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Article ; Online: Sex disparities in cancer: An ongoing quest.

Luo, Jingqin R / Colditz, Graham A

2022 Volume 128, Issue 19, Page(s) 3446–3448

MeSH term(s)	Health Status Disparities ; Humans ; Longitudinal Studies ; Neoplasms/epidemiology ; Neoplasms/therapy
Language	English
Publishing date	2022-08-08
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.34389
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Uh III Zs.146: Show issues

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Article ; Online: ISIT-QA: In Silico Imaging Trial to Evaluate a Low-Count Quantitative SPECT Method Across Multiple Scanner-Collimator Configurations for

Li, Zekun / Benabdallah, Nadia / Luo, Jingqin / Wahl, Richard L / Thorek, Daniel L J / Jha, Abhinav K

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2024 Volume 65, Issue 5, Page(s) 810–817

Abstract: Personalized dose-based treatment planning requires accurate and reproducible noninvasive measurements to ensure safety and effectiveness. Dose estimation using SPECT is possible but challenging for alpha (α)-particle-emitting radiopharmaceutical therapy ...

Abstract	Personalized dose-based treatment planning requires accurate and reproducible noninvasive measurements to ensure safety and effectiveness. Dose estimation using SPECT is possible but challenging for alpha (α)-particle-emitting radiopharmaceutical therapy (α-RPT) because of complex γ-emission spectra, extremely low counts, and various image-degrading artifacts across a plethora of scanner-collimator configurations. Through the incorporation of physics-based considerations and skipping of the potentially lossy voxel-based reconstruction step, a recently developed projection-domain low-count quantitative SPECT (LC-QSPECT) method has the potential to provide reproducible, accurate, and precise activity concentration and dose measures across multiple scanners, as is typically the case in multicenter settings. To assess this potential, we conducted an in silico imaging trial to evaluate the LC-QSPECT method for a
MeSH term(s)	Tomography, Emission-Computed, Single-Photon ; Humans ; Radiopharmaceuticals ; Computer Simulation ; Radium/therapeutic use ; Male ; Image Processing, Computer-Assisted/methods ; Reproducibility of Results ; Quality Control
Chemical Substances	Radiopharmaceuticals ; Radium (W90AYD6R3Q) ; Radium-223 (8BR2SOL3L1)
Language	English
Publishing date	2024-05-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.123.266719
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Zs.A 114: 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.MO 328: Show issues

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Article ; Online: Aspirin Metabolites and Mammographic Breast Density in Premenopausal Women.

Singh, Ramkrishna Kumar / Getz, Kayla R / Kyeyune, Joy K / Jeon, Myung Sik / Luo, Chongliang / Luo, Jingqin / Toriola, Adetunji T

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

2024

Abstract: Background: Studies investigating the associations of self-reported aspirin use and mammographic breast density (MBD) have reported conflicting results. We, therefore, investigated the associations of aspirin metabolites, with MBD in premenopausal women. ...

Abstract	Background: Studies investigating the associations of self-reported aspirin use and mammographic breast density (MBD) have reported conflicting results. We, therefore, investigated the associations of aspirin metabolites, with MBD in premenopausal women. Methods: We performed this study on 705 premenopausal women who had fasting blood draw for metabolomic profiling. We performed covariate-adjusted linear regression models to calculate the least squares means of volumetric measures of MBD (volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV)) by quartiles of aspirin metabolites (salicyluric glucuronide, 2-hydroxyhippurate (salicylurate), salicylate, and 2,6-dihydroxybenzoic acid). Results: Approximately 13% of participants reported taking aspirin in the past 12 months. Aspirin users had higher levels of 2-hydroxyhippurate (salicylurate), salicylate, and salicyluric glucuronide (peak area) than non-users, but only mean peak area of salicyluric glucuronide increased by both dose (1-2 tabs per day=1,140,663.7, and ≥3 tabs per day=1,380,476.0) and frequency (days per week: 1 day=888,129.3, 2-3 days=1,199,897.9 and ≥4 days=1,654,637.0). Aspirin metabolites were not monotonically associated with VPD, DV, or NDV. Conclusions: Given the null results, additional research investigating the associations of aspirin metabolites in breast tissue and MBD is necessary. Impact: Elucidating the determinants of MBD, a strong risk factor for breast cancer, can play an important role in breast cancer prevention. Future studies should determine the associations of non-aspirin non-steroidal anti-inflammatory drug metabolites with MBD.
Language	English
Publishing date	2024-05-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	1153420-5
ISSN	1538-7755 ; 1055-9965
ISSN (online)	1538-7755
ISSN	1055-9965
DOI	10.1158/1055-9965.EPI-24-0017
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Zs.A 3693: Show issues

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Article ; Online: Lipidome of mammographic breast density in premenopausal women.

Getz, Kayla R / Jeon, Myung Sik / Luo, Chongliang / Luo, Jingqin / Toriola, Adetunji T

Breast cancer research : BCR

2023 Volume 25, Issue 1, Page(s) 121

Abstract: Background: High mammographic breast density (MBD) is a strong risk factor for breast cancer development, but the biological mechanisms underlying MBD are unclear. Lipids play important roles in cell differentiation, and perturbations in lipid ... ...

Abstract	Background: High mammographic breast density (MBD) is a strong risk factor for breast cancer development, but the biological mechanisms underlying MBD are unclear. Lipids play important roles in cell differentiation, and perturbations in lipid metabolism are implicated in cancer development. Nevertheless, no study has applied untargeted lipidomics to profile the lipidome of MBD. Through this study, our goal is to characterize the lipidome of MBD in premenopausal women. Methods: Premenopausal women were recruited during their annual screening mammogram at the Washington University School of Medicine in St. Louis, MO. Untargeted lipidomic profiling for 982 lipid species was performed at Metabolon (Durham, NC®), and volumetric measures of MBD (volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV)) was assessed using Volpara 1.5 (Volpara Health®). We performed multivariable linear regression models to investigate the associations of lipid species with MBD and calculated the covariate-adjusted least square mean of MBD by quartiles of lipid species. MBD measures were log Results: Of the 705 premenopausal women, 72% were non-Hispanic white, and 23% were non-Hispanic black. Mean age, and BMI were 46 years and 30 kg/m Conclusions: We report novel lipid species that are associated with MBD in premenopausal women. Studies are needed to validate our results and the translational potential.
MeSH term(s)	Female ; Humans ; Breast Density ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/etiology ; Lipidomics ; Mammography ; Risk Factors ; Lipids
Chemical Substances	Lipids
Language	English
Publishing date	2023-10-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-023-01725-1
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Zs.A 5494: Show issues

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Article ; Online: Associations of Vitamins and Related Cofactor Metabolites with Mammographic Breast Density in Premenopausal Women.

Matthew, Kayode A / Getz, Kayla R / Jeon, Myung Sik / Luo, Chongliang / Luo, Jingqin / Toriola, Adetunji T

The Journal of nutrition

2023 Volume 154, Issue 2, Page(s) 424–434

Abstract: Background: Identifying biological drivers of mammographic breast density (MBD), a strong risk factor for breast cancer, could provide insight into breast cancer etiology and prevention. Studies on dietary factors and MBD have yielded conflicting ... ...

Abstract	Background: Identifying biological drivers of mammographic breast density (MBD), a strong risk factor for breast cancer, could provide insight into breast cancer etiology and prevention. Studies on dietary factors and MBD have yielded conflicting results. There are, however, very limited data on the associations of dietary biomarkers and MBD. Objective: We aimed to investigate the associations of vitamins and related cofactor metabolites with MBD in premenopausal women. Methods: We measured 37 vitamins and related cofactor metabolites in fasting plasma samples of 705 premenopausal women recruited during their annual screening mammogram at the Washington University School of Medicine, St. Louis, MO. Volpara was used to assess volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV). We estimated the least square means of VPD, DV, and NDV across quartiles of each metabolite, as well as the regression coefficient of a metabolite in continuous scale from multiple covariate-adjusted linear regression. We corrected for multiple testing using the Benjamini-Hochberg procedure to control the false discover rate (FDR) at a 5% level. Results: Participants' mean VPD was 10.5%. Two vitamin A metabolites (β-cryptoxanthin and carotene diol 2) were positively associated, and one vitamin E metabolite (γ-tocopherol) was inversely associated with VPD. The mean VPD increased across quartiles of β-cryptoxanthin (Q1 = 7.2%, Q2 = 7.7%, Q3 = 8.4%%, Q4 = 9.2%; P-trend = 1.77E-05, FDR P value = 1.18E-03). There was a decrease in the mean VPD across quartiles of γ-tocopherol (Q1 = 9.4%, Q2 = 8.1%, Q3 = 8.0%, Q4 = 7.8%; P -trend = 4.01E-03, FDR P value = 0.04). Seven metabolites were associated with NDV: 3 vitamin E (γ-CEHC glucuronide, δ-CEHC, and γ-tocopherol) and 1 vitamin C (gulonate) were positively associated, whereas 2 vitamin A (carotene diol 2 and β-cryptoxanthin) and 1 vitamin C (threonate) were inversely associated with NDV. No metabolite was significantly associated with DV. Conclusion: We report novel associations of vitamins and related cofactor metabolites with MBD in premenopausal women.
MeSH term(s)	Female ; Humans ; Breast Density ; Vitamins ; Vitamin A ; gamma-Tocopherol ; Beta-Cryptoxanthin ; Breast Neoplasms/etiology ; Risk Factors ; Vitamin K ; Ascorbic Acid
Chemical Substances	Vitamins ; Vitamin A (11103-57-4) ; gamma-Tocopherol (8EF1Z1238F) ; Beta-Cryptoxanthin ; Vitamin K (12001-79-5) ; Ascorbic Acid (PQ6CK8PD0R)
Language	English
Publishing date	2023-12-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.1016/j.tjnut.2023.12.023
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Article ; Online: Does circulating progesterone mediate the associations of single nucleotide polymorphisms in progesterone receptor (PGR)-related genes with mammographic breast density in premenopausal women?

Akinjiyan, Favour A / Han, Yunan / Luo, Jingqin / Toriola, Adetunji T

Discover. Oncology

2021 Volume 12, Issue 1, Page(s) 47

Abstract: Progesterone is a proliferative hormone in the breast but the associations of genetic variations in progesterone-regulated pathways with mammographic breast density (MD) in premenopausal women and whether these associations are mediated through ... ...

Abstract	Progesterone is a proliferative hormone in the breast but the associations of genetic variations in progesterone-regulated pathways with mammographic breast density (MD) in premenopausal women and whether these associations are mediated through circulating progesterone are not clearly defined. We, therefore, investigated these associations in 364 premenopausal women with a median age of 44 years. We sequenced 179 progesterone receptor (PGR)-related single nucleotide polymorphisms (SNPs). We measured volumetric percent density (VPD) and non-dense volume (NDV) using Volpara. Linear regression models were fit on circulating progesterone or VPD/NDV separately. We performed mediation analysis to evaluate whether the effect of a SNP on VPD/NDV is mediated through circulating progesterone. All analyses were adjusted for confounders, phase of menstrual cycle and the Benjamini-Hochberg false discovery (FDR) adjusted p-value was applied to correct for multiple testing. In multivariable analyses, only PGR rs657516 had a direct effect on VPD (averaged direct effect estimate = - 0.20, 95%CI = - 0.38 ~ - 0.04, p-value = 0.02) but this was not statistically significant after FDR correction and the effect was not mediated by circulating progesterone (mediation effect averaged across the two genotypes = 0.01, 95%CI = - 0.02 ~ 0.03, p-value = 0.70). Five SNPs (PGR rs11571241, rs11571239, rs1824128, rs11571150, PGRMC1 rs41294894) were associated with circulating progesterone but these were not statistically significant after FDR correction. SNPs in PGR-related genes were not associated with VPD, NDV and circulating progesterone did not mediate the associations, suggesting that the effects, if any, of these SNPs on MD are independent of circulating progesterone. Supplementary information: The online version contains supplementary material available at 10.1007/s12672-021-00438-1.
Language	English
Publishing date	2021-11-03
Publishing country	United States
Document type	Journal Article
ISSN	2730-6011
ISSN (online)	2730-6011
DOI	10.1007/s12672-021-00438-1
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Article ; Online: De novo

Sponagel, Jasmin / Devarakonda, Siddhartha / Rubin, Joshua B / Luo, Jingqin / Ippolito, Joseph E

iScience

2022 Volume 25, Issue 11, Page(s) 105339

Abstract: Lung cancer is the leading cause of cancer-related death. Intriguingly, males with non-small cell lung cancer (NSCLC) have a higher mortality rate than females. Here, we investigated the role of serine metabolism as a predictive marker for sensitivity to ...

Abstract	Lung cancer is the leading cause of cancer-related death. Intriguingly, males with non-small cell lung cancer (NSCLC) have a higher mortality rate than females. Here, we investigated the role of serine metabolism as a predictive marker for sensitivity to the antifolate pemetrexed in male and female NSCLC cell lines. Using [
Language	English
Publishing date	2022-10-12
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.105339
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Article ; Online: A family of estimators to diagnostic accuracy when candidate tests are subject to detection limits-Application to diagnosing early stage Alzheimer disease.

Xiong, Chengjie / Luo, Jingqin / Agboola, Folasade / Grant, Elizabeth / Morris, John C

Statistical methods in medical research

2022 Volume 31, Issue 5, Page(s) 882–898

Abstract: In disease diagnosis, individuals are usually assumed to be one of the two basic types, healthy or diseased, as typically based on an established gold standard. Candidate markers for diagnosing a disease often are much cheaper and less invasive than the ... ...

Abstract	In disease diagnosis, individuals are usually assumed to be one of the two basic types, healthy or diseased, as typically based on an established gold standard. Candidate markers for diagnosing a disease often are much cheaper and less invasive than the gold standard but must be evaluated against the gold standard for their sensitivity and specificity to accurately diagnose the disease. When candidate diagnostic markers are fully measured, receiver operating characteristic curves have been the standard approaches for assessing diagnostic accuracy. However, full measurements of diagnostic markers may not be available above or below certain limits due to various practical and technical limitations. For example, in the diagnosis of Alzheimer disease using cerebrospinal fluid biomarkers, the Roche Elecsys® immunoassays have a measuring range for multiple cerebrospinal fluid molecular concentrations. Many cognitive tests used in diagnosing dementia due to Alzheimer disease are also subject to detection limits, often referred to as the floor and ceiling effects in the neuropsychological literature. We propose a new statistical methodology for estimating the diagnostic accuracy when a diagnostic marker is subject to detection limits by dividing the entire study sample into two sub-samples by a threshold of the diagnostic marker. We then propose a family of estimators to the area under the receiver operating characteristic curve by combining a conditional nonparametric estimator and another conditional semi-parametric estimator derived from Cox's proportional hazards model. We derive the variance to the proposed estimators, and further, assess the performance of the proposed estimators as a function of possible thresholds through an extensive simulation study, and recommend the optimum thresholds. Finally, we apply the proposed methodology to assess the ability of several cerebrospinal fluid biomarkers and cognitive tests in diagnosing early stage Alzheimer disease dementia.
MeSH term(s)	Alzheimer Disease/diagnosis ; Biomarkers ; Humans ; Limit of Detection ; ROC Curve ; Sensitivity and Specificity
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-01-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1136948-6
ISSN	1477-0334 ; 0962-2802
ISSN (online)	1477-0334
ISSN	0962-2802
DOI	10.1177/09622802211072511
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Zs.A 3564: Show issues

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Article ; Online: Comparing statistical methods in assessing the prognostic effect of biomarker variability on time-to-event clinical outcomes.

Gao, Feng / Luo, Jingqin / Liu, Jingxia / Wan, Fei / Wang, Guoqiao / Gordon, Mae / Xiong, Chengjie

BMC medical research methodology

2022 Volume 22, Issue 1, Page(s) 201

Abstract: Background: In recent years there is increasing interest in modeling the effect of early longitudinal biomarker data on future time-to-event or other outcomes. Sometimes investigators are also interested in knowing whether the variability of biomarkers ... ...

Abstract	Background: In recent years there is increasing interest in modeling the effect of early longitudinal biomarker data on future time-to-event or other outcomes. Sometimes investigators are also interested in knowing whether the variability of biomarkers is independently predictive of clinical outcomes. This question in most applications is addressed via a two-stage approach where summary statistics such as variance are calculated in the first stage and then used in models as covariates to predict clinical outcome in the second stage. The objective of this study is to compare the relative performance of various methods in estimating the effect of biomarker variability. Methods: A joint model and 4 different two-stage approaches (naïve, landmark analysis, time-dependent Cox model, and regression calibration) were illustrated using data from a large multi-center randomized phase III trial, the Ocular Hypertension Treatment Study (OHTS), regarding the association between the variability of intraocular pressure (IOP) and the development of primary open-angle glaucoma (POAG). The model performance was also evaluated in terms of bias using simulated data from the joint model of longitudinal IOP and time to POAG. The parameters for simulation were chosen after OHTS data, and the association between longitudinal and survival data was introduced via underlying, unobserved, and error-free parameters including subject-specific variance. Results: In the OHTS data, joint modeling and two-stage methods reached consistent conclusion that IOP variability showed no significant association with the risk of POAG. In the simulated data with no association between IOP variability and time-to-POAG, all the two-stage methods (except the naïve approach) provided a reliable estimation. When a moderate effect of IOP variability on POAG was imposed, all the two-stage methods underestimated the true association as compared with the joint modeling while the model-based two-stage method (regression calibration) resulted in the least bias. Conclusion: Regression calibration and joint modelling are the preferred methods in assessing the effect of biomarker variability. Two-stage methods with sample-based measures should be used with caution unless there exists a relatively long series of longitudinal measurements and/or strong effect size (NCT00000125).
MeSH term(s)	Biomarkers ; Clinical Trials, Phase III as Topic ; Glaucoma, Open-Angle ; Humans ; Intraocular Pressure ; Multicenter Studies as Topic ; Ocular Hypertension ; Prognosis ; Randomized Controlled Trials as Topic ; Risk Factors ; Tonometry, Ocular ; Visual Fields
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-07-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2041362-2
ISSN	1471-2288 ; 1471-2288
ISSN (online)	1471-2288
ISSN	1471-2288
DOI	10.1186/s12874-022-01686-7
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Article ; Online: Analysis of anemia and iron supplementation among glioblastoma patients reveals sex-biased association between anemia and survival.

Shenoy, Ganesh / Slagle-Webb, Becky / Khunsriraksakul, Chachrit / Pandya Shesh, Bhavyata / Luo, Jingqin / Khristov, Vladimir / Smith, Nataliya / Mansouri, Alireza / Zacharia, Brad E / Holder, Sheldon / Lathia, Justin D / Barnholtz-Sloan, Jill S / Connor, James R

Scientific reports

2024 Volume 14, Issue 1, Page(s) 2389

Abstract: The association between anemia and outcomes in glioblastoma patients is unclear. We analyzed data from 1346 histologically confirmed adult glioblastoma patients in the TriNetX Research Network. Median hemoglobin and hematocrit levels were quantified for ... ...

Abstract	The association between anemia and outcomes in glioblastoma patients is unclear. We analyzed data from 1346 histologically confirmed adult glioblastoma patients in the TriNetX Research Network. Median hemoglobin and hematocrit levels were quantified for 6 months following diagnosis and used to classify patients as anemic or non-anemic. Associations of anemia and iron supplementation of anemic patients with median overall survival (median-OS) were then studied. Among 1346 glioblastoma patients, 35.9% of male and 40.5% of female patients were classified as anemic using hemoglobin-based WHO guidelines. Among males, anemia was associated with reduced median-OS compared to matched non-anemic males using hemoglobin (HR 1.24; 95% CI 1.00-1.53) or hematocrit-based cutoffs (HR 1.28; 95% CI 1.03-1.59). Among females, anemia was not associated with median-OS using hemoglobin (HR 1.00; 95% CI 0.78-1.27) or hematocrit-based cutoffs (HR: 1.10; 95% CI 0.85-1.41). Iron supplementation of anemic females trended toward increased median-OS (HR 0.61; 95% CI 0.32-1.19) although failing to reach statistical significance whereas no significant association was found in anemic males (HR 0.85; 95% CI 0.41-1.75). Functional transferrin-binding assays confirmed sexually dimorphic binding in resected patient samples indicating underlying differences in iron biology. Anemia among glioblastoma patients exhibits a sex-specific association with survival.
MeSH term(s)	Adult ; Humans ; Male ; Female ; Iron ; Glioblastoma/complications ; Anemia/complications ; Hemoglobins/metabolism ; Dietary Supplements
Chemical Substances	Iron (E1UOL152H7) ; Hemoglobins
Language	English
Publishing date	2024-01-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-52492-8
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