Functional dissection of complex and molecular trait variants at single nucleotide resolution.

Identifying the causal variants and mechanisms that drive complex traits and diseases remains a core problem in human genetics. The majority of these variants have individually weak effects and lie in non-coding gene-regulatory elements where we lack a complete understanding of how single nucleotide alterations modulate transcriptional processes to affect human phenotypes. To address this, we measured the activity of 221,412 trait-associated variants that had been statistically fine-mapped using a Massively Parallel Reporter Assay (MPRA) in 5 diverse cell-types.

Can We Use Artificial Intelligence Cluster Analysis to Identify Patients with Metastatic Breast Cancer to the Spine at Highest Risk of Postoperative Adverse Events?

Objective: Group patients who required open surgery for metastatic breast cancer to the spine by functional level and metastatic disease characteristics to identify factors that predispose to poor outcomes.

Methods: A retrospective analysis included patients managed at 2 tertiary referral centers from 2008 to 2020. The primary outcome was a 90-day adverse event.

Assessment of Spinal Metastases Surgery Risk Stratification Tools in Breast Cancer by Molecular Subtype.

Background: Breast cancer molecular features and modern therapies are not included in spine metastasis prediction algorithms.

Objective: To examine molecular differences and the impact of postoperative systemic therapy to improve prognosis prediction for spinal metastases surgery and aid surgical decision making.

Methods: This is a retrospective multi-institutional study of patients who underwent spine surgery for symptomatic breast cancer spine metastases from 2008 to 2021 at the Massachusetts General Hospital and Brigham and Women's Hospital.

Inferring gene regulation from stochastic transcriptional variation across single cells at steady state.

Regulatory relationships between transcription factors (TFs) and their target genes lie at the heart of cellular identity and function; however, uncovering these relationships is often labor-intensive and requires perturbations. Here, we propose a principled framework to systematically infer gene regulation for all TFs simultaneously in cells at steady state by leveraging the intrinsic variation in the transcriptional abundance across single cells. Through modeling and simulations, we characterize how transcriptional bursts of a TF gene are propagated to its target genes, including the expected ranges of time delay and magnitude of maximum covariation.

Feeding intolerance in critically ill patients with COVID-19.

Background & Aims: Early reports suggest significant difficulty with enteral feeding in critically ill COVID-19 patients. This study aimed to characterize the prevalence, clinical manifestations, and outcomes of feeding intolerance in critically ill patients with COVID-19.

Methods: We examined 323 adult patients with COVID-19 admitted to the intensive care units (ICUs) of Massachusetts General Hospital between March 11 and June 28, 2020 who received enteral nutrition.

Engineered composite fascia for stem cell therapy in tissue repair applications.

Unlabelled: A critical challenge in tissue regeneration is to develop constructs that effectively integrate with the host tissue. Here, we describe a composite, laser micromachined, collagen-alginate construct containing human mesenchymal stem cells (hMSCs) for tissue repair applications. Collagen type I was fashioned into laminated collagen sheets to form a mechanically robust fascia that was subsequently laser micropatterned with pores of defined dimension and spatial distribution as a means to modulate mechanical behavior and promote tissue integration.

Programmable bacteria detect and record an environmental signal in the mammalian gut.

The mammalian gut is a dynamic community of symbiotic microbes that interact with the host to impact health, disease, and metabolism. We constructed engineered bacteria that survive in the mammalian gut and sense, remember, and report on their experiences. Based on previous genetic memory systems, we constructed a two-part system with a "trigger element" in which the lambda Cro gene is transcribed from a tetracycline-inducible promoter, and a "memory element" derived from the cI/Cro region of phage lambda.