Analysis Of Patterns Research Articles

Carrier-frequency specific omission-related neural activity in ordered sound sequences is independent of omission-predictability.

Regularities in our surroundings lead to predictions about upcoming events. Previous research has shown that omitted sounds during otherwise regular tone sequences elicit frequency-specific neural activity related to the upcoming but omitted tone. We tested whether this neural response is depending on the unpredictability of the omission. Therefore, we recorded magnetencephalography (MEG) data while participants listened to ordered or random tone sequences with omissions occurring either ordered or randomly. Using multivariate pattern analysis shows that the frequency-specific neural pattern during omission within ordered tone sequences occurs independent of the regularity of the omissions. These results suggest that the auditory predictions based on sensory experiences are not immediately updated by violations of those expectations.

Genome-wide identification and expression pattern analysis of the GRF transcription factor family in Astragalus mongholicus.

Astragalus membranaceus is a plant of the Astragalus genus, which is used as a traditional Chinese herbal medicine with extremely high medicinal and edible value. Astragalus mongholicus, as one of the representative medicinal materials with the same origin of medicine and food, has a rising market demand for its raw materials, but the quality is different in different production areas. Growth-regulating factors (GRF) are transcription factors unique to plants that play important roles in plant growth and development. Up to now, there is no report about GRF in A. mongholicus. This study conducted a genome-wide analysis of the AmGRF gene family, identifying a total of nine AmGRF genes that were classified into subfamily V based on phylogenetic relationships. In the promoter region of the AmGRF gene, we successfully predicted cis-elements that respond to abiotic stress, growth, development, and hormone production in plants. Based on transcriptomic data and real-time quantitative polymerase chain reaction (qPCR) validation, the results showed that AmGRFs were expressed in the roots, stems, and leaves, with overall higher expression in leaves, higher expression of AmGRF1 and AmGRF8 in roots, and high expression levels of AmGRF1 and AmGRF9 in stems. The results of this study provide a theoretical basis for the further exploration of the functions of AmGRFs in plant growth and development.

Differential analysis of histopathological and genetic markers of cancer aggressiveness, and survival difference in EBV-positive and EBV-negative prostate carcinoma

Several studies have shown an association between prostate carcinoma (PCa) and Epstein-Barr virus (EBV); however, none of the studies so far have identified the histopathological and genetic markers of cancer aggressiveness associated with EBV in PCa tissues. In this study, we used previously characterized EBV-PCR-positive (n = 39) and EBV-negative (n = 60) PCa tissues to perform an IHC-based assessment of key histopathological and molecular markers of PCa aggressiveness (EMT markers, AR expression, perineural invasion, and lymphocytic infiltration characterization). Additionally, we investigated the differential expression of key oncogenes, EMT-associated genes, and PCa-specific oncomiRs, in EBV-positive and -negative tissues, using the qPCR array. Finally, survival benefit analysis was also performed in EBV-positive and EBV-negative PCa patients. The EBV-positive PCa exhibited a higher percentage (80%) of perineural invasion (PNI) compared to EBV-negative PCa (67.3%) samples. Similarly, a higher lymphocytic infiltration was observed in EBV-LMP1-positive PCa samples. The subset characterization of T and B cell lymphocytic infiltration showed a trend of higher intratumoral and tumor stromal lymphocytic infiltration in EBV-negative tissues compared with EBV-positive tissues. The logistic regression analysis showed that EBV-positive status was associated with decreased odds (OR = 0.07; p-value < 0.019) of CD3 intratumoral lymphocytic infiltration in PCa tissues. The analysis of IHC-based expression patterns of EMT markers showed comparable expression of all EMT markers, except vimentin, which showed higher expression in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Furthermore, gene expression analysis showed a statistically significant difference (p < 0.05) in the expression of CDH1, AR, CHEK-2, CDKN-1B, and CDC-20 and oncomiRs miR-126, miR-152-3p, miR-452, miR-145-3p, miR-196a, miR-183-3p, and miR-146b in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Overall, the survival proportion was comparable in both groups. The presence of EBV in the PCa tissues results in an increased expression of certain oncogenes, oncomiRs, and EMT marker (vimentin) and a decrease in CD3 ITL, which may be associated with the aggressive forms of PCa.

Online Interest in Urology Residency: A Comprehensive Analysis of Current Internet Temporal and Geographic Patterns

Urology is one of the most competitive specialties in medicine, creating a challenge for prospective students looking to secure a residency position. Our study aims to assess online interest in urology residency by querying online interaction with search terms and criteria for urology residency programs. Utilizing Google Trends analysis from 2011 to 2024, this study examined urology-related search volume indexes, as well as temporal and geographical patterns. Furthermore, the number of residency positions from the American Urological Association database for the 2022 match process was evaluated. Our analysis of temporal trends revealed increased interest in urologist salaries from 2011 to 2019, followed by a decline from 2019 to 2023. Interest in urology-related interviews, applications, research, and letters increased in 2019, marked by the start of the COVID-19 pandemic. California, New York, and Texas had the lowest interest-to-position (IP) ratio, while Maryland, New Jersey, and Virginia had the highest IP ratio. Our analysis reveals an evolving interest in salaries, residency programs, and USMLE Step 1 changes in areas connected with urology. We report key geographical areas with high urology residency interest and low numbers of programs, implying a need for expanded residencies in underserved yet high-interest areas. Awareness and continued interest monitoring after the COVID-19 pandemic is critical for understanding interest in urology applicants.

Clarification of taxonomic status of Pseudochorthippus geminus (Mistshenko, 1951) (Orthoptera: Acrididae: Gomphocerinae) based on male calling song analysis

Pseudochorthippus geminus is redescribed and illustrated based on specimens from southern Kazakhstan and northern Kyrgyzstan. Oscillograms of the male calling songs of P. geminus from these localities and of P. parallelus from southern Kazakhstan are given. Comparative analysis of the song temporal patterns of P. geminus and P. parallelus clearly indicates that they represent separate biological species, but the morphological differences between them are indistinct and do not always provide reliable characters for species diagnostics.

Pan-Canadian Analysis of Practice Patterns in Small Cell Carcinoma of the Cervix: Insights from a Multidisciplinary Survey

Small-cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare cancer with poor prognosis, with limited data to guide its treatment. The objective of this study was to evaluate practice patterns in the management of SCNECC. A 23-question online survey on management of SCNECC was disseminated to Canadian gynecologic oncologists (GO), radiation oncologists (RO) and medical oncologists (MO). In total, 34 practitioners from eight provinces responded, including 17 GO, 13 RO and four MO. During staging and diagnosis, 74% of respondents used a trimodality imaging approach, and 85% tested for neuroendocrine markers. In early-stage (1A1-1B2) SCNECC, 87% of practitioners used a surgical-based approach with various adjuvant and neoadjuvant treatments. In locally advanced (1B3-IVA) SCNECC, 53% favored primary chemoradiation, with cisplatin and etoposide, with the remainder using surgical or radiation-based approaches. In metastatic and recurrent SCNECC, the most common first-line regimen was etoposide and platinum, and 63% of practitioners considered clinical trials in the first line setting or beyond. This survey highlights diverse practice patterns in the treatment of SCNECC. Interdisciplinary input is crucial to individualizing multimodality treatment, and there is a need for prospective trials and intergroup collaboration to define the optimal approach towards managing this rare cancer type.

Observations of root hair patterning in soils: Insights from synchrotron-based X-ray computed microtomography

Abstract Background And Aims Root hair emergence is affected by heterogeneities in water availability in the growth medium. Root hairs preferentially emerge into air, whereas their emergence into water is inhibited. Yet, these results were based either on destructive methods or on roots grown on an agar-air interface. Additionally, there is a lack of knowledge about the spatial distribution of root hairs as hairs elongate radially across the rhizosphere. Therefore, root hair growth in soils remains largely unexplored. Methods Maize (Zea Mays L.) plants were grown in microcosms which were scanned with a synchrotron-based X-ray $$\mu $$ μ CT. The distribution of root hairs along the root epidermis and radially across the rhizosphere (i.e. as function of distance from the root epidermis) was analysed using spatial point pattern analysis. Results While hairs emerged randomly in air-filled pores, their emergence was inhibited where the root was in contact with the soil matrix. As hairs elongated radially into the soil, they were preferentially located in the close proximity of soil particles. In maize, we rarely observed root hairs penetrating into soil aggregates. Conclusion We conclude that in maize, root hairs grow in air-filled pores at the root-soil interface, where the flow of nutrients and water is impeded. Across the rhizosphere, hairs establish contact to the soil by growing in the proximity to soil particles. The effect of hairs on uptake processes, plant anchorage and rhizosheath formation might be limited (in maize) as they hardly penetrate into soil aggregates.

Abstract PO3-09-11: Age Group Analysis of Breast Cancer Patterns in Brazil: Findings from Population-Based Registries

Abstract Background: The rising breast cancer (BC) incidence among young women is potentially influenced by modifiable genetic and reproductive risk factors, as well as the increased incidence among older women may be associated with lifestyle-related factors and screening programs. This study examines BC incidence and mortality rates across different age groups in Brazil, focusing on clinicopathological and sociodemographic variations. Patients and methods: By using data from 13 Brazilian Population-Based Cancer Registries spanning the period 2010-2015, this study analyzed incidence trends among women with BC. Crude incidence ratios (CIRs) and the annual average percent change (AAPC) were computed. Additionally, clinical and sociodemographic information from 348 Hospital-Based Cancer Registries covering 2000-2019 was incorporated. Mortality data for the years 2000-2020 were obtained from the National Mortality Information System. Comparative analyses were conducted across three predefined age groups: &amp;lt; 40, 40-69, and ≥ 70 years. Statistical significance was defined as a p-value &amp;lt; 0.05, while a threshold of more than 5% difference in proportional values was used as a criterion to identify clinically relevant differentials. Results: Between 2010 and 2015, a total of 205,966 newly diagnosed cases of BC were documented. The CIRs were 7.1/100,000 for the age group &amp;lt; 40, 156.5/100,000 for the age group 40-69, and 247.5/100,000 for the age group ≥ 70 years. Within the scope of the analyzed age groups, it was observed that solely the age group &amp;lt; 40 years exhibited a noteworthy and persistent increase in the rate of occurrence (AAPC +1.6; 95% CI: 1.0 to 2.2; p &amp;lt; 0.001). This age group also displayed a significantly higher proportion of black women (53%, p &amp;lt; 0.001), a higher prevalence of alcohol consumption (20.5%, p &amp;lt; 0.001), and a greater likelihood of receiving multiple treatment modalities (60.7%, p &amp;lt; 0.001). In contrast, the age group ≥ 70 years experienced a more extended time delay of &amp;gt; 60 days from diagnosis to treatment onset (54%, p &amp;lt; 0.001), while exhibiting a higher utilization rate of hormone therapy (45.3%, p &amp;lt; 0.01). The mortality rates witnessed a significant increase across all age categories, with the age group &amp;lt; 40 years manifesting the most substantial escalation (AAPC +1.8%; 95% CI: 1.6 to 2.1; p &amp;lt; 0.001). This rise was comparatively more than double the rate observed in the 40-69 age group (AAPC +0.7%; 95% CI: 0.5 to 0.8; p &amp;lt; 0.001) and exactly twice as high as the rate recorded in the age group &amp;gt; 70 years (AAPC +0.9%; 95% CI: 0.7 to 1.1 ; p &amp;lt; 0.001). Conclusion: This study reveals substantial disparities in BC incidence and mortality rates, as well as significant differences in clinicopathological and sociodemographic features, among women aged &amp;lt; 40 compared to those in the 40-69 and ≥ 70 years in Brazil. Keywords: Breast cancer; age groups; incidence; mortality. Citation Format: Jesse Lopes da Silva, Andreia Cristina De Melo, Lucas Zanetti de Albuquerque, Mariana Espirito Santo Rodrigues, Luiz Claudio Santos Thuler. Age Group Analysis of Breast Cancer Patterns in Brazil: Findings from Population-Based Registries [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-11.

Short-term number sense training recapitulates long-term neurodevelopmental changes from childhood to adolescence.

Number sense is fundamental to the development of numerical problem-solving skills. In early childhood, children establish associations between non-symbolic (e.g., a set of dots) and symbolic (e.g., Arabic numerals) representations of quantity. The developmental estrangement theory proposes that the relationship between non-symbolic and symbolic representations of quantity evolves with age, with increased dissociation across development. Consistent with this theory, recent research suggests that cross-format neural representational similarity (NRS) between non-symbolic and symbolic quantities is correlated with arithmetic fluency in children but not in adolescents. However, it is not known if short-term training (STT) can induce similar changes as long-term development. In this study, children aged 7-10 years underwent a theoretically motivated 4-week number sense training. Using multivariate neural pattern analysis, we investigated whether short-term learning could modify the relation between cross-format NRS and arithmetic skills. Our results revealed a significant correlation between cross-format NRS and arithmetic fluency in distributed brain regions, including the parietal and prefrontal cortices, prior to training. However, this association was no longer observed after training, and multivariate predictive models confirmed these findings. Our findings provide evidence that intensive STT during early childhood can promote behavioral improvements and neural plasticity that resemble and recapitulate long-term neurodevelopmental changes that occur from childhood to adolescence. More generally, our study contributes to our understanding of the malleability of number sense and highlights the potential for targeted interventions to shape neurodevelopmental trajectories in early childhood. RESEARCH HIGHLIGHTS: We tested the hypothesis that short-term number sense training induces the dissociation of symbolic numbers from non-symbolic representations of quantity in children. We leveraged a theoretically motivated intervention and multivariate pattern analysis to determine training-induced neurocognitive changes in the relation between number sense and arithmetic problem-solving skills. Neural representational similarity between non-symbolic and symbolic quantity representations was correlated with arithmetic skills before training but not after training. Short-term training recapitulates long-term neurodevelopmental changes associated with numerical problem-solving from childhood to adolescence.

Development of antibiotic metrics for hospitalists via multi-institutional modified Delphi survey.

Closing the gap between evidence-supported antibiotic use and real-world prescribing among clinicians is vital for curbing excessive antibiotic use, which fosters antimicrobial resistance and exposes patients to antimicrobial side effects. Providing prescribing information via scorecard improves clinician adherence to quality metrics. We aimed to delineate actionable, relevant antimicrobial prescribing metrics extractable from the electronic health record in an automated way. We used a modified Delphi consensus-building approach. Our study entailed two iterations of an electronic surveydisseminated to hospital medicine physicians at 10 academic medical centers nationwide. Main outcomes comprised consensus metrics describing the quality of antibiotic prescribing to hospital medicine physicians. Twenty-eight participants from 10 United States institutions completed the first survey version containing 38 measures. Sixteen respondents completed the second survey, which contained 37 metrics. Sixteen metrics, which were modified based on qualitative survey feedback, met criteria for inclusion in the final scorecard. Metrics considered most relevant by hospitalists focused on the appropriate de-escalation of antimicrobial therapy, selection of guideline-concordant antibiotics, and appropriate duration of treatment for common infectious syndromes. Next steps involve prioritization and implementation of these metrics based on quality gaps at our institution, focus groups exploring impressions of clinicians who receive a scorecard,and analysis of antibiotic prescribing patterns before and after metric implementation. Other institutions may be able to implement metrics from this scorecard based on their own quality gaps to provide hospitalists with automated feedback related to antibiotic prescribing.

Combination of cytoplasmic and nuclear patterns on Hep-2 antinuclear antibody is useful as a screening test for anti-synthetase syndrome.

This study aimed to establish a screening model for differentiating anti-synthetase syndrome (ASS) from other antinuclear antibody (ANA)-associated rheumatic diseases (AARD) using a combination of cytoplasmic and non-cytoplasmic ANA (ncANA) patterns. This retrospective observational study included patients with AARDs such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren's syndrome (SS), mixed connective tissue disease (MCTD), and polymyositis/dermatomyositis (PM/DM) who underwent ANA screening between April 2012 and December 2021. Variables included age, sex, ANA patterns (Cytoplasmic and ncANA), and titers. Logistic regression analysis of Cytoplasmic and ncANA patterns was performed to differentiate ASS from other AARDs. The 981 diagnosed cases of AARDs consisted of SS (n = 451), SSc (n = 264), SLE (n = 201), PM/DM (n = 104), MCTD (n = 52), and ASS, including PM/DM (n = 64). Of these, 155 patients had ≥2 overlapping diseases; however, there was no overlap between AARDs and ASS. ASS is more likely to occur when the cytoplasmic titer is positive and the ncANA <320. Receiver operating characteristic (ROC) analysis of the Cytoplasmic and ncANA range revealed an area under the ROC curve (AUC) of 0.885 (95% CI: 0.844 to 0.927). It is important to detect cytoplasmic patterns as an ANA screening test for ASS diagnosis, even if the titer is low. Additionally, combining the cytoplasmic and ncANA patterns yields more accurate ASS screening results.

FACTORS INFLUENCING STOCK PRICES: AN ANALYSIS OF COMPANY PERFORMANCE METRICS ON NSE

This study examines the factors that affect NSE stock values, focusing on metrics that quantify company performance. We look at a number of ratios, including price-to-earnings (P/E), return on equity (ROE), debt-to-equity (D/E), and earnings per share (EPS), to understand how they affect stock prices. The study uses quantitative approaches like regression analysis and qualitative evaluations to find out how these measures are related to stock prices. In order to provide a comprehensive analysis of stock price patterns, we also consider market sentiment and macroeconomic factors. By showing how politicians, financial analysts, and investors perceive and react to metrics of a company's performance, the findings are helpful for all three groups. Keywords: stock prices, National Stock Exchange (NSE), company performance metrics, earnings per share (EPS), price-to-earnings ratio (P/E ratio), return on equity (ROE), debt-to-equity ratio (D/E ratio), regression analysis, market sentiment, macroeconomic factors.

Abstract PO1-07-02: Sensitive tumor detection, accurate quantification, and ER subtyping using low-pass methylome of liquid biopsy samples from patients (pts) with metastatic breast cancer (mBC)

Abstract Background The presence and amount of blood circulating tumor DNA (Tumor Content, TC) is emerging as a clinically relevant factor in many cancers, including BC. In the metastatic setting, a commonly used tumor tissue agnostic approach involves analyzing Copy Number Alterations (CNA) from low-pass whole-genome sequencing (lpWGS) by ichorCNA. However, with a lower limit of detection of 3%, it is unsuitable for low TC applications, such as monitoring disease in response to treatment. Here we report on the use of low-pass whole genome bisulfite sequencing (lpWGBS) coupled with a novel tool, METER (METhylation analyzER), to overcome current limitations of lpWGS, enabling sensitive TC detection, accurate quantification, and ER subtyping from mBC liquid biopsies. Methods METER is a computational tool to analyse TC exploiting BC-specific Differentially Methylated Sites (DMS) and Regions (DMR) in lpWGBS data. To define BC DMSs and DMRs, Rocker-meth was applied to the WGBS profiles of 30 BC tissue (BASIS dataset) and 23 healthy donor cell free DNA (cfDNA) (Fox-Fisher 2021). METER consists of three modules: 1) METER-quant, a DMS-based quantifier of TC; 2) METER-detect, a DMR-based z-score method to classify samples as TC+ (METER+) or TC- (METER-); 3) METER-subtype, to infer ER status via Robust Partial Correlation applied to ER+ vs. ER- BC DMR. We generated lpWGBS data (coverage 0.5-1X) of 135 cfDNA samples from 58 pts (45 ER+, 13 ER-, 55 (95%) up to 3 previous lines of treatment; before starting treatment (T0, n=58), after the first cycle (T1, n=25), and at progression (T2, n=22)) and 30 from healthy individuals as controls. ichorCNA using sensitive parameters (allowing normal fraction up to 0.99) was used to estimate reference TC. A leave-one-out strategy applied to the control samples was used to estimate the false discovery rate (FDR) of METER-detect classification. METER+/- pts were tested for association with OS and PFS using the log-rank test and compared with ichorCNA detection (TC by ichorCNA above or below 3%, ichorCNA+/-). Results TC of 105 cfDNA BC samples by METER-quant was concordant with estimates from the state-of-the-art tool ichorCNA (R &amp;gt;0.90, p&amp;lt; 1e-10). In 22 pts with complete longitudinal data, METER-quant median TC of 0.05 at T0 (IQR 0.02-0.12), 0.02 at T1 (0.01-0.07), and 0.06 at T2 (0.03-0.11) were obtained, with significant difference observed for T0 vs T1 and T2 vs T1 (paired Wilcoxon p&amp;lt; 0.05). Across all time points, METER-detect classified 43% of the n=42 ichorCNA- samples as METER+. The reliability and prognostic performance of METER and ichorCNA detection classification were then compared using clinical outcome data. Based on T0 data, METER+ pts had significantly worse OS than METER- (HR=4.2 CI=2.0-8.9, p&amp;lt; 0.001). This effect was stronger than using ichorCNA (HR=2.3 CI=1.3-4.0, p=0.006). Worse PFS at T0 was observed for METER+ compared with METER- pts (HR=3.7 CI=1.8-7.9, p&amp;lt; 0.001), while no significant association was observed for ichorCNA+ pts (HR=1.4 CI=0.8-2.5, p=0.2). Of note, ichorCNA-/METER+ pts (N=11) at T0 had worse PFS compared with ichorCNA-/METER- (N=11) (HR=3.7 CI 1.4-9.7, p=0.005). Considering the 73 METER+ and 53 samples with METER-quant &amp;gt;5%, METER-subtype showed an accuracy of 0.84 (CI=0.73-0.92) and 0.94 (CI=0.83-0.99) respectively in classifying ER status based on IHC. Discussion lpWGBS enables tumor tissue agnostic analysis and concurrent investigation of complementary molecular features, including CNA and DNA methylation patterns. In a small and heterogeneous cohort, METER showed comparable performance to state-of-the-art tools in terms of TC quantification (ichorCNA) and ER subtyping (IHC), while offering enhanced sensitivity and ensuring a low FDR. METER showed promising prognostic stratification capabilities, particularly for patients with low TC. Validation in an extended prospective cohort is currently ongoing. Citation Format: Marta Paoli, Agostina Nardone, Francesca Galardi, Chiara Biagioni, Dario Romagnoli, Francesca De Luca, Gian Marco Franceschini, Ilenia Migliaccio, Marta Pestrin, Giuseppina Sanna, Emanuela Risi, Luca Livraghi, Erica Moretti, Laura Biganzoli, Luca Malorni, Francesca Demichelis, Matteo Benelli. Sensitive tumor detection, accurate quantification, and ER subtyping using low-pass methylome of liquid biopsy samples from patients (pts) with metastatic breast cancer (mBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-07-02.

Abstract PS06-09: Fragmentomic analysis of a circulating tumor DNA targeted cancer gene panel discriminates ER status in metastatic breast cancer liquid biopsies

Abstract Background: Circulating tumor DNA (ctDNA) isolated from the peripheral blood of patients with cancer is now routinely used in the clinic to detect tumor somatic mutations, with multiple ctDNA-targeted sequencing panels commercially available for Food and Drug Administration (FDA)-approved biomarker indications to guide targeted therapy options. More recently, it has been appreciated that ctDNA fragmentation patterns are influenced by the chromatin structure of the cell of origin, with greater diversity in fragment size in areas with open chromatin and less diversity in fragment size in areas with closed chromatin. In consequence, multiple studies have found that ctDNA fragmentation patterns can be used to accurately infer epigenomic and transcriptomic phenotypes from their tumor cells of origin. However, these analyses have previously relied on whole-genome sequencing (WGS), and it is not feasible to identify FDA-approved biomarker indications in a cost-effective manner with WGS. Methods: Peripheral blood was collected from a cohort of 90 patients with metastatic HER2-negative breast cancer (ER-positive n=71, ER-negative n=19). Cell-free DNA was extracted from plasma and sequenced using a custom 822 gene pan-cancer targeted sequencing panel (IDT). Shannon entropy of first coding exon fragment sizes (E1SE) was used to quantify fragmentation patterns. Higher diversity of fragment sizes, leading to a higher E1SE, are expected in ctDNA derived from areas of the genome with more open chromatin. A machine learning model utilizing the E1SE metric across all genes in the targeted panel was developed to distinguish between ER-positive and ER-negative disease. Results: Training cross-validated accuracy of the machine learning model was 87.8% with AUC of 0.91 to distinguish between ER-positive and ER-negative disease, despite a median ctDNA fraction of only 0.02. E1SE metrics for ESR1 and CCND1 were significantly higher in ER-positive than ER-negative samples, while E1SE metrics for EGFR, c-Kit and members of the MAP kinase family were significantly higher in ER-negative than ER-positive samples, consistent with anticipated differences in gene expression between ER-positive and ER-negative triple negative breast cancers. In contrast, HER2 E1SE was similar between groups, as expected in this clinically HER2-negative cohort. Conclusions: We have shown for the first time that sequencing from standard targeted ctDNA panels can be utilized to infer phenotypic information through analysis of ctDNA fragmentation patterns in patients with metastatic breast cancer. This expands the depth of potential biologic data that can be extracted from targeted ctDNA sequencing panels in addition to DNA mutation status in a cost-effective manner. In the future, this approach can be exploited to expand ctDNA-based biomarker development beyond DNA mutation status. Citation Format: Kyle Helzer, Jamie Sperger, Yue Shi, Viridiana Carreno, Hannah Krause, Katherine Kaufmann, Leilani Mora-Rodriguez, Matthew Bootsma, Mark Burkard, Ruth O'Regan, Kari Wisinski, Joshua Lang, Shuang (George) Zhao, Malinda West, Marina Sharifi. Fragmentomic analysis of a circulating tumor DNA targeted cancer gene panel discriminates ER status in metastatic breast cancer liquid biopsies [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS06-09.

Ghost guns and crime: a tale of two California cities

BackgroundPrivately made firearms (PMFs) or “ghost guns” are homemade, unserialized, untraceable firearms that have been increasingly used in violent crime in the United States. Very little is known about the types of PMFs recovered by law enforcement agencies and the crimes associated with these recoveries. This lack of information limits effective violence prevention policies and practices. Comparative analysis of PMF recoveries in specific cities helps clarify whether local PMF patterns and characteristics vary or reflect more general trends. This research advances epidemiological understanding of emergent violent gun injury prevention challenges by identifying variations in recovered PMF types and use in violent, drug, and weapon-related offenses in Los Angeles and San Diego, California.MethodsConjunctive analysis of case configurations (CACC) identifies patterns among observations (i.e., case configurations) and calculates their probability associated with a given outcome. CACC was used to identify the most common types of PMFs recovered by the Los Angeles (LAPD) and San Diego (SDPD) police departments. For each department and offense type, case configurations with above-average probabilities of offense involvement were determined. Comparisons across departments were made to identify similarities and differences in PMF characteristics and usage.ResultsPMFs were more likely to be involved in violent and weapon-related offenses in Los Angles but more likely to be involved in drug-related offenses in San Diego. In both cities, the 9 mm Polymer 80 handgun was the dominant PMF. However, 9 mm handguns were most likely to be involved in weapon-related offenses in Los Angeles compared to 0.40 handguns in San Diego. Furthermore, large-caliber handguns tended to display above-average probabilities of involvement in violent and drug offenses in Los Angeles. Long guns were represented in case configurations with above-average probabilities of involvement in substantive crimes, including violence.ConclusionsComparative analyses of PMF recovery patterns in Los Angeles and San Diego reveal meaningful contextual variations in PMF characteristics and suggest intentional firearm type selections by offenders. The results support increased regulation of PMFs and highlight the importance of efforts to identify and disrupt the illicit supply of large-caliber PMF handguns and PMF long guns.

Abstract PO2-01-08: Differential HOXB13 gene expression and promoter methylation analysis in breast cancer

Abstract Background: The Breast Cancer Index (BCI) is a gene expression-based signature comprising two functional biomarker panels: the Molecular Grade Index (MGI) and BCI (H/I), which is a ratio of the HOXB13 and IL17BR gene expression. Several studies have shown that BCI (H/I) is a predictive biomarker for extended adjuvant endocrine therapy benefit in hormone receptor-positive (HR+) early-stage breast cancer. Molecular mechanisms underlying endocrine responsiveness remain to be fully explored. The objective of this analysis is to evaluate the correlation between gene expression and methylation in breast cancer patients displaying different HOXB13 mRNA expression levels from The Cancer Genome Atlas (TCGA) project. Methods: Data from methylation microarrays and mRNA sequencing were examined in combination with clinical metadata from 1,095 TCGA breast cancer patients. After removing outliers, HR+ samples were ordered based on their HOXB13 expression levels and the top 10% of samples (HOXB13-high; n=95) and bottom 10% (HOXB13-low; n=95) were selected for further analysis. Differentially expressed genes (DEGs) were determined by comparing all protein-coding genes between the HOXB13-high and HOXB13-low sets, based on an absolute log-fold change above 2 and a Benjamini-Hochberg adjusted p-value threshold of 0.01. Among the subset of samples with matching methylation data (n=60 for the HOXB13-high group and n=48 for the HOXB13-low group), hypo-methylated and hyper-methylated differentially methylated probes (DMPs) were identified based on at least 10% change of β (i.e., average promoter methylation) and a Benjamini-Hochberg adjusted p-value threshold of 0.01. Motif and transcription factor (TF) enrichment analyses were identified at a minimum incidence of 10 and a lower boundary of 1.5 for the 95% confidence interval of the odds ratio. Results: Our analysis identified a total of 613 DEGs between the HOXB13-high and HOXB13-low groups. Gene ontology analysis of DEGs revealed a statistically significant enrichment of genes associated with PTK6 regulated cell cycle, oncogene-induced cellular senescence, and regulation of T cell activation. Analysis of protein-protein interactions of differentially expressed genes revealed differences in key biological processes including changes in cell cycle regulation, p53 pathway, and IL-17 signaling. A total of 5,295 hyper-methylated and 580 hypo-methylated DMPs were discovered when comparing HOXB13-high and HOXB13-low samples. Changes in global methylation patterns enabled classification of breast cancer samples with high or low HOXB13 expression with an accuracy of 0.90. Reconstruction of gene regulatory networks from DNA methylation and transcriptome profiles elucidated significant pairs of DMPs and differentially expressed genes. Specifically, a total of 197 differentially expressed genes were attributed to hyper-methylated DMPs, including genes involved in response to estrogen, activation of HOX genes during differentiation, and drug-mediated inhibition of CDK4/6 activity. Additionally, 8 differentially expressed genes were attributed to hypo-methylated DMPs and were associated with proteasomal protein catabolic processes. Lastly, motif analysis of transcriptional factors for the hyper-methylated DMPs revealed enrichment of binding motifs attributed to FOXA1, ESR1, XBR1, and FOXP1. Conclusion: A comprehensive and comparative analysis of mRNA expression levels and methylation patterns between TCGA breast cancer samples with high and low expression of HOXB13 revealed key signaling pathways and biological processes that may provide insights on the molecular mechanism of HOXB13 in the regulation of response to endocrine therapy in HR+ breast cancer. Citation Format: Natalia Siuliukina, Yi Zhang, Kai Treuner, Mark Pegram. Differential HOXB13 gene expression and promoter methylation analysis in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-08.

Aberrant concordance among dynamics of spontaneous brain activity in patients with migraine without aura: A multivariate pattern analysis study

BackgroundAlterations in the static and dynamic characteristics of spontaneous brain activity have been extensively studied to investigate functional brain changes in migraine without aura (MwoA). However, alterations in concordance among the dynamics of spontaneous brain activity in MwoA remain largely unknown. This study aimed to determine the possibilities of diagnosis based on the concordance indices. MethodsResting-state functional MRI scans were performed on 32 patients with MwoA and 33 matched healthy controls (HCs) in the first cohort, as well as 36 patients with MwoA and 32 HCs in the validation cohort. The dynamic indices including fractional amplitude of low-frequency fluctuation, regional homogeneity, voxel-mirrored homotopic connectivity, degree centrality and global signal connectivity were analyzed. We calculated the concordance of grey matter volume-wise (across voxels) and voxel-wise (across time windows) to quantify the degree of integration among different functional levels represented by these dynamic indices. Subsequently, the voxel-wise concordance alterations were analyzed as features for multi-voxel pattern analysis (MVPA) utilizing the support vector machine. ResultsCompared with that of HCs, patients with MwoA had lower whole-grey matter volume-wise concordance, and the mean value of volume-wise concordance was negatively correlated with the frequency of migraine attacks. The MVPA results revealed that the most discriminative brain regions were the right thalamus, right cerebellar Crus II, left insula, left precentral gyrus, right cuneus, and left inferior occipital gyrus. ConclusionsConcordance alterations in the dynamics of spontaneous brain activity in brain regions could be an important feature in the identification of patients with MwoA.

Spatio-Temporal Variation in the Exceedance of Enterococci in Lake Burley Griffin: An Analysis of 16 Years’ Recreational Water Quality Monitoring Data

Recreational waterbodies with high levels of faecal indicator bacteria (FIB) pose health risks and are an ongoing challenge for urban-lake managers. Lake Burley Griffin (LBG) in the Australian Capital city of Canberra is a popular site for water-based recreation, but analyses of seasonal and long-term patterns in enterococci that exceed alert levels (&gt;200 CFU per 100 mL, leading to site closures) are lacking. This study analysed enterococci concentrations from seven recreational sites from 2001–2021 to examine spatial and temporal patterns in exceedances during the swimming season (October–April), when exposure is highest. The enterococci concentrations varied significantly across sites and in the summer months. The frequency of the exceedances was higher in the 2009–2015 period than in the 2001–2005 and 2015–2021 periods. The odds of alert-level concentrations were greater in November, December, and February compared to October. The odds of exceedance were higher at the Weston Park East site (swimming beach) and lower at the Ferry Terminal and Weston Park West site compared to the East Basin site. This preliminary examination highlights the need for site-specific assessments of environmental and management-related factors that may impact the public health risks of using the lake, such as inflows, turbidity, and climatic conditions. The insights from this study confirm the need for targeted monitoring efforts during high-risk months and at specific sites. The study also advocates for implementing measures to minimise faecal pollution at its sources.

Screening Disinfection Byproducts in Arid-Coastal Wastewater: A Workflow Using GC×GC-TOFMS, Passive Sampling, and NMF Deconvolution Algorithm

Disinfection during tertiary municipal wastewater treatment is a necessary step to control the spread of pathogens; unfortunately, it also gives rise to numerous disinfection byproducts (DBPs), only a few of which are regulated because of the analytical challenges associated with the vast number of potential DBPs. This study utilized polydimethylsiloxane (PDMS) passive samplers, comprehensive two-dimensional gas chromatography (GC×GC) coupled with time-of-flight mass spectrometry (TOFMS), and non-negative matrix factorization (NMF) spectral deconvolution for suspect screening of DBPs in treated wastewater. PDMS samplers were deployed upstream and downstream of the chlorination unit in a municipal wastewater treatment plant located in Abu Dhabi, and their extracts were analyzed using GC×GC-TOFMS. A workflow incorporating a multi-tiered, eight-filter screening process was developed, which successfully enabled the reliable isolation of 22 candidate DBPs from thousands of peaks. The NMF spectral deconvolution improved the match factor score of unknown mass spectra to the reference mass spectra available in the NIST library by 17% and facilitated the identification of seven additional DBPs. The close match of the first-dimension retention index data and the GC×GC elution patterns of DBPs, both predicted using the Abraham solvation model, with their respective experimental counterparts—with the measured data available in the NIST WebBook and the GC×GC elution patterns being those observed for the candidate peaks—significantly enhanced the accuracy of peak assignment. Isotopic pattern analysis revealed a close correspondence for 11 DBPs with clearly visible isotopologues in reference spectra, thereby further strengthening the confidence in the peak assignment of these DBPs. Brominated analogues were prevalent among the detected DBPs, possibly due to seawater intrusion. The fate, behavior, persistence, and toxicity of tentatively identified DBPs were assessed using EPI Suite™ and the CompTox Chemicals Dashboard. This revealed their significant toxicity to aquatic organisms, including developmental, mutagenic, and endocrine-disrupting effects in certain DBPs. Some DBPs also showed activity in various CompTox bioassays, implicating them in adverse molecular pathways. Additionally, 11 DBPs demonstrated high environmental persistence and resistance to biodegradation. This combined approach offers a powerful tool for future research and environmental monitoring, enabling accurate identification and assessment of DBPs and their potential risks.

Tb-doped strontium aluminate nanophosphor: cytotoxicity, phytotoxicity, and bioimaging in plant cells

This study explores the novel application of terbium-doped strontium aluminate nanoparticles for fluorescence imaging in plant cells. The study encompasses microwave assisted solid state synthesis as well as the structural and optical characterization of terbium-doped strontium aluminate nanophosphors, their toxicity studies in plant and animal cells and their use as a fluorescent dye for plant imaging. The X-ray diffraction pattern analysis, along with Rietveld refinement studies, show the formation of SrAl2O4 as a dominant crystalline phase. Photoluminescence investigations demonstrate green emission from Tb3+ transition levels. In vitro biocompatibility of terbium-doped strontium aluminate nanophosphors was studied using L929 fibroblast cells. The plant Clitoria ternatea was used to examine phytotoxicity. The samples' potential for bioimaging was further investigated. Our findings reveal improved growth of seedlings, positioning these nanoparticles as promising tools in plant-related research. This study advances our understanding of nanoparticle-plant interactions and holds potential for transformative applications in agriculture.