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Article: Reduced Mortality With Ondansetron Use in SARS-CoV-2-Infected Inpatients.

Bayat, Vafa / Ryono, Russell / Phelps, Steven / Geis, Eugene / Sedghi, Farshid / Etminani, Payam / Holodniy, Mark

2021 Volume 8, Issue 7, Page(s) ofab336

Abstract: Background: The coronavirus disease 2019 (COVID-19) pandemic has led to a surge in clinical trials evaluating investigational and approved drugs. Retrospective analysis of drugs taken by COVID-19 inpatients provides key information on drugs associated ... ...

Abstract	Background: The coronavirus disease 2019 (COVID-19) pandemic has led to a surge in clinical trials evaluating investigational and approved drugs. Retrospective analysis of drugs taken by COVID-19 inpatients provides key information on drugs associated with better or worse outcomes. Methods: We conducted a retrospective cohort study of 10 741 patients testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 3 days of admission to compare risk of 30-day all-cause mortality in patients receiving ondansetron using multivariate Cox proportional hazard models. All-cause mortality, length of hospital stay, adverse events such as ischemic cerebral infarction, and subsequent positive COVID-19 tests were measured. Results: Administration of ≥8 mg of ondansetron within 48 hours of admission was correlated with an adjusted hazard ratio for 30-day all-cause mortality of 0.55 (95% CI, 0.42-0.70; Conclusions: If confirmed by prospective clinical trials, our results suggest that ondansetron, a safe, widely available drug, could be used to decrease morbidity and mortality in at-risk populations.
Language	English
Publishing date	2021-07-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofab336
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Prediction Model From Standard Laboratory Tests.

Bayat, Vafa / Phelps, Steven / Ryono, Russell / Lee, Chong / Parekh, Hemal / Mewton, Joel / Sedghi, Farshid / Etminani, Payam / Holodniy, Mark

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2020 Volume 73, Issue 9, Page(s) e2901–e2907

Abstract: Background: With the limited availability of testing for the presence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and concerns surrounding the accuracy of existing methods, other means of identifying patients are urgently ... ...

Abstract	Background: With the limited availability of testing for the presence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and concerns surrounding the accuracy of existing methods, other means of identifying patients are urgently needed. Previous studies showing a correlation between certain laboratory tests and diagnosis suggest an alternative method based on an ensemble of tests. Methods: We have trained a machine learning model to analyze the correlation between SARS-CoV-2 test results and 20 routine laboratory tests collected within a 2-day period around the SARS-CoV-2 test date. We used the model to compare SARS-CoV-2 positive and negative patients. Results: In a cohort of 75 991 veteran inpatients and outpatients who tested for SARS-CoV-2 in the months of March through July 2020, 7335 of whom were positive by reverse transcription polymerase chain reaction (RT-PCR) or antigen testing, and who had at least 15 of 20 lab results within the window period, our model predicted the results of the SARS-CoV-2 test with a specificity of 86.8%, a sensitivity of 82.4%, and an overall accuracy of 86.4% (with a 95% confidence interval of [86.0%, 86.9%]). Conclusions: Although molecular-based and antibody tests remain the reference standard method for confirming a SARS-CoV-2 diagnosis, their clinical sensitivity is not well known. The model described herein may provide a complementary method of determining SARS-CoV-2 infection status, based on a fully independent set of indicators, that can help confirm results from other tests as well as identify positive cases missed by molecular testing.
MeSH term(s)	COVID-19 ; COVID-19 Testing ; Clinical Laboratory Techniques ; Humans ; SARS-CoV-2 ; Sensitivity and Specificity
Keywords	covid19
Language	English
Publishing date	2020-07-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciaa1175
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Article ; Online: A COVID-19 Prediction Model from Standard Laboratory Tests and Vital Signs

Bayat, Vafa / Phelps, Steven / Ryono, Russell / Lee, Chong / Parekh, Hemal / Mewton, Joel / Sedghi, Farshid / Etminani, Payam / Holodniy, Mark

SSRN Electronic Journal ; ISSN 1556-5068

2020

Keywords	covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
DOI	10.2139/ssrn.3594614
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Instructional interventions for improving COVID-19 knowledge, attitudes, behaviors: Evidence from a large-scale RCT in India.

Mistree, Dinsha / Loyalka, Prashant / Fairlie, Robert / Bhuradia, Ashutosh / Angrish, Manyu / Lin, Jason / Karoshi, Amar / Yen, Sara J / Mistri, Jamsheed / Bayat, Vafa

Social science & medicine (1982)

2021 Volume 276, Page(s) 113846

Abstract: Seeking ways to encourage broad compliance with health guidelines during the pandemic, especially among youth, we test two hypotheses pertaining to the optimal design of instructional interventions for improving COVID-19-related knowledge, attitudes, and ...

Abstract	Seeking ways to encourage broad compliance with health guidelines during the pandemic, especially among youth, we test two hypotheses pertaining to the optimal design of instructional interventions for improving COVID-19-related knowledge, attitudes, and behaviors. We randomly assigned 8376 lower-middle income youth in urban India to three treatments: a concentrated and targeted fact-based, instructional intervention; a longer instructional intervention that provided the same facts along with underlying scientific concepts; and a control. Relative to existing efforts, we find that both instructional interventions increased COVID-19-related knowledge immediately after intervention. Relative to the shorter fact-based intervention, the longer intervention resulted in sustained improvements in knowledge, attitudes, and self-reported behavior. Instead of reducing attention and comprehension by youth, the longer scientific based treatment appears to have increased understanding and retention of the material. The findings are instrumental to understanding the design of instruction and communication in affecting compliance during this and future pandemics.
MeSH term(s)	Adolescent ; COVID-19 ; Health Knowledge, Attitudes, Practice ; Humans ; India ; Pandemics ; SARS-CoV-2
Language	English
Publishing date	2021-03-17
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	4766-1
ISSN	1873-5347 ; 0037-7856 ; 0277-9536
ISSN (online)	1873-5347
ISSN	0037-7856 ; 0277-9536
DOI	10.1016/j.socscimed.2021.113846
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Article ; Online: Regulation of lipid homeostasis by the TBC protein dTBC1D22 via modulation of the small GTPase Rab40 to facilitate lipophagy.

Duan, Xiuying / Xu, Lingna / Li, Yawen / Jia, Lijun / Liu, Wei / Shao, Wenxia / Bayat, Vafa / Shang, Weina / Wang, Liquan / Liu, Jun-Ping / Tong, Chao

Cell reports

2021 Volume 36, Issue 9, Page(s) 109541

Abstract: The regulation of lipid homeostasis is not well understood. Using forward genetic screening, we demonstrate that the loss of dTBC1D22, an essential gene that encodes a Tre2-Bub2-Cdc16 (TBC) domain-containing protein, results in lipid droplet accumulation ...

Abstract	The regulation of lipid homeostasis is not well understood. Using forward genetic screening, we demonstrate that the loss of dTBC1D22, an essential gene that encodes a Tre2-Bub2-Cdc16 (TBC) domain-containing protein, results in lipid droplet accumulation in multiple tissues. We observe that dTBC1D22 interacts with Rab40 and exhibits GTPase activating protein (GAP) activity. Overexpression of either the GTP- or GDP-binding-mimic form of Rab40 results in lipid droplet accumulation. We observe that Rab40 mutant flies are defective in lipid mobilization. The lipid depletion induced by overexpression of Brummer, a triglyceride lipase, is dependent on Rab40. Rab40 mutant flies exhibit decreased lipophagy and small size of autolysosomal structures, which may be due to the defective Golgi functions. Finally, we demonstrate that Rab40 physically interacts with Lamp1, and Rab40 is required for the distribution of Lamp1 during starvation. We propose that dTBC1D22 functions as a GAP for Rab40 to regulate lipophagy.
MeSH term(s)	Animals ; Animals, Genetically Modified ; Autophagy ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Drosophila melanogaster/ultrastructure ; Eye/metabolism ; Eye/ultrastructure ; GTPase-Activating Proteins/genetics ; GTPase-Activating Proteins/metabolism ; Golgi Apparatus/genetics ; Golgi Apparatus/metabolism ; Golgi Apparatus/ultrastructure ; HeLa Cells ; Homeostasis ; Humans ; Lipase/genetics ; Lipase/metabolism ; Lipid Droplets/metabolism ; Lipid Metabolism ; Lysosomal-Associated Membrane Protein 1/genetics ; Lysosomal-Associated Membrane Protein 1/metabolism ; Lysosomes/genetics ; Lysosomes/metabolism ; Lysosomes/ultrastructure ; Mutation ; rab GTP-Binding Proteins/genetics ; rab GTP-Binding Proteins/metabolism
Chemical Substances	Drosophila Proteins ; GTPase-Activating Proteins ; Lysosomal-Associated Membrane Protein 1 ; TBC1D22 protein, Drosophila ; Lipase (EC 3.1.1.3) ; BMM protein, Drosophila (EC 3.1.1.3.) ; Rab40 protein, Drosophila (EC 3.6.5.2) ; rab GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2021-09-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.109541
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Article ; Online: Integrative analyses highlight functional regulatory variants associated with neuropsychiatric diseases.

Guo, Margaret G / Reynolds, David L / Ang, Cheen E / Liu, Yingfei / Zhao, Yang / Donohue, Laura K H / Siprashvili, Zurab / Yang, Xue / Yoo, Yongjin / Mondal, Smarajit / Hong, Audrey / Kain, Jessica / Meservey, Lindsey / Fabo, Tania / Elfaki, Ibtihal / Kellman, Laura N / Abell, Nathan S / Pershad, Yash / Bayat, Vafa /

Etminani, Payam / Holodniy, Mark / Geschwind, Daniel H / Montgomery, Stephen B / Duncan, Laramie E / Urban, Alexander E / Altman, Russ B / Wernig, Marius / Khavari, Paul A

Nature genetics

2023 Volume 55, Issue 11, Page(s) 1876–1891

Abstract: Noncoding variants of presumed regulatory function contribute to the heritability of neuropsychiatric disease. A total of 2,221 noncoding variants connected to risk for ten neuropsychiatric disorders, including autism spectrum disorder, attention deficit ...

Abstract	Noncoding variants of presumed regulatory function contribute to the heritability of neuropsychiatric disease. A total of 2,221 noncoding variants connected to risk for ten neuropsychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, bipolar disorder, borderline personality disorder, major depression, generalized anxiety disorder, panic disorder, post-traumatic stress disorder, obsessive-compulsive disorder and schizophrenia, were studied in developing human neural cells. Integrating epigenomic and transcriptomic data with massively parallel reporter assays identified differentially-active single-nucleotide variants (daSNVs) in specific neural cell types. Expression-gene mapping, network analyses and chromatin looping nominated candidate disease-relevant target genes modulated by these daSNVs. Follow-up integration of daSNV gene editing with clinical cohort analyses suggested that magnesium transport dysfunction may increase neuropsychiatric disease risk and indicated that common genetic pathomechanisms may mediate specific symptoms that are shared across multiple neuropsychiatric diseases.
MeSH term(s)	Humans ; Autism Spectrum Disorder/genetics ; Bipolar Disorder/genetics ; Schizophrenia/genetics ; Obsessive-Compulsive Disorder/genetics ; Obsessive-Compulsive Disorder/psychology ; Depressive Disorder, Major/genetics ; Attention Deficit Disorder with Hyperactivity/genetics
Language	English
Publishing date	2023-10-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-023-01533-5
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Article: A SARS-CoV-2 Prediction Model from Standard Laboratory Tests

Bayat, Vafa / Phelps, Steven / Ryono, Russell / Lee, Chong / Parekh, Hemal / Mewton, Joel / Sedghi, Farshid / Etminani, Payam / Holodniy, Mark

Clin. infect. dis

Abstract: BACKGROUND: With the limited availability of testing for the presence of the SARS-CoV-2 virus and concerns surrounding the accuracy of existing methods, other means of identifying patients are urgently needed. Previous studies showing a correlation ... ...

Abstract	BACKGROUND: With the limited availability of testing for the presence of the SARS-CoV-2 virus and concerns surrounding the accuracy of existing methods, other means of identifying patients are urgently needed. Previous studies showing a correlation between certain laboratory tests and diagnosis suggest an alternative method based on an ensemble of tests. METHODS: We have trained a machine learning model to analyze the correlation between SARS-CoV-2 test results and 20 routine laboratory tests collected within a 2-day period around the SARS-CoV-2 test date. We used the model to compare SARS-CoV-2 positive and negative patients. RESULTS: In a cohort of 75,991 veteran inpatients and outpatients who tested for SARS-CoV-2 in the months of March through July, 2020, 7,335 of whom were positive by RT-PCR or antigen testing, and who had at least 15 of 20 lab results within the window period, our model predicted the results of the SARS-CoV-2 test with a specificity of 86.8%, a sensitivity of 82.4%, and an overall accuracy of 86.4% (with a 95% confidence interval of [86.0%, 86.9%]). CONCLUSIONS: While molecular-based and antibody tests remain the reference standard method for confirming a SARS-CoV-2 diagnosis, their clinical sensitivity is not well known. The model described herein may provide a complementary method of determining SARS-CoV-2 infection status, based on a fully independent set of indicators, that can help confirm results from other tests as well as identify positive cases missed by molecular testing.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #712974
Database	COVID19

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Article ; Online: A Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Prediction Model From Standard Laboratory Tests

Bayat, Vafa / Phelps, Steven / Ryono, Russell / Lee, Chong / Parekh, Hemal / Mewton, Joel / Sedghi, Farshid / Etminani, Payam / Holodniy, Mark

Clinical Infectious Diseases ; ISSN 1058-4838 1537-6591

2020

Abstract: Abstract Background With the limited availability of testing for the presence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and concerns surrounding the accuracy of existing methods, other means of identifying patients are ... ...

Abstract	Abstract Background With the limited availability of testing for the presence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and concerns surrounding the accuracy of existing methods, other means of identifying patients are urgently needed. Previous studies showing a correlation between certain laboratory tests and diagnosis suggest an alternative method based on an ensemble of tests. Methods We have trained a machine learning model to analyze the correlation between SARS-CoV-2 test results and 20 routine laboratory tests collected within a 2-day period around the SARS-CoV-2 test date. We used the model to compare SARS-CoV-2 positive and negative patients. Results In a cohort of 75 991 veteran inpatients and outpatients who tested for SARS-CoV-2 in the months of March through July 2020, 7335 of whom were positive by reverse transcription polymerase chain reaction (RT-PCR) or antigen testing, and who had at least 15 of 20 lab results within the window period, our model predicted the results of the SARS-CoV-2 test with a specificity of 86.8%, a sensitivity of 82.4%, and an overall accuracy of 86.4% (with a 95% confidence interval of [86.0%, 86.9%]). Conclusions Although molecular-based and antibody tests remain the reference standard method for confirming a SARS-CoV-2 diagnosis, their clinical sensitivity is not well known. The model described herein may provide a complementary method of determining SARS-CoV-2 infection status, based on a fully independent set of indicators, that can help confirm results from other tests as well as identify positive cases missed by molecular testing.
Keywords	Microbiology (medical) ; Infectious Diseases ; covid19
Language	English
Publisher	Oxford University Press (OUP)
Publishing country	uk
Document type	Article ; Online
DOI	10.1093/cid/ciaa1175
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Article ; Online: Gastrointestinal histoplasmosis in a hepatitis C-infected individual.

Rodriguez-Waitkus, Paul M / Bayat, Vafa / George, Elias / Sule, Norbert

Mycopathologia

2013 Volume 176, Issue 1-2, Page(s) 161–164

Abstract: Gastrointestinal histoplasmosis is a rare manifestation of this fungal infection, typically identified in immunocompromised patients, such as those with HIV/AIDS. Here, we report a case of disseminated histoplasmosis with gastrointestinal involvement in ... ...

Abstract	Gastrointestinal histoplasmosis is a rare manifestation of this fungal infection, typically identified in immunocompromised patients, such as those with HIV/AIDS. Here, we report a case of disseminated histoplasmosis with gastrointestinal involvement in a Hepatitis C-infected patient. The fungal agent was confirmed to be Histoplasma capsulatum by a DNA probe assay performed on a bone marrow sample. We propose that this fungal disease should be kept on the differential of patients infected with the Hepatitis C virus, as it has been reported to have numerous damaging effects on the adaptive immune system.
MeSH term(s)	Bone Marrow/microbiology ; Bone Marrow/pathology ; Female ; Gastrointestinal Diseases/diagnosis ; Gastrointestinal Diseases/microbiology ; Gastrointestinal Diseases/pathology ; Hepatitis C, Chronic/complications ; Histocytochemistry/methods ; Histoplasma/genetics ; Histoplasma/isolation & purification ; Histoplasmosis/diagnosis ; Histoplasmosis/microbiology ; Histoplasmosis/pathology ; Humans ; Lung/pathology ; Microbiological Techniques ; Middle Aged ; Molecular Diagnostic Techniques
Language	English
Publishing date	2013-06-13
Publishing country	Netherlands
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391081-7
ISSN	1573-0832 ; 0369-299X ; 0301-486X ; 0027-5530
ISSN (online)	1573-0832
ISSN	0369-299X ; 0301-486X ; 0027-5530
DOI	10.1007/s11046-013-9669-5
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Article ; Online: Protein phosphatase 1ß limits ring canal constriction during Drosophila germline cyst formation.

Yamamoto, Shinya / Bayat, Vafa / Bellen, Hugo J / Tan, Change

PloS one

2013 Volume 8, Issue 7, Page(s) e70502

Abstract: Germline cyst formation is essential for the propagation of many organisms including humans and flies. The cytoplasm of germline cyst cells communicate with each other directly via large intercellular bridges called ring canals. Ring canals are often ... ...

Abstract	Germline cyst formation is essential for the propagation of many organisms including humans and flies. The cytoplasm of germline cyst cells communicate with each other directly via large intercellular bridges called ring canals. Ring canals are often derived from arrested contractile rings during incomplete cytokinesis. However how ring canal formation, maintenance and growth are regulated remains unclear. To better understand this process, we carried out an unbiased genetic screen in Drosophila melanogaster germ cells and identified multiple alleles of flapwing (flw), a conserved serine/threonine-specific protein phosphatase. Flw had previously been reported to be unnecessary for early D. melanogaster oogenesis using a hypomorphic allele. We found that loss of Flw leads to over-constricted nascent ring canals and subsequently tiny mature ring canals, through which cytoplasmic transfer from nurse cells to the oocyte is impaired, resulting in small, non-functional eggs. Flw is expressed in germ cells undergoing incomplete cytokinesis, completely colocalized with the Drosophila myosin binding subunit of myosin phosphatase (DMYPT). This colocalization, together with genetic interaction studies, suggests that Flw functions together with DMYPT to negatively regulate myosin activity during ring canal formation. The identification of two subunits of the tripartite myosin phosphatase as the first two main players required for ring canal constriction indicates that tight regulation of myosin activity is essential for germline cyst formation and reproduction in D. melanogaster and probably other species as well.
MeSH term(s)	Actin Cytoskeleton ; Amino Acid Sequence ; Animals ; Cell Differentiation ; Cell Proliferation ; Cytokinesis/genetics ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/cytology ; Drosophila melanogaster/enzymology ; Drosophila melanogaster/genetics ; Drosophila melanogaster/growth & development ; Female ; Gene Expression Regulation, Developmental ; Germ Cells/cytology ; Germ Cells/enzymology ; Male ; Molecular Sequence Data ; Myosin-Light-Chain Phosphatase/genetics ; Myosin-Light-Chain Phosphatase/metabolism ; Myosins/genetics ; Myosins/metabolism ; Oocytes/cytology ; Oocytes/enzymology ; Oogenesis/genetics ; Phosphoprotein Phosphatases/genetics ; Phosphoprotein Phosphatases/metabolism ; Protein Subunits/genetics ; Protein Subunits/metabolism
Chemical Substances	Drosophila Proteins ; Protein Subunits ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; flw protein, Drosophila (EC 3.1.3.16) ; Myosin-Light-Chain Phosphatase (EC 3.1.3.53) ; Myosins (EC 3.6.4.1)
Language	English
Publishing date	2013-07-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0070502
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