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2019’s top five most viewed articles in Clinical Chemistry highlight the new and now, addressing key cardiac biomarkers, a mass spectrometry pen’s ability to identify ovarian cancer tissue, revelations on men’s health and miscarriages, and a novel test for determining single-base methylation. The top five articles appeared in the journal from January through October. Most-read rankings are based on full-text and PDF views.

The five most viewed 2019 articles include:

  1. Reduced Testicular Steroidogenesis and Increased Semen Oxidative Stress in Male Partners as Novel Markers of Recurrent Miscarriage;
  2. Full-Size and Partially Truncated Cardiac Troponin Complexes in the Blood of Patients with Acute Myocardial Infarction;
  3. Performance of the MassSpec Pen for Rapid Diagnosis of Ovarian Cancer;
  4. Novel Assay for Quantitative Analysis of DNA Methylation at Single-Base Resolution; and
  5. Increased Inflammatory Activity in Patients 3 Months after Myocardial Infarction with Nonobstructive Coronary Arteries.

The most read Clinical Chemistry article of 2019 spotlights the role of men’s health and its impact on fertility. Recurrent miscarriage or pregnancy loss (RPL) is a devastating condition affecting 1% to 2% of all couples, lead author Channa Jayasena, PhD, MRCP, FRCPATH, clinical senior lecturer and consultant in reproductive endocrinology and andrology at Imperial College and Hammersmith Hospital, London, told CLN Stat. While routine screening takes place in affected women with RPL, their male partners are often not investigated at all, he noted. His research team hypothesized that certain reproductive and metabolic impairments in these men might be affecting sperm supply.

The study’s breakthrough finding showed that men affected by recurrent miscarriage had a higher risk of elevated reactive oxidative species (ROS) in their semen and sperm DNA damage. “Our data suggest that men affected by recurrent miscarriage may benefit from routine assessment of novel markers of reproductive potential such as semen ROS,” said Jayasena.

Moving on from reproductive to cardiovascular health, another top five study delved into the widely read topic of biomarker function and heart attack. “Cardiac biomarker papers always generate a lot of interest because of the role troponin assays play in ruling in and out myocardial infarction (MI) and in demonstrating the presence of cardiac injury due to nonischemic causes,” offered Mitchell G. Scott, PhD, DABCC, who edited the paper. Used worldwide, high-sensitivity cardiac troponin (hs-cTn) assays were recently introduced in the United States, after the Food and Drug Administration’s approval of several hs-cTn methods. “This has likely resulted in even more recent interest in troponin methods,” added Scott, a professor of pathology and immunology in the division of laboratory and genomic medicine at Washington University School of Medicine.

The paper describes the molecular forms of circulating cardiac troponin I (cTnI) and troponin T (cTnT) complexes and fragments following an MI. Investigators used classic biochemical approaches such as gel filtration chromatography, novel sandwich immunoassays, and western blotting to identify troponin complexes I, T, and C. Their research revealed the presence of full-size complexes and I and T truncated ITC complexes, and truncated free forms of I and T. “They also demonstrated a time-dependent transformation of full-size molecule to low molecular weight forms of cardiac troponins during acute MI progress,” said Scott.

Having additional knowledge of the troponin forms that circulate in blood at different times will help select appropriate antibodies to further improve the diagnosis of MI, he concluded.

On a related topic, another study dug deeper into the connection between MI and nonobstructive coronary arteries (MINOCA). Using a proximity extension assay to measure 91 cardiovascular biomarkers in MINOCA patients, healthy controls, and MI patients with obstructive coronary artery disease (MI-CAD), researchers discovered higher inflammatory activity in the MINOCA patients 3 months following an MI.

The paper on the MasSpec Pen addressed two rapidly developing areas in laboratory medicine and patient care: mass spectrometry (MS) and point-of-care diagnostics. “The ability to bring a remarkably sensitive and specific technique to point-of-care diagnosis represents a major advance,” Thomas Annesley, PhD, deputy editor of Clinical Chemistry and editor of this article, told CLN Stat. The pen allows for rapid and accurate intraoperative tissue evaluation, which could improve diagnosis during cytoreductive surgery and the overall management of patients with ovarian cancer, Annesley said. The instrument’s simple design, ease of operation, and biocompatibility make it attractive for clinical use. “Thus, the MasSpec Pen could be envisioned as a tool in the operating room for in vivo and/or ex vivo use in conjunction with standard surgical tools,” he added.

In the study, investigators evaluated the pen’s ability to distinguish ovarian cancer from healthy ovarian tissue using training, validation, and test sets of samples, the study’s lead authors explained to CLN Stat. Their results reflected more than 94% clinical sensitivity and specificity. “We were able to observe variations in the mass spectra obtained from high-grade and low-grade ovarian carcinomas, which present with different behaviors and clinical outcomes,” the investigators said. The instrument also enabled them to differentiate ovarian cancer tissue from healthy fallopian tube and peritoneum tissues with high accuracy (92.6% and 87.9%, respectively), “further demonstrating the potential use of this technology to help guide ovarian cancer surgical resections in cases of metastases,” the researchers added.

Another research team developed a novel PCR-based assay (QASM) able to determine methylation at a single-based resolution with high sensitivity and specificity. Applying the TaqMan genotyping principle to the assay, the team used paired probes binding to the methylated and unmethylated allele of targeted single CpGs, according to lead study author Yanxin Luo MD, PhD. “The QASM assay can be easily applied to determine single-CpG methylation as biomarkers in clinical practice and laboratory research,” Luo, associate professor of surgery with the 6th Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China, told CLN Stat.

Using a custom probe-based QASM in a low-throughput assay is also quicker and less expensive than using pyrosequencing, he said.

AACC members can look back on any of these articles in the 2019 Clinical Chemistry archives while looking ahead to new content that advances science and practice in clinical laboratory medicine.