diet before and during pregnancy. Cardiac function was assessed in a cohort of offspring on postnatal days (PD) 4, 14, and 28 by echocardiography; a separate cohort was euthanized for tissue collection and hearts underwent quantitative shotgun proteomic analysis. ID reduced body weight and increased relative heart weights at all time points assessed, despite recovering from anemia by PD28. Echocardiographic studies revealed unique functional impairments in ID male and female offspring, characterized by greater systolic dysfunction in the former and greater diastolic dysfunction in the latter. Proteomic analysis revealed down-regulation of structural components by ID, as well as enriched cellular responses to stress; in general, these effects were more pronounced in males. ID causes functional changes in the neonatal heart, which may reflect an inadequate or maladaptive compensation to anemia. This identifies systolic and diastolic dysfunction as comorbidities to perinatal ID anemia which may have important implications for both the short- and long-term cardiac health of newborn babies. Furthermore, therapies which improve cardiac output may mitigate the effects of ID on organ development.
MeSH term(s)	Pregnancy ; Rats ; Animals ; Male ; Female ; Iron ; Rats, Sprague-Dawley ; Proteomics ; Iron Deficiencies ; Anemia, Iron-Deficiency
Chemical Substances	Iron (E1UOL152H7)
Language	English
Publishing date	2023-07-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	206835-7
ISSN	1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
ISSN (online)	1470-8736
ISSN	0301-0538 ; 0009-0360 ; 0143-5221
DOI	10.1042/CS20230594
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