Coding of Childhood Psychiatric and Neurodevelopmental Disorders in Electronic Health Records of a Large Integrated Health Care System: Validation Study.

Background: Mental, emotional, and behavioral disorders are chronic pediatric conditions, and their prevalence has been on the rise over recent decades. Affected children have long-term health sequelae and a decline in health-related quality of life. Due to the lack of a validated database for pharmacoepidemiological research on selected mental, emotional, and behavioral disorders, there is uncertainty in their reported prevalence in the literature. objectives: We aimed to evaluate the accuracy of coding related to pediatric mental, emotional, and behavioral disorders in a large integrated health care system's electronic health records (EHRs) and compare the coding quality before and after the implementation of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) coding as well as before and after the COVID-19 pandemic. Methods: Medical records of 1200 member children aged 2-17 years with at least 1 clinical visit before the COVID-19 pandemic (January 1, 2012, to December 31, 2014, the ICD-9-CM coding period; and January 1, 2017, to December 31, 2019, the ICD-10-CM coding period) and after the COVID-19 pandemic (January 1, 2021, to December 31, 2022) were selected with stratified random sampling from EHRs for chart review. Two trained research associates reviewed the EHRs for all potential cases of autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), major depression disorder (MDD), anxiety disorder (AD), and disruptive behavior disorders (DBD) in children during the study period. Children were considered cases only if there was a mention of any one of the conditions (yes for diagnosis) in the electronic chart during the corresponding time period. The validity of diagnosis codes was evaluated by directly comparing them with the gold standard of chart abstraction using sensitivity, specificity, positive predictive value, negative predictive value, the summary statistics of the F-score, and Youden J statistic. κ statistic for interrater reliability among the 2 abstractors was calculated. Results: The overall agreement between the identification of mental, behavioral, and emotional conditions using diagnosis codes compared to medical record abstraction was strong and similar across the ICD-9-CM and ICD-10-CM coding periods as well as during the prepandemic and pandemic time periods. The performance of AD coding, while strong, was relatively lower compared to the other conditions. The weighted sensitivity, specificity, positive predictive value, and negative predictive value for each of the 5 conditions were as follows: 100%, 100%, 99.2%, and 100%, respectively, for ASD; 100%, 99.9%, 99.2%, and 100%, respectively, for ADHD; 100%, 100%, 100%, and 100%, respectively for DBD; 87.7%, 100%, 100%, and 99.2%, respectively, for AD; and 100%, 100%, 99.2%, and 100%, respectively, for MDD. The F-score and Youden J statistic ranged between 87.7% and 100%. The overall agreement between abstractors was almost perfect (κ=95%). Conclusions: Diagnostic codes are quite reliable for identifying selected childhood mental, behavioral, and emotional conditions. The findings remained similar during the pandemic and after the implementation of the ICD-10-CM coding in the EHR system.

Modeling direct air carbon capture and storage in a 1.5 °C climate future using historical analogs.

Limiting the rise in global temperature to 1.5 °C will rely, in part, on technologies to remove CO2 from the atmosphere. However, many carbon dioxide removal (CDR) technologies are in the early stages of development, and there is limited data to inform predictions of their future adoption. Here, we present an approach to model adoption of early-stage technologies such as CDR and apply it to direct air carbon capture and storage (DACCS). Our approach combines empirical data on historical technology analogs and early adoption indicators to model a range of feasible growth pathways. We use these pathways as inputs to an integrated assessment model (the Global Change Analysis Model, GCAM) and evaluate their effects under an emissions policy to limit end-of-century temperature change to 1.5 °C. Adoption varies widely across analogs, which share different strategic similarities with DACCS. If DACCS growth mirrors high-growth analogs (e.g., solar photovoltaics), it can reach up to 4.9 GtCO2 removal by midcentury, compared to as low as 0.2 GtCO2 for low-growth analogs (e.g., natural gas pipelines). For these slower growing analogs, unabated fossil fuel generation in 2050 is reduced by 44% compared to high-growth analogs, with implications for energy investments and stranded assets. Residual emissions at the end of the century are also substantially lower (by up to 43% and 34% in transportation and industry) under lower DACCS scenarios. The large variation in growth rates observed for different analogs can also point to policy takeaways for enabling DACCS.

Slow wave activity disruptions and memory impairments in a mouse model of aging.

The aging population suffers from memory impairments. Slow-wave activity (SWA) is composed of slow (0.5-1 Hz) and delta (1-4 Hz) oscillations, which play important roles in long-term memory and working memory function respectively. SWA disruptions might lead to memory disturbances often experienced by older adults. We conducted behavioral tests in young and older C57BL/6 J mice. SWA was monitored using wide-field imaging with voltage sensors. Cell-specific calcium imaging was used to monitor the activity of excitatory and inhibitory neurons in these mice. Older mice exhibited impairments in working memory but not memory consolidation. Voltage-sensor imaging revealed aberrant synchronization of neuronal activity in older mice. Notably, we found older mice exhibited no significant alterations in slow oscillations, whereas there was a significant increase in delta power compared to young mice. Calcium imaging revealed hypoactivity in inhibitory neurons of older mice. Combined, these results suggest that neural activity disruptions might correlate with aberrant memory performance in older mice.

Examining the Effects of Supplemental Magnesium on Self-Reported Anxiety and Sleep Quality: A Systematic Review.

Self-treatment with vitamin, mineral, and herbal supplements has become increasingly common among patients for the treatment of psychiatric disorders. Magnesium, in particular, is popular on social media for the treatment of anxiety and insomnia. Meanwhile, preclinical studies support associations between magnesium status, sleep quality, and symptoms of anxiety. The extent to which these claims are evidence-based is unclear. Therefore, a systematic review was performed to provide an updated examination of the clinical evidence on the use of magnesium for the treatment of the above conditions given the popularity of such supplements among patients and the public at large. A thorough search of the PubMed database was performed and results were systematically reviewed using PRISMA guidelines. The search was limited to anxiety disorders and sleep disorders and included interventional trials only. Exclusion criteria included insufficient (<50 mg/12.5% of recommended daily allowance (RDA)) or unknown magnesium dose, >3 other potentially active compounds present in the formulation, and articles in languages other than English. This query returned 860 articles of which 15 met full inclusion criteria. Eight measured sleep-related outcomes, seven measured anxiety-related outcomes, and one examined both. Sleep quality was measured most frequently using the Pittsburg Sleep Quality Index (PSQI). Anxiety measures included self-reported measures such as the Hamilton Anxiety Scale. The majority of included studies demonstrated improvement in at least one sleep- or anxiety-related parameter. Five out of eight sleep-related studies reported improvements in sleep parameters, while two studies reported no improvements, and one reported mixed results. Five out of seven studies measuring anxiety-related outcomes reported improvements in self-reported anxiety. Firm conclusions were limited by the heterogeneity of the data and the small number of participants involved in most of the studies. The dosages, formulations, and durations of the magnesium interventions used also differed across studies. Furthermore, some studies included additional, potentially active ingredients, further complicating interpretations. Given the generally positive results across studies, the preponderance of preclinical evidence, and minimal side effects, however, supplemental magnesium is likely useful in the treatment of mild anxiety and insomnia, particularly in those with low magnesium status at baseline. Notably, both negative anxiety trials featured populations with underlying endocrine factors likely contributing to their symptoms (patients with premenstrual symptoms and post-partum women). Nonetheless, larger, randomized clinical trials are needed to confirm efficacy and to establish the most effective forms and dosages of magnesium for the treatment of insomnia and anxiety disorders.

Acute Simple Elbow Dislocations in the United States: An Epidemiological Analysis of Trends Including COVID-19.

Background Elbows are one of the most frequently dislocated large joints; however, there is limited epidemiological data, especially during the coronavirus disease 2019 (COVID-19) pandemic. This study characterizes elbow dislocations presenting to Emergency Departments (EDs) over the last decade. Methods This study is a cross-sectional, descriptive, epidemiologic analysis of isolated elbow dislocations presenting to EDs from 2011-2020 using the National Electronic Injury Surveillance System (NEISS) database. Patients under 10, those with radial head subluxation, and those with complex fractures were excluded. Data on incidence ratios, patient demographics, mechanisms of injury, and incident locales were analyzed. Results Approximately 83,996 simple, primary elbow dislocations occurred from 2011-2020 (n=2,328), generating an incidence of 2.98/100,000 person-years. Incidence was higher among males (3.26 versus 2.69/100,000 person-years). Dislocations peaked in patients aged 10-19, with higher rates in males (11.12 versus 5.31/100,000 person-years; injury rate ratio 2.09, CI=2.05-2.14, p<0.001). Rates of elbow dislocations decreased with age in males (age 20-29=11.12, age >80=0.63/100,000) but increased in females over 40 (age 40-49=1.59, age 70-79=2.83/100,000). Athletic activities accounted for 55% of dislocations (n=45,902), with 15% from football and 14% from wrestling. The fewest annual dislocations occurred during COVID-19 (n=6440). Injuries occurring at schools and during contact and indoor sports decreased, while those from soccer increased. Conclusions Elbow dislocations are common, with trends of decreasing incidence with age among men and increasing incidence in women over 40. COVID-19 impacted sports-related and epidemiologic injury patterns. Ultimately, understanding population-level risks for elbow dislocations enables orthopaedic surgeons to predict injury trends and conceive educational preventative measures.

Medication recommendations for treatment of lumbosacral radiculopathy: A systematic review of clinical practice guidelines.

OBJECTIVE: The purpose of this systematic review was to ascertain guideline-recommended pharmaceutical approaches to lumbosacral radicular symptoms, assess the quality of the clinical practice guidelines (CPGs) with the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool, and qualitatively synthesize the guideline recommendations. LITERATURE SURVEY: Literature searches were performed in PubMed, Cochrane Database of Systematic Reviews, Index to Chiropractic Literature, Allied and Complementary Medicine Database (AMED), Cumulative Index for Nursing and Allied Health Literature (CINAHL), and Physiotherapy Evidence Database (PEDro). We included guidelines published between January 1, 2017, and January 9, 2022, written in the English language, related to radiculopathy, sciatica, and/or low back pain with leg pain, and that provided recommendations on oral medication. METHODOLOGY: The review was performed in accordance with Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) and the protocol was pre-registered with the International Prospective Register of Systematic Reviews (PROSPERO). Eligibility screening, full-text review, extraction of information pertaining to pharmacological management, and synthesis of results were performed independently by two authors and a third investigator was recruited to arbitrate any disagreements. The AGREE II tool was administered by four authors to appraise CPG quality. SYNTHESIS: After screening 413 citations and assessing 37 full-text articles, 11 CPGs met the inclusion criteria. They represented seven countries (Belgium, Canada, England, France, Japan, Korea, and United States) and three continents (Asia, Europe, and North America), as well as the Global Spine Care Initiative aimed at a worldwide presence. The mean overall AGREE II score was 87.1% (standard deviation [SD] 12.6%), generally reflecting high-quality CPGs. The highest domain mean score was for Clarity of Presentation (96.7%, SD 4.4%), and the lowest was Applicability (75.6%, SD 22.8%). Five classes of medications were recommended by at least one CPG: anticonvulsants, antidepressants, oral corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids. CONCLUSIONS: The most common medication class recommended by the CPGs for lumbar radiculopathy was antidepressants. No CPGs recommended prescribing acetaminophen, benzodiazepines, muscle relaxants, or antibiotics. There was very little agreement between the CPGs, and all the medication classes had at least one CPG recommended against its use. Three guidelines reviewed did not recommend any medications due to lack of supporting literature, and instead recommended nonpharmacologic therapy.

An isolable, chelating bis[cyclic (alkyl)(amino)carbene] stabilizes a strongly bent, dicoordinate Ni(0) complex.

Chelating ligands have had a tremendous impact in coordination chemistry and catalysis. Notwithstanding their success as strongly σ-donating and π-accepting ligands, to date no chelating bis[cyclic (alkyl)(amino)carbenes] have been reported. Herein, we describe a chelating, C2-symmetric bis[cyclic (alkyl)(amino)carbene] ligand, which was isolated as a racemic mixture. The isolation and structural characterization of its isostructural, pseudotetrahedral complexes with iron, cobalt, nickel, and zinc dihalides featuring eight-membered metallacycles demonstrates the binding ability of the bis(carbene). Reduction of the nickel(II) dibromide with potassium graphite produces a dicoordinate nickel(0) complex that features one of the narrowest angles measured in any unsupported dicoordinate transition metal complexes.

Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine.

A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole sporozoite PfSPZ Vaccine in African infants. Innate immune activation and myeloid signatures at pre-vaccination baseline correlated with protection from Pf parasitemia in placebo controls. These same signatures were associated with susceptibility to parasitemia among infants who received the highest and most protective PfSPZ Vaccine dose. Machine learning identified spliceosome, proteosome, and resting dendritic cell signatures as pre-vaccination features predictive of protection after highest-dose PfSPZ vaccination, whereas baseline CSP-specific IgG predicted non-protection. Pre-vaccination innate inflammatory and myeloid signatures were associated with higher sporozoite-specific IgG Ab response but undetectable PfSPZ-specific CD8+ T-cell responses post-vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against infection by sporozoite injection in malaria-naïve mice while diminishing the CD8+ T-cell response to radiation-attenuated sporozoites. These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity of whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8+ T cell responses suggest that PfSPZ Vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways.

NB-02 Protects Neurons and Astrocytes from Oligomeric Amyloid-ß-Mediated Damage.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with limited therapeutic strategies. NB-02 is a novel botanical drug that has shown promise as a protective and therapeutic treatment for AD in an APP/PS1 preclinical mouse model. In this paper, we investigate the underlying mechanisms by which NB-02 provides these therapeutic advantages using in vitro neuron-astrocyte co-cultures. Pretreatment with NB-02 prevented pathological calcium elevations in neurons and astrocytes after application of toxic soluble amyloid-ß (Aß) oligomers. NB-02 also prevented cell death associated with the addition of soluble Aß oligomers suggesting NB-02 is effective at protecting both neurons and astrocytes from Aß-mediated damage.

Trends and Costs of Minimally Invasive Surgery for Kidney Cancer in the US: A Population-based Study.

OBJECTIVE: To analyze temporal trends and costs associated with the use of minimally invasive surgery (MIS) for kidney cancer in the US over the past decade. To examine the impact of social determinants of health (SDOH) on perioperative outcomes. METHODS: The PearlDiver Mariner, a national database of insurance billing records, was queried for this retrospective observational cohort analysis. The MIS population was identified and stratified according to treatment modality, using International Classification of Diseases and current procedural terminology codes. SDOH were assessed using International Classification of Diseases codes. Negative binomial regression was used to evaluate the overall number of renal MIS and Cochran-Armitage tests to compare the utilization of different treatment modalities, over the study period. Multivariable logistic regression analysis identified predictors of perioperative complications. RESULTS: A total of 80,821 MIS for kidney cancer were included. Minimally invasive partial nephrectomy adoption as a fraction of total MIS increased significantly (slope of regression line, reg. = 0.026, P <.001). Minimally invasive radical nephrectomy ($26.9k ± 40.9k) and renal ablation ($18.9k ± 31.6k) were the most expensive and cheapest procedures, respectively. No statistically significant difference was observed in terms of number of complications (P = .06) and presence of SDOH (P = .07) among the treatment groups. At multivariable analysis, patients with SDOH undergoing minimally invasive radical nephrectomy had higher odds of perioperative complications, while renal ablation had a significantly lower probability of perioperative complications. CONCLUSION: This study describes the current management of kidney cancer in the US, offering a socioeconomic perspective on the impact of this disease in everyday clinical practice.

Association between SARS-CoV-2 Infection and Adverse Perinatal Outcomes by Race/Ethnicity in a Large Integrated Health Care System.

OBJECTIVE: Recent studies have reported associations between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy and adverse perinatal outcomes but the extent to which these associations vary by race/ethnicity remains uncertain. Therefore, we examined how the association between prenatal SARS-CoV-2 infection and adverse perinatal outcomes may be modified by race/ethnicity. STUDY DESIGN: A retrospective cohort study was performed using data on 67,986 pregnant women extracted from the Kaiser Permanente Southern California electronic health records between April 6, 2020, and December 31, 2021. Upon admission to labor and delivery, all women were routinely tested for coronavirus disease 2019 (COVID-19) using real-time reverse-transcriptase polymerase chain reaction test. Adjusted odds ratios (aORs) were used to estimate associations. RESULTS: During the study period, COVID-19 was diagnosed in 4,960 (7%) of singleton pregnancies, with the highest rates observed among Hispanics (9.4%) and non-Hispanic Blacks (6.2%). Compared with non-Hispanic Whites, Hispanics (aOR: 1.12, 95% CI: 1.03, 1.21) with SARS-CoV-2 infection had the highest odds of a pregnancy associated with nonreassuring fetal heart rate tracing. Neonates of all races/ethnicities, except for non-Hispanic Blacks, showed significantly increased odds of SARS-CoV-2 infection, with the highest risk observed among Asians/Pacific Islanders (aOR: 10.88, 95% CI: 1.33, 89.04). Non-Hispanic White mothers who tested positive were admitted to intensive care unit (ICU) at a higher rate at delivery and within 7 days of delivery (aOR: 34.77, 95% CI: 11.3, 107.04; aOR: 26.48, 95% CI: 9.55, 73.46, respectively). Hispanics were also at a significantly higher odds of admission to ICU (aOR: 4.62, 95% CI: 2.69, 7.94; aOR: 4.42, 95% CI: 2.58, 7.56, respectively). Non-Hispanic Black, Hispanic, and Asian/Pacific Islander mothers who tested positive for SARS-CoV-2 prenatally, were at increased risk for preeclampsia/eclampsia, and preterm birth as compared to non-Hispanic White mothers. CONCLUSION: The findings highlight racial/ethnic disparities in the association between SARS-CoV-2 infection and adverse perinatal outcomes. The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders. We also observed a remarkably high risk of ICU admission for non-Hispanic White mothers infected with SARS-CoV-2. KEY POINTS: · Race/ethnicity influences perinatal outcomes in pregnancies impacted by SARS-CoV-2.. · The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders.. · White mothers had a notably high risk of ICU admission at delivery following SARS-CoV-2 infection..

Merging Modular Molecular Design with High Throughput Screening of Cell Adhesion on Antimicrobial Supramolecular Biomaterials.

A polymer microarray based on the supramolecular ureido-pyrimidinone (UPy) moiety is fabricated to screen antimicrobial materials for their ability to support cell adhesion. UPy-functionalized additives, either cell-adhesive, antimicrobial or control peptides, are used, and investigated in different combinations at different concentrations, resulting in a library of 194 spots. These are characterized on composition and morphology to evaluate the microarray fabrication. Normal human dermal fibroblasts are cultured on the microarrays and cell adhesion to the spots is systematically analyzed. Results demonstrate enhanced cell adhesion on spots with combinations including the antimicrobial peptides. This study clearly proves the power of the high throughput approach in combination with supramolecular molecules, to screen additive libraries for desired biological response.

Examining associations between disordered eating and harmful substance use in a nationally representative sample of US veterans.

OBJECTIVE: The association between eating disorders (EDs) and harmful substance use (substance use that causes psychosocial impairment) is well recognized in the literature, and military veterans may be at heightened risk for both issues due to deployment-related stressors. However, little is known about which ED-related symptoms are associated with harmful substance use in veterans, and whether gender plays a differential role in this relationship. Our aims were to: (1) examine gender differences in ED-related symptoms; and (2) examine whether ED-related symptoms differentially predict harmful substance use in US veteran men and women who had recently separated from service. METHOD: This study was based on a nationally representative four-wave longitudinal sample of post-9/11 veterans (N = 835; 61.2% female). Longitudinal mixed modeling was used to test whether specific ED-related behaviors at baseline predicted harmful substance use at follow-ups. RESULTS: We replicated gendered patterns of ED-related symptoms observed in civilian populations, wherein men had higher weight-and-body-related concerns (including excessive exercise and muscle building) and negative attitude toward obesity, and women had higher bulimic and restricting symptoms. For women, alcohol, drug, and marijuana problems were predicted by higher bulimic symptoms, whereas for men, these problems were predicted by higher restricting symptoms. CONCLUSION: Gender played a differential role in the relationship between EDs and harmful substance use. Bulimic symptoms were the most robust predictor for harmful substance use among veteran women, whereas restricting was the most robust predictor for harmful substance use among veteran men. PUBLIC SIGNIFICANCE: The current study found that veteran women had higher bulimic symptoms (characterized by binge eating and purging) and restricting than veteran men. In women, bulimic symptoms predicted future harmful use of alcohol, marijuana, and other drugs. In contrast, veteran men had higher weight-and-body-related concerns (characterized by excessive exercise and muscle building) than veteran women. In men, restricting symptoms predicted future harmful use of alcohol, marijuana, and other drugs.

Dealing with complications in interventional radiology.

It is widely accepted that most misadventures, which lead to harm have not occurred because of a single individual but rather due to a failure of process that results in healthcare workers making mistakes. This failure of process and the pervasiveness of adverse events is just as prevalent in Interventional Radiology (IR) as it is in other specialities. The true prevalence and prevailing aetiology of complications in IR are not exactly known as there is a paucity of investigative literature into this area; especially when compared with other more established disciplines such as Surgery. Some IR procedures have a higher risk profile than others. However, published data suggests that many adverse events in IR are preventable (55-84%) and frequently involve a device related complication such as improper usage or malfunction. This article aims to discuss factors that contribute to complications in IR along with tools and strategies for dealing with them to achieve optimal patient outcomes.

Rising Trends of Childhood Attention-Deficit/Hyperactivity Disorder in a Large Integrated Healthcare Delivery System in Southern California, 2010-2021.

OBJECTIVE: To evaluate trends of attention-deficit/hyperactivity disorder (ADHD) diagnosis rates among children aged 5-17 years over the past decade (2010-2021) and to investigate whether there have been differences in temporal changes based on race and ethnicity, sex, or income. STUDY DESIGN: Childhood ADHD diagnosis was ascertained from electronic health records using International Classification of Diseases ninth revision (314.xx) and International Classification of Diseases tenth revision (F90.x) codes. Data were stratified by child's sex, race and ethnicity, and household income, and rates of ADHD were estimated before and after adjustment for potential confounders. RESULTS: The overall ADHD diagnosis rates increased from 3.5% in 2010 to 4.0% in 2021. ADHD diagnosis was most prevalent among White children (6.1%), then Black (4.6%), Other/multiple (3.7%), Hispanic (3.1%), and Asian/Pacific Islander (PI) (1.7%). ADHD was also highly prevalent among boys (73.3%) or family income≥$70,000 (50.0%). ADHD diagnosis increased among Black (4.2% to 5.1%), Hispanic (2.8% to 3.6%), and Asian/PI children (1.5% to 2.0%) but remained stable for White (6.2% to 6.1%) and Other/multiple race/ethnic children (3.7% to 3.7%). Increases in the prevalence among girls were also observed. CONCLUSION: The prevalence of ADHD in children has risen with the largest increases observed for Black, Hispanic, and Asian/PI children. Rates among less affluent families and girls have also been increasing, narrowing the gaps in diagnosis rates previously observed. These increases may reflect improvements in screening and provision of care among demographics where ADHD has been historically underdiagnosed.

Equity and modeling in sustainability science: Examples and opportunities throughout the process.

Equity is core to sustainability, but current interventions to enhance sustainability often fall short in adequately addressing this linkage. Models are important tools for informing action, and their development and use present opportunities to center equity in process and outcomes. This Perspective highlights progress in integrating equity into systems modeling in sustainability science, as well as key challenges, tensions, and future directions. We present a conceptual framework for equity in systems modeling, focused on its distributional, procedural, and recognitional dimensions. We discuss examples of how modelers engage with these different dimensions throughout the modeling process and from across a range of modeling approaches and topics, including water resources, energy systems, air quality, and conservation. Synthesizing across these examples, we identify significant advances in enhancing procedural and recognitional equity by reframing models as tools to explore pluralism in worldviews and knowledge systems; enabling models to better represent distributional inequity through new computational techniques and data sources; investigating the dynamics that can drive inequities by linking different modeling approaches; and developing more nuanced metrics for assessing equity outcomes. We also identify important future directions, such as an increased focus on using models to identify pathways to transform underlying conditions that lead to inequities and move toward desired futures. By looking at examples across the diverse fields within sustainability science, we argue that there are valuable opportunities for mutual learning on how to use models more effectively as tools to support sustainable and equitable futures.

Spatially Resolved Molecular Analysis of Host Response to Medical Device Implantation Using the 3D OrbiSIMS Highlights a Critical Role for Lipids.

A key goal for implanted medical devices is that they do not elicit a detrimental immune response. Macrophages play critical roles in the modulation of the host immune response and are the cells responsible for persistent inflammatory reactions to implanted biomaterials. Two novel immune-instructive polymers that stimulate pro- or anti-inflammatory responses from macrophages in vitro are investigated. These also modulate in vivo foreign body responses (FBR) when implanted subcutaneously in mice. Immunofluorescent staining of tissue abutting the polymer reveals responses consistent with pro- or anti-inflammatory responses previously described for these polymers. Three Dimensional OrbiTrap Secondary Ion Mass Spectrometry (3D OrbiSIMS) analysis to spatially characterize the metabolites in the tissue surrounding the implant, providing molecular histology insight into the metabolite response in the host is applied. For the pro-inflammatory polymer, monoacylglycerols (MG) and diacylglycerols (DG) are observed at increased intensity, while for the anti-inflammatory coating, the number of phospholipid species detected decreased, and pyridine and pyrimidine levels are elevated. Small molecule signatures from single-cell studies of M2 macrophages in vitro correlate with the in vivo observations, suggesting potential for prediction. Metabolite characterization by the 3D OrbiSIMS is shown to provide insight into the mechanism of bio-instructive materials as medical devices and to inform on the FBR to biomaterials.

Synthesis, SARS-CoV-2 main protease inhibition, molecular docking and in silico ADME studies of furanochromene-quinoline hydrazone derivatives.

Seven furanochromene-quinoline derivatives containing a hydrazone linker were synthesized by condensing a furanochromene hydrazide with quinoline 2-, 3-, 4-, 5-, 6-, and 8-carbaldehydes, including 8-hydroxyquinoline-2-carbaldehye. Structure-activity correlations were investigated to determine the influence of the location of the hydrazone linker on the quinoline unit on SARS-CoV-2 Mpro enzyme inhibition. The 3-, 5-, 6- and 8-substituted derivatives showed moderate inhibition of SARS-CoV-2 Mpro with IC50 values ranging from 16 to 44 µM. Additionally, all of the derivatives showed strong interaction with the SARS-CoV-2 Mpro substrate binding pocket, with docking energy scores ranging from -8.0 to -8.5 kcal/mol. These values are comparable to that of N3 peptide (-8.1 kcal/mol) and more favorable than GC-373 (-7.6 kcal/mol) and ML-188 (-7.5 kcal/mol), all of which are known SARS-CoV-2 Mpro inhibitors. Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) profiles indicate that the derivatives have good drug-likeness properties. Overall, this study highlights the potential of the furanochromene-quinoline hydrazone scaffold as a SARS-CoV-2 Mpro inhibitor.

Development of PainFace software to simplify, standardize, and scale up mouse grimace analyses.

ABSTRACT: Facial grimacing is used to quantify spontaneous pain in mice and other mammals, but scoring relies on humans with different levels of proficiency. Here, we developed a cloud-based software platform called PainFace (http://painface.net) that uses machine learning to detect 4 facial action units of the mouse grimace scale (orbitals, nose, ears, whiskers) and score facial grimaces of black-coated C57BL/6 male and female mice on a 0 to 8 scale. Platform accuracy was validated in 2 different laboratories, with 3 conditions that evoke grimacing-laparotomy surgery, bilateral hindpaw injection of carrageenan, and intraplantar injection of formalin. PainFace can generate up to 1 grimace score per second from a standard 30 frames/s video, making it possible to quantify facial grimacing over time, and operates at a speed that scales with computing power. By analyzing the frequency distribution of grimace scores, we found that mice spent 7x more time in a "high grimace" state following laparotomy surgery relative to sham surgery controls. Our study shows that PainFace reproducibly quantifies facial grimaces indicative of nonevoked spontaneous pain and enables laboratories to standardize and scale-up facial grimace analyses.