Diagnostic Evaluation for Abnormal Uterine Bleeding at Emergency Departments in the United States.

Objectives: We aimed to examine patterns of diagnostic evaluations for abnormal uterine bleeding (AUB) in a national sample of emergency department (ED) visits and identify potential racial and ethnic differences.

Methods: Using the 2014-2021 National Hospital Ambulatory Medical Care Survey data, we identified 1,049 (unweighted; 7,900,653 weighted) women age ≥18 years without previous cancer diagnosis who visited EDs for non-pregnancy-related AUB. The primary outcomes were whether an ultrasound was provided/ordered and whether referral/follow-up consultation was recommended.

Advances and Challenges in the Management of Myelodysplastic Syndromes.

Myelodysplastic syndromes/neoplasms (MDS) represent a biologically and clinically diverse group of myeloid malignancies marked by cytopenias, morphological dysplasia, and an inherent risk of progression to acute myeloid leukemia. Over the past two decades, the field has made significant advances in characterizing the molecular landscape of MDS, leading to refined classification systems to reflect the underlying genetic and biological diversity. In 2025, the treatment of MDS is increasingly individualized, guided by integrated clinical, cytogenetic, and molecular risk stratification tools.

Management of Anemia in Lower-Risk Myelodysplastic Syndromes/Neoplasms With Novel Agents.

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases that are prognostically stratified into lower-risk (LR-MDS) and higher-risk MDS on the basis of the International Prognostic Scoring System (eg, IPSS, revised IPSS, and molecular IPSS). Anemia is a hallmark of MDS and can lead to worsening of preexisting comorbidities, long-term RBC transfusion dependence, and profound fatigue. Although RBC transfusion support provides rapid relief of anemia-associated symptoms, it also carries a risk of iron overload and alloimmunization, and is associated with a decreased quality of life.

Cell Marker Accordion: interpretable single-cell and spatial omics annotation in health and disease.

Single-cell technologies offer a unique opportunity to explore cellular heterogeneity in health and disease. However, reliable identification of cell types and states represents a bottleneck. Available databases and analysis tools employ dissimilar markers, leading to inconsistent annotations and poor interpretability.

More than just another IDH inhibitor: Insights from the HMPL-306 phase 1 trial.

Resistance to isocitrate dehydrogenase (IDH) inhibitors poses a significant challenge in acute myeloid leukemia (AML), indicating a need for novel IDH inhibitors. Hu et al. report the results of a phase 1 study of the dual IDH1/2 inhibitor HMPL-306 in relapsed/refractory IDH-mutant AML.

Treatment of Older Adults with Newly Diagnosed Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia.

Background: Approximately half of newly diagnosed cases of acute lymphoblastic leukemia (ALL) occur in adults, but adults experience significantly higher rates of treatment failure and treatment-related mortality due to frequent presence of adverse disease biology and limited tolerability of conventional chemotherapy.

Summary: Here, we discuss recent data from clinical trials investigating new approaches for initial treatment of Philadelphia chromosome-negative ALL in older adults. These trials investigate the incorporation of novel agents including the anti-CD22 antibody-drug conjugate inotuzumab, the CD19-CD3 bi-specific T-cell engager blinatumomab, and the BCL2 inhibitor venetoclax into treatment regimens, with some studies attenuating or omitting chemotherapy.

Navigating the dynamic landscape of lower-risk MDS: Advances and emerging insights.

Myelodysplastic syndromes/neoplasms (MDS) are a group of clonal myeloid malignancies characterized by ineffective hematopoiesis, cytopenias, and an increased risk of transformation to acute myeloid leukemia (AML). In lower-risk (LR) MDS, as defined by the revised and molecular international prognostic scoring systems (IPSS-R and IPSS-M), anemia is often the predominant clinical manifestation. Treatment strategies have traditionally focused on supportive care, including transfusion support and erythropoiesis stimulating agents (ESAs).

Computational limitations and future needs to unravel the full potential of 2'-O-methylation and C/D box snoRNAs.

This review evaluates the current state of C/D snoRNA databases and prediction tools in relation to 2'-O-methylation (2'-O-Me). It highlights the limitations of existing resources in accurately annotating and predicting guide snoRNAs, particularly for newly identified 2'-O-Me sites. We emphasize the need for advanced computational approaches specifically tailored to 2'-O-Me to enable the discovery and functional analysis of snoRNAs.

Treatment Patterns and Real-World Outcomes of Molecular Subgroups in Patients With AML Receiving Frontline Venetoclax-Based Therapy.

Purpose: For patients with newly diagnosed AML not suitable for intensive induction chemotherapy, venetoclax (VEN) plus azacitidine (AZA) is a standard of care therapy. This study describes real-world (rw) treatment patterns and outcomes of patients with AML receiving initial VEN-based therapy.

Methods: Patients age ≥18 years diagnosed with AML who received first-line (1L) VEN-based therapy and had available dosing information were included from the COTA rw, electronic health records-based database.

Contemporary management paradigms and emerging therapeutics for myelodysplastic syndromes/neoplasms.

From a historical perspective, the treatment landscape of myelodysplastic syndromes/neoplasms (MDS) has experienced a standstill in terms of new approvals by the U.S. Food and Drug Administration up until the recent 5 years.

Sensitive detection of synthetic response to cancer immunotherapy driven by gene paralog pairs.

Immunotherapies, including checkpoint blockade and chimeric antigen receptor T cell (CAR-T) therapy, have revolutionized cancer treatment; however, many patients remain unresponsive to these treatments or relapse following treatment. CRISPR screenings have been used to identify novel single gene targets that can enhance immunotherapy effectiveness, but the identification of combinational targets remains a challenge. Here, we introduce a computational approach that uses sgRNA set enrichment analysis to identify cancer-intrinsic paralog pairs for enhancing immunotherapy using genome-wide screens.

A phase 1 study of durvalumab as monotherapy or combined with tremelimumab with or without azacitidine in patients with myelodysplastic syndrome.

Upregulation of programmed death ligand-1 (PD-L1) has been observed in patients with MDS, and its expression on myeloblasts is associated with progression to AML. This open-label, phase 1 study evaluated the safety and tolerability of the PD-L1 antibody durvalumab as monotherapy (part 1) and in combination with tremelimumab, with or without azacitidine (part 2), in patients with MDS who progressed following hypomethylating agent treatment. Sixty-seven adults with MDS were enrolled (part 1, 40 with low/intermediate-1 or intermediate-2/high IPSS risk status; part 2, 27 with intermediate-2/high IPSS risk status).

Cas12a-knock-in mice for multiplexed genome editing, disease modelling and immune-cell engineering.

The pleiotropic effects of human disease and the complex nature of gene-interaction networks require knock-in mice allowing for multiplexed gene perturbations. Here we describe a series of knock-in mice with a C57BL/6 background and with the conditional or constitutive expression of LbCas12a or of high-fidelity enhanced AsCas12a, which were inserted at the Rosa26 locus. The constitutive expression of Cas12a in the mice did not lead to discernible pathology and enabled efficient multiplexed genome engineering.

Initial management of patients with acquired aplastic anemia in the United States: results from a large national claims database.

Acquired aplastic anemia (AA) is an immune-mediated disorder leading to bone marrow failure characterized by pancytopenia, with infectious and bleeding complications. The disease course may be complicated by paroxysmal nocturnal hemoglobinuria (PNH), necessitating screening with flow cytometry (FC) at the time of AA diagnosis. Management strategies vary based on disease severity.

Wild Florida mottled ducks demonstrate strong heterogeneity in their humoral innate immune response.

The Florida Mottled Duck (Anas fulvigula fulvigula) is a unique subspecies of waterfowl whose range is limited to peninsular Florida, USA. As an endemic subspecies, Florida Mottled Ducks face numerous conservation stressors, such as habitat conversion and hybridization with non-native Mallards (Anas platyrhynchos). In addition to these numerous stressors, Mottled Ducks are also contending with emerging and/or geographically expanding waterborne pathogens such as Vibrio spp.

Dissecting the stress granule RNA world: dynamics, strategies, and data.

Stress granules (SGs) are cytoplasmic ribonucleoprotein granules that commonly nucleate from the interaction of translationally stalled mRNAs and RNA-binding proteins. SGs are involved in the cellular adaptation to stress conditions participating in the regulation of gene expression and cell signaling. While dysregulation of SG dynamics has been increasingly implicated in human disease, a comprehensive understanding of SG composition, particularly of the RNA component, across various conditions remains elusive.

OATP1B-type Transport Function Is a Determinant of Aromatase Inhibitor-Associated Arthralgia Susceptibility.

Abstract: Aromatase inhibitors (AI) such as anastrozole, letrozole, and exemestane are used as adjuvant treatment for postmenopausal women with hormone receptor–positive breast cancer. The interindividual pharmacokinetic variability seen with AIs is extensive, and this phenomenon may have important ramification for AI-associated arthralgia, a common toxicity of which the etiology remains unclear. We speculated that hepatic uptake transporters involved in the elimination of AIs play a crucial role in explaining this pharmacologic variability.

Standardization of Bone Marrow Reporting for Myelodysplastic Syndromes/Neoplasms on Behalf of the International Consortium for Myelodysplastic Syndromes/Neoplasms.

Context.—: Standardized bone marrow reporting specifically for myelodysplastic syndromes/neoplasms (MDS) is currently lacking in the literature and much needed in practice.

Objective.

Perinatal exposure to ambient fine particle air pollution and risk of childhood ewing sarcoma in a population-based case-control study in California (1988-2015).

Background: Incidence of childhood Ewing sarcoma, a rare cancer affecting bones and soft tissues, is increasing. Environmental exposures during the perinatal period, like air pollution, may play a role. We examined exposure to perinatal ambient fine particulate matter (PM) and childhood Ewing sarcoma risk in a case-control linkage study nested within a California birth cohort.

Preferences for Care among African American Women Considering Postmastectomy Breast Reconstruction.

Background: Approximately 20% of patients report inadequate discussions with their providers about reconstructive options, with an increased frequency reported by non-White women. Eliciting treatment preferences with adaptive choice-based conjoint (ACBC) analysis can improve understanding of what patients value. The authors aimed to determine what African American patients value when considering breast reconstruction options.

Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy.

The complex nature of the immunosuppressive tumor microenvironment (TME) requires multi-agent combinations for optimal immunotherapy. Here we describe multiplex universal combinatorial immunotherapy via gene silencing (MUCIG), which uses CRISPR-Cas13d to silence multiple endogenous immunosuppressive genes in the TME, promoting TME remodeling and enhancing antitumor immunity. MUCIG vectors targeting four genes delivered by adeno-associated virus (AAV) (Cd274/Pdl1, Lgals9/Galectin9, Lgals3/Galectin3 and Cd47; AAV-Cas13d-PGGC) demonstrate significant antitumor efficacy across multiple syngeneic tumor models, remodeling the TME by increasing CD8 T-cell infiltration while reducing neutrophils.

Advancing drug development in myelodysplastic syndromes.

Myelodysplastic syndromes/neoplasms (MDSs) are heterogeneous stem cell malignancies characterized by poor prognosis and no curative therapies outside of allogeneic hematopoietic stem cell transplantation. Despite some recent approvals by the US Food and Drug Administration, (eg, luspatercept, ivosidenib, decitabine/cedazuridine, and imetelstat), there has been little progress in the development of truly transformative therapies for the treatment of patients with MDS. Challenges to advancing drug development in MDS are multifold but may be grouped into specific categories, including criteria for risk stratification and eligibility, response definitions, time-to-event end points, transfusion end points, functional assessments, and biomarker development.