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1. Use of at-home sperm concentration testing in a male hormonal contraceptive efficacy clinical trial

Author

Wang, Christina, Lue, Yanhe, Swerdloff, Ronald S, Morris, Dayton, Pak, Youngju, Nguyen, Brian T, Liu, Peter Y, Creinin, Mitchell D, Surampudi, Prasanth, Turok, David, Aston, Kenneth I, Anderson, Richard, Reynolds-Wright, John, Page, Stephanie T, Amory, John K, Dart, Clint, Kroopnick, Jeffrey M, Lee, Min S, Sitruk Ware, Regine, and Blithe, Diana L

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Clinical Sciences, Paediatrics and Reproductive Medicine, Public Health and Health Services, Obstetrics & Reproductive Medicine, Reproductive medicine
Published
2024

2. HyperGALE: ASD Classification via Hypergraph Gated Attention with Learnable Hyperedges

Author

Arora, Mehul, Jain, Chirag Shantilal, Baru, Lalith Bharadwaj, Dadi, Kamalaker, and Surampudi, Bapi Raju

Subjects
Computer Science - Machine Learning, Computer Science - Artificial Intelligence, Computer Science - Computer Vision and Pattern Recognition, Computer Science - Neural and Evolutionary Computing
Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by varied social cognitive challenges and repetitive behavioral patterns. Identifying reliable brain imaging-based biomarkers for ASD has been a persistent challenge due to the spectrum's diverse symptomatology. Existing baselines in the field have made significant strides in this direction, yet there remains room for improvement in both performance and interpretability. We propose \emph{HyperGALE}, which builds upon the hypergraph by incorporating learned hyperedges and gated attention mechanisms. This approach has led to substantial improvements in the model's ability to interpret complex brain graph data, offering deeper insights into ASD biomarker characterization. Evaluated on the extensive ABIDE II dataset, \emph{HyperGALE} not only improves interpretability but also demonstrates statistically significant enhancements in key performance metrics compared to both previous baselines and the foundational hypergraph model. The advancement \emph{HyperGALE} brings to ASD research highlights the potential of sophisticated graph-based techniques in neurodevelopmental studies. The source code and implementation instructions are available at GitHub:https://github.com/mehular0ra/HyperGALE., Comment: Accepted to IJCNN 2024

Published
2024
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4. Transparency in Sleep Staging: Deep Learning Method for EEG Sleep Stage Classification with Model Interpretability

Author

Sharma, Shivam, Maiti, Suvadeep, Mythirayee, S., Rajendran, Srijithesh, and Bapi, Raju Surampudi

Subjects
Electrical Engineering and Systems Science - Signal Processing, Computer Science - Machine Learning
Abstract

Automated Sleep stage classification using raw single channel EEG is a critical tool for sleep quality assessment and disorder diagnosis. However, modelling the complexity and variability inherent in this signal is a challenging task, limiting their practicality and effectiveness in clinical settings. To mitigate these challenges, this study presents an end-to-end deep learning (DL) model which integrates squeeze and excitation blocks within the residual network to extract features and stacked Bi-LSTM to understand complex temporal dependencies. A distinctive aspect of this study is the adaptation of GradCam for sleep staging, marking the first instance of an explainable DL model in this domain with alignment of its decision-making with sleep expert's insights. We evaluated our model on the publically available datasets (SleepEDF-20, SleepEDF-78, and SHHS), achieving Macro-F1 scores of 82.5, 78.9, and 81.9, respectively. Additionally, a novel training efficiency enhancement strategy was implemented by increasing stride size, leading to 8x faster training times with minimal impact on performance. Comparative analyses underscore our model outperforms all existing baselines, indicating its potential for clinical usage., Comment: 12 pages, 9 figures, Under review at IEEE Journal of Biomedical and Health Informatics

Published
2023

6. Intended Outcomes Expand In Time: Evidence from the Temporal Reproduction Task

Author

Donapati, Rohan R., Shukla, Anuj, and Bapi, Raju Surampudi

Subjects
Psychology, Action, Behavioral Science, Cognition of Time, Perception, Computer-based experiment
Abstract

The intentional binding (IB) phenomenon reflects a perceived attraction between a voluntary action and an intended consequence. Recent research has shown that during IB, intended outcomes expand in time. Although, this effect was significant only for shorter action-outcome delays. However, literature on IB suggests it can also exist for long delays. To address this, we implemented a temporal reproduction task to observe the expansion of an intended outcome. Results revealed the expansion of an intended outcome in the shorter and longer action-outcome delays. These results were discussed under the PIDI (proximal intent distal intent) framework since, using this methodology, both types of intention can be operationalized. Proximal for shorter delays under the motor action, and distal for longer delays as the inference made towards the objective duration to be reproduced. Our implementation allows a robust way to observe the temporal dynamics of an intended outcome, irrespective of the action-outcome delay.

Published
2023

7. Safety assessment of rat embryonic fraction for in vivo regenerative therapy

Author

Sivarama Prasad Darsi, Somorita Baishya, Veerababu Nagati, Kala Kumar Bharani, Satyanarayana Swamy Cheekatla, Sujesh Kumar Darsi, Adi Reddy Kamireddy, Ram Reddy Barra, Ashok Kumar Devarasetti, Sreedhar Surampudi, Jayaram Reddy Singireddy, Siva Kumar Kandula, and Anil Kumar Pasupulati

Subjects
embryonic protein fraction, regenerative therapy, immunogenicity, tumorigenicity, proteomic analysis, Science, Biology (General), QH301-705.5
Published
2024
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8. Neural Language Taskonomy: Which NLP Tasks are the most Predictive of fMRI Brain Activity?

Author

Oota, Subba Reddy, Arora, Jashn, Agarwal, Veeral, Marreddy, Mounika, Gupta, Manish, and Surampudi, Bapi Raju

Subjects
Computer Science - Computation and Language, Computer Science - Artificial Intelligence, Computer Science - Machine Learning, Quantitative Biology - Neurons and Cognition
Abstract

Several popular Transformer based language models have been found to be successful for text-driven brain encoding. However, existing literature leverages only pretrained text Transformer models and has not explored the efficacy of task-specific learned Transformer representations. In this work, we explore transfer learning from representations learned for ten popular natural language processing tasks (two syntactic and eight semantic) for predicting brain responses from two diverse datasets: Pereira (subjects reading sentences from paragraphs) and Narratives (subjects listening to the spoken stories). Encoding models based on task features are used to predict activity in different regions across the whole brain. Features from coreference resolution, NER, and shallow syntax parsing explain greater variance for the reading activity. On the other hand, for the listening activity, tasks such as paraphrase generation, summarization, and natural language inference show better encoding performance. Experiments across all 10 task representations provide the following cognitive insights: (i) language left hemisphere has higher predictive brain activity versus language right hemisphere, (ii) posterior medial cortex, temporo-parieto-occipital junction, dorsal frontal lobe have higher correlation versus early auditory and auditory association cortex, (iii) syntactic and semantic tasks display a good predictive performance across brain regions for reading and listening stimuli resp., Comment: 18 pages, 18 figures

Published
2022
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9. Micronutrient Deficiency as a Confounder in Ascertaining the Role of Obesity in Severe COVID-19 Infection

Author

Chu, Brian A, Surampudi, Vijaya, Li, Zhaoping, Harris, Christina, Seeman, Teresa, Norris, Keith C, and Vijayan, Tara

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Clinical Research, Obesity, Emerging Infectious Diseases, Prevention, Coronaviruses, Lung, Coronaviruses Disparities and At-Risk Populations, Infectious Diseases, Nutrition, Dietary Supplements, 2.1 Biological and endogenous factors, Zero Hunger, COVID-19, Humans, Micronutrients, SARS-CoV-2, Vitamins, micronutrients, vitamin D, vitamin A, coronavirus, respiratory infection, obesity, food insecurity, Toxicology
Abstract

Food insecurity in the United States has been exacerbated due to the socioeconomic strain of the coronavirus disease 2019 (COVID-19) pandemic. Populations experiencing poverty and, as a consequence, food insecurity in the United States are disproportionately affected by obesity, which was identified early in the pandemic as a major risk factor for increased susceptibility to COVID-19 infection and mortality. Given the focus on obesity and its role in immune dysregulation, it is also important to note the role of micronutrient deficiency, another sequalae of food insecurity. Micronutrients play an important role in the ability of the immune system to mount an appropriate response. Moreover, OBESE individuals are more likely to be micronutrient deficient. This review will explore the role of micronutrients, vitamin A, vitamin D, vitamin C, and zinc in respiratory immunity and COVID-19 and how micronutrient deficiency may be a possible confounder in obesity's association with severe outcomes. By illuminating the role of micronutrients in COVID-19, this paper expands the discussion from food insecurity and obesity to include micronutrient deficiency and how all of these interact in respiratory illnesses such as COVID-19.

Published
2022

10. Deep Learning for Brain Encoding and Decoding

Author

Oota, Subba Reddy, Arora, Jashn, Gupta, Manish, Bapi, Raju Surampudi, and Toneva, Mariya

Subjects
Cognitive Neuroscience, Neuroscience, Cognitive architectures, Language understanding, Computational neuroscience, fMRI, Neural Networks
Abstract

How does the brain represent different modes of information? Can we design a system that can automatically understand what the user is thinking? We can make progress towards answering such questions by studying brain recordings from devices such as functional magnetic resonance imaging (fMRI). The brain encoding problem aims to automatically generate fMRI brain representations given a stimulus. The brain decoding problem is the inverse problem of reconstructing the stimuli given the fMRI brain representation. Both the brain encoding and decoding problems have been studied in detail in the past two decades and the foremost attraction of studying these solutions is that they serve as additional tools for basic research in cognitive science and cognitive neuroscience. Recently, inspired by the effectiveness of deep learning models for natural language processing and computer vision, such models have been applied for neuroscience as well. In this tutorial, we plan to discuss different kinds of stimulus representations, and popular encoding and decoding architectures in detail. The tutorial will provide a working knowledge of the state of the art methods for encoding and decoding, a thorough understanding of the literature, and a better understanding of the benefits and limitations of encoding/decoding with deep learning.

Published
2022

11. Relative Numerical Context Affects Temporal Processing

Author

Shukla, Anuj and Bapi, Raju Surampudi

Subjects
Psychology, Cognition of Time, Perception, Psychophysics
Abstract

Several studies have reported that numerical magnitudes biases temporal judgments, i.e., large numerical magnitude, were perceived to last longer than small numerical magnitude. However, these predictions have been predominantly verified only when the large and small numerical magnitudes were presented in an intermixed fashion where numerical magnitudes varied randomly from trial to trial. We conducted two experiments (Blocked-magnitude and Mixed-Magnitude) using a temporal bisection paradigm to investigate whether numerical context affects temporal processing in a sub-second timescale. The numbers were presented with varying durations. Participants were asked to judge whether the presented durations were shorter or longer. The results suggest that the temporal judgments were affected when small and large numbers were randomly presented in an intermixed manner. However, such effects disappeared when the number magnitudes were presented separately. These results indicate the modulation of attention in number-time interaction, and such crosstalk may not require a generalized magnitude system.

Published
2022

12. Coverage Analysis of a Thinned LiFi Optical Attocell Network

Author

Surampudi, Atchutananda

Subjects
Computer Science - Information Theory, Electrical Engineering and Systems Science - Signal Processing
Abstract

This work analyzes coverage in the downlink of a thinned LiFi attocell network of deterministically arranged LEDs. The network is thinned by a Bernoulli probability p over all the LEDs to decide whether each one of them acts as a LiFi source or not. Then we use the series approximation approach used in [1] to obtain closed form expressions for the probability of coverage in such thinned LiFi attocell networks and validate them using numerical simulations.

Published
2020

13. Analyzing Optical TDMA to Mitigate Interference in Downlink LiFi Optical Attocell Networks

Author

Surampudi, Atchutananda

Subjects
Computer Science - Information Theory, Electrical Engineering and Systems Science - Signal Processing
Abstract

Co-channel interference in the downlink of LiFi attocell networks significantly decreases the network performance in terms of rate. Analysis of multiple access schemes is essential to mitigate interference and improve rate. The light emitting diodes (LEDs) being centrally monitored, the time division multiple access (TDMA) scheme over the LEDs will be suitable to analyze. This work considers the interference characterization in [1] over M-PAM modulated signals to derive an exact expression for the goodput G of the time scheduled attocell network, which is arranged as a deterministic square lattice in two dimensions. Given this TDMA over the LEDs, numerical simulations show that the LEDs can be optimally time scheduled to maximize the goodput, which implies that the TDMA mitigates interference in an attocell network compared to the case when the LEDs are unscheduled.

Published
2020

14. The Impact of Obesity on SARS-CoV-2 Pandemic Mortality Risk.

Author

Li, Zhaoping, Surampudi, Vijaya, and Heber, David

Subjects
Humans, Obesity, Risk Assessment, Pandemics, COVID-19, SARS-CoV-2, ACE2, coronavirus, obesity, thrombosis, Lung, Prevention, Emerging Infectious Diseases, Pneumonia & Influenza, Nutrition, Biodefense, Infectious Diseases, Vaccine Related, 2.1 Biological and endogenous factors, Infection, Food Sciences, Nutrition and Dietetics
Abstract

The COVID-19 pandemic has uncovered the increased susceptibility of individuals with obesity to infection and severe disease leading to hospitalization and death. Studies in New York City demonstrated that after advanced age, obesity was the most common risk factor leading to severe disease and death from COVID-19. While the connection has been recognized, there has not been a general recognition of the potential mechanisms for this link between excess body fat and mortality from this viral pandemic including respiratory complications and sequelae of increased activation of the immune system. Despite plans for vaccination of the global population, the risk community spread of COVID-19 and future pandemics will be linked in part to obesity and immunity. This review will detail a number of potential mechanisms through which obesity may contribute to the lethality of this viral infection. These insights will hopefully lead to a greater emphasis on obesity prevention and treatment as part of the global response to this and future pandemic threats.

Published
2021

15. Relation between Retinopathy and Progression of Coronary Artery Calcium in Individuals with Versus Without Diabetes Mellitus (From the Multi-Ethnic Study of Atherosclerosis).

Author

Khazai, Bahram, Adabifirouzjaei, Fatemeh, Guo, Mengye, Ipp, Eli, Klein, Ronald, Klein, Barbara, Cotch, Mary, Wong, Tien, Swerdloff, Ronald, Wang, Christina, Surampudi, Prasanth, Kaufman, Joel, Park, Claire, Hendel, Robert, and Budoff, Matthew

Subjects
Case-Control Studies, Coronary Artery Disease, Coronary Disease, Diabetes Mellitus, Diabetic Retinopathy, Disease Progression, Female, Humans, Incidence, Male, Middle Aged, Retinal Diseases, Retinal Vessels, United States, Vascular Calcification
Abstract

Retinopathy is a microvascular complication of diabetes mellitus (DM); however, it is also increasingly recognized in persons without DM. The microvascular diseases may play a prominent role in coronary heart disease (CHD) development in individuals with DM. We performed the study to evaluate the relation between non-DM retinopathy and CHD and also the association between baseline retinopathy and incidence and progression of CHD in individuals with and without DM. We included 5709 subjects with and without DM from the Multi-Ethnic Study of Atherosclerosis, who had retinal photos and coronary artery calcium score (CACS) available. We studied the association between baseline retinopathy and incidence and progression of coronary artery calcification (CAC) in subjects with and without DM. In DM group, the presence of retinopathy was significantly associated with an increased rate of CAC (RR 1.3 (95% CI [1.02, 1.66]) after adjusting for age, sex, race, follow-up time, and CHD risk factors. In non-DM group, the presence of retinopathy was not significantly associated with increased risk of CAC, however, the interaction between presence of retinopathy and DM status was not statistically significant. Within the DM group with CAC present at baseline, the presence of retinopathy was significantly associated with greater CAC progression (113 Agatson units (AU) greater, (95% CI [51-174]). In the non-DM group with present CAC at baseline; the presence of retinopathy was associated with 24 (95% CI [-0.69, 48.76]) AU higher CAC progression. All findings were adjusted for CHD risk factors. In conclusion, after adjustment for major CHD risk factors, retinopathy was associated with progression of CAC in both DM and non-DM individuals. However, the association was stronger in those with DM.

Published
2021

16. Association of a Self-Paid Medically Supervised Weight Management Program with Reversal of Obesity-Associated Impaired Fasting Glucose.

Author

Surampudi, Vijaya, Zhou, Xinkai, Tseng, Chi-Hong, Heber, David, and Li, Zhaoping

Subjects
impaired fasting glucose, obesity, personalized weight management, prediabetes, weight loss, Nutrition, Clinical Research, Prevention, Obesity, Diabetes, Metabolic and endocrine
Abstract

AimsThe progression of prediabetes to T2DM can be delayed through diet modification and weight management. However, the intensive lifestyle program is often not covered by medical insurance. This retrospective analysis evaluates the association of a patient self-paid weight management program on an improvement of blood sugar in overweight and obese patients with impaired fasting glucose (IFG).MethodsThe medical records of 4634 patients who participated in the self-pay UCLA Weight Management Program were reviewed and 2572 patients met the criteria for this retrospective analysis to examine whether this program was associated with the reversal of IFG over 3 months among 1396 patients with normal fasting glucose (NFG) and 1176 with IFG.ResultsThe patients with IFG lost comparable amounts of weight (10.5 ± 1.3 kg) at three months, as did the subjects with NFG (10.1 ± 1.3 kg). Fasting blood glucose in the IFG group decreased from 108.49 ± 6.4 to 101.8 ± 9.41 mg/dL (p < 0.0001) after three months. There were also significant reductions in triglycerides, and both systolic and diastolic blood pressure in both groups in association with weight loss.ConclusionOur medically supervised self-pay multidisciplinary weight management program was associated with reduced fasting blood glucose levels in patients with IFG over three months with comparable weight loss to patients with NFG.

Published
2021

17. The IL-27 component EBI-3 and its receptor subunit IL-27Rα are essential for the cytoprotective action of humanin on male germ cells†

Author

Jia, Yue, Swerdloff, Ronald S, Lue, YanHe, Dai-Ju, Jenny, Surampudi, Prasanth, Cohen, Pinchas, and Wang, Christina

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Contraception/Reproduction, Urologic Diseases, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Generic health relevance, Adult Germline Stem Cells, Animals, Antibodies, Neutralizing, Apoptosis, Gene Expression Regulation, Hot Temperature, Immunoglobulin Fc Fragments, Immunoglobulin G, Interleukins, Intracellular Signaling Peptides and Proteins, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Minor Histocompatibility Antigens, Receptors, Cytokine, Receptors, Interleukin, STAT3 Transcription Factor, humanin, spermatogenesis, apoptosis, EBI-3, IL-27R alpha, STAT3, humanin-receptor, signal transduction, mouse, IL-27Rα, Medical and Health Sciences, Obstetrics & Reproductive Medicine, Animal production, Zoology, Reproductive medicine
Abstract

Humanin (HN) is a mitochondrial-derived peptide that protects many cells/tissues from damage. We previously demonstrated that HN reduces stress-induced male germ cell apoptosis in rodents. HN action in neuronal cells is mediated through its binding to a trimeric cell membrane receptor composed of glycoprotein 130 (gp130), IL-27 receptor subunit (IL-27R, also known as WSX-1/TCCR), and ciliary neurotrophic factor receptor subunit (CNTFR). The mechanisms of HN action in testis remain unclear. We demonstrated in ex-vivo seminiferous tubules culture that HN prevented heat-induced germ cell apoptosis was blocked by specific anti-IL-27R, anti-gp130, and anti-EBI-3, but not by anti-CNTFR antibodies significantly. The cytoprotective action of HN was studied by using groups of il-27r-/- or ebi-3-/- mice administered the following treatment: (1) vehicle; (2) a single intraperitoneal (IP) injection of HN peptide; (3) testicular hyperthermia; and (4) testicular hyperthermia plus HN. We demonstrated that HN inhibited heat-induced germ cell apoptosis in wildtype but not in il-27r-/- or ebi-3-/- mice. HN restored heat-suppressed STAT3 phosphorylation in wildtype but not il-27r-/- or ebi-3-/- mice. Dot blot analyses showed the direct interaction of HN with IL-27R or EBI-3 peptide. Immunofluorescence staining showed the co-localization of IL-27R with HN and gp130 in Leydig cells and germ cells. We conclude that the anti-apoptotic effects of HN in mouse testes are mediated through interaction with EBI-3, IL-27R, and activation of gp130, whereas the role of CNTFR needs further studies. This suggests a multicomponent tissue-specific receptor for HN in the testis and links HN action with the IL-12/IL-27 family of cytokines.

Published
2021

18. Meal Timing and Glycemic Control during Pregnancy—Is There a Link?

Author

Zhu, Shengjie, Surampudi, Prasanth, Field, Nancy T, and Chondronikola, Maria

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Nutrition, Prevention, Women's Health, Pregnancy, Diabetes, Perinatal Period - Conditions Originating in Perinatal Period, Pediatric, Obesity, Metabolic and endocrine, Reproductive health and childbirth, Carbohydrate Metabolism, Energy Metabolism, Fasting, Female, Glucose, Glycemic Control, Humans, Meals, glucose metabolism, time-restricted eating, intermittent fasting, gestation, gestation diabetes mellitus, hormones, Food Sciences, Nutrition and Dietetics, Clinical sciences, Nutrition and dietetics, Public health
Abstract

Hyperglycemia during pregnancy and gestational diabetes mellitus (GDM) constitute an important public health problem due to their prevalence and long-term health consequences both for the mother and offspring. Results from studies in rodents and some clinical investigations suggest that meal time manipulation may be a potential lifestyle approach against conditions involving perturbations in glucose homeostasis (e.g., hyperglycemia, insulin resistance, diabetes, etc.). The purpose of this review is to summarize and critically evaluate the current literature on the role of meal timing and daily nutrient distribution on glycemic control during pregnancy. Only a small number of mostly observational studies have assessed the role of meal timing in glucose homeostasis during pregnancy. Food consumption earlier in the day and short-term fasting with adequate nutrient intake may improve glycemic control during the second and third trimester of gestation. Considering that the field of chrononutrition is still in its infancy and many questions remain unanswered, future prospective and carefully designed studies are needed to better understand the role of meal timing in metabolic homeostasis and maternal and fetal health outcomes during pregnancy.

Published
2021

19. Effect of Standardized Grape Powder Consumption on the Gut Microbiome of Healthy Subjects: A Pilot Study

Author

Yang, Jieping, Kurnia, Patrick, Henning, Susanne M, Lee, Rupo, Huang, Jianjun, Garcia, Michael C, Surampudi, Vijaya, Heber, David, and Li, Zhaoping

Subjects
Nutrition, Clinical Research, Complementary and Integrative Health, Adult, Akkermansia, Bifidobacterium, Bile Acids and Salts, Cholesterol, Female, Gastrointestinal Microbiome, Healthy Volunteers, Humans, Male, Middle Aged, Pilot Projects, Plant Extracts, Polyphenols, Powders, Triglycerides, Verrucomicrobia, Vitis, Young Adult, grape powder, gut microbiome, cholesterol, bile acids, healthy adults, Food Sciences, Nutrition and Dietetics
Abstract

Grapes provide a rich source of polyphenols and fibers. This study aimed to evaluate the effect of the daily consumption of 46 g of whole grape powder, providing the equivalent of two servings of California table grapes, on the gut microbiome and cholesterol/bile acid metabolism in healthy adults. This study included a 4-week standardization to a low-polyphenol diet, followed by 4 weeks of 46 g of grape powder consumption while continuing the low-polyphenol diet. Compared to the baseline, 4 weeks of grape powder consumption significantly increased the alpha diversity index of the gut microbiome. There was a trend of increasing Verrucomicrobia (p = 0.052) at the phylum level, and a significant increase in Akkermansia was noted. In addition, there was an increase in Flavonifractor and Lachnospiraceae_UCG-010, but a decrease in Bifidobacterium and Dialister at the genus level. Grape powder consumption significantly decreased the total cholesterol by 6.1% and HDL cholesterol by 7.6%. There was also a trend of decreasing LDL cholesterol by 5.9%, and decreasing total bile acid by 40.9%. Blood triglyceride levels and body composition were not changed by grape powder consumption. In conclusion, grape powder consumption significantly modified the gut microbiome and cholesterol/bile acid metabolism.

Published
2021

20. Gynecomastia and hypertension in a patient treated with posaconazole

Author

Thompson, George R, Surampudi, Prasanth N, and Odermatt, Alex

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, 11beta-hydroxylase, adverse drug effect, estradiol, gynecomastia, hypertension, hypokalemia, posaconazole, 11beta‐hydroxylase, Agricultural, veterinary and food sciences, Biomedical and clinical sciences, Health sciences
Abstract

Posaconazole therapy may lead to increased serum estradiol levels and development of gynecomastia. Early detection by endocrine hormone measurements may help preventing gynecomastia.

Published
2020

21. Intermittent fasting as a nutrition approach against obesity and metabolic disease.

Author

Zhu, Shengjie, Surampudi, Prasanth, Rosharavan, Baback, and Chondronikola, Maria

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Prevention, Obesity, Nutrition, Oral and gastrointestinal, Cardiovascular, Metabolic and endocrine, Stroke, Caloric Restriction, Fasting, Humans, Metabolic Diseases, Weight Loss, alternate day fasting, glucose, insulin, lipids, time-restricted eating, Medical and Health Sciences, Nutrition & Dietetics, Clinical sciences, Medical biochemistry and metabolomics, Nutrition and dietetics
Abstract

Purpose of reviewIntermittent fasting has been proposed as a potential nutrition approach against obesity and metabolic disease. Although data from studies in rodents convincingly support the antiobesity and cardiometabolic benefits of intermittent fasting, its effects in human health are still debatable.Recent findingsRecent studies have examined the effect of two intermittent fasting approaches, that is, alternate day fasting (ADF) and time-restricted eating (TRE), on weight loss and cardiometabolic risk factors. ADF seems to be an equally effective weight loss approach to caloric restriction, but adherence to ADF is more challenging. ADF improves cardiometabolic risk factors, whereas it may have superior metabolic benefits compared to caloric restriction in people with insulin resistance. TRE with ad libitum food intake is well tolerated and induces 2-4% weight loss in approximatively 3 months. Additionally, TRE may have metabolic benefits particularly in people with metabolically abnormal obesity even without weight loss.SummaryIntermittent fasting is a promising nutritional approach against obesity and its related metabolic diseases. Further research is needed to: i) establish the long-term effectiveness of TRE in weight loss and metabolic health, ii) improve the long-term adherence to ADF and investigate its weight loss independent effects in metabolic health, and iii) determine the mechanisms underlying the potential cardiometabolic benefits of intermittent fasting in humans.

Published
2020

22. Weight loss for critical care patient to improve lung transplantation candidacy: A case report

Author

Garcia, Michael C, Surampudi, Vijaya, Li, Zhaoping, Saggar, Rajan, and Shah, Sapna

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Research, Nutrition, Lung, Obesity, Rare Diseases, Transplantation, Evaluation of treatments and therapeutic interventions, 6.7 Physical, Respiratory, Good Health and Well Being, Lung transplantation, Weight loss, Survival, BMI, body mass index, ICU, Intensive care unit, MVLCD, modified very low calorie diet, kcal, kilocalorie, kg, kilogram, Cardiovascular medicine and haematology
Abstract

A 47-year-old male with morbid obesity and progressive pulmonary fibrosis was admitted to the intensive care unit (ICU) with worsening hypoxia and nocturnal ventilator dependence. Due to a significant oxygen requirement, the patient could only safely remain in an acute care setting. Unfortunately, he was not eligible for lung transplantation due to having obesity, a relative contraindication to lung transplantation due to potential for post transplantation complications and increased mortality. Therefore, we treated the patient with a modified very low calorie diet (MVLCD) to achieve weight loss. He had successful, sustained weight loss over a period of seven weeks and reached a target weight that made him eligible for transplantation. He subsequently underwent successful bilateral lung transplantation. The patient had improved metabolic parameters and no side effects attributable to the reduced calorie diet. This report shows that in patients with end stage lung disease and a poor prognosis without transplantation, inpatient weight loss is safe and may allow for potentially lifesaving lung transplantation.

Published
2020

23. Flood Depth Estimation in Agricultural Lands From L and C-Band Synthetic Aperture Radar Images and Digital Elevation Model

Author

Samvedya Surampudi and Vijay Kumar

Subjects
DEM statistical analysis, flood depth, SAR, water surface levels wavelet fusion, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract

Flood depth is one of the important attributes in damage assessment especially in areas where agro-based activities takes place. Assessing impacted region turns out to be exceptionally difficult in the case of low-lying catchments with arable lands, which inundates due to extreme precipitation and flood modelling becomes impossible. Under these circumstances, SAR derived flood maps are valuable in removing different constraints related to flood modelling with high degree of profundity. Depth estimation from non-contact based methods requires, flood boundary as a primary input. However, detecting flood depth in emerging vegetation poses a complex challenge in terms of boundary estimation due to composite signatures that are manifested on SAR data. In this paper, a new approach is proposed to extract flood boundaries by fusing SAR data of two different frequencies, which are sensitive to water level changes. In the first step, wavelet fusion is applied to combine L- and C- band SAR data followed by Otsu’s segmentation method to extract varying levels of flood boundaries. In the second step, SRTM Digital Elevation Model (DEM) with 30m horizontal resolution is used on each boundary for statistical analysis based on which water surface levels are extracted. In the final step, depth levels are calculated from the water surface elevation and DEM. Floodwater Depth Estimation tool (FwDET) derived depth measurements are used to calibrate the statistical thresholds for derived flood depths. The study carried out on 2016 Assam flood event shows maximum flood depth of 1.56 meters in the selected study area and the results are verified with evidence-based ground truth collections which showed RMSE error of 0.25 meters from the measured values.

Published
2023
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24. Towards building AI Life-coach agent for honing creativity

Author

Dasaka, Amarnath, S., Preeti, and Surampudi, Bapiraju

Abstract

World Economic Forum report predicts that 35% of the skills needed to navigate the world of work will have changed by2020. By 2020, creativity will be the third most sought-after skill, behind complex problem solving and critical thinking.Creative skills are future-proof, in that they cannot be Automated. Art and creativity are essentially what makes us humanand this is being backed up by research. (Elaine Rumbol) How do you hone creativity? This seems to be an open question.The present study aims to build an architecture for AI agent(life-coach) that incorporates the latest research on creativityand guides the user based on the users personality traits, context, emotions, mood and cognitive load. The agent will detectthe users emotional valance & Motivational Intensity which in turn will influence the attention focus (Broaden the mind(for free floating ideas) or result in narrow focus (linear, step by step goal attainment)). Toward this aim, we plan to run aseries of tests for gathering user feedback. Design of the tests are underway.

Published
2019

25. Can Balloons Produce Li-Fi? A Disaster Management Perspective

Author

Surampudi, Atchutananda, Chapalgaonkar, Sankalp Shirish, and Arumugam, Paventhan

Subjects
Computer Science - Information Theory, Computer Science - Networking and Internet Architecture
Abstract

Natural calamities and disasters disrupt the conventional communication setups and the wireless bandwidth becomes constrained. A safe and cost-effective solution for communication and data access in such scenarios is long needed. Light-Fidelity (Li-Fi) which promises wireless access to data at high speeds using visible light can be a good option. Visible light being safe to use for wireless access in such affected environments also provides illumination. Importantly, when a Li-Fi unit is attached to an air balloon and a network of such Li-Fi balloons are coordinated to form a Li-Fi balloon network, data can be accessed anytime and anywhere required and hence many lives can be tracked and saved. We propose this idea of a Li-Fi balloon and give an overview of its design using the Philips Li-Fi hardware. Further, we propose the concept of a balloon network and coin it with an acronym, the LiBNet. We consider the balloons to be arranged as a homogeneous Poisson point process in the LiBNet and we derive the mean co-channel interference for such an arrangement., Comment: To be presented as a poster at the IEEE Global Li-Fi Congress 2018

Published
2017

26. Interference Characterization in Downlink Li-Fi Optical Attocell Networks

Author

Surampudi, Atchutananda and Ganti, Radha Krishna

Subjects
Computer Science - Information Theory
Abstract

Wireless access to data using visible light, popularly known as light-fidelity (Li-Fi), is one of the key emerging technologies which promises huge bandwidths and data rates. In Li-Fi, the data is modulated on optical intensities and transmitted and detected using light-emitting-diodes (LED) and photodiodes respectively. A network of such LED access points illuminates a given region in the form of attocells. Akin, to wireless networks, co-channel interference or simply interference is a major impediment in Li-Fi attocell networks. Also, when in such networks, the field-of-view (FOV) of a photodiode is limited, the network interference distribution gets affected significantly. So, for any given network scenario, interference characterization is critical for good system design. Currently, there are no good closed-form approximations to interference in Li-Fi attocell networks, that can be used for the analysis of signal-to-interference-plus-noise-ratio (or coverage), particularly for the case of limited FOVs. In this paper, using a technique from Fourier analysis, we provide a very close approximation to interference in one and two dimension Li-Fi attocell networks for any given finite inter-LED separation. We validate the interference approximation by providing theoretical error bounds using asymptotics and by performing numerical simulations. We show that our method of approximation can be extended to characterize interference in limited FOV scenarios as well., Comment: Submitted to the IEEE/OSA Journal of Lightwave Technology

Published
2017
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27. An Energy Efficient Spectrum Sensing in Cognitive Radio Wireless Sensor Networks

Author

Surampudi, Atchutananda and Kalimuthu, Krishnamoorthy

Subjects
Computer Science - Information Theory
Abstract

The cognitive radio wireless sensor networks have become an integral part of communicating spectrum information to the fusion center, in a cooperative spectrum sensing environment. A group of battery operated sensors or nodes, sensing information about spectrum availability in the radio links, needs an energy efficient strategy to pass on the binary information. A proper routing method through intelligent decision making can be a good solution. In this paper, an energy efficient routing protocol has been introduced and a performance comparison is made with the existing system in terms of its energy consumption. The proposed routing technique considers both uniform and non-uniform clustering strategies and proves to be an energy efficient method of communication.

Published
2017

28. Liquid Crystals for Luminescent Concentrators: A Review

Author

Atchutananda Surampudi, Guanxiong Zhang, Ravinder Singh, Grahame Faulkner, Dominic C. O’Brien, Martin J. Booth, and Stephen M. Morris

Subjects
liquid crystals, luminescent concentrators, guest–host systems, cholesteric reflectors, Crystallography, QD901-999
Abstract

Luminescent optical concentrators are thin films containing fluorescent dyes that enable light collection over a wide field of view without the need to track the path of the Sun. However, a disadvantage when using luminescent concentrators is that the performance is often impeded by surface losses through these films. Liquid-crystal (LC) hosts are attractive for luminescent concentrators, as they impart, at the very least, an orientational ordering to the transition dipole moment of the dyes dispersed within these films. This enables the directivity of both the absorption and emission and can reduce surface losses by, for example, adopting the homeotropic alignment of the LC director. This article reviews the developments and applications of LCs to luminescent optical concentrators and describes the strategies that have been introduced to further combat losses by decoupling the absorption and emission processes through Förster energy transfer, the approaches employed to enhance the chemical structures of the dyes, and the methods of using alternative LC phases and external configurations. The review presents a comprehensive summary of the material combinations and the techniques that have been considered in the development of LC-based concentrator films and concludes with a discussion about the future perspectives for these exciting optical concentrators.

Published
2023
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29. Creating an affordable ,effective, adaptive & personalized attention tasks for children with developmental disorders.

Author

Dasaka, Amarnath and Surampudi, Bapiraju

Abstract

The main challenge in studying cognition & designing effective tasks for children with learning disorders is creatingpersonalized & adaptive tasks in line with the current abilities & mood of the child. The current study confronts thischallenge by testing a new paradigm to access the current state of mind and adapting the tasks based on the current mood& abilities of the child. Children were given chess puzzles with various levels of difficulty (from just identifying thepieces, legal moves and eventually even capturing pieces with depth=1). while the children were performing the tasks thepupil-metric data (for cognitive load), facial expressions and the head pose were used to gauge the current-state and adaptthe puzzles accordingly. Further development of dynamic feedback and providing rewards for looking at the right squaresare also underway. custom software with off the shelf web-cameras were used as the current solutions in the market areprohibitively expensive for testing on large scale.

Published
2018

30. Ayu-Characterization of healthy aging from neuroimaging data with deep learning and rsfMRI

Author

Kushal Borkar, Anusha Chaturvedi, P. K. Vinod, and Raju Surampudi Bapi

Subjects
rs-fMRI, attention, static functional connectivity matrix, age estimation, interpretability, classification, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Estimating brain age and establishing functional biomarkers that are prescient of cognitive declines resulting from aging and different neurological diseases are still open research problems. Functional measures such as functional connectivity are gaining interest as potentially more subtle markers of neurodegeneration. However, brain functions are also affected by “normal” brain aging. More information is needed on how functional connectivity relates to aging, particularly in the absence of neurodegenerative disorders. Resting-state fMRI enables us to investigate functional brain networks and can potentially help us understand the processes of development as well as aging in terms of how functional connectivity (FC) matures during the early years and declines during the late years. We propose models for estimation of the chronological age of a healthy person from the resting state brain activation (rsfMRI). In this work, we utilized a dataset (N = 638, age-range 20–88) comprising rsfMRI images from the Cambridge Centre for Aging and Neuroscience (Cam-CAN) repository of a healthy population. We propose an age prediction pipeline Ayu which consists of data preprocessing, feature selection, and an attention-based model for deep learning architecture for brain age assessment. We extracted features from the static functional connectivity (sFC) to predict the subject's age and classified them into different age groups (young, middle, middle, and old ages). To the best of our knowledge, a classification accuracy of 72.619 % and a mean absolute error of 6.797, and an r2 of 0.754 reported by our Ayu pipeline establish competitive benchmark results as compared to the state-of-the-art-approach. Furthermore, it is vital to identify how different functional regions of the brain are correlated. We also analyzed how functional regions contribute differently across ages by applying attention-based networks and integrated gradients. We obtained well-known resting-state networks using the attention model, which maps to within the default mode network, visual network, ventral attention network, limbic network, frontoparietal network, and somatosensory network connected to aging. Our analysis of fMRI data in healthy elderly Age groups revealed that dynamic FC tends to slow down and becomes less complex and more random with increasing age.

Published
2022
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31. Association of a Self-Paid Medically Supervised Weight Management Program with Reversal of Obesity-Associated Impaired Fasting Glucose

Author

Vijaya Surampudi, Xinkai Zhou, Chi-Hong Tseng, David Heber, and Zhaoping Li

Subjects
obesity, impaired fasting glucose, prediabetes, weight loss, personalized weight management, Medicine (General), R5-920
Abstract

Aims: The progression of prediabetes to T2DM can be delayed through diet modification and weight management. However, the intensive lifestyle program is often not covered by medical insurance. This retrospective analysis evaluates the association of a patient self-paid weight management program on an improvement of blood sugar in overweight and obese patients with impaired fasting glucose (IFG). Methods: The medical records of 4634 patients who participated in the self-pay UCLA Weight Management Program were reviewed and 2572 patients met the criteria for this retrospective analysis to examine whether this program was associated with the reversal of IFG over 3 months among 1396 patients with normal fasting glucose (NFG) and 1176 with IFG. Results: The patients with IFG lost comparable amounts of weight (10.5 ± 1.3 kg) at three months, as did the subjects with NFG (10.1 ± 1.3 kg). Fasting blood glucose in the IFG group decreased from 108.49 ± 6.4 to 101.8 ± 9.41 mg/dL (p < 0.0001) after three months. There were also significant reductions in triglycerides, and both systolic and diastolic blood pressure in both groups in association with weight loss. Conclusion: Our medically supervised self-pay multidisciplinary weight management program was associated with reduced fasting blood glucose levels in patients with IFG over three months with comparable weight loss to patients with NFG.

Published
2021
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33. Gynecomastia and hypertension in a patient treated with posaconazole

Author

George R. Thompson III, Prasanth N. Surampudi, and Alex Odermatt

Subjects
11beta‐hydroxylase, adverse drug effect, estradiol, gynecomastia, hypertension, hypokalemia, Medicine, Medicine (General), R5-920
Abstract

Abstract Posaconazole therapy may lead to increased serum estradiol levels and development of gynecomastia. Early detection by endocrine hormone measurements may help preventing gynecomastia.

Published
2020
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35. Humanin protects against chemotherapy‐induced stage‐specific male germ cell apoptosis in rats

Author

Surampudi, P, Chang, I, Lue, Y, Doumit, T, Jia, Y, Atienza, V, Liu, PY, Swerdloff, RS, and Wang, C

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Rare Diseases, Brain Disorders, Pediatric, Cancer, Underpinning research, 1.1 Normal biological development and functioning, Animals, Apoptosis, Apoptosis Regulatory Proteins, Cyclophosphamide, Intracellular Signaling Peptides and Proteins, Ketoconazole, Leydig Cells, Male, Mesylates, Rats, Rats, Sprague-Dawley, Spermatozoa, Testosterone, cyclophosphamide, ethane dimethanesulfonate, germ cell apoptosis, humanin, ketoconazole, Leydig cells, Genetics, Clinical Sciences, Paediatrics and Reproductive Medicine, Clinical sciences, Reproductive medicine
Abstract

Humanin (HN) has cytoprotective action on male germ cells after testicular stress induced by heat and hormonal deprivation. To examine whether HN has protective effects on chemotherapy-induced male germ cell apoptosis, we treated four groups of adult rats with (i) vehicle (control), (ii) HN, (iii) cyclophosphamide (CP); or (iv) HN+CP. To investigate whether the protective effects of HN on germ cells require the presence of Leydig cells, another four groups of rats were pre-treated with ethane dimethanesulfonate (EDS), a Leydig cell toxicant, to eliminate Leydig cells. After 3 days, when Leydig cells were depleted by EDS, we administered: (i) vehicle, (ii) HN, (iii) CP; or (iv) HN+CP to rats. All rats were killed 12 h after the injection of HN and/or CP. Germ cell apoptosis was detected by TUNEL assay and quantified by numerical count. Compared with control and HN (alone), CP significantly increased germ cell apoptosis; HN +CP significantly reduced CP-induced apoptosis at early (I-VI) and late stages (IX-XIV) but not at middle stages (VII-VIII) of the seminiferous epithelial cycle. Pre-treatment with EDS markedly suppressed serum and intratesticular testosterone (T) levels, and significantly increased germ cell apoptosis at the middle (VII-VIII) stages. CP did not further increase germ cell apoptosis in the EDS-pre-treated rats. HN significantly attenuated germ cell apoptosis at the middle stages in EDS pre-treated rats. To investigate whether HN has any direct effects on Leydig cell function, adult Leydig cells were isolated and treated with ketoconazole (KTZ) to block testosterone synthesis. HN was not effective in preventing the reduction of T production by KTZ in vitro. We conclude that HN decreases CP and/or EDS-induced germ cell apoptosis in a stage-specific fashion. HN acts directly on germ cells to protect against EDS-induced apoptosis in the absence of Leydig cells and intratesticular testosterone levels are very low.

Published
2015

36. Effects of Meditation on Structural Changes of the Brain in Patients With Mild Cognitive Impairment or Alzheimer’s Disease Dementia

Author

Madhukar Dwivedi, Neha Dubey, Aditya Jain Pansari, Raju Surampudi Bapi, Meghoranjani Das, Maushumi Guha, Rahul Banerjee, Gobinda Pramanick, Jayanti Basu, and Amitabha Ghosh

Subjects
meditation, mild cognitive impairment, Alzheimer’s disease, cortical thickness, gray matter volume, imaging, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Previous cross-sectional studies reported positive effects of meditation on the brain areas related to attention and executive function in the healthy elderly population. Effects of long-term regular meditation in persons with mild cognitive impairment (MCI) and Alzheimer’s disease dementia (AD) have rarely been studied. In this study, we explored changes in cortical thickness and gray matter volume in meditation-naïve persons with MCI or mild AD after long-term meditation intervention. MCI or mild AD patients underwent detailed clinical and neuropsychological assessment and were assigned into meditation or non-meditation groups. High resolution T1-weighted magnetic resonance images (MRI) were acquired at baseline and after 6 months. Longitudinal symmetrized percentage changes (SPC) in cortical thickness and gray matter volume were estimated. Left caudal middle frontal, left rostral middle frontal, left superior parietal, right lateral orbitofrontal, and right superior frontal cortices showed changes in both cortical thickness and gray matter volume; the left paracentral cortex showed changes in cortical thickness; the left lateral occipital, left superior frontal, left banks of the superior temporal sulcus (bankssts), and left medial orbitofrontal cortices showed changes in gray matter volume. All these areas exhibited significantly higher SPC values in meditators as compared to non-meditators. Conversely, the left lateral occipital, and right posterior cingulate cortices showed significantly lower SPC values for cortical thickness in the meditators. In hippocampal subfields analysis, we observed significantly higher SPC in gray matter volume of the left CA1, molecular layer HP, and CA3 with a trend for increased gray matter volume in most other areas. No significant changes were found for the hippocampal subfields in the right hemisphere. Analysis of the subcortical structures revealed significantly increased volume in the right thalamus in the meditation group. The results of the study point out that long-term meditation practice in persons with MCI or mild AD leads to salutary changes in cortical thickness and gray matter volumes. Most of these changes were observed in the brain areas related to executive control and memory that are prominently at risk in neurodegenerative diseases.

Published
2021
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37. Learning brain dynamics for decoding and predicting individual differences.

Author

Joyneel Misra, Srinivas Govinda Surampudi, Manasij Venkatesh, Chirag Limbachia, Joseph Jaja, and Luiz Pessoa

Subjects
Biology (General), QH301-705.5
Abstract

Insights from functional Magnetic Resonance Imaging (fMRI), as well as recordings of large numbers of neurons, reveal that many cognitive, emotional, and motor functions depend on the multivariate interactions of brain signals. To decode brain dynamics, we propose an architecture based on recurrent neural networks to uncover distributed spatiotemporal signatures. We demonstrate the potential of the approach using human fMRI data during movie-watching data and a continuous experimental paradigm. The model was able to learn spatiotemporal patterns that supported 15-way movie-clip classification (∼90%) at the level of brain regions, and binary classification of experimental conditions (∼60%) at the level of voxels. The model was also able to learn individual differences in measures of fluid intelligence and verbal IQ at levels comparable to that of existing techniques. We propose a dimensionality reduction approach that uncovers low-dimensional trajectories and captures essential informational (i.e., classification related) properties of brain dynamics. Finally, saliency maps and lesion analysis were employed to characterize brain-region/voxel importance, and uncovered how dynamic but consistent changes in fMRI activation influenced decoding performance. When applied at the level of voxels, our framework implements a dynamic version of multivariate pattern analysis. Our approach provides a framework for visualizing, analyzing, and discovering dynamic spatially distributed brain representations during naturalistic conditions.

Published
2021
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38. Mars Oxygen ISRU Experiment (MOXIE)

Author

Hecht, M., Hoffman, J., Rapp, D., McClean, J., SooHoo, J., Schaefer, R., Aboobaker, A., Mellstrom, J., Hartvigsen, J., Meyen, F., Hinterman, E., Voecks, G., Liu, A., Nasr, M., Lewis, J., Johnson, J., Guernsey, C., Swoboda, J., Eckert, C., Alcalde, C., Poirier, M., Khopkar, P., Elangovan, S., Madsen, M., Smith, P., Graves, C., Sanders, G., Araghi, K., de la Torre Juarez, M., Larsen, D., Agui, J., Burns, A., Lackner, K., Nielsen, R., Pike, T., Tata, B., Wilson, K., Brown, T., Disarro, T., Morris, R., Schaefer, R., Steinkraus, R., Surampudi, R., Werne, T., and Ponce, A.

Published
2021
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39. Weight loss for critical care patient to improve lung transplantation candidacy: A case report

Author

Michael C. Garcia, Vijaya Surampudi, Zhaoping Li, Rajan Saggar, and Sapna Shah

Subjects
Lung transplantation, Obesity, Weight loss, Survival, Diseases of the respiratory system, RC705-779
Abstract

A 47-year-old male with morbid obesity and progressive pulmonary fibrosis was admitted to the intensive care unit (ICU) with worsening hypoxia and nocturnal ventilator dependence. Due to a significant oxygen requirement, the patient could only safely remain in an acute care setting. Unfortunately, he was not eligible for lung transplantation due to having obesity, a relative contraindication to lung transplantation due to potential for post transplantation complications and increased mortality. Therefore, we treated the patient with a modified very low calorie diet (MVLCD) to achieve weight loss. He had successful, sustained weight loss over a period of seven weeks and reached a target weight that made him eligible for transplantation. He subsequently underwent successful bilateral lung transplantation. The patient had improved metabolic parameters and no side effects attributable to the reduced calorie diet. This report shows that in patients with end stage lung disease and a poor prognosis without transplantation, inpatient weight loss is safe and may allow for potentially lifesaving lung transplantation.

Published
2020
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40. A Comparative Study of Machine Learning Approaches for the Detection of SARS-CoV-2 and its Variants.

Author

Vesapogu, Praveen Kumar and Surampudi, Bapi Raju

Subjects
SARS-CoV-2, MACHINE learning, COVID-19, WHOLE genome sequencing, CORONAVIRUSES
Abstract

The coronavirus disease (COVID-19) caused over 170 million illnesses and over 3 million deaths worldwide. Researchers from all over the world have been using a variety of machine-learning techniques to classify the DNA sequences of the SARS-CoV-2 virus. To classify SARS-CoV-2 (Covid-19) whole genome sequences with other viruses including Dengue, Ebola, Influenza, and also Coronaviruses that may infect humans and are members of the family of Coronaviridae like SARS-CoV, MERS-CoV, we have proposed a multi-dimensional frequency encoding scheme. In the proposed method each genome is converted into four frequency-encoded sequences for each nucleotide. Then each encoded sequence is partitioned into quartiles and fed to the CNN. The findings of the binary classification of SARS-CoV-2 with other viruses and multi-class classification of six different viruses using five well-known machine learning algorithms and the proposed approach using CNN were reported in this study. Furthermore, we applied machine learning methods for the multi-class classification of eight different SARS-CoV-2 variants. The proposed approach performed well among all machine-learning techniques for classifying genome sequences of viruses and SARS-CoV-2 variants with accuracy of 99% and 98% respectively. In addition, we have also compared the performance of our proposed approach with the existing methods from the literature. [ABSTRACT FROM AUTHOR]

Published
2024
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44. Severe Vitamin A Deficiency After Biliopancreatic Diversion

Author

Lauren M. Lemieux MD and Vijaya Surampudi MD

Subjects
Medicine (General), R5-920, Pathology, RB1-214
Abstract

Biliopancreatic diversion is a surgical procedure that causes weight loss via volume restriction and malabsorption. It is now rarely performed due to the risk of severe nutritional deficiencies including vitamin A. We report a case of severe vitamin A deficiency due to malabsorption from a biliopancreatic diversion procedure for weight loss. By the time the patient presented to our department, she had developed blindness refractory to parenteral vitamin A treatment. A unique feature of her case is the development of a rash with vitamin A injections. This reaction has only been reported in one case series of 3 patients in the published literature. Her case highlights the importance of vitamin deficiency screening in patients after bariatric surgery, and her skin reaction to the injections is a unique side effect that is not frequently observed.

Published
2019
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46. Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

Author

Zhou, Z, Jardine, M, Li, Q, Neuen, B, Cannon, C, De Zeeuw, D, Edwards, R, Levin, A, Mahaffey, K, Perkovic, V, Neal, B, Lindley, R, Guerrero, R, Aizenberg, D, Albisu, J, Alvarisqueta, A, Bartolacci, I, Berli, M, Bordonava, A, Calella, P, Cantero, M, Cartasegna, L, Cercos, E, Coloma, G, Colombo, H, Commendatore, V, Cuadrado, J, Cuneo, C, Cusumano, A, Douthat, W, Dran, R, Farias, E, Fernandez, M, Finkelstein, H, Fragale, G, Fretes, J, Garcia, N, Gastaldi, A, Gelersztein, E, Glenny, J, Gonzalez, J, Del Carmen Gonzalez Colaso, P, Goycoa, C, Greloni, G, Guinsburg, A, Hermida, S, Juncos, L, Klyver, M, Kraft, F, Krynski, F, Lanchiotti, P, De La Fuente, R, Marchetta, N, Mele, P, Nicolai, S, Novoa, P, Orio, S, Otreras, F, Oviedo, A, Raffaele, P, Resk, J, Rista, L, Papini, N, Sala, J, Santos, J, Schiavi, L, Sessa, H, Casabella, T, Ulla, M, Valdez, M, Vallejos, A, Villarino, A, Visco, V, Wassermann, A, Zaidman, C, Cheung, N, Droste, C, Fraser, I, Johnson, D, Mah, P, Nicholls, K, Packham, D, Proietto, J, Roberts, A, Roger, S, Tsang, V, Raduan, R, Da Costa, F, Amodeo, C, Turatti, L, Bregman, R, Sanches, F, Canani, L, Chacra, A, Borges, J, Vencio, S, Da Silva Franco, R, D'Avila, D, De Souza Portes, E, De Souza, P, Deboni, L, Filho, F, Neto, B, Gomes, M, Kohara, S, Keitel, E, Saraiva, J, Lisboa, H, De Carvalho Contieri, F, Milagres, R, Junior, R, De Brito, C, Hissa, M, Sabbag, A, Noronha, I, Panarotto, D, Filho, R, Pereira, M, Saporito, W, Scotton, A, Schuch, T, De Almeida, R, Ramos, C, Felicio, J, Thome, F, Hachmann, J, Yamada, S, Hayashida, C, Petry, T, Zanella, M, Andreeva, V, Angelova, A, Dimitrov, S, Genadieva, V, Genova-Hristova, G, Hristozov, K, Kamenov, Z, Koundurdjiev, A, Lozanov, L, Margaritov, V, Nonchev, B, Rangelov, R, Shinkov, A, Temelkova, M, Velichkova, E, Yakov, A, Aggarwal, N, Aronson, R, Bajaj, H, Cherney, D, Chouinard, G, Conway, J, Cournoyer, S, Daroza, G, De Serres, S, Dube, F, Goldenberg, R, Gupta, A, Gupta, M, Henein, S, Khandwala, H, Leiter, L, Madore, F, Mc-Mahon, A, Muirhead, N, Pichette, V, Rabasa-Lhoret, R, Steele, A, Tangri, N, Torshizi, A, Woo, V, Zalunardo, N, Montenegro, M, Jorquera, J, Farina, M, Gajardo, V, Vejar, M, Chen, N, Chen, Q, Gan, S, Kong, Y, Li, D, Li, W, Li, X, Lin, H, Liu, J, Lu, W, Mao, H, Ren, Y, Song, W, Sun, J, Sun, L, Tu, P, Wang, G, Yang, J, Yin, A, Yu, X, Zhao, M, Zheng, H, Mendoza, J, Arcos, E, Avendano, J, Ruiz, J, Ortiz, L, Gonzalez, A, Triana, E, Higuera, J, Malaver, N, De Salazar, D, Rosero, R, Lozano, M, Cometa, L, Valenzuela, A, Alonso, R, Villegas, I, Yupanqui, H, Bartaskova, D, Barton, P, Belobradkova, J, Dohnalova, L, Drasnar, T, Ferkl, R, Halciakova, K, Klokocnikova, V, Kovar, R, Lastuvka, J, Lukac, M, Pesickova, S, Peterka, K, Pumprla, J, Rychlik, I, Saudek, F, Tesar, V, Valis, M, Weiner, P, Zemek, S, Alamartine, E, Borot, S, Cariou, B, Dussol, B, Fauvel, J, Gourdy, P, Klein, A, Le Meur, Y, Penfornis, A, Roussel, R, Saulnier, P, Thervet, E, Zaoui, P, Burst, V, Faghih, M, Faulmann, G, Haller, H, Jerwan-Keim, R, Maxeiner, S, Paschen, B, Plassmann, G, Rose, L, Orellana, R, Haase, F, Diaz, J, Roca, L, Arenales, J, Polo, J, Juarez, E, Csecsei, G, Csiky, B, Danos, P, Deak, L, Dudas, M, Harcsa, E, Keltai, K, Keresztesi, S, Kiss, K, Konyves, L, Major, L, Mileder, M, Molnar, M, Mucsi, J, Oroszlan, T, Ory, I, Paragh, G, Peterfai, E, Petro, G, Revesz, K, Takacs, R, Vangel, S, Vasas, S, Zsom, M, Oomman, A, Raju, S, Dewan, D, Fernando, M, Gopalakrishnan, N, Gracious, N, Alva, H, Jain, D, Keshavamurthy, C, Khullar, D, Sahay, M, Peringat, J, Prasad, N, Rao, K, Reddy, S, Melemadathil, S, Sudhakar, B, Vyasam, R, Bonadonna, R, Castellino, P, Ceriello, A, Chiovato, L, De Cosmo, S, De Nicola, L, Derosa, G, Carlo, A, Cianni, G, Frasca, G, Fuiano, G, Gambaro, G, Garibotto, G, Giorda, C, Malberti, F, Mandreoli, M, Mannucci, E, Orsi, E, Piatti, P, Santoro, D, Sasso, F, Serviddio, G, Stella, A, Trevisan, R, Veronelli, A, Zanoli, L, Akiyama, H, Aoki, H, Asano, A, Iitsuka, T, Kajiyama, S, Kashine, S, Kawada, T, Kodera, T, Kono, H, Koyama, K, Kumeda, Y, Miyauchi, S, Mizuyama, K, Niiya, T, Oishi, H, Ota, S, Sakakibara, T, Takai, M, Tomonaga, O, Tsujimoto, M, Wada, T, Wakasugi, M, Wakida, Y, Watanabe, T, Yamada, M, Yanagida, K, Yanase, T, Yumita, W, Gaupsiene, E, Kozloviene, D, Navickas, A, Urbanaviciene, E, Ghani, R, Kadir, K, Ali, N, Yusof, M, Gan, C, Ismail, M, Kong, W, Lam, S, Lee, L, Lim, S, Loh, C, Manocha, A, Ng, K, Ahmad, N, Ratnasingam, V, Shudim, S, Vengadasalam, P, Munoz, L, Salazar, M, Cruz, J, Soto, M, Ramos, J, Wong, A, Rotter, J, Escalante, T, Sosa, F, Lozano, F, Cervera, L, Baron, P, Ballesteros, C, Rangel, J, Jimenez, L, Santana, S, Flores, F, Molina, H, Ceballos, R, Del Campo Blanco, B, Franco, G, Loza, O, Rocha, C, Vera, G, Castellanos, R, Calcaneo, J, Rosano, M, Pattzi, H, Guzman, J, Joerg, I, Sanchez, S, Mijangos, J, Sanson, P, Tamayo Y Orozco, J, Chavez, E, Cepeda, A, Carrillo, L, Mesa, J, Escobedo, R, Baker, J, Noonan, P, Scott, R, Walker, R, Watson, 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Y., Lim S. K., Loh C. L., Manocha A. B., Ng K. S., Ahmad N. N. F. N., Ratnasingam V., Shudim S. S. B., Vengadasalam P., Munoz L. D. A., Salazar M. A., Cruz J. B., Soto M. B., Ramos J. C., Wong A. C., Rotter J. R. C., Escalante T. D., Sosa F. E. E., Lozano F. F., Cervera L. F. F., Baron P. F., Ballesteros C. G., Rangel J. D. G., Jimenez L. E. H., Santana S. S. I., Flores F. J., Molina H. L., Ceballos R. I. L., Del Campo Blanco B. M., Franco G. M., Loza O. T. M., Rocha C. M., Vera G. O., Castellanos R. O., Calcaneo J. P., Rosano M. A. R., Pattzi H. R., Guzman J. R., Joerg I. E. R., Sanchez S. B. S., Mijangos J. H. S., Sanson P. S., Tamayo Y Orozco J. A., Chavez E. T., Cepeda A. V., Carrillo L. V., Mesa J. V., Escobedo R. Z., Baker J., Noonan P., Scott R., Walker R., Watson E., Williams M., Young S., Abejuela Z., Agra J., Aquitania G., Caringal C., Comia R. S., Santos L. D., Gomez O., Jimeno C., Santos F., Tan G., Tolentino M., Yao C., Yap Y. E., Ygpuara M. D. L., Bijata-Bronisz R., Hotlos L., Januszewicz A., Kaczmarek B., Kaminska A., Lazuka L., Madej A., Mazur S., Mlodawska-Choluj D., Nowicki M., Orlowska-Kowalik G., Popenda G., Rewerska B., Sowinski D., Angelescu L. M., Anghel V., Avram R. -I., Busegeanu M. -M., Cif A., Cosma D., Crisan C., Demian L. D., Ferariu I. E., Halmagyi I., Hancu N., Munteanu M., Negru D., Onaca A. G., Petrica L., Popa A. R., Ranetti A. -E., Serafinceanu C., Toarba C., Agafyina A., Barbarash O., Barysheva O., Chizhov D., Dobronravov V., Dreval A., Glinkina I., Grineva E., Khirmanov V., Kolmakova E., Koroleva T., Kvitkova L., Marasaev V., Mkrtumyan A., Morugova T., Nagibovich G., Nagibovich O., Nedogoda S., Osipova I., Raskina T., Samoylova Y., Sazonova O., Shamkhalova M., Shutemova E., Shwartz Y., Uriasyev O., Vorobyev S., Zateyshchikova A., Zateyshshikov D., Zykova T., Antic S., Djordjevic M., Kendereski A., Lalic K., Lalic N., Popovic-Radinovic V., Babikova J., Benusova O., Buganova I., Culak J., Dzupina A., Dzuponova J., Fulop P., Ilavska A., Martinka E., Ochodnicka Z., Pella D., Smatanova I., Ahmed F., Badat A., Breedt J., Distiller L., Govender V., Govender R., Joshi M., Jurgens J., Latiff G., Lombard L., Mookadam M., Ngcakani N., Nortje H., Oosthuizen H., Pillay-Ramaya L., Prozesky H., Reddy J., Rheeder P., Seeber M., Chae D. -W., Cho Y. M., Jeong I. -K., Kim S. G., Kim Y. H., Kwon H. -S., Kwon M. J., Lee B. -W., Lee J., Lee M. -K., Nam M. -S., Oh K. -H., Park C. -Y., Park S. -H., Yoon K. H., Garcia P. A., Mercadal L. A., Barrios C., Castro F. C., Guldris S. C., Lopez M. D., De Los Rios J. E., Fresnedo G. F., Serrano A. G., Garcia I., Martinez F. J. G., Gimeno J. E. J., Mendoza M. L., Marin T. M., Portillo C. M., Vila M. A. M., Torres M. M., Iglesias J. N., Perez J. P., Vera M. P., Perez J. M. P., Simon M. A. Q., Canonge R. S., Gonzalez A. S., Riera M. T., Madueno F. J. T., Plaza M. V., Chang C. -T., Chuang L. -M., Hsia T. -L., Hsieh C. -H., Hwang S. -J., Lin C. -C., Lu Y. -C., Sheu W. H. -H., Barna O., Bilyk S. D., Botsyurko V., Dudar I., Fushtey I., Godlevska O., Golovchenko O., Gyrina O., Kazmirchuk A., Kolesnyk M., Komisarenko I., Korzh O., Kravchun N., Legun O., Mankovskyy B., Martynyuk L., Mostovoy Y., Pashkovska N., Pererva L., Pertseva T., Samoylov O., Smirnov I., Svyshchenko Y., Tomashkevych H., Topchii I., Tryshchuk N., Tseluyko V., Vizir V., Vlasenko M., Zlova T., Zub L., Abusnana S., Railey M., Abouglila K., Ainsworth P., Ali Z., Arutchelvam V., Barnard M., Bellary S., Davies E., Davies M., Davies S., Dawson A., Kossi M. E., English P., Fraser D., Gnudi L., Gunstone A., Hall T., Hanif W., Jackson A., Johnson A., Joseph F., Krishnan S., Kumwenda M., MacDougall I., Nixon P., O'Hare J., Philip S., Ramtoola S., Saxena M., Sennik D., Simon G., Singh B., Stephens J., Strzelecka A., Symonds R., Turner W., Wahba M., Wakeling J., Wheeler D., Winocour P., Abdallah J., Abdullah R., Abramowitz M., Acosta I., Aiello J., Akright L., Akyea-Djamson A., Alappan R., Alicic R., Al-Karadsheh A., Allison D. C., Arauz-Pacheco C., Arfeen S., Arif A., Arvind M., Atray N., Awad A., Bakris G., Barnhill P., Barranco E., Barrera C., Beacom M., Behara V., Belo D., Bentley-Lewis R., Berenguer R., Bermudez L., Bernardo M., Biscoveanu M., Bowman-Stroud C., Brandon D., Brusco O., Busch R., Canaan Y., Chilito A., Christensen T., Christiano C., Christofides E., Chuateco C., Cohen K., Cohen R., Cohen-Stein D., Cook C., Coyne D., Daboul N., Darwish R., Daswani A., Deck K., Desouza C., Dev D., Dhillon M., Dua S., Eder F., Elosegui A. M., El-Shahawy M., Ervin J., Esquenazi A., Evans J., Fishbane S., Frias J., Galindo-Ramos E., Galphin C., Ghazi A., Gonzalez E., Gorson D., Gowda A., Greco B., Grubb S., Gulati R., Hammoud J., Handelsman S., Hartman I., Hershon K., Hiser D., Hon G., Jacob R., Jaime M., Jamal A., Kaupke C., Keightley G., Kern E., Khanna R., Khitan Z., Kim S., Kopyt N., Kovesdy C., Krishna G., Kropp J., Kumar A., Kumar J., Kumar N., Kusnir J., Lane W., Lawrence M., Lehrner L., Lentz J., Levinson D., Lewis D., Liss K., Maddux A., Maheshwari H., Mandayam S., Marar I., Mehta B., Middleton J., Mordujovich J., Moreda R., Moustafa M., Trenche S. M., Narayanan M., Narvarte J., Nassar T., Newman G., Nichol B., Nicol P., Nisnisan J., Nossuli A. K., Obialo C., Olelewe S., Oliver M., O'Shaughnessy A., Padron J., Pankhaniya R., Parker R., Patel D., Patel G., Patel N., Pavon H., Perez A., Perez C., Perlman A., Pettis K., Pharr W., Phillips A., Purighalla R., Quesada-Suarez L., Ranjan R., Rastogi S., Rendell M., Rich L., Robinson M., Rodriguez H., Rosas S., Saba F., Sankaram R., Sarin R., Schreiman R., Scott D., Sekkarie M., Sensenbrenner J., Shakeel M., Shanik M., Shaw S., Smith S., Solomon R., Sprague A., Spry L., Suchinda P., Sultan S., Surampudi P., Sussman S., Tan A., Terrelonge A., Thompson M., Trespalacios F., Trippe B., Trueba P., Twahirwa M., Updegrove J., Van Buren P., Vannorsdall M., Varghese F., Velasquez-Mieyer P., Ventrapragada S., Vukotic G., Wadud K., Warren M., Watson H., Watts R., Weiner D., Welker J., Welsh J., Williams S., and Zaniewski-Singh M.

Abstract

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect

Published
2021

47. Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

Author

Zhou Z., Jardine M. J., Li Q., Neuen B. L., Cannon C. P., De Zeeuw D., Edwards R., Levin A., Mahaffey K. W., Perkovic V., Neal B., Lindley R. I., Guerrero R. A. A., Aizenberg D., Albisu J. P., Alvarisqueta A., Bartolacci I., Berli M. A., Bordonava A., Calella P., Cantero M. C., Cartasegna L. R., Cercos E., Coloma G. C., Colombo H., Commendatore V., Cuadrado J., Cuneo C. A., Cusumano A. M., Douthat W. G., Dran R. D., Farias E., Fernandez M. F., Finkelstein H., Fragale G., Fretes J. O., Garcia N. H., Gastaldi A., Gelersztein E., Glenny J. A., Gonzalez J. P., Del Carmen Gonzalez Colaso P., Goycoa C., Greloni G. C., Guinsburg A., Hermida S., Juncos L. I., Klyver M. I., Kraft F., Krynski F., Lanchiotti P. V., De La Fuente R. A. L., Marchetta N., Mele P., Nicolai S., Novoa P. A., Orio S. I., Otreras F., Oviedo A., Raffaele P., Resk J. H., Rista L., Papini N. R., Sala J., Santos J. C., Schiavi L. B., Sessa H., Casabella T. S., Ulla M. R., Valdez M., Vallejos A., Villarino A., Visco V. E., Wassermann A., Zaidman C. J., Cheung N. W., Droste C., Fraser I., Johnson D., Mah P. M., Nicholls K., Packham D., Proietto J., Roberts A., Roger S., Tsang V., Raduan R. A., Da Costa F. A. A., Amodeo C., Turatti L. A. A., Bregman R., Sanches F. C. C., Canani L. H., Chacra A. R., Borges J. L. C., Vencio S. A. C., Da Silva Franco R. J., D'Avila D., De Souza Portes E., De Souza P., Deboni L. M., Filho F. F., Neto B. G., Gomes M., Kohara S. K., Keitel E., Saraiva J. F. K., Lisboa H. R. K., De Carvalho Contieri F. L., Milagres R., Junior R. M., De Brito C. M., Hissa M. N., Sabbag A. R. N., Noronha I., Panarotto D., Filho R. P., Pereira M. A., Saporito W., Scotton A. S., Schuch T., De Almeida R. S., Ramos C. S., Felicio J. S., Thome F., Hachmann J. C. T., Yamada S., Hayashida C. Y., Petry T. B. Z., Zanella M. T., Andreeva V., Angelova A., Dimitrov S., Genadieva V., Genova-Hristova G., Hristozov K., Kamenov Z., Koundurdjiev A., Lozanov L., Margaritov V., Nonchev B., Rangelov R., Shinkov A., Temelkova M., Velichkova E., Yakov A., Aggarwal N., Aronson R., Bajaj H., Cherney D., Chouinard G., Conway J., Cournoyer S., DaRoza G., De Serres S., Dube F., Goldenberg R., Gupta A., Gupta M., Henein S., Khandwala H., Leiter L., Madore F., Mc-Mahon A., Muirhead N., Pichette V., Rabasa-Lhoret R., Steele A., Tangri N., Torshizi A., Woo V., Zalunardo N., Montenegro M. A. F., Jorquera J. G. G., Farina M. M., Gajardo V. S., Vejar M., Chen N., Chen Q., Gan S., Kong Y., Li D., Li W., Li X., Lin H., Liu J., Lu W., Mao H., Ren Y., Song W., Sun J., Sun L., Tu P., Wang G., Yang J., Yin A., Yu X., Zhao M., Zheng H., Mendoza J. L. A., Arcos E., Avendano J., Ruiz J. E. A. D., Ortiz L. H. G., Gonzalez A., Triana E. H., Higuera J. D., Malaver N., De Salazar D. I. M., Rosero R., Lozano M. A. T., Cometa L. V., Valenzuela A., Alonso R. D. V., Villegas I., Yupanqui H., Bartaskova D., Barton P., Belobradkova J., Dohnalova L., Drasnar T., Ferkl R., Halciakova K., Klokocnikova V., Kovar R., Lastuvka J., Lukac M., Pesickova S., Peterka K., Pumprla J., Rychlik I., Saudek F., Tesar V., Valis M., Weiner P., Zemek S., Alamartine E., Borot S., Cariou B., Dussol B., Fauvel J. -P., Gourdy P., Klein A., Le Meur Y., Penfornis A., Roussel R., Saulnier P. -J., Thervet E., Zaoui P., Burst V., Faghih M., Faulmann G., Haller H., Jerwan-Keim R., Maxeiner S., Paschen B., Plassmann G., Rose L., Orellana R. A. G., Haase F. P., Diaz J. P. M., Roca L. A. R., Arenales J. A. S., Polo J. V. S., Juarez E. T., Csecsei G., Csiky B., Danos P., Deak L., Dudas M., Harcsa E., Keltai K., Keresztesi S., Kiss K., Konyves L., Major L., Mileder M., Molnar M., Mucsi J., Oroszlan T., Ory I., Paragh G., Peterfai E., Petro G., Revesz K., Takacs R., Vangel S., Vasas S., Zsom M., Oomman A., Raju S. B., Dewan D., Fernando M. E., Gopalakrishnan N., Gracious N., Alva H., Jain D., Keshavamurthy C. B., Khullar D., Sahay M., Peringat J., Prasad N., Rao K. S., Reddy S., Melemadathil S., Sudhakar B., Vyasam R. C., Bonadonna R., Castellino P., Ceriello A., Chiovato L., De Cosmo S., De Nicola L., Derosa G., Carlo A. D., Cianni G. D., Frasca G., Fuiano G., Gambaro G., Garibotto G., Giorda C., Malberti F., Mandreoli M., Mannucci E., Orsi E., Piatti P., Santoro D., Sasso F. C., Serviddio G., Stella A., Trevisan R., Veronelli A. M., Zanoli L., Akiyama H., Aoki H., Asano A., Iitsuka T., Kajiyama S., Kashine S., Kawada T., Kodera T., Kono H., Koyama K., Kumeda Y., Miyauchi S., Mizuyama K., Niiya T., Oishi H., Ota S., Sakakibara T., Takai M., Tomonaga O., Tsujimoto M., Wada T., Wakasugi M., Wakida Y., Watanabe T., Yamada M., Yanagida K., Yanase T., Yumita W., Gaupsiene E., Kozloviene D., Navickas A., Urbanaviciene E., Ghani R. A., Kadir K. A., Ali N., Yusof M. D. C., Gan C. L., Ismail M., Kong W. Y., Lam S. W., Lee L. Y., Lim S. K., Loh C. L., Manocha A. B., Ng K. S., Ahmad N. N. F. N., Ratnasingam V., Shudim S. S. B., Vengadasalam P., Munoz L. D. A., Salazar M. A., Cruz J. B., Soto M. B., Ramos J. C., Wong A. C., Rotter J. R. C., Escalante T. D., Sosa F. E. E., Lozano F. F., Cervera L. F. F., Baron P. F., Ballesteros C. G., Rangel J. D. G., Jimenez L. E. H., Santana S. S. I., Flores F. J., Molina H. L., Ceballos R. I. L., Del Campo Blanco B. M., Franco G. M., Loza O. T. M., Rocha C. M., Vera G. O., Castellanos R. O., Calcaneo J. P., Rosano M. A. R., Pattzi H. R., Guzman J. R., Joerg I. E. R., Sanchez S. B. S., Mijangos J. H. S., Sanson P. S., Tamayo Y Orozco J. A., Chavez E. T., Cepeda A. V., Carrillo L. V., Mesa J. V., Escobedo R. Z., Baker J., Noonan P., Scott R., Walker R., Watson E., Williams M., Young S., Abejuela Z., Agra J., Aquitania G., Caringal C., Comia R. S., Santos L. D., Gomez O., Jimeno C., Santos F., Tan G., Tolentino M., Yao C., Yap Y. E., Ygpuara M. D. L., Bijata-Bronisz R., Hotlos L., Januszewicz A., Kaczmarek B., Kaminska A., Lazuka L., Madej A., Mazur S., Mlodawska-Choluj D., Nowicki M., Orlowska-Kowalik G., Popenda G., Rewerska B., Sowinski D., Angelescu L. M., Anghel V., Avram R. -I., Busegeanu M. -M., Cif A., Cosma D., Crisan C., Demian L. D., Ferariu I. E., Halmagyi I., Hancu N., Munteanu M., Negru D., Onaca A. G., Petrica L., Popa A. R., Ranetti A. -E., Serafinceanu C., Toarba C., Agafyina A., Barbarash O., Barysheva O., Chizhov D., Dobronravov V., Dreval A., Glinkina I., Grineva E., Khirmanov V., Kolmakova E., Koroleva T., Kvitkova L., Marasaev V., Mkrtumyan A., Morugova T., Nagibovich G., Nagibovich O., Nedogoda S., Osipova I., Raskina T., Samoylova Y., Sazonova O., Shamkhalova M., Shutemova E., Shwartz Y., Uriasyev O., Vorobyev S., Zateyshchikova A., Zateyshshikov D., Zykova T., Antic S., Djordjevic M., Kendereski A., Lalic K., Lalic N., Popovic-Radinovic V., Babikova J., Benusova O., Buganova I., Culak J., Dzupina A., Dzuponova J., Fulop P., Ilavska A., Martinka E., Ochodnicka Z., Pella D., Smatanova I., Ahmed F., Badat A., Breedt J., Distiller L., Govender V., Govender R., Joshi M., Jurgens J., Latiff G., Lombard L., Mookadam M., Ngcakani N., Nortje H., Oosthuizen H., Pillay-Ramaya L., Prozesky H., Reddy J., Rheeder P., Seeber M., Chae D. -W., Cho Y. M., Jeong I. -K., Kim S. G., Kim Y. H., Kwon H. -S., Kwon M. J., Lee B. -W., Lee J., Lee M. -K., Nam M. -S., Oh K. -H., Park C. -Y., Park S. -H., Yoon K. H., Garcia P. A., Mercadal L. A., Barrios C., Castro F. C., Guldris S. C., Lopez M. D., De Los Rios J. E., Fresnedo G. F., Serrano A. G., Garcia I., Martinez F. J. G., Gimeno J. E. J., Mendoza M. L., Marin T. M., Portillo C. M., Vila M. A. M., Torres M. M., Iglesias J. N., Perez J. P., Vera M. P., Perez J. M. P., Simon M. A. Q., Canonge R. S., Gonzalez A. S., Riera M. T., Madueno F. J. T., Plaza M. V., Chang C. -T., Chuang L. -M., Hsia T. -L., Hsieh C. -H., Hwang S. -J., Lin C. -C., Lu Y. -C., Sheu W. H. -H., Barna O., Bilyk S. D., Botsyurko V., Dudar I., Fushtey I., Godlevska O., Golovchenko O., Gyrina O., Kazmirchuk A., Kolesnyk M., Komisarenko I., Korzh O., Kravchun N., Legun O., Mankovskyy B., Martynyuk L., Mostovoy Y., Pashkovska N., Pererva L., Pertseva T., Samoylov O., Smirnov I., Svyshchenko Y., Tomashkevych H., Topchii I., Tryshchuk N., Tseluyko V., Vizir V., Vlasenko M., Zlova T., Zub L., Abusnana S., Railey M., Abouglila K., Ainsworth P., Ali Z., Arutchelvam V., Barnard M., Bellary S., Davies E., Davies M., Davies S., Dawson A., Kossi M. E., English P., Fraser D., Gnudi L., Gunstone A., Hall T., Hanif W., Jackson A., Johnson A., Joseph F., Krishnan S., Kumwenda M., MacDougall I., Nixon P., O'Hare J., Philip S., Ramtoola S., Saxena M., Sennik D., Simon G., Singh B., Stephens J., Strzelecka A., Symonds R., Turner W., Wahba M., Wakeling J., Wheeler D., Winocour P., Abdallah J., Abdullah R., Abramowitz M., Acosta I., Aiello J., Akright L., Akyea-Djamson A., Alappan R., Alicic R., Al-Karadsheh A., Allison D. C., Arauz-Pacheco C., Arfeen S., Arif A., Arvind M., Atray N., Awad A., Bakris G., Barnhill P., Barranco E., Barrera C., Beacom M., Behara V., Belo D., Bentley-Lewis R., Berenguer R., Bermudez L., Bernardo M., Biscoveanu M., Bowman-Stroud C., Brandon D., Brusco O., Busch R., Canaan Y., Chilito A., Christensen T., Christiano C., Christofides E., Chuateco C., Cohen K., Cohen R., Cohen-Stein D., Cook C., Coyne D., Daboul N., Darwish R., Daswani A., Deck K., Desouza C., Dev D., Dhillon M., Dua S., Eder F., Elosegui A. M., El-Shahawy M., Ervin J., Esquenazi A., Evans J., Fishbane S., Frias J., Galindo-Ramos E., Galphin C., Ghazi A., Gonzalez E., Gorson D., Gowda A., Greco B., Grubb S., Gulati R., Hammoud J., Handelsman S., Hartman I., Hershon K., Hiser D., Hon G., Jacob R., Jaime M., Jamal A., Kaupke C., Keightley G., Kern E., Khanna R., Khitan Z., Kim S., Kopyt N., Kovesdy C., Krishna G., Kropp J., Kumar A., Kumar J., Kumar N., Kusnir J., Lane W., Lawrence M., Lehrner L., Lentz J., Levinson D., Lewis D., Liss K., Maddux A., Maheshwari H., Mandayam S., Marar I., Mehta B., Middleton J., Mordujovich J., Moreda R., Moustafa M., Trenche S. M., Narayanan M., Narvarte J., Nassar T., Newman G., Nichol B., Nicol P., Nisnisan J., Nossuli A. K., Obialo C., Olelewe S., Oliver M., O'Shaughnessy A., Padron J., Pankhaniya R., Parker R., Patel D., Patel G., Patel N., Pavon H., Perez A., Perez C., Perlman A., Pettis K., Pharr W., Phillips A., Purighalla R., Quesada-Suarez L., Ranjan R., Rastogi S., Rendell M., Rich L., Robinson M., Rodriguez H., Rosas S., Saba F., Sankaram R., Sarin R., Schreiman R., Scott D., Sekkarie M., Sensenbrenner J., Shakeel M., Shanik M., Shaw S., Smith S., Solomon R., Sprague A., Spry L., Suchinda P., Sultan S., Surampudi P., Sussman S., Tan A., Terrelonge A., Thompson M., Trespalacios F., Trippe B., Trueba P., Twahirwa M., Updegrove J., Van Buren P., Vannorsdall M., Varghese F., Velasquez-Mieyer P., Ventrapragada S., Vukotic G., Wadud K., Warren M., Watson H., Watts R., Weiner D., Welker J., Welsh J., Williams S., Zaniewski-Singh M., Zhou, Z., Jardine, M. J., Li, Q., Neuen, B. L., Cannon, C. P., De Zeeuw, D., Edwards, R., Levin, A., Mahaffey, K. W., Perkovic, V., Neal, B., Lindley, R. I., Guerrero, R. A. A., Aizenberg, D., Albisu, J. P., Alvarisqueta, A., Bartolacci, I., Berli, M. A., Bordonava, A., Calella, P., Cantero, M. C., Cartasegna, L. R., Cercos, E., Coloma, G. C., Colombo, H., Commendatore, V., Cuadrado, J., Cuneo, C. A., Cusumano, A. M., Douthat, W. G., Dran, R. D., Farias, E., Fernandez, M. F., Finkelstein, H., Fragale, G., Fretes, J. O., Garcia, N. H., Gastaldi, A., Gelersztein, E., Glenny, J. A., Gonzalez, J. P., Del Carmen Gonzalez Colaso, P., Goycoa, C., Greloni, G. C., Guinsburg, A., Hermida, S., Juncos, L. I., Klyver, M. I., Kraft, F., Krynski, F., Lanchiotti, P. V., De La Fuente, R. A. L., Marchetta, N., Mele, P., Nicolai, S., Novoa, P. A., Orio, S. I., Otreras, F., Oviedo, A., Raffaele, P., Resk, J. H., Rista, L., Papini, N. R., Sala, J., Santos, J. C., Schiavi, L. B., Sessa, H., Casabella, T. S., Ulla, M. R., Valdez, M., Vallejos, A., Villarino, A., Visco, V. E., Wassermann, A., Zaidman, C. J., Cheung, N. W., Droste, C., Fraser, I., Johnson, D., Mah, P. 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T., Csecsei, G., Csiky, B., Danos, P., Deak, L., Dudas, M., Harcsa, E., Keltai, K., Keresztesi, S., Kiss, K., Konyves, L., Major, L., Mileder, M., Molnar, M., Mucsi, J., Oroszlan, T., Ory, I., Paragh, G., Peterfai, E., Petro, G., Revesz, K., Takacs, R., Vangel, S., Vasas, S., Zsom, M., Oomman, A., Raju, S. B., Dewan, D., Fernando, M. E., Gopalakrishnan, N., Gracious, N., Alva, H., Jain, D., Keshavamurthy, C. B., Khullar, D., Sahay, M., Peringat, J., Prasad, N., Rao, K. S., Reddy, S., Melemadathil, S., Sudhakar, B., Vyasam, R. C., Bonadonna, R., Castellino, P., Ceriello, A., Chiovato, L., De Cosmo, S., De Nicola, L., Derosa, G., Carlo, A. D., Cianni, G. D., Frasca, G., Fuiano, G., Gambaro, G., Garibotto, G., Giorda, C., Malberti, F., Mandreoli, M., Mannucci, E., Orsi, E., Piatti, P., Santoro, D., Sasso, F. C., Serviddio, G., Stella, A., Trevisan, R., Veronelli, A. 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M., Franco, G. M., Loza, O. T. M., Rocha, C. M., Vera, G. O., Castellanos, R. O., Calcaneo, J. P., Rosano, M. A. R., Pattzi, H. R., Guzman, J. R., Joerg, I. E. R., Sanchez, S. B. S., Mijangos, J. H. S., Sanson, P. S., Tamayo Y Orozco, J. A., Chavez, E. T., Cepeda, A. V., Carrillo, L. V., Mesa, J. V., Escobedo, R. Z., Baker, J., Noonan, P., Scott, R., Walker, R., Watson, E., Williams, M., Young, S., Abejuela, Z., Agra, J., Aquitania, G., Caringal, C., Comia, R. S., Santos, L. D., Gomez, O., Jimeno, C., Santos, F., Tan, G., Tolentino, M., Yao, C., Yap, Y. E., Ygpuara, M. D. L., Bijata-Bronisz, R., Hotlos, L., Januszewicz, A., Kaczmarek, B., Kaminska, A., Lazuka, L., Madej, A., Mazur, S., Mlodawska-Choluj, D., Nowicki, M., Orlowska-Kowalik, G., Popenda, G., Rewerska, B., Sowinski, D., Angelescu, L. M., Anghel, V., Avram, R. -I., Busegeanu, M. -M., Cif, A., Cosma, D., Crisan, C., Demian, L. D., Ferariu, I. E., Halmagyi, I., Hancu, N., Munteanu, M., Negru, D., Onaca, A. 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R., Ranetti, A. -E., Serafinceanu, C., Toarba, C., Agafyina, A., Barbarash, O., Barysheva, O., Chizhov, D., Dobronravov, V., Dreval, A., Glinkina, I., Grineva, E., Khirmanov, V., Kolmakova, E., Koroleva, T., Kvitkova, L., Marasaev, V., Mkrtumyan, A., Morugova, T., Nagibovich, G., Nagibovich, O., Nedogoda, S., Osipova, I., Raskina, T., Samoylova, Y., Sazonova, O., Shamkhalova, M., Shutemova, E., Shwartz, Y., Uriasyev, O., Vorobyev, S., Zateyshchikova, A., Zateyshshikov, D., Zykova, T., Antic, S., Djordjevic, M., Kendereski, A., Lalic, K., Lalic, N., Popovic-Radinovic, V., Babikova, J., Benusova, O., Buganova, I., Culak, J., Dzupina, A., Dzuponova, J., Fulop, P., Ilavska, A., Martinka, E., Ochodnicka, Z., Pella, D., Smatanova, I., Ahmed, F., Badat, A., Breedt, J., Distiller, L., Govender, V., Govender, R., Joshi, M., Jurgens, J., Latiff, G., Lombard, L., Mookadam, M., Ngcakani, N., Nortje, H., Oosthuizen, H., Pillay-Ramaya, L., Prozesky, H., Reddy, J., Rheeder, P., Seeber, M., Chae, D. -W., Cho, Y. M., Jeong, I. -K., Kim, S. G., Kim, Y. H., Kwon, H. -S., Kwon, M. J., Lee, B. -W., Lee, J., Lee, M. -K., Nam, M. -S., Oh, K. -H., Park, C. -Y., Park, S. -H., Yoon, K. H., Garcia, P. A., Mercadal, L. A., Barrios, C., Castro, F. C., Guldris, S. C., Lopez, M. D., De Los Rios, J. E., Fresnedo, G. F., Serrano, A. G., Garcia, I., Martinez, F. J. G., Gimeno, J. E. J., Mendoza, M. L., Marin, T. M., Portillo, C. M., Vila, M. A. M., Torres, M. M., Iglesias, J. N., Perez, J. P., Vera, M. P., Perez, J. M. P., Simon, M. A. Q., Canonge, R. S., Gonzalez, A. S., Riera, M. T., Madueno, F. J. T., Plaza, M. V., Chang, C. -T., Chuang, L. -M., Hsia, T. -L., Hsieh, C. -H., Hwang, S. -J., Lin, C. -C., Lu, Y. -C., Sheu, W. H. -H., Barna, O., Bilyk, S. D., Botsyurko, V., Dudar, I., Fushtey, I., Godlevska, O., Golovchenko, O., Gyrina, O., Kazmirchuk, A., Kolesnyk, M., Komisarenko, I., Korzh, O., Kravchun, N., Legun, O., Mankovskyy, B., Martynyuk, L., Mostovoy, Y., Pashkovska, N., Pererva, L., Pertseva, T., Samoylov, O., Smirnov, I., Svyshchenko, Y., Tomashkevych, H., Topchii, I., Tryshchuk, N., Tseluyko, V., Vizir, V., Vlasenko, M., Zlova, T., Zub, L., Abusnana, S., Railey, M., Abouglila, K., Ainsworth, P., Ali, Z., Arutchelvam, V., Barnard, M., Bellary, S., Davies, E., Davies, M., Davies, S., Dawson, A., Kossi, M. E., English, P., Fraser, D., Gnudi, L., Gunstone, A., Hall, T., Hanif, W., Jackson, A., Johnson, A., Joseph, F., Krishnan, S., Kumwenda, M., Macdougall, I., Nixon, P., O'Hare, J., Philip, S., Ramtoola, S., Saxena, M., Sennik, D., Simon, G., Singh, B., Stephens, J., Strzelecka, A., Symonds, R., Turner, W., Wahba, M., Wakeling, J., Wheeler, D., Winocour, P., Abdallah, J., Abdullah, R., Abramowitz, M., Acosta, I., Aiello, J., Akright, L., Akyea-Djamson, A., Alappan, R., Alicic, R., Al-Karadsheh, A., Allison, D. C., Arauz-Pacheco, C., Arfeen, S., Arif, A., Arvind, M., Atray, N., Awad, A., Bakris, G., Barnhill, P., Barranco, E., Barrera, C., Beacom, M., Behara, V., Belo, D., Bentley-Lewis, R., Berenguer, R., Bermudez, L., Bernardo, M., Biscoveanu, M., Bowman-Stroud, C., Brandon, D., Brusco, O., Busch, R., Canaan, Y., Chilito, A., Christensen, T., Christiano, C., Christofides, E., Chuateco, C., Cohen, K., Cohen, R., Cohen-Stein, D., Cook, C., Coyne, D., Daboul, N., Darwish, R., Daswani, A., Deck, K., Desouza, C., Dev, D., Dhillon, M., Dua, S., Eder, F., Elosegui, A. 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K., Obialo, C., Olelewe, S., Oliver, M., O'Shaughnessy, A., Padron, J., Pankhaniya, R., Parker, R., Patel, D., Patel, G., Patel, N., Pavon, H., Perez, A., Perez, C., Perlman, A., Pettis, K., Pharr, W., Phillips, A., Purighalla, R., Quesada-Suarez, L., Ranjan, R., Rastogi, S., Rendell, M., Rich, L., Robinson, M., Rodriguez, H., Rosas, S., Saba, F., Sankaram, R., Sarin, R., Schreiman, R., Scott, D., Sekkarie, M., Sensenbrenner, J., Shakeel, M., Shanik, M., Shaw, S., Smith, S., Solomon, R., Sprague, A., Spry, L., Suchinda, P., Sultan, S., Surampudi, P., Sussman, S., Tan, A., Terrelonge, A., Thompson, M., Trespalacios, F., Trippe, B., Trueba, P., Twahirwa, M., Updegrove, J., Van Buren, P., Vannorsdall, M., Varghese, F., Velasquez-Mieyer, P., Ventrapragada, S., Vukotic, G., Wadud, K., Warren, M., Watson, H., Watts, R., Weiner, D., Welker, J., Welsh, J., Williams, S., Zaniewski-Singh, M., Groningen Kidney Center (GKC), Zhou, Z, Jardine, M, Li, Q, Neuen, B, Cannon, C, De Zeeuw, D, Edwards, R, 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Subjects
medicine.medical_specialty, Original Contributions, atrial fibrillation, canagliflozin, glomerular filtration rate, hemorrhagic stroke, ischemic stroke, Renal function, Disease, Brain Ischemia, Clinical and Population Sciences, Meta-Analysis as Topic, Internal medicine, CREDENCE Trial Investigators, Atrial Fibrillation, medicine, Diabetes Mellitus, Humans, Diabetic Nephropathies, Canagliflozin, Stroke, 1102 Cardiorespiratory Medicine and Haematology, Sodium-Glucose Transporter 2 Inhibitors, Advanced and Specialized Nursing, Neurology & Neurosurgery, business.industry, Atrial fibrillation, 1103 Clinical Sciences, medicine.disease, Diabetes Mellitus, Type 2, Meta-analysis, Cardiology, Albuminuria, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, 1109 Neurosciences, Kidney disease, medicine.drug
Abstract

Supplemental Digital Content is available in the text., Background and Purpose: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis. Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55–1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61–1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19–1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20–1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53–1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82–1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89–1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30–0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49–1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71–0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (

Published
2021

48. A unique microRNA profile in end-stage heart failure indicates alterations in specific cardiovascular signaling networks.

Author

Sathyamangla V Naga Prasad, Manveen K Gupta, Zhong-Hui Duan, Venkata Suresh K Surampudi, Chang-Gong Liu, Ashwin Kotwal, Christine S Moravec, Randall C Starling, Dianne M Perez, Subha Sen, Qingyu Wu, Edward F Plow, and Sadashiva Karnik

Subjects
Medicine, Science
Abstract

It is well established that the gene expression patterns are substantially altered in cardiac hypertrophy and heart failure, however, less is known about the reasons behind such global differences. MicroRNAs (miRNAs) are short non-coding RNAs that can target multiple molecules to regulate wide array of proteins in diverse pathways. The goal of the study was to profile alterations in miRNA expression using end-stage human heart failure samples with an aim to build signaling network pathways using predicted targets for the altered miRNA and to determine nodal molecules regulating individual networks. Profiling of miRNAs using custom designed microarray and validation with an independent set of samples identified eight miRNAs that are altered in human heart failure including one novel miRNA yet to be implicated in cardiac pathology. To gain an unbiased perspective on global regulation by top eight altered miRNAs, functional relationship of predicted targets for these eight miRNAs were examined by network analysis. Ingenuity Pathways Analysis network algorithm was used to build global signaling networks based on the targets of altered miRNAs which allowed us to identify participating networks and nodal molecules that could contribute to cardiac pathophysiology. Majority of the nodal molecules identified in our analysis are targets of altered miRNAs and known regulators of cardiovascular signaling. Cardio-genomics heart failure gene expression public data base was used to analyze trends in expression pattern for target nodal molecules and indeed changes in expression of nodal molecules inversely correlated to miRNA alterations. We have used NF kappa B network as an example to show that targeting other molecules in the network could alter the nodal NF kappa B despite not being a miRNA target suggesting an integrated network response. Thus, using network analysis we show that altering key functional target proteins may regulate expression of the myriad signaling pathways underlying the cardiac pathology.

Published
2017
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