SARS-CoV-2 and Variant Diagnostic Testing Approaches in the United States

Purpose of Review Given the rapid development of diagnostic approaches to test for and diagnose infection with SARS-CoV-2 and its associated variants including Omicron (B.1.1.529), many options are available to diagnose infection. Multiple established diagnostic companies are now providing testing platforms whereas initially, testing was being performed with simple PCR-based tests using standard laboratory reagents. Recent Findings Additional testing platforms continue to be developed, including those to detect specific variants, but challenges with testing, including obtaining testing reagents and other related supplies, are frequently encountered. With time, the testing supply chain has improved, and more established companies are providing materials to support these testing efforts. In the United States (U.S.), the need for rapid assay development and subsequent approval through the attainment of emergency use authorization (EUA) has superseded the traditional arduous diagnostic testing approval workflow mandated by the FDA. Through these efforts, the U.S. has been able to continue to significantly increase its testing capabilities to address this pandemic; however, challenges still remain due to the diversity of the performance characteristics of tests being utilized and newly discovered viral variants. Summary This review provides an overview of the current diagnostic testing landscape, with pertinent information related to SARS-CoV-2 virology, variants and antibody responses that are available to diagnose infection in the U.S.

Exploring the Mystery of the Sweetness of Baijiu by Sensory Evaluation, Compositional Analysis and Multivariate Data Analysis

Sweetness is an important Baijiu quality marker, but there is limited research on it. In this study, the main contributors to Baijiu sweetness were identified by “sensomics” combined with “flavoromics”. A total of 43 volatile compounds (mostly esters) were found that appeared to contribute to Baijiu sweetness, through sensory-guided fractionation and compositional analysis. Correlation analysis between the volatile composition and perceived sweetness of 18 Baijiu samples with different sweet intensities identified 14 potential contributors. Additional testing verified that combining the 14 compounds reproduced Baijiu sweetness exactly, and omission testing identified ethyl hexanoate, hexyl hexanoate and ethyl 3-methylbutanoate as the major contributors to Baijiu sweetness. These findings not only broadened our understanding of Baijiu sweetness, but also highlighted the major contribution of volatile compounds to sweetness perception, knowledge which may facilitate future flavor modification of a wide variety of foods and beverages.

Research of Vibrations of an Armoured Personnel Carrier Hull with FE Implementation

Modern wheeled armoured vehicles can perform a variety of tasks, making the development of weapon systems that can be safely and effectively integrated with the vehicle structure an area of interest. Due to the cost of implementing new models, it is more economical to test potential configurations using numerical methods, such as the finite element method. The numerical model has been validated to confirm the reliability of the obtained results. Modal tests were also performed using four configurations to identify the frequency and mode shape of natural vibrations occurring within the support structure. In an experimental setting, hull vibrations were forced using the modal hammer testing method. The modal assurance criterion (MAC) and the authors’ procedure were used to confirm the experimental and numerical test results. Additional testing in the form of impact loads was carried out for turret-containing structures. Structural strain at indicated points and forces transmitted by brackets to the bottom of the hull were compared.

Diagnostic Testing for SARS-CoV-2 Infection

Purpose of Review Given the rapid development of diagnostic approaches to test for and diagnose infection with SARS-CoV-2, many options are available to assess infection. Multiple established diagnostic companies are now providing testing platforms whereas initially, testing was being performed with simple PCR-based tests using standard laboratory reagents. Recent Findings. Additional testing platforms continue to be developed but challenges with testing, including obtaining testing reagents and other related supplies, are frequently encountered. With time, the testing supply chain will improve and more companies will be providing materials to support these testing efforts. In the USA, the need for rapid assay development and subsequent approval through attainment of emergency use authorization (EUA) has superseded the traditional arduous diagnostic testing approval workflow mandated by the FDA. It is anticipated that the USA will be able to continue to significantly increase its testing capabilities to address this pandemic; however, challenges remain due to the diversity of the performance characteristics of tests being utilized. Summary This review provides an overview of the current diagnostic testing landscape, with pertinent information related to SARS-CoV-2 virology and antibody responses, that is available to diagnose infection.

Experimental Investigation of the Wear Behaviour of Coated Polymer Gears

A comprehensive experimental investigation of the wear behaviour of coated spur polymer gears made of POM is performed in this study. The three physical vapour deposition (PVD) coatings investigated were aluminium (Al), chromium (Cr), and chromium nitrite (CrN). Al was deposited in three process steps: By plasma activation, metallisation of Al by the magnetron sputtering process, and by plasma polymerisation. Cr deposition was performed in only one step, namely, the metallization of Cr by the magnetron sputtering process. The deposition of CrN was carried out in two steps: the first involved the metallization of Cr by the magnetron sputtering process while the second step, vapour deposition, involved the reactive metallisation of Cr with nitrogen, also by the magnetron sputtering process. The gears were tested on an in-house developed testing rig for different torques (16, 20, 24 and 30 Nm) and rotational speed of 1000 rpm. The duration of the experiments was set to 13 h, when the tooth thickness, and, consequently, the wear of the tooth flank was recorded. The experimental results showed that the influence of metallisation with aluminium, chromium, and chromium nitrite surface coatings on the wear behaviour of the analysed polymer gear is not significant. This is probably due to the fact that the analysed coatings were, in all cases, very thin (less than 500 nm), and therefore did not influence the wear resistance significantly. In that respect, an additional testing using thicker coatings should be applied in the further research work.

Application of Polymerase Chain Reaction in Diphtheria Laboratory Examination: A Field Need

Background: Indonesia is one of the five countries with the highest number of diphtheria cases worldwide. Diphtheria is caused by the toxigenic strains Corynebacterium diphtheriae, C. ulcerans, and C. pseudotuberculosis. The diphtheria-causing bacteria can be identified using conventional and molecular methods, including polymerase chain reaction (PCR) assay. We used the PCR assay as additional testing, because in island countries like Indonesia, specimen transport is a serious challenge to maintaining bacterial survival. Objectives: This study aimed to evaluate the PCR assay as additional testing to identify diphtheria-causing bacteria in the diphtheria laboratory. Methods: In this cross-sectional study, a total of 178 pairs of the throat and nasal swabs from diphtheria suspected cases and close contacts were collected from seven provinces in Indonesia in 2016. All samples were directly identified by the conventional method and multiplex PCR assay. Statistical analysis was conducted using the 2 × 2 tables to determine the sensitivity and specificity of both methods, while the χ2 test was used to examine the correlation between specimen examination delay and the differentiation of results. A P-value < 0.05 was considered as statistically significant. Results: Out of 178 examined samples, eight samples were identified as diphtheria-positive by both the conventional method and PCR assay, while nine samples were only detected by the PCR assay. All diphtheria-causing bacteria found in the positive samples were toxigenic C. diphtheriae. The diphtheria-causing bacteria were found in 27.6% of cases and 6.0% of close contacts using the PCR assay versus 13.8% of cases and 2.7% of close contacts using the conventional method. Statistical analysis showed that the PCR assay is about twice more sensitive than the conventional method. There was a significant correlation between the differentiation of results and > 72 hours’ specimen examination delay with a P-value of 0.04 (< 0.05). Conclusions: The PCR assay is more sensitive than the conventional method to identify diphtheria-causing bacteria and may be applied as additional testing to increase the positivity rate of diphtheria-confirmed cases in Indonesia as an archipelago country where geographical factors and specimen transport are real obstacles.

Exploring Intuitive Approaches to Protein Conformation Clustering Using Regions of High Structural Variance

This paper presents a method to find structurally high variance segments of the different conformations of a single protein and uses clusters them using different distance metrics and interpretation of coordinate and angle data presented by three different methods: root mean squared derivation RMSD, t-distributed Stochastic Neighbor Embedding (t-SNE) based map, and dihedral-based clustering. The methods were applied on the human cylin-dependent kinase 2 (CDK2) protein, code P24941 uniprot using a series of python scripts and clustering packages. We test our methods on the data of the CDK2 protein as it is a highly researched protein, with practical applications of clustering in cancer research, crucial in the regulation of the cell-cycle, and has a sizeable amount of experimental data collected on the confirmation structures. While using the distance based root mean squared deviation RMSD provides data of structure to structure dissimilarity between different conformations, a simple RMSD matrix lacks to ability to describe the subsequence-wise in shape and absolute position which could be the main identifying elements for a protein's conformation and state. To make up for this loss we explore an intuitive and more flexible method, able to accept multiple high structural variance segments, which takes coordinate based data, through a series of maps and with the help of t-SNE, and maps each segment as a feature in the clustering matrix. This method, however, would require additional testing on other proteins and modifications to verify its consistency and test its robustness. In the end we explore the pros and cons of the three methods applied on the high structural variance regions. Despite the randomness factor by the t-SNE used in mapping the coordinates to lower dimensions, the coordinate-based approach consistently performed better than the RSMD and dihedral based methods in clustering the three groups of the CDK2 protein kinase. We also found that analyzing only the substructures identified by the high variance detection algorithm consistently provided more distinct clusters with higher multi-class F1 scores.

Large renal leiomyoma: A multidisciplinary approach to diagnosis

We report the case of a 45-year-old woman who presented with a large palpable abdominal mass. Initial sonographic and computed tomographic studies prompted a differential diagnosis of retroperitoneal or renal sarcoma, leiomyoma, and lipid-poor angiomyolipoma. A final diagnosis of renal leiomyoma was reached based on a consensus among radiology, surgery and pathology. In addition to reviewing the features of this entity, this case demonstrates the process of developing a working diagnosis, narrowing the differential as additional testing is performed and establishing a final diagnosis with interdepartmental coordination. Despite the rarity of this condition, the ability to recognize and apply imaging features to differentiate between abdominal masses of unknown origin is important for clinicians and researchers.

Discrepancy between PCR based SARS-CoV-2 tests suggests the need to re-evaluate diagnostic assays

Objective We investigated the discrepancy between clinical and PCR-based diagnosis of COVID-19. We compared results of ten patients with mild to severe COVID-19. Respiratory samples from all cases were tested on the Roche SARS-CoV-2 (Cobas) assay, Filmarray RP2.1 (bioMereiux) and TaqPath™ COVID19 (Thermofisher) PCR assays. Results Laboratory records of ten patients with mild to severe COVID-19 were examined. Initially, respiratory samples from the patients were tested as negative on the SARS-CoV-2 Roche® assay. Further investigation using the BIOFIRE® Filmarray RP2.1 assay identified SARS-CoV-2 as the pathogen in all ten cases. To investigate possible discrepancies between PCR assays, additional testing was conducted using the TaqPath™ COVID19 PCR. Eight of ten samples were positive for SARS-CoV-2 on the TaqPath assay. Further, Spike gene target failures (SGTF) were identified in three of these eight cases. Discrepancy between the three PCR assays could be due to variation in PCR efficiencies of the amplification reactions or, variation at primer binding sites. Strains with SGTF indicate the presence of new SARS-CoV-2 variant strains. Regular modification of gene targets in diagnostic assays may be necessary to maintain robustness and accuracy of SARS-CoV-2 diagnostic assays to avoid reduced case detection, under-surveillance, and missed opportunities for control.

Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association

Background Recently there has been increased interest in a possible association between mast cell activation (MCA) disorder and postural orthostatic tachycardia syndrome (POTS). This study examined the frequency with which symptoms and laboratory findings suggesting MCA disorder occurred in patients diagnosed with POTS. Methods and Results Data were obtained from patients in whom symptoms and orthostatic testing were consistent with a POTS diagnosis. Individuals with <4 months symptom duration, evident ongoing inflammatory disease, suspected volume depletion, or declined consent were excluded. All patients had typical POTS symptoms; some, however, had additional nonorthostatic complaints not usually associated with POTS. The latter patients underwent additional testing for known MCA biochemical mediators including prostaglandins, histamine, methylhistamine, and plasma tryptase. The study comprised 69 patients who met POTS diagnostic criteria. In 44 patients (44/69, 64%) additional nonorthostatic symptoms included migraine, allergic complaints, skin rash, or gastrointestinal symptoms. Of these 44 patients, 29 (66%) exhibited at least 1 laboratory abnormality suggesting MCA disorder, and 11/29 patients had 2 or more such abnormalities. Elevated prostaglandins (n=16) or plasma histamine markers (n=23) were the most frequent findings. Thus, 42% (29/69) of patients initially diagnosed with POTS exhibited both additional symptoms and at least 1 elevated biochemical marker suggesting MCA disorder. Conclusions Laboratory findings suggesting MCA disorder were relatively common in patients diagnosed with POTS and who present with additional nonorthostatic gastrointestinal, cutaneous, and allergic symptoms. While solitary abnormal laboratory findings are not definitive, they favor MCA disorder being considered in such cases.