Quantitative Viscoelastic Response (QVisR): Direct Estimation of Viscoelasticity with Neural Networks.

We present a machine learning method to directly estimate viscoelastic moduli from displacement time-series profiles generated by Viscoelastic Response (VisR) ultrasound excitations. VisR uses two colocalized acoustic radiation force pushes to approximate tissue viscoelastic creep response and tracks displacements on-axis to measure the material relaxation. A fully-connected neural network is trained to learn a nonlinear mapping from VisR displacements, the push focal depth, and the measurement axial depth to the material elastic and viscous moduli. In this work, we assess the validity of Quantitative Viscoelastic Response (QVisR) in simulated materials, propose a method of domain adaption to phantom VisR displacements, and show in vivo estimates from a clinically acquired dataset.

Space-Efficient 3D Microalgae Farming with Optimized Resource Utilization for Regenerative Food.

Photosynthetic microalgae produce valuable metabolites and are a source of sustainable food that supports life without compromising arable land. However, the light self-shading, excessive water supply, and insufficient space utilization in microalgae farming have limited its potential in the inland areas most in need of regenerative food solutions. Herein, this work develops a 3D polysaccharide-based hydrogel scaffold for vertically farming microalgae without needing liquid media. This liquid-free strategy is compatible with diverse microalgal species and enables the design of living microalgal frameworks with customizable architectures that enhance light and water utilization. This approach significantly increases microalgae yield per unit water consumption, with an 8.8-fold increase compared to traditional methods. Furthermore, the dehydrated hydrogels demonstrate a reduced size and weight (≈70% reduction), but readily recover their vitality upon rehydration. Importantly, valuable natural products can be produced in this system including proteins, carbohydrates, lipids, and carotenoids. This study streamlines microalgae regenerative farming for low-carbon biomanufacturing by minimizing light self-shading, relieving water supply, and reducing physical footprints, and democratizing access to efficient aquatic food production.

Metal-Phenolic Nanocloaks on Cancer Cells Potentiate STING Pathway Activation for Synergistic Cancer Immunotherapy.

Due to the presence of natural neoantigens, autologous tumor cells hold great promise as personalized therapeutic vaccines. Yet autologous tumor cell vaccines require multi-step production that frequently leads to the loss of immunoreactive antigens, causing insufficient immune activation and significantly hampering their clinical applications. Herein, we introduce a novel whole-cell cancer vaccine by cloaking cancer cells with lipopolysaccharide-decorated manganese(II)-phenolic networks (MnTA nanocloaks) to evoke tumor-specific immune response for highly efficacious synergistic cancer immunotherapy. The natural polyphenols coordinate with Mn2+ and immediately adhere to the surface of individual cancer cells, thereby forming a nanocloak and encapsulating tumor neoantigens. Subsequent decoration with lipopolysaccharide induces internalization by dendritic cells, where Mn2+ ions are released in the cytosol, further facilitating the activation of the stimulator of the interferon genes (STING) pathway. Highly effective tumor suppression was observed by combining the nanocloaked cancer cell treatment with anti-programmed cell death ligand 1 (anti-PD-L1) antibodies-mediated immune checkpoint blockade therapy. Our work demonstrates a universal yet simple strategy to engineer a cell-based nanobiohybrid system for enhanced cancer immunotherapy.

Cytoprotective Metal-Phenolic Network Sporulation to Modulate Microalgal Mobility and Division.

Synthetic cell exoskeletons created from abiotic materials have attracted interest in materials science and biotechnology, as they can regulate cell behavior and create new functionalities. Here, a facile strategy is reported to mimic microalgal sporulation with on-demand germination and locomotion via responsive metal-phenolic networks (MPNs). Specifically, MPNs with tunable thickness and composition are deposited on the surface of microalgae cells via one-step coordination, without any loss of cell viability or intrinsic cell photosynthetic properties. The MPN coating keeps the cells in a dormant state, but can be disassembled on-demand in response to environmental pH or chemical stimulus, thereby reviving the microalgae within 1 min. Moreover, the artificial sporulation of microalgae resulted in resistance to environmental stresses (e.g., metal ions and antibiotics) akin to the function of natural sporulation. This strategy can regulate the life cycle of complex cells, providing a synthetic strategy for designing hybrid microorganisms.

Peptide-Based Coacervate Protocells with Cytoprotective Metal-Phenolic Network Membranes.

Protocells have garnered considerable attention from cell biologists, materials scientists, and synthetic biologists. Phase-separating coacervate microdroplets have emerged as a promising cytomimetic model because they can internalize and concentrate components from dilute surrounding environments. However, the membrane-free nature of such coacervates leads to coalescence into a bulk phase, a phenomenon that is not representative of the cells they are designed to mimic. Herein, we develop a membranized peptide coacervate (PC) with oppositely charged oligopeptides as the molecularly crowded cytosol and a metal-phenolic network (MPN) coating as the membrane. The hybrid protocell efficiently internalizes various bioactive macromolecules (e.g., bovine serum albumin and immunoglobulin G) (>90%) while also resisting radicals due to the semipermeable cytoprotective membrane. Notably, the resultant PC@MPNs are capable of anabolic cascade reactions and remain in discrete protocellular populations without coalescence. Finally, we demonstrate that the MPN protocell membrane can be postfunctionalized with various functional molecules (e.g., folic acid and fluorescence dye) to more closely resemble actual cells with complex membranes, such as recognition molecules, which allows for drug delivery. This membrane-bound cytosolic protocell structure paves the way for innovative synthetic cells with structural and functional complexity.

Analysis of Social Media Involvement in Violent Injury.

This cross-sectional study uses police agency­collected information to quantify the association among social media involvement, crime, and violence.

Using phenolic polymers to control the size and morphology of calcium carbonate microparticles.

Calcium carbonate (CaCO3) is a naturally occurring mineral that occurs in biology and is used industrially. Due to its benign nature, CaCO3 microparticles have found use in the food and medical fields, where the specific size of the microparticles determine their functionality and potential applications. We demonstrate that phenolic polymers with different numbers of hydroxy groups can be used to control the diameter of CaCO3 microparticles in a range of 2-9 µm, and obtained particles were relatively uniform. The largest particles (∼9 µm in diameter) were obtained using poly(2,3,4,5-tetrahydroxystyrene) (P4HS), which showed the highest water solubility among the tested phenolic polymers. The polymer concentration and stirring speed influenced the size of microparticles, where the size of the obtained particles became smaller as the concentrations of phenolic polymers increased and as the stirring speed increased, both likely due to promoting the formation of a large number of individual crystal seeds by shielding seed-seed fusion and increasing the chances for precursor contact, respectively. The preparation time and temperature had a great influence on the morphology of the CaCO3 particles, where vaterite transforms into calcite over time. Specifically, aragonite crystals were observed at preparation temperature of 80 °C and vaterite particles with rough surfaces were obtained at 40 °C. Molecular weight and scale of reaction were also factors which affect the size and morphologies of CaCO3 particles. This research represents a facile method for producing relatively monodisperse CaCO3 microparticles with diameters that have previously proven difficult to access.

Creation of standardized tools to evaluate reporting in health research: Population Reporting Of Gender, Race, Ethnicity & Sex (PROGRES).

Despite increasing diversity in research recruitment, research finding reporting by gender, race, ethnicity, and sex has remained up to the discretion of authors. This study developped and piloted tools to standardize the inclusive reporting of gender, race, ethnicity, and sex in health research. A modified Delphi approach was used to develop standardized tools for the inclusive reporting of gender, race, ethnicity, and sex in health research. Health research, social epidemiology, sociology, and medical anthropology experts from 11 different universities participated in the Delphi process. The tools were pilot tested on 85 health research manuscripts in top health research journals to determine inter-rater reliability of the tools. The tools each spanned five dimensions for both sex and gender as well as race and ethnicity: Author inclusiveness, Participant inclusiveness, Nomenclature reporting, Descriptive reporting, and Outcomes reporting for each subpopulation. The sex and gender tool had a median score of 6 and a range of 1-15 out of 16 possible points. The percent agreement between reviewers piloting the sex and gender tool was 82%. The interrater reliability or average Cohen's Kappa was 0.54 with a standard deviation of 0.33 demonstrating moderate agreement. The race and ethnicity tool had a median score of 1 and a range of 0-15 out of 16 possible points. Race and ethnicity were both reported in only 25.8% of studies evaluated. Most studies that reported race reported only the largest subgroups; White, Black, and Latinx. The percent agreement between reviewers piloting the race and ethnicity tool was 84 and average Cohen's Kappa was 0.61 with a standard deviation of 0.38 demonstrating substantial agreement. While the overall dimension scores were low (indicating low inclusivity), the interrater reliability measures indicated moderate to substantial agreement for the respective tools. Efforts in recruitment alone will not provide more inclusive literature without improving reporting.

Supramolecular nanoarchitectonics of phenolic-based nanofiller for controlled diffusion of versatile drugs in hydrogels.

Drug-dependent design of hydrogels is currently required for engineering the controlled release of therapeutics, which is a major contributor to the technical challenges relating to the clinical translation of hydrogel-drug systems. Herein, by integrating supramolecular phenolic-based nanofillers (SPFs) into hydrogel microstructures we developed a facile strategy to endow a range of clinically relevant hydrogels with controlled release properties for diverse therapeutic agents. The assembly of multiscale SPF aggregates leads to tunable mesh size and multiple dynamic interactions between SPF aggregates and drugs, which relaxes the available choices of drugs and hydrogels. This simple approach allowed for the controlled release of 12 representative drugs evaluated with 8 commonly used hydrogels. Moreover, the anesthetic drug lidocaine was loaded into SPF-integrated alginate hydrogel and demonstrated sustained release for 14 days in vivo, validating the potential for long-term anesthesia in patients.

Synergistic Adsorption and In Situ Catalytic Conversion of SO2 by Transformed Bimetal-Phenolic Functionalized Biomass.

SO2 removal is critical to flue gas purification. However, based on performance and cost, materials under development are hardly adequate substitutes for active carbon-based materials. Here, we engineered biomass-derived nanostructured carbon nanofibers integrated with highly dispersed bimetallic Ti/CoOx nanoparticles through the thermal transition of metal-phenolic functionalized industrial leather wastes for synergistic SO2 adsorption and in situ catalytic conversion. The generation of surface-SO32- and peroxide species (O22-) by Ti/CoOx achieved catalytic conversion of adsorbed SO2 into value-added liquid H2SO4, which can be discharged from porous nanofibers. This approach can also avoid the accumulation of the adsorbed SO2, thereby achieving high desulfurization activity and a long operating life over 6000 min, preceding current state-of-the-art active carbon-based desulfurization materials. Combined with the techno-economic and carbon footprint analysis from 36 areas in China, we demonstrated an economically viable and scalable solution for real-world SO2 removal on the industrial scale.

Customizable Supraparticles Constructed from Catechol-Terminated Molecular Building Blocks with Controllable Intermolecular Interactions.

Colloidal supraparticles integrated with multicomponent primary particles come with emerging or synergetic functionalities. However, achieving the functional customization of supraparticles remains a great challenge because of the limited options of building blocks with tailorability and functional extensibility. Herein, we developed a universal approach to construct customizable supraparticles with desired properties from molecular building blocks obtained by the covalent conjugation of catechol groups with a series of orthogonal functional groups. These catechol-terminated molecular building blocks can assemble into primary particles driven by various intermolecular interactions (i.e. metal-organic coordination, host-guest, and hydrophobic interactions), and then further assemble into supraparticles governed by catechol-mediated interfacial interactions. Our strategy enables the formation of supraparticles with diverse functionalities, such as dual-pH responsiveness, light-controllable permeability, and non-invasive fluorescence labeling of living cells. The ease with which these supraparticles can be fabricated, and the ability to tailor their chemical and physical properties through the choice of metals and orthogonal functional groups used, should enable a variety of applications.

Direct synthesis of amorphous coordination polymers and metal-organic frameworks.

Coordination polymers (CPs) and their subset, metal-organic frameworks (MOFs), can have porous structures and hybrid physicochemical properties that are useful for diverse applications. Although crystalline CPs and MOFs have received the most attention to date, their amorphous states are of growing interest as they can be directly synthesized under mild conditions. Directly synthesized amorphous CPs (aCPs) can be constructed from a wider range of metals and ligands than their crystalline and crystal-derived counterparts and demonstrate numerous unique material properties, such as higher mechanical robustness, increased stability and greater processability. This Review examines methods for the direct synthesis of aCPs and amorphous MOFs, as well as their properties and characterization routes, and offers a perspective on the opportunities for the widespread adoption of directly synthesized aCPs.

Illicit Fentanyl Exposure Among Victims of Violence Treated at a Trauma Center.

INTRODUCTION: Opioid overdoses and violent injury are leading causes of death in the United States, yet testing for novel opioids like fentanyl remains uncommon. The purpose of this investigation is to characterize a population of victims of violence who test positive for illicit fentanyl. METHODS: Retrospective cohort study of patients treated at a level-one trauma center between January 31, 2019 and February 21, 2020. Data were extracted from the electronic medical record. Subjects were included if they had an encounter diagnosis for a violent or intentional injury, using the International Classification of Diseases, v10 (X92-Y09). We excluded patients who received licit fentanyl as a part of their care before testing. Those who tested positive for fentanyl exposure on our standard hospital urine drug screen were considered to have been exposed to illicit fentanyl. Those testing negative for fentanyl were considered controls. RESULTS: Of the 1132 patients treated for intentional injuries during the study period, 366 were included in the study (32.3%). Of these, 133 (36.3%) subjects were exposed to illicit fentanyl prehospital. There were no demographic differences between cases and controls. Cases had a lower GCS voice score on arrival (median = 4, interquartile range [IQR] = 4-5 versus median = 5, IQR = 4-5, P = 0.02), higher rates of ventilator usage (32.3% versus 21.5%, P = 0.02), and more intensive care unit admissions (27.1% versus 12.0%, P = 0.005). More than half of cases tested negative for opiates (78/133, 58.6%). Cases had more trauma center encounters (26.3% had ≥2 visits versus 15.5%). CONCLUSIONS: Exposure to illicit fentanyl was common among victims of violence in this single-center study. These patients are at increased risk of being admitted to intensive care units and repeated trauma center visits, suggesting fentanyl testing may help identify those who could benefit from violence prevention and substance abuse treatment.

Modular Metal-Quinone Networks with Tunable Architecture and Functionality.

Nanostructured materials with tunable structures and functionality are of interest in diverse areas. Herein, metal ions are coordinated with quinones through metal-acetylacetone coordination bonds to generate a class of structurally tunable, universally adhesive, hydrophilic, and pH-degradable materials. A library of metal-quinone networks (MQNs) is produced from five model quinone ligands paired with nine metal ions, leading to the assembly of particles, tubes, capsules, and films. Importantly, MQNs show bidirectional pH-responsive disassembly in acidic and alkaline solutions, where the quinone ligands mediate the disassembly kinetics, enabling temporal and spatial control over the release of multiple components using multilayered MQNs. Leveraging this tunable release and the inherent medicinal properties of quinones, MQN prodrugs with a high drug loading (>89 wt %) are engineered using doxorubicin for anti-cancer therapy and shikonin for the inhibition of the main protease in the SARS-CoV-2 virus.

Site-Specific Antibody Assembly on Nanoparticles via a Versatile Coating Method for Improved Cell Targeting.

Antibody-nanoparticle conjugates are promising candidates for precision medicine. However, developing a controllable method for conjugating antibodies to nanoparticles without compromising the antibody activity represents a critical challenge. Here, a facile and generalizable film-coating method is presented using zeolitic imidazole framework-8 (ZIF-8) to immobilize antibodies on various nanoparticles in a favorable orientation for enhanced cell targeting. Different model and therapeutic antibodies (e.g., Herceptin) are assembled on nanoparticles via a biomineralized film-coating method and exhibited high antibody loading and targeting efficiencies. Importantly, the antibodies selectively bind to ZIF-8 via their Fc regions, which favorably exposes the functional Fab regions to the biological target, thus improving the cell targeting ability of antibody-coated nanoparticles. In combination, molecular dynamics simulations and experimental studies on antibody immobilization, orientation efficiency, and biofunctionality collectively demonstrate that this versatile site-specific antibody conjugation method provides effective control over antibody orientation and leads to improved cell targeting for a variety of nanoparticles.

Implementation of an Outpatient Violence Intervention Program to Increase Service Uptake.

Challenges in participant recruitment and retention limit the effectiveness of hospital-based violence intervention programs (HVIPs). This study aimed to determine if an outpatient violence intervention program (VIP) could be integrated into a trauma clinic and increase uptake of violence prevention services. Patients previously hospitalized for intent-to-harm being seen for outpatient follow-up were eligible. VIP counselors met with participants during their clinic visit, administered the survey, and offered violence prevention services (April to June 2019). Patients were followed for 6 months to assess involvement. The primary outcome of interest was long-term participation in the VIP, defined as uptake of services at 6 months, in comparison to inpatient recruitment. Out of 76 patients, 34 (44.7%) did not appear for their appointment. The remainder (n = 42) were offered participation in the study, of which 32 (76.2%) completed the survey. From the group offered VIP services, 57.1% expressed interest, and 5 (20.8%) ultimately took part yielding an overall participation rate of 11.9% at 6 months. The inpatient recruitment rate in 2019 was 2.4%. An outpatient VIP program can be integrated into a clinic setting but suffers from the same challenges faced by inpatient programs resulting in low rates of long-term participation in services. Although a high proportion of participants reported interest, actual engagement at 6 months was low. Reasons behind low participation in VIP services must be investigated.

"We're playing on the same team": Communication (dis)connections between trauma patients and surgical residents.

BACKGROUND: Patient-physician communication is key to better clinical outcomes and patient well-being. Communication between trauma patients and their physicians remains relatively unexplored. We aimed to identify and characterize the range of strengths and challenges in patient-physician communication in the setting of trauma care. METHODS: A qualitative, grounded theory approach was used to explore communication strengths and challenges for patients and residents. Patients previously admitted to the trauma service for violent injuries were recruited and interviewed in-person during their trauma clinic appointments. Surgical residents were recruited via email and interviewed virtually via Zoom. Anonymous, semistructured interviews were conducted until thematic saturation was reached. RESULTS: Twenty-nine interviews with patients and 14 interviews with residents were conducted. Patients reported feeling ignored and misunderstood and having inadequate communication with physicians. Residents cited lack of time, patients' lack of health literacy, differences in background, and emotional responses to trauma as barriers to effective communication with patients. Patients and residents reported an understanding of each other's stressors, similar emotional experiences regarding traumatic stress, and a desire to communicate with each other in greater depth both inside and outside of the hospital. CONCLUSION: Trauma patients and residents can feel disconnected due to the lack of time for thorough communication and differences in background; however, they understand each other's stressors and share similar emotional responses regarding trauma and a desire for increased communication, connection, and solidarity. Leveraging these shared values to guide interventions, such as a resident curriculum, may help bridge disconnects and improve their communication. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Exploring emergent barriers to hospital-based violence intervention programming during the COVID-19 pandemic.

National rates of gun violence have risen during the COVID-19 pandemic. There are many contributing factors to this increase, including the compounding consequences of social isolation, unstable housing, decreased economic stability, and ineffective and violent policing of communities of color. The effects of these factors are exacerbated by the pandemic's impact on the provision and availability of psychosocial services for individuals in marginalized communities, particularly those who have been violently injured. Hospital-based violence intervention programs (HVIPs) have been identified as a crucial intervention strategy in reducing repeat violent injury. The ongoing COVID-19 pandemic has engendered, significant barriers in HVIPs' attempts to assist program participants in achieving their health-related and social goals. This research offers insight into the complexities of providing social services during the convergence of two public health crises-COVID-19 and gun violence-at the HVIPs associated with the two busiest trauma centers in the state of Maryland. In considering the effects of inadequate financial support and resources, issues with staffing, and the shift to virtual programming due to restrictions on in-person care, we suggest possible changes to violence prevention programming to increase the quality of care provided to participants in a manner reflective of their unique structural positions.

Tannic acid-inspired star polymers for functional metal-phenolic networks with tunable pore sizes.

Tannic acid (TA) is a structurally undefined natural dendritic polyphenol. Here, we introduce a series of TA-inspired polymers with different arm lengths, Mn, and phenolic groups that can be used to engineer metal-phenolic network (MPN) capsules with different properties including controlled permeability, high biocompatibility, and fluorescence.

Role of Molecular Interactions in Supramolecular Polypeptide-Polyphenol Networks for Engineering Functional Materials.

Supramolecular assembly affords the development of a wide range of polypeptide-based biomaterials for drug delivery and nanomedicine. However, there remains a need to develop a platform for the rapid synthesis and study of diverse polypeptide-based materials without the need for employing complex chemistries. Herein, we develop a versatile strategy for creating polypeptide-based materials using polyphenols that display multiple synergistic cross-linking interactions with different polypeptide side groups. We evaluated the diverse interactions operating within these polypeptide-polyphenol networks via binding affinity, thermodynamics, and molecular docking studies and found that positively charged polypeptides (Ka of ∼2 × 104 M-1) and polyproline (Ka of ∼2 × 106 M-1) exhibited stronger interactions with polyphenols than other amino acids (Ka of ∼2 × 103 M-1). Free-standing particles (capsules) were obtained from different homopolypeptides using a template-mediated strategy. The properties of the capsules varied with the homopolypeptide used, for example, positively charged polypeptides produced thicker shell walls (120 nm) with reduced permeability and involved multiple interactions (i.e., electrostatic and hydrogen), whereas uncharged polypeptides generated thinner (10 nm) and more permeable shell walls due to the dominant hydrophobic interactions. Polyarginine imparted cell penetration and endosomal escape properties to the polyarginine-tannic acid capsules, enabling enhanced delivery of the drug doxorubicin (2.5 times higher intracellular fluorescence after 24 h) and a corresponding higher cell death in vitro when compared with polyproline-tannic acid capsules. The ability to readily complex polyphenols with different types of polypeptides highlights that a wide range of functional materials can be generated for various applications.