Physiological iron chelators pyrophosphate and citrate have different effects on the proportions of monoferric transferrin metalloforms.

Human serum transferrin can bind up to two iron atoms, one in each of its two domains which are known as the N-lobe and the C-lobe. Ferric pyrophosphate and ferric citrate have been shown to direct loading into the C-lobe and N-lobe, respectively. We report that the iron supplement ferric pyrophosphate citrate directs iron to the C-lobe.

Successful generation of fully human, second generation, anti-CD19 CAR T cells for clinical use in patients with diverse autoimmune disorders.

Background: B-cell targeting chimeric antigen receptor (CAR) T-cell therapies, which lead to profound B-cell depletion, have been well-established in hematology-oncology. This deep B-cell depletion mechanism has prompted the exploration of their use in B-cell driven autoimmune diseases. We herein report on the manufacturing of KYV-101, a fully human anti-CD19 CAR T-cell therapy, derived from patients who were treated across a spectrum of autoimmune diseases.

Empowering Victims of Lived Violence: Delaware's Hospital Violence Intervention Program (HVIP).

Hospital Violence Intervention Programs (HVIP) are increasingly implemented across a variety of healthcare-associated contexts to prevent and address violent intentional injury. We describe the establishment of a health system funded HVIP in Delaware and the direct experiences of staff and violence-specialized Community Health Workers.

Inverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder loci.

The duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a complex genomic rearrangement (CGR). Although it has been identified as an important pathogenic DNA mutation signature in genomic disorders and cancer genomes, its architecture remains unresolved. Here, we studied the genomic architecture of DUP-TRP/INV-DUP by investigating the DNA of 24 patients identified by array comparative genomic hybridization (aCGH) on whom we found evidence for the existence of 4 out of 4 predicted structural variant (SV) haplotypes.

Break-induced replication underlies formation of inverted triplications and generates unexpected diversity in haplotype structures.

Background: The duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a type of complex genomic rearrangement (CGR) hypothesized to result from replicative repair of DNA due to replication fork collapse. It is often mediated by a pair of inverted low-copy repeats (LCR) followed by iterative template switches resulting in at least two breakpoint junctions . Although it has been identified as an important mutation signature of pathogenicity for genomic disorders and cancer genomes, its architecture remains unresolved and is predicted to display at least four structural variation (SV) haplotypes.

Radiation-induced changes in load-sharing and structure-function behavior in murine lumbar vertebrae.

In this study, we used micro-CT-based finite element analysis to investigate the biomechanical effects of radiation on the microstructure and mechanical function of murine lumbar vertebrae. Specifically, we evaluated vertebral microstructure, whole-bone stiffness, and cortical-trabecular load sharing in the L5 vertebral body of mice exposed to ionizing radiation 11 days post exposure (5 Gy total dose;  = 13) and controls ( = 14). Our findings revealed the irradiated group exhibited reduced trabecular bone volume and microstructure ( < 0.

Payment Methods and Demographics Influence Patterns of Dental Service Utilization.

Objective: To describe the patterns of specific dental service utilization among the various sociodemographic groups in North Carolina served by the East Carolina University School of Dental Medicine (ECU SoDM).

Design: This was a descriptive study utilizing self-reported patients' sociodemographic information, payment method history, and CDT codes of procedures performed. Deidentified clinical data recorded for 26 710 patients and 534 983 procedures from 2011 to 2020 were extracted from a centralized axiUm database.

The State of Health and Intentions for Action to Advance Mental Health and Well-being for the Nursing Workforce.

Objective: The aims of this study were to explore the health of nurse leaders and assess intentions to integrate workplace mental health/wellness practices.

Background: National efforts address high rates of poor mental health and lifestyle behaviors among nurses. Few studies describe the extent to which nurse leaders in academic and clinical environments can influence a strategic mission for health/well-being among the nursing workforce.

Barriers to and Outcomes of Initiating Clinical Research at Two Trauma Centers in Mexico.

Introduction: Despite efforts to advance clinical research through collaboration between Latin and North American partners, there remains persistent barriers to performing investigative work. To overcome these obstacles, a team of over 100 surgeon-leaders from 18 Latin American countries founded the Asociación de Cirujanos Traumatólogos de las Américas (ACTUAR). One of ACTUAR's first major collaborative projects, initiated in 2018, was a prospective, observational, multicenter study evaluating quality of life after open tibia fracture management.

The multiple de novo copy number variant (MdnCNV) phenomenon presents with peri-zygotic DNA mutational signatures and multilocus pathogenic variation.

Background: The multiple de novo copy number variant (MdnCNV) phenotype is described by having four or more constitutional de novo CNVs (dnCNVs) arising independently throughout the human genome within one generation. It is a rare peri-zygotic mutational event, previously reported to be seen once in every 12,000 individuals referred for genome-wide chromosomal microarray analysis due to congenital abnormalities. These rare families provide a unique opportunity to understand the genetic factors of peri-zygotic genome instability and the impact of dnCNV on human diseases.

Metal concentrations in wetland plant tissues influences transfer to terrestrial food webs.

Wetland plants tolerate potentially hazardous metals through a variety of strategies, including exclusion or accumulation. Whether plants sequester metals and where they store them in their tissues is important for understanding the potential role of plants as remediators or vectors of metals to terrestrial food webs. Here we evaluate metal sequestration in Great Salt Lake wetlands for one invasive (Phragmites australis; phragmites) and three native plant species, i.

Effect of Computer-Assisted Cognitive Behavior Therapy vs Usual Care on Depression Among Adults in Primary Care: A Randomized Clinical Trial.

Importance: Depression is a common disorder that may go untreated or receive suboptimal care in primary care settings. Computer-assisted cognitive behavior therapy (CCBT) has been proposed as a method for improving access to effective psychotherapy, reducing cost, and increasing the convenience and efficiency of treatment for depression.

Objectives: To evaluate whether clinician-supported CCBT is more effective than treatment as usual (TAU) in primary care patients with depression and to examine the feasibility and implementation of CCBT in a primary care population with substantial numbers of patients with low income, limited internet access, and low levels of educational attainment.

Enhancing the Natural Biological Control in the Thyroid Hormone Homeostasis As a First-Order Control System.

This study explores the natural control system that exists within the pituitary gland. More specifically, this study investigates the regulation of the thyroid stimulating hormone (TSH), released by the anterior pituitary, with regards to the thyroid releasing hormone (TRH), which is released by the hypothalamus. Using appropriate assumptions on the behavior of the hormones, along with relevant boundary conditions, we modeled an output of TSH using constant TRH input over the course of a six-hour period.

Relations Between Bone Quantity, Microarchitecture, and Collagen Cross-links on Mechanics Following In Vivo Irradiation in Mice.

Humans are exposed to ionizing radiation via spaceflight or cancer radiotherapy, and exposure from radiotherapy is known to increase risk of skeletal fractures. Although irradiation can reduce trabecular bone mass, alter trabecular microarchitecture, and increase collagen cross-linking, the relative contributions of these effects to any loss of mechanical integrity remain unclear. To provide insight, while addressing both the monotonic strength and cyclic-loading fatigue life, we conducted total-body, acute, gamma-irradiation experiments on skeletally mature (17-week-old) C57BL/6J male mice ( = 84).

Sustained impact of an academic-practice partnership.

Academic-practice partnerships foster innovation and transition to nursing practice in healthcare systems. The purpose of this paper is to describe the impact of a public-private academic-practice partnership for Doctor of Nursing Practice (DNP) education designed to transform a large healthcare system's nursing workforce and model of care. The conceptual framework is organized around Rogers's (2003) principles of diffusion of innovation in organizations.

Protecting endangered species in the USA requires both public and private land conservation.

Crucial to the successful conservation of endangered species is the overlap of their ranges with protected areas. We analyzed protected areas in the continental USA to assess the extent to which they covered the ranges of endangered tetrapods. We show that in 80% of ecoregions, protected areas offer equal (25%) or worse (55%) protection for species than if their locations were chosen at random.

Dietary countermeasure mitigates simulated spaceflight-induced osteopenia in mice.

Spaceflight is a unique environment that includes at least two factors which can negatively impact skeletal health: microgravity and ionizing radiation. We have previously shown that a diet supplemented with dried plum powder (DP) prevented radiation-induced bone loss in mice. In this study, we investigated the capacity of the DP diet to prevent bone loss in mice following exposure to simulated spaceflight, combining microgravity (by hindlimb unloading) and radiation exposure.

Effects of ex vivo ionizing radiation on collagen structure and whole-bone mechanical properties of mouse vertebrae.

Bone can become brittle when exposed to ionizing radiation across a wide range of clinically relevant doses that span from radiotherapy (accumulative 50 Gy) to sterilization (~35,000 Gy). While irradiation-induced embrittlement has been attributed to changes in the collagen molecular structure, the relative role of collagen fragmentation versus non-enzymatic collagen crosslinking remains unclear. To better understand the effects of radiation on the bone material without cellular activity, we conducted an ex vivo x-ray radiation experiment on excised mouse lumbar vertebrae.

Interchromosomal template-switching as a novel molecular mechanism for imprinting perturbations associated with Temple syndrome.

Background: Intrachromosomal triplications (TRP) can contribute to disease etiology via gene dosage effects, gene disruption, position effects, or fusion gene formation. Recently, post-zygotic de novo triplications adjacent to copy-number neutral genomic intervals with runs of homozygosity (ROH) have been shown to result in uniparental isodisomy (UPD). The genomic structure of these complex genomic rearrangements (CGRs) shows a consistent pattern of an inverted triplication flanked by duplications (DUP-TRP/INV-DUP) formed by an iterative DNA replisome template-switching mechanism during replicative repair of a single-ended, double-stranded DNA (seDNA), the ROH results from an interhomolog or nonsister chromatid template switch.

Impact of Kamishibai Card Process on Compliance With the Central Venous Line Maintenance Bundle.

Background: The Kamishibai Card (K-Card) process is a storytelling methodology designed to help identify barriers and remove or redesign them.

Purpose: The purpose of this study was to evaluate the effectiveness of the K-Card process for central venous line (CVL) maintenance bundle compliance in a pediatric intensive care unit.

Methods: A retrospective evaluation of the implementation of the K-Card process was performed using a pretest and posttest design.

Impact of HCV core gene quasispecies on hepatocellular carcinoma risk among HALT-C trial patients.

Mutations at positions 70 and/or 91 in the core protein of genotype-1b, hepatitis C virus (HCV) are associated with hepatocellular carcinoma (HCC) risk in Asian patients. To evaluate this in a US population, the relationship between the percentage of 70 and/or 91 mutant HCV quasispecies in baseline serum samples of chronic HCV patients from the HALT-C trial and the incidence of HCC was determined by deep sequencing. Quasispecies percentage cut-points, ≥42% of non-arginine at 70 (non-R(70)) or ≥98.

An integrated map of structural variation in 2,504 human genomes.

Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes.