NeoGenomics (United States)

Despite advances in multimodal therapy, survival in advanced head and neck squamous cell carcinoma (HNSCC) has improved only modestly. Tumor-informed circulating tumor DNA (ctDNA) assays allow early detection of molecular residual disease (MRD) and recurrence after curative treatment. We analyzed ctDNA in plasma from 76 and saliva from 54 HNSCC patients before and after curative-intent surgery, testing 656 plasma and 128 saliva samples longitudinally. High preoperative ctDNA shedding correlated with advanced pathological stage, lymph node involvement, adverse histologic features, and molecular markers including PD-1 expression and tumor mutational burden. Transcriptomic profiling showed associations between high shedding and increased proliferation, EGFR/MAPK pathway activity, and upregulation of EGFR-related invasion and metastasis genes. Plasma ctDNA detected ≥14 days post-surgery identified 91.3% of recurrences, with lead times up to 500 days before clinical confirmation. These results highlight the value of serial ctDNA monitoring for early relapse detection and potentially improved treatment guidance in HNSCC.

Plasmopara viticola, an obligate biotrophic oomycete, is the causal agent of downy mildew in grapevine (Vitis vinifera) and a major constraint to viticulture worldwide. Here, we report the first high-quality whole-genome assembly of an Indian P. viticola isolate (PV01), generated using a hybrid sequencing approach combining Illumina and Oxford Nanopore platforms. The assembled genome spans 84.09 Mb across 182 contigs, with an N50 of ~971 kb and 97% BUSCO completeness, and encodes 12,404 predicted protein-coding genes, diverse transposable elements, and lineage-specific expansions. Functional annotation revealed a rich repertoire of effectors, including RXLR, CRN, and apoplastic effectors, as well as putative virulence-associated and secretory proteins likely involved in host manipulation and immune suppression. Comparative ortholog analysis across P. viticola isolates and representative oomycetes identified a conserved core genome alongside 164 PV01-specific orthogroups, reflecting isolate-level diversification. Dual RNA-seq analysis of infected grapevine leaves revealed strong suppression of chloroplast- and photosynthesis-associated pathways in the host, coupled with induction of defense-related genes, including PR proteins, WRKY transcription factors, calcium signaling components, and JA/ET-mediated pathways. Concurrently, P. viticola displayed infection-stage–specific expression of effectors, apoplastic proteases, vesicle trafficking components, and genes associated with autophagy suppression and redox homeostasis. Together, these integrated genomic and transcriptomic analyses provide insights into the molecular mechanisms underlying P. viticola pathogenicity and grapevine immune modulation.

Accurate emulation of satellite communication links is vital for testing and evaluating performance under conditions that mirror the real world variability. As satellite systems strive for ever higher data rates and increasingly adaptive behaviors, the challenge lies not only in replicating signal impairments but also in exercising algorithms that dynamically mitigate them to maximize throughput. The Adaptive Coding and Modulation (ACM) Testbed inserts in the topic providing a modular, high fidelity platform to support the design and validation of satellite communication links. This paper presents an overview of the ACM Testbed architecture and its core components, including Control/Simulation, Mass Memory Emulator, Transmitter, Channel Emulator, and Receiver. Designed to emulate real satellite orbits and link impairments, the system supports advanced modulation and coding schemes, orbit-aware link adaptation, and modular configuration of mission scenarios. The architecture includes a physics-based orbit emulator that computes key signal propagation parameters such as Doppler shift, signal-to-noise ratio (SNR), path loss, and antenna gain patterns. Furthermore, the testbed enables accurate modeling of atmospheric losses, thermal noise, and antenna effects based on user-configurable parameters, allowing high-resolution emulation of dynamic satellite-ground link conditions. These features make the platform well suited for validating link performance, ACM/VCM algorithms, and third-party equipment such as payload data transmitters (PDT).

Accurate measurement of breast cancer metastatic deposits in sentinel lymph nodes (SLNs) can be challenging despite the presence of guidelines. To assess interobserver variability in measuring metastatic breast carcinoma involving axillary SLNs. A survey of 10 microscopic images of lymph nodes involved by metastatic carcinoma was electronically shared with a large group of practicing pathologists. Images were all taken at ×1 or ×10 magnification from AE1/3-stained slides. Three options were included on how to measure metastatic foci (a, b, c) without providing the size. A fourth option for uncertain responses was included (not sure/other, d). A total of 88 pathologists completed the survey. We observed significant variability regarding how metastatic deposits are measured. Cases with extracapsular extension were prone to more variability (cases 5, 9, 10) with a significant number of the responders demonstrating uncertainty or excluding the extracapsular extension from the metastatic size. Our results underscore the inherent difficulty and thus the interobserver variability that exist when measuring and classifying small metastatic tumor deposits in SLNs, even when definitive guidelines have already been established.

This study identifies elevated CH with distinct, nonclassical mutations in 9/11 first responders, particularly younger individuals, and links CH to increased leukemia risk. Findings suggest broader relevance to other genotoxic environmental exposures and highlight IL1RAP as a critical driver of CH expansion and a promising therapeutic target for inflammation-driven malignancies. See related commentary by Safina and van Galen, p. 2406.

e15180 Background: Pancreatic cancer has apoor prognosis and limited therapeutic options. While K-RAS mutations are prevalent in this malignancy, a subset of patients harboring wild-type K-RAS presents distinct clinical behavior. Gene fusions have been discerned in pancreatic cancer and are promising candidates for administering targeted therapies. Methods: We conducted a retrospective analysis of 926 pancreatic cancer patients of which 165 (18%) carried a wild-type K-RAS gene, by next generation sequencing (NGS) or polymerase chain reaction (PCR) testing. Tumors were analyzed with a clinical-grade hybrid capture-based RNA-seq clinical fusionome test, evaluating gene fusions between 1104 genes or to other known or novel partners as well as gene expression transcript analysis. Single nucleotide variants/insertions deletions (SNV/Indels) were tested with a clinical-grade NGS assay targeting > 300 cancer genes. Results: Gene fusions were detected in 32% of K-RAS wild-type pancreatic cancers, with 75% involving known oncogenic, clinically actionable genes including FGFR (two FGFR2 and one FGFR1 fusion), two NTRK3 and one each of RAF1, RET, ROS1 and BRAF fusions. Deleterious SNVs were frequently found in both fusion-positive and fusion-negative K-RAS wild-type pancreatic cancers. Transcriptomic expression revealed additional potentially druggable targets, e.g., ROS1 and FGFR3 overexpression in a tumor harboring an NTRK3 fusion, BRAF overexpression in the context of an otherwise non-actionable ETV6 fusion, and MET overexpression in a TES::TFEC -fusion bearing cancer. Conclusions: Druggable fusions are frequent in K-RAS wild-type pancreatic cancers. Moreover, RNA fusion assays as well as transcriptomic expression testing can identify candidate personalized therapies for patients with K-RAS wild-type pancreatic cancer.

Background/Purpose: Coronavirus disease 2019 (COVID-19) has become the cause of a global health crisis during the pandemic. This research aimed to study the impact of symptomatic COVID-19 on children’s oral health indices and salivary microbiome composition during the post-COVID-19 period. Methods: An observational, cross-sectional study was conducted in Tbilisi (Georgia) among children aged 7–12 years. A total of 421 children included in the study had a history of laboratory-confirmed COVID-19 within one year of exposure. No participants met the criteria for comorbid conditions or for PCC. A stratified simple random selection of schools and among selected clusters was used. The selected children were divided into two groups: the exposed group, who were patients with a history of symptomatic COVID-19, and the control group, who were patients with a history of asymptomatic COVID-19. The data were collected from August 2022 to December 2023. Oral screening, microbiological examination of saliva, and administration of questionnaires were also performed. Logistic regression was used to calculate ORs with 95% confidence intervals. The statistical processing of the data was performed with SPSS 23.0. This study was approved by the Biomedical Research Ethical Council of the University of Georgia (UGREC–04–22/9 March 2022). Results: Statistically significant differences in the means of the oral health indicators between the studied groups were detected (exposed: DMFT + deft = 5.9; MGI = 0.92; S-OHI = 1.9; control: DMFT + deft = 3.8; MGI = 0.56; S-OHI = 1.4). According to the logistic regression, symptomatic COVID-19 had a significant effect on the following oral health indicators: DMFT + deft (OR = 1.26; 95% CI = 1.14–1.39), MGI (OR = 2.31; 95% CI = 1.50–3.55), and S-OHI (OR = 3.43; 95% CI = 2.03–5.76). The effect of symptomatic COVID-19 on the frequency of eradication of the studied microbiome was also significant (OR = 2.12; 95% CI = 1.23–3.63). Conclusions: A close association was established between symptomatic COVID-19 and microbiome changes in the oral saliva of children, as well as between oral health indicators and symptomatic COVID-19. Considering the research results, it is assumed that a symptomatic course of COVID-19 may be an additional risk factor associated with poor oral health in the pediatric population in the post-COVID-19 period.