Benjamin D. Singer
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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: Umbilical Cord Blood Cell Transcriptional and Methylation Signatures at Birth Are Associated with BPD Development
Umbilical Cord Blood Cell Transcriptional and Methylation Signatures at Birth Are Associated with BPD Development Open
Bronchopulmonary dysplasia (BPD) is the most common respiratory disease in preterm infants born at less than 28 weeks gestation. Most existing clinical prediction models for BPD show limited accuracy in predicting BPD development when vali…
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: Maintenance DNA methylation is required for induced Treg reparative function following viral pneumonia in mice
Maintenance DNA methylation is required for induced Treg reparative function following viral pneumonia in mice Open
FOXP3+ natural regulatory T cells (nTregs) promote resolution of inflammation and repair of epithelial damage following viral pneumonia-induced lung injury, thus representing a cellular therapy for patients with severe viral pneumonia and …
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: Understanding Diagnostic Uncertainty: Comparing Pre-Test Probability of Pneumonia to Bronchoalveolar Lavage Results in Critically Ill Patients
Understanding Diagnostic Uncertainty: Comparing Pre-Test Probability of Pneumonia to Bronchoalveolar Lavage Results in Critically Ill Patients Open
Rationale: While clinical criteria are used to diagnose and treat pneumonia in critically ill patients, rates of concordance between a clinicians suspicion for pneumonia and a confirmed diagnosis using bronchoalveolar lavage (BAL) results …
View article: Novel enzyme-based reduced representation method for DNA methylation profiling with low inputs
Novel enzyme-based reduced representation method for DNA methylation profiling with low inputs Open
Commonly used bisulfite-based procedures for DNA methylation sequencing can degrade DNA, worsening signal-to-noise ratios in samples with low DNA input. Enzymatic methylation sequencing (EM-seq) has been proposed as a less biased alternati…
View article: Antibiotic de-escalation patterns and outcomes in critically ill patients with suspected pneumonia as informed by bronchoalveolar lavage results
Antibiotic de-escalation patterns and outcomes in critically ill patients with suspected pneumonia as informed by bronchoalveolar lavage results Open
Purpose Antibiotic stewardship in critically ill pneumonia patients is crucial yet challenging, partly due to the limitations of noninvasive diagnostic tests. This study reports an antibiotic de-escalation pattern informed by bronchoalveol…
View article: AMPK is necessary for Treg functional adaptation to microenvironmental stress during malignancy and viral pneumonia
AMPK is necessary for Treg functional adaptation to microenvironmental stress during malignancy and viral pneumonia Open
CD4+FOXP3+ Treg cells maintain self tolerance, suppress the immune response to cancer, and protect against tissue injury during acute inflammation. Treg cells require mitochondrial metabolism to function, but how Treg cells adapt their met…
View article: Maintenance DNA methylation is required for induced regulatory T cell reparative function following viral pneumonia
Maintenance DNA methylation is required for induced regulatory T cell reparative function following viral pneumonia Open
FOXP3+ natural regulatory T cells (nTregs) promote resolution of inflammation and repair of epithelial damage following viral pneumonia-induced lung injury, thus representing a cellular therapy for patients with acute respiratory distress …
View article: An Observational Cohort Study of Bronchoalveolar Lavage Fluid Galactomannan and <i>Aspergillus</i> Culture Positivity in Patients Requiring Mechanical Ventilation
An Observational Cohort Study of Bronchoalveolar Lavage Fluid Galactomannan and <i>Aspergillus</i> Culture Positivity in Patients Requiring Mechanical Ventilation Open
Background Critically ill patients who develop invasive pulmonary aspergillosis (IPA) have high mortality rates despite antifungal therapy. Diagnosis is difficult in these patients and incidences vary in the literature. Bronchoalveolar lav…
View article: Distinct Control of histone H1 expression within the Histone Locus body by CRAMP1
Distinct Control of histone H1 expression within the Histone Locus body by CRAMP1 Open
Proper histone gene expression is critical to cell viability and maintaining genomic integrity. Multiple histone genes organized into three genomic loci encode for replication coupled core and linker histones. Histone gene expression and t…
View article: The Fifth Annual Symposium of the Midwest Aging Consortium
The Fifth Annual Symposium of the Midwest Aging Consortium Open
As the healthcare burden caused by an increasingly aging population rapidly rises, a pressing need exists for innovative geroscience research that can elucidate aging mechanisms and precipitate the development of therapeutic interventions …
View article: DNAR-11. INHIBITION OF RAD52 ACTIVITY INDUCES DNA DAMAGE BY ACCUMULATING R-LOOPS IN DIFFUSE MIDLINE GLIOMA
DNAR-11. INHIBITION OF RAD52 ACTIVITY INDUCES DNA DAMAGE BY ACCUMULATING R-LOOPS IN DIFFUSE MIDLINE GLIOMA Open
Diffuse midline glioma (DMG) is one of the most devastating childhood cancers with a median survival of < 1year from diagnosis. There is a critical need for new therapeutics for improving treatment outcomes for DMG patients. We performe…
View article: Antibiotic De-escalation Patterns and Outcomes in Critically Ill Patients with Suspected Pneumonia as Informed by Bronchoalveolar Lavage Results
Antibiotic De-escalation Patterns and Outcomes in Critically Ill Patients with Suspected Pneumonia as Informed by Bronchoalveolar Lavage Results Open
Background Antibiotic stewardship in critically ill pneumonia patients is crucial yet challenging, partly due to the limited diagnostic yield of noninvasive infectious tests. In this study, we report an antibiotic prescription pattern info…
View article: Developing and validating a machine learning model to predict successful next-day extubation in the ICU
Developing and validating a machine learning model to predict successful next-day extubation in the ICU Open
Background Criteria to identify patients who are ready to be liberated from mechanical ventilation are imprecise, often resulting in prolonged mechanical ventilation or reintubation, both of which are associated with adverse outcomes. Dail…
View article: DIPG-82. RADIOSENSITIZATION WITH RAD52 INHIBITION IN DIFFUSE MIDLINE GLIOMA
DIPG-82. RADIOSENSITIZATION WITH RAD52 INHIBITION IN DIFFUSE MIDLINE GLIOMA Open
BACKGROUND Diffuse midline glioma (DMG) is one of the most devastating childhood cancers that limited response to radiation therapy (RT). There is a critical need for new therapeutics that enhance the radiation effect. We, therefore, teste…
View article: FOXP3+ Regulatory T Cells Require TBET to Regulate Activated CD8+ T Cells During Recovery from Influenza Infection
FOXP3+ Regulatory T Cells Require TBET to Regulate Activated CD8+ T Cells During Recovery from Influenza Infection Open
FOXP3+ regulatory T (Treg) cells are necessary to coordinate resolution of lung inflammation and a return to homeostasis after respiratory viral infections, but the specific molecular requirements for these functions and the cell types gov…
View article: Novel enzyme-based reduced representation method for DNA methylation profiling with low inputs
Novel enzyme-based reduced representation method for DNA methylation profiling with low inputs Open
DNA methylation at cytosine-phospho-guanine (CpG) residues is a vital biological process that regulates cell identity and function. Although widely used, bisulfite-based cytosine conversion procedures for DNA methylation sequencing require…
View article: Mitochondria regulate proliferation in adult cardiac myocytes
Mitochondria regulate proliferation in adult cardiac myocytes Open
Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of adult cardiomyocytes back to a fe…
View article: Neutrophil percentages in bronchoalveolar lavage fluid: Implications for diagnosing bacterial pneumonia in patients with immunocompromise and neutropenia
Neutrophil percentages in bronchoalveolar lavage fluid: Implications for diagnosing bacterial pneumonia in patients with immunocompromise and neutropenia Open
Rationale Pneumonia is the most common infection in ICU patients and a leading cause for death. Assessment of bronchoalveolar lavage fluid (BALF) cellularity can aid in pneumonia diagnosis. Low percentages (<50%) of BALF neutrophils have a…
View article: Prolonged exposure to lung-derived cytokines is associated with activation of microglia in patients with COVID-19
Prolonged exposure to lung-derived cytokines is associated with activation of microglia in patients with COVID-19 Open
BACKGROUNDSurvivors of pneumonia, including SARS-CoV-2 pneumonia, are at increased risk for cognitive dysfunction and dementia. In rodent models, cognitive dysfunction following pneumonia has been linked to the systemic release of lung-der…
View article: Mediator complex subunit 1 architects a tumorigenic Treg cell program independent of inflammation
Mediator complex subunit 1 architects a tumorigenic Treg cell program independent of inflammation Open
While immunotherapy has revolutionized cancer treatment, its safety has been hampered by immunotherapy-related adverse events. Unexpectedly, we show that Mediator complex subunit 1 (MED1) is required for T regulatory (Treg) cell function s…