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Article ; Online: Problematic alcohol use and its impact on liver disease quality of life in a multicenter study of patients with cirrhosis.

Luk, Jeremy W / Satre, Derek D / Cheung, Ramsey / Wong, Robert J / Monto, Alexander / Chen, Jennifer Y / Batki, Steven L / Ostacher, Michael J / Snyder, Hannah R / Shui, Amy M / Liao, Meimei / Haight, Christina G / Khalili, Mandana

Hepatology communications

2024 Volume 8, Issue 2

Abstract: Background: Management of cirrhosis is challenging and has been complicated by the COVID-19 pandemic due to decreased access to care, increased psychological distress, and alcohol misuse. Recently, The National Institute on Alcohol Abuse and Alcoholism ... ...

Abstract	Background: Management of cirrhosis is challenging and has been complicated by the COVID-19 pandemic due to decreased access to care, increased psychological distress, and alcohol misuse. Recently, The National Institute on Alcohol Abuse and Alcoholism has broadened the definition of recovery from alcohol use disorder to include quality of life (QoL) as an indicator of recovery. This study examined the associations of alcohol-associated cirrhosis etiology and problematic drinking with liver disease QoL (LDQoL). Methods: Patients with cirrhosis (N=329) were recruited from 3 sites (63% from 2 Veterans Affairs Health Care Systems and 37% from 1 safety net hospital) serving populations that are economically or socially marginalized. Cirrhosis etiology was ascertained by chart review of medical records. Problematic drinking was defined by ≥8 on the Alcohol Use Disorders Identification Test. Multivariable general linear modeling adjusting for age, sex, race/ethnicity, site, pandemic-related stress, and history of anxiety/depressive disorder were conducted. Sensitivity analyses further adjusted for indicators of liver disease severity. Results: Participants were on average 64.6 years old, 17% female, 58% non-White, 44% with alcohol-associated cirrhosis, and 17% with problematic drinking. Problematic drinking was significantly associated with worse LDQoL scores in the overall scale and in the memory/concentration and health distress subscales. These associations remained significant after adjusting for indicators of liver disease severity, including Model for End-Stage Liver Disease-Sodium score and decompensated cirrhosis status. Conclusions: Among patients with cirrhosis, problematic drinking was associated with worse LDQoL, especially in the domains of memory/concentration and health distress. Assessment and awareness of cognitive deficits and negative emotionality within the context of cirrhosis and problematic drinking may help clinicians provide better integrated care for this population.
MeSH term(s)	Humans ; Female ; Middle Aged ; Male ; Quality of Life/psychology ; Alcoholism/complications ; Alcoholism/epidemiology ; Pandemics ; End Stage Liver Disease ; Severity of Illness Index ; Liver Cirrhosis/epidemiology ; Liver Cirrhosis/complications ; Ethanol
Chemical Substances	Ethanol (3K9958V90M)
Language	English
Publishing date	2024-02-03
Publishing country	United States
Document type	Multicenter Study ; Journal Article
ISSN	2471-254X
ISSN (online)	2471-254X
DOI	10.1097/HC9.0000000000000379
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Article ; Online: Eating and Psychiatric Disorders Are Independent Risk Factors for Rumination Syndrome.

Cai, Jennifer X / Wong, Danny / Lee, Darren J H / Chan, Walter W

Journal of clinical gastroenterology

2021 Volume 56, Issue 3, Page(s) 228–233

Abstract: Goal: The goal of this study was to evaluate whether a history of eating disorders (EDs) or psychiatric disorders (PDs) are risk factors for rumination syndrome (RS).: Background: RS is a disorder of gut-brain interaction characterized by an ... ...

Abstract	Goal: The goal of this study was to evaluate whether a history of eating disorders (EDs) or psychiatric disorders (PDs) are risk factors for rumination syndrome (RS). Background: RS is a disorder of gut-brain interaction characterized by an effortless postprandial retrograde flow of ingested contents. Disorder of gut-brain interactions have been associated with psychiatric and behavioral comorbidities. No prior comparative study has assessed the relationship between RS and ED or PD. Methods: This was a case-control study of adults with RS at a tertiary center in January 2013 to January 2018. Two age-matched/gender-matched controls per RS case were identified. The Fisher exact test (categorical)/Student t test (continuous) and forward stepwise logistic regression were performed for univariate and multivariable analyses, respectively. Results: Seventy-two patients (24 cases/48 controls) were included. Baseline demographics and characteristics were similar between cases and controls. Among RS patients, 9 (37.5%) had a history of ED, including 3 (12.5%) anorexia nervosa and 4 (16.7%) bulimia nervosa; and 20 (83.3%) had a PD, including 9 (37.5%) anxiety and 7 (29.2%) depression. Prevalence of ED (37.5% vs. 4.2%, P=0.0002) and PD (83.3% vs. 50.0%, P=0.0062) were higher among RS patients than controls. Specifically, the risks of anorexia nervosa (16.7% vs. 0%, P=0.005) and bulimia nervosa (21.1% vs. 0%, P=0.001) were both increased in RS patients. On multivariable analysis, ED (adjusted odds ratio=16.4, P=0.0033) and PD (adjusted odds ratio=4.47, P=0.029) remained independent predictors for RS. Conclusions: A history of ED and PD were independent risk factors for RS. Abnormal eating behaviors and psychiatric comorbidities may contribute to the pathogenesis of RS. Evaluation of RS should include a detailed history for ED and PD.
MeSH term(s)	Adult ; Bulimia Nervosa/epidemiology ; Bulimia Nervosa/psychology ; Case-Control Studies ; Feeding and Eating Disorders/epidemiology ; Humans ; Risk Factors ; Rumination Syndrome
Language	English
Publishing date	2021-05-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	448460-5
ISSN	1539-2031 ; 0192-0790
ISSN (online)	1539-2031
ISSN	0192-0790
DOI	10.1097/MCG.0000000000001510
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Article ; Online: A novel role for PGE

Yarboro, Michael T / Boatwright, Naoko / Sekulich, Deanna C / Hooper, Christopher W / Wong, Ting / Poole, Stanley D / Berger, Courtney D / Brown, Alexus J / Jetter, Christopher S / Sucre, Jennifer M S / Shelton, Elaine L / Reese, Jeff

American journal of physiology. Heart and circulatory physiology

2023 Volume 325, Issue 4, Page(s) H687–H701

Abstract: The ductus arteriosus (DA) is a vascular shunt that allows oxygenated blood to bypass the developing lungs in utero. Fetal DA patency requires vasodilatory signaling via the prostaglandin ... ...

Abstract	The ductus arteriosus (DA) is a vascular shunt that allows oxygenated blood to bypass the developing lungs in utero. Fetal DA patency requires vasodilatory signaling via the prostaglandin E
MeSH term(s)	Mice ; Animals ; Infant, Newborn ; Female ; Pregnancy ; Humans ; Ductus Arteriosus/metabolism ; Dinoprostone/metabolism ; Receptors, Prostaglandin E, EP4 Subtype/genetics ; Receptors, Prostaglandin E, EP4 Subtype/metabolism ; Ductus Arteriosus, Patent/genetics ; Mice, Knockout
Chemical Substances	Dinoprostone (K7Q1JQR04M) ; Receptors, Prostaglandin E, EP4 Subtype
Language	English
Publishing date	2023-08-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00294.2023
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Article ; Online: Microbial co-occurrences on catheters from long-term catheterized patients.

Nye, Taylor M / Zou, Zongsen / Obernuefemann, Chloe L P / Pinkner, Jerome S / Lowry, Erin / Kleinschmidt, Kent / Bergeron, Karla / Klim, Aleksandra / Dodson, Karen W / Flores-Mireles, Ana L / Walker, Jennifer N / Wong, Daniel Garrett / Desai, Alana / Caparon, Michael G / Hultgren, Scott J

Nature communications

2024 Volume 15, Issue 1, Page(s) 61

Abstract: Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in catheter ... ...

Abstract	Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in catheter and urine samples from 55 human long-term catheterized patients collected over one year. Although most of these patients were prescribed antibiotics over several collection periods, their catheter samples remain colonized by one or more bacterial species. Examination of a total of 366 catheter and urine samples identify 13 positive and 13 negative genus co-occurrences over 12 collection periods, representing associations that occur more or less frequently than expected by chance. We find that for many patients, the microbial species composition between collection periods is similar. In a subset of patients, we find that the most frequently sampled bacteria, Escherichia coli and Enterococcus faecalis, co-localize on catheter samples. Further, co-culture of paired isolates recovered from the same patients reveals that E. coli significantly augments E. faecalis growth in an artificial urine medium, where E. faecalis monoculture grows poorly. These findings suggest novel strategies to collapse polymicrobial CAUTI in long-term catheterized patients by targeting mechanisms that promote positive co-associations.
MeSH term(s)	Humans ; Escherichia coli ; Catheter-Related Infections/microbiology ; Catheters ; Urinary Tract Infections/microbiology ; Enterococcus faecalis ; Bacteria
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-44095-0
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Article ; Online: Relationship of SARS-CoV-2 Antigen and Reverse Transcription PCR Positivity for Viral Cultures.

Emerging infectious diseases

2022 Volume 28, Issue 3, Page(s) 717–720

Abstract: We assessed the relationship between antigen and reverse transcription PCR (RT-PCR) test positivity and successful virus isolation. We found that antigen test results were more predictive of virus recovery than RT-PCR results. However, virus was isolated ...

Abstract	We assessed the relationship between antigen and reverse transcription PCR (RT-PCR) test positivity and successful virus isolation. We found that antigen test results were more predictive of virus recovery than RT-PCR results. However, virus was isolated from some antigen-negative and RT-PCR‒positive paired specimens, providing support for the Centers for Disease Control and Prevention antigen testing algorithm.
MeSH term(s)	Antigens, Viral ; COVID-19/diagnosis ; Humans ; Polymerase Chain Reaction ; Reverse Transcription ; SARS-CoV-2/genetics ; Sensitivity and Specificity
Chemical Substances	Antigens, Viral
Language	English
Publishing date	2022-02-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2803.211747
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Article ; Online: Parallel recovery of chromatin accessibility and gene expression dynamics from frozen human regulatory T cells.

Wong, Ying Y / Harbison, Jessica E / Hope, Christopher M / Gundsambuu, Batjargal / Brown, Katherine A / Wong, Soon W / Brown, Cheryl Y / Couper, Jennifer J / Breen, Jimmy / Liu, Ning / Pederson, Stephen M / Köhne, Maren / Klee, Kathrin / Schultze, Joachim / Beyer, Marc / Sadlon, Timothy / Barry, Simon C

Scientific reports

2023 Volume 13, Issue 1, Page(s) 5506

Abstract: Epigenetic features such as DNA accessibility dictate transcriptional regulation in a cell type- and cell state- specific manner, and mapping this in health vs. disease in clinically relevant material is opening the door to new mechanistic insights and ... ...

Abstract	Epigenetic features such as DNA accessibility dictate transcriptional regulation in a cell type- and cell state- specific manner, and mapping this in health vs. disease in clinically relevant material is opening the door to new mechanistic insights and new targets for therapy. Assay for Transposase Accessible Chromatin Sequencing (ATAC-seq) allows chromatin accessibility profiling from low cell input, making it tractable on rare cell populations, such as regulatory T (Treg) cells. However, little is known about the compatibility of the assay with cryopreserved rare cell populations. Here we demonstrate the robustness of an ATAC-seq protocol comparing primary Treg cells recovered from fresh or cryopreserved PBMC samples, in the steady state and in response to stimulation. We extend this method to explore the feasibility of conducting simultaneous quantitation of chromatin accessibility and transcriptome from a single aliquot of 50,000 cryopreserved Treg cells. Profiling of chromatin accessibility and gene expression in parallel within the same pool of cells controls for cellular heterogeneity and is particularly beneficial when constrained by limited input material. Overall, we observed a high correlation of accessibility patterns and transcription factor dynamics between fresh and cryopreserved samples. Furthermore, highly similar transcriptomic profiles were obtained from whole cells and from the supernatants recovered from ATAC-seq reactions. We highlight the feasibility of applying these techniques to profile the epigenomic landscape of cells recovered from cryopreservation biorepositories.
MeSH term(s)	Humans ; Chromatin/genetics ; T-Lymphocytes, Regulatory ; Leukocytes, Mononuclear ; High-Throughput Nucleotide Sequencing/methods ; Transcriptome
Chemical Substances	Chromatin
Language	English
Publishing date	2023-04-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-32256-6
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Article ; Online: Microbial co-occurrences on catheters from long-term catheterized patients

Taylor M. Nye / Zongsen Zou / Chloe L. P. Obernuefemann / Jerome S. Pinkner / Erin Lowry / Kent Kleinschmidt / Karla Bergeron / Aleksandra Klim / Karen W. Dodson / Ana L. Flores-Mireles / Jennifer N. Walker / Daniel Garrett Wong / Alana Desai / Michael G. Caparon / Scott J. Hultgren

Nature Communications, Vol 15, Iss 1, Pp 1-

2024 Volume 13

Abstract: Abstract Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in ... ...

Abstract	Abstract Catheter-associated urinary tract infections (CAUTIs), a common cause of healthcare-associated infections, are caused by a diverse array of pathogens that are increasingly becoming antibiotic resistant. We analyze the microbial occurrences in catheter and urine samples from 55 human long-term catheterized patients collected over one year. Although most of these patients were prescribed antibiotics over several collection periods, their catheter samples remain colonized by one or more bacterial species. Examination of a total of 366 catheter and urine samples identify 13 positive and 13 negative genus co-occurrences over 12 collection periods, representing associations that occur more or less frequently than expected by chance. We find that for many patients, the microbial species composition between collection periods is similar. In a subset of patients, we find that the most frequently sampled bacteria, Escherichia coli and Enterococcus faecalis, co-localize on catheter samples. Further, co-culture of paired isolates recovered from the same patients reveals that E. coli significantly augments E. faecalis growth in an artificial urine medium, where E. faecalis monoculture grows poorly. These findings suggest novel strategies to collapse polymicrobial CAUTI in long-term catheterized patients by targeting mechanisms that promote positive co-associations.
Keywords	Science ; Q
Subject code	610
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Characterizing the cascade of care for hepatitis C virus infection among Status First Nations peoples in Ontario: a retrospective cohort study.

Mendlowitz, Andrew B / Bremner, Karen E / Krahn, Murray / Walker, Jennifer D / Wong, William W L / Sander, Beate / Jones, Lyndia / Isaranuwatchai, Wanrudee / Feld, Jordan J

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne

2023 Volume 195, Issue 14, Page(s) E499–E512

Abstract: Background: As First Nations Peoples are a priority focus of Canada's commitment to eliminating hepatitis C virus (HCV) as a public health threat, understanding individuals' progression from diagnosis to cure can guide prioritization of elimination ... ...

Abstract	Background: As First Nations Peoples are a priority focus of Canada's commitment to eliminating hepatitis C virus (HCV) as a public health threat, understanding individuals' progression from diagnosis to cure can guide prioritization of elimination efforts. We sought to characterize and identify gaps in the HCV care cascade for Status First Nations peoples in Ontario. Methods: In this retrospective cohort study, a partnership between the Ontario First Nations HIV/AIDS Education Circle and academic researchers, HCV testing records (1999-2018) for Status First Nations peoples in Ontario were linked to health administrative data. We defined the cascade of care as 6 stages, as follows: tested positive for HCV antibody, tested for HCV RNA, tested positive for HCV RNA, HCV genotyped, initiated treatment and achieved sustained viral response (SVR). We mapped the care cascade from 1999 to 2018, and estimated the number and proportion of people at each stage. We stratified analyses by sex, diagnosis date and location of residence. We used Cox regression to analyze the secondary outcomes, namely the associations between undergoing HCV RNA testing and initiating treatment, and demographic and clinical predictors. Results: By Dec. 31, 2018, 4962 people tested positive for HCV antibody. Of those testing positive, 4118 (83.0%) were tested for HCV RNA, with 2480 (60.2%) testing positive. Genotyping was completed in 2374 (95.7%) of those who tested positive for HCV RNA, with 1002 (42.2%) initiating treatment. Nearly 80% ( Interpretation: In comparison with HCV testing and diagnosis, a substantial gap in treatment initiation remains among Status First Nations populations in Ontario. Elimination efforts that prioritize linkage to care and integration with harm reduction and substance use services are needed to close gaps in HCV care among First Nations populations in Ontario.
MeSH term(s)	Humans ; Hepacivirus ; Antiviral Agents/therapeutic use ; Retrospective Studies ; Ontario ; Hepatitis C, Chronic/drug therapy ; Hepatitis C ; Substance-Related Disorders ; RNA, Viral
Chemical Substances	Antiviral Agents ; RNA, Viral
Language	English
Publishing date	2023-04-11
Publishing country	Canada
Document type	Journal Article
ZDB-ID	215506-0
ISSN	1488-2329 ; 0008-4409 ; 0820-3946
ISSN (online)	1488-2329
ISSN	0008-4409 ; 0820-3946
DOI	10.1503/cmaj.220717
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Article: Direct Detection of 4-Dimensions of SARS-CoV-2: Infection (vRNA), Infectivity (Antigen), Binding Antibody, and Functional Neutralizing Antibody in Saliva.

Mohammadi, Aida / Chiang, Samantha / Li, Feng / Wei, Fang / Lau, Chang S / Aziz, Mohammad / Ibarrondo, Francisco J / Fulcher, Jennifer A / Yang, Otto O / Chia, David / Kim, Yong / Wong, David T W

Research square

2023

Abstract: We developed a 4-parameter clinical assay using Electric Field Induced Release and Measurement (EFIRM) technology to simultaneously assess SARS-CoV-2 RNA (vRNA), nucleocapsid antigen, host binding (BAb) and neutralizing antibody (NAb) levels from a drop ... ...

Abstract	We developed a 4-parameter clinical assay using Electric Field Induced Release and Measurement (EFIRM) technology to simultaneously assess SARS-CoV-2 RNA (vRNA), nucleocapsid antigen, host binding (BAb) and neutralizing antibody (NAb) levels from a drop of saliva with performance that equals or surpasses current EUA-approved tests. The vRNA and antigen assays achieved lower limit of detection (LOD) of 100 copies/reaction and 3.5 TCID₅₀/mL, respectively. The vRNA assay differentiated between acutely infected (n=10) and infection-naïve patients (n=33) with an AUC of 0.9818, sensitivity of 90%, and specificity of 100%. The antigen assay similarly differentiated these patient populations with an AUC of 1.000. The BAb assay detected BAbs with an LOD of 39 pg/mL and distinguished acutely infected (n=35), vaccinated with prior infection (n=13), and vaccinated infection-naïve patients (n=13) from control (n=81) with AUC of 0.9481, 1.000, and 0.9962, respectively. The NAb assay detected NAbs with an LOD of 31.6 Unit/mL and differentiated between COVID-19 recovered or vaccinated patients (n=31) and pre-pandemic controls (n=60) with an AUC 0.923, sensitivity of 87.10%, and specificity of 86.67%. Our multiparameter assay represents a significant technological advancement to simultaneously address SARS-CoV-2 infection and immunity, and it lays the foundation for tackling potential future pandemics.
Language	English
Publishing date	2023-12-28
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3745787/v1
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Article ; Online: Oxidative stress from DGAT1 oncoprotein inhibition in melanoma suppresses tumor growth when ROS defenses are also breached.

Cell reports

2024 Volume 39, Issue 12, Page(s) 110995

Abstract: Dysregulated cellular metabolism is a cancer hallmark for which few druggable oncoprotein targets have been identified. Increased fatty acid (FA) acquisition allows cancer cells to meet their heightened membrane biogenesis, bioenergy, and signaling needs. ...

Abstract	Dysregulated cellular metabolism is a cancer hallmark for which few druggable oncoprotein targets have been identified. Increased fatty acid (FA) acquisition allows cancer cells to meet their heightened membrane biogenesis, bioenergy, and signaling needs. Excess FAs are toxic to non-transformed cells but surprisingly not to cancer cells. Molecules underlying this cancer adaptation may provide alternative drug targets. Here, we demonstrate that diacylglycerol O-acyltransferase 1 (DGAT1), an enzyme integral to triacylglyceride synthesis and lipid droplet formation, is frequently up-regulated in melanoma, allowing melanoma cells to tolerate excess FA. DGAT1 over-expression alone transforms p53-mutant zebrafish melanocytes and co-operates with oncogenic BRAF or NRAS for more rapid melanoma formation. Antagonism of DGAT1 induces oxidative stress in melanoma cells, which adapt by up-regulating cellular reactive oxygen species defenses. We show that inhibiting both DGAT1 and superoxide dismutase 1 profoundly suppress tumor growth through eliciting intolerable oxidative stress.
MeSH term(s)	Animals ; Diacylglycerol O-Acyltransferase/genetics ; Diacylglycerol O-Acyltransferase/metabolism ; Melanoma ; Oncogene Proteins/metabolism ; Oxidative Stress ; Reactive Oxygen Species ; Triglycerides ; Zebrafish/metabolism
Chemical Substances	Oncogene Proteins ; Reactive Oxygen Species ; Triglycerides ; Diacylglycerol O-Acyltransferase (EC 2.3.1.20)
Language	English
Publishing date	2024-02-05
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.2022.110995
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