Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation.

Hematopoietic cell transplantation (HCT) uses cytotoxic chemotherapy and/or radiation followed by intravenous infusion of stem cells to cure malignancies, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. Lung injury is a known complication of the process, due in part to disruption in the pulmonary microenvironment by insults such as infection, alloreactive inflammation and cellular toxicity. How microorganisms, immunity and the respiratory epithelium interact to contribute to lung injury is uncertain, limiting the development of prevention and treatment strategies.

Fuel-Driven Redox Reactions in Electrolyte-Free Polymer Actuators for Soft Robotics.

Polymers that undergo shape changes in response to external stimuli can serve as actuators and offer significant potential in a variety of technologies, including biomimetic artificial muscles and soft robotics. Current polymer artificial muscles possess major challenges for various applications as they often require extreme and non-practical actuation conditions. Thus, exploring actuators with new or underutilized stimuli may broaden the application of polymer-based artificial muscles.

Secondary Impact of the Coronavirus Disease 19 Pandemic on Patients and the Cellular Therapy Healthcare Ecosystem.

The Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has significantly impacted global health and healthcare delivery systems. To characterize the secondary effects of the COVID-19 pandemic and mitigation strategies used in the delivery of hematopoietic stem cell transplantation (HSCT) care, we performed a comprehensive literature search encompassing changes in specific donor collection, processing practices, patient outcomes, and patient-related concerns specific to HSCT and HSCT-related healthcare delivery. In this review, we summarize the available literature on the secondary impacts the COVID-19 pandemic on the fields of HSCT and cellular therapy.

Human Complement C4B Allotypes and Deficiencies in Selected Cases With Autoimmune Diseases.

Human complement C4 is one of the most diverse but heritable effectors for humoral immunity. To help understand the roles of C4 in the defense and pathogenesis of autoimmune and inflammatory diseases, we determined the bases of polymorphisms including the frequent genetic deficiency of C4A and/or C4B isotypes. We demonstrated the diversities of C4A and C4B proteins and their gene copy number variations (CNVs) in healthy subjects and patients with autoimmune disease, such as type 1 diabetes, systemic lupus erythematosus (SLE) and encephalitis.

Impact of Previously Unrecognized HLA Mismatches Using Ultrahigh Resolution Typing in Unrelated Donor Hematopoietic Cell Transplantation.

Purpose: Ultrahigh resolution (UHR) HLA matching is reported to result in better outcomes following unrelated donor hematopoietic cell transplantation, improving survival and reducing post-transplant complications. However, most studies included relatively small numbers of patients. Here we report the findings from a large, multicenter validation study.

Virus detection in the cerebrospinal fluid of hematopoietic stem cell transplant recipients is associated with poor patient outcomes: a CIBMTR contemporary longitudinal study.

Limited data exist on characteristics of central nervous system viruses (CNS-V) in allogeneic hematopoietic stem cell transplant (HCT) recipients. Between 2007 and 2015, the Center for International Blood and Marrow Transplant Research (CIBMTR) received information on 27,532 patients undergoing HCT. Of these, centers reported 165 HCT recipients with CNS-V detected in cerebrospinal fluid within 6 months after HCT.

Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation.

Data are limited on whether to adjust high-dose chemotherapy before autologous hematopoietic cell transplant (autoHCT) in obese patients. This study explores the effects of dose adjustment on the outcomes of obese patients, defined as body mass index (BMI) ≥ 30 kg/m. Dose adjustment was defined as a reduction in standard dosing ≥20%, based on ideal, reported dosing and actual weights.

Neurocognitive Dysfunction in Hematopoietic Cell Transplant Recipients: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Complications and Quality of Life Working Party of the European Society for Blood and Marrow Transplantation.

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and nonmalignant diseases. Despite increasing survival rates, long-term morbidity after HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction after HCT.

Infection Rates among Acute Leukemia Patients Receiving Alternative Donor Hematopoietic Cell Transplantation.

Alternative graft sources (umbilical cord blood [UCB], matched unrelated donors [MUD], or mismatched unrelated donors [MMUD]) enable patients without a matched sibling donor to receive potentially curative hematopoietic cell transplantation (HCT). Retrospective studies demonstrate comparable outcomes among different graft sources. However, the risk and types of infections have not been compared among graft sources.

Surface Disinfection Enabled by a Layer-by-Layer Thin Film of Polyelectrolyte-Stabilized Reduced Graphene Oxide upon Solar Near-Infrared Irradiation.

We report an antibacterial surface that kills airborne bacteria on contact upon minutes of solar near-infrared (NIR) irradiation. This antibacterial surface employs reduced graphene oxide (rGO), a well-known near-infrared photothermal conversion agent, as the photosensitizer and is prepared by assembling oppositely charged polyelectrolyte-stabilized rGO sheets (PEL-rGO) on a quartz substrate with the layer-by-layer (LBL) technique. Upon solar irradiation, the resulting PEL-rGO LBL multilayer efficiently generates rapid localized heating and, within minutes, kills >90% airborne bacteria, including antibiotic-tolerant persisters, on contact, likely by permeabilizing their cellular membranes.

Availability of the basal planes of graphene oxide determines whether it is antibacterial.

There are significant controversies on the antibacterial properties of graphene oxide (GO): GO was reported to be bactericidal in saline, whereas its activity in nutrient broth was controversial. To unveil the mechanisms underlying these contradictions, we performed antibacterial assays under comparable conditions. In saline, bare GO sheets were intrinsically bactericidal, yielding a bacterial survival percentage of <1% at 200 μg/mL.

Chemical and Electrochemical Manipulation of Mechanical Properties in Stimuli-Responsive Copper-Cross-Linked Hydrogels.

Inspiration for the design of new synthetic polymers can be found in the natural world, where materials often exhibit complex properties that change depending on external stimuli. A new synthetic electroplastic elastomer hydrogel (EPEH) that undergoes changes in mechanical properties in response to both chemical and electrochemical stimuli has been prepared based on these precedents. In addition to having the capability to switch between hard and soft states, the presence of both permanent covalent and dynamic copper-based cross links also allows this stimuli-responsive material to exhibit a striking shape memory capability.

Hydrolysis of low concentrations of the acetylthiocholine analogs acetyl(homo)thiocholine and acetyl(nor)thiocholine by acetylcholinesterase may be limited by selective gating at the enzyme peripheral site.

Hydrolysis of acetylcholine by acetylcholinesterase (AChE) is extremely rapid, with a second-order hydrolysis rate constant k(E) (often denoted k(cat)/K(M)) that approaches 10(8) M(-1) s(-1). AChE contains a deep active site gorge with two sites of ligand binding, an acylation site (or A-site) containing the catalytic triad at the base of the gorge and a peripheral site (or P-site) near the gorge entrance. The P-site is known to contribute to catalytic efficiency with acetylthiocholine (AcSCh) by transiently trapping the substrate in a low affinity complex on its way to the A-site, where a short-lived acyl enzyme intermediate is produced.

Manipulating Mechanical Properties with Electricity: Electroplastic Elastomer Hydrogels.

The dawn of the 21st century has brought with it an increasing interest in emulating the adaptive finesse of natural systems by designing materials with on-demand, tunable properties. The creation of such responsive systems could be expected, based on historical precedent, to lead to completely new engineering design paradigms. Using a bioinspired approach of coupling multiple equilibria that operate on different length scales, a material whose bulk mechanical properties can be manipulated by electrical input has been developed.

Drug-like leads for steric discrimination between substrate and inhibitors of human acetylcholinesterase.

Protection of the enzyme acetylcholinesterase (AChE) from the toxic effects of organophosphate insecticides and chemical warfare agents (OPs) may be provided by inhibitors that bind at the peripheral binding site (P-site) near the mouth of the active-site gorge. Compounds that bind to this site may selectively block access to the acylation site (A-site) catalytic serine for OPs, but not acetylcholine itself. To identify such compounds, we employed a virtual screening approach using AutoDock 4.

Molecular basis of inhibition of substrate hydrolysis by a ligand bound to the peripheral site of acetylcholinesterase.

Acetylcholinesterase (AChE) contains a narrow and deep active site gorge with two sites of ligand binding, an acylation site (or A-site) at the base of the gorge and a peripheral site (or P-site) near the gorge entrance. The P-site contributes to the catalytic efficiency of substrate hydrolysis by transiently binding substrates on their way to the acylation site, where a short-lived acyl enzyme intermediate is produced. Ligands that bind to the A-site invariably inhibit the hydrolysis of all AChE substrates, but ligands that bind to the P-site inhibit the hydrolysis of some substrates but not others.

CD22 expression on blastic plasmacytoid dendritic cell neoplasms and reactivity of anti-CD22 antibodies to peripheral blood dendritic cells.

We identified CD22 expression on a blastic plasmacytoid dendritic cell (pDC) neoplasm presenting as a leukemia in a child. CD22 expression, as determined by the antibody s-HCL-1, was also noted on the neoplastic cells from three additional patients with blastic pDC tumors identified at our institution. Subsequently we determined that peripheral blood pDCs react with the s-HCL-1 antibody demonstrating that normal pDCs express CD22.