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Article ; Online: ColocQuiaL: a QTL-GWAS colocalization pipeline.

Chen, Brian Y / Bone, William P / Lorenz, Kim / Levin, Michael / Ritchie, Marylyn D / Voight, Benjamin F

2022 Volume 38, Issue 18, Page(s) 4409–4411

Abstract: Summary: Identifying genomic features responsible for genome-wide association study (GWAS) signals has proven to be a difficult challenge; many researchers have turned to colocalization analysis of GWAS signals with expression quantitative trait loci ( ... ...

Abstract	Summary: Identifying genomic features responsible for genome-wide association study (GWAS) signals has proven to be a difficult challenge; many researchers have turned to colocalization analysis of GWAS signals with expression quantitative trait loci (eQTL) and splicing quantitative trait loci (sQTL) to connect GWAS signals to candidate causal genes. The ColocQuiaL pipeline provides a framework to perform these colocalization analyses at scale across the genome and returns summary files and locus visualization plots to allow for detailed review of the results. As an example, we used ColocQuiaL to perform colocalization between a recent type 2 diabetes GWAS and Genotype-Tissue Expression (GTEx) v8 single-tissue eQTL and sQTL data. Availability and implementation: ColocQuiaL is primarily written in R and is freely available on GitHub: https://github.com/bvoightlab/ColocQuiaL.
MeSH term(s)	Humans ; Genome-Wide Association Study/methods ; Quantitative Trait Loci ; Diabetes Mellitus, Type 2/genetics ; Genomics ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease
Language	English
Publishing date	2022-07-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btac512
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Article ; Online: Mixed methods evaluation of handshake antimicrobial stewardship on adult inpatient medicine floors.

Neuner, Elizabeth A / Atkinson, Andrew / Ilges, Dan / Krekel, Tamara / Ritchie, David J / Bewley, Alice F / Durkin, Michael J / Hsueh, Kevin / Sayood, Sena

Antimicrobial stewardship & healthcare epidemiology : ASHE

2023 Volume 3, Issue 1, Page(s) e210

Abstract: Objective: To evaluate the effects of handshake antimicrobial stewardship on medicine floors at a large tertiary care hospital.: Design: Retrospective observational study.: Setting: 1,278-bed academic hospital.: Patients: Adults admitted to non- ...

Abstract	Objective: To evaluate the effects of handshake antimicrobial stewardship on medicine floors at a large tertiary care hospital. Design: Retrospective observational study. Setting: 1,278-bed academic hospital. Patients: Adults admitted to non-ICU medicine services. Interventions: A handshake stewardship team consisting of an infectious diseases (ID) physician and pharmacist reviewed charts of patients receiving antimicrobials on medicine floors without a formal ID consult. Recommendations were communicated in-person to providers and acceptance rates were examined with descriptive statistics. Additional data regarding program perception among providers were obtained via surveys. Antibiotic usage trends were extracted from National Healthcare Safety Network Antimicrobial Use option data and evaluated using an interrupted time-series analysis pre- and post-intervention. Results: The overall acceptance rate of interventions was 80%, the majority being recommendations either to discontinue (37%) or de-escalate therapy (28%). Medical residents and hospitalists rated the intervention favorably with 90% reporting recommendations were helpful all or most of the time. There was a statistically significant decrease in vancomycin (78 vs 70 DOT/1,000 d present (DP), Conclusion: The addition of handshake stewardship with adult medicine services was favorably viewed by participants and led to shifts in antibiotic usage.
Language	English
Publishing date	2023-11-16
Publishing country	England
Document type	Journal Article
ISSN	2732-494X
ISSN (online)	2732-494X
DOI	10.1017/ash.2023.465
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Article: Temporal changes in skin and gill microbiomes of Atlantic salmon in a recirculating aquaculture system – Why do they matter?

Lorgen-Ritchie, Marlene / Clarkson, Michael / Chalmers, Lynn / Taylor, John F. / Migaud, Herve / Martin, Samuel A.M.

Aquaculture. 2022 Sept. 15, v. 558

2022

Abstract: Mucosal surfaces are key components of teleost health, providing defence against opportunistic pathogens and other insults. Maintaining the integrity of mucosal surfaces and their associated microbial communities, especially the gill and skin that have ... ...

Abstract	Mucosal surfaces are key components of teleost health, providing defence against opportunistic pathogens and other insults. Maintaining the integrity of mucosal surfaces and their associated microbial communities, especially the gill and skin that have large surface areas exposed to the environment is essential. Production of Atlantic salmon in land-based recirculating aquaculture systems (RAS) has increased significantly in recent years as it allows greater control over stability of the environment in which fish are reared, reduces water demand and minimises environmental impacts. However, little is known about the impact of the RAS environment upon the temporal dynamics of skin and gill mucosal microbiomes. In this study we examined microbial communities in gill mucus, skin mucus and rearing water throughout freshwater (FW) RAS production, and at 1-week and 4-weeks following transfer to seawater (SW) in open cage production using 16S rRNA sequencing. Microbial diversity and richness in skin and gill mucus of fish reared in a RAS system were temporally dynamic. Dynamics in richness and diversity were similar in the two mucosal tissues, and to some extent also mirrored that of the surrounding water. Dysbiosis indicated by an abrupt decline in diversity during FW production coincided with an increase in the relative abundance of two taxa belonging to the RAS-biofilter-associated nitrogen-cycling genus Hydrogenophaga in RAS tank water and this was also observed in gill and skin mucus. Extensive overlap in core taxa was observed between gill and skin mucus, but host-specific cores were non-existent during the dysbiotic event with all cores present in the rearing water. Diversity remained stable during the transition from FW to SW, but distinct community composition and core taxa were observed in the two environments. Although RAS are closely controlled, significant temporal variation could be observed in temperature as well as levels of CO₂ and nitrogen compounds, reflecting the increasing biological load within the system over time. The results presented here suggest that, in terms of microbiomes, dysbiosis may occur in both the RAS environment and fish mucosal surfaces over time, but microbial communities have the capability to recover.
Keywords	Hydrogenophaga ; Salmo salar ; carbon dioxide ; community structure ; dysbiosis ; fish ; freshwater ; host specificity ; microbiome ; mucus ; nitrogen ; seawater ; temperature ; temporal variation
Language	English
Dates of publication	2022-0915
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	185380-6
ISSN	0044-8486 ; 0044-8516
ISSN	0044-8486 ; 0044-8516
DOI	10.1016/j.aquaculture.2022.738352
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Article ; Online: Allogeneic stem cell transplantation achieves long-term remissions in mantle cell lymphoma, including in

Lew, Thomas E / Cliff, Edward R Scheffer / Dickinson, Michael / Tam, Constantine S / Seymour, John F / Blombery, Piers / Bajel, Ashish / Ritchie, David / Khot, Amit

Leukemia & lymphoma

2023 Volume 64, Issue 11, Page(s) 1792–1800

Abstract: Cytarabine-containing chemoimmunotherapy followed by autologous transplantation and rituximab maintenance achieves durable remissions for most patients with mantle cell lymphoma (MCL). However, patients ... ...

Abstract	Cytarabine-containing chemoimmunotherapy followed by autologous transplantation and rituximab maintenance achieves durable remissions for most patients with mantle cell lymphoma (MCL). However, patients with
MeSH term(s)	Adult ; Humans ; Lymphoma, Mantle-Cell/therapy ; Lymphoma, Mantle-Cell/drug therapy ; Neoplasm Recurrence, Local ; Hematopoietic Stem Cell Transplantation/adverse effects ; Rituximab/therapeutic use ; Transplantation, Autologous ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Stem Cell Transplantation ; Tumor Suppressor Protein p53/genetics
Chemical Substances	Rituximab (4F4X42SYQ6) ; TP53 protein, human ; Tumor Suppressor Protein p53
Language	English
Publishing date	2023-08-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2023.2241095
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Article ; Online: Treatment approaches for patients with TP53-mutated mantle cell lymphoma.

Lew, Thomas E / Minson, Adrian / Dickinson, Michael / Handunnetti, Sasanka M / Blombery, Piers / Khot, Amit / Anderson, Mary Ann / Ritchie, David / Tam, Constantine S / Seymour, John F

The Lancet. Haematology

2023 Volume 10, Issue 2, Page(s) e142–e154

Abstract: Mantle cell lymphoma is an uncommon subtype of lymphoma characterised by clinical and biological heterogeneity. Although most patients with mantle cell lymphoma have durable responses after chemoimmunotherapy, there is a need to prospectively identify ... ...

Abstract	Mantle cell lymphoma is an uncommon subtype of lymphoma characterised by clinical and biological heterogeneity. Although most patients with mantle cell lymphoma have durable responses after chemoimmunotherapy, there is a need to prospectively identify high-risk subsets of patients for whom disease control with standard chemotherapy will be short lived. Among the available prognostic factors, TP53 mutations are uniquely informative owing to their strong association with early disease progression and death among patients receiving conventional chemoimmunotherapy, with the highest negative prognostic value compared with other established risk indicators, including the mantle cell lymphoma international prognostic index, histological features, elevated Ki-67, and other genetic lesions. The poor outcomes for patients with TP53-mutated mantle cell lymphoma receiving chemoimmunotherapy and second-line Bruton tyrosine kinase inhibitors represent an urgent need for alternative approaches. In this Review, we synthesise the available data to inform the management of this high-risk subset of patients and present a treatment strategy prioritising clinical trials and early use of cellular therapies.
MeSH term(s)	Humans ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Immunotherapy ; Lymphoma, Mantle-Cell/drug therapy ; Lymphoma, Mantle-Cell/genetics ; Patients ; Prognosis ; Tumor Suppressor Protein p53/genetics
Chemical Substances	TP53 protein, human ; Tumor Suppressor Protein p53
Language	English
Publishing date	2023-02-01
Publishing country	England
Document type	Journal Article ; Review
ISSN	2352-3026
ISSN (online)	2352-3026
DOI	10.1016/S2352-3026(22)00355-6
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Article: SLC19A1 Is an Importer of the Immunotransmitter cGAMP

Ritchie, Christopher / Cordova, Anthony F / Hess, Gaelen T / Bassik, Michael C / Li, Lingyin

Molecular cell. 2019 July 25, v. 75, no. 2

2019

Abstract: 2′3′-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antiviral stimulator of interferon genes (STING) pathway. We recently identified a novel role for cGAMP as a soluble, extracellular immunotransmitter that is produced and secreted by ... ...

Abstract	2′3′-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antiviral stimulator of interferon genes (STING) pathway. We recently identified a novel role for cGAMP as a soluble, extracellular immunotransmitter that is produced and secreted by cancer cells. Secreted cGAMP is then sensed by host cells, eliciting an antitumoral immune response. Due to the antitumoral effects of cGAMP, other CDN-based STING agonists are currently under investigation in clinical trials for metastatic solid tumors. However, it is unknown how cGAMP and other CDNs cross the cell membrane to activate intracellular STING. Using a genome-wide CRISPR screen, we identified SLC19A1 as the first known importer of cGAMP and other CDNs, including the investigational new drug 2′3′-bisphosphosphothioate-cyclic-di-AMP (2′3′-CDAS). These discoveries will provide insight into cGAMP’s role as an immunotransmitter and aid in the development of more targeted CDN-based cancer therapeutics.
Keywords	agonists ; antineoplastic activity ; cell membranes ; clinical trials ; drugs ; gene editing ; genes ; immune response ; interferons ; metastasis ; neoplasm cells ; neoplasms ; second messengers ; therapeutics
Language	English
Dates of publication	2019-0725
Size	p. 372-381.e5.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2019.05.006
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Article ; Online: Mixed methods evaluation of handshake antimicrobial stewardship on adult inpatient medicine floors

Elizabeth A. Neuner / Andrew Atkinson / Dan Ilges / Tamara Krekel / David J. Ritchie / Alice F. Bewley / Michael J. Durkin / Kevin Hsueh / Sena Sayood

Antimicrobial Stewardship & Healthcare Epidemiology, Vol

2023 Volume 3

Abstract: Abstract Objective: To evaluate the effects of handshake antimicrobial stewardship on medicine floors at a large tertiary care hospital. Design: Retrospective observational study. Setting: 1,278-bed academic hospital. Patients: Adults admitted to non-ICU ...

Abstract	Abstract Objective: To evaluate the effects of handshake antimicrobial stewardship on medicine floors at a large tertiary care hospital. Design: Retrospective observational study. Setting: 1,278-bed academic hospital. Patients: Adults admitted to non-ICU medicine services. Interventions: A handshake stewardship team consisting of an infectious diseases (ID) physician and pharmacist reviewed charts of patients receiving antimicrobials on medicine floors without a formal ID consult. Recommendations were communicated in-person to providers and acceptance rates were examined with descriptive statistics. Additional data regarding program perception among providers were obtained via surveys. Antibiotic usage trends were extracted from National Healthcare Safety Network Antimicrobial Use option data and evaluated using an interrupted time-series analysis pre- and post-intervention. Results:The overall acceptance rate of interventions was 80%, the majority being recommendations either to discontinue (37%) or de-escalate therapy (28%). Medical residents and hospitalists rated the intervention favorably with 90% reporting recommendations were helpful all or most of the time. There was a statistically significant decrease in vancomycin (78 vs 70 DOT/1,000 d present (DP), p = 0.002) and meropenem (24 vs 17 DOT/1,000 DP, p = 0.007) usage and a statistically significant increase in amoxicillin-clavulanate usage (11 vs 15 DOT/1,000 DP, p < 0.001). Overall antibiotic usage remained unchanged by the intervention, though pre-intervention there was a nonsignificant overall increasing trend while post-intervention there was a nonsignificant decreasing trend in overall usage. There was no change in in-hospital mortality. Conclusion: The addition of handshake stewardship with adult medicine services was favorably viewed by participants and led to shifts in antibiotic usage.
Keywords	Infectious and parasitic diseases ; RC109-216 ; Public aspects of medicine ; RA1-1270
Subject code	796
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Cambridge University Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SLC19A1 Is an Importer of the Immunotransmitter cGAMP.

Ritchie, Christopher / Cordova, Anthony F / Hess, Gaelen T / Bassik, Michael C / Li, Lingyin

Molecular cell

2019 Volume 75, Issue 2, Page(s) 372–381.e5

Abstract: 2'3'-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antiviral stimulator of interferon genes (STING) pathway. We recently identified a novel role for cGAMP as a soluble, extracellular immunotransmitter that is produced and secreted by ... ...

Abstract	2'3'-cyclic-GMP-AMP (cGAMP) is a second messenger that activates the antiviral stimulator of interferon genes (STING) pathway. We recently identified a novel role for cGAMP as a soluble, extracellular immunotransmitter that is produced and secreted by cancer cells. Secreted cGAMP is then sensed by host cells, eliciting an antitumoral immune response. Due to the antitumoral effects of cGAMP, other CDN-based STING agonists are currently under investigation in clinical trials for metastatic solid tumors. However, it is unknown how cGAMP and other CDNs cross the cell membrane to activate intracellular STING. Using a genome-wide CRISPR screen, we identified SLC19A1 as the first known importer of cGAMP and other CDNs, including the investigational new drug 2'3'-bisphosphosphothioate-cyclic-di-AMP (2'3'-CDA
MeSH term(s)	CRISPR-Cas Systems/genetics ; Cell Line, Tumor ; Cell Membrane/genetics ; Genome, Human/genetics ; Humans ; Immunity, Innate/genetics ; Membrane Proteins/genetics ; Neoplasms/genetics ; Neoplasms/immunology ; Nucleotides, Cyclic/genetics ; Nucleotides, Cyclic/immunology ; Reduced Folate Carrier Protein/genetics ; Signal Transduction/genetics
Chemical Substances	Membrane Proteins ; Nucleotides, Cyclic ; Reduced Folate Carrier Protein ; SLC19A1 protein, human ; STING1 protein, human ; cyclic guanosine monophosphate-adenosine monophosphate
Language	English
Publishing date	2019-05-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2019.05.006
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Article ; Online: COVID-19 outcomes and the human genome.

Murray, Michael F / Kenny, Eimear E / Ritchie, Marylyn D / Rader, Daniel J / Bale, Allen E / Giovanni, Monica A / Abul-Husn, Noura S

Genetics in medicine : official journal of the American College of Medical Genetics

2020 Volume 22, Issue 7, Page(s) 1175–1177

MeSH term(s)	Betacoronavirus/pathogenicity ; COVID-19 ; Coronavirus Infections/epidemiology ; Coronavirus Infections/genetics ; Coronavirus Infections/mortality ; Coronavirus Infections/virology ; Disease Resistance/genetics ; Genetic Predisposition to Disease ; Genome, Human/genetics ; Host-Pathogen Interactions/genetics ; Humans ; Pandemics ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/genetics ; Pneumonia, Viral/mortality ; Pneumonia, Viral/virology ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-05-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	1455352-1
ISSN	1530-0366 ; 1098-3600
ISSN (online)	1530-0366
ISSN	1098-3600
DOI	10.1038/s41436-020-0832-3
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Article ; Online: Evaluation of SAMBA II: A Qualitative and Semiquantitative HIV Point-of-Care Nucleic Acid Test.

Violette, Lauren R / Cornelius-Hudson, Andy / Snidarich, Madison / Niemann, Lisa A / Assennato, Sonny Michael / Ritchie, Allyson / Goel, Neha / Chavez, Pollyanna R / Ethridge, Steven F / Katz, David A / Lee, Helen / Delaney, Kevin P / Stekler, Joanne D

Journal of acquired immune deficiency syndromes (1999)

2022 Volume 89, Issue 5, Page(s) 537–545

Abstract: Background: Point-of-care (POC) nucleic acid tests (NATs) have potential to diagnose acute HIV infection and monitor persons taking pre-exposure prophylaxis or antiretroviral therapy (ART). POC NATs have not yet been evaluated in the US.: Methods: ... ...

Abstract	Background: Point-of-care (POC) nucleic acid tests (NATs) have potential to diagnose acute HIV infection and monitor persons taking pre-exposure prophylaxis or antiretroviral therapy (ART). POC NATs have not yet been evaluated in the US. Methods: From June 2018-March 2019, we conducted a cross-sectional evaluation of the Simple Amplification-Based Assay version II (SAMBA II) POC NAT. People with HIV (PWH) and persons testing for HIV were tested with the SAMBA II qualitative (Qual) whole blood (WB) test. From April-September 2019, the Qual test was used on persons who were ART-naive, and SAMBA II Semi-quantitative (Semi-Q) WB was used with ART-experienced PWH. Both were performed on unprocessed venipuncture (VP) and, when indicated by protocol, fingerstick (FS) WB and plasma. SAMBA results were compared with Abbott RealTime HIV-1 polymerase chain reaction results on plasma. We calculated sensitivity, specificity, and concordance between tests. Results: SAMBA was used in 330 visits among 280 participants: 202 (61.2%) visits from PWH, and 128 (38.8%) from HIV-negative persons. Qual test sensitivity with ART-naive participants was 91.4% [32/35, 95% confidence interval (CI): 77.6% to 97.0%] using VP WB and 100% (27/27, 95% CI: 87.5% to 100%) using FS WB. Specificity was 100% using both specimen types. Concordance between the gold standard and Semi-Q at 1000 copies/mL among PWH on ART was 97.7% (86/88, 95% CI: 92.1% to 99.4%) and 100% (30/30, 95% CI: 88.7% to 100%) using VP and FS WB, respectively. Conclusions: The SAMBA II POC NATs showed high sensitivity, specificity, and concordance with the gold standard assay, indicating its potential use in diagnostics and monitoring. Future work will evaluate POC NAT implementation in the US.
MeSH term(s)	Cross-Sectional Studies ; HIV Infections/diagnosis ; HIV Infections/drug therapy ; Humans ; Nucleic Acids/therapeutic use ; Point-of-Care Systems ; Point-of-Care Testing ; Sensitivity and Specificity ; Viral Load/methods
Chemical Substances	Nucleic Acids
Language	English
Publishing date	2022-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	645053-2
ISSN	1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
ISSN (online)	1944-7884 ; 1077-9450
ISSN	0897-5965 ; 0894-9255 ; 1525-4135
DOI	10.1097/QAI.0000000000002902
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