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Trigger finger (TF), a painful condition involving a finger flexor tendon, is a common problem with a prevalence of ~2-3% in the general population. However, the TF prevalence is higher among diabetic patients-ranges from 6.7% to 10%. We have analyzed the expression of the extracellular matrix, inflammation, and epigenetic related genes in diabetic and non-diabetes TF. We hypothesized that Diabetes condition induces alter the expression of epigenetic modification genes in diabetic patients and one of the underlying determinants for more prevalence of TF in diabetic patients.

Osteoarthritis (OA) is a chronic degenerative joint disease. The pathogenesis is poorly understood. What is known is that OA is characterized by imbalance in anabolic and catabolic gene expression in articular chondrocytes. This results in bone on bone articulations resulting in impaired mobility and joint pain. Although the cause of OA is unknown, comorbidities include: aging, obesity, and mechanical stress. Currently the only diagnostic modalities are radiology and physical examination, and early detection is rare. Biomarkers are quantifiable substances, and their presence can be suggestive of a certain phenomenon or disease. Biomarkers are popular for early diagnosis for pathological conditions in the fields of oncology, cardiology, and endocrinology. This review has systematically reviewed the literature about biomarkers in the field of OA, specifically protein, miRNA, and metabolic biomarkers found in the blood, urine, and synovial fluid.

For monitoring the activity of Japanese encephalitis (JE) in pigs, no effective assay is available in Indian context. Being its endemicity in India and role of pigs as amplifiers, there was need to develop rapid and sensitive assay for serosurveillance of JE in pigs. An Indirect ELISA (I-ELISA) was standardized using ultracentrifuge sucrose density gradient purified JE antigen from standard virus strain. Cross reaction studies were done with West Nile antigen and comparative efficacy of IELISA assessed with Virus Neutralization Test (VNT). Optimum results recorded for detection of IgG and IgM, respectively, at 50 ng/well antigen and 1:200 and 1:300 serum dilutions. The positive - to - negative ratio of ≥2 considered positive for JE antibodies. The overall prevalence of JE in pigs recorded to be 28.89 %. The concordance of the indirect ELISA (IgG) vis-à- vis VNT revealed good agreement (kappa = 0.66) and moderate agreement (kappa = 0.56) of standardized I- ELISA towards detection of IgG and IgM, respectively. The assay standardized in the present study could be useful for JE serosurveillance in pig population from endemic and non endemic areas in India. [ABSTRACT FROM AUTHOR]

The article explores the isolation and genotypic characterization of rotavirus from stool samples of children who suffered acute gastroenteritis. The cytopathiceffects observed in the virus after three passages were mentioned. The virus' double-stranded ribonucleic acid (dsRNA) has 11 banded pattern. It also compares the sensitivity of sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE) and reverse transcription polymerase chain reaction (RT-PCR) in the detection of the virus.

Prenatal diagnostic testing of amniotic fluid, chorionic villi, or more rarely, fetal cord blood is recommended following a positive or unreportable noninvasive cell-free fetal DNA test, abnormal maternal biochemical serum screen, abnormal ultrasound, or increased genetic risk for a cytogenomic abnormality based on family history. Although chromosomal microarray is recommended as the first-tier prenatal diagnostic test, in practice, multiple assays are often assessed in concert to achieve a final diagnostic result. The use of multiple methodologies is costly, time consuming, and labor intensive. Optical genome mapping (OGM) is an emerging technique with application for prenatal diagnosis because of its ability to detect and resolve, in a single assay, all classes of pathogenic cytogenomic aberrations. In an effort to characterize the potential of OGM as a novel alternative to traditional standard of care (SOC) testing of prenatal samples, OGM was performed on a total of 200 samples representing 123 unique cases, which were previously tested with SOC methods (92/123 = 74.7% cases tested with at least two SOCs). OGM demonstrated an overall accuracy of 99.6% when compared with SOC methods, a positive predictive value of 100%, and 100% reproducibility between sites, operators, and instruments. The standardized workflow, cost-effectiveness, and high-resolution cytogenomic analysis demonstrate the potential of OGM to serve as a first-tier test for prenatal diagnosis., Competing Interests: Disclosure Statement R.E.S. is a consultant of Bionano; R.K. has received honoraria and/or travel funding and/or research support from Illumina, Bionano, Agena, and PGDx. F.B. was an employee of Quest Diagnostics at the time of this work., (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Multidrug-resistant HIV strains challenge treatment efficacy and increase mortality rates. Next-generation sequencing (NGS) technology swiftly detects variants, facilitating personalized antiretroviral therapy., Aim: This study aimed to validate the Vela Diagnostics NGS platform for HIV drug resistance mutation analysis, rigorously assessed with clinical samples and CAP proficiency testing controls previously analyzed by Sanger sequencing., Method: The experimental approach involved the following: RNA extraction from clinical specimens, reverse transcription polymerase chain reaction (RT-PCR) utilizing the Sentosa SX 101 platform, library preparation with the Sentosa SQ HIV Genotyping Assay, template preparation, sequencing using the Sentosa SQ301 instrument, and subsequent data analysis employing the Sentosa SQ Suite and SQ Reporter software. Drug resistance profiles were interpreted using the Stanford HIV Drug Resistance Database (HIVdb) with the HXB2 reference sequence., Results: The Vela NGS system successfully identified a comprehensive array of drug resistance mutations across the tested samples: 28 nucleoside reverse transcriptase inhibitors (NRTI), 25 non-nucleoside reverse transcriptase inhibitors (NNRTI), 25 protease inhibitors (PI), and 10 integrase gene-specific variants. Dilution experiments further validated the system's sensitivity, detecting drug resistance mutations even at viral loads lower than the recommended threshold (1000 copies/mL) set by Vela Diagnostics., Scope: This study underscores the validation and clinical applicability of the Vela NGS system, and its implementation may offer clinicians enhanced precision in therapeutic decision-making for individuals living with HIV.

Objectives: To describe mismatch repair (MMR) and microsatellite instability (MSI) testing practices in laboratories using the College of American Pathologists (CAP) MSI/MMR proficiency testing programs prior to the 2022 publication of the MSI/MMR practice guidelines copublished by CAP and the Association of Molecular Pathology (AMP)., Methods: Data from supplemental questionnaires provided with the 2020-B MSI/MMR programs to 542 laboratories across different practice settings were reviewed. Questionnaires contained 21 questions regarding the type of testing performed, specimen/tumor types used for testing, and clinical practices for checkpoint blockade therapy., Results: Domestic laboratories test for MSI/MMR more often than international laboratories (P = .04) and academic hospitals/medical centers test more frequently than nonhospital sites/clinics (P = .03). The most commonly used testing modality is immunohistochemistry, followed by polymerase chain reaction, then next-generation sequencing. Most laboratories (72.6%; 347/478) reported awareness of the use of immune checkpoint inhibitor therapy for patients with high MSI or MMR-deficient results., Conclusions: The results demonstrate the state of MMR and MSI testing in laboratories prior to the publication of the CAP/AMP best practice guidelines, highlighting differences between various laboratory types. The findings indicate the importance of consensus guidelines and provide a baseline for comparison after their implementation., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

A glioma is a solid brain tumor which originates in the brain or brain stem area. The diagnosis of gliomas based on standard-of-care (SOC) techniques includes karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA), for detecting the pathogenic variants and chromosomal abnormalities. But these techniques do not reveal the complete picture of genetic complexity, thus requiring an alternative technology for better characterization of these tumors. The present study aimed to evaluate the clinical performance and feasibility of using optical genome mapping (OGM) for chromosomal characterization of gliomas. Herein, we evaluated 10 cases of gliomas that were previously characterized by CMA. OGM analysis showed concordance with the results of CMA in identifying the characterized Structural Variants (SVs) in these cases. More notably, it also revealed additional clinically relevant aberrations, demonstrating a higher resolution and sensitivity. These clinically relevant SVs included cryptic translocation, and SVs which are beyond the detection capabilities of CMA. Our analysis highlights the unique capability of OGM to detect all classes of SVs within a single assay, thereby unveiling clinically significant data with a shorter turnaround time. Adopting this diagnostic tool as a standard of care for solid tumors like gliomas shows potential for improving therapeutic management, potentially leading to more personalized and timely interventions for patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), induced a global pandemic with a diverse array of clinical manifestations. While the acute phase of the pandemic may be waning, the intricacies of COVID-19's impact on neurological health remain a crucial area of investigation. Early recognition of the spectrum of COVID-19 symptoms, ranging from mild fever and cough to life-threatening respiratory distress and multi-organ failure, underscored the significance of neurological complications, including anosmia, seizures, stroke, disorientation, encephalopathy, and paralysis. Notably, patients requiring intensive care unit (ICU) admission due to neurological challenges or due to them exhibiting neurological abnormalities in the ICU have shown increased mortality rates. COVID-19 can lead to a range of neurological complications such as anosmia, stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, seizures, etc., in affected patients. This review elucidates the burgeoning landscape of neurological sequelae associated with SARS-CoV-2 infection and explores the underlying neurobiological mechanisms driving these diverse manifestations. A meticulous examination of potential neuroinvasion routes by SARS-CoV-2 underscores the intricate interplay between the virus and the nervous system. Moreover, we dissect the diverse neurological manifestations emphasizing the necessity of a multifaceted approach to understanding the disease's neurological footprint. In addition to elucidating the pathophysiological underpinnings, this review surveys current therapeutic modalities and delineates prospective avenues for neuro-COVID research. By integrating epidemiological, clinical, and diagnostic parameters, we endeavor to foster a comprehensive analysis of the nexus between COVID-19 and neurological health, thereby laying the groundwork for targeted therapeutic interventions and long-term management strategies.

This study investigates COVID-19 outcomes and immune response in chronic myeloid leukemia (CML) patients post-SARS-CoV-2 vaccination, comparing effectiveness of various vaccine options. Data from 118 CML patients (85 in Brazil, 33 in the US) showed similar infection rates prior (14% Brazil, 9.1% US) and post-vaccination (24.7% vs. 27.3%, respectively). In Brazil, AstraZeneca and CoronaVac were the most commonly used vaccine brands, while in the US, Moderna and Pfizer-BioNTech vaccines dominated. Despite lower seroconversion in the Brazilian cohort, all five vaccine brands analyzed prevented severe COVID-19. Patients who received mRNA and recombinant viral vector vaccines (HR: 2.20; 95%CI 1.07-4.51; p  < .031) and those that had achieved at least major molecular response (HR: 1.51; 95% CI 1.01-3.31; p  < .0001) showed higher seroconversion rates. Our findings suggest that CML patients can generate antibody responses regardless of the vaccine brand, thereby mitigating severe COVID-19. This effect is more pronounced in patients with well-controlled disease.

The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as one of the most significant global health crises in recent history. The clinical characteristics of COVID-19 patients have revealed the possibility of immune activity changes contributing to disease severity. Nevertheless, limited information is available regarding the immune response in human lung tissue, which is the primary site of infection. In this study, we conducted an extensive analysis of lung tissue to screen for differentially expressed miRNAs and mRNAs in five individuals who died due to COVID-19 and underwent a rapid autopsy, as well as seven control individuals who died of other causes unrelated to COVID-19. To analyze the host response gene expression, miRNA microarray and Nanostring's nCounter XT gene expression assay were performed. Our study identified 37 downregulated and 77 upregulated miRNAs in COVID-19 lung biopsy samples compared to the controls. A total of 653 mRNA transcripts were differentially expressed between the two sample types, with most transcripts (472) being downregulated in COVID-19-positive specimens. Hierarchical and PCA K-means clustering analysis showed distinct clustering between COVID-19 and control samples. Enrichment and network analyses revealed differentially expressed genes important for innate immunity and inflammatory response in COVID-19 lung biopsies. The interferon-signaling pathway was highly upregulated in COVID-19 specimens while genes involved in interleukin-17 signaling were downregulated. These findings shed light on the mechanisms of host cellular responses to COVID-19 infection in lung tissues and could help identify new targets for the prevention and treatment of COVID-19 infection.

Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is crucial in maintaining the skeletal system. Our study focuses on encapsulating the role of AhR in bone biology and identifying novel signaling pathways in musculoskeletal pathologies using the GEO dataset. The GEO2R analysis identified 8 genes (CYP1C1, SULT6B1, CYB5A, EDN1, CXCR4B, CTGFA, TIPARP, and CXXC5A) involved in the AhR pathway, which play a pivotal role in bone remodeling. The AhR knockout in hematopoietic stem cells showed alteration in several novel bone-related transcriptomes (eg, Defb14, ZNF 51, and Chrm5). Gene Ontology Enrichment Analysis demonstrated 54 different biological processes associated with bone homeostasis. Mainly, these processes include bone morphogenesis, bone development, bone trabeculae formation, bone resorption, bone maturation, bone mineralization, and bone marrow development. Employing Functional Annotation and Clustering through DAVID, we further uncovered the involvement of the xenobiotic metabolic process, p450 pathway, oxidation-reduction, and nitric oxide biosynthesis process in the AhR signaling pathway. The conflicting evidence of current research of AhR signaling on bone (positive and negative effects) homeostasis may be due to variations in ligand binding affinity, binding sites, half-life, chemical structure, and other unknown factors. In summary, our study provides a comprehensive understanding of the underlying mechanisms of the AhR pathway in bone biology., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Traumatic brain injury (TBI) is one of the foremost causes of disability and mortality globally. While the scientific and medical emphasis is to save lives and avoid disability during acute period of injury, a severe health problem can manifest years after injury. For instance, TBI increases the risk of cognitive impairment in the elderly. Remote TBI history was reported to be a cause of the accelerated clinical trajectory of Alzheimer's disease-related dementia (ADRD) resulting in earlier onset of cognitive impairment and increased AD-associated pathological markers like greater amyloid deposition and cortical thinning. It is not well understood whether a single TBI event may increase the risk of dementia. Moreover, the cellular signaling pathways remain elusive for the chronic effects of TBI on cognition. We have hypothesized that a single TBI induces sustained neuroinflammation and disrupts cellular communication in a way that results later in ADRD pathology. To test this, we induced TBI in young adult CD1 mice and assessed the behavioral outcomes after 11 months followed by pathological, histological, transcriptomic, and MRI assessment. On MRI scans, these mice showed significant loss of tissue, reduced CBF, and higher white matter injury compared to sham mice. We found these brains showed progressive atrophy, markers of ADRD, sustained astrogliosis, loss of neuronal plasticity, and growth factors even after 1-year post-TBI. Because of progressive neurodegeneration, these mice had motor deficits, showed cognitive impairments, and wandered randomly in open field. We, therefore, conclude that progressive pathology after adulthood TBI leads to neurodegenerative conditions such as ADRD and impairs neuronal functions., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Optical Genome Mapping (OGM) is rapidly emerging as an exciting cytogenomic technology both for research and clinical purposes. In the last 2 years alone, multiple studies have demonstrated that OGM not only matches the diagnostic scope of conventional standard of care cytogenomic clinical testing but it also adds significant new information in certain cases. Since OGM consolidates the diagnostic benefits of multiple costly and laborious tests (e.g., karyotyping, fluorescence in situ hybridization, and chromosomal microarrays) in a single cost-effective assay, many clinical laboratories have started to consider utilizing OGM. In 2021, an international working group of early adopters of OGM who are experienced with routine clinical cytogenomic testing in patients with hematological neoplasms formed a consortium (International Consortium for OGM in Hematologic Malignancies, henceforth "the Consortium") to create a consensus framework for implementation of OGM in a clinical setting. The focus of the Consortium is to provide guidance for laboratories implementing OGM in three specific areas: validation, quality control and analysis and interpretation of variants. Since OGM is a complex technology with many variables, we felt that by consolidating our collective experience, we could provide a practical and useful tool for uniform implementation of OGM in hematologic malignancies with the ultimate goal of achieving globally accepted standards., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Copy number alterations (CNAs) are significant in tumor initiation and progression. Identifying these aberrations is crucial for targeted therapies and personalized cancer diagnostics. Next-generation sequencing (NGS) methods present advantages in scalability and cost-effectiveness, surpassing limitations associated with reference assemblies and probe capacities in traditional laboratory approaches. This retrospective study evaluated CNAs in 50 FFPE tumor samples (breast cancer, ovarian carcinoma, pancreatic cancer, melanoma, and prostate carcinoma) using Illumina's TruSight Oncology 500 (TSO500) and the Affymetrix Oncoscan Molecular Inversion Probe (OS-MIP) (ThermoFisher Scientific, Waltham, MA, USA). NGS analysis with the NxClinical 6.2 software demonstrated a high sensitivity and specificity (100%) for CNA detection, with a complete concordance rate as compared to the OS-MIP. All 54 known CNAs were identified by NGS, with gains being the most prevalent (63%). Notable CNAs were observed in MYC (18%), TP53 (12%), BRAF (8%), PIK3CA , EGFR , and FGFR1 (6%) genes. The diagnostic parameters exhibited high accuracy, including a positive predictive value, negative predictive value, and overall diagnostic accuracy. This study underscores NxClinical as a reliable software for identifying clinically relevant gene alterations using NGS TSO500, offering valuable insights for personalized cancer treatment strategies based on CNA analysis.

Optical genome mapping is a high-resolution technology that can detect all types of structural variations in the genome. This second phase of a multisite study compares the performance of optical genome mapping and current standard-of-care methods for diagnostic testing of individuals with constitutional disorders, including neurodevelopmental impairments and congenital anomalies. Among the 627 analyses in phase 2, 405 were of retrospective samples supplied by five diagnostic centers in the United States and 94 were prospective samples collected over 18 months by two diagnostic centers (June 2021 to October 2022). Additional samples represented a family cohort to determine inheritance (n = 119) and controls (n = 9). Full concordance of results between optical genome mapping and one or more standard-of-care diagnostic tests was 98.6% (618/627), with partial concordance in an additional 1.1% (7/627)., Competing Interests: Disclosure Statement R.S. is a consultant of Bionano Genomics. R.K. has received honoraria and/or travel funding and/or research support from Illumina, Bionano Genomics, Agena, and PGDx., (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Aging is a major risk factor for multiple chronic disorders in the elderly population, including Alzheimer's disease (AD) and Osteoporosis. AD is a progressive neurodegenerative disease characterized by memory loss. In addition to dementia, several studies have shown that AD patients experience an increased rate of musculoskeletal co-morbidities, such as osteoporosis. Since tissue-specific macrophages contribute to both diseases, this study analyzed the microglia transcriptome of AD mice to determine a common gene signature involved in osteoclast biology. After comparing differentially regulated genes from GEO data sets (GSE93824 and GSE212277), there were 35 common upregulated genes and 89 common downregulated genes. Of these common genes, seven genes are known to play an important role in bone homeostasis. CSF1, SPP1, FAM20C, and Cst7 were upregulated and are associated with osteoclastogenesis and inflammation. Among the downregulated genes, LILRA6, MMP9, and COL18A1 are involved in bone formation and osteoclast regulation. We further validated some of these genes (CSF1, Cst7, and SPP1) in the cortex and the bone of AD mice models. The dysregulation of these microglial genes in AD might provide insights into the co-occurrence of AD and osteoporosis and offer potential therapeutic targets to combat disease progression., Competing Interests: Declaration of competing interest The authors also declare that there is no other conflict of interest regarding the publication of this manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Colorectal cancer (CRC) is one of the most heterogeneous and deadly diseases, with a global incidence of 1.5 million cases per year. Genomics has revolutionized the clinical management of CRC by enabling comprehensive molecular profiling of cancer. However, a deeper understanding of the molecular factors is needed to identify new prognostic and predictive markers that can assist in designing more effective therapeutic regimens for the improved management of CRC. Recent breakthroughs in single-cell analysis have identified new cell subtypes that play a critical role in tumor progression and could serve as potential therapeutic targets. Spatial analysis of the transcriptome and proteome holds the key to unlocking pathogenic cellular interactions, while liquid biopsy profiling of molecular variables from serum holds great potential for monitoring therapy resistance. Furthermore, gene expression signatures from various pathways have emerged as promising prognostic indicators in colorectal cancer and have the potential to enhance the development of equitable medicine. The advancement of these technologies for identifying new markers, particularly in the domain of predictive and personalized medicine, has the potential to improve the management of patients with CRC. Further investigations utilizing similar methods could uncover molecular subtypes specific to emerging therapies, potentially strengthening the development of personalized medicine for CRC patients.

Structural variations (SVs) play a key role in the pathogenicity of hematological malignancies. Standard-of-care (SOC) methods such as karyotyping and fluorescence in situ hybridization (FISH), which have been employed globally for the past three decades, have significant limitations in terms of resolution and the number of recurrent aberrations that can be simultaneously assessed, respectively. Next-generation sequencing (NGS)-based technologies are now widely used to detect clinically significant sequence variants but are limited in their ability to accurately detect SVs. Optical genome mapping (OGM) is an emerging technology enabling the genome-wide detection of all classes of SVs at a significantly higher resolution than karyotyping and FISH. OGM requires neither cultured cells nor amplification of DNA, addressing the limitations of culture and amplification biases. This study reports the clinical validation of OGM as a laboratory-developed test (LDT) according to stringent regulatory (CAP/CLIA) guidelines for genome-wide SV detection in different hematological malignancies. In total, 60 cases with hematological malignancies (of various subtypes), 18 controls, and 2 cancer cell lines were used for this study. Ultra-high-molecular-weight DNA was extracted from the samples, fluorescently labeled, and run on the Bionano Saphyr system. A total of 215 datasets, Inc.luding replicates, were generated, and analyzed successfully. Sample data were then analyzed using either disease-specific or pan-cancer-specific BED files to prioritize calls that are known to be diagnostically or prognostically relevant. Sensitivity, specificity, and reproducibility were 100%, 100%, and 96%, respectively. Following the validation, 14 cases and 10 controls were run and analyzed using OGM at three outside laboratories showing reproducibility of 96.4%. OGM found more clinically relevant SVs compared to SOC testing due to its ability to detect all classes of SVs at higher resolution. The results of this validation study demonstrate the superiority of OGM over traditional SOC methods for the detection of SVs for the accurate diagnosis of various hematological malignancies.

Optical genome mapping (OGM) is a next-generation cytogenomic technology that has the potential to replace standard-of-care technologies used in the genetic workup of various malignancies. The ability to detect various classes of structural variations that include copy number variations, deletions, duplications, balanced and unbalanced events (insertions, inversions, and translocation) and complex genomic rearrangements in a single assay and analysis demonstrates the utility of the technology in tumor research and clinical application. Herein, we provide the methodological details for performing OGM and pre- and post-analytical quality control (QC) checks and describe critical steps that should be performed with caution, probable causes for specific QC failures, and potential method modifications that could be implemented as part of troubleshooting. The protocol description and troubleshooting guide should help new and current users of the technology to improve or troubleshoot the problems (if any) in their workflow. © 2023 Wiley Periodicals LLC. Basic Protocol: Optical genome mapping., (© 2023 Wiley Periodicals LLC.)

The COVID-19 pandemic had a profound impact on global health, but rapid vaccine administration resulted in a significant decline in morbidity and mortality rates worldwide. In this study, we sought to explore the temporal changes in the humoral immune response against SARS-CoV-2 healthcare workers (HCWs) in Augusta, GA, USA, and investigate any potential associations with ethno-demographic features. Specifically, we aimed to compare the naturally infected individuals with naïve individuals to understand the immune response dynamics after SARS-CoV-2 vaccination. A total of 290 HCWs were included and assessed prospectively in this study. COVID status was determined using a saliva-based COVID assay. Neutralizing antibody (NAb) levels were quantified using a chemiluminescent immunoassay system, and IgG levels were measured using an enzyme-linked immunosorbent assay method. We examined the changes in antibody levels among participants using different statistical tests including logistic regression and multiple correspondence analysis. Our findings revealed a significant decline in NAb and IgG levels at 8-12 months postvaccination. Furthermore, a multivariable analysis indicated that this decline was more pronounced in White HCWs (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.07-4.08, p = 0.02) and IgG (OR = 2.07, 95% CI = 1.04-4.11, p = 0.03) among the whole cohort. Booster doses significantly increased IgG and NAb levels, while a decline in antibody levels was observed in participants without booster doses at 12 months postvaccination. Our results highlight the importance of understanding the dynamics of immune response and the potential influence of demographic factors on waning immunity to SARS-CoV-2. In addition, our findings emphasize the value of booster doses to ensure durable immunity., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Homologous recombination deficiency (HRD) is characterized by the inability of a cell to repair the double-stranded breaks using the homologous recombination repair (HRR) pathway. The deficiency of the HRR pathway results in defective DNA repair, leading to genomic instability and tumorigenesis. The presence of HRD has been found to make tumors sensitive to ICL-inducing platinum-based therapies and poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi). However, there are no standardized methods to measure and report HRD phenotypes. Herein, we compare optical genome mapping (OGM), chromosomal microarray (CMA), and a 523-gene NGS panel for HRD score calculations. This retrospective study included the analysis of 196 samples, of which 10 were gliomas, 176 were hematological malignancy samples, and 10 were controls. The 10 gliomas were evaluated with both CMA and OGM, and 30 hematological malignancy samples were evaluated with both the NGS panel and OGM. To verify the scores in a larger cohort, 135 cases were evaluated with the NGS panel and 71 cases with OGM. The HRD scores were calculated using a combination of three HRD signatures that included loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale transitions (LST). In the ten glioma cases analyzed with OGM and CMA using the same DNA (to remove any tumor percentage bias), the HRD scores (mean ± SEM) were 13.2 (±4.2) with OGM compared to 3.7 (±1.4) with CMA. In the 30 hematological malignancy cases analyzed with OGM and the 523-gene NGS panel, the HRD scores were 7.6 (±2.2) with OGM compared to 2.6 (±0.8) with the 523-gene NGS panel. OGM detected 70.8% and 66.8% of additional variants that are considered HRD signatures in gliomas and hematological malignancies, respectively. The higher sensitivity of OGM to capture HRD signature variants might enable a more accurate and precise correlation with response to PARPi and platinum-based drugs. This study reveals HRD signatures that are cryptic to current standard of care (SOC) methods used for assessing the HRD phenotype and presents OGM as an attractive alternative with higher resolution and sensitivity to accurately assess the HRD phenotype.

The standard-of-care (SOC) for genomic testing of myeloid cancers primarily relies on karyotyping/fluorescent in situ hybridization (FISH) (cytogenetic analysis) and targeted gene panels (usually ≤54 genes) that harbor hotspot pathogenic variants (molecular genetic analysis). Despite this combinatorial approach, ~50% of myeloid cancer genomes remain cytogenetically normal, and the limited sequencing variant profiles obtained from targeted panels are unable to resolve the molecular etiology of many myeloid tumors. In this study, we evaluated the performance and clinical utility of combinatorial use of optical genome mapping (OGM) and a 523-gene next-generation sequencing (NGS) panel for comprehensive genomic profiling of 30 myeloid tumors and compared it to SOC cytogenetic methods (karyotyping and FISH) and a 54-gene NGS panel. OGM and the 523-gene NGS panel had an analytical concordance of 100% with karyotyping, FISH, and the 54-gene panel, respectively. Importantly, the IPSS-R cytogenetic risk group changed from very good/good to very poor in 22% of MDS (2/9) cases based on comprehensive profiling (karyotyping, FISH, and 54-gene panel vs. OGM and 523-gene panel), while additionally identifying six compound heterozygous events of potential clinical relevance in six cases (6/30, 20%). This cost-effective approach of using OGM and a 523-gene NGS panel for comprehensive genomic profiling of myeloid cancers demonstrated increased yield of actionable targets that can potentially result in improved clinical outcomes.