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Lanthanide rare-earth metals are ubiquitous in modern technologies1-5, but we know little about chemistry of the 61st element, promethium (Pm)6, a lanthanide that is highly radioactive and inaccessible. Despite its importance7,8, Pm has been conspicuously absent from the experimental studies of lanthanides, impeding our full comprehension of the so-called lanthanide contraction phenomenon: a fundamental aspect of the periodic table that is quoted in general chemistry textbooks. Here we demonstrate a stable chelation of the 147Pm radionuclide (half-life of 2.62 years) in aqueous solution by the newly synthesized organic diglycolamide ligand. The resulting homoleptic PmIII complex is studied using synchrotron X-ray absorption spectroscopy and quantum chemical calculations to establish the coordination structure and a bond distance of promethium. These fundamental insights allow a complete structural investigation of a full set of isostructural lanthanide complexes, ultimately capturing the lanthanide contraction in solution solely on the basis of experimental observations. Our results show accelerated shortening of bonds at the beginning of the lanthanide series, which can be correlated to the separation trends shown by diglycolamides9-11. The characterization of the radioactive PmIII complex in an aqueous environment deepens our understanding of intra-lanthanide behaviour12-15 and the chemistry and separation of the f-block elements16.
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Deep proteomic profiling of complex biological and medical samples available at low nanogram and subnanogram levels is still challenging. Thorough optimization of settings, parameters, and conditions in nanoflow liquid chromatography-tandem mass spectrometry (MS)-based proteomic profiling is crucial for generating informative data using amount-limited samples. This study demonstrates that by adjusting selected instrument parameters, e.g., ion injection time, automated gain control, and minimally altering the conditions for resuspending or storing the sample in solvents of different compositions, up to 15-fold more thorough proteomic profiling can be achieved compared to conventionally used settings. More specifically, the analysis of 1 ng of the HeLa protein digest standard by Q Exactive HF-X Hybrid Quadrupole-Orbitrap and Orbitrap Fusion Lumos Tribrid mass spectrometers yielded an increase from 1758 to 5477 (3-fold) and 281 to 4276 (15-fold) peptides, respectively, demonstrating that higher protein identification results can be obtained using the optimized methods. While the instruments applied in this study do not belong to the latest generation of mass spectrometers, they are broadly used worldwide, which makes the guidelines for improving performance desirable to a wide range of proteomics practitioners.
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Proteômica , Espectrometria de Massas em Tandem , Proteômica/métodos , Humanos , Espectrometria de Massas em Tandem/métodos , Células HeLa , Cromatografia Líquida/métodos , Proteoma/análise , Peptídeos/análise , Peptídeos/químicaRESUMO
The surging demand for high-purity individual lanthanides necessitates the development of novel and exceptionally selective separation strategies. At the heart of these separation systems is an organic compound that, based on its structural features, selectively recognizes the lighter or heavier lanthanides in the trivalent lanthanide (Ln) series. This work emphasizes the significant implications resulting from modifying the donor group configuration within an N,O-based tetradentate ligand and the changes in the solvation environment of Ln ions in the process of separating Lns, with the unique ability to achieve peak selectivity in the light, medium, and heavy Ln regions. The structural rigidity of the bis-lactam-1,10-phenanthroline ligand enforces size-based selectivity, displaying an exceptional affinity for Lns having larger ionic radii such as La. Modifying the ligand by eliminating one preorganization element (phenanthroline â bipyridine) results in the fast formation of complexes with light Lns, but, in the span of hours, the peak selectivity shifts toward middle Ln (Sm), resulting in time-resolved separation. As expected, at low nitric acid concentrations, the neutral tetradentate ligand complexes with Ln3+ ions. However, the change in extraction mechanism is observed at high nitric acid concentrations, leading to the formation and preferential extraction of anionic heavy Ln species, [Ln(NO3)x+3]x-, that self-assemble with two ligands that have undergone protonation, forming intricate supramolecular architectures. The tetradentate ligand that is structurally balanced with restrictive and unrestrictive motifs demonstrates unique, controllable selectivity for light, middle, and heavy Lns, underscoring the pivotal role of solvation and ion interactions within the first and second coordination spheres.
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Uranium is arguably the most essential element in the actinide series, serving as a crucial component of nuclear fuels. While U is recognized for engaging the 5f orbitals in chemical bonds under normal conditions, little is known about its coordination chemistry and the nature of bonding interactions at extreme conditions of high temperature. Here we report experimental and computational evidence for the shrinkage of the average U-ligand distance in UCl3 upon the solid-to-molten phase transition, leading to the formation of a significant fraction of short, transient U-Cl bonds with the enhanced involvement of U 5f valence orbitals. These findings reveal that extreme temperatures create an unusual heterogeneous bonding environment around U(III) with distinct inner- and outer-coordination subshells.
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The covalent organic frameworks (COFs) possessing high crystallinity and capability to capture low-concentration CO2 (400 ppm) from air are still underdeveloped. The challenge lies in simultaneously incorporating high-density active sites for CO2 insertion and maintaining the ordered structure. Herein, a structure engineering approach is developed to afford an ionic pair-functionalized crystalline and stable fluorinated COF (F-COF) skeleton. The ordered structure of the F-COF is well maintained after the integration of abundant basic fluorinated alcoholate anions, as revealed by synchrotron X-ray scattering experiments. The breakthrough test demonstrates its attractive performance in capturing (400 ppm) CO2 from gas mixtures via OâC bond formation, as indicated by the in situ spectroscopy and operando nuclear magnetic resonance spectroscopy using 13C-labeled CO2 sources. Both theoretical and experimental thermodynamic studies reveal the reaction enthalpy of ≈-40 kJ mol-1 between CO2 and the COF scaffolds. This implies weaker interaction strength compared with state-of-the-art amine-derived sorbents, thus allowing complete CO2 release with less energy input. The structure evolution study from synchrotron X-ray scattering and small-angle neutron scattering confirms the well-maintained crystalline patterns after CO2 insertion. The as-developed proof-of-concept approach provides guidance on anchoring binding sites for direct air capture (DAC) of CO2 in crystalline scaffolds.
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Photostasis is the light-dependent maintenance of energy balance associated with cellular homeostasis in photoautotrophs. We review evidence that illustrates how photosynthetic adaptation in polar photoautrophs such as aquatic green algae, cyanobacteria, boreal conifers as well as terrestrial angiosperms exhibit an astonishing plasticity in structure and function of the photosynthetic apparatus. This plasticity contributes to the maintenance of photostasis, which is essential for the long-term survival in the seemingly inhospitable Antarctic and Arctic habitats. However, evidence indicates that polar photoautrophic species exhibit different functional solutions for the maintenance of photostasis. We suggest that this reflects, in part, the genetic diversity symbolized by inherent genetic redundancy characteristic of polar photoautotrophs which enhances their survival in a thermodynamically challenging environment.
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Adaptação Fisiológica , Fotossíntese , Fotossíntese/fisiologia , Regiões Árticas , Regiões Antárticas , Cianobactérias/fisiologia , Cianobactérias/genética , Clorófitas/fisiologia , Clorófitas/genética , Ecossistema , Luz , Magnoliopsida/fisiologia , Magnoliopsida/genética , Traqueófitas/fisiologia , Traqueófitas/genéticaRESUMO
PURPOSE: Vision loss associated with opacification of the cornea is one of the leading causes of blindness globally. However, the epidemiological data pertaining to the demographics, associated etiological causes and reduced vision in corneal opacity patients continue to be sparse. This study assesses the case frequencies, underlying etiologies, and vision outcomes in patients diagnosed with corneal opacity, in the United States. DESIGN: Retrospective cohort study PARTICIPANTS: Patients in the IRIS® Registry (Intelligent Research in Sight) who were diagnosed with corneal opacity between January 1st, 2013, and November 30th, 2020. METHODS: The IRIS Registry contains demographic and clinical data of 79,887,324 patients who presented to eye clinics during the study period. We identified patients with corneal opacity using International Classification of Disease (ICD) codes (ICD-9, and -10) of "371" (corneal scar) and "H17" (corneal opacity), respectively. The analyzed data included demographic parameters included age, sex, race, ethnicity, and geographical location. We evaluated clinical data including laterality, etiology, disease descriptors, and best-corrected visual acuity (VA) up to 1 year before the onset (± 30 days), at the time of diagnosis, and at one year following diagnosis (± 30 days). MAIN OUTCOME MEASURES: Case frequencies, etiology, and vision outcomes in patients diagnosed with corneal opacity. RESULTS: We identified 5,220,382 patients who were diagnosed with corneal opacity and scars using H17 (ICD-10) and 371.0 (ICD-9) codes over seven years. The case frequency of corneal opacity during the study period was 6,535 cases per 100,000 patients (6.5%). The mean age of the patients was 63.36±18.14 years and the majority were female (57.6%). In the cohort, 38.39% and 30.00% of patients had bilateral and unilateral corneal opacity, respectively. Most of the patients were White (69.13%), followed by Black or African American (6.84%), Asian (2.45%), American Indian or Alaska Native(0.34%), Native Hawaii or other Pacific Islander(0.19%). Among the patients with corneal opacity, 7.34% had Hispanic or Latino ethnicity. The primary etiologies associated with corneal opacity included corneal dystrophies (64.66%) followed by edema (18.25%), ulcer (7.78%), keratoconjunctivitis (7.18%), degeneration (5.62%), neovascularization (6.27%), and trauma (5.28%). Visual acuity of the patients significantly worsened due to corneal opacity (0.46±0.74 logMAR; â¼20/58 in Snellen) and did not improve to the baseline (0.37±0.68 logMAR, â¼20/46 in Snellen) post-management (0.43±0.77 logMAR, â¼20/54 in Snellen). The multiple linear regression analysis showed worse vision outcomes in females (compared to males), and Asian, Black or African American, and American Indian or Alaska Native (compared to White) patients. Additionally, worse vision outcomes were observed in patients with opacity associated with corneal malformation, degenerative disorders, edema, injury, and ulcer compared to those with hereditary corneal dystrophy. CONCLUSIONS: Our study shows that the corneal opacity was diagnosed in 6.5% of the patients in the IRIS Registry and it was primarily associated with corneal dystrophies. The final vision outcomes in corneal opacity patients were significantly worse compared to baseline. The worse vision outcomes were associated with sociodemographic differences that might be associated with disparities in access, utilization, and care patterns.
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Conjugates of benzothiophene-fused azacyclononyne BT9N-NH2 with fluorescent dyes were developed to visualise azidoglycans intracellularly. The significance of the cycloalkyne core was demonstrated by comparing new reagents with DBCO- and BCN-dye conjugates. To reduce non-specificity during intracellular bioconjugation using SPAAC, less reactive BT9N-dye reagents are preferred over highly reactive DBCO- and BCN-dye conjugates.
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Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes. Encapsulating α-emitting radionuclides within nanoparticles can help overcome many of these challenges. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are a biodegradable and biocompatible delivery platform that has been used for drug delivery. In this study, PLGA nanoparticles are utilized for encapsulation and retention of actinium-225 ([225Ac]Ac3+). Encapsulation of [225Ac]Ac3+ within PLGA nanoparticles (Zave = 155.3 nm) was achieved by adapting a double-emulsion solvent evaporation method. The encapsulation efficiency was affected by both the solvent conditions and the chelation of [225Ac]Ac3+. Chelation of [225Ac]Ac3+ to a lipophilic 2,9-bis-lactam-1,10-phenanthroline ligand ([225Ac]AcBLPhen) significantly decreased its release (< 2%) and that of its decay daughters (< 50%) from PLGA nanoparticles. PLGA nanoparticles encapsulating [225Ac]AcBLPhen significantly increased the delivery of [225Ac]Ac3+ to murine (E0771) and human (MCF-7 and MDA-MB-231) breast cancer cells with a concomitant increase in cell death over free [225Ac]Ac3+ in solution. These results demonstrate that PLGA nanoparticles have potential as radionuclide delivery platforms for TAT to advance precision radiotherapy for cancer. In addition, this technology offers an alternative use for ligands with poor aqueous solubility, low stability, or low affinity, allowing them to be repurposed for TAT by encapsulation within PLGA nanoparticles.
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Actínio , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Actínio/química , Humanos , Linhagem Celular Tumoral , Animais , Partículas alfa/uso terapêutico , Camundongos , Feminino , Materiais Biocompatíveis/química , Neoplasias da Mama/tratamento farmacológico , Radioimunoterapia/métodosRESUMO
Papain-like protease PLpro, a domain within a large polyfunctional protein, nsp3, plays key roles in the life cycle of SARS-CoV-2, being responsible for the first events of cleavage of a polyprotein into individual proteins (nsp1-4) as well as for the suppression of cellular immunity. Here, we developed a new genetically encoded fluorescent sensor, named PLpro-ERNuc, for detection of PLpro activity in living cells using a translocation-based readout. The sensor was designed as follows. A fragment of nsp3 protein was used to direct the sensor on the cytoplasmic surface of the endoplasmic reticulum (ER) membrane, thus closely mimicking the natural target of PLpro. The fluorescent part included two bright fluorescent proteins-red mScarlet I and green mNeonGreen-separated by a linker with the PLpro cleavage site. A nuclear localization signal (NLS) was attached to ensure accumulation of mNeonGreen into the nucleus upon cleavage. We tested PLpro-ERNuc in a model of recombinant PLpro expressed in HeLa cells. The sensor demonstrated the expected cytoplasmic reticular network in the red and green channels in the absence of protease, and efficient translocation of the green signal into nuclei in the PLpro-expressing cells (14-fold increase in the nucleus/cytoplasm ratio). Then, we used PLpro-ERNuc in a model of Huh7.5 cells infected with the SARS-CoV-2 virus, where it showed robust ER-to-nucleus translocation of the green signal in the infected cells 24 h post infection. We believe that PLpro-ERNuc represents a useful tool for screening PLpro inhibitors as well as for monitoring virus spread in a culture.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Células HeLa , COVID-19/virologia , COVID-19/diagnóstico , COVID-19/metabolismo , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/virologia , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , Proteínas Luminescentes/metabolismo , Proteínas Luminescentes/genética , Proteases 3C de Coronavírus/metabolismo , Transporte Proteico , Técnicas Biossensoriais/métodosRESUMO
The preparation and application of the composite material "crosslinked polyvinyl alcohol-magnetite" as a sensitive matrix for use in digital colorimetry and optical micrometry methods are discussed. The material was synthesized in the form of spherical granules (for micrometry) and thin films (for digital colorimetry). The obtained composites were characterized by the registration of magnetization curves. It was shown that the amount of grown Fe3O4 particles in the polymer gel is in linear dependence with the iron salt concentrations in the impregnating solutions. The composite granules were applied to determining monosaccharides using optical micrometry. The optimal pH value for the total amount of monosaccharides' determination was 8.6. The study of the analytical response of composite granules and films performed with a low limit of detection (7.9 mmol/dm3) of both glucose and fructose and a possibility of the control of high alcohol contention in water media. The granules were used to determine the total carbohydrate content in samples of natural honey and syrups with high fructose contents, while the films were used to control the alcohol content in hand antiseptics. The results obtained are in good agreement with the data provided by the manufacturers.
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Method development for mass spectrometry (MS)-based thermal shift proteomic assays have advanced to probe small molecules with known and unknown protein-ligand interaction mechanisms and specificity, which is predominantly used in characterization of drug-protein interactions. In the discovery of target and off-target protein-ligand interactions, a thorough investigation of method development and their impact on the sensitivity and accuracy of protein-small molecule and protein-protein interactions is warranted. In this review, we discuss areas of improvement at each stage of thermal proteome profiling data analysis that includes processing of MS-based data, method development, and their effect on the overall quality of thermal proteome profiles. We also overview the optimization of experimental strategies and prioritization of an increased number of independent biological replicates over the number of evaluated temperatures.
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Proteoma , Proteômica , Proteoma/análise , Proteômica/métodos , Ligantes , Espectrometria de Massas/métodos , Análise de DadosRESUMO
Infections are responsible for approximately one out of six cases of cancer worldwide [...].
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Clinical and biological samples are often scarce and precious (e.g., rare cell isolates, microneedle tissue biopsies, small-volume liquid biopsies, and even single cells or organelles). Typical large-scale proteomic methods, where significantly higher protein amounts are analyzed, are not directly transferable to the analysis of limited samples due to their incompatibility with pg-, ng-, and low-µg-level protein sample amounts. Here, we report the on-microsolid-phase extraction tip (OmSET)-based sample preparation workflow for sensitive analysis of limited biological samples to address this challenge. The developed platform was successfully tested for the analysis of 100-10,000 typical mammalian cells and is scalable to allow for lower and larger protein amounts and more samples to be analyzed (i.e., higher throughput of analysis).
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Proteômica , Extração em Fase Sólida , Fluxo de Trabalho , Proteômica/métodos , Humanos , Extração em Fase Sólida/métodos , Proteínas/análise , Proteoma/análiseRESUMO
The development of reliable single-cell dispensers and substantial sensitivity improvement in mass spectrometry made proteomic profiling of individual cells achievable. Yet, there are no established methods for single-cell glycome analysis due to the inability to amplify glycans and sample losses associated with sample processing and glycan labeling. In this work, we present an integrated platform coupling online in-capillary sample processing with high-sensitivity label-free capillary electrophoresis-mass spectrometry for N-glycan profiling of single mammalian cells. Direct and unbiased quantitative characterization of single-cell surface N-glycomes are demonstrated for HeLa and U87 cells, with the detection of up to 100 N-glycans per single cell. Interestingly, N-glycome alterations are unequivocally detected at the single-cell level in HeLa and U87 cells stimulated with lipopolysaccharide. The developed workflow is also applied to the profiling of ng-level amounts (5-500 ng) of blood-derived protein, extracellular vesicle, and total plasma isolates, resulting in over 170, 220, and 370 quantitated N-glycans, respectively.
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Eletroforese Capilar , Glicômica , Espectrometria de Massas , Polissacarídeos , Análise de Célula Única , Humanos , Eletroforese Capilar/métodos , Polissacarídeos/metabolismo , Polissacarídeos/sangue , Análise de Célula Única/métodos , Células HeLa , Espectrometria de Massas/métodos , Glicômica/métodos , Proteômica/métodos , Vesículas Extracelulares/metabolismo , Lipopolissacarídeos , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/metabolismoRESUMO
PURPOSE: The current study queries the American Academy of Ophthalmology (AAO) Intelligent Research in Sight (IRIS) registry for data on the epidemiology, work-up, and management patterns of autoimmune orbital inflammation. METHODS: Analysis and description of patient data from the IRIS registry between 2013 and 2019 reviewing patients with autoimmune or idiopathic orbital inflammation with filters based on International Classification of Disease (ICD) and Current Procedural Terminology (CPT) codes. Patients with thyroid eye disease, orbital cellulitis, and orbital abscess were excluded. MAIN OUTCOME MEASURES: Demographic descriptions included gender, age, geographic region, and treatment. Sub-analysis was performed by assessing rates of imaging, biopsy, lab work-up, and diagnostic categories. RESULTS: In a final cohort of 20,584 patients, the mean age of onset of orbital inflammation was 51.7 years; 67% female; and 63% Caucasian, 21% unknown, 12% Black, 2.6% Asian, and 1.5% other. Only 49 had imaging, 78 had laboratory work-up, and 1,411 had biopsy codes. Treatment results showed 166 patients receiving antibiotics, 224 patients receiving steroids, and 35 patients receiving both. CONCLUSIONS: This study assessed the epidemiology, diagnostic patterns, and treatment patterns for orbital inflammation through the AAO IRIS registry. Practise patterns suggest a relatively low overall rate of imaging and laboratory studies compared to biopsies, although this certainly under-represents the actual number of imaging and laboratory studies and exemplifies the inherent imprecision of using a large database. However, the methodology of this study provides a framework of approaching the IRIS registry for oculoplastic research.
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Protein complexes are essential for proteins' folding and biological function. Currently, native analysis of large multimeric protein complexes remains challenging. Structural biology techniques are time-consuming and often cannot monitor the proteins' dynamics in solution. Here, a capillary electrophoresis-mass spectrometry (CE-MS) method is reported to characterize, under near-physiological conditions, the conformational rearrangements of â½1 MDa GroEL upon complexation with binding partners involved in a protein folding cycle. The developed CE-MS method is fast (30 min per run), highly sensitive (low-amol level), and requires â½10 000-fold fewer samples compared to biochemical/biophysical techniques. The method successfully separates GroEL14 (â½800 kDa), GroEL7 (â½400 kDa), GroES7 (â½73 kDa), and NanA4 (â½130 kDa) oligomers. The non-covalent binding of natural substrate proteins with GroEL14 can be detected and quantified. The technique allows monitoring of GroEL14 conformational changes upon complexation with (ATPγS)4-14 and GroES7 (â½876 kDa). Native CE-pseudo-MS3 analyses of wild-type (WT) GroEL and two GroEL mutants result in up to 60% sequence coverage and highlight subtle structural differences between WT and mutated GroEL. The presented results demonstrate the superior CE-MS performance for multimeric complexes' characterization versus direct infusion ESI-MS. This study shows the CE-MS potential to provide information on binding stoichiometry and kinetics for various protein complexes.
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Dobramento de Proteína , Proteínas , Conformação Proteica , Eletroforese Capilar , Espectrometria de MassasRESUMO
The development of an effective combined vaccine represents a crucial strategy for preventing outbreaks of infectious diseases and reducing the burden on healthcare resources. Developing a combined vaccine against both influenza and the coronavirus is a promising approach, but it is still in the early stages of development. This paper reports on a novel combined pentavalent candidate vaccine that has shown promising results in mice, with statistically significant differences in mean antibody titer against the coronavirus and the influenza antigens compared to placebo. We have shown that the coronavirus antigen is capable of inducing an immune response autonomously, regardless of the presence of the influenza antigens in a combined vaccine. On the other hand, the presence of the coronavirus antigen in a combined vaccine showed to enhance the immune response against some of the studied influenza antigens, suggesting that these antigens may act in synergy and elicit an enhanced immune response. The absence of dose-dependent difference in mean antibody titer within the same antigenic groups of vaccine preparations suggested that even small amounts of the coronavirus and the influenza antigens could induce an immune response just as good as high-dose vaccine preparations, which certainly has important safety and cost implications. The vaccine is soon to be ready for clinical trials and mass production.
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Ácido Betulínico , COVID-19 , Vacinas contra Influenza , Influenza Humana , Animais , Camundongos , Humanos , Influenza Humana/prevenção & controle , COVID-19/prevenção & controle , Adjuvantes Imunológicos , Vacinação , Vacinas Combinadas , Anticorpos AntiviraisRESUMO
Purpose: To describe the prevalence of missing sociodemographic data in the IRIS® (Intelligent Research in Sight) Registry and to identify practice-level characteristics associated with missing sociodemographic data. Design: Cross-sectional study. Participants: All patients with clinical encounters at practices participating in the IRIS Registry prior to December 31, 2020. Methods: We describe geographic and temporal trends in the prevalence of missing data for each sociodemographic variable (age, sex, race, ethnicity, geographic location, insurance type, and smoking status). Each practice contributing data to the registry was categorized based on the number of patients, number of physicians, geographic location, patient visit frequency, and patient population demographics. Main Outcome Measures: Multivariable linear regression was used to describe the association of practice-level characteristics with missing patient-level sociodemographic data. Results: This study included the electronic health records of 66 477 365 patients receiving care at 3306 practices participating in the IRIS Registry. The median number of patients per practice was 11 415 (interquartile range: 5849-24 148) and the median number of physicians per practice was 3 (interquartile range: 1-7). The prevalence of missing patient sociodemographic data were 0.1% for birth year, 0.4% for sex, 24.8% for race, 30.2% for ethnicity, 2.3% for 3-digit zip code, 14.8% for state, 5.5% for smoking status, and 17.0% for insurance type. The prevalence of missing data increased over time and varied at the state-level. Missing race data were associated with practices that had fewer visits per patient (P < 0.001), cared for a larger nonprivately insured patient population (P = 0.001), and were located in urban areas (P < 0.001). Frequent patient visits were associated with a lower prevalence of missing race (P < 0.001), ethnicity (P < 0.001), and insurance (P < 0.001), but a higher prevalence of missing smoking status (P < 0.001). Conclusions: There are geographic and temporal trends in missing race, ethnicity, and insurance type data in the IRIS Registry. Several practice-level characteristics, including practice size, geographic location, and patient population, are associated with missing sociodemographic data. While the prevalence and patterns of missing data may change in future versions of the IRIS registry, there will remain a need to develop standardized approaches for minimizing potential sources of bias and ensure reproducibility across research studies. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.