LIVIVO - Search results -

Search results

Result 1 - 10 of total 80

Search options

Article ; Online: Hereditary variants of unknown significance in African American women with breast cancer

J. Tyson McDonald / Luisel J. Ricks-Santi

PLoS ONE, Vol 17, Iss

2022 Volume 10

Abstract: Expanded implementation of genetic sequencing has precipitously increased the discovery of germline and somatic variants. The direct benefit of identifying variants in actionable genes may lead to risk reduction strategies such as increased surveillance, ...

Abstract	Expanded implementation of genetic sequencing has precipitously increased the discovery of germline and somatic variants. The direct benefit of identifying variants in actionable genes may lead to risk reduction strategies such as increased surveillance, prophylactic surgery, as well as lifestyle modifications to reduce morbidity and mortality. However, patients with African ancestry are more likely to receive inconclusive genetic testing results due to an increased number of variants of unknown significance decreasing the utility and impact on disease management and prevention. This study examines whole exome sequencing results from germline DNA samples in African American women with a family history of cancer including 37 cases that were diagnosed with breast cancer and 51 family members. Self-identified ancestry was validated and compared to the 1000 genomes population. The analysis of sequencing results was limited to 85 genes from three clinically available common genetic screening platforms. This target region had a total of 993 variants of which 6 (<1%) were pathogenic or likely pathogenic, 736 (74.1%) were benign, and 170 (17.1%) were classified as a variant of unknown significance. There was an average of 3.4±1.8 variants with an unknown significance per individual and 85 of 88 individuals (96.6%) harbored at least one of these in the targeted genes. Pathogenic or likely pathogenic variants were only found in 6 individuals for the BRCA1 (p.R1726fs, rs80357867), BRCA2 (p.K589fs, rs397507606 & p.L2805fs, rs397507402), RAD50 (p.E995fs, rs587780154), ATM (p.V2424G, rs28904921), or MUTYH (p.G396D, rs36053993) genes. Strategies to functionally validate the remaining variants of unknown significance, especially in understudied and hereditary cancer populations, are greatly needed to increase the clinical utility and utilization of clinical genetic screening platforms to reduce cancer incidence and mortality.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Hereditary variants of unknown significance in African American women with breast cancer.

McDonald, J Tyson / Ricks-Santi, Luisel J

PloS one

2022 Volume 17, Issue 10, Page(s) e0273835

Abstract	Expanded implementation of genetic sequencing has precipitously increased the discovery of germline and somatic variants. The direct benefit of identifying variants in actionable genes may lead to risk reduction strategies such as increased surveillance, prophylactic surgery, as well as lifestyle modifications to reduce morbidity and mortality. However, patients with African ancestry are more likely to receive inconclusive genetic testing results due to an increased number of variants of unknown significance decreasing the utility and impact on disease management and prevention. This study examines whole exome sequencing results from germline DNA samples in African American women with a family history of cancer including 37 cases that were diagnosed with breast cancer and 51 family members. Self-identified ancestry was validated and compared to the 1000 genomes population. The analysis of sequencing results was limited to 85 genes from three clinically available common genetic screening platforms. This target region had a total of 993 variants of which 6 (<1%) were pathogenic or likely pathogenic, 736 (74.1%) were benign, and 170 (17.1%) were classified as a variant of unknown significance. There was an average of 3.4±1.8 variants with an unknown significance per individual and 85 of 88 individuals (96.6%) harbored at least one of these in the targeted genes. Pathogenic or likely pathogenic variants were only found in 6 individuals for the BRCA1 (p.R1726fs, rs80357867), BRCA2 (p.K589fs, rs397507606 & p.L2805fs, rs397507402), RAD50 (p.E995fs, rs587780154), ATM (p.V2424G, rs28904921), or MUTYH (p.G396D, rs36053993) genes. Strategies to functionally validate the remaining variants of unknown significance, especially in understudied and hereditary cancer populations, are greatly needed to increase the clinical utility and utilization of clinical genetic screening platforms to reduce cancer incidence and mortality.
MeSH term(s)	Female ; Humans ; African Americans/genetics ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Breast Neoplasms/ethnology ; Breast Neoplasms/genetics ; Genes, BRCA2 ; Genetic Predisposition to Disease ; Genetic Testing/methods ; Germ-Line Mutation ; Whole Exome Sequencing
Chemical Substances	BRCA1 Protein ; BRCA2 Protein
Language	English
Publishing date	2022-10-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0273835
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: SARS-CoV-2 Seroprevalence and Cross-Variant Antibody Neutralization in Cats, United Kingdom.

Tyson, Grace B / Jones, Sarah / Logan, Nicola / McDonald, Michael / Marshall, Leigh / Murcia, Pablo R / Willett, Brian J / Weir, William / Hosie, Margaret J

Emerging infectious diseases

2023 Volume 29, Issue 6, Page(s) 1223–1227

Abstract: Anthropogenic transmission of SARS-CoV-2 to pet cats highlights the importance of monitoring felids for exposure to circulating variants. We tested cats in the United Kingdom for SARS-CoV-2 antibodies; seroprevalence peaked during September 2021-February ...

Abstract	Anthropogenic transmission of SARS-CoV-2 to pet cats highlights the importance of monitoring felids for exposure to circulating variants. We tested cats in the United Kingdom for SARS-CoV-2 antibodies; seroprevalence peaked during September 2021-February 2022. The variant-specific response in cats trailed circulating variants in humans, indicating multiple human-to-cat transmissions over a prolonged period.
MeSH term(s)	Humans ; Cats ; Animals ; SARS-CoV-2 ; Seroepidemiologic Studies ; COVID-19/epidemiology ; COVID-19/veterinary ; Antibodies, Viral ; United Kingdom/epidemiology
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2023-05-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2906.221755
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4778: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Increase in SARS-CoV-2 Seroprevalence in UK Domestic Felids Despite Weak Immunogenicity of Post-Omicron Variants.

Tyson, Grace B / Jones, Sarah / Montreuil-Spencer, Chloe / Logan, Nicola / Scott, Sam / Sasvari, Hagar / McDonald, Michael / Marshall, Leigh / Murcia, Pablo R / Willett, Brian J / Weir, William / Hosie, Margaret J

Viruses

2023 Volume 15, Issue 8

Abstract: Throughout the COVID-19 pandemic, SARS-CoV-2 infections in domestic cats have caused concern for both animal health and the potential for inter-species transmission. Cats are known to be susceptible to the Omicron variant and its descendants, however, ... ...

Abstract	Throughout the COVID-19 pandemic, SARS-CoV-2 infections in domestic cats have caused concern for both animal health and the potential for inter-species transmission. Cats are known to be susceptible to the Omicron variant and its descendants, however, the feline immune response to these variants is not well defined. We aimed to estimate the current seroprevalence of SARS-CoV-2 in UK pet cats, as well as characterise the neutralising antibody response to the Omicron (BA.1) variant. A neutralising seroprevalence of 4.4% and an overall seroprevalence of 13.9% was observed. Both purebred and male cats were found to have the highest levels of seroprevalence, as well as cats aged between two and five years. The Omicron variant was found to have a lower immunogenicity in cats than the B.1, Alpha and Delta variants, which reflects previous reports of immune and vaccine evasion in humans. These results further underline the importance of surveillance of SARS-CoV-2 infections in UK cats as the virus continues to evolve.
MeSH term(s)	Cats ; Animals ; Male ; Humans ; Child, Preschool ; SARS-CoV-2/genetics ; COVID-19/epidemiology ; Pandemics ; Seroepidemiologic Studies ; United Kingdom/epidemiology
Language	English
Publishing date	2023-07-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15081661
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Characterization of GATA3 and Mammaglobin in breast tumors from African American women.

Ricks-Santi, Luisel J / Fredenburg, Kristianna / Rajaei, Moein / Esnakula, Ashwin / Naab, Tammey / McDonald, J Tyson / Kanaan, Yasmine

Research square

2023

Abstract: GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African ... ...

Abstract	GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes. Tissue microarrays (TMAs) were constructed from well preserved, morphologically representative tumors in archived formalin-fixed, paraffin-embedded (FFPE) surgical blocks from 202 patients with primary invasive ductal carcinoma. Mammaglobin, and GATA3 expression was assessed using immunohistochemistry (IHC). Univariate analysis was carried out to determine the association between expression of GATA3, mammaglobin and clinicopathological characteristics. Kaplan-Meier estimates of overall survival and disease-free survival were also plotted and a log-rank test performed to compare estimates among groups. GATA3 expression showed statistically significant association with lower grade (p<0.001), ER-positivity (p<0.001), PR-positivity (p<0.001), and the luminal subtype (p<0.001). Mammaglobin expression was also significantly associated with lower grade (p=0.031), ER-positivity (p=0.007), and PR-positivity (p=0.022). There was no association with recurrence-free or overall survival. Our results confirm that GATA3 and mammaglobin demonstrate expression predominantly in luminal breast cancers from African American women. Markers with improved specificity and sensitivity are warranted given the high prevalence of triple negative breast cancer in the group.
Language	English
Publishing date	2023-01-25
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-2463961/v1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: Characterization of GATA3 and Mammaglobin in breast tumors from African American Women.

Ricks-Santi, Luisel J / Fredenburg, Kristianna / Rajaei, Moein / Esnakula, Ashwin / Naab, Tammey / McDonald, J Tyson / Kanaan, Yasmine

Archives of microbiology & immunology

2023 Volume 7, Issue 1, Page(s) 18–28

Abstract	GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin in breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes. Tissue microarrays (TMAs) were constructed from well preserved, morphologically representative tumors in archived formalin-fixed, paraffin-embedded (FFPE) surgical blocks from 202 patients with primary invasive ductal carcinoma. Mammaglobin and GATA3 expression was assessed using immunohistochemistry (IHC). Univariate analysis was carried out to determine the association between expression of GATA3, mammaglobin and clinicopathological characteristics. Kaplan-Meier estimates of overall survival and disease-free survival were also plotted and a log-rank test performed to compare estimates among groups. GATA3 expression showed statistically significant association with lower grade (p<0.001), ER-positivity (p<0.001), PR-positivity (p<0.001), and the luminal subtype (p<0.001). Mammaglobin expression was also significantly associated with lower grade (p=0.031), ER-positivity (p=0.007), and PR-positivity (p=0.022). There was no association with recurrence-free or overall survival. Our results confirm that GATA3 and mammaglobin demonstrate expression predominantly in luminal breast cancers from African American women. Additional markers with improved specificity and sensitivity are warranted for triple negative breast tumors given the high prevalence in women of African descent.
Language	English
Publishing date	2023-03-17
Publishing country	United States
Document type	Journal Article
ISSN	2572-9365
ISSN (online)	2572-9365
DOI	10.26502/ami.936500101
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Delayed effects of radiation exposure in a C57L/J mouse model of partial body irradiation with ~2.5% bone marrow shielding.

Beach, Tyler / Bakke, James / McDonald, J Tyson / Riccio, Edward / Javitz, Harold S / Nishita, Denise / Kapur, Shweta / Bunin, Deborah I / Chang, Polly Y

Frontiers in public health

2024 Volume 12, Page(s) 1349552

Abstract: ... The C57L/J mouse model of partial body irradiation (PBI) with 2.5% bone marrow shielding (BM2.5) is being ... the dose response relationship and progression of radiation injury in the C57L/J mouse and to evaluate its suitability for use ... female C57L/J mice were exposed to PBI BM2.5 with one hindlimb shielded from radiation, representing ~2.5 ...

Abstract	Introduction: Mouse models of radiation injury are critical to the development of medical countermeasures (MCMs) against radiation. Now that MCMs against hematopoietic acute radiation syndrome (H-ARS) have achieved regulatory approval, attention is shifting to develop MCMs against the adverse effects of gastrointestinal acute radiation syndrome (GI-ARS) and delayed effects of acute radiation exposure (DEARE). The C57L/J mouse model of partial body irradiation (PBI) with 2.5% bone marrow shielding (BM2.5) is being leveraged to examine both GI-ARS and DEARE effects. Within days of PBI, mice may develop H- and GI-ARS followed several months later by DEARE as a multi-organ injury, which typically involves the lung and kidney (L- and K-DEARE, respectively). The objective of this manuscript is to describe the dose response relationship and progression of radiation injury in the C57L/J mouse and to evaluate its suitability for use in DEARE MCM testing. Materials and methods: In two separate studies conducted over 2 years, male and female C57L/J mice were exposed to PBI BM2.5 with one hindlimb shielded from radiation, representing ~2.5% bone marrow shielding/sparing. Mice were X-ray irradiated at doses ranging from 9 to 13 Gy at 10 to 12 weeks of age for the purposes of assessing ARS survival at 30 days and DEARE survival at 182 days post-irradiation. Clinical indicators of ARS and DEARE were determined by clinical observations, body weights, hematology, clinical chemistry, magnetic resonance imaging (MRI) of lung, and histopathology of selected tissues. Results: C57L/J mice developed canonical ARS responses of hematopoietic atrophy and gastrointestinal injury resulting in dose dependent mortality at doses ≥11 Gy between 1- and 15-days post-irradiation. In animals that survived ARS, DEARE associated mortality occurred in dose dependent fashion at ≥9 Gy for both sexes between 60- and 159-days post-irradiation with histopathology examinations indicating lung injury as the primary cause of death in moribund animals. Conclusion: The PBI BM2.5 C57L/J mouse model reliably produced known H- and GI-ARS effects at doses greater than those resulting in DEARE effects. Because of this, the C57L/J mouse can be used to test MCMs against L-DEARE injury, while avoiding ARS associated mortality.
MeSH term(s)	Male ; Female ; Mice ; Animals ; Bone Marrow/pathology ; Bone Marrow/radiation effects ; Acute Radiation Syndrome/etiology ; Acute Radiation Syndrome/pathology ; Disease Models, Animal ; Lung/pathology
Language	English
Publishing date	2024-03-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2024.1349552
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: SARS-CoV-2 in Domestic UK Cats from Alpha to Omicron: Swab Surveillance and Case Reports.

Jones, Sarah / Tyson, Grace B / Orton, Richard J / Smollett, Katherine / Manna, Federica / Kwok, Kirsty / Suárez, Nicolás M / Logan, Nicola / McDonald, Michael / Bowie, Andrea / Filipe, Ana Da Silva / Willett, Brian J / Weir, William / Hosie, Margaret J

Viruses

2023 Volume 15, Issue 8

Abstract: Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive ... ...

Abstract	Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR. In addition, we appealed to veterinarians for swab samples from cats suspected of having clinical SARS-CoV-2 infections. Bespoke testing for SARS-CoV-2 neutralising antibodies was also performed, on request, in suspected cases. One RT-qPCR-positive cat was identified by active surveillance (1/549, 0.18%), during the Delta wave (1/175, 0.57%). Passive surveillance detected one cat infected with the Alpha variant, and two of ten cats tested RT-qPCR-positive during the Delta wave. No cats tested RT-qPCR-positive after the emergence of Omicron BA.1 and its descendants although 374 were tested by active and eleven by passive surveillance. We describe four cases of SARS-CoV-2 infection in pet cats, identified by RT-qPCR and/or serology, that presented with a range of clinical signs, as well as their SARS-CoV-2 genome sequences. These cases demonstrate that, although uncommon in cats, a variety of clinical signs can occur.
MeSH term(s)	Animals ; Cats ; SARS-CoV-2/genetics ; COVID-19/diagnosis ; COVID-19/veterinary ; Antibodies, Viral ; United Kingdom/epidemiology
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2023-08-19
Publishing country	Switzerland
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15081769
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: NRF2 Mediates Cellular Resistance to Transformation, Radiation, and Inflammation in Mice.

Schaue, Dörthe / Micewicz, Ewa D / Ratikan, Josephine A / Iwamoto, Keisuke S / Vlashi, Erina / McDonald, J Tyson / McBride, William H

Antioxidants (Basel, Switzerland)

2022 Volume 11, Issue 9

Abstract: Nuclear factor erythroid 2-related factor 2 (NRF2) is recognized as a master transcription factor that regulates expression of numerous detoxifying and antioxidant cytoprotective genes. In fact, models of NRF2 deficiency indicate roles not only in redox ... ...

Abstract	Nuclear factor erythroid 2-related factor 2 (NRF2) is recognized as a master transcription factor that regulates expression of numerous detoxifying and antioxidant cytoprotective genes. In fact, models of NRF2 deficiency indicate roles not only in redox regulation, but also in metabolism, inflammatory/autoimmune disease, cancer, and radioresistancy. Since ionizing radiation (IR) generates reactive oxygen species (ROS), it is not surprising it activates NRF2 pathways. However, unexpectedly, activation is often delayed for many days after the initial ROS burst. Here, we demonstrate that, as assayed by γ-H2AX staining, rapid DNA double strand break (DSB) formation by IR in primary mouse
Language	English
Publishing date	2022-08-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox11091649
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Genomic Changes Driven by Radiation-Induced DNA Damage and Microgravity in Human Cells.

Beheshti, Afshin / McDonald, J Tyson / Hada, Megumi / Takahashi, Akihisa / Mason, Christopher E / Mognato, Maddalena

International journal of molecular sciences

2021 Volume 22, Issue 19

Abstract: The space environment consists of a complex mixture of different types of ionizing radiation and altered gravity that represents a threat to humans during space missions. In particular, individual radiation sensitivity is strictly related to the risk of ... ...

Abstract	The space environment consists of a complex mixture of different types of ionizing radiation and altered gravity that represents a threat to humans during space missions. In particular, individual radiation sensitivity is strictly related to the risk of space radiation carcinogenesis. Therefore, in view of future missions to the Moon and Mars, there is an urgent need to estimate as accurately as possible the individual risk from space exposure to improve the safety of space exploration. In this review, we survey the combined effects from the two main physical components of the space environment, ionizing radiation and microgravity, to alter the genetics and epigenetics of human cells, considering both real and simulated space conditions. Data collected from studies on human cells are discussed for their potential use to estimate individual radiation carcinogenesis risk from space exposure.
MeSH term(s)	Adaptation, Physiological ; DNA Damage ; Genomics/methods ; Gravity, Altered ; Humans ; Radiation Injuries/genetics ; Radiation Protection/methods ; Space Flight/methods ; Weightlessness ; Weightlessness Simulation/methods
Language	English
Publishing date	2021-09-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms221910507
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito