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  1. Article ; Online: Learning from osteoporosis: TCF4 as a promising companion biomarker for breast cancer.

    Hsiao, Jui-Hu / Chou, Yi-Yu / Li, Chia-Jung / Tzeng, Yen-Dun Tony

    International journal of rheumatic diseases

    2023  Volume 26, Issue 7, Page(s) 1220–1221

    MeSH term(s) Humans ; Female ; Breast Neoplasms/genetics ; Biomarkers ; Osteoporosis/diagnostic imaging ; Osteoporosis/drug therapy ; Transcription Factor 4
    Chemical Substances Biomarkers ; TCF4 protein, human ; Transcription Factor 4
    Language English
    Publishing date 2023-06-30
    Publishing country England
    Document type Editorial ; Comment
    ZDB-ID 2426924-4
    ISSN 1756-185X ; 1756-1841
    ISSN (online) 1756-185X
    ISSN 1756-1841
    DOI 10.1111/1756-185X.14674
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    Zs.A 6098: Show issues Location:
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  2. Article: Automated Classification of Resting-State fMRI ICA Components Using a Deep Siamese Network.

    Chou, Yiyu / Chang, Catie / Remedios, Samuel W / Butman, John A / Chan, Leighton / Pham, Dzung L

    Frontiers in neuroscience

    2022  Volume 16, Page(s) 768634

    Abstract: Manual classification of functional resting state networks (RSNs) derived from Independent Component Analysis (ICA) decomposition can be labor intensive and requires expertise, particularly in large multi-subject analyses. Hence, a fully automatic ... ...

    Abstract Manual classification of functional resting state networks (RSNs) derived from Independent Component Analysis (ICA) decomposition can be labor intensive and requires expertise, particularly in large multi-subject analyses. Hence, a fully automatic algorithm that can reliably classify these RSNs is desirable. In this paper, we present a deep learning approach based on a Siamese Network to learn a discriminative feature representation for single-subject ICA component classification. Advantages of this supervised framework are that it requires relatively few training data examples and it does not require the number of ICA components to be specified. In addition, our approach permits one-shot learning, which allows generalization to new classes not seen in the training set with only one example of each new class. The proposed method is shown to out-perform traditional convolutional neural network (CNN) and template matching methods in identifying eleven subject-specific RSNs, achieving 100% accuracy on a holdout data set and over 99% accuracy on an outside data set. We also demonstrate that the method is robust to scan-rescan variation. Finally, we show that the functional connectivity of default mode and salience networks identified by the proposed technique is altered in a group analysis of mild traumatic brain injury (TBI), severe TBI, and healthy subjects.
    Language English
    Publishing date 2022-03-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2022.768634
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  3. Article ; Online: A Pilot Study Investigating the Use of serum GFAP to Monitor Changes in Brain White Matter Integrity after Repetitive Head Hits During a Single Collegiate football game.

    Bazarian, Jeffrey / Abar, Beau / Merchant-Borna, Kian / Pham, Dzung L / Rozen, Eric / Mannix, Rebekah / Kawata, Keisuke / Chou, Yi-Yu / Stephen, Steve J / Gill, Jessica

    Journal of neurotrauma

    2024  

    Abstract: Repetitive head hits (RHHs) in sports and military settings are increasingly recognized as a risk factor for adverse neurologic outcomes, but they are not currently tracked. Blood-based biomarkers of concussion have recently been shown to increase after ... ...

    Abstract Repetitive head hits (RHHs) in sports and military settings are increasingly recognized as a risk factor for adverse neurologic outcomes, but they are not currently tracked. Blood-based biomarkers of concussion have recently been shown to increase after non-concussive RHHs during a single sporting contest, raising the possibility that they could be used in real-time to monitor the brain's early response to repeated asymptomatic head hits. In order to test this hypothesis, we measured GFAP in serum immediately before (T0), immediately after (T1) and 45 minutes (T2) after a single collegiate football game in 30 athletes. GFAP changes were correlated to 3 measures of head impact exposure (number of hits, total linear acceleration, and total rotational acceleration captured by helmet impact sensors) and to changes in brain white matter (WM) integrity, estimated by regional changes in fractional anisotropy (FA) and mean diffusivity (MD) on diffusion tensor imaging from 24 hours before (T-1) to 48 hours after (T3) the game). To account for the potentially confounding effects of physical exertion on GFAP, correlations were adjusted for kilocalories of energy expended during the game measured by wearable body sensors. All 30 participants were male with a mean age of 19.5+1.2 years. No participant had a concussion during the index game. We observed a significant increase in GFAP from T0 to T1 (mean 79.69 vs 91.95 pg/mL, p=0.008) and from T0 to T2 (mean 79.69 vs 99.21 pg/mL, p<0.001). White matter integrity decreased in multiple WM regions but was statistically significant in the right fornix (mean % FA change -1.43, 95% CI:-2.20, -0.66). T0 to T2 increases in GFAP correlated with reduced FA in the left fornix, right fornix, and right medical meniscus, and with increased MD in the right fornix (|r-values| ranged from 0.59-0.61). Adjustment for exertion had minimal effect on these correlations. GFAP changes did not correlate to head hit exposure, but after adjustment for exertion, T0 to T2 increases correlated with all three hit metrics (r-values ranged from 0.69-0.74). Thus, acute elevations in GFAP after a single collegiate football game of RHHs correlated with in-game head hit exposure and with reduced WM integrity 2 days later. These results suggest that GFAP may be a biologically relevant indicator of the brain's early response to RHHs during a single sporting event. Developing tools to measure the neurologic response to RHHs on an individual level has the potential to provide insight into the heterogeneity in adverse outcomes after RHH exposure and for developing effective and personalized countermeasures. Due to small sample size, these findings should be considered preliminary; validation in a larger, independent cohort is necessary.
    Language English
    Publishing date 2024-05-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645092-1
    ISSN 1557-9042 ; 0897-7151
    ISSN (online) 1557-9042
    ISSN 0897-7151
    DOI 10.1089/neu.2023.0307
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  4. Article: Antibody Profiling in COVID-19 Patients with Different Severities by Using Spike Variant Protein Microarrays

    Su, Wen-Yu / Du, Pin-Xian / Santos, Harvey M. / Ho, Tzong-Shiann / Keskin, Batuhan Birol / Pau, Chi Ho / Yang, An-Ming / Chou, Yi-Yu / Shih, Hsi-Chang / Syu, Guan-Da

    Analytical chemistry. 2022 Apr. 20, v. 94, no. 17

    2022  

    Abstract: The disease progression of COVID-19 varies from mild to severe, even death. However, the link between COVID-19 severities and humoral immune specificities is not clear. Here, we developed a multiplexed spike variant protein microarray (SVPM) and utilized ...

    Abstract The disease progression of COVID-19 varies from mild to severe, even death. However, the link between COVID-19 severities and humoral immune specificities is not clear. Here, we developed a multiplexed spike variant protein microarray (SVPM) and utilized it for quantifying neutralizing activity, drug screening, and profiling humoral immunity. First, we demonstrated the competition between antispike antibody and ACE2 on SVPM for measuring the neutralizing activity against multiple spike variants. Next, we collected the serums from healthy subjects and COVID-19 patients with different severities and profile the neutralizing activity as well as antibody isotypes. We identified the inhibition of ACE2 binding was stronger against multiple variants in severe compared to mild/moderate or critical patients. Moreover, the serum IgG against nonstructural protein 3 was elevated in severe but not in mild/moderate and critical cases. Finally, we evaluated two ACE2 inhibitors, Ramipril and Perindopril, and found the dose-dependent inhibition of ACE2 binding to all the spike variants except for B.1.617.3. Together, the SVPM and the assay procedures provide a tool for profiling neutralizing antibodies, antibody isotypes, and reagent specificities.
    Keywords COVID-19 infection ; analytical chemistry ; blood serum ; death ; disease progression ; dose response ; drugs ; humoral immunity ; protein microarrays ; viral nonstructural proteins
    Language English
    Dates of publication 2022-0420
    Size p. 6529-6539.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 1508-8
    ISSN 1520-6882 ; 0003-2700
    ISSN (online) 1520-6882
    ISSN 0003-2700
    DOI 10.1021/acs.analchem.1c05567
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  5. Article: Development of SARS-CoV-2 variant protein microarray for profiling humoral immunity in vaccinated subjects

    Ho, Tzong-Shiann / Du, Pin-Xian / Su, Wen-Yu / Santos, Harvey M. / Lin, Ya-Lan / Chou, Yi-Yu / Keskin, Batuhan Birol / Pau, Chi Ho / Syu, Guan-Da

    Biosensors & bioelectronics. 2022 May 15, v. 204

    2022  

    Abstract: SARS-CoV-2 is quickly evolving from wild-type to many variants and spreading around the globe. Since many people have been vaccinated with various types of vaccines, it is crucial to develop a high throughput platform for measuring the antibody responses ...

    Abstract SARS-CoV-2 is quickly evolving from wild-type to many variants and spreading around the globe. Since many people have been vaccinated with various types of vaccines, it is crucial to develop a high throughput platform for measuring the antibody responses and surrogate neutralizing activities against multiple SARS-CoV-2 variants. To meet this need, the present study developed a SARS-CoV-2 variant (CoVariant) array which consists of the extracellular domain of spike variants, e.g., wild-type, D614G, B.1.1.7, B.1.351, P.1, B.1.617, B.1.617.1, B.1.617.2, and B.1.617.3. A surrogate virus neutralization on the CoVariant array was established to quantify the bindings of antibody and host receptor ACE2 simultaneously to spike variants. By using a chimeric anti-spike antibody, we demonstrated a broad binding spectrum of antibodies while inhibiting the bindings of ACE2 to spike variants. To monitor the humoral immunities after vaccination, we collected serums from unvaccinated, partial, or fully vaccinated individuals with either mRNA-1273 or AZD1222 (ChAdOx1). The results showed partial vaccination increased the surrogate neutralization against all the mutants while full vaccination boosted the most. Although IgG, IgA, and IgM isotypes correlated with surrogate neutralizing activities, they behave differently throughout the vaccination processes. Overall, this study developed CoVariant arrays and assays for profiling the humoral responses which are useful for immune assessment, vaccine research, and drug development.
    Keywords Severe acute respiratory syndrome coronavirus 2 ; antibodies ; biosensors ; drug development ; humoral immunity ; neutralization ; neutralization tests ; people ; protein microarrays ; vaccination ; vaccines
    Language English
    Dates of publication 2022-0515
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 1011023-9
    ISSN 1873-4235 ; 0956-5663
    ISSN (online) 1873-4235
    ISSN 0956-5663
    DOI 10.1016/j.bios.2022.114067
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  6. Article ; Online: Antibody Profiling in COVID-19 Patients with Different Severities by Using Spike Variant Protein Microarrays.

    Su, Wen-Yu / Du, Pin-Xian / Santos, Harvey M / Ho, Tzong-Shiann / Keskin, Batuhan Birol / Pau, Chi Ho / Yang, An-Ming / Chou, Yi-Yu / Shih, Hsi-Chang / Syu, Guan-Da

    Analytical chemistry

    2022  Volume 94, Issue 17, Page(s) 6529–6539

    Abstract: The disease progression of COVID-19 varies from mild to severe, even death. However, the link between COVID-19 severities and humoral immune specificities is not clear. Here, we developed a multiplexed spike variant protein microarray (SVPM) and utilized ...

    Abstract The disease progression of COVID-19 varies from mild to severe, even death. However, the link between COVID-19 severities and humoral immune specificities is not clear. Here, we developed a multiplexed spike variant protein microarray (SVPM) and utilized it for quantifying neutralizing activity, drug screening, and profiling humoral immunity. First, we demonstrated the competition between antispike antibody and ACE2 on SVPM for measuring the neutralizing activity against multiple spike variants. Next, we collected the serums from healthy subjects and COVID-19 patients with different severities and profile the neutralizing activity as well as antibody isotypes. We identified the inhibition of ACE2 binding was stronger against multiple variants in severe compared to mild/moderate or critical patients. Moreover, the serum IgG against nonstructural protein 3 was elevated in severe but not in mild/moderate and critical cases. Finally, we evaluated two ACE2 inhibitors, Ramipril and Perindopril, and found the dose-dependent inhibition of ACE2 binding to all the spike variants except for B.1.617.3. Together, the SVPM and the assay procedures provide a tool for profiling neutralizing antibodies, antibody isotypes, and reagent specificities.
    MeSH term(s) Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; COVID-19 ; Humans ; Immunoglobulin Isotypes ; Protein Array Analysis
    Chemical Substances Antibodies, Neutralizing ; Immunoglobulin Isotypes ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Language English
    Publishing date 2022-04-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1508-8
    ISSN 1520-6882 ; 0003-2700
    ISSN (online) 1520-6882
    ISSN 0003-2700
    DOI 10.1021/acs.analchem.1c05567
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    Zs.A 4033: Show issues Location:
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  7. Article ; Online: Development of SARS-CoV-2 variant protein microarray for profiling humoral immunity in vaccinated subjects.

    Ho, Tzong-Shiann / Du, Pin-Xian / Su, Wen-Yu / Santos, Harvey M / Lin, Ya-Lan / Chou, Yi-Yu / Keskin, Batuhan Birol / Pau, Chi Ho / Syu, Guan-Da

    Biosensors & bioelectronics

    2022  Volume 204, Page(s) 114067

    Abstract: SARS-CoV-2 is quickly evolving from wild-type to many variants and spreading around the globe. Since many people have been vaccinated with various types of vaccines, it is crucial to develop a high throughput platform for measuring the antibody responses ...

    Abstract SARS-CoV-2 is quickly evolving from wild-type to many variants and spreading around the globe. Since many people have been vaccinated with various types of vaccines, it is crucial to develop a high throughput platform for measuring the antibody responses and surrogate neutralizing activities against multiple SARS-CoV-2 variants. To meet this need, the present study developed a SARS-CoV-2 variant (CoVariant) array which consists of the extracellular domain of spike variants, e.g., wild-type, D614G, B.1.1.7, B.1.351, P.1, B.1.617, B.1.617.1, B.1.617.2, and B.1.617.3. A surrogate virus neutralization on the CoVariant array was established to quantify the bindings of antibody and host receptor ACE2 simultaneously to spike variants. By using a chimeric anti-spike antibody, we demonstrated a broad binding spectrum of antibodies while inhibiting the bindings of ACE2 to spike variants. To monitor the humoral immunities after vaccination, we collected serums from unvaccinated, partial, or fully vaccinated individuals with either mRNA-1273 or AZD1222 (ChAdOx1). The results showed partial vaccination increased the surrogate neutralization against all the mutants while full vaccination boosted the most. Although IgG, IgA, and IgM isotypes correlated with surrogate neutralizing activities, they behave differently throughout the vaccination processes. Overall, this study developed CoVariant arrays and assays for profiling the humoral responses which are useful for immune assessment, vaccine research, and drug development.
    MeSH term(s) Antibodies, Neutralizing ; Antibodies, Viral ; Biosensing Techniques ; COVID-19 ; ChAdOx1 nCoV-19 ; Humans ; Immunity, Humoral ; Protein Array Analysis ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; ChAdOx1 nCoV-19 (B5S3K2V0G8)
    Language English
    Publishing date 2022-02-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 1011023-9
    ISSN 1873-4235 ; 0956-5663
    ISSN (online) 1873-4235
    ISSN 0956-5663
    DOI 10.1016/j.bios.2022.114067
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    Zs.A 2275: Show issues Location:
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  8. Article ; Online: Effects of Physical Exertion on Early Changes in Blood-Based Brain Biomarkers: Implications for the Acute Point of Care Diagnosis of Concussion.

    Bazarian, Jeffrey J / Abar, Beau / Merchant-Borna, Kian / Pham, Dzung L / Rozen, Eric / Mannix, Rebekah / Kawata, Keisuke / Chou, Yiyu / Stephen, Steve / Gill, Jessica M

    Journal of neurotrauma

    2022  Volume 40, Issue 7-8, Page(s) 693–705

    Abstract: Blood-based brain biomarkers (BBM) such as glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have potential to aid in the diagnosis of concussion. Recently developed point-of-care test devices would enable BBMs ... ...

    Abstract Blood-based brain biomarkers (BBM) such as glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have potential to aid in the diagnosis of concussion. Recently developed point-of-care test devices would enable BBMs to be measured in field settings such military and sport environments within minutes of a suspicious head hit. However, head hits in these environments typically occur in the setting of vigorous physical exertion, which can itself increase BBMs levels. Thus, efforts to develop BBMs as acute concussion aids in field settings need to account for the effects of physical exertion. To determine the acute effects of physical exertion on the BBMs, we measured GFAP, UCH-L1, tau, and neurofilament light chain (NF-L) immediately before, immediately after, and 45 min after a single workout session consisting of aerobic and resistance exercises in 30 collegiate football players. Subjects wore body sensors measuring several aspects of exertion and underwent diffusion tensor imaging 24 h before and 48 h after exertion. All subjects were male with a mean age of 19.5 ± 1.2 years. The mean duration of activity during the workout session was 94 ± 31 min. There was a significant decrease in serum GFAP immediately after (median decrease of 27.76%,
    MeSH term(s) Humans ; Male ; Adolescent ; Young Adult ; Adult ; Female ; Physical Exertion ; Point-of-Care Systems ; Diffusion Tensor Imaging ; Brain Concussion/diagnosis ; Biomarkers ; Ubiquitin Thiolesterase ; Glial Fibrillary Acidic Protein ; Football ; Brain/diagnostic imaging
    Chemical Substances Biomarkers ; Ubiquitin Thiolesterase (EC 3.4.19.12) ; Glial Fibrillary Acidic Protein
    Language English
    Publishing date 2022-11-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 645092-1
    ISSN 1557-9042 ; 0897-7151
    ISSN (online) 1557-9042
    ISSN 0897-7151
    DOI 10.1089/neu.2022.0267
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  9. Book ; Online: Contrast Adaptive Tissue Classification by Alternating Segmentation and Synthesis

    Pham, Dzung L. / Chou, Yi-Yu / Dewey, Blake E. / Reich, Daniel S. / Butman, John A. / Roy, Snehashis

    2021  

    Abstract: Deep learning approaches to the segmentation of magnetic resonance images have shown significant promise in automating the quantitative analysis of brain images. However, a continuing challenge has been its sensitivity to the variability of acquisition ... ...

    Abstract Deep learning approaches to the segmentation of magnetic resonance images have shown significant promise in automating the quantitative analysis of brain images. However, a continuing challenge has been its sensitivity to the variability of acquisition protocols. Attempting to segment images that have different contrast properties from those within the training data generally leads to significantly reduced performance. Furthermore, heterogeneous data sets cannot be easily evaluated because the quantitative variation due to acquisition differences often dwarfs the variation due to the biological differences that one seeks to measure. In this work, we describe an approach using alternating segmentation and synthesis steps that adapts the contrast properties of the training data to the input image. This allows input images that do not resemble the training data to be more consistently segmented. A notable advantage of this approach is that only a single example of the acquisition protocol is required to adapt to its contrast properties. We demonstrate the efficacy of our approaching using brain images from a set of human subjects scanned with two different T1-weighted volumetric protocols.

    Comment: 10 pages. MICCAI SASHIMI Workshop 2021
    Keywords Electrical Engineering and Systems Science - Image and Video Processing ; Computer Science - Computer Vision and Pattern Recognition
    Subject code 004
    Publishing date 2021-03-03
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Imaging biomarkers of vascular and axonal injury are spatially distinct in chronic traumatic brain injury.

    Haber, Margalit / Amyot, Franck / Lynch, Cillian E / Sandsmark, Danielle K / Kenney, Kimbra / Werner, John K / Moore, Carol / Flesher, Kelley / Woodson, Sarah / Silverman, Erika / Chou, Yiyu / Pham, Dzung / Diaz-Arrastia, Ramon

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

    2021  Volume 41, Issue 8, Page(s) 1924–1938

    Abstract: Traumatic Brain Injury (TBI) is associated with both diffuse axonal injury (DAI) and diffuse vascular injury (DVI), which result from inertial shearing forces. These terms are often used interchangeably, but the spatial relationships between DAI and DVI ... ...

    Abstract Traumatic Brain Injury (TBI) is associated with both diffuse axonal injury (DAI) and diffuse vascular injury (DVI), which result from inertial shearing forces. These terms are often used interchangeably, but the spatial relationships between DAI and DVI have not been carefully studied. Multimodal magnetic resonance imaging (MRI) can help distinguish these injury mechanisms: diffusion tensor imaging (DTI) provides information about axonal integrity, while arterial spin labeling (ASL) can be used to measure cerebral blood flow (CBF), and the reactivity of the Blood Oxygen Level Dependent (BOLD) signal to a hypercapnia challenge reflects cerebrovascular reactivity (CVR). Subjects with chronic TBI (n = 27) and healthy controls (n = 14) were studied with multimodal MRI. Mean values of mean diffusivity (MD), fractional anisotropy (FA), CBF, and CVR were extracted for pre-determined regions of interest (ROIs). Normalized z-score maps were generated from the pool of healthy controls. Abnormal ROIs in one modality were not predictive of abnormalities in another. Approximately 9-10% of abnormal voxels for CVR and CBF also showed an abnormal voxel value for MD, while only 1% of abnormal CVR and CBF voxels show a concomitant abnormal FA value. These data indicate that DAI and DVI represent two distinct TBI endophenotypes that are spatially independent.
    MeSH term(s) Adult ; Anisotropy ; Axons/pathology ; Biomarkers/metabolism ; Brain/blood supply ; Brain/physiopathology ; Brain/ultrastructure ; Brain Injuries, Traumatic/diagnostic imaging ; Brain Injuries, Traumatic/pathology ; Brain Injury, Chronic/diagnostic imaging ; Brain Injury, Chronic/pathology ; Brain Mapping ; Case-Control Studies ; Cerebrovascular Circulation/physiology ; Female ; Humans ; Hypercapnia/diagnostic imaging ; Hypocapnia/physiopathology ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Spin Labels
    Chemical Substances Biomarkers ; Spin Labels
    Language English
    Publishing date 2021-01-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 604628-9
    ISSN 1559-7016 ; 0271-678X
    ISSN (online) 1559-7016
    ISSN 0271-678X
    DOI 10.1177/0271678X20985156
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