Achievements

Manuscripts

An ultraconserved snoRNA-like element in long noncoding RNA CRNDE promotes ribosome biogenesis and cell proliferation

BDSC Authors: He Zhang

Contributions: He Zhang performed an analysis to quantify the expression level of CRNDE using RNA-seq data from kidney cancer samples.

Summary: We performed CRISPR interference (CRISPRi) screens to identify essential long noncoding RNAs (lncRNAs) in renal cell carcinoma (RCC) cells. This revealed that an alternatively spliced isoform of lncRNA colorectal neoplasia differentially expressed (CRNDE) containing an ultraconserved element (UCE), referred to as CRNDEUCE, is required for RCC cell proliferation. CRNDEUCE localizes to the nucleolus and promotes 60S ribosomal subunit biogenesis. The UCE of CRNDE functions as an unprocessed C/D box snoRNA that directly interacts with ribosomal RNA precursors.

Comparative Risk of Infection and Prevalence of Combination Targeted Therapy in Psoriatic Arthritis

BDSC Authors: Yujia Guo, Jialiang Liu, and Donghan M. Yang

Contributions: Yujia Guo performed the acquisition, analysis, and interpretation of data, statistical analysis, and review of the manuscript. Jialiang Liu, assisted with the acquisition, analysis, interpretation of data and drafting of the manuscript. Donghan M. Yang assisted with the project’s concept and design, acquisition, analysis, interpretation of data, and drafting and editing of the manuscript.

Summary: Achieving optimal disease control in psoriatic arthritis (PsA) remains a major challenge. Although combining systemic immunomodulatory therapies has demonstrated benefit with acceptable safety in other immune-mediated diseases, evidence on the use and safety of combination targeted therapy (CTT) in PsA is limited. This study utilize data from the IBM MarketScan Commercial Claims Database to characterize treatment patterns and evaluate their association with safety outcomes. We found that CTT most often involved a biologic agent combined with apremilast and and had a similar infection risk as standard therapy.

Distinct autoantibody profiles across checkpoint inhibitor types and toxicities

BDSC Authors: Jialiang Liu, Yang Xie

Contributions: Jialiang Liu performed the data curation and formal analysis for this project. Jialiang also curated the original draft for statistical analysis section along with reviewing and editing the final draft. Yang Xie assisted with the conceptualization, formal analysis, investigation, methodology, project supervision, and manuscript writing.

Summary: This study aimed at characterizing changes in circulating autoantibodies and their association with immune-related adverse event (irAE) risk in a cohort of patients with Hodgkin lymphoma treated with multi-agent regimens incorporating anti-CD30, anti-PD1, and anti-CTLA4 treatments. We found that the combinations of PD1- and CTLA4-targeting agents may have distinct effects on autoantibody and toxicity profiles. These findings may have relevance to clinical monitoring and irAE treatment.

Factors Associated With Cost Barriers to Asthma Management by Insurance Coverage Status Among US Adults

BDSC Authors: Luyu "Amber" Xie

Contributions: Amber assisted with the study design and analysis for this manuscript.

Summary: Cost barriers are a well-known issue in asthma care. This study reveals that both partially or uninsured individuals and fully insured patients, especially non-Hispanic Black people, face significant financial challenges. These results emphasize the importance of targeted interventions and policy reforms to reduce cost barriers and promote equitable asthma care access for all patients, regardless of insurance coverage.

Geographic variation in Medicare Advantage nonemergency medical transportation benefits 2020-2024

BDSC Authors: Lesi He

Contributions: Lesi He provided statistical analysis.

Summary: Medicare Advantage (MA) plans increasingly offer nonemergency medical transportation (NEMT) as a benefit to help individuals overcome transportation challenges and access healthcare services. But are these benefits truly aligned with the needs of communities facing the most significant transportation barriers? In this study, we analyze data from 2764 US counties between 2020 and 2024 to explore how NEMT benefit availability matches local transportation challenges. Our findings reveal that NEMT offerings grew by nearly 14% points over the study period, with a higher prevalence of benefits in areas with greater transportation difficulties. Interestingly, counties with higher MA penetration were more likely to offer NEMT benefits in areas with greater transportation barriers, suggesting that MA plan behavior may be influenced by local population needs and market dynamics. These findings may help inform policymakers aiming to promote more targeted, transparent, and equitable benefit designs within MA.

Impact of Previous Pelvic Organ Prolapse Repair on Outcomes of Robotic-assisted Mesh Sacrocolpopexy

BDSC Authors: Kevin Lutz

Contributions: Kevin Lutz performed the statistical analysis for this project and helped with manuscript preparation.

Summary: This study evaluated whether previous pelvic organ prolapse (POP) surgery affects outcomes after robotic-assisted mesh sacrocolpopexy (RASC) in posthysterectomy women. Among 87 patients, success rates were slightly higher in first-time repairs (82%) compared to second-line repairs (73%), though not statistically significant. However, second-line repairs were associated with significantly more perioperative complications. Overall, prior POP surgery did not increase the risk of recurrence but did increase surgical morbidity.

Out-of-Pocket Expenses and Postoperative Therapy after Open Reduction and Internal Fixation of a Distal Radius Fracture

BDSC Authors: Pamela Chan, Jialiang Liu, Donghan Yang

Contributions: Pamela Chan performed the data curation, formal analysis, writing for statistical analysis section, reviewing and editing. Jialiang Liu worked on the data curation, formal analysis, and reviewing and editing of the statisical analysis section. Donghan Yang assisted with the project’s conceptualization, investigation, methodology, supervision, and manuscript writing.

Summary: Hand therapy can be costly because it is often not covered by insurance, excluded from the postoperative global period, and associated with high copayments or deductibles. However, limited data exist on the relationship between out-of-pocket (OOP) expenses and adherence to postoperative hand therapy. Using the Merative MarketScan Commercial Claims and Encounters database, we evaluated surgical- and therapy-related OOP expenses and their association with therapy adherence. We found that one in four patients undergoing open reduction and internal fixation of a distal radius fracture did not receive therapy, and higher surgical and therapy OOP expenses were associated with fewer therapy visits. Given the critical role of therapy in functional recovery, policy changes—such as including therapy visits in the global period—may help improve postinjury rehabilitation.

SBDH-Reader: a large language model-powered method for extracting social and behavioral determinants of health from clinical notes

BDSC Authors: Pamela Chan, Yujia Guo, Lesi He, Mo Yang

Contributions: Lesi He assisted with data curation, formal analysis, investigation, methodology, software, validation, visualization, and manuscript writing. Pamela Chan performed the data curation, formal analysis, and manuscript writing for this project. Yujia Guo assisted with data curation.

Summary: Social and behavioral determinants of health (SBDH) are increasingly recognized as essential for prognostication and informing targeted interventions. Clinical notes often contain details about SBDH in unstructured format. Conventional extraction methods for these data tend to be labor intensive, inaccurate, and/or unscalable. In this study, we aim to develop and validate a large language model (LLM)-powered method to extract structured SBDH data from clinical notes through prompt engineering.

Second-site POLE mutations in the long-term adaptation of ultramutant cancers

BDSC Authors: He Zhang

Contributions: He Zhang participated in the design of this study and performed the bioinformatics analyses, including mutation calling, copy number alteration detection, mutation load assessment, and mutation spectrum analysis.

Summary: Polymerase-associated ultramutagenesis causes extremely high mutation rates in human cancers and is linked to favorable clinical outcomes, including good prognosis and sensitivity to therapy. While high mutation burden could lower cell fitness, the “POL automutation hypothesis” suggests tumor cells may inactivate mutant POLE alleles through second-site mutations to survive. Using mouse models and sequencing, researchers found second-site mutations but not consistently in cis, and human cancer cell lines lacked them. Overall, the data do not support intrinsic cell fitness as the main explanation for ultramutant cancer behavior, pointing instead to immune surveillance or other adaptive mechanisms.

Grants

Examining real-world outcomes of patients with upper gastrointestinal cancers treated with ramucirumab and paclitaxel in the advanced lines

BDSC Authors: Peifeng Ruan

Contributions: Peifeng Ruan was the lead biostatistician for this grant application.

Summary: The approach to second-line treatment of advanced upper GI cancers is guided primarily by the results of a global randomized phase III trial demonstrating the benefit of the combination of ramucirumab and paclitaxel for these patients. However, this combination is associated with high rates of development of chemotherapy-induced peripheral neuropathy in a population of patients who have previously been treated with neurotoxic regimens. FOLFIRI-ramucirumab has emerged as a potential second line treatment strategy in the clinic and endorsed in the guidelines, however data comparing FOLFIRI-ramucirumab and ramucirumab-paclitaxel are sparse. We are proposing a propensity-score matched target trial in the Flatiron Health database to compare outcomes of patients treated with FOLFIRI-ramucirumab and ramucirumab-paclitaxel in the second line for refractory advanced upper GI cancers. We are further proposing an analysis of outcomes of patients treated with ramucirumab-paclitaxel by expression of HER2 and PDL1 biomarkers to better understand the impact of these biomarkers in the advanced line setting. Finally, we will perform an exploratory analysis of primary disease site and outcomes following receipt of ramucirumab-paclitaxel or FOLFIRI-ramucirumab and a description of post-progression therapies and outcomes for these patients.