Predictors of poor and excellent outcomes following reverse shoulder arthroplasty for glenohumeral osteoarthritis with an intact rotator cuff.

Background: As the indications for reverse total shoulder arthroplasty (RSA) continue to evolve, it has been more commonly utilized for the treatment of glenohumeral osteoarthritis with an intact rotator cuff (GHOA). Given the increased use of RSA for GHOA, it is important to identify factors influential of clinical outcomes. In this study, we sought to identify variables predictive of clinical outcomes following RSA for GHOA.

The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity.

Immune checkpoint blockade is effective for some patients with cancer, but most are refractory to current immunotherapies and new approaches are needed to overcome resistance. The protein tyrosine phosphatases PTPN2 and PTPN1 are central regulators of inflammation, and their genetic deletion in either tumour cells or immune cells promotes anti-tumour immunity. However, phosphatases are challenging drug targets; in particular, the active site has been considered undruggable.

Disease Course, Treatments, and Outcomes of Children With Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease.

Objective: Systemic juvenile idiopathic arthritis-associated lung disease (SJIA-LD) is a life-threatening disease complication. Key questions remain regarding clinical course and optimal treatment approaches. The objectives of the study were to detail management strategies after SJIA-LD detection, characterize overall disease courses, and measure long-term outcomes.

Deep Learning Body Region Classification of MRI and CT Examinations.

This study demonstrates the high performance of deep learning in identification of body regions covering the entire human body from magnetic resonance (MR) and computed tomography (CT) axial images across diverse acquisition protocols and modality manufacturers. Pixel-based analysis of anatomy contained in image sets can provide accurate anatomic labeling. For this purpose, a convolutional neural network (CNN)-based classifier was developed to identify body regions in CT and MRI studies.

Orally efficacious lead of the AVG inhibitor series targeting a dynamic interface in the respiratory syncytial virus polymerase.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory infections in infants and the immunocompromised, yet no efficient therapeutic exists. We have identified the AVG class of allosteric inhibitors of RSV RNA synthesis. Here, we demonstrate through biolayer interferometry and in vitro RNA-dependent RNA polymerase (RdRP) assays that AVG compounds bind to the viral polymerase, stalling the polymerase in initiation conformation.

Endothelial Cell Insulin Signaling Regulates CXCR4 (C-X-C Motif Chemokine Receptor 4) and Limits Leukocyte Adhesion to Endothelium.

Background: An activated, proinflammatory endothelium is a key feature in the development of complications of obesity and type 2 diabetes and can be caused by insulin resistance in endothelial cells.

Methods: We analyzed primary human endothelial cells by RNA sequencing to discover novel insulin-regulated genes and used endothelial cell culture and animal models to characterize signaling through CXCR4 (C-X-C motif chemokine receptor 4) in endothelial cells.

Results: CXCR4 was one of the genes most potently regulated by insulin, and this was mediated by PI3K (phosphatidylinositol 3-kinase), likely through FoxO1, which bound to the CXCR4 promoter.

Task-dependent neural control of regions within human genioglossus.

Anatomical and imaging evidence suggests neural control of oblique and horizontal compartments of the genioglossus differs. However, neurophysiological evidence for differential control remains elusive. This study aimed to determine whether there are differences in neural drive to the oblique and horizontal regions of the genioglossus during swallowing and tongue protrusion.

Data Sharing of Imaging in an Evolving Health Care World: Report of the ACR Data Sharing Workgroup, Part 2: Annotation, Curation, and Contracting.

A core principle of ethical data sharing is maintaining the security and anonymity of the data, and care must be taken to ensure medical records and images cannot be reidentified to be traced back to patients or misconstrued as a breach in the trust between health care providers and patients. Once those principles have been observed, those seeking to share data must take the appropriate steps to curate the data in a way that organizes the clinically relevant information so as to be useful to the data sharing party, assesses the ensuing value of the data set and its annotations, and informs the data sharing contracts that will govern use of the data. Embarking on a data sharing partnership engenders a host of ethical, practical, technical, legal, and commercial challenges that require a thoughtful, considered approach.

Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity.

Epigenetic dysregulation is a defining feature of tumorigenesis that is implicated in immune escape. Here, to identify factors that modulate the immune sensitivity of cancer cells, we performed in vivo CRISPR-Cas9 screens targeting 936 chromatin regulators in mouse tumour models treated with immune checkpoint blockade. We identified the H3K9 methyltransferase SETDB1 and other members of the HUSH and KAP1 complexes as mediators of immune escape.

Let's talk about sex.

Complement gene variation drives sex biases in autoimmune disease.

Nocturnal swallowing augments arousal intensity and arousal tachycardia.

Cortical arousal from sleep is associated with autonomic activation and acute increases in heart rate. Arousals vary considerably in their frequency, intensity/duration, and physiological effects. Sleep and arousability impact health acutely (daytime cognitive function) and long-term (cardiovascular outcomes).

Deep learning in chest radiography: Detection of findings and presence of change.

Background: Deep learning (DL) based solutions have been proposed for interpretation of several imaging modalities including radiography, CT, and MR. For chest radiographs, DL algorithms have found success in the evaluation of abnormalities such as lung nodules, pulmonary tuberculosis, cystic fibrosis, pneumoconiosis, and location of peripherally inserted central catheters. Chest radiography represents the most commonly performed radiological test for a multitude of non-emergent and emergent clinical indications.

Development of an allosteric inhibitor class blocking RNA elongation by the respiratory syncytial virus polymerase complex.

Respiratory syncytial virus (RSV) represents a significant health threat to infants and to elderly or immunocompromised individuals. There are currently no vaccines available to prevent RSV infections, and disease management is largely limited to supportive care, making the identification and development of effective antiviral therapeutics against RSV a priority. To identify effective chemical scaffolds for managing RSV disease, we conducted a high-throughput anti-RSV screen of a 57,000-compound library.

Value-based assessment of robotic pancreas and liver surgery.

Current healthcare economic evaluations are based only on the perspective of a single stakeholder to the healthcare delivery process. A true value-based decision incorporates all of the outcomes that could be impacted by a single episode of surgical care. We define the value proposition for robotic surgery using a stakeholder model incorporating the interests of all groups participating in the provision of healthcare services: patients, surgeons, hospitals and payers.

White Matter Hyperintensity-Adjusted Critical Infarct Thresholds to Predict a Favorable 90-Day Outcome.

Background And Purpose: There is increasing interest in defining stroke lesion volume thresholds to predict poststroke outcome. However, there is a paucity of data on factors that impact the association between critical infarct thresholds volume and outcome. We sought to determine whether lesion thresholds best predicting outcome depend on the degree of preexisting white matter hyperintensity (WMH) lesion burden.

2013 ACR presidential address: a personal view on the future of radiology.

In this address, John A. Patti, MD, acknowledges the celebration and success that radiologists have experienced throughout their careers but also asks incisive questions about how they will face the future. Answers to those questions require an analysis of the past, an understanding of the present, serious and penetrating introspection, and engagement of a process for moving forward.

Measuring membrane voltage with fluorescent proteins.

Measuring signal transduction in large numbers of cells with high spatial and temporal resolution is fundamental to studying information processing in the nervous system. DNA-encoded sensors have an advantage in that they can be introduced into an organism noninvasively and targeted to specific brain regions, cell types, or subcellular compartments. A variety of chimeric proteins that report transmembrane voltage have been developed.

Synthesis and evaluation against hepatitis C virus of 7-deaza analogues of 2'-C-methyl-6-O-methyl guanosine nucleoside and L-Alanine ester phosphoramidates.

7-Deazapurines are known to possess broad antiviral activity, however the 2'-C-methylguanosine analogue displays poor cell permeation and limited phosphorylation, thus is not an efficient inhibitor of hepatitis C virus (HCV) replication. We previously reported the 6-O-methyl entity as a prodrug moiety to increase liphophilicity of guanine nucleosides and the ProTide approach applied to 2'-C-methyl-6-O-methylguanosine has lead to potent HCV inhibitors now in clinical trials. In this Letter, we report the synthesis and biological evaluation of 2'-C-methyl-6-O-methyl-7-deaza guanosine and ProTide derivatives.

Distinct trends of pulsatility found at the necks of ruptured and unruptured aneurysms.

Background: Aneurysm hemodynamics has been shown to be an important factor in aneurysm growth and rupture. Although pulsatility is essential for blood flow and vascular wall function, studies of pulsatile flow properties in brain aneurysm disease are limited.

Objective: To investigate differences in pulsatility within a group of ruptured and unruptured aneurysms by implementing patient-specific pulsatile flow simulation.

Radiology in 2022: challenges and opportunities in the coming decade-proceedings of the 12th Annual ACR Forum.

The 2012 ACR Forum focused on the anticipated challenges and opportunities facing radiology in the next 10 years, centered on the themes of health care reform, future payment models, research and innovation, patient-centered radiology, and information management. The recommendations generated from the forum seek to inform ACR leadership on the best strategies to pursue to ensure the continued success of the profession in the coming decade.