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Article ; Online: Correlates of Rotavirus Vaccine Shedding and Seroconversion in a U.S. Cohort of Healthy Infants.

Burke, Rachel M / Payne, Daniel C / McNeal, Monica / Conrey, Shannon C / Burrell, Allison R / Mattison, Claire P / Casey-Moore, Mary C / Mijatovic-Rustempasic, Slavica / Gautam, Rashi / Esona, Mathew D / Thorman, Alexander W / Bowen, Michael D / Parashar, Umesh D / Tate, Jacqueline E / Morrow, Ardythe L / Staat, Mary A

The Journal of infectious diseases

2024

Abstract: Background: Rotavirus is a leading cause of severe pediatric gastroenteritis; two highly effective vaccines are used in the US. We aimed to identify correlates of immune response to rotavirus vaccination in a US cohort.: Methods: PREVAIL is a birth ... ...

Abstract	Background: Rotavirus is a leading cause of severe pediatric gastroenteritis; two highly effective vaccines are used in the US. We aimed to identify correlates of immune response to rotavirus vaccination in a US cohort. Methods: PREVAIL is a birth cohort of 245 mother-child pairs enrolled 2017-2018 and followed for 2 years. Infant stool samples and symptom information were collected weekly. Shedding was defined as RT-PCR detection of rotavirus vaccine virus in stools collected 4-28 days after dose one. Seroconversion was defined as a threefold rise in IgA between the six-week and six-month blood draws. Correlates were analyzed using generalized estimating equations and logistic regression. Results: Pre-vaccination IgG (OR=0.84, 95% CI [0.75-0.94] per 100-unit increase) was negatively associated with shedding. Shedding was also less likely among infants with a single-nucleotide polymorphism inactivating FUT2 antigen secretion ("non-secretors") with non-secretor mothers, versus all other combinations (OR 0.37 [0.16-0.83]). Of 141 infants with data, 105 (74%) seroconverted; 78 (77%) had shed vaccine virus following dose one. Pre-vaccination IgG and secretor status were significantly associated with seroconversion. Neither shedding nor seroconversion significantly differed by vaccine product. Discussion: In this US cohort, pre-vaccination IgG and maternal and infant secretor status were associated with rotavirus vaccine response.
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiae055
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Article ; Online: Loss of talin in cardiac fibroblasts results in augmented ventricular cardiomyocyte hypertrophy in response to pressure overload.

Noll, Natalie A / Riley, Lance A / Moore, Christy S / Zhong, Lin / Bersi, Mathew R / West, James D / Zent, Roy / Merryman, W David

American journal of physiology. Heart and circulatory physiology

2022 Volume 322, Issue 5, Page(s) H857–H866

Abstract: Pressure overload of the heart is characterized by concentric hypertrophy and interstitial fibrosis. Cardiac fibroblasts (CFs) in the ventricular wall become activated during injury and synthesize and compact the extracellular matrix, which causes ... ...

Abstract	Pressure overload of the heart is characterized by concentric hypertrophy and interstitial fibrosis. Cardiac fibroblasts (CFs) in the ventricular wall become activated during injury and synthesize and compact the extracellular matrix, which causes interstitial fibrosis and stiffening of the ventricular heart walls. Talin1 (Tln1) and Talin2 (Tln2) are mechanosensitive proteins that participate in focal adhesion transmission of signals from the extracellular environment to the actin cytoskeleton of CFs. The aim of the present study was to determine whether the removal of Tln1 and Tln2 from CFs would reduce interstitial fibrosis and cardiac hypertrophy. Twelve-week-old male and female Tln2-null (
MeSH term(s)	Angiotensin II/pharmacology ; Animals ; Cardiomegaly/metabolism ; Female ; Fibroblasts/metabolism ; Fibrosis ; Male ; Mice ; Mice, Knockout ; Myocardium/metabolism ; Myocytes, Cardiac/metabolism ; Talin/genetics ; Talin/metabolism
Chemical Substances	TLN2 protein, mouse ; Talin ; Angiotensin II (11128-99-7)
Language	English
Publishing date	2022-03-25
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.00632.2021
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Article ; Online: Addressing barriers to increased adoption of DPYD genotyping at a large multisite cancer center.

Morris, Sarah A / Moore, Donald C / Musselwhite, Laura W / Lopes, Karine Eboli / Hamilton, Alicia / Steuerwald, Nury / Hanson, Sarah L / Larck, Chris / Swift, Kristen / Smith, Mathew / Kadakia, Kunal C / Chai, Seungjean / Hwang, Jimmy J / Patel, Jai N

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists

2023 Volume 80, Issue 19, Page(s) 1342–1349

Abstract: Purpose: To describe the implementation of an in-house genotyping program to detect genetic variants linked to impaired dihydropyrimidine dehydrogenase (DPD) metabolism at a large multisite cancer center, including barriers to implementation and ... ...

Abstract	Purpose: To describe the implementation of an in-house genotyping program to detect genetic variants linked to impaired dihydropyrimidine dehydrogenase (DPD) metabolism at a large multisite cancer center, including barriers to implementation and mechanisms to overcome barriers to facilitate test adoption. Summary: Fluoropyrimidines, including fluorouracil and capecitabine, are commonly used chemotherapy agents in the treatment of solid tumors, such as gastrointestinal cancers. DPD is encoded by the DPYD gene, and individuals classified as DPYD intermediate and poor metabolizers due to certain genetic variations in DPYD can experience reduced fluoropyrimidine clearance and an increased risk of fluoropyrimidine-related adverse events. Although pharmacogenomic guidelines provide evidence-based recommendations for DPYD genotype-guided dosing, testing has not been widely adopted in the United States for numerous reasons, including limited education/awareness of clinical utility, lack of testing recommendations by oncology professional organizations, testing cost, lack of accessibility to a comprehensive in-house test and service, and prolonged test turnaround time. Based on stakeholder feedback regarding barriers to testing, we developed an in-house DPYD test and workflow to facilitate testing in multiple clinic locations at Levine Cancer Institute. Across 2 gastrointestinal oncology clinics from March 2020 through June 2022, 137 patients were genotyped, and 13 (9.5%) of those patients were heterozygous for a variant and identified as DPYD intermediate metabolizers. Conclusion: Implementation of DPYD genotyping at a multisite cancer center was feasible due to operationalization of workflows to overcome traditional barriers to testing and engagement from all stakeholders, including physicians, pharmacists, nurses, and laboratory personnel. Future directions to scale and sustain testing in all patients receiving a fluoropyrimidine across all Levine Cancer Institute locations include electronic medical record integration (eg, interruptive alerts), establishment of a billing infrastructure, and further refinement of workflows to improve the rate of pretreatment testing.
MeSH term(s)	Humans ; Dihydrouracil Dehydrogenase (NADP)/genetics ; Dihydrouracil Dehydrogenase (NADP)/metabolism ; Genotype ; Antimetabolites, Antineoplastic/therapeutic use ; Capecitabine/therapeutic use ; Fluorouracil ; Neoplasms/drug therapy ; Neoplasms/genetics
Chemical Substances	Dihydrouracil Dehydrogenase (NADP) (EC 1.3.1.2) ; Antimetabolites, Antineoplastic ; Capecitabine (6804DJ8Z9U) ; Fluorouracil (U3P01618RT)
Language	English
Publishing date	2023-05-24
Publishing country	England
Document type	Journal Article
ZDB-ID	1224627-x
ISSN	1535-2900 ; 1079-2082
ISSN (online)	1535-2900
ISSN	1079-2082
DOI	10.1093/ajhp/zxad117
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Article ; Online: Immunotherapy reverses glioma-driven dysfunction of immune system homeostasis.

DiVita Dean, Bayli / Wildes, Tyler / Dean, Joseph / Yegorov, Oleg / Yang, Changlin / Shin, David / Francis, Connor / Figg, John W / Sebastian, Mathew / Font, Laura Falceto / Jin, Dan / Reid, Alexandra / Moore, Ginger / Fernandez, Brandon / Wummer, Brandon / Kuizon, Carmelle / Mitchell, Duane / Flores, Catherine T

Journal for immunotherapy of cancer

2023 Volume 11, Issue 2

Abstract: Background: Glioma-induced immune dysregulation of the hematopoietic system has been described in a limited number of studies. In this study, our group further demonstrates that gliomas interrupt the cellular differentiation programming and outcomes of ... ...

Abstract	Background: Glioma-induced immune dysregulation of the hematopoietic system has been described in a limited number of studies. In this study, our group further demonstrates that gliomas interrupt the cellular differentiation programming and outcomes of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. HSPCs from glioma-bearing mice are reprogrammed and driven towards expansion of myeloid lineage precursors and myeloid-derived suppressor cells (MDSCs) in secondary lymphoid organs. However, we found this expansion is reversed by immunotherapy. Adoptive cellular therapy (ACT) has been demonstrably efficacious in multiple preclinical models of central nervous system (CNS) malignancies, and here we describe how glioma-induced dysfunction is reversed by this immunotherapeutic platform. Methods: The impact of orthotopic KR158B-luc glioma on HSPCs was evaluated in an unbiased fashion using single cell RNAseq (scRNAseq) of lineage Results: Using scRNAseq, we observed an altered HSPC landscape in glioma-bearing versus non-tumor-bearing mice . In addition, an expansion of myeloid lineage subsets, including granulocyte macrophage precursors (GMPs) and MDSCs, were observed in glioma-bearing mice relative to non-tumor-bearing controls. Furthermore, MDSCs from glioma-bearing mice demonstrated increased suppressive capacity toward tumor-specific T cells as compared with MDSCs from non-tumor-bearing hosts. Interestingly, treatment with ACT overcame these suppressive properties. When HSPCs from glioma-bearing mice were transferred in the context of ACT, we observed significant survival benefit and long-term cures in orthotopic glioma models compared with mice treated with ACT using non-glioma-bearing HSPCs.
MeSH term(s)	Mice ; Animals ; Cell Line, Tumor ; Glioma/pathology ; Immunotherapy ; Hematopoietic Stem Cells ; T-Lymphocytes ; Central Nervous System Neoplasms
Language	English
Publishing date	2023-02-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2022-004805
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Article: Exploring the Pharmacokinetics of Phenoxymethylpenicillin (Penicillin-V) in Adults: A Healthy Volunteer Study.

Rawson, Timothy M / Wilson, Richard C / Moore, Luke S P / Macgowan, Alasdair P / Lovering, Andrew M / Bayliss, Mark / Kyriakides, Mathew / Gilchrist, Mark / Roberts, Jason A / Hope, William W / Holmes, Alison H

Open forum infectious diseases

2021 Volume 8, Issue 12, Page(s) ofab573

Abstract: This healthy volunteer study aimed to explore phenoxymethylpenicillin (penicillin-V) pharmacokinetics (PK) to support the planning of large dosing studies in adults. Volunteers were dosed with penicillin-V at steady state. Total and unbound penicillin-V ... ...

Abstract	This healthy volunteer study aimed to explore phenoxymethylpenicillin (penicillin-V) pharmacokinetics (PK) to support the planning of large dosing studies in adults. Volunteers were dosed with penicillin-V at steady state. Total and unbound penicillin-V serum concentrations were determined, and a base population PK model was fitted to the data.
Language	English
Publishing date	2021-12-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofab573
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Article ; Online: Analytical performance evaluation of a commercial next generation sequencing liquid biopsy platform using plasma ctDNA, reference standards, and synthetic serial dilution samples derived from normal plasma.

Verma, Suman / Moore, Mathew W / Ringler, Rebecca / Ghosal, Abhisek / Horvath, Kyle / Naef, Theodore / Anvari, Sheri / Cotter, Philip D / Gunn, Shelly

BMC cancer

2020 Volume 20, Issue 1, Page(s) 945

Abstract: Background: Circulating tumor (ct) DNA assays performed in clinical laboratories provide tumor biomarker testing support for biopharmaceutical clinical trials. Yet it is neither practical nor economically feasible for many of these clinical laboratories ...

Abstract	Background: Circulating tumor (ct) DNA assays performed in clinical laboratories provide tumor biomarker testing support for biopharmaceutical clinical trials. Yet it is neither practical nor economically feasible for many of these clinical laboratories to internally develop their own liquid biopsy assay. Commercially available ctDNA kits are a potential solution for laboratories seeking to incorporate liquid biopsy into their test menus. However, the scarcity of characterized patient samples and cost of purchasing validation reference standards creates a barrier to entry. In the current study, we evaluated the analytical performance of the AVENIO ctDNA liquid biopsy platform (Roche Sequencing Solutions) for use in our clinical laboratory. Method: Intra-laboratory performance evaluation of AVENIO ctDNA Targeted, Expanded, and Surveillance kits (Research Use Only) was performed according to College of American Pathologists (CAP) guidelines for the validation of targeted next generation sequencing assays using purchased reference standards, de-identified human plasma cell-free (cf) DNA samples, and contrived samples derived from commercially purchased normal and cancer human plasma. All samples were sequenced at read depths relevant to clinical settings using the NextSeq High Output kit (Illumina). Results: At the clinically relevant read depth, Avenio ctDNA kits demonstrated 100% sensitivity in detecting single nucleotide variants (SNVs) at ≥0.5% allele frequency (AF) and 50% sensitivity in detecting SNVs at 0.1% AF using 20-40 ng sample input amount. The assay integrated seamlessly into our laboratory's NGS workflow with input DNA mass, target allele frequency (TAF), multiplexing, and number of reads optimized to support a high-throughput assay appropriate for biopharmaceutical trials. Conclusions: Our study demonstrates that AVENIO ctDNA liquid biopsy platform provides a viable alternative for efficient incorporation of liquid biopsy assays into the clinical laboratory for detecting somatic alterations as low as 0.5%. Accurate detection of variants lower than 0.5% could potentially be achieved by deeper sequencing when clinically indicated and economically feasible.
MeSH term(s)	Biomarkers, Tumor/blood ; Cell-Free Nucleic Acids/blood ; Cell-Free Nucleic Acids/genetics ; Circulating Tumor DNA/blood ; Circulating Tumor DNA/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Liquid Biopsy ; Mutation/genetics ; Neoplasms/blood ; Neoplasms/genetics
Chemical Substances	Biomarkers, Tumor ; Cell-Free Nucleic Acids ; Circulating Tumor DNA
Language	English
Publishing date	2020-10-01
Publishing country	England
Document type	Journal Article
ISSN	1471-2407
ISSN (online)	1471-2407
DOI	10.1186/s12885-020-07445-5
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Article ; Online: FISH as an effective diagnostic tool for the management of challenging melanocytic lesions.

Moore, Mathew W / Gasparini, Robert

Diagnostic pathology

2011 Volume 6, Page(s) 76

Abstract: Background: The accuracy of melanoma diagnosis continues to challenge the pathology community, even today with sophisticated histopathologic techniques. Melanocytic lesions exhibit significant morphological heterogeneity. While the majority of biopsies ... ...

Abstract	Background: The accuracy of melanoma diagnosis continues to challenge the pathology community, even today with sophisticated histopathologic techniques. Melanocytic lesions exhibit significant morphological heterogeneity. While the majority of biopsies can be classified as benign (nevus) or malignant (melanoma) using well-established histopathologic criteria, there exists a cohort for which the prediction of clinical behaviour and invasive or metastatic potential is difficult if not impossible to ascertain on the basis of morphological features alone. Multiple studies have shown that there is significant disagreement between pathologists and even expert dermatopathologists in the diagnosis of this subgroup of difficult melanocytic lesions. Methods: A four probe FISH assay was utilized to analyse a cohort of 500 samples including 157 nevus, 176 dysplastic nevus and 167 melanoma specimens. Results: Review of the lesions determined the assay identified genetic abnormalities in a total of 83.8% of melanomas, and 1.9% of nevus without atypia, while genetic abnormalities were identified in 6.3%, 6.7%, and 10.3% of nevus identified with mild, moderate and severe atypia, respectively. Conclusions: Based on this study, inheritable genetic damage/instability identified by FISH testing is a hallmark of a progressive malignant process, and a valuable diagnostic tool for the identification of high risk lesions.
MeSH term(s)	Biopsy ; Diagnosis, Differential ; Dysplastic Nevus Syndrome/diagnosis ; Dysplastic Nevus Syndrome/genetics ; Dysplastic Nevus Syndrome/therapy ; Genetic Predisposition to Disease ; Genomic Instability ; Heredity ; Humans ; In Situ Hybridization, Fluorescence ; Melanoma/diagnosis ; Melanoma/genetics ; Melanoma/therapy ; Nevus/diagnosis ; Nevus/genetics ; Nevus/therapy ; Phenotype ; Predictive Value of Tests ; Prognosis ; Skin Neoplasms/diagnosis ; Skin Neoplasms/genetics ; Skin Neoplasms/therapy
Language	English
Publishing date	2011-08-11
Publishing country	England
Document type	Journal Article
ISSN	1746-1596
ISSN (online)	1746-1596
DOI	10.1186/1746-1596-6-76
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Article ; Online: Coordinated Fc-effector and neutralization functions in HIV-infected children define a window of opportunity for HIV vaccination.

Nduati, Eunice W / Gorman, Mathew J / Sein, Yiakon / Hermanus, Tandile / Yuan, Dansu / Oyaro, Ian / Muema, Daniel M / Ndung'u, Thumbi / Alter, Galit / Moore, Penny L

AIDS (London, England)

2021 Volume 35, Issue 12, Page(s) 1895–1905

Abstract: Objectives: Antibody function has been extensively studied in HIV-infected adults but is relatively understudied in children. Emerging data suggests enhanced development of broadly neutralizing antibodies (bNAbs) in children but Fc effector functions in ...

Abstract	Objectives: Antibody function has been extensively studied in HIV-infected adults but is relatively understudied in children. Emerging data suggests enhanced development of broadly neutralizing antibodies (bNAbs) in children but Fc effector functions in this group are less well defined. Here, we profiled overall antibody function in HIV-infected children. Design: Plasma samples from a cross-sectional study of 50 antiretroviral therapy-naive children (aged 1-11 years) vertically infected with HIV-1 clade A were screened for HIV-specific binding antibody levels and neutralizing and Fc-mediated functions. Methods: Neutralization breadth was determined against a globally representative panel of 12 viruses. HIV-specific antibody levels were determined using a multiplex assay. Fc-mediated antibody functions measured were antibody-dependent: cellular phagocytosis (ADCP); neutrophil phagocytosis (ADNP); complement deposition (ADCD) and natural killer function (ADNK). Results: All children had HIV gp120-specific antibodies, largely of the IgG1 subtype. Fifty-four percent of the children exhibited more than 50% neutralization breadth, with older children showing significantly broader neutralization activity. Apart from ADCC, observed only in 16% children, other Fc-mediated functions were common (>58% children). Neutralization breadth correlated with Fc-mediated functions suggesting shared determinants of enhanced antibody function exist. Conclusions: These results are consistent with previous observations that children may develop high levels of neutralization breadth. Furthermore, the striking association between neutralization breadth and Fc effector function suggests that HIV vaccination in children could yield multifunctional antibodies. Paediatric populations may therefore provide an ideal window of opportunity for HIV vaccination strategies.
MeSH term(s)	Antibodies, Neutralizing ; Antibody-Dependent Cell Cytotoxicity ; Child ; Child, Preschool ; Cross-Sectional Studies ; HIV Antibodies ; HIV Infections ; HIV-1 ; Homeodomain Proteins ; Humans ; Infant ; Nerve Tissue Proteins ; Vaccination
Chemical Substances	ADNP protein, human ; Antibodies, Neutralizing ; HIV Antibodies ; Homeodomain Proteins ; Nerve Tissue Proteins
Language	English
Publishing date	2021-06-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639076-6
ISSN	1473-5571 ; 0269-9370 ; 1350-2840
ISSN (online)	1473-5571
ISSN	0269-9370 ; 1350-2840
DOI	10.1097/QAD.0000000000002976
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Article ; Online: FISH as an effective diagnostic tool for the management of challenging melanocytic lesions

Gasparini Robert / Moore Mathew W

Diagnostic Pathology, Vol 6, Iss 1, p

2011 Volume 76

Abstract: Abstract Background The accuracy of melanoma diagnosis continues to challenge the pathology community, even today with sophisticated histopathologic techniques. Melanocytic lesions exhibit significant morphological heterogeneity. While the majority of ... ...

Abstract	Abstract Background The accuracy of melanoma diagnosis continues to challenge the pathology community, even today with sophisticated histopathologic techniques. Melanocytic lesions exhibit significant morphological heterogeneity. While the majority of biopsies can be classified as benign (nevus) or malignant (melanoma) using well-established histopathologic criteria, there exists a cohort for which the prediction of clinical behaviour and invasive or metastatic potential is difficult if not impossible to ascertain on the basis of morphological features alone. Multiple studies have shown that there is significant disagreement between pathologists and even expert dermatopathologists in the diagnosis of this subgroup of difficult melanocytic lesions. Methods A four probe FISH assay was utilized to analyse a cohort of 500 samples including 157 nevus, 176 dysplastic nevus and 167 melanoma specimens. Results Review of the lesions determined the assay identified genetic abnormalities in a total of 83.8% of melanomas, and 1.9% of nevus without atypia, while genetic abnormalities were identified in 6.3%, 6.7%, and 10.3% of nevus identified with mild, moderate and severe atypia, respectively. Conclusions Based on this study, inheritable genetic damage/instability identified by FISH testing is a hallmark of a progressive malignant process, and a valuable diagnostic tool for the identification of high risk lesions.
Keywords	Pathology ; RB1-214 ; Medicine ; R ; DOAJ:Pathology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2011-08-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
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Article ; Online: Polygenic risk scores point toward potential genetic mechanisms of type 2 myocardial infarction in people with HIV.

Lee, Won Jun / Cheng, Haoxiang / Whitney, Bridget M / Nance, Robin M / Britton, Sierra R / Jordahl, Kristina / Lindstrom, Sara / Ruderman, Stephanie A / Kitahata, Mari M / Saag, Michael S / Willig, Amanda L / Burkholder, Greer / Eron, Joseph J / Kovacic, Jason C / Björkegren, Johan L M / Mathews, W Christopher / Cachay, Edward / Feinstein, Matthew J / Budoff, Mathew /

Hunt, Peter W / Moore, Richard D / Keruly, Jeanne / McCaul, Mary E / Chander, Geetanjali / Webel, Allison / Mayer, Kenneth H / Delaney, Joseph A / Crane, Paul K / Martinez, Claudia / Crane, Heidi M / Hao, Ke / Peter, Inga

International journal of cardiology

2023 Volume 383, Page(s) 15–23

Abstract: Background: People with human immunodeficiency virus (HIV) infection (PWH) are at higher risk of myocardial infarction (MI) than those without HIV. About half of MIs in PWH are type 2 (T2MI), resulting from mismatch between myocardial oxygen supply and ... ...

Abstract	Background: People with human immunodeficiency virus (HIV) infection (PWH) are at higher risk of myocardial infarction (MI) than those without HIV. About half of MIs in PWH are type 2 (T2MI), resulting from mismatch between myocardial oxygen supply and demand, in contrast to type 1 MI (T1MI), which is due to primary plaque rupture or coronary thrombosis. Despite worse survival and rising incidence in the general population, evidence-based treatment recommendations for T2MI are lacking. We used polygenic risk scores (PRS) to explore genetic mechanisms of T2MI compared to T1MI in PWH. Methods: We derived 115 PRS for MI-related traits in 9541 PWH enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort with adjudicated T1MI and T2MI. We applied multivariate logistic regression analyses to determine the association with T1MI and T2MI. Based on initial findings, we performed gene set enrichment analysis of the top variants composing PRS associated with T2MI. Results: We found that T1MI was strongly associated with PRS for cardiovascular disease, lipid profiles, and metabolic traits. In contrast, PRS for alcohol dependence and cholecystitis, significantly enriched in energy metabolism pathways, were predictive of T2MI risk. The association remained after the adjustment for actual alcohol consumption. Conclusions: We demonstrate distinct genetic traits associated with T1MI and T2MI among PWH further highlighting their etiological differences and supporting the role of energy regulation in T2MI pathogenesis.
MeSH term(s)	Humans ; Myocardial Infarction/diagnosis ; Myocardial Infarction/genetics ; Risk Factors ; Anterior Wall Myocardial Infarction/complications ; HIV Infections/epidemiology ; HIV Infections/genetics ; Myocardium
Language	English
Publishing date	2023-05-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	779519-1
ISSN	1874-1754 ; 0167-5273
ISSN (online)	1874-1754
ISSN	0167-5273
DOI	10.1016/j.ijcard.2023.04.058
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