The trial design of the concurrent optical and magnetic stimulation (COMS) therapy study for refractory diabetic foot ulcers (MAVERICKS): a multicenter, randomized, sham-controlled, double-blind investigational device exemption clinical study.

Background: Diabetic foot ulcers (DFUs) are a major clinical challenge, particularly among patients with refractory ulcers, that often lead to severe complications such as infection, amputation, and high mortality. Innovations supported by strong clinical evidence have the potential to improve healing outcomes, enhance quality of life, and reduce the economic burden on individuals and health care systems.

Objective: To describe the design of the concurrent optical and magnetic stimulation (COMS) therapy Investigational Device Exemption (IDE) study for refractory DFUs (MAVERICKS) trial.

LONP1 Variants Are Associated With Clinically Diverse Phenotypes.

LONP1 encodes a mitochondrial protease essential for protein quality control and metabolism. Variants in LONP1 are associated with a diverse and expanding spectrum of disorders, including Cerebral, Ocular, Dental, Auricular, and Skeletal anomalies syndrome (CODAS), congenital diaphragmatic hernia (CDH), and neurodevelopmental disorders (NDD), with some individuals exhibiting features of mitochondrial encephalopathy. We report 16 novel LONP1 variants identified in 16 individuals (11 with NDD, 5 with CDH), further expanding the clinical spectrum.

Population size in stochastic discrete-time ecological dynamics.

We study how environmental stochasticity influences the long-term population size in certain one- and two-species models. The difficulty is that even when one can prove that there is coexistence, it is usually impossible to say anything about the invariant probability measure which describes the coexisting species. We are able to circumvent this problem for some important ecological models by noticing that the per-capita growth rates at stationarity are zero, something which can sometimes yield information about the invariant probability measure.

Drug Delivery and Binding in a Tissue with Irregularly Shaped Binding Regions.

Objective: A fundamental understanding of drug diffusion and binding processes is critical for the design and optimization of a wide variety of drug delivery devices. Most of the past literature assume binding to occur uniformly throughout the tissue, or, at best, in specific layers of a multilayer tissue. However, in many realistic scenarios, such as in cancer-targeting drugs, drug binding occurs in discrete irregularly shaped regions.

Redox-driven mineral and organic associations in Jezero Crater, Mars.

The Perseverance rover has explored and sampled igneous and sedimentary rocks within Jezero Crater to characterize early Martian geological processes and habitability and search for potential biosignatures. Upon entering Neretva Vallis, on Jezero Crater's western edge, Perseverance investigated distinctive mudstone and conglomerate outcrops of the Bright Angel formation. Here we report a detailed geological, petrographic and geochemical survey of these rocks and show that organic-carbon-bearing mudstones in the Bright Angel formation contain submillimetre-scale nodules and millimetre-scale reaction fronts enriched in ferrous iron phosphate and sulfide minerals, likely vivianite and greigite, respectively.

DNA methylation cooperates with genomic alterations during non-small cell lung cancer evolution.

Aberrant DNA methylation has been described in nearly all human cancers, yet its interplay with genomic alterations during tumor evolution is poorly understood. To explore this, we performed reduced representation bisulfite sequencing on 217 tumor and matched normal regions from 59 patients with non-small cell lung cancer from the TRACERx study to deconvolve tumor methylation. We developed two metrics for integrative evolutionary analysis with DNA and RNA sequencing data.

Probing the anion binding promiscuity of the soluble nitrate sensor NreA from Staphylococcus carnosus.

Promiscuity, or selectivity on a spectrum, is an encoded feature in biomolecular anion recognition. To unravel the molecular drivers of promiscuous anion recognition, we have employed a comprehensive approach - spanning experiment and theory - with the Staphylococcus carnosus nitrate regulatory element A (ScNreA) as a model. Thermodynamic analysis reveals that ScNreA complexation with native nitrate and nitrite or non-native iodide is an exothermic process.

Low-grade non-muscle-invasive bladder cancer: molecular landscape, treatment strategies and emerging therapies.

Low-grade non-muscle invasive bladder cancer is a specific category of bladder cancer with a favourable prognosis; however, its management presents several challenges. The risk of stage progression is very low, but approximately half of patients will experience recurrence within the first 5 years after diagnosis. This high propensity for recurrence, coupled with the threat of progression, mandates ongoing surveillance.

Nanofibrous supramolecular peptide hydrogels for controlled release of small-molecule drugs and biologics.

Maintaining safe and potent drug levels in vivo is challenging. Multidomain peptides assemble into supramolecular hydrogels with a well-defined, highly porous nanostructure that makes them attractive for drug delivery. However, their ability to extend release is typically limited by rapid drug diffusion.

Proximity labeling of axonemal protein CFAP91 identifies EFCAB5 that regulates sperm motility.

Radial spokes (RSs) are conserved multimolecular structures attached to the axonemal microtubule doublets and are essential for the motility control of both cilia and sperm flagella. CFAP91, an RS3 protein, is implicated in human male infertility, yet its molecular function remains poorly understood. Here, we demonstrate that Cfap91 knockout (KO) mice exhibit impaired sperm flagellum formation and male infertility.

MAFLD: a ferroptotic disease.

Ferroptosis, a regulated cell death pathway driven by iron-catalyzed lipid peroxidation, has recently been implicated as a major cause of hepatic injury in metabolic dysfunction-associated fatty liver disease (MAFLD). This review highlights how the identification of hyperoxidized peroxiredoxin 3 (PRDX3) as a ferroptosis-specific marker has led to the discovery that ferroptosis contributes to liver injury in MAFLD, and summarizes other emerging evidence connecting ferroptosis to MAFLD pathogenesis. These new findings suggest that dietary fat composition and genetic variants such as PNPLA3(I148M) may affect the progression of MAFLD by regulating cellular sensitivity to ferroptosis.

Continuous bronchoscopy during exercise in a pediatric patient: A case report.

Exercise-induced respiratory symptoms limit physical activity and sport performance in adolescents. Etiologies include exercise-induced bronchoconstriction, laryngeal obstruction, dysfunctional breathing, and in rarer cases, large airway obstruction and cardiac pathologies. Accurate diagnosis requires assessment during exercise that elicits the symptoms patients experience in the field.

Genome-scale prediction of gene ontology from mass fingerprints reveals new metabolic gene functions.

Mass-based fingerprinting can characterize microorganisms; however, expansion of these methods to predict specific gene functions is lacking. Therefore, mass fingerprinting was developed to functionally profile a yeast knockout library. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) fingerprints of 3,238 knockouts were digitized for correlation with gene ontology (GO).

Innate and adaptive immune features associated with immune-related adverse events.

Background: While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.

Methods: We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.

Results: Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57 T and natural killer (NK) T cells, plasmablasts, proliferating and activated CXCR3 lymphocytes, CD8 effector and terminal effector memory T cells, along with reduced NK cells and elevated plasma ANA levels.

Assessing the importance of functional form selection in developing calibration functions for the highway safety manual predictive models.

Introduction: The Highway Safety Manual (HSM) offers crash prediction models for estimating the number and severity of crashes for several facility types. However, since these models were developed using data from selected states within the United States, they should be calibrated when applied to a new jurisdiction. The HSM recommended using a scalar calibration factor to calibrate the prediction models.

Examining pedestrian crash frequency and environmental factors for three subgroups of the older adult population: a micro-level analysis.

Introduction: Pedestrian safety has become a critical concern with the rising global population of older adults. Older pedestrians face higher crash risks due to age-related physical limitations, yet road infrastructure often fails to address their specific needs. Most studies treat older adults as a single group, overlooking variations in mobility and behavior.

Investigating hazard exposures and safety dynamics among researchers in academic settings: Insights from a large-scale survey study.

Introduction: Researchers, whether working in wet-labs, dry-labs, clinical settings, or field environments, encounter various hazards. However, there has been limited study on the health and safety of academic researchers. This study aimed to investigate hazardous occupational exposures and safety among researchers in academic settings at a large U.

Moderate Secondary Mitral Regurgitation: Evolving Evidence and Management Strategies.

Secondary mitral regurgitation (SMR) is common in patients with heart failure (HF). Although randomized clinical trials have been focused on the treatment of severe SMR, the prognostic role and potential for treatment of moderate SMR cannot be overlooked. The randomized RESHAPE-HF2 trial included patients with moderate and severe SMR with consistent findings in both groups, raising the hypothesis that transcatheter correction of moderate SMR could have beneficial effects, although this needs further investigation.

Improvements in Resting-State Functional Connectivity of the Cerebellum after Transcranial Photobiomodulation in Adults with a History of Repetitive Head Acceleration Events.

The current study sought to explore the impact of a novel noninvasive treatment called transcranial photobiomodulation (PBM) on resting-state functional connectivity (rsFC) of the cerebellum in individuals with a history of repetitive head acceleration events (RHAEs). RHAEs are associated with cumulative neurological compromise, including chronic alterations in rsFC; however, few treatments have been investigated to mitigate these effects. A recent study by our team demonstrated that PBM treatment led to improvements in measures of balance and motor function in adults with RHAE exposure.

Associations of body mass index, waist circumference, and weight-adjusted waist index with body composition and biomarkers: A multinational pooled analysis.

Background: The widely-used anthropometric indices, such as body mass index (BMI) and waist circumference (WC), have limitations in their use as indicators of body composition. Recent studies proposed weight-adjusted waist index (WWI=WC/√(body weight)) as an alternative index for body composition but it is unclear whether WWI reflects body composition in different racial/ethnic groups.

Objective: We examined the associations of WWI, BMI, and WC with dual-energy x-ray absorptiometry (DEXA)-measured body composition, biomarkers (fasting blood glucose, HDL-cholestrol, LDL-cholestrol, triglyceride), and handgrip strength.

Regulation of neurogenesis and neuronal migration by Rrm2 and Timp3 following seizures.

Temporal lobe epilepsy is associated with aberrant neurogenesis and ectopic migration of adult-born granule cells (abGCs), yet the molecular mechanisms driving these changes remain poorly defined. Using a pilocarpine-induced mouse model of temporal lobe epilepsy and chemogenetic silencing of abGCs via Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we previously demonstrated that abGC inhibition reduces both ectopic migration and seizure susceptibility. To identify underlying molecular regulators, we performed RNA sequencing of FACS-isolated abGCs and identified Rrm2 and Timp3 as top candidate genes modulated by seizure activity and neuronal silencing.