Publications

BACKGROUND: The field of transplant research has long been recognized for its innovative approaches and international collaborations. This study aims to dissect the landscape of global collaborations within transplant research during a past decade.

METHODS: Through a comprehensive bibliometric and network analysis of 5 high-impact factor transplantation journals from 2012 to 2021, we evaluated scientific production and collaboration patterns in 9 250 articles. International, national, and single-institution collaboration types were analyzed, using coauthorship as a measure of scientific collaboration.

RESULTS: The data set revealed 40 622 authors from 2 094 institutions across 94 countries, with a marked increase in international collaborations during the past decade. The United States and Western European countries emerged as central nodes in the global network, facilitating the majority of collaborative efforts. Only 2.2% of potential institutional collaborations were explored during the decade. We found a lower chance of citations for single-institution research over time. Low- and middle-income countries were underrepresented in high-impact transplant research.

CONCLUSIONS: The findings underscore the necessity of fostering inclusive, equitable research collaborations that bridge the gap between high-income countries and low- and middle-income countries, limiting their contributions to advancing global patient care. Practical recommendations for enhancing global collaboration in transplant research include facilitating academic exchanges, equitable collaboration practices, and increased funding opportunities. This study calls for a strategic shift toward a more inclusive and integrated global research landscape, aiming to advance transplant research and patient care universally. Addressing these disparities could lead to a more integrated global research landscape, benefiting transplant research and patient care universally.

MOTIVATION: Nonlinear low-dimensional embeddings allow humans to visualize high-dimensional data, as is often seen in bioinformatics, where datasets may have tens of thousands of dimensions. However, relating the axes of a nonlinear embedding to the original dimensions is a nontrivial problem. In particular, humans may identify patterns or interesting subsections in the embedding, but cannot easily identify what those patterns correspond to in the original data.

RESULTS: Thus, we present SlowMoMan (SLOW Motions on MANifolds), a web application which allows the user to draw a one-dimensional path onto a 2D embedding. Then, by back-projecting the manifold to the original, high-dimensional space, we sort the original features such that those most discriminative along the manifold are ranked highly. We show a number of pertinent use cases for our tool, including trajectory inference, spatial transcriptomics, and automatic cell classification.

AVAILABILITY AND IMPLEMENTATION: Software: https://yunwilliamyu.github.io/SlowMoMan/; Code: https://github.com/yunwilliamyu/SlowMoMan.

The Human BioMolecular Atlas Program (HuBMAP) aims to construct a reference 3D structural, cellular, and molecular atlas of the healthy adult human body. The HuBMAP Data Portal (https://portal.hubmapconsortium.org) serves experimental datasets and supports data processing, search, filtering, and visualization. The Human Reference Atlas (HRA) Portal (https://humanatlas.io) provides open access to atlas data, code, procedures, and instructional materials. Experts from more than 20 consortia are collaborating to construct the HRA's Common Coordinate Framework (CCF), knowledge graphs, and tools that describe the multiscale structure of the human body (from organs and tissues down to cells, genes, and biomarkers) and to use the HRA to understand changes that occur at each of these levels with aging, disease, and other perturbations. The 6th release of the HRA v2.0 covers 36 organs with 4,499 unique anatomical structures, 1,195 cell types, and 2,089 biomarkers (e.g., genes, proteins, lipids) linked to ontologies and 2D/3D reference objects. New experimental data can be mapped into the HRA using (1) three cell type annotation tools (e.g., Azimuth) or (2) validated antibody panels (OMAPs), or (3) by registering tissue data spatially. This paper describes the HRA user stories, terminology, data formats, ontology validation, unified analysis workflows, user interfaces, instructional materials, application programming interface (APIs), flexible hybrid cloud infrastructure, and previews atlas usage applications.

BACKGROUND:  While substantial anatomical study has been pursued throughout the human body, anatomical study of the human lymphatic system remains in its infancy. For microsurgeons specializing in lymphatic surgery, a better command of lymphatic anatomy is needed to further our ability to offer surgical interventions with precision. In an effort to facilitate the dissemination and advancement of human lymphatic anatomy knowledge, our teams worked together to create a map. The aim of this paper is to present our experience in mapping the anatomy of the human lymphatic system.

METHODS:  Three steps were followed to develop a modern map of the human lymphatic system: (1) identifying our source material, which was "Anatomy of the human lymphatic system," published by Rouvière and Tobias (1938), (2) choosing a modern platform, the Miro Mind Map software, to integrate the source material, and (3) transitioning our modern platform into The Human BioMolecular Atlas Program (HuBMAP).

RESULTS:  The map of lymphatic anatomy based on the Rouvière textbook contained over 900 data points. Specifically, the map contained 404 channels, pathways, or trunks and 309 lymph node groups. Additionally, lymphatic drainage from 165 distinct anatomical regions were identified and integrated into the map. The map is being integrated into HuBMAP by creating a standard data format called an Anatomical Structures, Cell Types, plus Biomarkers table for the lymphatic vasculature, which is currently in the process of construction.

CONCLUSION:  Through a collaborative effort, we have developed a unified and centralized source for lymphatic anatomy knowledge available to the entire scientific community. We believe this resource will ultimately advance our knowledge of human lymphatic anatomy while simultaneously highlighting gaps for future research. Advancements in lymphatic anatomy knowledge will be critical for lymphatic surgeons to further refine surgical indications and operative approaches.

OBJECTIVES: To demonstrate that 2 popular cohort discovery tools, Leaf and the Shared Health Research Information Network (SHRINE), are readily interoperable. Specifically, we adapted Leaf to interoperate and function as a node in a federated data network that uses SHRINE and dynamically generate queries for heterogeneous data models.

MATERIALS AND METHODS: SHRINE queries are designed to run on the Informatics for Integrating Biology & the Bedside (i2b2) data model. We created functionality in Leaf to interoperate with a SHRINE data network and dynamically translate SHRINE queries to other data models. We randomly selected 500 past queries from the SHRINE-based national Evolve to Next-Gen Accrual to Clinical Trials (ENACT) network for evaluation, and an additional 100 queries to refine and debug Leaf's translation functionality. We created a script for Leaf to convert the terms in the SHRINE queries into equivalent structured query language (SQL) concepts, which were then executed on 2 other data models.

RESULTS AND DISCUSSION: 91.1% of the generated queries for non-i2b2 models returned counts within 5% (or ±5 patients for counts under 100) of i2b2, with 91.3% recall. Of the 8.9% of queries that exceeded the 5% margin, 77 of 89 (86.5%) were due to errors introduced by the Python script or the extract-transform-load process, which are easily fixed in a production deployment. The remaining errors were due to Leaf's translation function, which was later fixed.

CONCLUSION: Our results support that cohort discovery applications such as Leaf and SHRINE can interoperate in federated data networks with heterogeneous data models.

BACKGROUND: While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking.

METHODS: A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1-365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021.

FINDINGS: Advanced age (HR 2.77, 95%CI 2.53-3.04, p < 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03-4.17, p < 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55-5.00, p < 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14-1.39, p < 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37-0.46, p < 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17-1.54, p < 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20-1.58, p < 0.0001), male sex (HR 1.67, 95%CI 1.45-1.93, p < 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80-13.91, p < 0.0001), and hypertension (HR 1.22, 95%CI 1.10-1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32-1.67) and 365 days (RR 1.54, 95%CI 1.21-1.96) compared to COVID-19 patients with no AKI.

INTERPRETATION: COVID-19-associated AKI was associated with higher mortality, and severe COVID-19-associated AKI was associated with worse long-term post-AKI kidney function recovery.

FUNDING: Authors are supported by various funders, with full details stated in the acknowledgement section.

PURPOSE: In young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population.

METHODS: A retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS.

RESULTS: Among the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%).

CONCLUSION: Trough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor.

Enhancing our understanding of lymphatic anatomy from the microscopic to the anatomical scale is essential to discern how the structure and function of the lymphatic system interacts with different tissues and organs within the body and contributes to health and disease. The knowledge of molecular aspects of the lymphatic network is fundamental to understand the mechanisms of disease progression and prevention. Recent advances in mapping components of the lymphatic system using state of the art single cell technologies, the identification of novel biomarkers, new clinical imaging efforts, and computational tools which attempt to identify connections between these diverse technologies hold the potential to catalyze new strategies to address lymphatic diseases such as lymphedema and lipedema. This manuscript summarizes current knowledge of the lymphatic system and identifies prevailing challenges and opportunities to advance the field of lymphatic research as discussed by the experts in the workshop.

BACKGROUND: In electronic health records, patterns of missing laboratory test results could capture patients' course of disease as well as ​​reflect clinician's concerns or worries for possible conditions. These patterns are often understudied and overlooked. This study aims to identify informative patterns of missingness among laboratory data collected across 15 healthcare system sites in three countries for COVID-19 inpatients.

METHODS: We collected and analyzed demographic, diagnosis, and laboratory data for 69,939 patients with positive COVID-19 PCR tests across three countries from 1 January 2020 through 30 September 2021. We analyzed missing laboratory measurements across sites, missingness stratification by demographic variables, temporal trends of missingness, correlations between labs based on missingness indicators over time, and clustering of groups of labs based on their missingness/ordering pattern.

RESULTS: With these analyses, we identified mapping issues faced in seven out of 15 sites. We also identified nuances in data collection and variable definition for the various sites. Temporal trend analyses may support the use of laboratory test result missingness patterns in identifying severe COVID-19 patients. Lastly, using missingness patterns, we determined relationships between various labs that reflect clinical behaviors.

CONCLUSION: In this work, we use computational approaches to relate missingness patterns to hospital treatment capacity and highlight the heterogeneity of looking at COVID-19 over time and at multiple sites, where there might be different phases, policies, etc. Changes in missingness could suggest a change in a patient's condition, and patterns of missingness among laboratory measurements could potentially identify clinical outcomes. This allows sites to consider missing data as informative to analyses and help researchers identify which sites are better poised to study particular questions.