Branched endosomal disruptor (BEND) lipids mediate delivery of mRNA and CRISPR-Cas9 ribonucleoprotein complex for hepatic gene editing and T cell engineering.

Lipid nanoparticles (LNPs) are the preeminent non-viral drug delivery vehicle for mRNA-based therapies. Immense effort has been placed on optimizing the ionizable lipid (IL) structure, which contains an amine core conjugated to lipid tails, as small molecular adjustments can result in substantial changes in the overall efficacy of the resulting LNPs. However, despite some advancements, a major barrier for LNP delivery is endosomal escape.

Network structure influences the strength of learned neural representations.

From sequences of discrete events, humans build mental models of their world. Referred to as graph learning, the process produces a model encoding the graph of event-to-event transition probabilities. Recent evidence suggests that some networks are easier to learn than others, but the neural underpinnings of this effect remain unknown.

A Call for a Neoadjuvant Kidney Cancer Consortium: Lessons Learned from Other Cancer Types.

Neoadjuvant systemic treatment strategies have improved outcomes in several solid tumour types. This success has not yet been replicated in renal cell carcinoma (RCC). A consensus and international collaboration are urgently needed for the development of adaptive perioperative immunotherapy strategies for patients with RCC at high risk of recurrence.

Biology of extracellular vesicles and the potential of tumor-derived vesicles for subverting immunotherapy of cancer.

Extracellular vesicles (EVs) are produced by all living cells and are present in all body fluids. EVs are heterogeneous in size, biogenesis, molecular/genetic content and functions. They constitute a part of the intercellular communication system.

Association of age, race, and ethnicity with access, response, and toxicities from CAR-T therapy in children and adults with B-cell malignancies: a review.

Chimeric antigen receptor T cell (CAR-T) therapies are now standard-of-care for several B-cell malignancies, and additional indications are being evaluated. In this review, we survey data on how outcomes after CAR-T therapies vary according to age, race, and ethnicity. We also review the representation of age, racial, and ethnic groups in key CAR-T clinical trials.

Mechanical thrombectomy in elderly stroke patients with low ASPECTS: insights from STAR.

Background: The elderly population (≥80 years) were underrepresented in recent trials of endovascular thrombectomy (EVT) for anterior circulation large vessel occlusion acute ischemic stroke (LVO-AIS) with low Alberta Stroke Program Early CT Score (ASPECTS) (≤5).

Methods: This study analyzed data from a prospectively maintained database of 37 thrombectomy centers. The primary cohort of the study comprised patients with LVO-AIS aged ≥80 who underwent EVT with ASPECTS≤5 from 2013 to 2023.

The Relationship Between Hispanic Ethnicity and Outcomes for Infants Born Extremely Preterm.

Objective: To characterize the association between maternal ethnicity and infant survival to discharge without major morbidity.

Study Design: This is secondary analysis of a prospective cohort of infants born <27 weeks of gestation at NICHD Neonatal Research Network centers from 2006 through 2020. The primary outcome was survival to discharge without major morbidity (sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia grade 3, intracranial hemorrhage grade ≥3, periventricular leukomalacia, and advanced retinopathy of prematurity).

Antinuclear antibodies and progression of quantitative interstitial lung changes: The Multi-Ethnic Study of Atherosclerosis (MESA)-Lung Study.

Antinuclear antibodies (ANA) are often found in ILD; whether ANA is associated with radiographic progression of quantitive interstital lung changes is unknown. We performed longitudinal analyses of adults in the Multi-Ethnic Study of Atherosclerosis using linear mixed effects models with random intercept and slope to evaluate whether baseline ANA was associated with change in the amount of lung with high attenuation areas on CT (HAAs, percentage of imaged lung with -600 to -250 HU). In 6,638 subjects with 17,293 CT scans over 18 years, 741 (11%) were ANA positive.

Implantable Cardioverter-Defibrillators and Cardiovascular Resynchronization Therapy with Left Ventricular Assist Devices: A MOMENTUM 3 Trial Analysis.

Background: The benefit of implantable cardioverter-defibrillators (ICD) and cardiovascular resynchronization therapy (CRT-D) in patients supported with a HeartMate 3 left ventricular assist device (LVAD) remains uncertain.

Methods: An analysis of the MOMENTUM 3 randomized clinical trial and the first 1000 patients in the Continued Access Protocol trial. Patients were divided into three groups based on the presence of ICD and/or CRT-D: No device (n=153, 11%), ICD only (n=699, 50.

Effect of equine transvaginal follicle aspiration on serum concentrations of acute phase proteins and their utility in diagnosis of ovarian abscess.

Transvaginal ultrasound-guided follicle aspiration (TVA) is being performed frequently in equine practice, to recover oocytes for in vitro embryo production via intracytoplasmic sperm injection. While complications from TVA are rare, one of the most prevalent major complications is formation of an ovarian abscess, which can result in the necessity for euthanasia. The acute-phase serum proteins, fibrinogen and serum amyloid A (SAA) are markers of inflammation that might be of use in diagnosis of ovarian abscess.

Characterizing brainstem glucagon-like peptide-1 control of sensory-specific-satiety in male and female rats across the estrous cycle.

Background: Meal variety promotes overconsumption by delaying sensory-specific-satiety (SSS), the transient reduction in reward value of a recently consumed food. Despite its role in meal cessation, the neuroendocrine mechanisms underlying SSS are largely unknown.

Methods: Here, we developed a preclinical model of SSS wherein rats consume more of a different food compared to the same food presented again, leading to greater caloric intake.

Raman Spectroscopic Probe Provides Optical Biomarkers of Cartilage Composition Predictive of Tissue Function.

Objective: The diagnosis of early osteoarthritis when therapeutic interventions may be most effective at reversing cartilage degeneration presents a clinical challenge. We describe a Raman arthroscopic probe and spectral analysis that measures biomarkers reflective of the content of predominant cartilage ECM constituents-glycosaminoglycans (GAG), collagen, water-essential to cartilage function. We compare the capability of Raman-probe-derived biomarkers to predict functional properties of cartilage to quantitative MRI and histopathology assessments.

Centromeric chromatin clearings demarcate the site of kinetochore formation.

The centromere is the chromosomal locus that recruits the kinetochore, directing faithful propagation of the genome during cell division. Using cryo-ET on human mitotic chromosomes, we reveal a distinctive architecture at the centromere: clustered 20- to 25-nm nucleosome-associated complexes within chromatin clearings that delineate them from surrounding chromatin. Centromere components CENP-C and CENP-N are each required for the integrity of the complexes, while CENP-C is also required to maintain the chromatin clearing.

Independent genetic strategies define the scope and limits of CDKL5 deficiency disorder reversal.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a neurodevelopmental syndrome caused by mutations in the X-linked CDKL5 gene. The early onset of CDD suggests that CDKL5 is essential during development, but post-developmental re-expression rescues multiple CDD-related phenotypes in hemizygous male mice. Since most patients are heterozygous females, studies in clinically relevant female models are essential.

Risk Factors for Delayed (>30 Days) Readmission Following Rectal Cancer Surgery.

Introduction: Unplanned, delayed readmissions (>30 ds) following oncologic surgeries can increase mortality and care costs and affect hospital quality indices. However, there is a dearth of literature on rectal cancer surgery. Hence, we aimed to assess the risk factors associated with delayed readmissions following rectal cancer surgery to improve targeted interventions, patient outcomes, and quality indices.

Neuroendoscopic lavage for posthemorrhagic hydrocephalus of prematurity: preliminary results at a single institution in the United States.

Objective: The current neurosurgical treatment for intraventricular hemorrhage (IVH) of prematurity resulting in posthemorrhagic hydrocephalus (PHH) seeks to reduce intracranial pressure with temporary and then permanent CSF diversion. In contrast, neuroendoscopic lavage (NEL) directly addresses the intraventricular blood that is hypothesized to damage the ependyma and parenchyma, leading to ventricular dilation and hydrocephalus. The authors sought to determine the feasibility of NEL in PHH.

Smartphone accelerometers as tools to study the effect of socioeconomic disparities in neurosurgical outcomes: a multi-institutional retrospective analysis.

Objective: Smartphones and wearable devices can be effective tools to objectively assess patient mobility and well-being before and after spine surgery. In this retrospective observational study, the authors investigated the relationship between these longitudinal perioperative patient activity data and socioeconomic and demographic correlates, assessing whether smartphone-captured metrics may allow neurosurgeons to distinguish intergroup patterns.

Methods: A multi-institutional retrospective study of patients who underwent spinal decompression with and without fusion between 2017 and 2021 was conducted.

Competing pathways of intracranial aneurysm growth: linking regional growth distribution and hemodynamics.

Objective: The complex mix of factors, including hemodynamic forces and wall remodeling mechanisms, that drive intracranial aneurysm growth is unclear. This study focuses on the specific regions within aneurysm walls where growth occurs and their relationship to the prevalent hemodynamic conditions to reveal critical mechanisms leading to enlargement.

Methods: The authors examined hemodynamic models of 67 longitudinally followed aneurysms, identifying 88 growth regions.

One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them.

Leukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.

Evolution of SARS-CoV-2 in white-tailed deer in Pennsylvania 2021-2024.

SARS-CoV-2 continues to transmit and evolve in humans and animals. White-tailed deer (Odocoileus virginianus) have been previously identified as a zoonotic reservoir for SARS-CoV-2 with high rates of infection and probable spillback into humans. Here we report sampling 1,127 white-tailed deer (WTD) in Pennsylvania, and a genomic analysis of viral dynamics spanning 1,017 days between April 2021 and January 2024.

Virtual reality perimetry compared to standard automated perimetry in adults with glaucoma: A systematic review.

Purpose: The purpose of this systematic review was to consolidate and summarize available data comparing virtual reality perimetry (VRP) with standard automated perimetry (SAP) in adults with glaucoma. Understanding the utility and diagnostic performance of emerging VRP technology may expand access to visual field testing but requires evidence-based validation.

Methods: A systematic literature search was conducted in 3 databases (PubMed Central, Embase, and Cochrane Central Register of Controlled Trials) from the date of inception to 10/09/2024.

Lisfranc Fracture-dislocation With Extensor Hallucis Brevis Tendon Interposition: A Case Report.

Case: A 14-year-old adolescent girl sustained a Lisfranc fracture-dislocation with an interposed extensor hallucis brevis (EHB) tendon. Following multiple failed attempts at closed reduction in both the emergency department and the operating room, the patient was treated in a staged manner with temporizing closed reduction and percutaneous pinning in improved alignment, followed by definitive open reduction and internal fixation once soft tissues allowed.

Conclusions: Anatomic reduction and stable fixation of Lisfranc injuries is vital to regain stability and reduce the risk of midfoot arthritis and collapse.

The X chromosome's influences on the human brain.

Genes on the X chromosome are extensively expressed in the human brain. However, little is known for the X chromosome's impact on the brain anatomy, microstructure, and functional networks. We examined 1045 complex brain imaging traits from 38,529 participants in the UK Biobank.

Bioprinted optoelectronically active cardiac tissues.

Electrical stimulation of existing three-dimensional bioprinted tissues to alter tissue activities is typically associated with wired delivery, invasive electrode placement, and potential cell damage, minimizing its efficacy in cardiac modulation. Here, we report an optoelectronically active scaffold based on printed gelatin methacryloyl embedded with micro-solar cells, seeded with cardiomyocytes to form light-stimulable tissues. This enables untethered, noninvasive, and damage-free optoelectronic stimulation-induced modulation of cardiac beating behaviors without needing wires or genetic modifications to the tissue solely with light.