University of Pennsylvania

All-optical multimodal mapping of single-cell-type-specific metabolic activities via REDCAT

Abstract Metabolism is fundamental to cell function, yet its activities vary across tissue environments. Resolving these processes in situ at single-cell resolution is crucial for understanding physiology in health and disease. However, existing methods lack biochemical specifici...

Metabolic control of smooth muscle cell phenotype switching in atherosclerosis

Abstract The loss of smooth muscle cell (SMC) contractile phenotype contributes to various diseases including atherosclerosis. However, its metabolic basis is not entirely elucidated. Since the transforming growth factor beta (TGFβ) signaling is among principal regulators of SMC...

Reconstruction of epithelial transcriptional trajectories reveals heterogeneous progression and early therapy-resistance programs in high-grade serous carcinoma precursors

Abstract Background Serous-tubal intraepithelial-carcinoma (STIC) is considered the principal precursor of tubo-ovarian high-grade serous-carcinoma (HGSC), yet its biological uniformity, progression risk and potential response to poly(ADP-ribose) polymerase-inhibitors (PARPi) rem...

Self-rankings as a predictor of scientific impact beyond peer review

Abstract Peer review in academic research aims to ensure factual correctness and identify work of high scientific potential, but rapid submission growth has made this increasingly difficult. Here we investigate an additional measure for identifying high-impact research: authors’...

Adaptive model-guided protein evolution with sparse data optimizes compact eukaryotic genome editors

Efficient protein engineering is constrained by vast sequence space and limited experimental throughput, particularly for protein families that lack large mutational datasets. Here we combine Fanzor2 (Fz2) ortholog discovery, ωRNA scaffold engineering and EvoMax, a model-guided p...

Minimax-Optimal Reward-Agnostic Exploration in Reinforcement Learning

This paper studies reward-agnostic exploration in reinforcement learning (RL)—a scenario where the learner is unaware of the reward functions during the exploration stage—and designs an algorithm that improves over the state of the art. More precisely, consider a finite-horizon i...

Videographic Assessment of Preintubation Checklist Use in Pediatric Emergency Departments: A NEAR4PEM Checklist Feasibility Study

OBJECTIVES: Cognitive aids are widely used in pediatric emergency departments (PEDs), yet real-world use is difficult to assess via self-report or the medical record. We used video review to assess whether (adoption) and how (fidelity) the NEAR4PEM Preintubation Checklist was use...

Total-body [11C]carfentanil PET: Liver-brain axis in methadone vs. buprenorphine treatment

Abstract Purpose To examine the relationship between brain mu opioid receptor (MOR) availability and liver activity in opioid use disorder (OUD) patients treated with methadone (MET) or buprenorphine (BUP). Methods 10 OUD patients, 5 treated with MET and 5 with BUP, as well as 13...

Longitudinal weighted and trimmed treatment effects with flip interventions

Weighting and trimming are popular methods for addressing positivity violations in causal inference. While well-studied with single-timepoint data, standard methods do not easily generalize to longitudinal data and remain vulnerable to time-varying positivity violations. We exten...

Engineering a biomimetic multiphasic suture anchor system for enhanced rotator cuff enthesis regeneration

Abstract Conventional suture anchor methods in rotator cuff repair often fail to replicate the native tendon-to-bone interface, leading to re-tears due to stress concentrations and poor biological integration at anchor sites. To address these challenges, we engineered a biomimeti...

Selecting the number of components in PCA via random signflips

Principal component analysis (PCA) is a foundational tool in modern data analysis, and a crucial step in PCA is selecting the number of components to keep. However, classical selection methods (e.g., scree plots, parallel analysis, etc.) lack statistical guarantees in the increas...

Single-Molecule Imaging Reveals ERK-Dependent Spatial Translation in Cardiomyocytes

BACKGROUND: Translational control of gene expression is crucial in cardiomyocytes, particularly in response to hypertrophic stimuli. The ERK (extracellular signal-regulated kinase) pathway plays a key role in inducing cardiac hypertrophy and regulating specific protein translatio...

Assessing the need for reproductive genetic counseling among adults with cystic fibrosis

Abstract Background Reproductive health has become an increasingly important focus for people with cystic fibrosis (CF), and guidelines have recommended routine inclusion of genetic counselors on care teams to address questions regarding infertility, pregnancy planning, prenatal...

Improved specificity of a probe-based real-time PCR for the detection of Dirofilaria immitis in canine blood

Abstract Background Dirofilaria immitis is a vector-borne filarioid nematode distributed worldwide and endemic across most of North America. In dogs, it is considered the most important parasite and a known cause of acquired cardiomyopathy. Clinically, canine heartworm disease ca...

Corticolimbic structure-function coupling is sensitive to childhood adversity and buffers adversity-related symptoms during development

Abstract Childhood adversity is a potent predictor of mental health problems across the lifespan, and a rich cross-species literature implicates stress-sensitive corticolimbic circuits in adversity-related psychopathology. Structure-function coupling (SFC) is a promising multimod...

Conformal network link prediction with false discovery rate control under unstructured missingness

We propose a new method for predicting multiple missing links in partially observed networks while controlling the false discovery rate (FDR), a largely unresolved challenge in network analysis. The main difficulty lies in handling complex dependencies and unknown missing pattern...

Conceptual Shift inOur Understanding of DegenerateRadical Spin Systems: Spin-Rotation Coupling Turned on Its Head

Abstract For most chemists, Kramers’ degeneracy refers to the fact that for any radical system, every potential energy surface is at least doubly degenerate (with spin up and spin down, time-reversed solutions) for all nuclear positions X. Yet, as is well-known to the community o...

Long-Term Fatigue After Treatment for Breast Cancer

Importance Patients with breast cancer (BC) may have long-term fatigue after treatment, which is associated with reduced quality of life. Objective To identify cardiac, psychological, and cancer treatment factors associated with fatigue before and 24 months after BC treatment. De...

Restoration of oscillatory shear stress in humans activates an endothelial protective genetic program and prevents DVT

Deep vein thrombosis (DVT) is a major cause of morbidity and mortality in critically ill patients. DVT clots typically form in the sinus of the deep venous valves and are strongly associated with immobility and reduced venous flow. Physical activity alters venous blood flow, gene...

A nose-to-brain circuit underlies anxiety regulation by nasal afferent frequency in mice

Slow nasal breathing alleviates negative moods, but the precise nose-to-limbic pathways and their causal contributions remain unclear. Here, we identify a pathway in mice from olfactory sensory neurons (OSNs) in the nasal cavity to mitral cells in the olfactory bulb (OB), then to...