SPACe: an open-source, single-cell analysis of Cell Painting data.

Phenotypic profiling by high throughput microscopy, including Cell Painting, has become a leading tool for screening large sets of perturbations in cellular models. To efficiently analyze this big data, available open-source software requires computational resources usually not available to most laboratories. In addition, the cell-to-cell variation of responses within a population, while collected and analyzed, is usually averaged and unused.

Factors Associated With Recurrent Pediatric Firearm Injury : A 10-Year Retrospective Cohort Analysis.

Background: Firearm injuries are the leading cause of death among children aged 0 to 17 years in the United States.

Objective: To examine the factors associated with recurrent firearm injury among children who presented with acute (index) nonfatal firearm injury in the St. Louis region.

Open Bankart Repair: Technique and Outcomes for the High-Level Athlete.

Historically considered the gold standard technique for glenohumeral instability, the open Bankart repair is being performed at decreased rates because of the current trends favoring arthroscopic Bankart repair and the lack of consistent training of the open technique. However, open Bankart repairs may be more appropriate for certain high-risk populations (ie, high-level collision athletes) because of their reduced recurrent instability rates. Further investigations are needed to identify the indications for arthroscopic versus open Bankart repair and compare their outcomes in high-level athletes.

Clinical Outcomes of Prone Transpsoas Lumbar Interbody Fusion: A 1-Year Follow-Up.

Background: Lateral lumbar interbody fusion (LLIF) is commonly used to address various lumbar pathologies. LLIF using the prone transpsoas (PTP) approach has several potential advantages, allowing simultaneous access to the anterior and posterior columns of the spine. The aim of this study was to report the 1-year outcomes of LLIF via PTP.

Transcriptional coactivation of NRF2 signaling in cardiac fibroblasts promotes resistance to oxidative stress.

We recently discovered that steroid receptor coactivators (SRCs) SRCs-1, 2 and 3, are abundantly expressed in cardiac fibroblasts (CFs) and their activation with the SRC small molecule stimulator MCB-613 improves cardiac function and dramatically lowers pro-fibrotic signaling in CFs post-myocardial infarction. These findings suggest that CF-derived SRC activation could be beneficial in the mitigation of chronic heart failure after ischemic insult. However, the cardioprotective mechanisms by which CFs contribute to cardiac pathological remodeling are unclear.

Characterization of flavonoids with potent and subtype-selective actions on estrogen receptors alpha and beta.

The initial step in estrogen-regulated transcription is the binding of a ligand to its cognate receptors, named estrogen receptors (ERα and ERβ). Phytochemicals present in foods and environment can compete with endogenous hormones to alter physiological responses. We screened 224 flavonoids in our engineered biosensor ERα and ERβ PRL-array cell lines to characterize their activity on several steps of the estrogen signaling pathway.

eEF1A2 promotes PTEN-GSK3β-SCF complex-dependent degradation of Aurora kinase A and is inactivated in breast cancer.

The translation elongation factor eEF1A promotes protein synthesis. Its methylation by METTL13 increases its activity, supporting tumor growth. However, in some cancers, a high abundance of eEF1A isoforms is associated with a good prognosis.

Personal goals of young survivors of violent injury: implications for practice.

Introduction: Firearm injuries are the leading cause of death among young people in the USA and disproportionately impact communities of colour and those experiencing socioeconomic distress. Understanding the personal goals of violently injured patients is essential to identifying protective factors and developing interventions that promote them. However, limited research characterising these personal goals exists.

C5 nerve root palsy (without prior cervical decompression) case series: 9 patients with critical delay to presentation.

Background: Distinguishing between cervical nerve root and intrinsic shoulder pathology can be a difficult task given the overlapping and often coexisting symptoms.

Objective: The objective of this study was to highlight the often-complicated presentation of these symptoms and the subsequent potential for delay in care regarding this subset of patients.

Methods: A total of 9 patients, managed by one of two different surgeons, were identified with a history of C5 nerve root palsy.

A novel ERβ high throughput microscopy platform for testing endocrine disrupting chemicals.

In this study we present an inducible biosensor model for the Estrogen Receptor Beta (ERβ), GFP-ERβ:PRL-HeLa, a single-cell-based high throughput (HT) assay that allows direct visualization and measurement of GFP-tagged ERβ binding to ER-specific DNA response elements (EREs), ERβ-induced chromatin remodeling, and monitor transcriptional alterations via mRNA fluorescence in situ hybridization for a prolactin (PRL)-dsRED2 reporter gene. The model was used to accurately (Z' = 0.58-0.

Gene transcription regulation by ER at the single cell and allele level.

In this short review we discuss the current view of how the estrogen receptor (ER), a pivotal member of the nuclear receptor superfamily of transcription factors, regulates gene transcription at the single cell and allele level, focusing on in vitro cell line models. We discuss central topics and new trends in molecular biology including phenotypic heterogeneity, single cell sequencing, nuclear phase separated condensates, single cell imaging, and image analysis methods, with particular focus on the methodologies and results that have been reported in the last few years using microscopy-based techniques. These observations augment the results from biochemical assays that lead to a much more complex and dynamic view of how ER, and arguably most transcription factors, act to regulate gene transcription.

Analysis and Modeling of Early Estradiol-induced GREB1 Single Allele Gene Transcription at the Population Level.

Unlabelled: Single molecule fluorescence in situ hybridization (smFISH) can be used to visualize transcriptional activation at the single allele level. We and others have applied this approach to better understand the mechanisms of activation by steroid nuclear receptors. However, there is limited understanding of the interconnection between the activation of target gene alleles inside the same nucleus and within large cell populations.

High throughput microscopy and single cell phenotypic image-based analysis in toxicology and drug discovery.

Measuring single cell responses to the universe of chemicals (drugs, natural products, environmental toxicants etc.) is of paramount importance to human health as phenotypic variability in sensing stimuli is a hallmark of biology that is considered during high throughput screening. One of the ways to approach this problem is via high throughput, microscopy-based assays coupled with multi-dimensional single cell analysis methods.

Incidence of and Factors Associated With Recurrent Firearm Injury Among Patients Presenting to St. Louis Trauma Centers, 2010 to 2019 : A Cohort Study.

Background: Firearm injuries are a public health crisis in the United States.

Objective: To examine the incidence and factors associated with recurrent firearm injuries and death among patients presenting with an acute (index), nonfatal firearm injury.

Design: Multicenter, observational, cohort study.

Machine Learning Methods for Endocrine Disrupting Potential Identification Based on Single-Cell Data.

Humans are continuously exposed to a variety of toxicants and chemicals which is exacerbated during and after environmental catastrophes such as floods, earthquakes, and hurricanes. The hazardous chemical mixtures generated during these events threaten the health and safety of humans and other living organisms. This necessitates the development of rapid decision-making tools to facilitate mitigating the adverse effects of exposure on the key modulators of the endocrine system, such as the estrogen receptor alpha (ERα), for example.

Binary Classification of the Endocrine Disrupting Chemicals by Artificial Neural Networks.

We develop a machine learning framework that integrates high content/high throughput image analysis and artificial neural networks (ANNs) to model the separation between chemical compounds based on their estrogenic receptor activity. Natural and man-made chemicals have the potential to disrupt the endocrine system by interfering with hormone actions in people and wildlife. Although numerous studies have revealed new knowledge on the mechanism through which these compounds interfere with various hormone receptors, it is still a very challenging task to comprehensively evaluate the endocrine disrupting potential of all existing chemicals and their mixtures by pure or approaches.

Implementing a hospital-based violence intervention program for assault-injured youth: implications for social work practice.

Youth in the U.S. experience a high rate of assault-related injuries resulting in physical, psychological and social sequelae that require a wide range of services after discharge from the hospital.

Human Rotator Cuff Tears Reveal an Age-Dependent Increase in Markers of Cellular Senescence and Selective Removal of Senescent Cells With Dasatinib + Quercetin Increases Genetic Expression of COL1A1 In Vitro.

Purpose: To quantify cellular senescence in supraspinatus tendon and subacromial bursa of humans with rotator cuff tears and to investigate the in vitro efficacy of the senolytic dasatinib + quercetin (D+Q) to eliminate senescent cells and alter tenogenic differentiation.

Methods: Tissue was harvested from 41 patients (mean age, 62 years) undergoing arthroscopic rotator cuff repairs. In part 1 (n = 35), senescence was quantified using immunohistochemistry and gene expression for senescent cell markers (p16 and p21) and the senescence-associated secretory phenotype (SASP) (interleukin [IL] 6, IL-8, matrix metalloproteinase [MMP] 3, monocyte chemoattractant protein [MCP] 1).

Correlates of Homelessness Among Adults with Personality Disorder.

Although personality disorders (PDs) are more common among persons experiencing homelessness than the general population, few studies have investigated the risk of experiencing homelessness among persons with PDs. This study seeks to identify the demographic, socioeconomic, and behavioral health correlates of past-year homelessness among persons with antisocial, borderline, and schizotypal PDs. Nationally representative data of the civilian, noninstitutionalized population of the United States was used to identify correlates of homelessness.

Anterior Bankart Repair With Superior Capsular Plication Causes Increased Mean Tension in Posterior Glenohumeral Capsule.

Purpose: The purpose of this study is to investigate if a biomechanical difference exists in the prerepair and postrepair states of the posterior inferior glenohumeral ligament (PIGHL) following anterior Bankart repair with respect to capsular tension, labral height, and capsular shift.

Methods: In this study, 12 cadaveric shoulders were dissected to the glenohumeral capsule and disarticulated. The specimens were loaded to 5-mm displacement using a custom shoulder simulator, and measurements were taken for posterior capsular tension, labral height, and capsular shift.

Biomechanical Evaluation of the Efficacy of Suture Tape Augmentation for Subscapularis Peel Repair.

Background: Failure of a subscapularis repair construct after anatomic total shoulder arthroplasty can result in difficulty with internal rotation and an increased likelihood of dislocation. Although suture tape has been demonstrated to be an efficacious augment for tendonous repairs elsewhere in the body, it has not been investigated as a method for augmenting subscapularis peel repairs.

Purpose: To determine the biomechanical efficacy of suture tape augmentation for the repair of a subscapularis peel.

Helping families heal in substance use treatment: A qualitative study about the role of peer support specialists with client families.

Introduction: Peer support specialists (PSS) are people with previous psychiatric illness or substance use disorders who use their experience to support those facing similar hardships. PSS offer a range of beneficial outcomes to both the PSS and clients. The most immediate social connections to those seeking treatment are often their families, yet no PSS studies are inclusive of family involvement.