Modular DNA origami-based electrochemical detection of DNA and proteins.

The diversity and heterogeneity of biomarkers has made the development of general methods for single-step quantification of analytes difficult. For individual biomarkers, electrochemical methods that detect a conformational change in an affinity binder upon analyte binding have shown promise. However, because the conformational change must operate within a nanometer-scale working distance, an entirely new sensor, with a unique conformational change, must be developed for each analyte.

A detailed spatiotemporal atlas of the white matter tracts for the fetal brain.

This study presents the construction of a comprehensive spatiotemporal atlas of white matter tracts in the fetal brain for every gestational week between 23 and 36 wk using diffusion MRI (dMRI). Our research leverages data collected from fetal MRI scans, capturing the dynamic changes in the brain's architecture and microstructure during this critical period. The atlas includes 60 distinct white matter tracts, including commissural, projection, and association fibers.

Population encoding of observed and actual somatosensations in the human posterior parietal cortex.

Cognition relies on transforming sensory inputs into a generalizable understanding of the world. Mirror neurons have been proposed to underlie this process, mapping visual representations of others' actions and sensations onto neurons that mediate our own, providing a conduit for understanding. However, this theory has limitations.

Climate change could amplify weak synchrony in large marine ecosystems.

Climate change is increasing the frequency of large-scale, extreme environmental events and flattening environmental gradients. Whether such changes will cause spatially synchronous, large-scale population declines depends on mechanisms that limit metapopulation synchrony, thereby promoting rescue effects and stability. Using long-term data and empirical dynamic models, we quantified spatial heterogeneity in density dependence, spatial heterogeneity in environmental responses, and environmental gradients to assess their role in inhibiting synchrony across 36 marine fish and invertebrate species.

Electron transfer in polysaccharide monooxygenase catalysis.

Polysaccharide monooxygenase (PMO) catalysis involves the chemically difficult hydroxylation of unactivated C-H bonds in carbohydrates. The reaction requires reducing equivalents and will utilize either oxygen or hydrogen peroxide as a cosubstrate. Two key mechanistic questions are addressed here: 1) How does the enzyme regulate the timely and tightly controlled electron delivery to the mononuclear copper active site, especially when bound substrate occludes the active site? and 2) How does this electron delivery differ when utilizing oxygen or hydrogen peroxide as a cosubstrate? Using a computational approach, potential paths of electron transfer (ET) to the active site copper ion were identified in a representative AA9 family PMO from (PMO9E).

Mechanism-guided engineering of a minimal biological particle for genome editing.

The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization.

Deep conservation complemented by novelty and innovation in the insect eye ground plan.

A spectacular diversity of forms and features allow species to thrive in different environments, yet some structures remain relatively unchanged. Insect compound eyes are easily recognizable despite dramatic differences in visual abilities across species. It is unknown whether distant insect species use similar or different mechanisms to pattern their eyes or what types of genetic changes produce diversity of form and function.

Unlocking the catalytic precision of ligand-controlled enzymatic halogenation.

A single-component flavin-dependent halogenase, AetF, has emerged as an attractive biocatalyst for catalyzing halogenation. However, its flavin chemistry remains unexplored and cannot be predicted due to its uniqueness in sequence and structure compared to other flavin-dependent monooxygenases. Here, we investigated the flavin reactions of AetF using transient kinetics.

Association between meningioma consistency and surgical outcomes.

Objective: Tumor consistency, or fibrosity, affects the ability to optimally resect meningiomas, especially with recent trends evolving toward minimally invasive approaches. The authors' team previously validated a practical 5-point scale for intraoperative grading of meningioma consistency. The impact of meningioma consistency on surgical management and outcomes, however, has yet to be explored.

Patient-reported outcome trajectories the first 24 months after surgery for cervical spondylotic myelopathy: a Quality Outcomes Database study.

Objective: Cervical spondylotic myelopathy (CSM) shows varying levels of improvement after surgical treatment. While some patients improve soon after surgery, others may take months to years to show any signs of improvement. The goal of this study was to evaluate postoperative improvement, patient-reported outcomes, and patient satisfaction up to 2 years after surgical treatment for CSM, which will help optimize the current treatment strategies and effectively manage patient expectations.

The impact of lower thoracic versus upper lumbar upper instrumented vertebra in minimally invasive correction of adult spinal deformity.

Objective: The goal of this study was to compare the impact of using a lower thoracic (LT) versus upper lumbar (UL) level as the upper instrumented vertebra (UIV) on clinical and radiographic outcomes following minimally invasive surgery for adult spinal deformity.

Methods: A multicenter retrospective study design was used. Inclusion criteria were age ≥ 18 years, and one of the following: coronal Cobb angle > 20°, sagittal vertical axis > 50 mm, pelvic tilt > 20°, pelvic incidence-lumbar lordosis mismatch > 10°.

Detection of Extracochlear Electrodes Using Electrical Field Imaging (EFI).

Objective: To analyze the use of electrical field imaging (EFI) in the detection of extracochlear electrodes in cochlear implants (CI).

Study Design: Retrospective cohort study.

Setting: Tertiary academic medical center.

Voices of Nanomedicine: Blueprint Guidelines for Collaboration in Addressing Global Unmet Medical Needs.

The "" under this Perspective underline the importance of interdisciplinary collaboration and partnerships across several disciplines, such as medical science and technology, medicine, bioengineering, and computational approaches, in bridging the gap between research, manufacturing, and clinical applications. Effective communication is key to bridging team gaps, enhancing trust, and resolving conflicts, thereby fostering teamwork and individual growth toward shared goals. Drawing from the success of the COVID-19 vaccine development, we advocate the application of similar collaborative models in other complex health areas such as nanomedicine and biomedical engineering.

Dengue severity by serotype and immune status in 19 years of pediatric clinical studies in Nicaragua.

Background: Dengue virus, a major global health threat, consists of four serotypes (DENV1-4) that cause a range of clinical manifestations from mild to severe and potentially fatal disease.

Methods: This study, based on 19 years of data from the Pediatric Dengue Cohort Study and Pediatric Dengue Hospital-based Study in Managua, Nicaragua, investigates the relationship of serotype and immune status with dengue severity. Dengue cases were confirmed by molecular, serological, and/or virological methods, and study participants 6 months to 17 years old were followed during their hospital stay or as ambulatory patients.

SIV Env RhmAbs + N-803 at ART initiation prolongs viral decay without disrupting reservoir establishment in SIV-infected infant macaques.

The latent viral reservoir remains the major barrier to HIV cure, placing the burden of strict adherence to antiretroviral therapy (ART) on people living with HIV to prevent recrudescence of viremia. For infants with perinatally acquired HIV, adherence is anticipated to be a lifelong need. In this study, we tested the hypothesis that administration of ART and viral Envelope-specific rhesus-derived IgG1 monoclonal antibodies (RhmAbs) with or without the IL-15 superagonist N-803 early in infection would limit viral reservoir establishment in SIV-infected infant rhesus macaques.

Donor Regulatory T-Cell Therapy to Prevent Graft-Versus-Host Disease.

Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy limited by graft-versus-host disease (GVHD). In preclinical studies and early-phase clinical studies enrichment of donor regulatory T cells (Tregs) appears to prevent GVHD and promote healthy immunity.We enrolled 44 patients on an open-label, single-center, phase 2 efficacy study investigating if a precision selected and highly purified Treg cell therapy manufactured from donor mobilized peripheral blood improves one-year GVHD-free relapse free survival (GRFS) after myeloablative conditioning (trial NCT01660607).

Internal validation of a convolutional neural network pipeline for assessing meibomian gland structure from meibography.

Significance: Optimal meibography utilization and interpretation are hindered due to poor lid presentation, blurry images, or image artifacts and the challenges of applying clinical grading scales. These results, using the largest image dataset analyzed to date, demonstrate development of algorithms that provide standardized, real-time inference that addresses all of these limitations.

Purpose: This study aimed to develop and validate an algorithmic pipeline to automate and standardize meibomian gland absence assessment and interpretation.

National assessment on the frequency of pain medication prescribed for intrauterine device insertion procedures within the Veterans Affairs Health Care System.

Background: The intrauterine device (IUD) is a highly effective form of long-acting reversible contraception, widely recognized for its convenience and efficacy. Despite its benefits, many patients report moderate to severe pain during and after their IUD insertion procedure. Furthermore, reports suggest significant variability in pain control medications, including no adequate pain medication.

The Effectiveness and Safety of Beta Antagonists in Patients With Burns: An Updated Meta-Analysis.

Aims: The purpose of this systematic review was to assess the safety and effectiveness of beta antagonists for improving clinical care in burn patients, compared to placebo.

Methods: Articles from randomized-controlled trials were identified by a literature search on PubMed and Cochrane. We included relevant trials involving patients with burn.

Ten simple rules for good model-sharing practices.

Computational models are complex scientific constructs that have become essential for us to better understand the world. Many models are valuable for peers within and beyond disciplinary boundaries. However, there are no widely agreed-upon standards for sharing models.

Neonatal and Home-Based PT Improves Neurodevelopmental Outcomes of Preterm Infants-A Randomized Clinical Trial.

Purpose: Investigate the effect of structured neonatal physical therapy program (SNP) on neurodevelopmental outcomes of moderate and late preterm (MLP) infants.

Methods: Sixty MLP infants were randomly allocated to usual care (UC) or SNP. A previous publication reported the effect of neonatal component of SNP at hospital discharge.

Primary solitary fibrous tumor of the stomach: A case report and a review of literature.

Rationale: Solitary fibrous tumors (SFTs) are spindle cell tumors that typically occur in the pleura and peritoneum, but very rarely in the stomach. To our best knowledge, there are only 10 cases reported in English literature. We reported a case of primary stomach SFT and summarized the characteristics of all previous cases, suggesting that pathologists and surgeons should include this disease in the differential diagnosis list of primary mesenchymal tumor of the stomach.

Development of endosome-related gene signature for the prediction of prognosis and therapeutic response in breast cancer.

Endosomes play a pivotal role in cellular biology, orchestrating processes such as endocytosis, molecular trafficking, signal transduction, and recycling of cellular materials. This study aims to construct an endosome-related gene (ERG)-derived risk signature for breast cancer prognosis. Transcriptomic and clinical data were retrieved from The Cancer Genome Atlas and the University of California Santa Cruz databases to build and validate the model.

Tailoring glaucoma education using large language models: Addressing health disparities in patient comprehension.

This study evaluates the efficacy of GPT-4, a Large Language Model, in simplifying medical literature for enhancing patient comprehension in glaucoma care. GPT-4 was used to transform published abstracts from 3 glaucoma journals (n = 62) and patient education materials (Patient Educational Model [PEMs], n = 9) to a 5th-grade reading level. GPT-4 was also prompted to generate de novo educational outputs at 6 different education levels (5th Grade, 8th Grade, High School, Associate's, Bachelor's and Doctorate).

Evaluation of Larger Side-Group Functionalities and the Side/End-Group Interplay in Ritonavir-Like Inhibitors of CYP3A4.

A new series of 13 ritonavir-like inhibitors of human drug-metabolizing CYP3A4 was rationally designed to study the R side-group and R end-group interplay when the R side-group is represented by phenyl. Spectral, functional, and structural characterization showed no improvement in the binding affinity and inhibitory potency of R/R-phenyl inhibitors upon elongation and/or fluorination of R-Boc (tert-butyloxycarbonyl) or its replacement with benzenesulfonyl. When R is pyridine, the impact of R-phenyl-to-indole/naphthalene substitution was multidirectional and highly dependent on side-group stereo configuration.