Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Effectiveness of virtual reality distraction on pain perception and fear among children with cancer undergoing IV cannulation

Background: Cancer children are subjected to multiple cannulations during hospitalization. Pain and fear are most common during invasive procedures that are performed, especially IV cannulation, which can lead to worry. Exactly 25% of children are reported to have a fear of needle-related procedures. To examine the impact of virtual reality (VR) distraction on pain perception and fear in children with cancer undergoing IV cannulation. Materials and Methods: Using a quasi-experimental design, 80 cancer children with IV cannulation between ages 7–18 were recruited to the intervention and control group (N = 40 + 40) using the purposive sampling technique. The virtual reality distraction device was used 10 min before the peripheral IV cannulation procedure and remained in place until the procedure was completed in the intervention group, and no device was used in the control group. Wong–Baker Faces Pain Rating Scale and Children's Fear Scale were used to assess the pain and fear of children and their mothers. Result: Pain perception was found to be significantly lower in the VR distraction group among both children and mothers (1.82 ± 0.18, 8.01 ± 3.21) 95% confidence interval (CI) [0.82, 2.16] compared to the control group, respectively (P = 0.001**). Fear was found to be significantly lower in the VR distraction group among both children and mothers (0.81 ± 0.71, 3.01 ± 1.42) 95% CI [0.46, 0.91]. A strong positive correlation was found between children's and mothers' pain perception (r = 0.91, P = 0.001**) and fear (r = 0.84, P = 0.001**). Conclusion: VR distraction can be used as an effective device in pain and fear management among children undergoing IV cannulation

Vagus nerve stimulation primes platelets and reduces bleeding in hemophilia A male mice

Abstract Deficiency of coagulation factor VIII in hemophilia A disrupts clotting and prolongs bleeding. While the current mainstay of therapy is infusion of factor VIII concentrates, inhibitor antibodies often render these ineffective. Because preclinical evidence shows electrical vagus nerve stimulation accelerates clotting to reduce hemorrhage without precipitating systemic thrombosis, we reasoned it might reduce bleeding in hemophilia A. Using two different male murine hemorrhage and thrombosis models, we show vagus nerve stimulation bypasses the factor VIII deficiency of hemophilia A to decrease bleeding and accelerate clotting. Vagus nerve stimulation targets acetylcholine-producing T lymphocytes in spleen and α7 nicotinic acetylcholine receptors (α7nAChR) on platelets to increase calcium uptake and enhance alpha granule release. Splenectomy or genetic deletion of T cells or α7nAChR abolishes vagal control of platelet activation, thrombus formation, and bleeding in male mice. Vagus nerve stimulation warrants clinical study as a therapy for coagulation disorders and surgical or traumatic bleeding

Proceedings of International Web Conference in Civil Engineering for a Sustainable Planet

This proceeding contains articles of the various research ideas of the academic community and practitioners accepted at the "International Web Conference in Civil Engineering for a Sustainable Planet (ICCESP 2021)". ICCESP 2021 is being Organized by the Habilete Learning Solutions, Kollam in Collaboration with American Society of Civil Engineers (ASCE), TKM College of Engineering, Kollam, and Baselios Mathews II College of Engineering, Kollam, Kerala, India. Conference Title: International Web Conference in Civil Engineering for a Sustainable PlanetConference Acronym: ICCESP 2021Conference Date: 05–06 March 2021Conference Location: Online (Virtual Mode)Conference Organizer: Habilete Learning Solutions, Kollam, Kerala, IndiaCollaborators: American Society of Civil Engineers (ASCE), TKM College of Engineering, Kollam, and Baselios Mathews II College of Engineering, Kollam, Kerala, India