Donor Specific Antibodies in Extracorporeal Membrane Oxygenation-Bridged Lung Transplant Recipients.

Background: Extracorporeal membrane oxygenation (ECMO) is increasingly used as a bridge to lung transplantation. Although other mechanical circulatory support devices have been associated with anti-human leukocyte antigen antibody formation, including de novo donor-specific antibodies (dnDSA), it is unknown whether ECMO is a sensitizing exposure.

Methods: This was a single-center retrospective cohort study of lung transplant recipients.

Layer-specific anatomical and physiological features of the retina's neurovascular unit.

The neurovascular unit (NVU), comprising vascular, glial, and neural elements, supports the energetic demands of neural computation, but this aspect of the retina's trilaminar vessel network is poorly understood. Only the innermost vessel layer-the superficial vascular plexus (SVP)-is associated with astrocytes, like brain capillaries, whereas radial Müller glia interact with vessels in the other layers. Using serial electron microscopic reconstructions from mouse and primate retina, we find that Müller processes cover capillaries in a tessellating pattern, mirroring the wrapping of brain capillaries by tiled astrocytic endfeet.

Co-regulator activity of Mediator of DNA Damage Checkpoint 1 (MDC1) is associated with DNA repair dysfunction and PARP inhibitor sensitivity in lobular carcinoma of the breast.

Invasive lobular carcinoma of the breast (ILC) are typically estrogen receptor α (ER)-positive and present with biomarkers of anti-estrogen sensitive disease, yet patients with ILC face uniquely poor long-term outcomes with increased recurrence risk, suggesting endocrine response and ER function are unique in ILC. We previously found specifically in ILC cells that ER is co-regulated by the DNA repair protein Mediator of DNA Damage Checkpoint 1 (MDC1). This novel MDC1 activity, however, was associated with dysfunction in the canonical DNA repair activity of MDC1, but absent typical features of DNA repair deficiency.

An injury-induced mesenchymal-epithelial cell niche coordinates regenerative responses in the lung.

Severe lung injury causes airway basal stem cells to migrate and outcompete alveolar stem cells, resulting in dysplastic repair. We found that this "stem cell collision" generates an injury-induced tissue niche containing keratin 5 epithelial cells and plastic Pdgfra mesenchymal cells. Single-cell analysis revealed that the injury-induced niche is governed by mesenchymal proliferation and Notch signaling, which suppressed Wnt/Fgf signaling in the injured niche.

Implementing Precision Medicine for Dilated Cardiomyopathy: Insights from The DCM Consortium.

Background: Clinical genetic evaluation of dilated cardiomyopathy (DCM) is implemented variably or not at all. Identifying needs and barriers to genetic evaluations will enable strategies to enhance precision medicine care.

Methods: An online survey was conducted in June 2024 among cardiologist investigators of the DCM Consortium from US advanced heart failure/transplant (HF/TX) programs to collect demographics, training, program characteristics, genetic evaluation practices for DCM, and implementation needs.

Tolerability and Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists in Lung Transplant Recipients: A Single Center Report.

Introduction: Diabetes and obesity increase risk of death after lung transplantation. Optimal treatment of diabetes and obesity may improve post-transplant outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are FDA-approved to treat diabetes and obesity and demonstrate improvement in renal and cardiovascular outcomes in the general population.

Geometric tortuosity at invaginating rod synapses slows glutamate diffusion and shapes synaptic responses: insights from anatomically realistic Monte Carlo simulations.

At the first synapse in the vertebrate retina, rod photoreceptor terminals form deep invaginations occupied by multiple second-order rod bipolar and horizontal cell (RBP and HC) dendrites. Synaptic vesicles are released into this invagination at multiple sites beneath an elongated presynaptic ribbon. We investigated the impact of this complex architecture on the diffusion of synaptic glutamate and activity of postsynaptic receptors.

Cytokines in chest tube drainage after pediatric cardiac surgery - Is chylothorax the only phenotype?

Background: Chylothorax after pediatric cardiac surgery is associated with increased morbidity and mortality. Poor understanding exists regarding inflammation within the pleural fluid. Our aim was to determine the relationship between proinflammatory markers and chylothorax.

Lifetime fitness benefits of breeding site fidelity and low costs of inbreeding permit inbreeding tolerance in an avian cooperative breeder.

Inbreeding, or breeding with close relatives, often decreases individual fitness, but mate choice in many species can increase inbreeding risk. Inbreeding is more likely in species with limited dispersal, such as cooperative breeders where non-parental individuals-often offspring from previous broods-provide parental care and frequently breed close to home. We leverage 32 years of data from a population of Florida Scrub-Jays ( ), an avian cooperative breeder, to investigate whether mate choice, and its lifetime fitness outcomes, affects inbreeding tolerance.

Time Lens Photon Doppler Velocimetry (TL-PDV) for extreme measurements.

Capturing extreme surface velocities with  >50 km/s dynamic range, which arise in shock physics such as inertial confinement fusion (ICF), is beyond the reach of conventional photon Doppler velocimetry (PDV) systems due to the need for extremely large electrical bandwidth under such conditions. The recent ignition in ICF calls for new velocimetry that can measure velocities exceeding 100 km/s. Time lens PDV (TL-PDV) is a solution where the high frequency beat signal from a conventional PDV system is periodically temporally magnified in the optical domain using a time lens.

Evaluating US Multiple Listing Practices in Lung Transplantation: Unveiling Hidden Disparities.

Background: Multiple listing (ML) is a practice used to increase the potential for transplant but is controversial due to concerns that it disproportionately benefits patients with greater access to health care resources.

Research Question: Is there disparity in ML practices based on social deprivation in the United States and does ML lead to quicker time to transplant?

Study Design And Methods: A retrospective cohort study of adult (≥ 18 years of age) lung transplant candidates listed for transplant (2005-2018) was conducted. Exclusion criteria included heart only or heart and lung transplant and patients relisted during the observation period.

Focal seizures induce spatiotemporally organized spiking activity in the human cortex.

Epileptic seizures are debilitating because of the clinical symptoms they produce. These symptoms, in turn, may stem directly from disruptions in neural coding. Recent evidence has suggested that the specific temporal order, or sequence, of spiking across a population of cortical neurons may encode information.

The Impact of Prelung Transplant HLA Antibodies on Post-transplant Outcomes in Recipients With Autoimmune Lung Disease.

Introduction: Patients with advanced lung disease who have HLA antibodies against potential donors have reduced opportunities for transplant. Not all HLA antibodies, however, have the same impact on post-transplant outcomes. It is unknown whether HLA antibodies arising in the context of autoimmune lung disease are associated with increased antibody mediated rejection (AMR) or bronchiolitis obliterans stage 1 (BOS1)-free survival.

The Impact of Donor-Recipient Human Leukocyte Antigen Matching on Bronchiolitis Obliterans-Free Survival Among Lung Transplant Recipients With Connective Tissue Diseases.

Background: The development of connective tissue disease-associated lung diseases (CTD-LD) occurs in association with specific human leukocyte antigens (HLA). For CTD-LD patients who require lung transplant, it is unknown whether utilization of donor organs expressing these same HLA impacts posttransplant outcomes.

Methods: Using the Scientific Registry of Transplant Recipients, we assessed whether CTD-LD lung transplant recipients in the United States have worse bronchiolitis obliterans (BOS)-free survival based on the degree of donor HLA matching.

Long-term air pollution exposure and the risk of primary graft dysfunction after lung transplantation.

Background: Primary graft dysfunction (PGD) contributes substantially to both short- and long-term mortality after lung transplantation, but the mechanisms that lead to PGD are not well understood. Exposure to ambient air pollutants is associated with adverse events during waitlisting for lung transplantation and chronic lung allograft dysfunction, but its association with PGD has not been studied. We hypothesized that long-term exposure of the lung donor and recipient to high levels of ambient air pollutants would increase the risk of PGD in lung transplant recipients.

The retina's neurovascular unit: Müller glial sheaths and neuronal contacts.

The neurovascular unit (NVU), comprising vascular, glial and neural elements, supports the energetic demands of neural computation, but this aspect of the retina's trilaminar vessel network is poorly understood. Only the innermost vessel layer - the superficial vascular plexus (SVP) - is ensheathed by astrocytes, like brain capillaries, whereas glial ensheathment in other layers derives from radial Müller glia. Using serial electron microscopy reconstructions from mouse and primate retina, we find that Müller processes cover capillaries in a tessellating pattern, mirroring the tiled astrocytic endfeet wrapping brain capillaries.

A metabotropic glutamate receptor agonist enhances visual signal fidelity in a mouse model of retinitis pigmentosa.

Many inherited retinal diseases target photoreceptors, which transduce light into a neural signal that is processed by the downstream visual system. As photoreceptors degenerate, physiological and morphological changes to retinal synapses and circuitry reduce sensitivity and increase noise, degrading visual signal fidelity. Here, we pharmacologically targeted the first synapse in the retina in an effort to reduce circuit noise without sacrificing visual sensitivity.

Photo-modulated activation of organic bases enabling microencapsulation and on-demand reactivity.

A method is developed for facile encapsulation of reactive organic bases with potential application for autonomous damage detection and self-healing polymers. Highly reactive chemicals such as bases and acids are challenging to encapsulate by traditional oil-water emulsion techniques due to unfavorable physical and chemical interactions. In this work, reactivity of the bases is temporarily masked with photo-removable protecting groups, and the resulting inactive payloads are encapsulated via an in situ emulsion-templated interfacial polymerization method.

Feasibility and Acceptability of Using Wireless Limited Polysomnography to Capture Sleep Before, During, and After Hospitalization for Patients With Planned Cardiothoracic Surgery.

Background: Sleep disruption, a common symptom among patients requiring cardiovascular surgery, is a potential risk factor for the development of postoperative delirium. Postoperative delirium is a disorder of acute disturbances in cognition associated with prolonged hospitalization, cognitive decline, and mortality.

Objective: The aim of this study was to evaluate the feasibility and acceptability of using polysomnography (PSG) to capture sleep in patients with scheduled cardiothoracic surgery.

Percutaneous Venopulmonary Extracorporeal Membrane Oxygenation as Bridge to Lung Transplantation.

Mechanical circulatory support (MCS) as a bridge to lung transplant is an infrequent but accepted pathway in patients who have refractory end-stage pulmonary failure. The American Association of Thoracic Surgeons Expert Consensus Guidelines, published in 2023, recommends venovenous (VV) extracorporeal membrane oxygenation (ECMO) as the initial configuration for those patients who have failed conventional medical therapy, including mechanical ventilation, while waiting for lung transplantation and needing MCS. Alternatively, venoarterial (VA) ECMO can be used in patients with acute right ventricular failure, hemodynamic instability, or refractory respiratory failure.

Overcoming doxorubicin resistance in triple-negative breast cancer using the class I-targeting HDAC inhibitor bocodepsin/OKI-179 to promote apoptosis.

Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with a poor prognosis. Doxorubicin is part of standard curative therapy for TNBC, but chemotherapy resistance remains an important clinical challenge. Bocodepsin (OKI-179) is a small molecule class I histone deacetylase (HDAC) inhibitor that promotes apoptosis in TNBC preclinical models.

The impact of high volumes of COVID-related lung transplant on waitlist mortality for non-COVID candidates in the United States.

Some patients with coronavirus disease 19 (COVID) develop serious, irreversible lung disease, including acute respiratory distress syndrome or pulmonary fibrosis. For select candidates, lung transplant is the only option to improve quality and length of life. Because of the severity of end-stage COVID-related lung disease, these candidates receive high allocation priority in the United States, including higher priority than many patients without COVID-related lung disease.