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Article ; Online: Oldest evidence of abundant C

Peppe, Daniel J / Cote, Susanne M / Deino, Alan L / Fox, David L / Kingston, John D / Kinyanjui, Rahab N / Lukens, William E / MacLatchy, Laura M / Novello, Alice / Strömberg, Caroline A E / Driese, Steven G / Garrett, Nicole D / Hillis, Kayla R / Jacobs, Bonnie F / Jenkins, Kirsten E H / Kityo, Robert M / Lehmann, Thomas / Manthi, Fredrick K / Mbua, Emma N /

Michel, Lauren A / Miller, Ellen R / Mugume, Amon A T / Muteti, Samuel N / Nengo, Isaiah O / Oginga, Kennedy O / Phelps, Samuel R / Polissar, Pratigya / Rossie, James B / Stevens, Nancy J / Uno, Kevin T / McNulty, Kieran P

Science (New York, N.Y.)

2023 Volume 380, Issue 6641, Page(s) 173–177

Abstract: The assembly of Africa's iconic C ...

Abstract	The assembly of Africa's iconic C
MeSH term(s)	Animals ; Africa, Eastern ; Biological Evolution ; Ecosystem ; Grassland ; Hominidae ; Mammals ; Poaceae
Language	English
Publishing date	2023-04-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abq2834
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 77: Show issues

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Article ; Online: Where to Next? Research Directions after the First Hepatitis C Vaccine Efficacy Trial.

Phelps, Christopher C / Walker, Christopher M / Honegger, Jonathan R

Viruses

2021 Volume 13, Issue 7

Abstract: Thirty years after its discovery, the hepatitis C virus (HCV) remains a leading cause ...

Abstract	Thirty years after its discovery, the hepatitis C virus (HCV) remains a leading cause of liver disease worldwide. Given that many countries continue to experience high rates of transmission despite the availability of potent antiviral therapies, an effective vaccine is seen as critical for the elimination of HCV. The recent failure of the first vaccine efficacy trial for the prevention of chronic HCV confirmed suspicions that this virus will be a challenging vaccine target. Here, we examine the published data from this first efficacy trial along with the earlier clinical and pre-clinical studies of the vaccine candidate and then discuss three key research directions expected to be important in ongoing and future HCV vaccine development. These include the following: 1. design of novel immunogens that generate immune responses to genetically diverse HCV genotypes and subtypes, 2. strategies to elicit broadly neutralizing antibodies against envelope glycoproteins in addition to cytotoxic and helper T cell responses, and 3. consideration of the unique immunological status of individuals most at risk for HCV infection, including those who inject drugs, in vaccine platform development and early immunogenicity trials.
MeSH term(s)	Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Neutralizing/immunology ; Hepacivirus/genetics ; Hepacivirus/immunology ; Hepacivirus/pathogenicity ; Hepatitis C/prevention & control ; Hepatitis C/virology ; Hepatitis C Antibodies/immunology ; Hepatitis C Antigens/immunology ; Humans ; Viral Envelope Proteins/genetics ; Viral Hepatitis Vaccines/immunology ; Viral Hepatitis Vaccines/pharmacology
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Neutralizing ; Hepatitis C Antibodies ; Hepatitis C Antigens ; Viral Envelope Proteins ; Viral Hepatitis Vaccines
Language	English
Publishing date	2021-07-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13071351
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Where to Next? Research Directions after the First Hepatitis C Vaccine Efficacy Trial

Phelps, Christopher C. / Walker, Christopher M. / Honegger, Jonathan R.

Viruses. 2021 July 13, v. 13, no. 7

2021

Abstract: Thirty years after its discovery, the hepatitis C virus (HCV) remains a leading cause ...

Abstract	Thirty years after its discovery, the hepatitis C virus (HCV) remains a leading cause of liver disease worldwide. Given that many countries continue to experience high rates of transmission despite the availability of potent antiviral therapies, an effective vaccine is seen as critical for the elimination of HCV. The recent failure of the first vaccine efficacy trial for the prevention of chronic HCV confirmed suspicions that this virus will be a challenging vaccine target. Here, we examine the published data from this first efficacy trial along with the earlier clinical and pre-clinical studies of the vaccine candidate and then discuss three key research directions expected to be important in ongoing and future HCV vaccine development. These include the following: 1. design of novel immunogens that generate immune responses to genetically diverse HCV genotypes and subtypes, 2. strategies to elicit broadly neutralizing antibodies against envelope glycoproteins in addition to cytotoxic and helper T cell responses, and 3. consideration of the unique immunological status of individuals most at risk for HCV infection, including those who inject drugs, in vaccine platform development and early immunogenicity trials.
Keywords	Hepatitis C virus ; T-lymphocytes ; antigens ; cytotoxicity ; glycoproteins ; hepatitis C ; immunogenicity ; risk ; vaccine development ; vaccines ; viruses
Language	English
Dates of publication	2021-0713
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13071351
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: PP2A is a therapeutically targetable driver of cell fate decisions via a c-Myc/p21 axis in human and murine acute myeloid leukemia.

Goswami, Swagata / Mani, Rajeswaran / Nunes, Jessica / Chiang, Chi-Ling / Zapolnik, Kevan / Hu, Eileen / Frissora, Frank / Mo, Xiaokui / Walker, Logan A / Yan, Pearlly / Bundschuh, Ralf / Beaver, Larry / Devine, Raymond / Tsai, Yo-Ting / Ventura, Ann / Xie, Zhiliang / Chen, Min / Lapalombella, Rosa / Walker, Alison /

Mims, Alice / Larkin, Karilyn / Grieselhuber, Nicole / Bennett, Chad / Phelps, Mitch / Hertlein, Erin / Behbehani, Gregory / Vasu, Sumithira / Byrd, John C / Muthusamy, Natarajan

Blood

2021 Volume 139, Issue 9, Page(s) 1340–1358

Abstract: ... pharmacological agent, OSU-2S, in parallel with genetic approaches, we discovered that PP2A enforced c-Myc and p21 ... in vivo. Our findings identify the PP2A/c-Myc/p21 axis as a critical regulator of the differentiation ...

Abstract	Dysregulated cellular differentiation is a hallmark of acute leukemogenesis. Phosphatases are widely suppressed in cancers but have not been traditionally associated with differentiation. In this study, we found that the silencing of protein phosphatase 2A (PP2A) directly blocks differentiation in acute myeloid leukemia (AML). Gene expression and mass cytometric profiling revealed that PP2A activation modulates cell cycle and transcriptional regulators that program terminal myeloid differentiation. Using a novel pharmacological agent, OSU-2S, in parallel with genetic approaches, we discovered that PP2A enforced c-Myc and p21 dependent terminal differentiation, proliferation arrest, and apoptosis in AML. Finally, we demonstrated that PP2A activation decreased leukemia-initiating stem cells, increased leukemic blast maturation, and improved overall survival in murine Tet2-/-Flt3ITD/WT and human cell-line derived xenograft AML models in vivo. Our findings identify the PP2A/c-Myc/p21 axis as a critical regulator of the differentiation/proliferation switch in AML that can be therapeutically targeted in malignancies with dysregulated maturation fate.
MeSH term(s)	Animals ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p21/genetics ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Humans ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/metabolism ; Mice ; Mice, Knockout ; Protein Phosphatase 2/genetics ; Protein Phosphatase 2/metabolism ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism
Chemical Substances	CDKN1A protein, human ; Cdkn1a protein, mouse ; Cyclin-Dependent Kinase Inhibitor p21 ; MYC protein, human ; Myc protein, mouse ; Proto-Oncogene Proteins c-myc ; Protein Phosphatase 2 (EC 3.1.3.16)
Language	English
Publishing date	2021-11-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2020010344
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 364: Show issues

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Article ; Online: Aerosol infection of Balb/c mice with eastern equine encephalitis virus; susceptibility and lethality.

Phelps, Amanda L / O'Brien, Lyn M / Eastaugh, Lin S / Davies, Carwyn / Lever, Mark S / Ennis, Jane / Zeitlin, Larry / Nunez, Alejandro / Ulaeto, David O

Virology journal

2019 Volume 16, Issue 1, Page(s) 2

Abstract: Background: Eastern equine encephalitis virus is an alphavirus that naturally cycles between mosquitoes and birds or rodents in Eastern States of the US. Equine infection occurs by being bitten by cross-feeding mosquitoes, with a case fatality rate of ... ...

Abstract	Background: Eastern equine encephalitis virus is an alphavirus that naturally cycles between mosquitoes and birds or rodents in Eastern States of the US. Equine infection occurs by being bitten by cross-feeding mosquitoes, with a case fatality rate of up to 75% in humans during epizootic outbreaks. There are no licensed medical countermeasures, and with an anticipated increase in mortality when exposed by the aerosol route based on anecdotal human data and experimental animal data, it is important to understand the pathogenesis of this disease in pursuit of treatment options. This report details the clinical and pathological findings of mice infected with EEEV by the aerosol route, and use as a model for EEEV infection in humans. Methods: Mice were exposed by the aerosol route to a dose range of EEEV to establish the median lethal dose. A pathogenesis study followed whereby mice were exposed to a defined dose of virus and sacrificed at time-points thereafter for histopathological analysis and virology. Results: Clinical signs of disease appeared within 2 days post challenge, culminating in severe clinical signs within 24 h, neuro-invasion and dose dependent lethality. EEEV was first detected in the lung 1 day post challenge, and by day 3 peak viral titres were observed in the brain, spleen and blood, corresponding with severe meningoencephalitis, indicative of encephalitic disease. Lethality follows severe neurological signs, and may be linked to a threshold level of virus replication in the brain. Effective medical countermeasures for EEEV may necessitate early inoculation to inhibit infection of the brain in zoonotic incidents, and be able to traverse the blood-brain barrier to sufficiently interrupt replication in the brain in cases of aerosol infection. Conclusions: There is little human data on the hazard posed by aerosol infection with encephalitic alphaviruses, and use of EEEV as a bioweapon may be by the aerosol route. A well characterized model of aerosol exposure that recapitulates some of the most severe human clinical features is necessary to evaluate the efficacy of putative medical countermeasures, and to increase our understanding about how this route of infection induces such rapid neuro-invasion and resulting disease.
MeSH term(s)	Aerosols ; Animals ; Brain/virology ; Disease Models, Animal ; Disease Susceptibility/virology ; Encephalitis Virus, Eastern Equine/pathogenicity ; Encephalitis, Viral/mortality ; Encephalitis, Viral/pathology ; Female ; Lung/virology ; Mice ; Mice, Inbred BALB C ; Virus Replication
Chemical Substances	Aerosols
Language	English
Publishing date	2019-01-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1743-422X
ISSN (online)	1743-422X
DOI	10.1186/s12985-018-1103-7
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Article ; Online: Susceptibility and Lethality of Western Equine Encephalitis Virus in Balb/c Mice When Infected by the Aerosol Route.

Phelps, Amanda L / O'Brien, Lyn M / Eastaugh, Lin S / Davies, Carwyn / Lever, Mark S / Ennis, Jane / Zeitlin, Larry / Nunez, Alejandro / Ulaeto, David O

Viruses

2017 Volume 9, Issue 7

Abstract: ... and use as a model for WEEV infection in humans. Balb/c mice were infected by the aerosol route ...

Abstract	Western equine encephalitis virus (WEEV) naturally cycles between mosquitos and birds or rodents, with a case fatality rate of up to 15% in humans during epizootic outbreaks. There are no medical countermeasures to treat WEEV infection, and accidental aerosol exposure increases the case fatality rate up to 40%. Understanding the pathogenesis of infection is required to develop and assess medical countermeasures. This study describes the clinical and pathological findings of mice infected with WEEV by the aerosol route, and use as a model for WEEV infection in humans. Balb/c mice were infected by the aerosol route with a dose range of high-virulence WEEV strain Fleming to establish the median lethal dose (MLD). The disease course was acute, culminating in severe clinical signs, neuroinvasion, and dose-dependent mortality. Further groups of mice were exposed by the aerosol route, periodically sacrificed, and tissues excised for histopathological examination and virology. Viral titres peaked four days post-challenge in the brain and lungs, corresponding with severe bilateral lesions in rostroventral regions of the encephalon, especially in the olfactory bulb and piriform cortex. Recapitulation of the most serious clinical presentations of human WEEV disease in mice may prove a useful tool in the evaluation of medical countermeasures.
Language	English
Publishing date	2017-06-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v9070163
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Inflammatory Bowel Disease Outcomes Following Fecal Microbiota Transplantation for Recurrent C. difficile Infection.

Allegretti, Jessica R / Kelly, Colleen R / Grinspan, Ari / Mullish, Benjamin H / Hurtado, Jonathan / Carrellas, Madeline / Marcus, Jenna / Marchesi, Julian R / McDonald, Julie A K / Gerardin, Ylaine / Silverstein, Michael / Pechlivanis, Alexandros / Barker, Grace F / Miguens Blanco, Jesus / Alexander, James L / Gallagher, Kate I / Pettee, Will / Phelps, Emmalee / Nemes, Sara /

Sagi, Sashidhar V / Bohm, Matthew / Kassam, Zain / Fischer, Monika

Inflammatory bowel diseases

2020 Volume 27, Issue 9, Page(s) 1371–1378

Abstract: Background: Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding ... ...

Abstract	Background: Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited. Methods: Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement-all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling. Results: Fifty patients enrolled in the study, among which 15 had Crohn's disease (mean HBI, 5.8 ± 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 ± 2.1). Overall, 49 patients received treatment. Among the Crohn's disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn's disease patients (P = 0.04). Conclusion: This prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies.
MeSH term(s)	Clostridioides difficile ; Clostridium Infections/therapy ; Colitis, Ulcerative/therapy ; Crohn Disease/therapy ; Fecal Microbiota Transplantation ; Humans ; Prospective Studies ; Recurrence ; Treatment Outcome
Language	English
Publishing date	2020-11-03
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1340971-2
ISSN	1536-4844 ; 1078-0998
ISSN (online)	1536-4844
ISSN	1078-0998
DOI	10.1093/ibd/izaa283
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Article: Abstract of the Proceedings of Buffalo Medical Association.

Phelps, W C

Buffalo medical and surgical journal

2023 Volume 11, Issue 1, Page(s) 10–13

Language	English
Publishing date	2023-01-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	426472-1
ISSN	1040-3825
ISSN	1040-3825
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Article: Luxation of Femur on Dorsum Ilii-Reduction by Manipulation.

Phelps, Wm C

Buffalo medical and surgical journal

2023 Volume 19, Issue 4, Page(s) 145–147

Language	English
Publishing date	2023-01-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	426472-1
ISSN	1040-3825
ISSN	1040-3825
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Article: Abstract of the Proceedings of the Buffalo Medical Association.

Phelps, Wm C

Buffalo medical and surgical journal

2023 Volume 10, Issue 2, Page(s) 48–52

Language	English
Publishing date	2023-01-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	426472-1
ISSN	1040-3825
ISSN	1040-3825
Database	MEDical Literature Analysis and Retrieval System OnLINE

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