Defining 2 Biologically and Clinically Distinct Groups in Acute Leukemia with a Mixed Phenotype.

A mixed phenotype is characteristic of de novo Mixed Phenotype Acute Leukemia (MPAL) but can also be seen in other leukemias. It poses substantial classification and management dilemmas. Herein, we report a large cohort of acute leukemia with a mixed phenotype and define Acute Myeloid Leukemia with Mixed Phenotype (AML-MP) and MPAL as two distinct groups by characterizing the clinical, genetic, and transcriptomic features.

Advances in Analytical Methodologies for Detecting Novel Psychoactive Substances (NPS): A Review.

Novel psychoactive substances (NPS) have historically been difficult compounds to analyze in forensic toxicology. The identification, detection and quantitation of these analytes and their metabolites has been difficult due to their rapid emergence, short life span and various potencies. Advancements in analytical instrumentation are fundamental to mitigating these NPS challenges by providing reliable identification and sensitivity.

Outcomes From Real-World Data on Intraoperative Electronic Radiotherapy for the Treatment of Early-Stage Breast Cancer: Long-Term Recurrence and Survival Outcomes From a Single Center.

This study is aimed at investigating the 10-year outcomes of intraoperative radiotherapy (IORT) in Mexican women with early breast cancer (EBC) treated at the Centro Medico ABC, Mexico City. A cohort study included women with early-stage invasive ductal carcinoma aged ≥ 45 years without prior oncologic treatment, tumor size ≤ 3.5 cm, cN0M0, positive hormone receptors, margins ≥ 2 mm, negative sentinel lymph nodes, and no extensive lymphovascular invasion.

Pan-tumor validation of a NGS fraction-based MSI analysis as a predictor of response to Pembrolizumab.

Microsatellite instability high (MSI-H) and mismatch repair deficient (dMMR) tumor status have been demonstrated to predict patient response to immunotherapies. We developed and validated a next-generation sequencing (NGS)-based companion diagnostic (CDx) to detect MSI-H solid tumors via a comprehensive genomic profiling (CGP) assay, FoundationOne®CDx (F1CDx). To determine MSI status, F1CDx calculates the fraction of unstable microsatellite loci across >2000 loci using a fraction-based (FB) analysis.

Intratumoral Escherichia Is Associated With Improved Survival to Single-Agent Immune Checkpoint Inhibition in Patients With Advanced Non-Small-Cell Lung Cancer.

PURPOSEThe impact of the intratumoral microbiome on immune checkpoint inhibitor (ICI) efficacy in patients with non-small-cell lung cancer (NSCLC) is unknown. Preclinically, intratumoral Escherichia is associated with a proinflammatory tumor microenvironment and decreased metastases. We sought to determine whether intratumoral Escherichia is associated with outcome to ICI in patients with NSCLC.

Undifferentiated Round Cell Sarcoma With CRTC1::SS18 Fusion: Expanding Clinicopathologic Features of a Rare Translocation Sarcoma With Prominent Desmoplastic Stroma.

Undifferentiated round cell sarcomas (URCS) represent a diverse group of tumors, including conventional Ewing sarcoma, round cell sarcoma with EWSR1/FUS-non-ETS fusions, CIC-rearranged sarcoma, and sarcoma with BCOR alterations. Since 2018, 3 cases of URCS with a novel CRTC1::SS18 gene fusion have been reported in the literature. Herein, we report 3 additional cases of CRTC1::SS18 sarcoma, thereby doubling the number of described cases and expanding the clinicopathologic features of this rare translocation sarcoma.

Unveiling Tst3, a Multi-Target Gating Modifier Scorpion α Toxin from Venom of Northeast Brazil: Evaluation and Comparison with Well-Studied Ts3 Toxin of .

Studies on the interaction sites of peptide toxins and ion channels typically involve site-directed mutations in toxins. However, natural mutant toxins exist among them, offering insights into how the evolutionary process has conserved crucial sequences for activities and molecular target selection. In this study, we present a comparative investigation using electrophysiological approaches and computational analysis between two alpha toxins from evolutionarily close scorpion species of the genus , namely, Tst3 and Ts3 from and , respectively.

Seized drug reporting of NPS helps to guide regional toxicological practice: A 17 month review between 2022 and 2023.

Novel psychoactive substances (NPS) are everchanging and plague forensic laboratories who must identify an unending variety of emerging substances and evolve current methodologies to detect these substances. Identifying potential regional NPS targets and timely examining trends in seized drug data could help mitigate the burden laboratories face. Over 17 months, NPS seized drug data were processed and categorized from three laboratories located across the United States to determine any NPS regional similarities and prevalent NPS drug categories: the South Carolina Law Enforcement Division (SLED), the Sedgwick County Regional Forensic Science Center (SCRFSC), and the Orange County Crime Laboratory (OCCL).

Precision needle-punch tumor enrichment from paraffin blocks improves the detection of clinically actionable genomic alterations and biomarkers.

Background: While many molecular assays can detect mutations at low tumor purity and variant allele frequencies, complex biomarkers such as tumor mutational burden (TMB), microsatellite instability (MSI), and genomic loss of heterozygosity (gLOH) require higher tumor purity for accurate measurement. Scalable, quality-controlled, tissue-conserving methods to increase tumor nuclei percentage (TN%) from tumor specimens are needed for complex biomarkers and hence necessary to maximize patient matching to approved therapies or clinical trial enrollment. We evaluated the clinical utility and performance of precision needle-punch enrichment (NPE) compared with traditional razor blade macroenrichment of tumor specimens on molecular testing success.

Liquid biopsy-based circulating tumour (ct)DNA analysis of a spectrum of myeloid and lymphoid malignancies yields clinically actionable results.

Aims: Liquid biopsy (LBx)-based next-generation sequencing (NGS) of circulating tumour DNA (ctDNA) can facilitate molecular profiling of haematopoietic neoplasms (HNs), particularly when tissue-based NGS is infeasible.

Methods And Results: We studied HN LBx samples tested with FoundationOne Liquid CDx, FoundationOne Liquid, or FoundationACT between July 2016 and March 2022. We identified 271 samples: 89 non-Hodgkin lymphoma (NHL), 43 plasma-cell neoplasm (PCN), 41 histiocytoses, 27 myelodysplastic syndrome (MDS), 25 diffuse large B-cell lymphoma (DLBCL), 22 myeloproliferative neoplasm (MPN), 14 Hodgkin lymphoma (HL), and 10 acute myeloid leukaemia (AML).

Pan-cancer Genomic Analysis of AXL Mutations Reveals a Novel, Recurrent, Functionally Activating AXL W451C Alteration Specific to Myxofibrosarcoma.

Myxofibrosarcoma (MFS) is a common soft tissue sarcoma of the elderly that typically shows low tumor mutational burden, with mutations in TP53 and in genes associated with cell cycle checkpoints ( RB1 , CDKN2A ). Unfortunately, no alterations or markers specific to MFS have been identified and, as a consequence, there are no effective targeted therapies. The receptor tyrosine kinase AXL, which drives cellular proliferation, is targetable by new antibody-based therapeutics.

The patient journey of fibromyalgia in Latin America.

Objectives: To explore the patient journey of people with fibromyalgia (FM) in Latin American countries in order to identify problems in health care and other areas that may be resolvable.

Methods: Qualitative study with phenomenological and content analysis approach through focus groups and patient journey (Ux; User Experience) methodology. Nine virtual focus groups were conducted with FM patients and healthcare professionals in Argentina, Mexico and Colombia recruited from key informants and social networks.

A Drosophila model relevant to chemotherapy-related cognitive impairment.

Chemotherapy-related cognitive impairment (CRCI) is a common adverse effect of treatment and is characterized by deficits involving multiple cognitive domains including memory. Despite the significant morbidity of CRCI and the expected increase in cancer survivors over the coming decades, the pathophysiology of CRCI remains incompletely understood, highlighting the need for new model systems to study CRCI. Given the powerful array of genetic approaches and facile high throughput screening ability in Drosophila, our goal was to validate a Drosophila model relevant to CRCI.

Microsatellite Instability and Mismatch Repair Deficiency Define a Distinct Subset of Lung Cancers Characterized by Smoking Exposure, High Tumor Mutational Burden, and Recurrent Somatic MLH1 Inactivation.

Introduction: Microsatellite instability (MSI) and mismatch repair (MMR) deficiency represent a distinct oncogenic process and predict response to immune checkpoint inhibitors (ICIs). The clinicopathologic features of MSI-high (MSI-H) and MMR deficiency (MMR-D) in lung cancers remain poorly characterized.

Methods: MSI status from 5171 patients with NSCLC and 315 patients with SCLC was analyzed from targeted next-generation sequencing data using two validated bioinformatic pipelines.

Programmed Cell Death Protein 1 Inhibitors and MET Targeted Therapies in NSCLC With Exon 14 Skipping Mutations: Efficacy and Toxicity as Sequential Therapies.

Introduction: NSCLC with exon 14 skipping mutation (ex14) is associated with poor outcomes. Integration of novel targeted therapies is challenging because of barriers in testing and drug access. We, therefore, sought to characterize the treatment patterns, outcomes, and emerging issues of treatment sequencing in patients with ex14-mutant NSCLC.

Mitragynine in the Orange County DUID population.

In recent years, mitragynine has been consistently detected in driving under the influence of drug (DUID) cases. In this paper, we evaluate 3 years (2017-2019) worth of DUID data from arrested drivers in Orange County, CA, USA. From the 25,398 DUID cases received in those 3 years, there were 60 (0.

Expanding Our Knowledge of Molecular Pathogenesis in Histiocytoses: Solitary Soft Tissue Histiocytomas in Children With a Novel CLTC::SYK Fusion.

The histiocytoses comprise a histopathologically and clinically diverse group of disorders bearing recurrent genomic alterations, commonly involving the BRAF gene and mitogen-activated protein kinase pathway. In the current study, a novel CLTC :: SYK fusion in 3 cases of a histopathologically distinct histiocytic neoplasm arising as solitary soft tissue lesions in children identified by next-generation sequencing and fluorescence in situ hybridization is described. Morphologically, all 3 neoplasms were composed of sheets of cells with round-oval nuclei and vacuolated eosinophilic cytoplasm but, in contrast to classic juvenile xanthogranuloma (JXG), Touton giant cells were absent.

Matrix Metalloproteinase-9 Expression Is Associated with the Absence of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients.

Triple-negative breast cancer (TNBC) is particularly challenging due to the weak or absent response to therapeutics and its poor prognosis. The effectiveness of neoadjuvant chemotherapy (NAC) response is strongly influenced by changes in elements of the tumor microenvironment (TME). This work aimed to characterize the residual TME composition in 96 TNBC patients using immunohistochemistry and in situ hybridization techniques and evaluate its prognostic implications for partial responders vs.

Antibody-Drug Conjugates in Breast Cancer: Ascent to Destiny and Beyond-A 2023 Review.

Antibody-drug conjugates (ADCs) are revolutionizing cancer treatment, adding another important new class of systemic therapy. ADCs are a specially designed class of therapeutics that target cells expressing specific cancer antigens using directed antibody-drug delivery and release a cytotoxic chemotherapeutic payload. Over the past two decades, improvements in ADC design, development, and research, particularly in breast cancer, have led to several recent landmark publications.

The impact of fentanyl on DUIDs and traffic fatalities: Blood and oral fluid data.

Fentanyl has emerged as the most prolific drug in the ongoing opioid epidemic and has greatly impacted traffic safety in recent years. This study aimed to evaluate fentanyl prevalence and concentrations in blood and oral fluid in driving under the influence of drugs (DUID) cases in three different regions (i.e.

Novel SOX10 indel mutations drive schwannomas through impaired transactivation of myelination gene programs.

Background: Schwannomas are common peripheral nerve sheath tumors that can cause severe morbidity given their stereotypic intracranial and paraspinal locations. Similar to many solid tumors, schwannomas and other nerve sheath tumors are primarily thought to arise due to aberrant hyperactivation of the RAS growth factor signaling pathway. Here, we sought to further define the molecular pathogenesis of schwannomas.