Analysis Of Patterns Research Articles

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.

Recurrence Patterns after Radiotherapy for Glioblastoma with [(11)C]methionine Positron Emission Tomography-Guided Irradiation for Target Volume Optimization.

11C methionine (11C-MET) is increasingly being used in addition to contrast-enhanced MRI to plan for radiotherapy of patients with glioblastomas. This study aimed to assess the recurrence pattern quantitatively. Glioblastoma patients undergoing 11C-MET PET examination before primary radiotherapy from 2018 to 2023 were included in the analysis. A clinical target volume was manually created and fused with MRI-based gross tumor volumes and MET PET-based biological target volume. The recurrence was noted as an area of contrast enhancement on the first MRI scan, which showed progression. The recurrent tumor was identified on the radiological MR images in terms of recurrent tumor volume, and recurrences were classified as central, in-field, marginal, or ex-field tumors. We then compared the MET-PET-defined biological target volume with the MRI-defined recurrent tumor volume regarding spatial overlap (the Dice coefficient) and the Hausdorff distance. Most recurrences occurred locally within the primary tumor area (64.8%). The mean Hausdorff distance was 39.4 mm (SD 32.25), and the mean Dice coefficient was 0.30 (SD 0.22). In patients with glioblastoma, the analysis of the recurrence pattern has been mainly based on FET-PET. Our study confirms that the recurrence pattern after gross tumor volume-based treatment contoured by MET-PET is consistent with the FET-PET-based treatment described in the literature.

Abnormal global and local connectivity in patients with anti-N-methyl-D-aspartate receptor encephalitis: A resting-state functional MRI study

ObjectiveWe decided to investigate the changes of global and local connectivity in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis patients based on eigenvector centrality (EC) and regional homogeneity (ReHo). We sought new biomarkers to identify the patients based on multivariate pattern analysis (MVPA). MethodsFunctional MRI (fMRI) was performed on all participants. EC, ReHo and MVPA were used to analyze the fMRI images. The correlation between the global or local connectivity and neuropsychology tests was detected. ResultsThe MoCA scores of the patients were lower than those of the healthy controls (HCs), while the HAMD24 and HAMA scores of the patients were higher than those of the HCs. Increased EC values in the right calcarine (CAL.R) and decreased EC values in the right putamen (PUT.R) distinguished these subjects with anti-NMDAR encephalitis from HCs. The higher ReHo values in the left postcentral gyrus (PoCG.L) were detected in the patients. The correlation analysis showed that the EC values in the PUT.R were negatively correlated with HAMD24 and HAMA scores, while the ReHo values in the PoCG.L were negatively correlated with MoCA scores. Better classification performance was reached in the EC-based classifier (AUC = 0.80), while weaker classification performance was achieved in the ReHo-based classifier (AUC = 0.74) or the classifier based on EC and ReHo (AUC = 0.74). The brain areas with large weights were located in the frontal lobe, parietal lobe, cerebellum and basal ganglia. ConclusionOur findings suggest that abnormal global and local connectivity may play an important part in the pathophysiological mechanism of neuropsychiatric symptoms in the anti-NMDAR encephalitis patients. The EC-based classifier may be better than the ReHo-based classifier in identifying anti-NMDAR encephalitis patients.

A comparative analysis of alternative splicing patterns in Atlantic salmon (Salmo salar) in response to Moritella viscosa and sea lice (Lepeophtheirus salmonis) infection

Moritella viscosa (M. viscosa) and sea lice (Lepeophtheirus salmonis) are severe pathogens that primarily infect the skin of Atlantic salmon (Salmo salar), which cause significant economic losses in the farming industry. However, the pathogenesis and molecular mechanisms underlying the host's immune defence at the post-transcriptional level remain unclear. Alternative splicing (AS) is an evolutionarily conserved post-transcriptional mechanism that can greatly increase the richness of the transcriptome and proteome. In this study, transcriptomic data derived from skin tissues of Atlantic salmon after M. viscosa and sea lice infections were used to examine the AS profiles and their differential expression patterns. In total, we identified 33,044 AS events (involving 13,718 genes) in the control (CON) group, 35,147 AS events (involving 14,340 genes) in the M. viscosa infection (MV) group, and 30,364 AS events (involving 13,142 genes) in the sea lice infection (LC) group, respectively. Among the five types of AS identified in our study (i.e., SE, A5SS, A3SS, MXE, and RI), SE was the most prevalent type in all three groups (i.e., CON, MV, and LC groups). Decreased percent-spliced-in (PSI) levels were observed in SE events under both MV- and LC-infected conditions, suggesting that MV or LC infection elevated exon-skipping isoforms and promoted the selection of shorter transcripts in numerous DAS genes. In addition, most of the differential AS genes were found to be associated with pathways related to mRNA regulation, epithelial or muscle development, and immune response. These findings provide novel insights into the role of AS in host-pathogen interactions and represent the first comparative analysis of AS in response to bacterial and parasitic infections in fish.

A systematic comparison of deep learning methods for Gleason grading and scoring

Prostate cancer is the second most frequent cancer in men worldwide after lung cancer. Its diagnosis is based on the identification of the Gleason score that evaluates the abnormality of cells in glands through the analysis of the different Gleason patterns within tissue samples. The recent advancements in computational pathology, a domain aiming at developing algorithms to automatically analyze digitized histopathology images, lead to a large variety and availability of datasets and algorithms for Gleason grading and scoring. However, there is no clear consensus on which methods are best suited for each problem in relation to the characteristics of data and labels. This paper provides a systematic comparison on nine datasets with state-of-the-art training approaches for deep neural networks (including fully-supervised learning, weakly-supervised learning, semi-supervised learning, Additive-MIL, Attention-Based MIL, Dual-Stream MIL, TransMIL and CLAM) applied to Gleason grading and scoring tasks. The nine datasets are collected from pathology institutes and openly accessible repositories. The results show that the best methods for Gleason grading and Gleason scoring tasks are fully supervised learning and CLAM, respectively, guiding researchers to the best practice to adopt depending on the task to solve and the labels that are available.

Spatial pattern analysis reveals intra-specific competition and fractal characteristics of Pinus sylvestris var. mongolica populations in Xiaotaojia Gulley Watershed

The imprudent cultivation of Pinus sylvestris var. mongolica has led to degradation in the watersheds surrounding Chongli County. This study investigates the artificial forests of P. sylvestris var. mongolica in the Xiaotaojiagou watershed, Chongli County. Twenty-five subplots measuring 20 m × 20 m were established at upper, upper-middle, middle, and lower positions within the watershed. Spatial distribution patterns and fractal characteristics of P. sylvestris var. mongolica were analyzed using univariate pair correlation function g(r), marked correlation functions (marked correlation function Kmm(r), marked variation function γm(r), and Schlather’s Im(r) function), and fractal dimensions (box-counting dimension, information dimension). The findings are as follows: (1) P. sylvestris var. mongolica in the middle section of the watershed displayed the largest average diameters at breast height and tree height, while those in the lower section exhibited the largest average crown width. (2) P. sylvestris var. mongolica populations in the upstream, middle, and downstream sections of the watershed exhibited three alternating states: aggregated distribution, uniform distribution, and random distribution. However, with increasing spatial scale, the distribution gradually tended towards randomness. P. sylvestris var. mongolica in the upper-middle section of the watershed showed aggregated distribution at scales of 1.5–32.5 m, transitioning to random distribution and then to uniform distribution with increasing spatial scale. (3) Individual attributes of P. sylvestris var. mongolica (diameter at breast height, tree height, and crown width) exhibited high correlation and facilitation in the upstream and upper-middle sections at small-to-medium scales, whereas negative correlations and inhibitions were observed in the middle and lower sections. These attributes tended to be uncorrelated with increasing spatial scale. (4) Fractal dimensions indicated that the degree of aggregation of P. sylvestris var. mongolica population was lowest in the downstream section of the watershed. In conclusion, spatial distribution patterns and intraspecies relationships of P. sylvestris var. mongolica populations are influenced by spatial scale and environmental conditions, particularly in more resource-competitive downstream areas. Effective management and protection of P. sylvestris var. mongolica populations require targeted measures such as adjusting afforestation density, improving soil conditions, and implementing differentiated ecological restoration strategies to alleviate intraspecies competitive pressures and promote population health and sustainable development.

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.

Performance of recycled refractory brick fine aggregate on diverse properties of Portland slag cement based heat resistant concrete

Utilization of industrial by-products generated through thermal processes is a critical approach in response to the industrialization and urbanization trends, may contribute to the creation of sustainable concrete, which might experience fire through its lifespan and its residual properties, are of specific interest. Hence, this innovation initiates a comprehensive experimental program to analyse the properties of novel heat resistant concrete, that blends Portland Slag Cement and Recycled Refractory Brick at distinct substitution levels (10,20,30,40,50,70, and 100 % of natural fine aggregate), including a control mix. The concrete samples are exposed to elevated temperatures (200,400,600,800, and 1000 °C) to assess the impact of Recycled Refractory Brick and develop a novel heat-resistant sustainable concrete, assuming the inherent heat resistance properties of Refractory Brick as it is prepared under high heating conditions. Subsequently, thermo-mechanical properties viz. weight loss, density loss, modulus of elasticity, ultrasonic pulse velocity, stress-strain behaviour, compressive strength, damage degree, failure pattern and Scanning Electron Microscopic analyses are executed. The experimental results displayed 1.01, 5.15, 6.01, 6.26 and 6.68 % of mass loss in the specimens after exposure to diverse elevated temperatures. The compressive strength significantly improved up to 29 %(10.57 MPa), 67 %(24.26 MPa) and 44 %(12.85 MPa) after exposure to 200, 400 and 600 °C temperature respectively compared to compressive strength at ambient temperature. The results pointedly indicate that higher substitution levels (70 and 100 %) have exhibited superior retention of mechanical properties compared to lower replacement levels after exposure to 800 and 1000 °C temperatures particularly. In authors’ view, substituting 10–40 % of natural fine aggregate with recycled refractory brick combining with Portland Slag Cement shows significant promise in the production of sustainable concrete intended for diverse applications under elevated temperature conditions.

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.