G. R. Scott Budinger
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View article: Influenza A infection accelerates disease-associated microglia formation during physiological aging
Influenza A infection accelerates disease-associated microglia formation during physiological aging Open
Severe pneumonia is associated with an increased risk of cognitive decline and dementia, particularly in the elderly. Changes in microglia, the most abundant immune cell population in the brain, are also associated with cognitive decline a…
View article: SuperAging is associated with reduced age‐related cortical neuroinflammation in the absence of neuropathology
SuperAging is associated with reduced age‐related cortical neuroinflammation in the absence of neuropathology Open
Background It is well‐established that average or “normal” aging is associated with a gradual decline of memory capacity. SuperAgers are defined as unique individuals ≥80 years of age who show exceptional memory at least as good as individ…
View article: Age-Based Screening for Lung Cancer Surveillance in the US
Age-Based Screening for Lung Cancer Surveillance in the US Open
Importance Lung cancer is increasingly diagnosed in never-smokers, suggesting that the current US Preventive Services Task Force (USPSTF) screening criteria using low-dose computed tomography exclude many at-risk individuals, thus raising …
View article: Microbial cell-free DNA sequencing of bronchoalveolar lavage fluid improves diagnostic yield and may add clinical utility in immunocompromised patients with severe pneumonia
Microbial cell-free DNA sequencing of bronchoalveolar lavage fluid improves diagnostic yield and may add clinical utility in immunocompromised patients with severe pneumonia Open
Background Despite sophisticated standard of care (SOC) testing (including bronchoalveolar lavage (BAL) fluid culture and multiplex PCR), the etiology of pneumonia in immunocompromised patients is frequently unknown. Microbial cell-free DN…
View article: Systematic data capture reduces the need for source data verification: exploratory analysis from a phase 2 multicenter randomized controlled platform trial
Systematic data capture reduces the need for source data verification: exploratory analysis from a phase 2 multicenter randomized controlled platform trial Open
Background The COVID-19 pandemic gave rise to clinical trials focused on systematic, accurate primary data capture, and reduced reliance on source data verification (SDV). Here, we report on a natural experiment that allowed us to assess t…
View article: Single-cell dissection of chronic lung allograft dysfunction reveals convergent and distinct fibrotic mechanisms
Single-cell dissection of chronic lung allograft dysfunction reveals convergent and distinct fibrotic mechanisms Open
Chronic lung allograft dysfunction (CLAD) is the leading cause of mortality after lung transplantation, yet its molecular mechanisms remain poorly understood. To elucidate the pathogenesis of CLAD, we conducted a comprehensive single-cell …
View article: REN: Anatomically-Informed Mixture-of-Experts for Interstitial Lung Disease Diagnosis
REN: Anatomically-Informed Mixture-of-Experts for Interstitial Lung Disease Diagnosis Open
Mixture-of-Experts (MoE) architectures have significantly contributed to scalable machine learning by enabling specialized subnetworks to tackle complex tasks efficiently. However, traditional MoE systems lack domain-specific constraints e…
View article: Evaluating mortality risk in elderly lung transplant patients
Evaluating mortality risk in elderly lung transplant patients Open
These findings are indicative of advancements in lung transplantation and suggest that the current age-based eligibility standards merit re-evaluation.
View article: Long Term Outcomes of Lung Transplantation in Sensitized Patients Following Eculizumab Use With the Desensitization Protocol
Long Term Outcomes of Lung Transplantation in Sensitized Patients Following Eculizumab Use With the Desensitization Protocol Open
Lung transplantation remains a life-saving option for end-stage pulmonary diseases, but sensitized patients with anti HLA antibodies carry high risk; recent desensitization advances, such as eculizumab, may permit outcomes comparable to no…
View article: Hypercapnia promotes maladaptive airway and vascular remodeling in mice
Hypercapnia promotes maladaptive airway and vascular remodeling in mice Open
CO2 isn't just a gas-it can remodel lungs and worsen COPD, but may be reversible with CO2-lowering therapies.
View article: Profibrotic monocyte-derived alveolar macrophages as a biomarker and therapeutic target in systemic sclerosis-associated interstitial lung disease
Profibrotic monocyte-derived alveolar macrophages as a biomarker and therapeutic target in systemic sclerosis-associated interstitial lung disease Open
Interstitial lung disease (ILD) is present in over 60% of patients with systemic sclerosis (SSc) and is the leading cause of SSc-related deaths. Profibrotic monocyte-derived alveolar macrophages (MoAM) play a causal role in the pathogenesi…
View article: Large language models accurately identify immunosuppression in intensive care unit patients
Large language models accurately identify immunosuppression in intensive care unit patients Open
Objective Rule-based structured data algorithms and natural language processing (NLP) approaches applied to unstructured clinical notes have limited accuracy and poor generalizability for identifying immunosuppression. Large language model…
View article: Developing and validating machine learning models to predict next-day extubation
Developing and validating machine learning models to predict next-day extubation Open
Criteria to identify patients who are ready to be liberated from mechanical ventilation (MV) are imprecise, often resulting in prolonged MV or reintubation, both of which are associated with adverse outcomes. Daily protocol-driven assessme…
View article: Development of a pilot machine learning model to predict successful cure in critically ill patients with community-acquired pneumonia
Development of a pilot machine learning model to predict successful cure in critically ill patients with community-acquired pneumonia Open
Severe community-acquired pneumonia (CAP) remains a major cause of critical illness, yet there are no validated early clinical criteria to predict short-term treatment outcomes in these patients. Short-term pneumonia treatment outcomes are…
View article: Mitochondria dysfunction: cause or consequence of physiologic aging?
Mitochondria dysfunction: cause or consequence of physiologic aging? Open
Mitochondria are no longer viewed solely as ATP- or metabolite-generating organelles but as key regulators of cellular signaling that shape physiologic aging. Contrary to earlier theories linking aging to mitochondrial DNA mutations and ox…
View article: Machine Learning Analysis of Electronic Health Records Identifies Interstitial Lung Disease and Predicts Mortality in Patients with Systemic Sclerosis
Machine Learning Analysis of Electronic Health Records Identifies Interstitial Lung Disease and Predicts Mortality in Patients with Systemic Sclerosis Open
Background Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis (SSc), affecting more than 40% of this population. Despite the availability of effective treatments to stabilize or improve lung f…
View article: Mitochondria complex III–generated superoxide is essential for IL-10 secretion in macrophages
Mitochondria complex III–generated superoxide is essential for IL-10 secretion in macrophages Open
Mitochondrial electron transport chain (ETC) function modulates macrophage biology; however, mechanisms underlying mitochondria ETC control of macrophage immune responses are not fully understood. Here, we report that mutant mice with mito…
View article: Large language models outperform traditional structured data-based approaches in identifying immunosuppressed patients
Large language models outperform traditional structured data-based approaches in identifying immunosuppressed patients Open
Identifying immunosuppressed patients using structured data can be challenging. Large language models effectively extract structured concepts from unstructured clinical text. Here we show that GPT-4o outperforms traditional approaches in i…
View article: Tissue-resident skeletal muscle macrophages promote recovery from viral pneumonia-induced sarcopenia in normal aging
Tissue-resident skeletal muscle macrophages promote recovery from viral pneumonia-induced sarcopenia in normal aging Open
Sarcopenia, which diminishes lifespan and healthspan in the elderly, is commonly exacerbated by viral pneumonia, including influenza and COVID-19. In a study of influenza A pneumonia in mice, young mice fully recovered from sarcopenia, whi…
View article: Metformin targets mitochondrial complex I to lower blood glucose levels
Metformin targets mitochondrial complex I to lower blood glucose levels Open
Metformin is among the most prescribed antidiabetic drugs, but the primary molecular mechanism by which metformin lowers blood glucose levels is unknown. Previous studies have proposed numerous mechanisms by which acute metformin lowers bl…
View article: <i>In silico</i>perturbations provide multivariate interpretability in predicting post-lung transplant outcomes
<i>In silico</i>perturbations provide multivariate interpretability in predicting post-lung transplant outcomes Open
Lung transplantation is a life-saving therapy for end-stage lung disease but has the poorest survival among solid organ transplants. We analyzed standardized electronic health record (EHR) data from the United Network for Organ Sharing (UN…
View article: Inducible CCR2+ nonclassical monocytes mediate the regression of cancer metastasis
Inducible CCR2+ nonclassical monocytes mediate the regression of cancer metastasis Open
A major limitation of immunotherapy is the development of resistance resulting from cancer-mediated inhibition of host lymphocytes. Cancer cells release CCL2 to recruit classical monocytes expressing its receptor CCR2 for the promotion of …