Delivery of Plasmid DNA by Ionizable Lipid Nanoparticles to Induce CAR Expression in T Cells.

Introduction: Chimeric antigen receptor (CAR) cell therapy represents a hallmark in cancer immunotherapy, with significant clinical results in the treatment of hematological tumors. However, current approved methods to engineer T cells to express CAR use viral vectors, which are integrative and have been associated with severe adverse effects due to constitutive expression of CAR. In this context, non-viral vectors such as ionizable lipid nanoparticles (LNPs) arise as an alternative to engineer CAR T cells with transient expression of CAR.

Long-Term Outcomes and Predictors of Response in Breast Cancer Patients with Advanced Nodal Involvement.

Background: Advanced nodal disease is associated with poor prognosis. However, modern neoadjuvant systemic therapy (NST) regimens have resulted in higher pathologic complete response (pCR) rates, which are associated with improved survival. We sought to assess contemporary outcomes in patients with advanced nodal involvement and response to NST.

A review of ecosystem services from edge-of-field practices in tile-drained agricultural systems in the United States Corn Belt Region.

Edge-of-field management practices that reduce nutrient pollution from tile drainage while contributing habitat and other ecosystem services are needed to enhance agricultural systems in the US Corn Belt Region. In this review, we identified edge-of-field and catchment scale agricultural conservation practices for intercepting and treating tile drainage. The reviewed conservation practices were (1) controlled drainage, also known as drainage water management (USDA-NRCS Code 554); (2) drainage water recycling (USDA-NRCS Code 447); (3) denitrifying bioreactors (USDA-NRCS Code 605); (4) saturated buffers (USDA-NRCS Code 604); and (5) constructed or restored wetlands designed for water quality improvement (USDA-NRCS Code 656) herein referred to as water quality wetlands.

Neck scar perception after neck dissection in HPV-associated oropharyngeal squamous cell carcinoma.

Importance: While there has been an increased understanding of the impact of visible neck scars in some patients with certain diseases, this has not yet been explored in the HPV+ OPSCC population.

Objective: To understand patients' perception of their scar and the impact on their quality of life (QOL) at least 6 months after neck dissection (ND) for HPV+ oropharyngeal squamous cell carcinoma (OPSCC).

Design, Setting, And Participants: In this retrospective case-control study, patients who underwent primary transoral robotic surgery (TORS) and ND for HPV+ OPSCC between 2016 and 2021 at a single tertiary care center were identified.

Latent class analysis of perceived stigma among older adults receiving medications for opioid use disorder.

Rationale: Public stigma surrounds individuals who use medication for their recovery from a substance use disorder. However, we know little about subgroups of individuals with varying levels of perceived stigma and how these levels may be associated with physical and mental health-related quality of life (HRQOL) and social support.

Methods: We used latent class analysis to define subgroups of people aged 50-72 years of age (N = 104) who were enrolled in eight medication for opioid use disorder (MOUD) programs to explore subgroupings and correlates of group membership.

Clinical characteristics of chylothorax: results from the International Collaborative Effusion database.

Background: Chylothorax is an uncommon medical condition for which limited data are available regarding the contemporary aetiology, management and outcomes. The goal of this study was to better define these poorly characterised features.

Methods: The medical records of adult patients diagnosed with chylothorax at 12 centres across Europe, America and South Africa from 2009-2021 were retrospectively reviewed.

Quantum-Enhanced Magnetometry at Optimal Number Density.

We study the use of squeezed probe light and evasion of measurement backaction to enhance the sensitivity and measurement bandwidth of an optically pumped magnetometer (OPM) at sensitivity-optimal atom number density. By experimental observation, and in agreement with quantum noise modeling, a spin-exchange-limited OPM probed with off-resonance laser light is shown to have an optimal sensitivity determined by density-dependent quantum noise contributions. Application of squeezed probe light boosts the OPM sensitivity beyond this laser-light optimum, allowing the OPM to achieve sensitivities that it cannot reach with coherent-state probing at any density.

SWATH-MS Analysis of Blood Plasma and Circulating Small Extracellular Vesicles Enables Detection of Putative Protein Biomarkers of Fertility in Young and Aged Dairy Cows.

The development of biomarkers of fertility could provide benefits for the genetic improvement of dairy cows. Circulating small extracellular vesicles (sEVs) show promise as diagnostic or prognostic markers since their cargo reflects the metabolic state of the cell of origin; thus, they mirror the physiological status of the host. Here, we employed data-independent acquisition mass spectrometry to survey the plasma and plasma sEV proteomes of two different cohorts of Young (Peripubertal; = 30) and Aged (Primiparous; = 20) dairy cows () of high- and low-genetic merit of fertility and known pregnancy outcomes (ProteomeXchange data set identifier PXD042891).

The kid who couldn't burp: the management of a pediatric case of retrograde cricopharyngeal dysfunction.

Retrograde cricopharyngeal dysfunction is a newly described syndrome characterized by the inability to belch, loud abdominal gurgling, excessive flatulence, and pain or distension of the low neck, chest, or abdomen. Treatment is with botulinum toxin injection into the cricopharyngeus muscle. We present a pediatric case of this syndrome to increase awareness among the medical community and for clinicians to expand their index of suspicion for retrograde cricopharyngeal dysfunction.

Dysregulated meta-organismal metabolism of aromatic amino acids in alcohol-associated liver disease.

Background: Chronic alcohol consumption impairs gut barrier function and perturbs the gut microbiome. Although shifts in bacterial communities in patients with alcohol-associated liver disease (ALD) have been characterized, less is known about the interactions between host metabolism and circulating microbe-derived metabolites during the progression of ALD.

Methods: A large panel of gut microbiome-derived metabolites of aromatic amino acids was quantified by stable isotope dilution liquid chromatography with online tandem mass spectrometry in plasma from healthy controls (n = 29), heavy drinkers (n = 10), patients with moderate (n = 16) or severe alcohol-associated hepatitis (n = 40), and alcohol-associated cirrhosis (n = 10).

Evaluating a social and emotional well-being model of service piloted in Aboriginal Community Controlled Health Services in Western Australia: an Aboriginal Participatory Action Research approach.

Introduction: The delivery of services to improve Aboriginal health and well-being must centre culture and integrate a social and emotional well-being understanding and approaches. These approaches are essential in increasing access to, and engagement with, health services, as well as ensuring culturally safe, person-centred and community-centred care. This study will evaluate the Aboriginal Health Council of Western Australia's social and emotional well-being model of service being piloted in five Aboriginal Community Controlled Health Services across five of Western Australia's regions.

siRNA Lipid-Polymer Nanoparticles Targeting E-Selectin and Cyclophilin A in Bone Marrow for Combination Multiple Myeloma Therapy.

Introduction: Multiple myeloma (MM) is a hematological blood cancer of the bone marrow that remains largely incurable, in part due to its physical interactions with the bone marrow microenvironment. Such interactions enhance the homing, proliferation, and drug resistance of MM cells. Specifically, adhesion receptors and homing factors, E-selectin (ES) and cyclophilin A (CyPA), respectively, expressed by bone marrow endothelial cells enhance MM colonization and dissemination.

Upregulation of exosome secretion from tumor-associated macrophages plays a key role in the suppression of anti-tumor immunity.

Macrophages play a pivotal role in tumor immunity. We report that reprogramming of macrophages to tumor-associated macrophages (TAMs) promotes the secretion of exosomes. Mechanistically, increased exosome secretion is driven by MADD, which is phosphorylated by Akt upon TAM induction and activates Rab27a.

Patient Interest in Exploring Nonsurgical Treatment Approaches for Early-Stage Breast Cancer: A Qualitative Study.

Purpose: Advances in radiation therapy have enabled the ability to deliver ablative treatments, but there has been limited application of these treatments to early-stage breast cancers with a goal of omitting surgery. The purpose of this study was to explore patient interest in pursuing nonsurgical treatment approaches for their early-stage breast cancer.

Methods And Materials: We conducted a qualitative study involving interviews with 21 patients with early-stage breast cancer who were eligible for participation in a phase 2 clinical trial offering omission of definitive surgery.

The impact of a structured assessment and decision tool (I-DECIDED®) on improving care of peripheral intravenous catheters: A multicenter, interrupted time-series study.

Background: Peripheral intravenous catheters are the most widely used invasive device in hospitals but have serious risks.

Objective: To determine if a structured assessment and decision tool (I-DECIDED®) improves daily peripheral intravenous catheter assessment and care decisions.

Design: Prospective, interrupted time-series study.

Metastatic Leptomeningeal Carcinomatosis From Primary Lobular Breast Cancer Found in a Medical School Cadaveric Dissection.

Leptomeningeal carcinomatosis (LC) is an uncommon sequelae of metastatic cancer affecting the pia and arachnoid mater. It has been postulated that recent improvements in cancer patient survival time have increased the frequency of LC and other rare metastatic conditions that patients previously would not have lived long enough to experience. LC carries a universally poor prognosis with a mean survival of between two to four months if treated; however, the recent increase in incidence has allowed for further research into the condition and potential treatments.

Membrane protein chaperone and sodium chloride modulate the kinetics and morphology of amyloid beta aggregation.

Protein aggregation is a biological phenomenon caused by the accumulation of misfolded proteins. Amyloid beta (Aβ) peptides are derived from the cleavage of a larger membrane protein molecule and accumulate to form plaques extracellularly. According to the amyloid hypothesis, accumulation of Aβ aggregates in the brain is primarily responsible for the pathogenesis of Alzheimer's disease (AD).

Taxonomy and Molecular Phylogeny of the Sea Anemone (Haddon, 1898) (Cnidaria, Actiniaria), with a Description of a New Species from Singapore.

Sea anemones (Cnidaria, Actiniaria) are a successful group of marine invertebrates found in a diverse range of environments globally. In spite of their ubiquity, identities for many sea anemones remain unverified, especially those from the Indo-West Pacific region. Here, we clarify the taxonomy of the poorly known , a shallow-water species first described from the Torres Straits in northern Australia.

Circulating biomarkers of extracellular matrix dysregulation are associated with adverse post-stage 2 outcomes in infants with single ventricle heart disease.

Children with single ventricle heart disease (SVHD) experience morbidity due to inadequate pulmonary blood flow. Using proteomic screening, our group previously identified members of the matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP), and fibroblast growth factor (FGF) families as potentially dysregulated in SVHD. No prior study has taken a targeted approach to mapping circulating levels of these protein families or their relationship to pulmonary vascular outcomes in SVHD.

One size does not fit all - Trehalose metabolism by is variable across the five phylogenetic lineages.

, the leading cause of antibiotic-associated diarrhoea worldwide, is a genetically diverse species which can metabolise a number of nutrient sources upon colonising a dysbiotic gut environment. Trehalose, a disaccharide sugar consisting of two glucose molecules bonded by an α 1,1-glycosidic bond, has been hypothesised to be involved in the emergence of hypervirulence due to its increased utilisation by the RT027 and RT078 strains. Here, growth in trehalose as the sole carbon source was shown to be non-uniform across representative strains, even though the genes for its metabolism were induced.

Communicator Extraordinaire: Extracellular Vesicles in the Tumor Microenvironment Are Essential Local and Long-Distance Mediators of Cancer Metastasis.

Human tumors are increasingly being described as a complex "ecosystem", that includes many different cell types, secreted growth factors, extracellular matrix (ECM) components, and microvessels, that altogether create the tumor microenvironment (TME). Within the TME, epithelial cancer cells control the function of surrounding stromal cells and the non-cellular ECM components in an intricate orchestra of signaling networks specifically designed for cancer cells to exploit surrounding cells for their own benefit. Tumor-derived extracellular vesicles (EVs) released into the tumor microenvironment are essential mediators in the reprogramming of surrounding stromal cells, which include cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), tumor-infiltrating lymphocytes (TILs), and tumor endothelial cells (TECs), which are responsible for the promotion of neo-angiogenesis, immune cell evasion, and invasion which are essential for cancer progression.

Outcomes After Hybrid Palliation for Infants With Critical Left Heart Obstruction.

Background: Hybrid palliation (bilateral pulmonary artery banding with or without ductal stenting) is an initial management strategy for infants with critical left heart obstruction and serves as palliation until subsequent operations are pursued.

Objectives: This study sought to determine patient characteristics and factors associated with subsequent outcomes for infants who underwent hybrid palliation.

Methods: From 2005 to 2019, 214 of 1,236 prospectively enrolled infants within the Congenital Heart Surgeons' Society's critical left heart obstruction cohort underwent hybrid palliation across 24 institutions.

Values Expressed by Women Veterans Receiving Treatment for Chronic Insomnia Disorder.

Objectives: Insomnia may contribute to fewer value-consistent choices and less engagement in meaningful life activities. We sought to identify values commonly expressed by women veterans engaged in a trial testing psychological treatment of insomnia disorder.

Methods: Seventy-four women veterans (mean age = 48.

Automated contouring and statistical process control for plan quality in a breast clinical trial.

Background And Purpose: Automatic review of breast plan quality for clinical trials is time-consuming and has some unique challenges due to the lack of target contours for some planning techniques. We propose using an auto-contouring model and statistical process control to independently assess planning consistency in retrospective data from a breast radiotherapy clinical trial.

Materials And Methods: A deep learning auto-contouring model was created and tested quantitatively and qualitatively on 104 post-lumpectomy patients' computed tomography images (nnUNet; train/test: 80/20).

Patient-Reported Outcomes of Omission of Breast Surgery Following Neoadjuvant Systemic Therapy: A Nonrandomized Clinical Trial.

Importance: Patients should have an active role in decisions about pursuing or forgoing specific therapies in treatment de-escalation trials.

Objective: To evaluate longitudinal patient-reported outcomes (PROs) encompassing decisional comfort and health-related quality of life (HRQOL) among patients who elected to enroll in a clinical trial evaluating radiotherapy alone, without breast surgery, for invasive breast cancers with exceptional response to neoadjuvant systemic therapy (NST).

Design, Setting, And Participants: Prospective, single-group, phase 2 clinical trial at 7 US medical centers.