Citations

Lactococcosis has emerged as an economically and ecologically significant disease in aquatic animals worldwide. This study employed multilocus sequence typing (MLST) to investigate the genetic diversity of Lactococcus spp. strains from Brazilian fish species and evaluate their phylogenetic relationships with global isolates to elucidate potential epidemiological connections involving multiple host species and distinct geographic regions. A total of 55 isolates from different laboratories had their DNA extracted, followed by the amplification and sequencing of the internal fragments of seven housekeeping genes (als, atpA, tuf, gapC, gyrB, rpoC and galP). Sequence types (STs) and clonal complexes (CCs) were defined. An unrooted neighbor-joining phylogenetic tree was generated using allele profiles from this study and those previously reported from other aquatic animal species. The isolates comprised 29 STs (11 previously reported, 18 novel ones), which were grouped into species-specific CCs: CC5 (L. formosensis); CC4, CC17, CC62 (L. garvieae); CC24, CC29, CC97 (L. petauri). Considerable genetic divergence was observed, with L. formosensis and L. garvieae forming heterogeneous populations, while L. petauri was more homogeneous. These findings describe the MLST structure of the sampled isolates and should be interpreted as hypothesis-generating rather than population-level estimates of genotype prevalence. Phylogenetics confirmed groupings within the CCs and revealed additional phylogenetic clustering patterns. In conclusion, the Brazilian Lactococcus spp. strains analyzed in this study constitute a genetically diverse population based on their STs. MLST and phylogenetic analysis demonstrated genetic relatedness between the L. garvieae and L. formosensis isolates from this study and those from other aquatic animal species. In contrast, all the STs identified for L. petauri in this study were unrelated to the MLST lineages responsible for outbreaks in Brazilian Nile tilapia (Oreochromis niloticus) and North American rainbow trout (Oncorhynchus mykiss). This suggests that piscine L. petauri populations in the Americas evolved from distinct ancestral origins.

Abstract Introduction: Early relapse limits durable remissions in multiple myeloma (MM). Cell-free DNA (cfDNA) fragment patterns capture tumor burden and nucleosome positioning. We tested whether a fragmentomics signature trained at MRD time points stratifies progression-free survival (PFS) when applied to pretreatment plasma. Methods: We performed 30-40× whole-genome sequencing of plasma cfDNA from 43 newly diagnosed MM patients, with 65 additional MRD timepoint samples from 41 of those patients (post-ASCT n=30; 1-year maintenance n=30; other maintenance n=5) across eight Canadian sites (TFRIM4 and IMMAGINE studies) and one U.S. site (Mayo SPORE). MRD testing used multiparameter flow cytometry for all follow-up samples (n=65) and clonoSEQ in a subset (n=31). Logistic and elastic-net models were trained at MRD timepoints on fragmentomics features (short-fragment burden; a combined model integrating fragment-length distributions with inferred nucleosome positioning at MM-specific chromatin accessibility regions [Ordoñez et al., Genome Res. 2020]). A decision threshold was fixed by the Youden index during training and applied unchanged to diagnosis samples. PFS was analyzed by Kaplan-Meier, log-rank, and Cox models. Results: After a median follow-up of 49.1 months, 16 of 43 patients (37%) progressed. Using the prespecified locked threshold, patients classified as MRD+ by the proportion-of-short-fragments model had significantly shorter PFS than MRD- patients (HR = 5.12; 95% CI 1.16-22.57; log-rank p = 0.016), with median PFS of 49.2 months for MRD+ cases versus not reached for the MRD- group. Fixed-horizon PFS favored MRD- samples at 24/36/48 months (100/94/87% vs 85/81/53% for MRD+). A combined model integrating weighted fragment lengths with inferred nucleosome positioning also separated outcomes (log-rank p=0.054); the Cox HR was not estimable because no MRD- patients relapsed. At 24, 36, and 48 months, baseline MRD positivity by the short-fragment model identified 100%, 83%, and 86% of patients who relapsed within those intervals (specificity 44%, 43%, and 52%), while the combined model detected all early relapses across the same horizons (specificity 15-21%), indicating consistently high sensitivity but modest specificity for predicting early progression. Conclusions: A cfDNA fragmentomics signature trained at MRD time points stratified PFS when applied to diagnostic plasma, identifying patients at risk of early relapse. Short-fragment burden was most discriminative, and a combined model with nucleosome positioning recapitulated it with higher sensitivity, albeit lower specificity. These data support cfDNA fragmentomics as a practical liquid-biopsy risk biomarker in MM and suggest higher signals may proxy aggressive disease with greater tumor shedding and chromatin disorganization. Future work will validate findings in larger cohorts and integrate cytogenetic and immune features. Citation Format: Dor David Abelman, Jenna Eagles, Aimee Wong, Saumil Shah, Jeffrey Bruce, Stephanie Pedersen, David S. Scott, Cecilia Bonolo de Campos, Signy Chow, Darrell White, Irwindeed Sandhu, Kevin Song, Esteban Braggio, Shaji Kunnathu Kumar, Alli Murugesan, Tony Reiman, A. Keith Stewart, Suzanne Trudel, Trevor J. Pugh. Baseline cfDNA fragmentomics identifies multiple myeloma patients at risk of early progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2597.

Abstract Background: Prostate cancer (PCa) is the leading cause of cancer-related deaths globally and disproportionately affects men of African ancestry. African men often present at younger ages and with more aggressive disease, and approximately half of the PCa risk has been attributed to genetic factors. Africa is the most genetically diverse region of the world, and even within the continent, populations show important differences in allele frequencies and patterns of pathogenic variation. Despite this diversity, African men remain underrepresented in genomic studies, creating significant gaps in knowledge that limit precision medicine efforts. Methods: A total of 182 prostate cancer patients were recruited from teaching hospitals in Benin, Côte d’Ivoire, Ghana, Kenya and Nigeria. 50 cancer susceptibility genes using the Aviseq ONCO50 panel and the Illumina MiSeq platform. Variant calling was performed using an in-house Snakemake workflow, followed by additional bioinformatic steps to distinguish true PMS2 variants from PMS2CL-related artifacts. Pathogenicity assessment relied on annotations from ClinVar and LOVD databases. Results: Pathogenic and likely pathogenic variants were detected in 31.3% of the study group identified in 26 genes. The five most frequently altered genes were RAD50, PTCH1, MSH6, MUTYH, and NF1. Nigerian patients accounted for 52.6 percent of all pathogenic variants, with recurrent alterations observed in MSH6, MUTYH, NF1, and PTCH1. In contrast, pathogenic BRCA1 and BRCA2 variants were observed primarily in patients from Kenya, Benin, and Côte d’Ivoire. Several frameshift, nonsense, and splice-site variants identified in this study have not been previously reported in African populations.[SR1] Conclusion: This study provides one of the most detailed assessments of inherited cancer susceptibility gene variants in African PCa patients. The findings reveal substantial regional variation in the spectrum of pathogenic variants and highlight population-specific genomic signatures that may contribute to the unequal burden of PCa in men of African ancestry. These data emphasize the importance of expanding genomic research efforts within Africa to strengthen precision oncology and reduce global PCa disparities. Citation Format: Abimbola F. Onyia, Freeman Okwuchi, Opeyemi C. De Campos, Sylvester Divine, Olutola Olasehinde, Ayinde Yahaya, Ayo Salako, Aminu Zakari, Iya Bassey, Nicholas Titiloye, Bernard Petershie, Isidore GANDAHO, Luc Brun, Tore Sanni, Safiatou Coulibaly, Noel Coulibaly, Michael Fakayode, Coulibaly Issoufou, Valérie Gbonon, Kouame Benjamin, Yao Evrard, Peter Coleman, Ayun Cassell, Victor Ajumbo, Lilac Wattanga, Benson Ochieng Nyambega, Folakemi T. Odedina, Solomon Rotimi. Targeted sequencing of common cancer susceptibility genes reveals germline variants in African prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6289.

Background: Tumor mutational burden (TMB) is an FDA-approved biomarker for immune checkpoint inhibitor (ICI) therapy. However, its predictive value varies among tumor types and molecular contexts. We investigated whether a very high TMB identifies a biologically distinct subset and whether a higher cutoff provides additional clinical insights beyond the conventional high TMB threshold. Methods: We analyzed 133 patients with advanced solid tumors and TMB ≥ 10 mutations/Mb (mut/Mb) who underwent tumor genomic profiling using a 523-gene DNA/RNA next-generation sequencing panel. Tumors were stratified into prespecified TMB categories: 10–20 mut/Mb (TMB-H) and >20 mut/Mb (TMB-VH). The clinical characteristics, ICI outcomes (in the treated subset), and pathway-level genomic features were compared between groups. Results: TMB-VH was observed in 42/133 (31.6%) patients and spanned more than 20 tumor types. MSI was markedly more prevalent in TMB-VH than in TMB-H tumors (38.1% vs. 2.2%; Fisher’s exact p = 8.9 × 10−8). Pathway-level comparisons did not identify statistically significant differences after false discovery rate correction (all q > 0.05), and the observed patterns were descriptive in nature. In the ICI-treated subset with complete follow-up, objective response did not differ according to the TMB group. Overall survival (OS) was also similar between groups, whether measured from metastatic diagnosis (log-rank p = 0.937) or from ICI initiation (log-rank p = 0.814), although OS was numerically longer in the TMB-VH group in both analyses without reaching statistical significance. Conclusions: In this cohort study, TMB-VH was strongly associated with MSI but not independently associated with improved ICI outcomes. Larger multicenter cohorts are needed to validate pathway-oriented patterns and clarify the clinical utility of extreme TMB thresholds across various histologies. Integrating the functional context (e.g., MSI status, gene-level context, and pathway-level features) with TMB magnitude may enable more robust, tumor-aware biomarker models for immunotherapy selection.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vaginal Cancer outline the recommended diagnostic workup, staging considerations, and treatment options for this rare malignancy. Because vaginal cancer is uncommon and shares many biologic and clinical characteristics with cervical cancer, several management recommendations, particularly systemic therapy, are extrapolated from evidence and practices established for cervical cancer. This guideline excerpt summarizes key components of management, including diagnostic evaluation and workup, principles of staging, pathology considerations, radiation therapy principles, and primary treatment recommendations for both early-stage and advanced disease. It also details approaches to manage relapses, including locoregional recurrence and distant metastases, and provides an in-depth overview of systemic therapy recommendations for vaginal cancer.

ABSTRACT Objective This study compared the effects of phentermine‐topiramate‐ER (mid‐dose 7.5/46 mg) versus placebo on weight loss and cardiovascular disease (CVD) risk outcomes when used as an adjunct to a digitally enhanced lifestyle intervention (DELI). Methods We conducted a 12‐month, randomized, double‐blind, placebo‐controlled trial at a single tertiary academic center in the United States (June 2020–June 2022). Eighty participants with obesity (BMI ≥ 30 kg/m 2 ) were enrolled in the DELI program, consisting of in‐person and telehealth modalities, dietary and physical activity goals, and use of a smartphone application integrated with digital devices (Apple Watch and Bluetooth‐enabled weight scale and blood pressure monitor). Participants were randomized 1:1 to receive either phentermine‐topiramate‐ER ( n = 42) or placebo ( n = 38) in addition to the DELI. Results At 3 months, the phentermine‐topiramate group lost a mean of 10.82 kg versus 4.04 kg in the placebo group (mean difference −6.78 kg; p = 0.002). At 12 months, weight loss was 15.32 kg versus 5.85 kg, respectively (mean difference −9.48 kg; p < 0.001). Participants receiving phentermine‐topiramate‐ER experienced a 3.35% reduction in the estimated atherosclerotic CVD risk compared to baseline ( p = 0.004). Conclusions Phentermine‐topiramate‐ER, when combined with a DELI, produced significant and sustained weight loss and reduced CVD risk in adults with obesity. Trial Registration ClinicalTrials.gov : NCT04408586

373 Background: Recent studies have demonstrated encouraging outcomes with neoadjuvant ICIs in pts with localized deficient mismatch repair (dMMR) and/or microsatellite instability-high (MSI-H) GEC, prompting discussions around the feasibility of nonoperative management (NOM). However, current evidence is largely from phase 1 and 2 clinical trials with limited sample sizes. Thus, the efficacy and safety of neoadjuvant ICI in this pt population remain subject to ongoing debate. Methods: We conducted a systematic review and meta-analysis of prospective and retrospective studies evaluating neoadjuvant ICIs in pts with localized dMMR/MSI-H GEC according to the PRISMA guidelines. The primary outcomes were pathological complete response (pCR) and complete clinical response (cCR) rates. cCR was defined as no evidence of residual disease on tumor-specific imaging and on endoscopy with biopsy. Secondary outcomes included major pathologic response (MPR) rates and the incidence of grade 3–4 immune-related adverse events (irAEs). Proportions with 95% confidence intervals (CI) were used to pool event rates for occurrence of cCR, pCR, MPR and grade 3-4 irAEs. The DerSimonian and Laird random-effects model was used. NOM was assessed as part of the qualitative analysis. Results: 20 studies comprising 396 pts treated with neoadjuvant ICIs were included. Three studies utilized double ICI blockade (PD-1/ PD-L1 inhibitor plus CTLA-4 inhibitor), while the remaining studies primarily utilized monotherapy with a PD-1 inhibitor, with or without chemotherapy. Overall, 320 (81.0%) underwent surgical resection. The pooled pCR rate was 41.6% (95% CI, 33.1%–50.8%), cCR 63.8% (95% CI, 45.6%–78.8%), and MPR 64.2% (95% CI, 49.1%–76.9%). The pooled incidence of grade 3–4 irAEs was 5.1% (95% CI, 0.6%–12.2%). Subgroup analysis showed higher pCR with ≥3 months versus <3 months of ICI (50.2% [95% CI 42.2–58.3] vs 28.4% [18.9–40.2]; χ²=8.69, p=0.003). Forty-four pts were managed with NOM, two experienced early local regrowth over median follow-up ranging from 11.5 to 28 months. Conclusions: Neoadjuvant ICI therapy appears to be a safe and effective therapeutic strategy for pts with localized dMMR/MSI-H GEC. Neoadjuvant ICI exposure for ≥3 months seems to yield higher pCR rates than <3 months. The high and prolonged cCR rates support the nonoperative strategy in selected patients with dMMR/MSI-H GEC.

Abstract Introduction Cannabidiol has been shown to exert significant anti-inflammatory effects and has demonstrated efficacy in murine models of autoimmune myocarditis, pericarditis, and heart failure. The ARCHER Study assessed whether a pharmaceutically produced cannabidiol formulation showed beneficial effects on cardiac magnetic resonance (CMR) endpoints known to predict prognosis in this patient population. Methods In a multicentre international double-blind placebo-controlled phase 2 study, we randomly assigned 109 patients within 10 days of CMR confirmed diagnosis of acute myocarditis to 12 weeks of pharmaceutically produced oral cannabidiol (active) or placebo. Dose was titrated up to 10 mg/kg of body weight twice daily. Primary endpoints were the difference in extracellular volume (ECV) and global longitudinal strain (GLS) measured by CMR at week 12. Other CMR endpoints included left-ventricular ejection fraction (LVEF), LV mass, intracellular volume (ICV), LV end-diastolic and end-systolic volumes (LVEDV, LVESV), and left-atrial end-systolic volume (LAESV). Results All randomized patients (56 active/53 placebo) completed the study with no loss to follow-up. Study drug appeared safe and well tolerated. Baseline mean ECV 38.9 ± 10.9 ml, GLS −15.3 ± 3.6%, and LVEF 60.6 ± 9.9% were consistent with mild to moderate myocarditis and predominantly intact LV function. Week 12 mean ECV was 33.6 ml in the active group and 37.3 ml in the placebo group, a difference of −3.7 ml, confidence interval (CI): −7.4 to 0.1; P = .0538; GLS was −16.0% in the active group and −15.9% in the placebo group, difference of −0.1, CI: −1.2 to 1.1; P = .90. Left ventricular mass was significantly reduced in the active group at 121.1 g compared to placebo 130.3 g, a difference of −9.2, CI: −16.4 to −2.1; P = .0117. In terms of remodelling, LAESV was significantly reduced in the active group (−8.1 ml; P = .0376) while the reduction in LVEDV failed to reach significance (−7.4 ml; P = .098). Conclusion In mild-to-moderate acute myocarditis, treatment with pharmaceutically manufactured cannabidiol was not associated with a statistically significant change in myocardial ECV or GLS, although a trend towards reduction in ECV was observed. In addition, improvement in other potential markers of myocardial recovery, including a significant reduction in LV mass, was seen in the active treatment group. Further investigation of the therapeutic potential of this therapy in inflammatory cardiac conditions is warranted.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cervical Cancer provide diagnostic workup, staging, and various treatment recommendations for cervical cancer based on clinical and surgical staging. This selection from the NCCN Guidelines for cervical cancer specifically focuses on diagnosis and workup, principles of staging and surgery, and primary treatment recommendations for early-stage and advanced disease and provides a detailed overview of systemic therapy recommendations for cervical cancer.

Nutritional supplement use is common among athletes aiming to enhance performance, recovery, and health. However, variable regulatory frameworks and limited safety oversight create risks for inadvertent doping violations. This article provides a global overview of supplement use, relevant authorities, legislation, and safety measures, with a focus on third-party testing (TPT) as a risk-mitigation strategy. Data from six global regions—Africa, Asia, Australia/New Zealand, Europe, Latin America, and North America—were synthesized from peer-reviewed studies, governmental sources, and regional expert contributions. Reported supplement use ranged from 7% to 100% among athletes (variability within regions), with protein powders, vitamins/minerals, creatine, caffeine, and sports drinks being most prevalent. High-risk products (potential anti-doping rule violations), including certain herbal blends, preworkouts, and weight-management supplements, were reported across all regions. While some countries have robust regulatory systems, most lack harmonized or enforceable safety frameworks. TPT programs, which independently verify products for prohibited substances, remain concentrated in the global northwest (Europe, North America, and Australia/New Zealand); awareness and use of TPT certification vary widely, and even in regions with established systems, athlete adherence is inconsistent. Barriers to low-risk supplement use are limited TPT availability, cost, differences in labeling (including language), and cultural factors. Firsthand experiences and perceptions highlight widespread misconceptions about supplement safety and certification. The authors recommend expanded athlete and team-around-the-athlete education, improved global access to TPT low-risk supplements, and policy initiatives to harmonize safety standards. This work emphasizes the need for coordinated international efforts to protect athlete health and integrity while allowing access to evidence-based supplementation.