Assessing the Quality of an Online Democratic Deliberation on COVID-19 Pandemic Triage Protocols for Access to Critical Care in an Extreme Pandemic Context: Mixed Methods Study.

Background: Online democratic deliberation (ODD) may foster public engagement in new health strategies by providing opportunities for knowledge exchange between experts, policy makers, and the public. It can favor decision-making by generating new points of view and solutions to existing problems. Deliberation experts recommend gathering feedback from participants to optimize future implementation.

Notch1 blockade by a novel, selective anti-Notch1 neutralizing antibody improves immunotherapy efficacy in melanoma by promoting an inflamed TME.

Background: Immune checkpoint inhibitors (ICI) have dramatically improved the life expectancy of patients with metastatic melanoma. However, about half of the patient population still present resistance to these treatments. We have previously shown Notch1 contributes to a non-inflamed TME in melanoma that reduces the response to ICI.

Morphine-induced intestinal microbial dysbiosis drives TLR-dependent IgA targeting of gram-positive bacteria and upregulation of CD11b and TLR2 on a sub-population of IgA B cells.

IgA binding dictates the composition of the intestinal microbiome and reflects dysbiotic states during chronic disease. Both pathogenic and commensal bacteria differentially bind to IgA with varying outcomes. Little is known regarding IgA dynamics immediately following microbial dysbiosis.

Graduate and Health Professional Student Knowledge, Attitudes, Beliefs, and Behavior Related to Human Papillomavirus and Human Papillomavirus Vaccination: A Scoping Review of the Literature.

Human papillomavirus (HPV) is a common sexually transmitted infection. Despite a safe and effective vaccine, uptake continues to be suboptimal. Recently, focus has moved to college campuses in an effort to increase vaccination rates.

Pharmacy Student Education Related to Opioids: A Scoping Review of the Literature.

Objectives: This scoping review explores and assesses the extent of the literature on the current state of opioid-related training and education of student pharmacists and identifies areas for further research to improve the preparedness of future pharmacists in managing care for patients using opioid medications. This review also examines and maps the literature as it relates to the 4 substance misuse educational content areas (legal/ethical issues; screening, treatment, and stigma; pharmacology and toxicology; and psychosocial aspects) recommended by the 2020 American Association of Colleges of Pharmacy Special Committee on Substance Use and Pharmacy Education.

Findings: A systematic literature search was conducted to identify articles reporting opioid-related educational and training initiatives for student pharmacists in the United States through May 2023.

What are the views of Quebec and Ontario citizens on the tiebreaker criteria for prioritizing access to adult critical care in the extreme context of a COVID-19 pandemic?

Background: The prioritization protocols for accessing adult critical care in the extreme pandemic context contain tiebreaker criteria to facilitate decision-making in the allocation of resources between patients with a similar survival prognosis. Besides being controversial, little is known about the public acceptability of these tiebreakers. In order to better understand the public opinion, Quebec and Ontario's protocols were presented to the public in a democratic deliberation during the summer of 2022.

Interleukin-2 signaling in the regulation of T cell biology in autoimmunity and cancer.

Interleukin-2 (IL-2) is a critical cytokine for T cell peripheral tolerance and immunity. Here, we review how IL-2 interaction with the high-affinity IL-2 receptor (IL-2R) supports the development and homeostasis of regulatory T cells and contributes to the differentiation of helper, cytotoxic, and memory T cells. A critical element for each T cell population is the expression of CD25 (Il2rα), which heightens the receptor affinity for IL-2.

Robust IL-2-dependent antitumor immunotherapy requires targeting the high-affinity IL-2R on tumor-specific CD8 T cells.

Background: Development of interleukin (IL)-2-dependent antitumor responses focus on targeting the intermediate affinity IL-2R to stimulate memory-phenotypic CD8 T and natural killer (NK) cells while minimizing regulatory T cell (Treg) expansion. However, this approach may not effectively engage tumor-specific T effector cells. Since tumor-antigen specific T cells upregulate the high-affinity IL-2R, we tested an IL-2 biologic, mouse IL-2/CD25, with selectivity toward the high-affinity IL-2R to support antitumor responses to tumors that vary in their immunogenicity.

Engineering IL-2 for immunotherapy of autoimmunity and cancer.

Preclinical studies of the T cell growth factor activity of IL-2 resulted in this cytokine becoming the first immunotherapy to be approved nearly 30 years ago by the US Food and Drug Administration for the treatment of cancer. Since then, we have learnt the important role of IL-2 in regulating tolerance through regulatory T cells (T cells) besides promoting immunity through its action on effector T cells and memory T cells. Another pivotal event in the history of IL-2 research was solving the crystal structure of IL-2 bound to its tripartite receptor, which spurred the development of cell type-selective engineered IL-2 products.

High-dose IL-2/CD25 fusion protein amplifies vaccine-induced CD4 and CD8 neoantigen-specific T cells to promote antitumor immunity.

Background: Immunization with tumor neoantigens is a promising vaccine approach to promote antitumor immunity due to their high immunogenicity, lack of expression in normal tissue, and preferential induction of tumor neoantigen-specific T cells, which are central mediators of the anti-cancer response. A drawback to targeting tumor neoantigen-specific T cells is that these cells are found at a low frequency in patients with cancer, limiting their therapeutic benefit. Interleukin-2 (IL-2) promotes expansion and persistence of tumor-reactive T cells.

Online Focus Groups with Parents And Adolescents with Heart Transplants: Challenges and Opportunities.

Pediatric heart transplant recipients are scarce and widely dispersed. Previous studies of adolescents in this population were limited to small homogenous samples. Although online focus groups are an emerging data collection method, its use in pediatric populations has not been fully realized.

Transition to self-management after pediatric heart transplant.

Context: Little is known about adolescent transition to self-management after heart transplant. This gap in knowledge is critically important because the consequences of poor self-management are costly and life-threatening, often resulting in nonadherence, rejection, repeated hospitalizations, and poor quality of life.

Objective: To explore how adolescents and parents perceive their roles in self-management, and how adolescents integrate self-management into their daily lives and navigate the transition from parent-dominated to self-management.

Indometacin ameliorates high glucose-induced proliferation and invasion via modulation of e-cadherin in pancreatic cancer cells.

Indometacin, an inhibitor of cyclooxygenase-2 (COX-2), has been shown to exert anticancer effects in a variety of cancers. However, the effect and mechanism of indometacin on high glucose (HG)-induced proliferation and invasion of pancreatic cancer (PC) cells remain unclear. Multiple lines of evidence suggest that a large portion of pancreatic cancer (PC) patients suffer from either diabetes or HG which contributing PC progression.

ABO-incompatible heart transplantation: analysis of the Pediatric Heart Transplant Study (PHTS) database.

Background: ABO incompatible (ABOi) heart transplantation is an accepted approach to increasing organ availability for young patients. Previous studies have suggested that early survival for ABOi transplants is similar to ABO compatible (ABOc) transplants. We analyzed the Pediatric Heart Transplant Study (PHTS) database from 1/96 to 12/08 to further assess this strategy.

The critical role of the constant region in thermal stability and aggregation of amyloidogenic immunoglobulin light chain.

Light chain (LC) amyloidosis (AL) is a fatal disease in which immunoglobulin LC deposit as fibrils. Although the LC amyloid-forming propensity is attributed primarily to the variable region, fibrils also contain full-length LC comprised of variable-joining (V(L)) and constant (C(L)) regions. To assess the role of C(L) in fibrillogenesis, we compared the thermal stability of full-length LC and corresponding V(L) and C(L) fragments.

Role of glycosaminoglycan sulfation in the formation of immunoglobulin light chain amyloid oligomers and fibrils.

Primary amyloidosis (AL) results from overproduction of unstable monoclonal immunoglobulin light chains (LCs) and the deposition of insoluble fibrils in tissues, leading to fatal organ disease. Glycosaminoglycans (GAGs) are associated with AL fibrils and have been successfully targeted in the treatment of other forms of amyloidosis. We investigated the role of GAGs in LC fibrillogenesis.

A phase I trial of outpatient weekly docetaxel and concurrent radiation therapy for stage III unresectable non small-cell lung cancer: a Vanderbilt Cancer Center Affiliate Network (VCCAN) Trial.

Docetaxel has demonstrated activity as a radiosensitizer in numerous preclinical studies, probably due to its role as a cell cycle synchronizer for the G2/M radiosensitive phase of the cell cycle. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of docetaxel with concurrent thoracic radiation therapy (TRT) to patients with unresectable stage III non small-cell lung cancer (NSCLC). Fifteen patients were entered into this study.

Phase I trial of outpatient weekly docetaxel, carboplatin and concurrent thoracic radiation therapy for stage III unresectable non-small-cell lung cancer: a Vanderbilt cancer center affiliate network (VCCAN) trial.

Purpose: Docetaxel, an active agent for non-small cell lung cancer (NSCLC), has demonstrated activity as a radiosensitizer in numerous pre-clinical studies. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of weekly Docetaxel, Carboplatin with concurrent thoracic radiation therapy (TRT) in patients with unresectable stage III NSCLC.

Patients And Methods: In this phase I clinical trial, Docetaxel was administered weekly as a 1-h intravenous infusion for 6 weeks with a starting dose of 20 mg/m(2).

Esophagitis in combined modality therapy for locally advanced non-small cell lung cancer.

Within the last 10 to 15 years, several randomized trials have validated the importance of chemotherapy in the treatment of locally advanced non-small cell lung cancer and have shown that combined modality therapy improves survival compared with radiotherapy alone. Esophagitis appears to be the primary toxicity, with an increased incidence in combined modality trials. Esophagitis is an inflammatory response of the esophageal mucosa.

Preliminary analysis of a phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small cell lung cancer.

We conducted a prospective phase II study to determine the response rate, toxicity profile, and survival rate among patients with locally advanced unresectable non-small cell lung cancer receiving concurrent weekly paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), carboplatin, and hyperfractionated radiation therapy followed by two cycles of adjuvant paclitaxel and carboplatin. The weekly paclitaxel/carboplatin regimen was designed to optimize the radiosensitizing properties of paclitaxel during the concurrent phase of treatment. Thirty-two patients with unresectable stage IIIA and IIIB non-small cell lung cancer from Vanderbilt Cancer Center Affiliate Network institutions entered the study from June 1996 until February 1997.