High Degree Of Concordance Research Articles

Abstract 1176: Leveraging the GENIE dataset to distinguish somatic cancer drivers from passenger events in routine oncology practice

Abstract Distinguishing genomic events that drive cancer (drivers) from inconsequential damage (passengers) is key to matching patients with biomarker-associated therapies and clinical trials. Whilst population level genomic analyses can estimate the proportion of driver events within a given gene, they cannot categorize individual variants. Reliable annotation remains a significant barrier to unlocking the full utility of cancer genomics. GENIE (Genomics Evidence Neoplasia Information Exchange) data was used to generate codon recurrence scores (CRS) for known cancer genes. GENIE was parsed to remove duplicates, sequencing artefact (recurrent variants reported by one institution, invariably associated with amplicon-based sequencing) and hypermutated samples (>15 mutations per megabase). For missense mutations, a codon recurrence of ≥10 was used to classify driver mutations. The table shows proportion of missense mutations classified as drivers by gene and cancer type, comparing population-based non-synonymous to synonymous mutation ratio; dN/dS (Martincorena 2017, PMID 29056346) with assessment of individual variants by CRS. This comparison demonstrates a high degree of concordance. For a few genes, CRS under called driver mutations (ie VHL in renal cancer) likely due to reduced power with small sample numbers. Importantly, CRS is able to assign driver status to individual missense mutations. Comparison with informatic analyses (PMIDs 28115009, 29247016, 30365005, 31034466) showed equivalent or superior performance of the GENIE approach. These findings demonstrate how a large (and expanding) real-world dataset can be used to predict the driver status of somatic missense mutations at the n=1 variant level. This process is amenable to implementation as a rules-based classification process for somatic missense mutations as part of an automated annotation pipeline. +corrected dN/dS ratio not significantly different from one. Pan- cancer Breast cancer Renal cancer Lung adenocarcinoma Gene dN/dS CRS dN/dS CRS dN/dS CRS dN/dS CRS BRAF 91% 76% <50% 34% <50% 33% 88% 74% PIK3CA 94% 89% 97% 95% 65%+ 84% 86% 76% KRAS 97% 98% 90% 95% 80%+ 100% 99% 99% IDH1 96% 81% <50% 16% <50% n/a <50% 47% EGFR 52% 51% <50% 7% <50% 17% 88% 81% TP53 96% 96% 99% 97% 82%+ 89% 96% 95% PTEN 94% 54% 90% 59% <50% 47% 70% 32% VHL 80% 22% <50% 8% 99% 33% <50% 0% CDKN2A 50% 51% <50% 43% <50% n/a <50% 46% APC <50% 1% <50% 1% <50% n/a <50% 1% RB1 <50% 6% <50% 6% <50% 50% <50% 5% ARID1A <50% 3% <50% 2% <50% 6% <50% 2% KMT2C <50% 0% <50% 0% <50% n/a <50% 0% Citation Format: Philip A. Beer, Susanna L. Cooke, Xuan Shirley Li, Andrew V. Biankin. Leveraging the GENIE dataset to distinguish somatic cancer drivers from passenger events in routine oncology practice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1176.

Abstract 6201: Cross-platform comparisons for DNA methylation sequencing

Abstract Introduction: Accurate, reproducible, and cost-effective NGS platform is essential to identify malignancy-related abnormal DNA methylation changes and translate them into clinical applications including cancer detection, prognosis, and surveillance. In this study we evaluated the performances by the MGISEQ-2000 sequencer in DNA methylation sequencing, using Illumina’s NovaSeq6000 as a benchmark. Materials and Methods: We performed both genome-wide methylation profiling and targeted methylation sequencing on reference DNA and clinical DNA samples. To minimize non-platform discrepancies, we prepared 2 libraries, one for NovaSeq600 and the other for MGISEQ-2000, from each DNA sample using the same experimental protocol except the last step, when we used indexed primers whose sequences and chemical modification are compatible with either NovaSeq600 or MGISEQ-2000 to amplify the corresponding library. We conducted standardized analyses on MGISEQ-2000’s reads quality, sequence bias, genome alignment and coverage, regional depth, limits of detection (LOD), etc. We compared methylation levels at CpG sites, and measurements of methylation haplotypes to assess the consistency in mapping and quantifying genome-wide and regional methylation by MGISEQ-2000 and between the 2 platforms. Furthermore, we analyzed inter-platform variations in classifying normal and malignant plasma DNA samples using targeted methylation sequencing data from either platform exclusively. Results: We prepared and sequenced libraries from over 100 DNA samples of normal or malignant tissue or blood samples for comparison, in addition to reference DNA. Overall, MGISEQ-2000 displayed high level of consistency, and little-to-no sequence bias in methylation sequencing. At genome-wide, regional, and individual-CpG levels, MGISEQ-2000 demonstrated high degree of concordance with NovaSeq6000 in quantifying DNA methylation, as the inter-platform Pearson correlation coefficients were consistently above 0.90 or higher for both targeted sequencing and whole-genome bisulfite sequencing, regardless of whether average methylation level (AMF) or methylation haplotype-specific metrics such as Methylation Haplotype Load (MHL) were used to quantify methylation. Additionally, MGISEQ-2000 is as sensitive as NovaSeq6000 at detecting spik-in methylation controls, as both reached an LOD of 0.1%. Lastly, MGISEQ-2000 produced similar results in classifying normal and malignant samples as NovaSeq6000, suggesting it had minimal distortion on the NovaSeq6000-based classifier. Conclusions: MGISEQ-2000 demonstrated comparable data quality, methylation-calling accuracy, and consistency as NovaSeq6000 in DNA methylation sequencing, supporting its application in future investigation on DNA methylation as cancer biomarkers. Citation Format: Mingyang Su, Jin Sun, Jianhua Ma, Jun Xia, Chengcheng Ma, Wei Li, Zhixi Su, Qiye He, Rui Liu. Cross-platform comparisons for DNA methylation sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6201.

Abstract 2499: Identifying DNA methylation signatures of retinoblastoma via aqueous humor, a novel ocular liquid biopsy

Abstract Introduction: Retinoblastoma (Rb) is the most common childhood intraocular cancer. Tissue biopsy of Rb can cause tumor spread, so it is contraindicated. We demonstrated that aqueous humor (AH), an ocular fluid, is a high yield liquid biopsy enabling in vivo detection of tumor-derived cell free DNA (cfDNA) thus overcoming the contraindication to biopsy. Prognostic genomic cfDNA biomarkers in Rb AH enables objective real time disease monitoring. In ~13% of Rb, tumor progression is driven by epigenetic deregulation of tumor-promoting pathways without detectable genomic alterations. However, epigenetic studies have been done only on tumor from surgically removed eyes. The frequency and effect of epigenomic regulation in eyes that have been saved with therapy is not clear due to no access to in vivo tumor. Therefore, epigenetic analysis of AH cfDNA is highly desired to understand the broader spectrum of Rb tumorigenesis and prognosis. Materials and Methods: 16 AH samples and 4 Rb tumors from 12 patients with 14 Rb eyes were included in the study. We conducted global DNA methylation profiling of tumor tissues from surgically removed Rb eyes, AH samples collected from different clinical stages with different treatment outcomes using the Illumina Infinium EPIC DNA methylation BeadArray platform. Publicly available DNA methylation data of normal retina, Rb eyes, and Rb patients were obtained from Gene Expression Omnibus (GEO, GSE57362) for cell type DNA methylation comparisons. Results: Our preliminary studies revealed a high degree of concordance in genome-wide differential DNA methylation patterns between paired AH and tumor samples. Integrating our data with large public datasets, we identified reliable RB DNA methylation signatures in cfDNA that have potential diagnostic and prognostic values. We also identified hypermethylation at RB1 promoter, which suggested RB1 is druggable to DNA methylation inhibitors. By integrating DNA methylation data with gene expression data, we identified over 300 differentially expressed genes potentially regulated by DNA methylation change. Pathway analysis indicated several tumor suppressor pathways (e.g., RB1 and P53 pathways) were suppressed and some oncogenic pathways were activated (e.g., E2F pathways). Conclusions: Our study sets the stage for exploiting epigenetic markers in AH and identifying potential therapeutic targets to improve the clinical management of patients with RB. Citation Format: Liya Xu, Hongtao Li, Dan Weisenberger, Gangning Liang, Jesse Berry. Identifying DNA methylation signatures of retinoblastoma via aqueous humor, a novel ocular liquid biopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2499.

Utility of liquid biopsy for identifying emerging mutations (mut) and novel treatment options in luminal metastatic breast cancer (LMBC).

1061 Background: Molecular characterization of LMBC for the choice of therapy and inclusion in clinical trials is frequently performed in archival biopsies procured several years before. Emerging mut secondary to therapeutic pressure are hence frequently missed but could be detected by real-time analysis of circulating tumor DNA. Aim: 1) To assess the emergence of ERBB2 and other mut upon therapeutic pressure; 2) To compare the concordance of mut in tumor and plasma samples between patients (pts) with metachronous and synchronous sample acquisition. Methods: Pts with LMBC and available tumor biopsy and plasma samples were identified and divided in two groups: 1) Cohort 1 (metachronous) if the time between tissue and plasma acquisition was > 3 months and systemic treatment was given between the sampling; 2) Cohort 2 (synchronous) if sampling occurred with < 3 months interval in the absence of systemic treatment. Tumor and plasma were analyzed using MiSeq Amplicon-based NGS (custom panel of 60 cancer-related genes). The emergent mut in plasma in Cohort 1 and the concordance of ESCAT Tier I and II mut ( PIK3CA, AKT1, ERBB2, ESR1, PTEN) in both Cohorts were determined and correlated with clinical features. Results: 176 pts were included, 112 in Cohort 1 and 64 in Cohort 2. In Cohort 1, emerging mut in PIK3CA were identified in 5 cases (14% of total cases with PIK3CA mut), ESR1 in 22 cases (85% of cases with ESR1 mut) and PTEN in 3 cases (43% of cases with PTEN mut). No emerging ERBB2 or AKT1 mut were seen in plasma. In Cohort 1 ERBB2 mut were identified in 10 pts (8.9%), 5 both in plasma and tissue and 5 only in tissue. Concordance between tumor and plasma was 53% in Cohort 1 and 66% in Cohort 2 (95% CI of the difference -2% to 38%, P =.09). In Cohort 1, concordance was not associated with (neo)adjuvant treatment, number of lines for MBC, presence of visceral metastasis, location of biopsy (primary tumor or metastasis), interval between sampling (range 3.6 – 288 months) or type of systemic treatment before plasma sampling. In Cohort 2, higher concordance associated with shorter interval between primary diagnosis and sampling (p = 0.02). PI3KCA and ESR1 were the two genes most frequently altered in both cohorts. PI3KCA mut had the highest degree of concordance in both groups (70% in Cohort 1 and 76% in Cohort 2). Concordance for ESR1 mut was low in both cohorts (20% and 48%, respectively). Conclusions: A significant number of ESR1 mut emerged upon therapeutic pressure in LMBC. Plasma analysis could also detect the emergence of PIK3CA and PTEN, but not ERBB2 mut. The trend towards lower concordance between metachronous and synchronous tumor and plasma sampling is probably due to increased tumor heterogeneity and clonal diversity secondary to systemic treatment. Our findings confirm that liquid biopsies provide complementary information respect to tumor tissue that may be potentially useful for clinical decisions.

Rapid molecular diagnostics of tuberculosis resistance by targeted stool sequencing

BackgroundStool is an important diagnostic specimen for tuberculosis in populations who struggle to provide sputum, such as children or people living with HIV. However, the culture of Mycobacterium tuberculosis (M. tuberculosis) complex strains from stool perform poorly. This limits the opportunity for phenotypic drug resistance testing with this specimen. Therefore, reliable molecular methods are urgently needed for comprehensive drug resistance testing on stool specimens.MethodsWe evaluated the performance of targeted next-generation sequencing (tNGS, Deeplex® Myc-TB) for the detection of mutations associated with M. tuberculosis complex drug resistance on DNA isolated from stool specimens provided by participants from a prospective cohort of patients treated for tuberculosis in Eswatini (n = 66; 56 with and 10 participants without M. tuberculosis complex DNA detected in stool by real-time quantitative PCR), and an independent German validation cohort of participants with culture-confirmed tuberculosis (n = 21).ResultsThe tNGS assay detected M. tuberculosis complex DNA in 38 of 56 (68%) samples; for 28 of 38 (74%) samples, a full M. tuberculosis complex drug resistance prediction report was obtained. There was a high degree of concordance with sputum phenotypic drug susceptibility results (κ = 0.82). The ability to predict resistance was concentration-dependent and successful in 7/10 (70%), 18/25 (72%), and 3/21 (14%) of samples with stool PCR concentration thresholds of > 100 femtogram per microliter (fg/μl), 1 to 100 fg/μl, and < 1 fg/μl, respectively (p = 0.0004). The German cohort confirmed these results and demonstrated a similarly high concordance between stool tNGS and sputum phenotypic drug susceptibility results (κ = 0.84).ConclusionstNGS can identify drug resistance from stool provided by tuberculosis patients. This affords the opportunity to obtain critical diagnostic information for tuberculosis patients who struggle to provide respiratory specimens.

Empowering Saudi women in leadership positions in the Ministry of Hajj and Umrah (1443 AH-2021 AD): تمكين المرأة السعودية في المناصب القيادية في وزارة الحج والعمرة (1443هـ-2021مـ)

Purpose - The purpose of this study is to assess the level of administrative empowerment of women and leadership positions in the Ministry of Hajj and Umrah, identify the most important challenges, and obstacles facing women working in leadership administrative positions. from the point of view of a sample of female employees and officials in the Ministry of Hajj and Umrah in the Kingdom of Saudi Arabia. Design/ Methodology/ Approach - To achieve the objectives of this study used the descriptive analytical method. The study population consisted of a number of female employees and officials in the Ministry of Hajj and Umrah, based on the intentional sampling method. Findings-The researcher reached the results show a high degree of concordance between the study vocabulary regarding the dimensions of empowerment in various jobs (74.18%), participation and qualification (72.06%), compared to the neutrality of consensus about the obstacles facing women’s empowerment in leadership positions (65.49%). With a varying level of agreement on the sub-items of those dimensions, which requires the need to establish the concept of women’s empowerment Administrative and leadership positions. In addition to the absence of statistically significant differences in the trends of the study vocabulary about the dimensions of administrative empowerment according to the educational level, social status and administrative experience. while there were statistically significant differences between the average estimates of the study sample members of the female employees to the degree of empowerment of Saudi women in leadership positions in the Ministry of Hajj and Umrah attributed for the functional status variable. The results also showed the obstacles to achieving women's empowerment in administrative work and leadership positions. The study recommended working on upgrading the role of women in the work environment and believing in their ability to achieve success in the operational job roles that they perform, directing their characteristics and their view of advantages to be used in reaching leadership positions, attracting women leaders with experience to work in departments and branches, benefiting from Technical development and electronic communication and its adaptation to develop women's work through remote work.

Clinical Utility of Implementing a Frontline NGS-Based DNA and RNA Fusion Panel Test for Patients with Suspected Myeloid Malignancies.

The use of molecular genetic biomarkers is rapidly advancing to aid diagnosis, prognosis, and clinical management of hematological disorders. We have implemented a next-generation sequencing (NGS) assay for detection of genetic variants and fusions as a frontline test for patients suspected with myeloid malignancy. In this study, we summarize the findings and assess the clinical impact in the first 1613 patients tested. All patients were assessed using NGS based Oncomine Myeloid Research Assay (ThermoFisher) including 40 genes (17 full genes and 23 genes with clinically relevant "hotspot" regions), along with a panel of 29 fusion driver genes (including over fusion 600 partners). Among 1613 patients with suspected myeloid malignancy, 43% patients harbored at least one clinically relevant variant: 91% (90/100) in acute myeloid leukemia patients, 71.7% (160/223) in myelodysplastic syndrome (MDS), 77.5% (308/397) in myeloproliferative neoplasm (MPN), 83% (34/41) in MPN/MDS, and 100% (40/40) in chronic myeloid leukemia patients. Comparison of NGS and cytogenetics results revealed a high degree of concordance in gene fusion detection. Our findings demonstrate clinical utility and feasibility of integrating a NGS-based gene mutation and fusion testing assay as a frontline diagnostic test in a large reported cohort of patients with suspected myeloid malignancy, in a clinical laboratory setting. Overlap with cytogenetic test results provides opportunity for testing reduction and streamlining.

Similarities in Hypertension Status but Differences in Mortality Risk: A Comparison of 2017 ACC/AHA and 2018 Chinese Hypertension Guidelines

BackgroundFew studies investigated the concordance in hypertension status and antihypertensive treatment recommendations between the 2018 Chinese Hypertension League (CHL) guidelines and the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines and assessed the change of premature mortality risk with hypertension defined by the ACC/AHA guidelines.MethodsWe used the baseline data of the China Health and Retirement Longitudinal Study (CHARLS) to estimate the population impact on hypertension management between CHL and ACC/AHA guidelines. Mortality risk from hypertension was estimated using the data from China Health and Nutrition Survey (CHNS). Cox proportional hazards model was used to estimate the hazard ratios (HRs) and their 95% confidence intervals(CIs).ResultsAmong 13,704 participants analyzed from the nationally representative data of CHARLS, 42.64% (95% CI: 40.35, 44.96) of Chinese adults were diagnosed by both CHL and ACC/AHA guidelines. 41.25% (39.17, 43.36) did not have hypertension according to either guideline. Overall, the concordance in hypertension status was 83.89% (81.69, 85.57). A high percentage of agreement was also found for recommendation to initiate treatment among untreated subjects (87.62% [86.67, 88.51]) and blood pressure (BP) above the goal among treated subjects (71.68% [68.16, 74.95]). Among 23,063 adults from CHNS, subjects with hypertension by CHL had a higher risk of premature mortality (1.75 [1.50, 2.04]) compared with those without hypertension. The association diminished for hypertension by ACC/AHA (1.46 [1.07, 1.30]). Moreover, the excess risk was not significant for the newly defined Grade 1 hypertension by ACC/AHA (1.15 [0.95, 1.38]) when compared with BP <120/80 mmHg. This contrasted with the estimate from CHL (1.54 [1.25, 1.89]). The same pattern was observed for total mortality.ConclusionsIf ACC/AHA guidelines were adopted, a high degree of concordance in hypertension status and initiation of antihypertensive treatment was found with CHL guidelines. However, the mortality risk with hypertension was reduced with a non-significant risk for Grade 1 hypertension defined by the ACC/AHA.

Wind Tunnel Investigation and Numerical Analysis of Fume Behavior in the Vicinity of Rectangular Building Under Moderate Velocity Wind

Abstract A research was conducted to examine the dispersion of pollutants ejected from a chimney around three-dimensional rectangular building. Regarding the experimental study, the wind tunnel experiment comprises data acquired through the dispersion of continuous source tracer discharges from a punctual source situated in a regular network of building-like obstacle, and these data include measurements of mean velocity and turbulence parameters. The relevant data are followed using Particle Image Velocimetry to track various instantaneous and mean dynamic characteristics. Concerning the numerical study, the suggested model simulates both the dynamics and the heat transfer flow field using the overall mean three-dimensional Navier-Stokes equations with an RSM turbulence closure model. The findings of a deep comparison of turbulent flow and dispersion between a full wind tunnel experiment and the model predictions are reported. A high degree of concordance was obtained with the experimental flow and numerical simulation data. The detailed investigation, in which numerical and wind tunnel studies, was performed to evaluate the impact of wind velocity on the pollutant dispersion issued from a chimney around the building in their vicinity. the results clearly showed how wind velocity influenced the environmental air flows and pollutant dispersal pathways. The results of this study show that the shape of the building and the resulting interaction between the wind structure play a determining factor in the distribution of pollutants around a building, thereby affecting the air quality in the various parts of the building.

Quantitative proteomic analysis of serum-purified exosomes identifies putative pre-eclampsia-associated biomarkers

BackgroundThe high incidence of pre-eclampsia, which affects 2–7% of all pregnancies, remains a major health concern. Detection of pre-eclampsia before the appearance of clinical symptoms is essential to allow early intervention, and would benefit from identification of plasma/serum biomarkers to help guide diagnosis and treatment. Liquid biopsy has emerged as a promising source of protein biomarkers that circumvents some of the inherent challenges of proteome-wide analysis of plasma/serum. In this respect, purified exosomes have the added benefit of being carriers of intercellular communication both in physiological and pathological conditions.MethodsWe compared the protein complement of purified exosomes from three different collections of control and pre-eclamptic serum samples, obtained at the end of the second trimester of pregnancy and at delivery. We employed shotgun label-free proteomics to investigate differential protein expression, which was then validated by targeted proteomics.ResultsWe developed a purification method that yielded highly enriched exosome preparations. The presence of specific pregnancy protein markers suggested that a significant proportion of purified exosomes derived from tissues related to pregnancy. Quantitative proteomic analyses allowed us to identify 10, 114 and 98 differentially-regulated proteins in the three sample collections, with a high degree of concordance. Functional analysis suggested that these proteins participate in biological processes related to pre-eclampsia, including angiogenesis, inflammation and cell migration. The differential abundance of 66 proteins was validated by targeted proteomics. Finally, we studied the impact of the pre-eclampsia-associated exosomes in the proteome using an in vitro cellular model.ConclusionsWe have identified and validated differential exosomal proteins in liquid biopsy of pregnant women that open new possibilities for early detection of pre-eclampsia. Additionally, the functional impact of the proteome composition of purified pre-eclamptic exosomes in target cells provides new information to better understand changes in embryo-maternal interactions and, consequently, the pathogenesis of this disease.

Characterization of m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration in acute myeloid leukemia.

BackgroundPrevious studies have confirmed the existence of epigenetic regulation of immune responses in acute myeloid leukemia. However, the potential role of RNA N6‐methyladenosine (m6A) remodeling in tumor microenvironment (TME) infiltration remains unclear.Methods and Materialsm6A patterns of 469 AML patients (420 of which provided survival data) based on 18 m6A regulators were systematically evaluated. Based on the expression of 18 m6A regulators, unsupervised agglomerative cluster analysis was applied to recognize the various m6A modification types and to classify patients. We linked these patterns to TME infiltration characteristics and identified three distinct populations of m6A modifications.ResultsThese three TME cell infiltration patterns are characterized by a high degree of concordance with the three tumor immunophenotypes, which include immunoinflammatory, immunorejection, and immune inert patterns. We showed that assessment of m6A modification patterns within individually neoplasms can forecast the stage of neoplasmic inflammation, TME basal activity, subtype, hereditary mutation, and clinical patient prognosis. Limited low m6Ascore, featuring increased mutational load and immune activation, indicates an inflammatory phenotype of TME with a 5‐year survival rate at 14.4% compared to the high‐m6Ascore group (40.9%).ConclusionsData from two different cohorts demonstrated that a higher m6Ascore showed a marked therapeutic superiority as well as clinical advantage. Assessing m6A modification patterns in AML patients could improve our knowledge of the TME infiltrative profile as well as directing effective immunotherapeutic approaches.

Evaluation of Cytological Scoring and Comparison with Histopathological Finding in a Palpable Breast Lump

Introduction: Breast cancer is the commonest malignancy worldwide in women. Preoperative evaluation of breast lump plays a major role in the early diagnosis and management of the breast lesions. This study helps in subgrouping the breast lesions into various categories and provides the line of management of each category accordingly. Aim: To evaluate the cytomorphology of various breast lesions, to compare with histopathological findings and to assess the usefulness of Modified Masood’s Scoring Index (MMSI) in palpable breast lumps. Materials and Methods: This was a cross-sectional study done in 61 female patients presented with palpable breast lump between March 2019 and February 2021 at Pathology Department, Sri Venkateshwaraa Medical College Hospital and Research Centre, Puducherry, India. Cytological examination along with MMSI was applied on Fine Needle Aspiration Cytology (FNAC) aspirates, followed by histological confirmation. Under MMSI, the breast lesions were categorised into four groups: Non Proliferative Breast Disease (Non PBD), PBD without atypia, PBD with atypia and carcinoma breast. The data were collected and complied in Microsoft excel programme, appropriate graphs were made and percentages were calculated. Results: Total of 61 cases were analysed, females with age range of 23 to 64 years, mean age of 38 years. Majority of the cases presented with unilateral breast lump (92.5%). In MMSI Scoring, 15/61 (24.5%) were found with the score of 6 followed by 12/61 (19.6%) score of 8 which falls under NPBD. Total of cases 2/61 (3.2%) score of 24 while 3/61 (4.9%) with the score of 23 fell under Carcinoma breast category. Overall concordance observed between MMSI and histopathology was 59/61 cases which is 96.72%, which indicates the high degree of concordance with histopathological diagnosis. Conclusion: MMSI is a simple and reliable scoring system and can be applied on FNAC aspirates. MMSI increase the diagnostic accuracy and provide better concordance with histopathology.

Testing Okun's law on the relationship between employment rate and economic growth in developed and developing countriesa

Regression models for panel data are increasingly widely used in socio-economic studies because they consider the relationship between many objects over time; thus they can better measure unobservable effects. This study aims to test Okun's law on the relationship between economic growth rate and unemployment rate in two groups of countries (developed and developing). The study was conducted on panel data for the period 2008–2019 using a number of static and dynamic regression models. The model test results show that the dynamic regression model (differential general moment model, DGMM) is a more suitable model in testing the validity of Okun's law for these two groups of countries. These results show that the relationship between unemployment and economic growth in both these groups of countries is quite consistent with Okun's law, in which developing countries have a higher degree of concordance. Moreover, the group of developing countries has a larger Okun coefficient, so economic growth in this group of countries is more affected by the unemployment rate. From the obtained results, we try to explain the causes leading to this difference in this influence level , and suggest some solutions that need special attention to achieve the goal of economic growth.

Qualitative evaluation of the symptoms and quality of life impacts of long-chain fatty acid oxidation disorders.

Background:Long-chain fatty acid oxidation disorders (LC-FAOD) are a group of rare autosomal-recessive genetic disorders characterized by metabolic deficiencies in which the body is unable to convert long-chain fatty acids into energy. To date, however, there is limited understanding of the patient experience of LC-FAOD.Methods:The symptoms, observable signs, and quality of life (QoL) impacts associated with LC-FAOD were explored via a focus group (n = 8) and semi-structured interviews (n = 6) with patients and caregivers of patients with LC-FAOD, and interviews (n = 4) with expert clinicians. Data were analyzed via thematic analysis and summarized in a conceptual model.Results:Participants reported a wide range of signs and symptoms associated with LC-FAOD, broadly categorized as musculoskeletal, endocrine/nutritional/metabolic, neurological, gastrointestinal/digestive, sensory, cardiovascular, respiratory, urological, and constitutional. LC-FAOD were reported to have a significant impact on various aspects of patients’ lives including physical functioning, participation in daily activities, emotional/psychological wellbeing, and social functioning. Lifestyle modifications (such as diet and exercise restrictions) were necessary because of the condition. Symptoms were typically episodic in presentation often arising or exacerbated during catabolic conditions such as prolonged exercise, fasting, physiological stress, and illness/infection. Symptoms were also commonly reported to lead to emergency room visits, hospitalization, and clinical complications.Conclusion:LC-FAOD have a considerable impact on patients’ lives. There is a high degree of concordance in the signs, symptoms, and impacts of LC-FAOD reported by patients, caregivers, and clinicians; however, there were many symptoms and impacts that were only reported by patients and caregivers, thus demonstrating that insights from patient/caregiver experience data are integral for informing medical product development and facilitating patient-centered care.

Splash Erosion on Terraces, Does It Make a Difference If the Terracing Is Done before or after a Fire?

Terraces are a common Mediterranean feature influencing soils, slopes and subsurface hydrology; however, little is known about their impact on erosion processes, especially in humid regions. The purpose of this study was to assess how terracing after a fire affected erosion processes such as splash erosion. For 8 months, the study monitored splash erosion in three terraced plots, one plot under pre-fire conditions and the other two under post-fire conditions. Assessment of the impact of the terracing treatment in such plots was carried out by the installation of two different splash erosion quantitative systems: cups and funnels. An analysis of the splash data obtained in 17 rainfall events and meteorological data collected during each one of those periods was then performed. A significant positive correlation between the amount of rainfall and the splash erosion was observed. The two splash sampling systems show a high degree of concordance; however, the funnel-type model seems to be the most appropriate when it comes to preventing loss of splashed soil samples. The post-fire treatment with terracing leads to a smaller stability of surface soil aggregates, causing higher splash erosion rates. Sampling using the funnel system collects three times the amount of splashed soil than that collected by the cup system, although both systems correlate appropriately with the meteorological parameters.

721. Diagnosis of Histoplasmosis Using the MVista Histoplasma Galactomannan Antigen Qualitative Lateral Flow-Based Immunoassay; A Multicenter Study

Abstract Background Accurate and timely methods for the diagnosis of histoplasmosis in endemic resource-limited settings are largely lacking. Histoplasma galactomannan antigen detection by enzyme immunoassay (EIA) is the most widely used method for the diagnosis of acute pulmonary and disseminated histoplasmosis in the United States (USA). EIA methods have constraints in resource-limited settings including cost, turnaround time, and the need for large reference laboratories, leading to missed or delayed diagnoses and poor outcomes. Lateral flow assays (LFA) are practical methods that can be used in this setting for Histoplasma antigen detection. Methods Frozen urine specimens were submitted to MiraVista (MVista) for Histoplasma antigen EIA testing from three academic medical centers in highly endemic areas of the USA. They were also blinded and tested for the MVista Histoplasma LFA by skilled MVista technologists. Medical records were reviewed for clinical information. Patients were classified as controls or cases of histoplasmosis. Cases were divided into proven or probable, pulmonary, or disseminated, immune competent or immune suppressed, and mild, moderate, or severe. Results 352 subjects were enrolled, including 66 cases of histoplasmosis (44 proven, 22 probable) and 286 controls. Most of the cases were immunocompromised (68%). 76% had disseminated histoplasmosis. 6% were mild, 66% moderate, and 28% severe. A high degree of concordance was found between LFA and EIA results (kappa 0.837, OR 372.7, LR 204, p&amp;lt; 0.001). Overall, the sensitivity and specificity of the LFA were 78.8% and 99.3% respectively (kappa 0.84, p&amp;lt; 0.001). The sensitivity was higher in proven cases (93.2%), in patient with disseminated (94.7%), moderate (80%) and severe disease (94%), and those with galactomannan levels ≥ 2 ng/mL (97.7%). Specificity was 99.3% in proven cases, 99.3% in patient with moderate and severe disease, and 96.4% in those with galactomannan levels ≥ 2 ng/mL. Table 1. Statistical characteristics of the LFA test for histoplasmosis in different categories. PPV: Positive Predictive Value. NPV: Negative Predictive Value. EIA: Enzyme Immunoassay. The LFA test for histoplasmosis is more accurate in patients with high burden of infection. Conclusion The MVista Histoplasma galactomannan LFA may meet the need for accurate rapid diagnosis of histoplasmosis in resource-limited settings, especially in patients with relatively high disease burden, potentially reducing morbidity and mortality. Disclosures Melissa Minderman, Bachelor's Degree, Molecular Biology, MiraVista Diagnostics (Employee) Suphansa Gunn, Bachelor's Degree, psychology, MiraVista Diagnostics (Employee) Lawrence J. Wheat, MD, MiraVista Diagnostics (Employee)

The Impact of Different Lung Ultrasound Protocols in the Assessment of Lung Lesions in COVID-19 Patients: Is There an Ideal Lung Ultrasound Protocol?

BackgroundIn the past months, several lung ultrasonography (LUS) protocols have been proposed, mainly on previously validated schemes independent of coronavirus disease 2019 (COVID-19).ObjectivesThe main purpose of this study was to determine the impact and accuracy of different LUS protocols proposed in COVID-19.MethodsPatients were evaluated with a standard sequence of LUS scans in 72 intercostal spaces along 14 anatomic lines in the chest. A scoring system of LUS findings was reported and then analyzed separately according to each proposed LUS protocol zones. This score was then correlated to a validated Pulmonary Inflammation Index (PII) on chest Computed Tomography (CT).ResultsThirty-two patients were enrolled. The most frequent pattern was ground-glass opacities in the chest X-ray (53.1%), chest CT (59.1%) and subpleural or lobar consolidations (40.8%) in the posteroinferior areas (p < 0.001) on LUS. The Interclass Correlation Coefficient (ICC) was significantly correlated with almost every protocol analyzed except the 8-zone (p = 0.119) and the 10-zone protocol that only included one posterior point (p = 0.052). The highest ICC was obtained with a 12-zone protocol (ICC 0.500; p = 0.027) and decreased as more points were included.ConclusionsIn conclusion, our study results suggest that performing an ultrasound protocol with 12-zone scanning, including the superior and inferior areas of the anterior, lateral and posterior regions of the chest was consistent with higher ICC and higher degree of concordance with CT. We emphasize the need of a more standardization technique to further implement and develop this imaging modality in COVID-19.

Prediction of outcome after spinal surgery\u2014using The Dialogue Support based on the Swedish national quality register

PurposeTo evaluate the predictive precision of the Dialogue Support, a tool for additional help in shared decision-making before surgery of the degenerative spine.MethodsData in Swespine (Swedish national quality registry) of patients operated between 2007 and 2019 found the development of prediction algorithms based on logistic regression analyses, where socio-demographic and baseline variables were included. The algorithms were tested in four diagnostic groups: lumbar disc herniation, lumbar spinal stenosis, degenerative disc disease and cervical radiculopathy. By random selection, 80% of the study population was used for the prediction of outcome and then tested against the actual outcome of the remaining 20%. Outcome measures were global assessment of pain (GA), and satisfaction with outcome.ResultsCalibration plots demonstrated a high degree of concordance on a group level. On an individual level, ROC curves showed moderate predictive capacity with AUC (area under the curve) values 0.67–0.68 for global assessment and 0.6–0.67 for satisfaction.ConclusionThe Dialogue Support can serve as an aid to both patient and surgeon when discussing and deciding on surgical treatment of degenerative conditions in the lumbar and cervical spine.Level of evidenceI.

Dynamical irreversible processes analysis of Poiseuille magneto-hybrid nanofluid flow in microchannel: A novel case study

In addition to solar water heating and transformers, these applications of research include heat exchangers and braking fluids, as well as acoustics and microelectronics. The mathematical model of Poiseuille hybrid nanofluid flow through a microchannel is considered with differing thermal conductivity and viscosity parameters. This mathematical model has mainly been developed to cater to the diversity of the hybrid nanofluid properties, which contains oxide and metal nanoparticles, for example, Cu and Al2O3 immersed in water (H2O) and Ethylene glycol (EG) as the base liquid. The substructure for hybrid nanofluid abides by the mixture of 20% water while the rest is filled with EG. Moreover, the perception of entropy is analyzed. The dimensional form of the current problem is deformed into a non-dimensional form using the appropriate choice of similarity transformation. Thence, the Runge–Kutta-Fehlberg method is being used to treat the numerical solution for the problem. The graphs spectacle the entropy, Bejan numbers, and physical behavior of the contributing factors to the flow phenomena. The numerical results of the rate coefficients for these parameters are shown in the table below. Furthermore, a comparison analysis is conducted to confirm the current result with prior work demonstrating a higher degree of concordance.

Comparative Reductions in Investigator-Reported and Adjudicated Ischemic Events in REDUCE-IT

BackgroundREDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial) randomized statin-treated patients with elevated triglycerides to icosapent ethyl (IPE) or placebo. There was a significant reduction in adjudicated events, including the primary endpoint (cardiovascular [CV] death, myocardial infarction [MI], stroke, coronary revascularization, unstable angina requiring hospitalization) and key secondary endpoint (CV death, MI, stroke) with IPE. ObjectivesThe purpose of this study was to determine the effects of IPE on investigator-reported events. MethodsPotential endpoints were collected by blinded site investigators and subsequently adjudicated by a blinded Clinical Endpoint Committee (CEC) according to a prespecified charter. Investigator-reported events were compared with adjudicated events for concordance. ResultsThere was a high degree of concordance between investigator-reported and adjudicated endpoints. The simple Kappa statistic between CEC-adjudicated vs site-reported events for the primary endpoint was 0.89 and for the key secondary endpoint was 0.90. Based on investigator-reported events in 8,179 randomized patients, IPE significantly reduced the rate of the primary endpoint (19.1% vs 24.6%; HR: 0.74 [95% CI: 0.67-0.81]; P < 0.0001) and the key secondary endpoint (10.5% vs 13.6%; HR: 0.75 [95% CI: 0.66-0.85]; P < 0.0001). Among adjudicated events, IPE similarly reduced the rate of the primary and key secondary endpoints. ConclusionsIPE led to consistent, significant reductions in CV events, including MI and coronary revascularization, as determined by independent, blinded CEC adjudication as well as by blinded investigator-reported assessment. These results highlight the robust evidence for the substantial CV benefits of IPE seen in REDUCE-IT and further raise the question of whether adjudication of CV outcome trial endpoints is routinely required in blinded, placebo-controlled trials. (Evaluation of the Effect of AMR101 on Cardiovascular Health and Mortality in Hypertriglyceridemic Patients With Cardiovascular Disease or at High Risk for Cardiovascular Disease: REDUCE-IT [Reduction of Cardiovascular Events With EPA - Intervention Trial]; NCT01492361)