Design and Validation of a High-Fidelity Left Atrial Cardiac Simulator for the Study and Advancement of Left Atrial Appendage Occlusion.

Purpose: Atrial fibrillation (AF) is the most common chronic cardiac arrhythmia that increases the risk of stroke, primarily due to thrombus formation in the left atrial appendage (LAA). Left atrial appendage occlusion (LAAO) devices offer an alternative to oral anticoagulation for stroke prevention. However, the complex and variable anatomy of the LAA presents significant challenges to device design and deployment.

Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer's disease.

Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directly observed. The residual approach has been widely applied to estimate CR, where the degree of resilience is estimated through a linear model's residuals.

Selective use of ferumoxytol-enhanced magnetic resonance angiography in patients with renal insufficiency: insights from a pilot study.

The use of conventional contrast agents in computed tomography (CT) and magnetic resonance (MR) imaging is often limited in patients with chronic kidney disease (CKD) due to potential nephrotoxicity. Ferumoxytol, originally developed for iron supplementation, has emerged as a promising alternative MR contrast agent that is safer for patients with CKD. This study aims to present our center's experience with ferumoxytol as a contrast agent in CKD patients.

A genome-wide atlas of human cell morphology.

A key challenge of the modern genomics era is developing empirical data-driven representations of gene function. Here we present the first unbiased morphology-based genome-wide perturbation atlas in human cells, containing three genome-wide genotype-phenotype maps comprising CRISPR-Cas9-based knockouts of >20,000 genes in >30 million cells. Our optical pooled cell profiling platform (PERISCOPE) combines a destainable high-dimensional phenotyping panel (based on Cell Painting) with optical sequencing of molecular barcodes and a scalable open-source analysis pipeline to facilitate massively parallel screening of pooled perturbation libraries.

Black-vs-white racial disparities in 30-day outcomes following primary and revisional metabolic and bariatric surgery: a MBSAQIP database analysis.

Background: Previous studies have demonstrated Black-vs-White disparities in postoperative outcomes following primary metabolic and bariatric surgery (MBS). With the rising prevalence of MBS, it is important to examine racial disparities using quality indicators in primary and revisional procedures. This study explores Black-vs-White disparities in postoperative outcomes following primary and revisional MBS.

International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma.

T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies.

Integrating representation learning, permutation, and optimization to detect lineage-related gene expression patterns.

Recent barcoding technologies allow reconstructing lineage trees while capturing paired single-cell RNA-sequencing (scRNA-seq) data. Such datasets provide opportunities to compare gene expression memory maintenance through lineage branching and pinpoint critical genes in these processes. Here we develop Permutation, Optimization, and Representation learning based single Cell gene Expression and Lineage ANalysis (PORCELAN) to identify lineage-informative genes or subtrees where lineage and expression are tightly coupled.

Not Like They Used To: The Decline of Procedural Competency in Medical Training.

As a primary care pediatrician trained before work hour restrictions were enacted, I spent hours mastering procedures that trainees today rarely perform. The changing landscape of health care clinician roles, technology, and work hour restrictions have all contributed to a remarkable decline in trainees' procedural competence which has significant negative effects for patients, health care systems, and physicians themselves. I suggest simulation, live training, mentoring, and scheduled opportunities as ways to reemphasize the importance of learning these technical skills.

Intervention Stage Completion and Behavioral Health Outcomes: An Integrated Behavioral Health and Primary Care Randomized Pragmatic Trial.

Purpose: We performed a pragmatic, cluster randomized controlled trial of a comprehensive practice-level, multistage practice transformation intervention aiming to increase behavioral health integration in primary care practices and improve patient outcomes. We examined associations between completion of intervention stages and patient outcomes across a heterogeneous national sample of primary care practices.

Methods: Forty-two primary care practices across the United States with colocated behavioral health and 2,945 patients with multiple chronic medical and behavioral health conditions completed surveys at baseline, midpoint, and 2-year follow-up.

Combined PARP14 inhibition and PD-1 blockade promotes cytotoxic T cell quiescence and modulates macrophage polarization in relapsed melanoma.

Background: Programmed cell death 1 (PD-1) signaling blockade by immune checkpoint inhibitors (ICI) effectively restores immune surveillance to treat melanoma. However, chronic interferon-gamma (IFNγ)-induced immune homeostatic responses in melanoma cells contribute to immune evasion and acquired resistance to ICI. Poly ADP ribosyl polymerase 14 (PARP14), an IFNγ-responsive gene product, partially mediates IFNγ-driven resistance.

Recovery Time and Success: A Comparative Study of Robotic and Manual Total Hip Arthroplasty Outcomes.

Background: Despite the growing utilization of robotic-assisted total hip arthroplasty (rTHA), major debate remains regarding its comparative effectiveness in achieving optimal patient outcomes compared to manual total hip arthroplasty (mTHA). This study aimed to compare both the rate and time to achieve minimal clinically important difference (MCID) between rTHA and mTHA.

Methods: We conducted a retrospective analysis comparing 341 rTHAs with a 1:3 propensity score-matched cohort of 1,023 mTHAs performed from 2016 to 2022.

Long-Term Cognitive Outcomes in Adult Patients Receiving Chimeric Antigen Receptor T-Cell Therapies.

Background: CAR T-cell therapy (CAR-T) is leading to durable responses in patients with cancer but there is concern that cytokine release syndrome (CRS) and neurotoxicity may impact survivors' cognitive function. We assessed long-term cognitive function in CAR-T recipients and examine factors associated with change in cognition over time.

Methods: We assessed perceived cognition (Functional Assessment of Cancer Therapy - Cognition) and neurocognitive performance (standardized neuropsychological battery) in adult patients prior to receiving CAR-T and at 6 month follow-up.

Construction, characterization and application of rutin loaded zein - Carboxymethyl starch sodium nanoparticles.

In this paper, zein-carboxymethyl starch (CMS) nanoparticles were prepared by antisolvent precipitation method to improve the stability of rutin (RT). The encapsulation efficiency, loading capacity, oxidation resistance, structural properties were evaluated. The results showed that electrostatic, hydrogen bond and hydrophobic interaction were the main driving forces for the formation of nanoparticles.

Comparison of temporary mechanical circulatory support devices for patients with cardiogenic shock after acute myocardial infarction: A network meta-analysis of randomized controlled trials.

Background: Despite the high mortality of cardiogenic shock after acute myocardial infarction (AMI-CS), the comparative efficacy and safety of mechanical circulatory support (MCS) in patients with AMI-CS is unknown. This study aimed to compare the efficacy and safety of various MCS with initial medical therapy for AMI-CS patients.

Methods: We searched PubMed and EMBASE in July 2024.

The Extended Mind in Young Children: Cost-Dependent Trade-Off Between External and Internal Memory.

Most work on working memory development has children remember a set of items as well as they can. However, this approach sidesteps the , the integration of external information with memory. Indeed, adults prefer to use external resources (e.

TractGraphFormer: Anatomically informed hybrid graph CNN-transformer network for interpretable sex and age prediction from diffusion MRI tractography.

The relationship between brain connections and non-imaging phenotypes is increasingly studied using deep neural networks. However, the local and global properties of the brain's white matter networks are often overlooked in convolutional network design. We introduce TractGraphFormer, a hybrid Graph CNN-Transformer deep learning framework tailored for diffusion MRI tractography.

The influence of exposure to early-life adversity on agency-modulated reinforcement learning.

Agency beliefs influence how humans learn from different contexts and outcomes. Research demonstrates that stressors, such as exposure to early-life adversity (ELA), are associated with both agency beliefs and learning, but how these processes interact remains unclear. The current study investigated whether exposure to ELA influences agency and interacts with reinforcement learning in adults.

Stimulant-involved overdose deaths: Constructing dynamic hypotheses.

The overdose epidemic in the United States is evolving, with a rise in stimulant (cocaine and/or methamphetamine)-only and opioid and stimulant-involved overdose deaths for reasons that remain unclear. We conducted interviews and group model building workshops in Massachusetts and South Dakota. Building on these data and extant research, we identified six dynamic hypotheses, explaining changes in stimulant-involved overdose trends, visualized using causal loop diagrams.

Muscle contributions to propelling the body upward differ between skipping and running.

Skipping represents a training alternative to running due to its lower knee contact forces and higher whole-body metabolic cost. The increased metabolic cost of skipping is associated with a higher vertical center-of-mass (COM) displacement during the support and flight phases of the skipping hop compared to running. However, skipping has lower muscle force impulses than running.

Correlates of Cetuximab Efficacy in Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma Previously Treated With Immunotherapy.

Purpose: Immune checkpoint inhibitors (ICIs) are now first-line therapy for most patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), and cetuximab is most often used as subsequent therapy. However, data describing cetuximab efficacy in the post-ICI setting are limited.

Methods: We performed a single-institution retrospective analysis of patients with R/M HNSCC treated with cetuximab, either as monotherapy or in combination with chemotherapy, after receiving an ICI.

Integrative genomic analysis of DLBCL identifies immune environments associated with bispecific antibody response.

Most diffuse large B-cell lymphoma (DLBCL) patients treated with immunotherapies such as bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was applied to multiple large independent datasets in order to characterize DLBCL immune environments, and to define their association with tumor cell-intrinsic genomic alterations and outcomes to CD19-directed CAR T-cell and CD20 x CD3 BsAb therapies. This approach effectively segregated DLBCLs into four immune quadrants (IQ) defined by cell-of-origin and immune-related gene set expression scores.

Protection of β2GPI-Deficient Mice from Thrombosis Reflects a Defect in PAR3-facilitated Platelet Activation.

Antibodies to β2-glycoprotein I (β2GPI) cause thrombosis in antiphospholipid syndrome, however the role of β2GPI in coagulation in vivo is not understood. To address this issue, we developed β2GPI-deficient mice (Apoh-/-) by deleting exon 2 and 3 of Apoh using CRISPR/Cas9 and compared the development of thrombosis in wild-type (WT) and Apoh-/- mice using rose bengal and FeCl3-induced carotid thrombosis, laser-induced cremaster arteriolar injury, and inferior vena cava (IVC) stasis models. We also compared tail bleeding times and activation of platelets from WT and Apoh-/- mice in the absence and presence of β2GPI.

Highly Optimized CNS Penetrant Inhibitors of EGFR Exon20 Insertion Mutations.

Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.

Daytime DNase-I Administration Protects Mice From Ischemic Stroke Without Inducing Bleeding or tPA-Induced Hemorrhagic Transformation, Even With Aspirin Pretreatment.

Background: Acute ischemic stroke treatment typically involves tissue-type plasminogen activator (tPA) or tenecteplase, but about 50% of patients do not achieve successful reperfusion. The causes of tPA resistance, influenced by thrombus composition and timing, are not fully clear. Neutrophil extracellular traps (NETs), associated with poor outcomes and reperfusion resistance, contribute to thrombosis.