Appropriate Use Criteria for Neoplastic Compression Fractures.

Background Context: Clinical outcomes are directly related to patient selection and treatment indications for improved quality of life. With emphasis on quality and value, it is essential that treatment recommendations are optimized.

Purpose: The purpose of the North American Spine Society (NASS) Appropriate Use Criteria (AUC) is to determine the appropriate (ie, reasonable) multidisciplinary treatment recommendations for patients with metastatic neoplastic vertebral fractures across a spectrum of more common clinical scenarios.

IFRD1 is required for maintenance of bladder epithelial homeostasis.

The maintenance of homeostasis and rapid regeneration of the urothelium following stress are critical for bladder function. Here, we identify a key role for IFRD1 in maintaining urothelial homeostasis in a mouse model. We demonstrate that the murine bladder expresses IFRD1 at homeostasis, particularly in the urothelium, and its loss alters the global transcriptome with significant accumulation of endolysosomes and dysregulated uroplakin expression pattern.

Inhibition of Ribosome Biogenesis Causes p53-Dependent Death and p53-Independent Dysfunction.

Ribosomes are critical for cell function; their synthesis (known as ribosome biogenesis; "RiBi") is complex and energy-intensive. Surprisingly little is known about RiBi in differentiated cells in adult tissue. Here, we generated mice with conditional deletion of , an essential gene for RiBi and translation, to investigate effects of RiBi blockade We focused on RiBi in a long-lived, ribosome-rich cell population, pancreatic acinar cells, during homeostasis and tumorigenesis.

Origins of cancer: ain't it just mature cells misbehaving?

A pervasive view is that undifferentiated stem cells are alone responsible for generating all other cells and are the origins of cancer. However, emerging evidence demonstrates fully differentiated cells are plastic, can be coaxed to proliferate, and also play essential roles in tissue maintenance, regeneration, and tumorigenesis. Here, we review the mechanisms governing how differentiated cells become cancer cells.

A new role for IFRD1 in regulation of ER stress in bladder epithelial homeostasis.

A healthy bladder requires the homeostatic maintenance of and rapid regeneration of urothelium upon stress/injury/infection. Several factors have been identified to play important roles in urothelial development, injury and disease response, however, little is known about urothelial regulation at homeostasis. Here, we identify a new role for IFRD1, a stress-induced gene that has recently been demonstrated to play a critical role in adult tissue proliferation and regeneration, in maintenance of urothelial function/ homeostasis in a mouse model.

Activation of human STING by a molecular glue-like compound.

Stimulator of interferon genes (STING) is a dimeric transmembrane adapter protein that plays a key role in the human innate immune response to infection and has been therapeutically exploited for its antitumor activity. The activation of STING requires its high-order oligomerization, which could be induced by binding of the endogenous ligand, cGAMP, to the cytosolic ligand-binding domain. Here we report the discovery through functional screens of a class of compounds, named NVS-STGs, that activate human STING.

The coordinated management of ribosome and translation during injury and regeneration.

Diverse acute and chronic injuries induce damage responses in the gastrointestinal (GI) system, and numerous cell types in the gastrointestinal tract demonstrate remarkable resilience, adaptability, and regenerative capacity in response to stress. Metaplasias, such as columnar and secretory cell metaplasia, are well-known adaptations that these cells make, the majority of which are epidemiologically associated with an elevated cancer risk. On a number of fronts, it is now being investigated how cells respond to injury at the tissue level, where diverse cell types that differ in proliferation capacity and differentiation state cooperate and compete with one another to participate in regeneration.

Bringing Excitement to Empirical Business Ethics Research: Thoughts on the Future of Business Ethics.

To commemorate 40 years since the founding of the Journal of Business Ethics, the editors-in-chief of the journal have invited the editors to provide commentaries on the future of business ethics. This essay comprises a selection of commentaries aimed at creating dialog around the theme (inspired by the title of the commentary by Babalola and van Gils). These editors, considering the diversity of empirical approaches in business ethics, envisage a future in which quantitative business ethics research is more bold and innovative, as well as reflexive about its techniques, and dialog between quantitative and qualitative research nourishes the enrichment of both.

An Evidence-Based Guideline for Surveillance of Patients after Curative Treatment for Colon and Rectal Cancer.

Objective: To provide recommendations for a surveillance regimen that leads to the largest overall survival benefit for patients after curative treatment for Stage I-IV colon and rectal cancer.

Methods: Consistent with the Program in Evidence-Based Care's standard approach, guideline databases, i.e.

Models of Follow-Up Care and Secondary Prevention Measures for Survivors of Colorectal Cancer: Evidence-Based Guidelines and Systematic Review.

Objective: To provide recommendations for preferred models of follow-up care for stage I-IV colorectal (CRC) cancer survivors in Ontario; to identify signs and symptoms of potential recurrence and when to investigate; and to evaluate patient information and support needs during the post-treatment survivorship period.

Methods: Consistent with the Program in Evidence-Based Medicine's standardized approach, MEDLINE, EMBASE, PubMed, Cochrane Library, and PROSPERO databases were systematically searched. The authors drafted recommendations and revised them based on the comments from internal and external reviewers.

Regulation of the double-stranded RNA response through ADAR1 licenses metaplastic reprogramming in gastric epithelium.

Cells recognize both foreign and host-derived double-stranded RNA (dsRNA) via a signaling pathway that is usually studied in the context of viral infection. It has become increasingly clear that the sensing and handling of endogenous dsRNA is also critical for cellular differentiation and development. The adenosine RNA deaminase, ADAR1, has been implicated as a central regulator of the dsRNA response, but how regulation of the dsRNA response might mediate cell fate during injury and whether such signaling is cell intrinsic remain unclear.

ELAPOR1 is a secretory granule maturation-promoting factor that is lost during paligenosis.

A single transcription factor, MIST1 (BHLHA15), maximizes secretory function in diverse secretory cells (like pancreatic acinar cells) by transcriptionally upregulating genes that elaborate secretory architecture. Here, we show that the scantly studied MIST1 target, ELAPOR1 (endosome/lysosome-associated apoptosis and autophagy regulator 1), is an evolutionarily conserved, novel mannose-6-phosphate receptor (M6PR) domain-containing protein. ELAPOR1 expression was specific to zymogenic cells (ZCs, the MIST1-expressing population in the stomach).

Direct brainstem somatosensory evoked potentials for cavernous malformations.

Objective: Brainstem cavernous malformations (CMs) often require resection due to their aggressive natural history causing hemorrhage and progressive neurological deficits. The authors report a novel intraoperative neuromonitoring technique of direct brainstem somatosensory evoked potentials (SSEPs) for functional mapping intended to help guide surgery and subsequently prevent and minimize postoperative sensory deficits.

Methods: Between 2013 and 2019 at the Stanford University Hospital, intraoperative direct brainstem stimulation of primary somatosensory pathways was attempted in 11 patients with CMs.

Paligenosis: Cellular Remodeling During Tissue Repair.

Complex multicellular organisms have evolved specific mechanisms to replenish cells in homeostasis and during repair. Here, we discuss how emerging technologies (e.g.

Single-Cell Transcriptomics Reveals a Conserved Metaplasia Program in Pancreatic Injury.

Background & Aims: Acinar to ductal metaplasia (ADM) occurs in the pancreas in response to tissue injury and is a potential precursor for adenocarcinoma. The goal of these studies was to define the populations arising from ADM, the associated transcriptional changes, and markers of disease progression.

Methods: Acinar cells were lineage-traced with enhanced yellow fluorescent protein (EYFP) to follow their fate post-injury.

ATF3 induces RAB7 to govern autodegradation in paligenosis, a conserved cell plasticity program.

Differentiated cells across multiple species and organs can re-enter the cell cycle to aid in injury-induced tissue regeneration by a cellular program called paligenosis. Here, we show that activating transcription factor 3 (ATF3) is induced early during paligenosis in multiple cellular contexts, transcriptionally activating the lysosomal trafficking gene Rab7b. ATF3 and RAB7B are upregulated in gastric and pancreatic digestive-enzyme-secreting cells at the onset of paligenosis Stage 1, when cells massively induce autophagic and lysosomal machinery to dismantle differentiated cell morphological features.

Close Observation versus Additional Surgery after Noncurative Endoscopic Resection of Esophageal Squamous Cell Carcinoma.

Introduction: After noncurative endoscopic submucosal dissection (ESD) of superficial esophageal squamous cell carcinoma (SESCC), additional esophagectomy is generally recommended. However, considering its high mortality and morbidity, it is uncertain if additional surgery improves the clinical outcomes. This study aimed to compare the clinical outcomes between patients who were observed without additional treatment and those who underwent radical esophagectomy.

Patterns of Interaction Between Diffuse Low-Grade Glioma and Pregnancy: An Institutional Case Series.

Background: The occurrence of pregnancy in patients with low-grade glioma (LGG) constitutes a unique therapeutic challenge. Owing to the rarity of cases, there is a dearth of information in existing literature.

Methods: We retrospectively identified all patients with a diagnosis of LGG and pregnancy at some point during their illness.

Management of degenerative spondylolisthesis: development of appropriate use criteria.

Background Context: Outcomes of treatment in care of patients with spinal disorders are directly related to patient selection and treatment indications. However, for many disorders, there is absence of consensus for precise indications. With the increasing emphasis on quality and value in spine care, it is essential that treatment recommendations and decisions are optimized.

Sharps Injuries Related to Subdermal Needles in the Orbicularis Oris During Intraoperative Neurophysiologic Monitoring.

Purpose: Little is known about the incidence and nature of sharps injuries caused by subdermal intraoperative neurophysiologic monitoring (IONM) needle electrodes. In their institution, the authors observed a series of sharps injuries attributed to placement of needles in the orbicularis oris (OO).

Methods: One large academic institution's sharps injury monitoring database was queried for all reported events over 3 years.

Stereotactic body radiation therapy for hepatocellular carcinoma with Macrovascular invasion.

Background: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MVI) is associated with a poor prognosis. The purpose of this study is to describe long-term outcomes of patients with HCC and MVI treated with stereotactic body radiation therapy (SBRT).

Methods: Patients with HCC and MVI who were treated with SBRT from January 2003 to December 2016 were analyzed.

Autophagy repurposes cells during paligenosis.

Differentiated cells have evolved paligenosis, a conserved program to return to a stem or progenitor state and reenter the cell cycle to fuel tissue repair. Paligenosis comprises three sequential stages: 1) quenching of MTORC1 activity with induction of massive macroautophagy/autophagy that remodels differentiated cell architecture; 2) induced expression of progenitor/repair-associated genes; 3) MTORC1 reactivation with cell cycle reentry. Here, we summarize work showing that evolutionarily conserved genes - and - are critical regulators of paligenosis.