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American Indian and Alaska Native individuals report higher rates of substance use disorders and psychological distress compared with individuals from other racial and ethnic groups. However, few evidence-based, culturally grounded programs address substance use and mental health for urban American Indian and Alaska Native emerging adults. To test 2 culturally grounded virtual interventions for substance use among urban American Indian and Alaska Native emerging adults. In this randomized clinical trial, participants were recruited across the US from December 1, 2020, to October 27, 2023. Participants completed an online screening questionnaire. Eligibility criteria included (1) age 18 to 25 years; (2) living in an urban area in the US (not a rancheria or a reservation); (3) self-identification as American Indian or Alaska Native; (4) no opioid use disorder; and (5) English speaking. The participants completed baseline surveys, were randomized to 1 of 2 culturally grounded virtual interventions, and completed 3-, 6-, and 12-month surveys. Follow-up was completed January 28, 2025. Analysis was based on intention to treat. Participants received either 3 Traditions and Connections for Urban Native Americans (TACUNA) workshops and a wellness circle, or an opioid education health and wellness cultural (HWC) workshop (usual care). Surveys focused on opioid, alcohol, and cannabis use (primary outcome) and consequences of alcohol and other drug use, mental health, cultural connection, and peer influence (secondary outcomes). Among the 541 randomized participants (451 [83.2%] female; mean [SD] age, 22.1 [2.2] years), the TACUNA and HWC groups both reported decreased frequency of cannabis use (B [SE],  -0.44 [0.20] and -0.54 [0.21], respectively) and decreased rates of positive screens for alcohol (B [SE], -0.03 [0.01] and -0.02 [0.01], respectively) and cannabis (B [SE], -0.02 [0.01] and -0.03 [0.01], respectively) use disorders. Rates of time spent with peers who use alcohol and prescription opioids, clinical depression and anxiety, alcohol and cannabis consequences, and peer norms around alcohol, cannabis, prescription opioids, and heroin use improved in both groups. Only TACUNA participants reported decreases in frequency (B [SE], -0.51 [0.20]) and quantity (B [SE], -0.25 [0.09]) of alcohol use and quantity of cannabis use (B [SE], -0.07 [0.03]). In addition, TACUNA participants reported greater decreases in time spent around peers using cannabis and heroin and greater decreases of anxiety compared with HWC participants. In this randomized clinical trial of 2 virtual culturally grounded interventions for substance use, virtual recruitment and intervention successfully reached urban American Indian or Alaska Native emerging adults with decreased access to resources. Both groups reduced consequences and cannabis use; however, only TACUNA participants reported decreases in quantity of alcohol and cannabis use and time spent around peers using cannabis and heroin and greater decreases in anxiety. These findings emphasize the role of bringing American Indian and Alaska Native emerging adults together to discuss ways to reduce alcohol and other drug use and socially connect with their tribal communities in the urban environment in a virtual setting. ClinicalTrials.gov Identifier: NCT04617938.

Native T1 mapping has become an essential tool for quantitative myocardial tissue characterization in cardiac magnetic resonance (CMR). However, widely used techniques such as Modified Look-Locker Inversion Recovery (MOLLI) remain limited by their proprietary nature and limited accessibility, particularly in resource-constrained settings. This study aimed to develop and validate a more accessible Single-Shot T1 mapping technique as a practical alternative to MOLLI, and to assess its agreement and diagnostic performance against a reference standard (Circle Cardiovascular Imaging, CVI&#x2074;&#xb2;). A retrospective study was conducted on 40 subjects (25 healthy controls and 15 patients with cardiac pathologies) who underwent 3T CMR imaging. Native T1 values were acquired using a modified Single-Shot inversion recovery scheme (3(3)3(3)5). Quantitative analysis was performed using custom MATLAB-based post-processing and compared with reference measurements obtained using CVI&#x2074;&#xb2; software. Agreement was assessed using Bland-Altman analysis, while group differences were evaluated using independent t-tests. Pathological subjects demonstrated significantly elevated native T1 values compared to healthy controls (1566 &#xb1; 65 ms vs. 1079 &#xb1; 80 ms, p < 0.001). The proposed method showed strong agreement with the reference standard, with a mean difference of 5.7 ms and no statistically significant bias. Additionally, the Single-Shot approach exhibited significantly reduced inter-subject variability compared to CVI&#x2074;&#xb2;-based measurements. The proposed Single-Shot T1 mapping technique provides a reliable, reproducible, and accessible alternative to MOLLI, with comparable accuracy and improved numerical stability. This approach may expand access to advanced myocardial tissue characterization, particularly in low-resource settings.

Xenogeneic scaffolds derived from porcine skin offer a promising alternative due to their structural and biochemical similarities to human skin. However, current decellularization strategies compromise extracellular matrix (ECM) integrity, porosity, or mechanical performance, limiting applicability. Here, we developed a decellularized porcine matrix (DEPOMA) scaffold using an ultrasound-assisted low-detergent strategy designed to achieve effective cellular removal while preserving ECM architecture. Specifically, we focused on combining ultrasonication, hypertonic/hypotonic treatments, and reduced Triton X-100 exposure. Our protocol effectively removed cellular components with over 99% deoxyribonucleic acid (DNA) removal, while preserving key basement membrane and dermal proteins, as seen by quantitative immunohistochemistry (IHC) demonstrating 76% Laminin, approximately 66% Collagen IV, and 889% Elastin retention relative to native tissue. Scanning electron microscopy (SEM) demostrated that DEPOMA maintained native dermal ultrastructure with enhanced and uniformly distributed porosity, quantified using DIGIMIZER image analysis. Uniaxial tensile testing on DEPOMA demonstrated preserved mechanical properties comparable to native skin. The DEPOMA scaffold demonstrated markedly enhanced biocompatibility, supporting a 3.4-fold increase in primary human fibroblast metabolic activity compared to controls. In a porcine full-thickness ex vivo wound model, DEPOMA showed progressive host-derived cellular infiltration reaching a penetration depth of 147 &#xb5;m after 21 days, consistent with active scaffold integration and remodeling. When benchmarked against a detergent-based decellularized scaffold and a commercial dermal regeneration template, DEPOMA exhibited significantly improved cell viability and proliferative capacity. Collectively, these findings demonstrate that ultrasound-assisted low-detergent decellularization enables superior ECM preservation, structural integrity, and biological performance, supporting DEPOMA as a translationally optimized dermal scaffold for wound healing and regenerative medicine applications.

Cobamides are tetrapyrrole cofactors whose core structure, diverse axial ligands, and ability to access distinct redox states underpin the reactivity of a variety of enzymes, including isomerases, methyltransferases, and reductive dehalogenases. These enzymes leverage precise scaffold-controlled interactions to direct radical rearrangement, methyl group transfer, and reductive bond cleavage with high selectivity and efficiency. Despite these capabilities, the native reactivity of cobamide-dependent enzymes remains relatively underutilized for biocatalysis, and their use as catalysts for non-native reactions has only recently emerged as a promising frontier. Mechanistic studies and advances in protein engineering and synthetic biology are beginning to establish these enzymes and other cobamide-containing proteins as versatile platforms for selective C-C bond formation, C-H functionalization, alkylation, and other transformations. This perspective summarizes key mechanistic aspects of cobamide-containing protein function, highlights progress in native biocatalysis and discusses emerging strategies to exploit cobamide-containing proteins for non-native biocatalysis.

Septic arthritis of native joints requires prompt diagnosis to prevent joint destruction and sepsis. Traditional diagnostic methods, such as synovial fluid culture and cell counts, are time-consuming and can be unreliable. The Synovasure&#xae; Alpha Defensin Lateral Flow Test (Zimmer Biomet, Claymont, DE, USA) detects alpha defensin in synovial fluid and is well-established for diagnosing periprosthetic joint infections. However, its diagnostic value in native joints remains insufficiently studied. This prospective cohort study enrolled 25 adults presenting with suspected septic arthritis of the knee. Patients were excluded if they had prior knee arthroplasty or orthopedic implants. Demographics, comorbidities, vitals, and lab values were collected. Patients who tested positive for alpha defensin on aspirated synovial fluid were compared to those who tested negative. Infection was defined as a positive synovial culture, while gout was defined as positive synovial crystals. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Nineteen patients tested positive for alpha defensin, of whom four had culture-confirmed septic arthritis. All six alpha defensin test-negative patients had negative cultures. The test demonstrated a sensitivity of 100% (CI: 39%-100%), specificity of 29% (CI: 11%-52%), PPV of 21% (CI: 16%-25%), and NPV of 100% (CI: 54%-100%). Demographics, comorbidities, and serum inflammatory markers were similar between test-positive and test-negative groups. Alpha defensin test-positive patients had a significantly higher synovial polymorphonuclear neutrophil (PMN) percentage (p<0.001). All nine patients with positive synovial crystals tested positive (p=0.04). The high sensitivity and NPV of the Synovasure&#xae; Alpha Defensin Lateral Flow Test (Zimmer Biomet) demonstrate its potential utility to rapidly rule out septic arthritis in native knees. However, the test's low specificity warrants caution, as false-positive results may occur with noninfectious inflammatory processes. While the rapid turnaround may aid in early triage and exclusion of infection, confirmatory evaluation with synovial culture remains essential to prevent misdiagnosis and overtreatment.

Large Language Models (LLMs) have emerged as a powerful paradigm for scientific discovery, yet adapting them to natively comprehend complex molecular structures remains a fundamental challenge. To capture structural nuances, the community has increasingly shifted towards multimodal architectures. Existing molecular LLMs typically integrate 2D and 3D modalities via continuous projection, mapping pretrained molecular embeddings directly into the backbone LLM. However, mapping continuous embeddings from pretrained encoders into the discrete token space of LLMs creates an inherent modality gap, hindering effective semantic transfer and limiting their performance. To address these challenges, we introduce MolLingua, a token-centric, dual-modal framework designed for native molecular understanding. Specifically, we leverage a dual-branch Residual Vector Quantization (RVQ) engine to discretize these heterogeneous, high-dimensional spatial 2D and 3D features into compact code sequences rather than relying solely on continuous projections. By integrating them as learnable tokens within the LLM vocabulary, MolLingua translates structural chemistry into the native discrete language of LLMs. Extensive experiments demonstrate that our fully discrete approach effectively aligns spatial knowledge with language models, achieving state-of-the-art performance in complex chemical reasoning and competitive results in generative tasks. Our work contributes an effective, unified framework for propelling essential applications of LLMs in biomedicine.

Underutilized native legumes may contribute to the development of sustainable, nutrient-dense foods with potential relevance to malnutrition and diet-related non-communicable diseases. This study evaluated the nutritional and functional profile of five native Ecuadorian legumes (Cajanus cajan, Lablab purpureus, Phaseolus lunatus baby lima, Phaseolus lunatus big lima, and Vigna unguiculata) through proximate composition, dietary fiber, mineral content, antioxidant capacity, amino acid profiles, amino acid scores (AAS), and phytate molar ratios. Lablab purpureus showed the highest amino acid score (166.30%), followed by P. lunatus baby lima (159.46%) and V. unguiculata (156.82%), and all species exceeded the FAO/WHO indispensable amino acid reference pattern for older children, adolescents, and adults. Cajanus cajan was characterized by high dietary fiber (31.44 g/100 g) and calcium contents (5750 mg/kg), whereas Lablab purpureus and Vigna unguiculata showed higher iron and magnesium contents, together with antioxidant responses associated with phenolic compounds. Although phytate molar ratios suggested potential constraints on non-heme iron bioavailability, the comparatively low phytate ratios indicated lower predicted interference with magnesium availability. Principal component analysis explained 77.6% of the total variance and revealed differentiated nutritional profiles among species. These findings support a cautious translational interpretation of underutilized Ecuadorian legumes as differentiated plant food matrices in which phenolic compounds, dietary fiber, amino acids, and minerals may contribute to redox balance, gut barrier physiology, protein adequacy, and micronutrient nutrition.

Breast augmentation has traditionally focused on implant volume and pocket selection, often overlooking the variability of native breast anatomy. Breast tissue preservation (BTP) emphasizes preservation of fascial planes and tissue integrity, enabling prepectoral implant placement within a preserved tissue envelope. When combined with 3-dimensional (3D) imaging and ultrasound-based geometric analysis, BTP supports selective implant positioning tailored to regional deficiencies, potentially improving stability and natural aesthetic outcomes while reducing reliance on larger implant volumes and the need for scaffold support. A single center retrospective study analyzed 111 patients undergoing primary breast augmentation or augmentation-mastopexy using tissue preservation techniques, including transaxillary and inframammary approaches. Pre- and 12-month postoperative assessments incorporated 3D imaging and high-resolution ultrasound to evaluate breast geometry, tissue distribution, volumetric and angular changes, and stability. Safety outcomes and patient satisfaction were evaluated over 12 months. Among 111 patients, complication rates were low (4.5%), with no Baker III-IV capsular contracture, no implant ruptures and high satisfaction scores. Geometric analysis demonstrated consistent increases in upper, medial, and lateral angles, procedure specific inferior angle changes, preserved nipple alignment with maximal projection, and improved breast stability, supporting controlled and reproducible volume redistribution. These changes were achieved through targeted regional volume placement. This study highlights the clinical value of a comprehensive native breast assessment in real-world practice. Integrating volumetric, topographic, and angular analysis enables individualized planning, precise implant positioning, with minimally invasive BTP techniques. This approach supports biomechanical stability, demonstrates a favorable safety profile, and promotes natural outcomes in everyday surgical practice. Level of Evidence: 4 (Therapeutic).

This study compared rates of non-traumatic lower limb amputations ('amputations') among Medicare beneficiaries with diabetic foot ulcers (DFUs) who initiated purified native type 1 collagen matrix plus polyhexamethylene biguanide (PHMB) antimicrobial (PCMP) versus those beneficiaries who did not receive PCMP. In this retrospective matched cohort study, two groups of beneficiaries with DFUs were retrospectively identified from 100% Medicare Fee-for-Service Standard Analytic Files (Quarter 1 2015-Quarter 3 2023)-those receiving PCMP within six months of DFU diagnosis (index date=first PCMP claim) and those who did not receive PCMP. Beneficiaries were matched 1:1. Using Wilcoxon signed-rank tests, six-month post-index amputation rates were compared. Stratified analysis evaluated amputation rates among beneficiaries initiating PCMP within 45, 60 or 90 days of DFU diagnosis, with follow-up applications every 7-14 days for one month. Before matching, beneficiaries receiving PCMP (n=10,939) had greater disease severity, as indicated by longer duration of active ulceration and higher amputation rates in the six months pre-index date than those beneficiaries who never received PCMP (n=657,233). After matching, baseline characteristics were well balanced (n=10,862). During follow-up, beneficiaries receiving PCMP had lower six-month amputation rates than those in the matched non-PCMP cohort (9.9% versus 12.2%, respectively; p<0.001). Beneficiaries with earlier initiation of PCMP within 45, 60 or 90 days of diagnosis had lower six-month amputation rates (4.0%, 4.1% and 4.8%, respectively) compared with non-PCMP recipients (8.4%; all p<0.001). PCMP was disproportionately used in the management of beneficiaries with more complex DFUs/wound care needs. After adjusting for baseline differences, PCMP use was associated with lower rates of lower limb amputations, particularly with earlier initiation within 90 days of DFU diagnosis.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children worldwide. In the United States, and in the state of Alaska in particular, American Indian/Alaska Native (AI/AN) children experience a disproportionate burden of healthcare disparities. Understanding the epidemiology, mechanisms of injury, access to care, and long-term clinical outcomes in this vulnerable population is crucial for guiding management strategies and prevention initiatives. This scoping review aimed to characterize the epidemiology of pediatric TBI among AI/AN children in the United States; examine mechanisms of injury, hospitalization, and mortality patterns; assess disparities in diagnostic evaluation, insurance status, inpatient and post-discharge care; evaluate current prevention and intervention strategies; and and propose future directions to reduce healthcare inequities among AI/AN children. we systematically searched PubMed/MEDLINE, Embase, Scopus, Web of Science, and Google Scholar for English-language, peer-reviewed studies examining TBI in AI/AN children (<18 years). Eligible studies reported epidemiology, clinical outcomes, healthcare disparities, or interventions. Data extraction and quality assessment were conducted independently by multiple reviewers, with methodological rigor assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. AI/AN children demonstrated the highest TBI-related hospitalization and mortality rates nationally, with the burden most pronounced in children < 4 years and in adolescents. Motor vehicle accidents were the leading cause of TBI-related hospitalization and mortality, often associated with alcohol involvement and low utilization of protective equipment. Violence, including blunt trauma and firearm injuries, accounted for disproportionately higher mortality rates, with firearm-related TBI deaths up to three-fold higher compared to that among white children. Disparities extended beyond the mechanism of injury, as AI/AN children were less likely to undergo advanced imaging and experienced longer hospital stays. Additionally, AI/AN children had the lowest rates of private insurance coverage and the highest reliance on Medicaid/Medicare, contributing to the limited access to rehabilitation services and post-discharge healthcare services. AI/AN children with TBI bear a substantial burden of healthcare disparities. The limited healthcare infrastructure, insurance disparities, and cultural barriers, in addition to the geographical isolation of those who live in the state of Alaska amplify the burden of healthcare disparities faced by these children. Addressing these disparities requires a multi-faceted approach, including improved surveillance, standardized case definitions, expansion of preventive initiatives, telemedicine, workforce development and diversification, and culturally sensitive care models.

East African cattle, including Malagasy native cattle (ZMA), are generally thought to have been shaped by admixture between African taurine and Asian indicine lineages, but the detailed position and formation history of ZMA within this broader diversity remain unclear. We analyzed worldwide SNP data from 145 cattle populations comprising 4093 individuals using principal component analysis (PCA), pairwise weighted FST, outgroup-f3, f4, qpWave, and qpGraph. ZMA fell along the African taurine-Asian cattle axis in PCA. Although several West African taurine populations showed the highest absolute outgroup-f3 values with ZMA, outgroup-f3 profile comparisons showed that ZMA was most closely matched by East African cattle, especially East African Shorthorn Zebu, Boran, and Sheko, consistent with a shared African taurine ancestry background. However, f4, qpWave, and qpGraph showed that these relationships are not adequately explained by a simple clade-like relationship or a single shared admixture event, but instead suggest multiple waves of gene flow from different Asian indicine populations. Our results refine African-wide models of heterogeneous indicine ancestry by showing that, in the East African-Malagasy context, ZMA are best understood as part of a shared African taurine-related ancestry background overlaid by later lineage-specific and internally heterogeneous indicine-related admixture histories.

Misfolding often underlies rhodopsin-linked retinitis pigmentosa, and small-molecule pharmacochaperones represent a promising therapeutic strategy. However, the mechanisms by which these compounds stabilize rhodopsin remain incompletely understood. We combine amide- and histidine-specific hydrogen-deuterium exchange (HDX) mass spectrometry, protein structure network analysis, molecular docking, and functional spectroscopy to define ligand-induced conformational signatures in rhodopsin elicited by quercetin, myricetin, and chromenone, and compare them with those of native chromophore. Binding of 11-cis-retinal to opsin produces a benchmark orthosteric signature characterized by backbone protection across TM4-TM7, suppression of EX1-like exchange at TM1 and TM4 N-termini, and reframing of residue interaction networks. All three non-retinoid ligands induce partially overlapping HDX footprints consistent with interaction within the orthosteric site, but with ligand-specific differences. Quercetin most closely resembles the 11-cis-retinal pattern, whereas myricetin and chromenone show reduced and redistributed protection. These findings define structural determinants of ligand-induced opsin stabilization and provide a framework for optimizing small-molecule opsin stabilizers.

Pandemic preparedness demands the availability of state-of-the-art tools for fundamental research on viruses to support rapid development of antiviral and prophylactic interventions. Virion composition is currently studied by a limited number of disruptive techniques, while here, a novel workflow for non-invasive and label-free biochemical fingerprinting is presented. Deep-Ultraviolet Resonance Raman spectroscopy is employed as the primary analytical tool, while stoichiometric-based spectral reconstruction and multilinear regression analysis are used to perform bottom-up and top-down biochemical characterization of the vesicular stomatitis virus (VSV) in physiological-like conditions, respectively. Raman spectra from virions and single biochemical components (lipids, amino acids and nucleotides) excited at 213&#xa0;nm are used to disentangle the virus biochemical composition and to probe the mechanism of action of a lipid-disrupting virucidal drug. Available biochemical and sequence information together with single-component spectra allows the reconstruction of the full virion spectrum with excellent accuracy. Altogether, this strategy of virion biochemical fingerprinting paves the way to a better understanding of virus composition and mechanisms for inactivation.