High-Throughput Covalent Modifier Screening with Acoustic Ejection Mass Spectrometry.

Interests in covalent drugs have grown in modern drug discovery as they could tackle challenging targets traditionally considered "undruggable". The identification of covalent binders to target proteins typically involves directly measuring protein covalent modifications using high-resolution mass spectrometry. With a continually expanding library of compounds, conventional mass spectrometry platforms such as LC-MS and SPE-MS have become limiting factors for high-throughput screening. Here, we introduce a prototype high-resolution acoustic ejection mass spectrometry (AEMS) system for the rapid screening of a covalent modifier library comprising ∼10,000 compounds against a 50 kDa-sized target protein─Werner syndrome helicase. The screening samples were arranged in a 1536-well format. The sample buffer containing high-concentration salts was directly analyzed without any cleanup steps, minimizing sample preparation efforts and ensuring protein stability. The entire AEMS analysis process could be completed within a mere 17 h. An automated data analysis tool facilitated batch processing of the sample data and quantitation of the formation of various covalent protein-ligand adducts. The screening results displayed a high degree of fidelity, with a Z' factor of 0.8 and a hit rate of 2.3%. The identified hits underwent orthogonal testing in a biochemical activity assay, revealing that 75% were functional antagonists of the target protein. Notably, a comparative analysis with LC-MS showcased the AEMS platform's low risk of false positives or false negatives. This innovative platform has enabled robust high-throughput covalent modifier screening, featuring a 10-fold increase in library size and a 10- to 100-fold increase in throughput when compared with similar reports in the existing literature.

Latent growth factors as predictors of distal outcomes.

A currently overlooked application of the latent curve model (LCM) is its use in assessing the consequences of development patterns of change-that is as a predictor of distal outcomes. However, there are additional complications for appropriately specifying and interpreting the distal outcome LCM. Here, we develop a general framework for understanding the sensitivity of the distal outcome LCM to the choice of time coding, focusing on the regressions of the distal outcome on the latent growth factors. Using artificial and real-data examples, we highlight the unexpected changes in the regression of the slope factor which stand in contrast to prior work on time coding effects, and develop a framework for estimating the distal outcome LCM at a point in the trajectory-known as the aperture-which maximizes the interpretability of the effects. We also outline a prioritization approach developed for assessing incremental validity to obtain consistently interpretable estimates of the effect of the slope. Throughout, we emphasize practical steps for understanding these changing predictive effects, including graphical approaches for assessing regions of significance similar to those used to probe interaction effects. We conclude by providing recommendations for applied research using these models and outline an agenda for future work in this area. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

MRI of the Spine in Patients who Toe Walk: Is There a Role?

BACKGROUND: Little is known about the prevalence of intraspinal pathology in children who toe walk, but magnetic resonance imaging (MRI) may be part of the diagnostic workup. The purpose of this study was to examine the role of MRI for children who toe walk with a focus on the rate of positive findings and associated neurosurgical interventions performed for children with said MRI findings. METHODS: A single-center tertiary hospital database was queried to identify a cohort of 118 subjects with a diagnosis of toe walking who underwent spinal MRI during a 5-year period. Patient and MRI characteristics were summarized and compared between subjects with a major abnormality, minor abnormality, or no abnormality on MRI using multivariable logistic regression. Major MRI abnormalities included those with a clear spinal etiology, such as fatty filum, tethered cord, syrinx, and Chiari malformation, while minor abnormalities had unclear associations with toe walking. RESULTS: The most common primary indications for MRI were failure to improve with conservative treatment, severe contracture, and abnormal reflexes. The prevalence of major MRI abnormalities was 25% (30/118), minor MRI abnormalities was 19% (22/118), and normal MRI was 56% (66/118). Patients with delayed onset of toe walking were significantly more likely to have a major abnormality on MRI ( P =0.009). The presence of abnormal reflexes, severe contracture, back pain, bladder incontinence, and failure to improve with conservative treatment were not significantly associated with an increased likelihood of major abnormality on MRI. Twenty-nine (25%) subjects underwent tendon lengthening, and 5 (4%) underwent neurosurgical intervention, the most frequent of which was detethering and sectioning of fatty filum. CONCLUSIONS: Spinal MRI in patients who toe walk has a high rate of major positive findings, some of which require neurosurgical intervention. The most significant predictor of intraspinal pathology was the late onset of toe walking after the child had initiated walking. MRI of the spine should be considered by pediatric orthopedic surgeons in patients with toe walking who present late with an abnormal clinical course. LEVEL OF EVIDENCE: Level III Retrospective Comparative Study.

Self-compassion and fear of compassion in the treatment of chronic depression: Mechanisms of change?

OBJECTIVE: The aim of this naturalistic process study was to investigate the relationship between self-compassion, fear of compassion from others, and depressive symptoms over the course of psychotherapy in patients with chronic depression. METHOD: A sample of 226 patients with chronic depression who received inpatient short-term psychodynamic psychotherapy (STPP) provided weekly self-report measures of self-compassion, fear of compassion, and depressive symptoms (Patient Health Questionnaire-9). Trivariate latent curve modeling with structured residuals was applied to investigate the between- and within-patient relationships among the variables. RESULTS: At the between-patient level, a significant positive correlation was found between slope of depression and the slope of fear of compassion. At the within-patient level, a lower than expected level of fear of compassion predicted a subsequent lower than expected level of depression (mean weekly effect size = 0.12), with a smaller reciprocal relationship (mean weekly effect size = 0.08). There was no significant within-patient effect of self-compassion predicting subsequent depression, but a significant effect of a lower than expected level of depression predicting a subsequent higher than expected level of self-compassion (mean weekly effect size = -0.13). No within-patient effect between self-compassion and fear of compassion was found. CONCLUSIONS: In the context of this study, it appears that fear of compassion may be a putative mechanism of change involved in alleviating depressive symptoms in patients with chronic depression treated with STPP. On the other hand, self-compassion appears to be an outcome of psychotherapy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Informing Harmonization Decisions in Integrative Data Analysis: Exploring the Measurement Multiverse.

Combining datasets in an integrative data analysis (IDA) requires researchers to make a number of decisions about how best to harmonize item responses across datasets. This entails two sets of steps: logical harmonization, which involves combining items which appear similar across datasets, and analytic harmonization, which involves using psychometric models to find and account for cross-study differences in measurement. Embedded in logical and analytic harmonization are many decisions, from deciding whether items can be combined prima facie to how best to find covariate effects on specific items. Researchers may not have specific hypotheses about these decisions, and each individual choice may seem arbitrary, but the cumulative effects of these decisions are unknown. In the current study, we conducted an IDA of the relationship between alcohol use and delinquency using three datasets (total N = 2245). For analytic harmonization, we used moderated nonlinear factor analysis (MNLFA) to generate factor scores for delinquency. We conducted both logical and analytic harmonization 72 times, each time making a different set of decisions. We assessed the cumulative influence of these decisions on MNLFA parameter estimates, factor scores, and estimates of the relationship between delinquency and alcohol use. There were differences across paths in MNLFA parameter estimates, but fewer differences in estimates of factor scores and regression parameters linking delinquency to alcohol use. These results suggest that factor scores may be relatively robust to subtly different decisions in data harmonization, and measurement model parameters are less so.

Molecular and behavioral consequences of Ube3a gene overdosage in mice.

Chromosome 15q11.2-q13.1 duplication syndrome (Dup15q syndrome) is a severe neurodevelopmental disorder characterized by intellectual disability, impaired motor coordination, and autism spectrum disorder. Chromosomal multiplication of the UBE3A gene is presumed to be the primary driver of Dup15q pathophysiology, given that UBE3A exhibits maternal monoallelic expression in neurons and that maternal duplications typically yield far more severe neurodevelopmental outcomes than paternal duplications. However, studies into the pathogenic effects of UBE3A overexpression in mice have yielded conflicting results. Here, we investigated the neurodevelopmental impact of Ube3a gene overdosage using bacterial artificial chromosome-based transgenic mouse models (Ube3aOE) that recapitulate the increases in Ube3a copy number most often observed in Dup15q. In contrast to previously published Ube3a overexpression models, Ube3aOE mice were indistinguishable from wild-type controls on a number of molecular and behavioral measures, despite suffering increased mortality when challenged with seizures, a phenotype reminiscent of sudden unexpected death in epilepsy. Collectively, our data support a model wherein pathogenic synergy between UBE3A and other overexpressed 15q11.2-q13.1 genes is required for full penetrance of Dup15q syndrome phenotypes.

Effects of Healthcare Organization Actions and Policies Related to COVID-19 on Perceived Organizational Support Among U.S. Internists: A National Study.

GOAL: Perceived organizational support (POS) may promote healthcare worker mental health, but organizational factors that foster POS during the COVID-19 pandemic are unknown. The goals of this study were to identify actions and policies regarding COVID-19 that healthcare organizations can implement to promote POS and to evaluate the impact of POS on physicians' mental health, burnout, and intention to leave patient care. METHODS: We conducted a cross-sectional national survey with an online panel of internal medicine physicians from the American College of Physicians in September and October of 2020. POS was measured with a 4-item scale, based on items from Eisenberger's Perceived Organizational Support Scale that were adapted for the pandemic. Mental health outcomes and burnout were measured with short screening scales. PRINCIPAL FINDINGS: The response rate was 37.8% (N = 810). Three healthcare organization actions and policies were independently associated with higher levels of POS in a multiple linear regression model that included all actions and policies as well as potential confounding factors: opportunities to discuss ethical issues related to COVID-19 (ß (regression coefficient) = 0.74, p = .001), adequate access to personal protective equipment (ß = 1.00, p = .005), and leadership that listens to healthcare worker concerns regarding COVID-19 (ß = 3.58, p < .001). Sanctioning workers who speak out on COVID-19 safety issues or refuse pandemic deployment was associated with lower POS (ß = -2.06, p < .001). In multivariable logistic regression models, high POS was associated with approximately half the odds of screening positive for generalized anxiety, depression, post-traumatic stress disorder, burnout, and intention to leave patient care within 5 years. APPLICATIONS TO PRACTICE: Our results suggest that healthcare organizations may be able to increase POS among physicians during the COVID-19 pandemic by guaranteeing adequate personal protective equipment, making sure that leaders listen to concerns about COVID-19, and offering opportunities to discuss ethical concerns related to caring for patients with COVID-19. Other policies and actions such as rapid COVID-19 tests may be implemented for the safety of staff and patients, but the policies and actions associated with POS in multivariable models in this study are likely to have the largest positive impact on POS. Warning or sanctioning workers who refuse pandemic deployment or speak up about worker and patient safety is associated with lower POS and should be avoided. We also found that high degrees of POS are associated with lower rates of adverse outcomes. So, by implementing the tangible support policies positively associated with POS and avoiding punitive ones, healthcare organizations may be able to reduce adverse mental health outcomes and attrition among their physicians.

Emotional clarity and tolerance of emotional distress as mechanisms of change in short-term psychodynamic psychotherapy for chronic depression.

OBJECTIVE: The aim of this naturalistic process study was to investigate the relationship between emotional clarity and tolerance of emotional distress and depressive symptoms over the course of short-term psychodynamic psychotherapy for chronically depressed patients. METHOD: Weekly self-reports of emotional clarity, tolerance of emotional distress, and depressive symptoms (PHQ-9) were provided by 252 patients with chronic depression who were admitted to a 13-week inpatient treatment program. Latent curve modeling with structured residuals (LCM-SR) was applied to investigate the between- and within-person effects of week-to-week change in emotional clarity and tolerance of emotional distress as predictors of subsequent depression. The relationship between emotional clarity and tolerance of emotional distress was also investigated. RESULTS: At the within-person level, higher level of emotional clarity and tolerance of emotional distress predicted subsequent lower level of depression. A reciprocal relationship was found for tolerance of emotional distress (lower level of depression predicted subsequent level of tolerance emotional distress) but not for emotional clarity. No within-person effect between emotional clarity and tolerance of emotional distress was found. DISCUSSION: The results indicate that emotional clarity and tolerance of emotional distress may be mechanisms of change in short-term psychodynamic psychotherapy for chronic depression. The results are consistent with previous findings of the importance of emotional clarity and tolerance of emotional distress in psychotherapy. This study demonstrated the utility of LCM-SR as a method to identity mechanisms of change in psychotherapy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Preoperative Considerations for Teenagers Undergoing Orthopaedic Surgery: VTE Prevention, Mental Health Assessment, Vaping, and Drug Addiction.

INTRODUCTION: Adolescents undergoing pediatric orthopaedic surgery typically experience an uncomplicated postoperative course. However, adolescence represents a unique transition period from pediatric to adult physiology. As a result, the astute pediatric orthopaedic surgeon will be aware of unique medical and social scenarios which are relevant to adolescents during the perioperative course including the risk of venous thromboembolism (VTE), prevalence of mental health conditions, and rising use of electronic cigarettes or "vaping" to consume nicotine and cannibas. DISCUSSION: Adolescents are at a greater risk of VTE after pediatric orthopaedic surgery. In particular, adolescent females with a family history of blood clotting disorders and those with a change in mobility after surgery should be considered for prophylaxis. The prevalence of adolescent mental health conditions including anxiety, depression, and behavioral issues is increasing in the United States. Higher levels of preoperative anxiety and the presence of mental health pathology are associated with slower recovery, higher levels of postoperative pain, and the increased likelihood for chronic pain. Several quick screening instruments are available to assess adolescents for preoperative anxiety risk, including the Visual Analogue Scale for Anxiety or the Amsterdam Perioperative Anxiety Information Scale. Unfortunately, electronic cigarettes have become increasingly popular for the consumption of nicotine and cannabis among adolescents. Preoperative use of combustive cigarettes (nicotine/cannabis) represents perioperative risks for induction/anesthesia, postoperative pain, and analgesia requirements and issues with delayed wound and fracture healing. CONCLUSIONS: VTE, underlying mental health conditions, and usage of nicotine and cannabis are clear detriments to the recovery and healing of adolescent patients following orthopaedic surgery. Therefore, standardized screening for adolescents before orthopaedic surgery is indicated to identify perioperative risk factors which have negative impacts on functional outcomes.

SAR towards indoline and 3-azaindoline classes of IDO1 inhibitors.

A novel series of IDO1 inhibitors have been identified with good IDO1 Hela cell and human whole blood activity. These inhibitors contain an indoline or a 3-azaindoline scaffold. Their structure-activity-relationship studies have been explored. Compounds 37 and 41 stood out as leads due to their good potency in IDO1 Hela assay, good IDO1 unbound hWB IC50s, reasonable unbound clearance, and good MRT in rat and dog PK studies.

Life-course trajectories of body mass index from adolescence to old age: Racial and educational disparities.

No research exists on how body mass index (BMI) changes with age over the full life span and social disparities therein. This study aims to fill the gap using an innovative life-course research design and analytic methods to model BMI trajectories from early adolescence to old age across 20th-century birth cohorts and test sociodemographic variation in such trajectories. We conducted the pooled integrative data analysis (IDA) to combine data from four national population-based NIH longitudinal cohort studies that collectively cover multiple stages of the life course (Add Health, MIDUS, ACL, and HRS) and estimate mixed-effects models of age trajectories of BMI for men and women. We examined associations of BMI trajectories with birth cohort, race/ethnicity, parental education, and adult educational attainment. We found higher mean levels of and larger increases in BMI with age across more recent birth cohorts as compared with earlier-born cohorts. Black and Hispanic excesses in BMI compared with Whites were present early in life and persisted at all ages, and, in the case of Black-White disparities, were of larger magnitude for more recent cohorts. Higher parental and adulthood educational attainment were associated with lower levels of BMI at all ages. Women with college-educated parents also experienced less cohort increase in mean BMI. Both race and education disparities in BMI trajectories were larger for women compared with men.

Excess mortality during the COVID-19 pandemic: a geospatial and statistical analysis in Aden governorate, Yemen.

BACKGROUND: The burden of COVID-19 in low-income and conflict-affected countries remains unclear, largely reflecting low testing rates. In parts of Yemen, reports indicated a peak in hospital admissions and burials during May-June 2020. To estimate excess mortality during the epidemic period, we quantified activity across all identifiable cemeteries within Aden governorate (population approximately 1 million) by analysing very high-resolution satellite imagery and compared estimates to Civil Registry office records. METHODS: After identifying active cemeteries through remote and ground information, we applied geospatial analysis techniques to manually identify new grave plots and measure changes in burial surface area over a period from July 2016 to September 2020. After imputing missing grave counts using surface area data, we used alternative approaches, including simple interpolation and a generalised additive mixed growth model, to predict both actual and counterfactual (no epidemic) burial rates by cemetery and across the governorate during the most likely period of COVID-19 excess mortality (from 1 April 2020) and thereby compute excess burials. We also analysed death notifications to the Civil Registry office over the same period. RESULTS: We collected 78 observations from 11 cemeteries. In all but one, a peak in daily burial rates was evident from April to July 2020. Interpolation and mixed model methods estimated ≈1500 excess burials up to 6 July, and 2120 up to 19 September, corresponding to a peak weekly increase of 230% from the counterfactual. Satellite imagery estimates were generally lower than Civil Registry data, which indicated a peak 1823 deaths in May alone. However, both sources suggested the epidemic had waned by September 2020. DISCUSSION: To our knowledge, this is the first instance of satellite imagery being used for population mortality estimation. Findings suggest a substantial, under-ascertained impact of COVID-19 in this urban Yemeni governorate and are broadly in line with previous mathematical modelling predictions, though our method cannot distinguish direct from indirect virus deaths. Satellite imagery burial analysis appears a promising novel approach for monitoring epidemics and other crisis impacts, particularly where ground data are difficult to collect.

Psychometric Models for Scoring Multiple Reporter Assessments: Applications to Integrative Data Analysis in Prevention Science and Beyond.

Conducting valid and reliable empirical research in the prevention sciences is an inherently difficult and challenging task. Chief among these is the need to obtain numerical scores of underlying theoretical constructs for use in subsequent analysis. This challenge is further exacerbated by the increasingly common need to consider multiple reporter assessments, particularly when using integrative data analysis to fit models to data that have been pooled across two or more independent samples. The current paper uses both simulated and real data to examine the utility of a recently proposed psychometric model for multiple reporter data called the trifactor model (TFM) in settings that might be commonly found in prevention research. Results suggest that numerical scores obtained using the TFM are superior to more traditional methods, particularly when pooling samples that contribute different reporter perspectives.

Carbamate and N-Pyrimidine Mitigate Amide Hydrolysis: Structure-Based Drug Design of Tetrahydroquinoline IDO1 Inhibitors.

Indoleamine-2,3-dioxygenase-1 (IDO1) has emerged as an attractive target for cancer immunotherapy. An automated ligand identification system screen afforded the tetrahydroquinoline class of novel IDO1 inhibitors. Potency and pharmacokinetic (PK) were key issues with this class of compounds. Structure-based drug design and strategic incorporation of polarity enabled the rapid improvement on potency, solubility, and oxidative metabolic stability. Metabolite identification studies revealed that amide hydrolysis in the D-pocket was the key clearance mechanism for this class. Strategic survey of amide isosteres revealed that carbamates and N-pyrimidines, which maintained exquisite potencies, mitigated the amide hydrolysis issue and led to an improved rat PK profile. The lead compound 28 is a potent IDO1 inhibitor, with clean off-target profiles and the potential for quaque die dosing in humans.

Harmonizing altered measures in integrative data analysis: A methods analogue study.

In the current study, we used an analogue integrative data analysis (IDA) design to test optimal scoring strategies for harmonizing alcohol- and drug-use consequence measures with varying degrees of alteration across four study conditions. We evaluated performance of mean, confirmatory factor analysis (CFA), and moderated nonlinear factor analysis (MNLFA) scores based on traditional indices of reliability (test-retest, internal, and score recovery or parallel forms) and validity. Participants in the analogue study included 854 college students (46% male; 21% African American, 5% Hispanic/Latino, 56% European American) who completed two versions of the altered measures at two sessions, separated by 2 weeks. As expected, mean, CFA, and MNLFA scores all resulted in scales with lower reliability given increasing scale alteration (with less fidelity to formerly developed scales) and shorter scale length. MNLFA and CFA scores, however, showed greater validity than mean scores, demonstrating stronger relationships with external correlates. Implications for measurement harmonization in the context of IDA are discussed.

Strategic Incorporation of Polarity in Heme-Displacing Inhibitors of Indoleamine-2,3-dioxygenase-1 (IDO1).

Indoleamine-2,3-dioxygenase-1 (IDO1) has emerged as a target of significant interest to the field of cancer immunotherapy, as the upregulation of IDO1 in certain cancers has been linked to host immune evasion and poor prognosis for patients. In particular, IDO1 inhibition is of interest as a combination therapy with immune checkpoint inhibition. Through an Automated Ligand Identification System (ALIS) screen, a diamide class of compounds was identified as a promising lead for the inhibition of IDO1. While hit 1 possessed attractive cell-based potency, it suffered from a significant right-shift in a whole blood assay, poor solubility, and poor pharmacokinetic properties. Through a physicochemical property-based approach, including a focus on lowering AlogP98 via the strategic introduction of polar substitution, compound 13 was identified bearing a pyridyl oxetane core. Compound 13 demonstrated improved whole blood potency and solubility, and an improved pharmacokinetic profile resulting in a low predicted human dose.

Cancer-Associated Fibroblasts Promote Immunosuppression by Inducing ROS-Generating Monocytic MDSCs in Lung Squamous Cell Carcinoma.

Cancer-associated fibroblasts (CAF) represent a functionally heterogeneous population of activated fibroblasts that constitutes a major component of tumor stroma. Although CAFs have been shown to promote tumor growth and mediate resistance to chemotherapy, the mechanisms by which they may contribute to immune suppression within the tumor microenvironment (TME) in lung squamous cell carcinoma (LSCC) remain largely unexplored. Here, we identified a positive correlation between CAF and monocytic myeloid cell abundances in 501 primary LSCCs by mining The Cancer Genome Atlas data sets. We further validated this finding in an independent cohort using imaging mass cytometry and found a significant spatial interaction between CAFs and monocytic myeloid cells in the TME. To delineate the interplay between CAFs and monocytic myeloid cells, we used chemotaxis assays to show that LSCC patient-derived CAFs promoted recruitment of CCR2+ monocytes via CCL2, which could be reversed by CCR2 inhibition. Using a three-dimensional culture system, we found that CAFs polarized monocytes to adopt a myeloid-derived suppressor cell (MDSC) phenotype, characterized by robust suppression of autologous CD8+ T-cell proliferation and IFNγ production. We further demonstrated that inhibiting IDO1 and NADPH oxidases, NOX2 and NOX4, restored CD8+ T-cell proliferation by reducing reactive oxygen species (ROS) generation in CAF-induced MDSCs. Taken together, our study highlights a pivotal role of CAFs in regulating monocyte recruitment and differentiation and demonstrated that CCR2 inhibition and ROS scavenging abrogate the CAF-MDSC axis, illuminating a potential therapeutic path to reversing the CAF-mediated immunosuppressive microenvironment.

Bidirectional Relations between Witnessing Violence, Victimization, Life Events, and Physical Aggression among Adolescents in Urban Schools.

Although there is empirical evidence supporting associations between exposure to violence and engaging in physically aggressive behavior during adolescence, there is limited longitudinal research to determine the extent to which exposure to violence is a cause or a consequence of physical aggression, and most studies have not addressed the influence of other negative life events experienced by adolescents. This study examined bidirectional relations between physical aggression, two forms of exposure to violence-witnessing violence and victimization, and other negative life events. Participants were a sample of 2568 adolescents attending three urban public middle schools who completed measures of each construct every 3 months during middle school. Their mean age was 12.76 (SD = 0.98); 52% were female. The majority were African American (89%); 17% were Hispanic or Latino/a. Cross-lagged regression analyses across four waves of data collected within the same grade revealed bidirectional relations between witnessing violence and physical aggression, and between witnessing violence and negative life events. Although physical aggression predicted subsequent changes in victimization, victimization predicted changes in physical aggression only when witnessing violence was not taken into account. Findings were consistent across sex and grades. Overall, these findings highlight the need for interventions that break the connection between exposure to violence and aggression during adolescence.

Practice Patterns for Management of Pediatric Femur Fractures in Low- and Middle-Income Countries.

BACKGROUND: Femoral shaft fractures in children are common in low and middle income countries. In high-income countries, patient age, fracture pattern, associated injuries, child/family socioeconomic status, and surgeon preference dictate fracture management. There is limited literature on treatment patterns for pediatric femur fractures in resource-limited settings. This study surveys surgeons from low (LIC), lower-middle (LMIC), and upper-middle income (UMIC) countries regarding treatment patterns for pediatric femur fractures. METHODS: Surgeons completed an electronic survey reporting surgeon demographics and treatment preference for pediatric femur fractures. Treatment preferences and indications for treatment were separated into 4 groups: infant (0 to 6 mo); toddler (7 mo to 4 y); child (5 to 12 y); adolescent (12 to 17 y). The survey was available in English, Spanish, and French. Analysis was completed with t test and χ test for continuous and categorical variables, respectively, and weighted Pearson correlation (P<0.05). RESULTS: Survey respondents consisted of 413 surgeons from 83 countries (20 LIC, 33 LMIC, 30 UMIC). The majority of respondents were fellowship trained (83%) most commonly in pediatrics (26%) and trauma (43%). Most treated >10 pediatric femur fractures per year (68%). Respondents reported treating infant femur fractures nonoperatively using Pavlik harness (19%), spica cast (60%), or traction with delayed spica cast (14%). Decreasing socioeconomic status was associated with higher nonoperative treatment rate in toddlers, children, and adolescents. Respondents commonly utilize bed rest and traction for child femur fractures in LICs (63%) and LMICs (65%) compared with UMICs (35%) (UMIC vs. LMIC P<0.001; UMIC vs. LIC P<0.001). Surgeries in children more commonly involve open reduction with internal fixation (UMIC 19%, LMIC 33%, LIC 40%; P<0.05 between UMIC-LMIC and UMIC-LIC). CONCLUSION: This is one of the largest surveys describing treatment patterns for pediatric femur fractures in low and middle income countries. Differences are evident including lower operative treatment rate in younger children and lower intramedullary fixation rates in older children. Future studies should investigate the value of treatment options in resource-limited settings. LEVEL OF EVIDENCE: Level II-prospective comparative study.