Association of Clinical Scientists

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Michael Laposata, MD, PhD, “The Diagnostic Management Team: How it Works and What it Does.”
This presentation will focus on the function of a diagnostic management team from the point at which the case is identified until the recommendations for test selection and correct interpretation of results are delivered into the medical chart. There is variability in how the diagnostic management team (DMT) operates in different clinical areas because of the different needs for information in different medical areas, such as coagulation vs. toxicology. For all diagnostic management teams, there is a role for the trainee to create tentative recommendations and interpretations for modification before final entry by the laboratory director into the medical record. The DMT is an opportunity to educate trainees on a case-by-case basis by the clinical laboratory scientist who leads diagnostic management team rounds, whose clinical expertise also continuously grows. The presentation will also note the clinical impacts of shortened length of stay and improved test utilization from the DMT.

Michael Laposata, MD, PhD, “The Implementation of a COVID-19 Specific Diagnostic Management Team with Clinical and Financial Impacts.”
There have been many diagnostic uncertainties related to testing for infection and for antibody response to the SARS-CoV-2 virus. The variability between the many PCR tests in sensitivity is substantial, at least a thousand fold from the most sensitive to the least sensitive. In addition, the false negatives associated with the inability to swab an infected area in the respiratory tract, and thereby obtaining a false negative result for patients who are truly infected, has been confusing to many healthcare providers. The clinical implications of positive tests for IgM antibodies and IgG antibodies were confounded by the different methodologies used to identify the antibodies and for some tests, quantify the antibodies. Many lateral flow tests to assess antibodies, in particular, showed significant cross-reactivity with antibodies to several different viruses. To address these difficulties, a diagnostic management team (DMT) focused on the interpretation of tests for each individual patient receiving Covid related tests was initiated. The major challenge was the large number of samples, and this forced an invention in which the EPIC medical database was “taught” to select 1 of more than 150 written interpretations written by the laboratory director and suggest it as the correct interpretation of the test results. It has been a substantial effort to create and then update on a near weekly basis the interpretive comments presented to EPIC as a possible interpretation as more information is learned and reported in the medical literature. The clinical impact of this patient specific expert driven report, which is available to both doctors and the patients who were tested, has been substantial. It has also possible to bill for these reports. The revenue generation from this single Covid DMT in our institution exceeded the revenue generated from surgical pathology.

Christopher Zahner, MD, “Length of Stay Reduction Using a Coagulation Diagnostic Management Team.”
The question posed in this presentation is whether the coagulation diagnostic management team (DMT) at the University of Texas Medical Branch has resulted in a shorter length of stay for patients with bleeding or clotting disorders. A previous study at Vanderbilt indicated that both pulmonary embolism and hemorrhagic stroke patients, specifically, experienced a major reduction in length of stay and lower expense per case upon the introduction of a coagulation diagnostic management team in July, 2010. The current study, unlike the previous one, involves the analysis of large amounts of data over several years. The same benefit was recognized, but this investigation indicated that the presence of a report with recommendations for testing and interpretation of test results was not likely to be the major reason for the observed improvement in clinical outcomes. The data show that the creation of a diagnostic management team within an institution leads to markedly enhanced, clinically meaningful communications between laboratory experts and patient facing providers. This is analogous to the longstanding valued communication between radiologists and clinicians about selection of an imaging study and the interpretation of the findings. It has been shown that a query to the clinical laboratory today too often leads to a person who performed the test but has no knowledge of the clinical case. The actual presence of a diagnostic management team appears to create a link for consultation about laboratory tests.

Peter McCaffery, MD, “Future of the Diagnostic Management Team: A Collaboration of Industry and Academia in a Global Network.”
From the experience of the diagnostic management team for SARS-CoV-2 related results at the University of Texas Medical Branch, it was clear that the challenge of creating "smart" programs within EPIC to select one of many prewritten comments, as a possible interpretation for entry into the medical record, required partners in industry for technological developments. Identifying experts within academia who can provide a series of recommendations for test selection and result interpretation is a major but manageable obstacle. However, the need for a smart system that can with very high likelihood suggest to a laboratory expert what the correct narrative report should be is a challenge of the highest magnitude. In this presentation, it will be described how a clinical laboratory expert focused on the generation of hundreds of possible comments related to more than 150 sets of laboratory test results, while the industry partner assumed responsibility for creation of the smart system which suggested the correct one for each specific set of results. It is expected that the product that results from the collaboration of academic experts and industry will make it possible to generate diagnostic management teams across the world who can assist health care providers as the test menu becomes increasingly large and more costly. This presentation will describe a specific academia and industry collaboration that is rapidly evolving.

Eddie Salazar, PhD, MLS(ASCP)cm, “A New Curriculum to Train Doctoral Level Clinical Laboratory Scientists to Optimize Consultation by Laboratory Directors.”
It has long been recognized that the clinical laboratory sciences graduate has not had a doctoral level opportunity within the field since its creation. At the same time, the complexity of laboratory testing and the cost associated with the misuse of tests both continue to grow. At the University of Texas Medical Branch, a curriculum was developed in 2016 to train clinical laboratory scientists at the doctoral level. There is a high degree of focus for these graduates to serve as intermediate care providers for clinical laboratory activities, like pathology assistants in anatomic pathology. This presentation will discuss the development of the curriculum, with a focus on the clinical training and development of diagnostic skills of the doctoral students. The students are educated along with medical students at DMT rounds. They are responsible for generating recommendations for test selection and correct interpretation of complex test results, just as the residents in pathology, in at least 6 different diagnostic management teams. The service roles of now 3 full classes of graduates, along with the individual thesis work of each, will be included in the presentation.

Christopher Zahner, MD, “The Participation of the Doctoral Scientist in Clinical Laboratory Science (DCLS) in the Diagnostic Management Team Service.”
It is impossible for most doctoral level laboratory directors to create and manage a diagnostic management team (DMT) without the support of an individual who queries the medical record and reviews all the laboratory test results to create a preliminary set of recommendations for testing and interpretation of the test results. Most pathology residency programs cannot provide a person to perform this duty for all the rotations which benefit from a patient specific, expert driven DMT report. As a result, there is abundant opportunity for graduates of the doctorate in clinical laboratory sciences (DCLS) program to serve in this role, especially because they could be "permanently" associated with a specific diagnostic management team rather than rotating from one to another as residents do. The impact of the DCLS graduate in the clinical laboratory may be larger in smaller institutions, where there is often less institutional expertise about test selection and result interpretation. This presentation focuses on the evolving role of DCLS graduate in connecting healthcare providers in a meaningful way to experts within the clinical laboratory.

Thursday, May 13     Theme: Emerging Technologies in Clinical Laboratory Medicine

Friday, May 14     Theme: COVID-19 Surveillance in Public Health

Faisal M. Khan, PhD, University of Calgary
Towards Improved Outcomes in Hematologic Malignancies: Three Approaches of Precision Medicine

Prognosis of hematological malignancies like Acute Myeloid Leukemia (AML) and B cell NonHodgkin’s Lymphoma (NHL) is far from ideal, primarily due to frequent relapse and/or failure of treatment. Management of relapse is ineffective, whereas preemptive treatment of impending relapse is effective. However, existing approaches for early and reliable detection of impending relapse of malignancy are not successful. Building upon the research of several years, our team at University of Calgary is studying three synchronized approaches to identify most effective treatment strategy for AML/B-cell NHL and provide early and accurate prediction of leukemia relapse.

David Murray, MD, PhD, Mayo Clinic
The Journey to Replace Immunofixation with Mass Spectroscopy for Plasma Cell Disorders

This presentation will focus on the development, validation and implementation of a MALDI-TOF MS method as a replacement for traditional immunofixation electrophoreses for isotyping monoclonal proteins. The journey began in 2014 with studies involving high resolution LC-Q-TOF MS of tryptic peptides and intact immunoglobulin light chains with a goal of a serum based minimum residual disease detection in multiple myeloma patients. Subsequently, the method was adapted to a MALDI-TOF MS platform and coupled to IgG, IgA, IgM and kappa and lambda immunoenrichment termed Mass-Fix at Mayo Clinic. This was a key step which afforded the ideas of using the method in all aspects of multiple myeloma. Several studies involving both clinical and analytical performance of the assay demonstrated improvement over traditional electrophoretic analysis. Several patient cases will be presented to demonstrate these improvements which include increased specificity, improved sensitivity and the detection of M-proteins with light chain glysoylation. The detection of light chain glycosylation was found to be a risk factor for the development of plasma cell disorders. Several challenges and hurdles were experienced during the automation and implementation of the assay. Currently, our lab has performed more than 50,000 assays by the Mass-Fix method.

James Broach, PhD, Penn State Cancer Institute
Comprehensive Identification of Structural Variants, the Dark Matter of Cancer Genomics

Genomic analysis of tumors has stimulated major advances in cancer diagnosis, prognosis and treatment, shifting the focus from morphological and histochemical characterization to consideration of the landscape of driver mutations in the tumor. To date such consideration has focused on somatic mutations comprising single nucleotide changes or small insertions or deletions. We have recently applied optical genomic imaging (OGM) to a variety of human tumors and showed that OGM can detect structural variants (SVs), including deletions, insertions, duplications, inversions and translocations, that are not easily detectable using standard methods of whole genome analysis. Our studies of more than 100 cases of Acute Myeloid Leukemia indicated that OGM identified all the clinically relevant SVs and copy number variants reported by standard cytogenetic methods, such as cytological karyotyping, fluorescent in situ hybridization and microarrays. Importantly, OGM identified clinically relevant SVs in a number of cases that had been missed by the routine methods and refined the underlying genomic structure reported by traditional cytogenomic testing in many other cases. We also applied OGM to Human Papilloma Virus (HPV) associated head and neck cancers, predominantly oropharyngeal carcinomas. We found the virus had integrated into the host genome in two thirds of the tumors examined but resided solely extrachromosomally in the other third. Focal amplification of the virus and the genomics sequences surrounding it often occurred subsequent to integration. In all cases, viral integration correlated with pervasive genome-wide somatic alterations, including multiple insertions, deletions, translocations, inversions and point mutations. Few or no somatic structural variants were present in tumors with only episomal HPV. In sum, our studies have shown that OGM identifies numerous somatic mutations that current genomic analysis methods fail to reveal and this capability can improve diagnostic and prognostic efforts when applied to a variety of cancers.

Maria Elena Bottazzi, PhD, Texas Children’s Center, Baylor College of Medicine
International Efforts in Combatting COVID19: Behind the Scenes of How to Develop a COVID-19 Vaccine Suitable for Global Access.

For the last two decades, the National School of Tropical Medicine and its Center for Vaccine Development in Houston, Texas has operated with the mission to develop and test new low-cost and effective vaccines against emerging and neglected tropical diseases, build capacity for vaccine development locally and with foreign nations and guide and influence vaccine policy and advocacy. This approach relies on the need for international diplomacy, solidarity, and cooperation. This presentation will provide a behind the scenes vignette and an overview of the vaccine development process as well as a review of the coronavirus vaccine development landscape. Finally, it will highlight a case study of how a COVID-19 vaccine, suitable for global access, was developed and is currently advancing towards achieving emergency use authorization for distribution and access this summer.

Michael A. Pentella PhD, MS, SM(ASCP), CIC, DABMM, University of Iowa, College of Public Health
The Collaboration of Clinical and Public Health Laboratories to Provide COVID Testing Services.

The risk of an emerging pathogen evolving into a pandemic is always present but, fortunately, it is a very rare event. The experience of COVID-19 is unprecedented and has reinforced to us the importance of preparedness for the rare event to prevent the devastation that the pandemic can cause. In considering COVID-19, never before has laboratory testing played such a vital role nor been in such high demand. As in past pandemics, there are several phases from the occurrence of a few human infections through widespread human infection, to the post peak phase, and eventual post pandemic phase. These phases must be considered when determining the need for laboratory testing. During past emerging infections, public health and clinical laboratories have worked in unison for effective care of the patient and prevention of further cases. For SARS-CoV-2 to make testing available to everyone who needed to be tested has taken the collaboration of clinical and public health laboratories to provide life-saving testing services. This was most critical at the start of the COVID-19 pandemic when few tests were available. Later, in the post peak phase, public health laboratories are dependent on clinical laboratories for samples to perform sequencing needed to track emergence of variants. Building statewide laboratory networks is a key factor in emergency preparedness efforts to respond to all phases of the pandemic, as well as outbreaks and epidemics. Leadership from public health laboratories is essential to build and maintain the network. Clinical laboratories must recognize their role in the network. The ongoing collaboration of clinical and public health laboratories to form a network best serves the patients and the population.

Kelly Oakeson, PhD, Utah Public Health Laboratory
Surveillance of SARS-CoV-2 Variants.

With the COVID-19 pandemic continuing, the SARS-CoV-2 is spreading and replicating and, as expected, mutating, evolving, and adapting. These variants lead to the rise of new lineages of SARS-CoV-2 that are more transmissible, can be resistant to medical interventions, and cause more severe illness. These new lineages or variants of concern pose new challenges for public health laboratories as they race to increase the genomic sequence of SARS-CoV-2 to detect variants of concern. The Utah Public Health Laboratory has been sequencing SARS-CoV-2 since the Pandemic started and is taking on the challenges of detecting variants of concern, including the issues of developing and validating whole-genome sequencing for SARS-CoV-2.

After listening to the presentation, the audience will understand the role that public health laboratories serve in the genomic surveillance of SARS-CoV-2.

Deblina Mukherjee¹, Michael Lamacchia^1,2 and Vincent A. DeBari ^1,3, ¹St. George’s University School of Medicine, St. George’s, Grenada, ²St. Joseph’s Children’s Hospital, Paterson, NJ, and St. Joseph’s University Medical Center, Paterson, NJ, Regression of COVID-19 ICFR to CFR for the United States and Europe.

Of obvious interest in the study of an epidemic is the case fatality rate (CFR), defined as the number of deaths divided by the number of cases, expressed as a percent.  However, the actual CFR can only be computed after an epidemic has run its course and the total number of deaths and cases can be accurately ascertained.  We define a metric, the Interim Case Fatality Rate (ICFR) computed as the longitudinal CFR on a bi-weekly basis.  Herein, we examine the ICFR over the period March 1, 2020 when COVID-19 first appeared in substantial numbers to Jan 15, 2021. The purpose of this study was to ascertain whether longitudinal changes in ICFR would predict the likely ultimate CFR of COVID-19. We used open public source databases and derived ICFR from point estimates of cases and deaths for geopolitical entities in four regions each of the United States and Europe.  Early in the pandemic, calculated ICFR were plotted and frequently found to represent a variably modal pattern with peak ICFR exceeding 15% in some cases.  However, the curves were found to decrease and regress to relatively constant ICFR values.  We postulated that actual CFR could be estimated when no statistically significant differences in sequential measurements of ICFR for the final monthly (three measurements) period could be detected.  This resulted in estimates of case-weighted CFR [mean (95% confidence interval)] ranging from 1.77% (0.59 to 2.95) for the USA to 2.31% (1.85 to 2.77).  We conclude that this suggests that early estimates of the CFR may provide highly erroneous estimates but that the ICFR may regress to an estimate of the actual CFR.

Upon completion of this activity, the participant should be able to: (1) recognize the variability in the ICFR of different geopolitical entities during the Covid-19 pandemic; (2) observe the manner in which the ICFR regresses to a constant value; and (3) calculate the weighted CFR predicted by this model.

Erica Fatica, Paige Menk, Darci Block, and Nikola Baumann, Mayo Clinic, Rochester, MN, Clinical laboratory testing for macro-aspartate aminotransferase (macroAST): 8 years of experience.

Macro-aspartate aminotransferase (macroAST) is a high-molecular weight complex that consists of aspartate aminotransferase (AST) bound to immunoglobulins. The macro-complex causes elevations in measured serum AST activity. Although clinically benign, identification of macroAST is important as patients may undergo years of unnecessary diagnostic investigations before macroAST is identified. To our knowledge, we are the only reference laboratory that offers macroAST testing. The aim of this retrospective analysis was to evaluate the distribution of results obtained, % of positive samples, and patient demographics for macroAST testing during an 8-year period (2013-2021). The macroAST assay involves measuring AST activity in serum before (total) and after polyethylene glycol (PEG) precipitation (post-PEG). PEG precipitation was performed by incubating samples with 25% PEG solution at a 1:1 ratio followed by centrifugation at room temperature for 5 minutes. The percent of PEG-precipitated AST activity (%PPA) was calculated as [(total – post-PEG)/total] x 100. A %PPA of >80% is positive for macroAST based on initial validation studies using controls and gel filtration chromatography-confirmed macroAST samples. 300 macroAST tests were ordered for 291 unique patients (181F, 110M). Patient ages ranged from 1 month to 93 years old with a median of 35 years (IQR 12-56).  There were 137/300 (45.7%) positive samples, of which 105 (76.6%) were from female patients and 32 (23.4%) were from males. The median(range) of total AST results was 75(15-1196) U/L for macroAST-negative samples and 253(56-954U/L) for macroAST-positive samples. There was a bimodal distribution of %PPA results with a mean±SD %PPA of 31.3%+13.9% for population 1 (negative) and 92.2%+4.8% for population 2 (positive). The results show that almost 50% of physician-ordered macroAST tests were positive with macroAST found more frequently in female patients.

Upon completion of this activity, participants will be able to: (1) Describe the molecular composition and analytical difficulty presented by macroAST; (2) Describe patient demographics and characteristics of patients negative for macroAST; and (3) Describe patient demographics and characteristics of patients positive for macroAST.

Norah Alghamdi and Roland Valdes, Jr., University of Louisville School of Medicine, Louisville, KY, A proposed novel biomarker for post-traumatic stress disorder (PTSD).

Our work aims to test the hypothesis that subjects who suffer from Post-Traumatic Stress Disorder (PTSD) have an inherent dysregulation of the corticotropin-axis involving the neuropeptide Urocortin3 (UCN3) and its receptor Corticotropin Releasing Factor Receptor2 (CRFR2). PTSD is a condition that develops after a set of traumatic stressors. UCN3 is a corticotropin-releasing factor (CRF)-related peptide which plays a role in restoring homeostasis in response to stress via activation its receptor, CRFR2, resulting in mediating/dampening stress sensitivity. The diagnosis of PTSD is currently based on mental disorder criteria which are complex, subjective, and require human judgment. No clinical laboratory test is currently available to aid in this diagnosis, thus having a rapid and inexpensive biomarker test for PTSD would have substantial clinical impact. We hypothesize that in PTSD UCN3 secretion is deficient, causing the inability to cope with stress. Testing our hypothesis requires a high-sensitivity assay able to measure UCN3 in the sub-picogram per milliliter (pg/mL) range. This level of sensitivity is achievable using a combination of high affinity aptamers and monoclonal antibodies. Aptamers are sequenced nucleotides that bind to their targets with high affinity and specificity making them ideal diagnostic reagents. Our focus is to develop a high-sensitivity assay required to measure samples from PTSD subjects available through the Department of Veterans Affairs PTSD Biorepository Brain Bank (VABBB).

Upon completion of this activity, participants should be able to: (1) describe the PTSD condition and the limitations in current approaches to its diagnosis; (2) discuss the rationale for targeting UCN34 as a biomarker for PTSD; and (3) describe the advantages of using aptamers in developing diagnostic tests.

Devereaux Sellers^1,2, Taha Keskin^1,2, Linlin Yang^1,2, and Mahesheema Ali^1,2, ¹Department of Pathology, The MetroHealth System, Cleveland, OH, and ² Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, Stark disparities between multiplex bead-based technology vs. immunofluorescence assay.

Objective: To retrospectively examine the outcome of anti-nuclear antibody (ANA) screen by comparing the performance of BioPlex 2200 and immunofluorescence assay (IFA)

Methods: We reviewed ANA performance (Feb 2020 to Jan 2021) on BioPlex 2200 ANA using multiplex florescent beads (antigens dsDNA, chromatin, SSA 60, SSA 52, SSB, Sm, SmRNP, RNP A, RNP 68, Scl-70, Jo-1, ribosomal P, and centromere B) and immunofluorescence assay (using HEp-2)

Results: Total number of cases tested on both multiplex flow and IFA platform were 133 (111 females and 22 males). The prevalence in our population divided by age groups 18 to 44 years (36%); 45 to 64 years (42%); 65 years or older, (22%) has reported lupus. The mean age of the lupus patients at diagnosis is clustering around 53 years. Out of 133 multiplex tests performed, 58 tests were negative and 75 were positive. 47% of the tests performed with a negative result (58 tests) on multiplex flow turned to positive on IFA assay. The breakdown of titers for these tests were: 30% (1:320); 30% (1:160); 15% (1:80); and 26% (1:20). 55% of the tests performed with a positive result (75 tests) on multiplex flow turned to negative on IFA assay. The breakdown of titers for these tests were: 12% (1:1280), 18% (1:320); 6% (1:640); 15% (1:160); 15% (1:40); and 35% (1:80). Upon scrutinizing further, data shows a significant disparity in the dsDNA (27%) and RNP antibodies (51%) of the multiplex positive tests turned to negative on IFA assay.

Conclusion: Our data suggests a disparity between the results obtained from both the platforms. The common notion of IFA being a gold standard is flawed therefore manufacturer’s need to invest in optimizing assays that are less prone to errors. Clinicians should interpret the test results in clinical context that includes history, assessment of signs & symptoms.

Upon completion of this activity, the participant will be able to (1) identify the gaps between multiplex bead-based technology and immunofluorescence assay; (2) compare the performance of multiplex bead-based technology and immunofluorescence assay; and (3) recommend education on the disconnect between a patient’s symptoms versus test results.

Brenda Mai, Mesk Alrais, Amanda Tchakarov, and Nina Tatevian, University of Texas Health Science Center, Houston, TX, A case report of fetal thrombotic vasculopathy in a COVID placenta.

The aims and scope of this presentation are to highlight an interesting case report of a third trimester pregnancy with symptomatic coronavirus disease 2019 (COVID-19) complicated by fetal thrombotic vasculopathy (FTV). COVID-19 has affected patients of all ages and demographics, not excluding pregnant women. The effects of COVID-19 on pregnant women are largely still unknown. Several adverse perinatal outcomes have been reported in COVID-19-positive pregnant women including pre-eclampsia, miscarriage, pre-term labor, and stillbirth. Histopathological examination of COVID-19 placentas can contribute significant data regarding maternal and fetal health and elucidate more findings in this novel disease. A 23-year old female with morbid obesity and scant antenatal care presented to the emergency department complaining of shortness of breath and fever; she was found to be positive for COVID-19. Grossly, her placenta showed no abnormalities. Histological examination of her placenta showed chronic lymphoplasmacytic deciduitis, villous fibrosis, loss of capillarization, extravasation of erythrocytes, chorangiosis, and thrombosis of upstream stem vessels, including large fetal vessels on the chorionic plate. These changes were deemed to be consistent with FTV. FTV is a condition where blood clots cause obstruction of both arteries and veins, causing downstream occlusion, decreasing placental oxygen flow, impairing nutritional exchange, and causing ischemic changes and infarctions in the placental villi. FTV can result in serious fetal sequelae such as miscarriage/stillbirth, fetal intrauterine growth restriction, infarcted organs, neonatal stroke, neonatal encephalopathy, and cerebral palsy. Grossly, thrombosis of chorionic vessels can result in pale and firm placental parenchyma. Microscopically, organizing thrombosis, endothelial cell destruction, avascular fibrinoid necrosis, hemorrhagic endovasculitis, stromal karyorrhexis, fibromuscular sclerosis, fibrosis, and septation are frequent features. In conclusion, this case of FTV in the placenta in a patient with COVID-19 is a significant finding as this can be critical to clinicians for the management of prenatal care for expecting mothers during this pandemic.

Upon completion of this activity, participants should be able to: (1) identify the gross macroscopic findings in fetal thrombotic vasculopathy (FTV); (2) describe the histopathologic features of FTV; and (3) explain the fetal sequelae of FTV.

George G Chen, Zhongqin Gong, Lingbin Xue, Jason YK Chan, C Andrew van Hasselt, Alexander C Vlantis, Michael CF Tong.  The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, Estrogen receptor alpha-mediated autophagy promotes the survival of papillary thyroid cancer via enhancing the levels of ERK1/2 and reactive oxygen species but inhibiting NRF2.

An increasing number of publications have indicated that estrogen receptor alpha (ERa) contributes to the development and growth of papillary thyroid cancer (PTC). However, the mechanism responsible remains largely unknown. Autophagy, a catabolic process by which cells degrade their own components by targeting them for lysosomal degradation. In this study, we aimed to explore the connections between ERa and autophagy in PTC. Using human PTC tissues, cell lines and mouse tumor models, we demonstrated that ERa could induce autophagy in PTC and that the upregulation of ERK1/2 and reactive oxygen species (ROS) predated the occurrence of autophagy. We also found that the level of heme oxygenase-1 (HO-1) was increased in the ERa-mediated autophagy cells compared with the control. The inhibition of Keap1further enhanced the expression of HO-1 but limited the levels of ROS as well as the autophagy, sensitizing PTC cells to chemotherapeutic agents. On the other hand, the inhibition of NRF2 led to the downregulation of HO-1 and further increase the autophagy, resulting in the tumor cells less sensitive to the chemotherapies. In the mouse tumor model, tumors formed by PTC cells with ERa overexpression grew significantly larger, with enhanced autophagy. The application of methyl-piperidino-pyrazole (MPP), a selective ERa antagonist could markedly reduce the growth of the tumor with decreasing autophagy. Therefore, our results have confirmed that ERa-induced autophagy is a survival factor for PTC. Importantly, it appears that increase of HO-1 in ERa-induced autophagy is a compensatory or control mechanism of the tumor cells to control their growth. These data suggest that there are potential therapeutic targets to arrest the growth of PTC, including ERa, HO-1 and Keap1 and NRF2 (Supported by grants from the National Natural Science Foundation of China, No.81972493, the Research Grants Council of the Hong Kong SAR, GRF 14109716).

After completing this activity, the learner will be able to (1) appreciate how ERa contributes to growth of papillary thyroid cancer (PTC); (2) discuss the role of HO-1 as a potential target for treatment of PTC; and (3) discuss the role of NRF2 as potential target for treatment of PTC

Prasenjit Mitra, All India Institute of Medical Sciences, Jodhpur, India, Molecular aspects of Lead toxicity.

This session will mainly highlight molecular aspects of Lead toxicity. The novel molecular markers that are involved in lead toxicity will be discussed in details. The markers will be classified as genomic and epigenetic markers. Genomic markers would include the Single Nucleotide Polymorphisms (SNPs).  Epigenetic markers would include DNA methylation, Histone modification and miRNAs. The latest molecular mechanism that are being identified would be enlightened. Lead toxicity is a big problem not only in developing countries like India but reports indicate it to be a grave issue even in developed countries like United States. In developed countries, children are more affected than adults, while in developing countries, both children and adults especially the occupationally exposed individuals are at high risk of developing lead toxicity. Earlier World Health Organization recommended a Blood Lead Level (BLL) of 5 µg/dl as a safe level. But the safety levels have changed and now no lead level is considered safe. Lead in children affects nervous system and gradually leads to IQ reduction along with other manifestations. In adults, it is a potent carcinogen. Research should identify novel biomarkers that may aid in the diagnosis and identification of individual at risk on the basis of which mass screening may be done to find the magnitude of the problem.
This session will discuss various molecular markers that have been found to be associated with lead toxicity highlighting their importance to be further evaluated and validated as markers of precision medicine in this public health problem.

Upon completion of this activity, participants should be able to (1) discuss novel molecular biomarkers that may aid in the help of precision medicine in the field of Lead toxicity; (2) describe various molecular mechanisms involved in Lead toxicity; and (3) discuss the directions for conducting future research studies in this field.

Taru Goyal, Shailja Sharma, Praveen Sharma, Prasenjit Mitra, All India Institute of Medical Sciences, Jodhpur, India, Assessment of circulating mir-20b, mir-155 and mir-221 in occupationally cadmium exposed workers.

Cadmium (Cd), a well-known environmental pollutant, can induce several adverse health effects following its accumulation in the human body. Cd is also a potential carcinogen, capable of causing multi-system alterations. The molecular mechanisms by which Cd exerts systemic damage in the human body are under exploration. The present study, aimed to evaluate levels of three candidate miRNAs (miR-20b, miR-155 and miR-221) in individuals exposed to Cd.

The study enrolled 110 individuals from handicraft and welding factories of Jodhpur, who were occupationally exposed to Cd and 97 apparently healthy individuals without any history of occupational exposure. Blood levels of Cd were determined by graphite furnace atomic absorption spectroscopy (GFAAS). Circulating miRNA were isolated from serum by Qiagen isolation kit and subsequently converted to cDNA using Qiagen miRCURY LNA RT kit. miRNA expression was assessed using Qiagen miRNA PCR assay in RT-PCR. The median Cd level in the exposed individuals (2.40μg/L) was significantly higher than the non-exposed (0.90μg/L) (p<0.0001). miRNA expression analysis revealed a significant upregulation in the expression of miR-221 in the exposed group with a fold change of 3.22, while miR-20b and miR-155 did not differ significantly between the groups. The findings of our study highlight the importance of miRNA dysregulation in Cd exposed individuals that may contribute to the systemic effects of Cd toxicity. The role of miR-221 and other miRNAs as a potential biomarker of Cd toxicity needs to be further validated in diverse population groups to highlight the possible molecular pathways through which Cd exerts its toxic manifestations.

Upon completion of this activity, participants should be able to: (1) discuss the status of miRNA expression in Cd toxicity; (2) describe downstream targets of these miRNAs; and (3) discuss future directions for further research studies in the field of epigenetics of Cd toxicity.

Toward Improved Outcomes in Hematologic Malignancies: Three Approaches of Precision Medicine

The Journey to Replace Immunofixation with Mass Spectrometry for Plasma Cell Disorders

Comprehensive Identification of Structural Variants, the Dark Matter of Cancer Genomics

Clinical Laboratory Testing for Macro-Aspartate Aminotransferase: 8 Years of Experience

A Proposed Novel Biomarker for Post-Traumatic Stress Disorder (PTSD)

A Case Report of Fetal Thrombotic Vasculopathy in a COVID Placenta

Stark Disparities between Multiplex Bead-based Technology vs Immunofluorescence Assay

Assessment of circulating mir-20b, mir-155 and mir-221 in occupationally cadmium exposed workers

International Efforts in Combatting COVID19: Behind the scenes of how to develop a COVID-19 vaccine

The Collaboration of Clinical and Public Health Laboratories to Provide Testing Services

Opening Remarks, Keri J. Donaldson, MD, MSCE, FACOP, President, Association of Clinical Scientists

Epidemic and Pandemics Through the Centuries: A Historical Perspective. .M. John Hicks, MD, DDS, PhD, Baylor College of Medicine\

Development of Molecular Testing for SARS-CoV-2: Challenges with Implementation during a Pandemic. James J. Dunn, PhD, D(ABMM), Texas Children’s Hospital

Saliva Testing for SARS-CoV-2: A Game Changer and the Challenges That Come With It. Salika M. Shakir, PhD, D(ABMM), ARUP Laboratories and University of Utah School of Medicine.

Serologic Testing for SARS-CoV-2: Much Ado About…Antibodies?, Elitza S. Theel, PhD, D(ABMM), Mayo Clinic

Epidemics and Pandemics Through the Centuries: A Historical Perspective
M. John Hicks, MD, DDS, MS. PhD, Baylor College of Medicine, Houston, TX

Development of Molecular Testing for SARS-CoV-2: Challenges with Implementation during a Pandemic
Jim Dunn, PhD, D(ABMM), Texas Children’s Hospital, Houston, TX

Saliva Testing for SARS-CoV-2: A Game Changer and the Challenges That Come With It.
Salika M. Shakir, PhD, D(ABMM), ARUP Laboratories and University of Utah School of Medicine, Salt Lake City, UT

SARS-CoV-2 Serologic Testing: Much Ado About…Antibodies?
Elitza S. Theel, PhD, D(ABMM), Mayo Clinic, Rochester, MN

The Association of Clinical Scientists sincerely expresses its gratitude to the following corporations for their support of the Association’s first ever virtual symposium. Clicking on each corporate logo will take the viewer to specific advertisements provided by the company for this event or to the company's website.

Epidemics & Pandemics Through the Centuries: A Historical Perspective:

Development of Molecular Testing for SARS-CoV-2: Challenges with Implementation During a Pandemic:

Saliva Testing for SARS-CoV-2: A Game Changer and the Challenges That Comes With It:

Serologic Testing for SARS-CoV-2: Much Ado About Antibodies: