Fred Hutch Cancer Center

First-In-Human Study of 211 At-CD45 Radioimmunotherapy With Nonmyeloablative Conditioning Hematopoietic Cell Transplantation for Adults With Hematologic Malignancies

Purpose Relapse is the dominant cause of failure after allogeneic hematopoietic cell transplantation (HCT) for aggressive hematologic malignancies. CD45-directed radioimmunotherapy (RIT) has been investigated to intensify conditioning and augment antitumor efficacy. After gaining...

Tree Rearrangement Graphs Admit Paths of Decreasing Robinson-Foulds Distance

Tree rearrangements such as Nearest Neighbor Interchange (NNI) and Subtree Prune and Regraft (SPR) are commonly used to explore phylogenetic treespace. Computing distances based on them, however, is often intractable, so the efficiently computable Robinson-Foulds (RF) distance is...

A DNA Typewriter records the cell lineage history of a mouse, from zygote to late organogenesis

Mammalian biology unfolds over time, within tissues and organs opaque to our eyes and instruments. We applied DNA Typewriter, a sequential molecular recorder, to record the cell lineage of a mouse over nearly two weeks of development. From one embryo, we reconstruct a time-calibr...

Impact of Primary Prophylactic Colony-Stimulating Factor Delivery Method on Febrile Neutropenia: Secondary Analysis of a Pragmatic Cluster Randomized Clinical Trial

Purpose Primary prophylactic colony-stimulating factor (PP-CSF) is recommended for patients receiving chemotherapy with high risk of febrile neutropenia (FN). The impact of PP-CSF delivery method on FN is unknown. We performed a secondary analysis of SWOG S1415CD (Trial Assessing...

Court-Documented Adverse Financial Events Before Cancer Diagnosis and Mortality Risk

This cohort study investigates the association between prediagnostic adverse financial events among individuals newly diagnosed with cancer and mortality risk.

Alzheimer’s disease neuropathological characterization of the dog brain and relationship to biofluid biomarkers and cognitive function

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting more than 55 million people worldwide and is characterized by cognitive decline, amyloid-beta (Aβ) plaques, and neurofibrillary tangles. Although transgenic rodent models have advanced understanding of...

A phase II pilot trial of an indoleamine 2,3-dioxygenase-1 (IDO1) inhibitor (INCB024360) plus a multipeptide melanoma vaccine (MELITAC 12.1) in patients with advanced melanoma, with sequential evaluation of the tumor microenvironment

Indoleamine 2,3-dioxygenase-1 (IDO1) can mediate immune dysfunction by reducing tryptophan (Trp) and increasing kynurenine (Kyn). The CITN-04 clinical trial (NCT01961115) tested the safety and clinical activity of combination therapy with IDO1 inhibitor epacadostat (INCB024360) p...

ATG exposure in T replete transplant for hematological malignancies: Real world analysis from BMT CTN 1202

Traditional weight-based dosing results in variable rabbit anti-thymocyte globulin (rATG) clearance, delaying CD4+Tcell-immune-reconstitution (CD4 + IR) and impacting outcomes. In a retrospective pharmacokinetic/pharmacodynamic analysis of patients undergoing first T-replete hema...

Loss of the tumor suppressor p53 generates a signaling gradient that drives epithelial clonal expansion

Although tumor protein p53 ( TP53 ) mutations are among the most common lesions in epithelial cancers, how p53 loss drives unrestrained clonal expansion remains unclear. Working with mouse epidermis, we found that p53 suppresses clonal expansion by limiting progenitor self-renewa...

Sugar-rich foods exacerbate antibiotic-induced microbiome disruption

Diet shapes the composition of the gut microbiota1; however, the specific effects of distinct food groups on microbiome dynamics are unclear, particularly in circumstances of extreme perturbation. Here we evaluated the relationship between diet and intestinal microbiome dynamics...

pileup-hi: an ultra-high-throughput, customizable alignment pileup program for large datasets

Abstract Motivation Recent advancements in next-generation sequencing have combined massive data throughput with high read accuracy to facilitate large-scale, rapid, and sensitive analysis of genetic variation. High-depth, high-quality platforms such as the Illumina NovaSeq X and...

Tumor microbial biodiversity and microsatellite instability in colorectal cancer

Background Growing evidence links the gut microbiome to colorectal cancer (CRC) progression, with certain bacterial species enriched in specific molecular tumor subtypes. DNA mismatch repair deficiency in CRC, evidenced by the presence of microsatellite instability (MSI), has bee...

Insights into the Datasets, Tools, and Training Needs of the AnVIL Community: 2024

Background The NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL) provides a secure cloud-based environment where research and education communities can analyze genomic and biomedical data. The platform supports a wide range of data analysis as...

Trends in Medicare Work Relative Value Unit Payment Rates Across Physician Specialties: 2018-2024

BACKGROUND: Recent Medicare Physician Fee Schedule revisions have sought to narrow perceived compensation differences between medical and surgical specialties, but their effects on work relative value unit (wRVU) payment rates are unknown. We estimated contemporary specialty-leve...

Per- and polyfluoroalkyl substances levels other than PFOS, PFOA, or PFHxS and liver cancer risk: a nested case-control analysis

Abstract Epidemiologic studies of PFAS and liver cancer risk have produced conflicting results with no strong or clear associations for pre-diagnostic perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS). We now report analyses of nine...

High-grade astrocytoma with piloid features: a clinical and genomic analysis of prognostic factors using a large cohort

BACKGROUND: High-grade astrocytoma with piloid features (HGAP) is a recently defined tumor type that is not well-understood. Prognostic factors of clinical outcomes are not well-established. METHODS: Methylation profiling was performed on tumor samples, many at the National Cance...

Menopausal hormone therapy and primary liver cancer: long-term follow-up of the women’s health initiative randomized trials

Abstract Background: Long-term results on liver cancer incidence and mortality are reported from two Women’s Health Initiative randomized trials evaluating menopausal hormone therapy. Methods: 16,608 postmenopausal women with a uterus were randomized to conjugated equine estrogen...

Artificial Intelligence Across the PET Reconstruction Pipeline: An Update

PET reconstruction has evolved from analytic and iterative physics-based methods toward hybrid approaches that increasingly incorporate artificial intelligence (AI). As digital detectors, long-axial FOV systems, and time-of-flight technology increase data richness and computation...

Uneven TCR chain pairing constraints govern epitope recognition

Combinatorial pairing of independently recombined T cell receptor (TCR) α- and β-chains is central to diversifying the TCR repertoire. Although sequence motifs in one chain correlate with epitope recognition, the extent to which a single chain dictates specificity remains unclear...

Hunting for microsatellite instability in long-read data with Owl

Abstract Microsatellite instability (MSI) is a key biomarker of mismatch repair deficiency and response to immunotherapy, yet most existing genomic detection methods are optimized for short-read sequencing and rely on small panels of homopolymer markers, limiting the ability to c...