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Multiplexing Homocysteine into First-Tier Newborn Screening Mass Spectrometry Assays Using Selective Thiol Derivatization

Overview of attention for article published in Clinical Chemistry, March 2023
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • One of the highest-scoring outputs from this source (#4 of 7,707)
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (98th percentile)

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Title
Multiplexing Homocysteine into First-Tier Newborn Screening Mass Spectrometry Assays Using Selective Thiol Derivatization
Published in
Clinical Chemistry, March 2023
DOI 10.1093/clinchem/hvad007
Pubmed ID
Authors

C Austin Pickens, Elya Courtney, Samantha L Isenberg, Carla Cuthbert, Konstantinos Petritis

Abstract

Classical homocystinuria (HCU) results from deficient cystathionine β-synthase activity, causing elevated levels of Met and homocysteine (Hcy). Newborn screening (NBS) aims to identify HCU in pre-symptomatic newborns by assessing Met concentrations in first-tier screening. However, unlike Hcy, Met testing leads to a high number of false-positive and -negative results. Therefore, screening for Hcy directly in first-tier screening would be a better biomarker for use in NBS. Dried blood spot (DBS) quality control and residual clinical specimens were used in analyses. Several reducing and maleimide reagents were investigated to aid in quantification of total Hcy (tHcy). The assay which was developed and validated was performed by flow injection analysis-tandem mass spectrometry (FIA-MS/MS). Interferents of tHcy measurement were identified, so selective derivatization of Hcy was employed. Using N-ethylmaleimide (NEM) to selectively derivatize Hcy allowed interferent-free quantification of tHcy by FIA-MS/MS in first-tier NBS. The combination of tris(2-carboxyethyl)phosphine (TCEP) and NEM yielded significantly less matrix effects compared to dithiothreitol (DTT) and NEM. Analysis of clinical specimens demonstrated that the method could distinguish between HCU-positive, presumptive normal newborns, and newborns receiving total parenteral nutrition. Here we present the first known validated method capable of screening tHcy in DBS during FIA-MS/S first-tier NBS.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 11 100%

Demographic breakdown

Readers by professional status Count As %
Student > Doctoral Student 3 27%
Student > Ph. D. Student 2 18%
Other 1 9%
Professor 1 9%
Unknown 4 36%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 1 9%
Agricultural and Biological Sciences 1 9%
Social Sciences 1 9%
Chemistry 1 9%
Unknown 7 64%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 578. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 October 2023.
All research outputs
#41,258
of 25,738,558 outputs
Outputs from Clinical Chemistry
#4
of 7,707 outputs
Outputs of similar age
#1,105
of 429,251 outputs
Outputs of similar age from Clinical Chemistry
#1
of 50 outputs
Altmetric has tracked 25,738,558 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 7,707 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one has done particularly well, scoring higher than 99% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 429,251 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 50 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 98% of its contemporaries.