Human sperm RNA in male infertility.

The function and value of specific sperm RNAs in apparently idiopathic male infertility are currently poorly understood. Whether differences exist in the sperm RNA profile between patients with infertility and fertile men needs clarification. Similarly, the utility of sperm RNAs in predicting successful sperm retrieval and assisted reproductive technique (ART) outcome is unknown. Patients with infertility and fertile individuals seem to have differences in the expression of non-coding RNAs that regulate genes controlling spermatogenesis. Several RNAs seem to influence embryo quality and development. Also, RNA types seem to predict successful sperm retrieval in patients with azoospermia. These findings suggest that sperm RNAs could influence decision-making during the management of patients with infertility. This evidence might help to identify possible therapeutic approaches aimed at modulating the expression of dysregulated genes in patients with infertility. Performing prospective studies with large sample sizes is necessary to investigate cost-effective panels consisting of proven molecular targets to ensure that this evidence can be translated to clinical practice.

Genomic prediction for potato (Solanum tuberosum) quality traits improved through image analysis.

Potato (Solanum tuberosum L.) is the most widely grown vegetable in the world. Consumers and processors evaluate potatoes based on quality traits such as shape and skin color, making these traits important targets for breeders. Achieving and evaluating genetic gain is facilitated by precise and accurate trait measures. Historically, quality traits have been measured using visual rating scales, which are subject to human error and necessarily lump individuals with distinct characteristics into categories. Image analysis offers a method of generating quantitative measures of quality traits. In this study, we use TubAR, an image-analysis R package, to generate quantitative measures of shape and skin color traits for use in genomic prediction. We developed and compared different genomic models based on additive and additive plus non-additive relationship matrices for two aspects of skin color, redness, and lightness, and two aspects of shape, roundness, and length-to-width ratio for fresh market red and yellow potatoes grown in Minnesota between 2020 and 2022. Similarly, we used the much larger chipping potato population grown during the same time to develop a multi-trait selection index including roundness, specific gravity, and yield. Traits ranged in heritability with shape traits falling between 0.23 and 0.85, and color traits falling between 0.34 and 0.91. Genetic effects were primarily additive with color traits showing the strongest effect (0.47), while shape traits varied based on market class. Modeling non-additive effects did not significantly improve prediction models for quality traits. The combination of image analysis and genomic prediction presents a promising avenue for improving potato quality traits.

Magnetic Resonance Neurography of the Foot and Ankle.

Peripheral neuropathies of the foot and ankle can be challenging to diagnose clinically due to concomitant traumatic and nontraumatic or degenerative orthopedic conditions. Although clinical history, physical examination, and electrodiagnostic testing comprised of nerve conduction velocities and electromyography are used primarily for the identification and classification of peripheral nerve disorders, MR neurography (MRN) can be used to visualize the peripheral nerves as well as the skeletal muscles of the foot and ankle for primary neurogenic pathology and skeletal muscle denervation effect. Proper knowledge of the anatomy and pathophysiology of peripheral nerves is important for an MRN interpretation.

A novel iPSC model of Bryant-Li-Bhoj neurodevelopmental syndrome demonstrates the role of histone H3.3 in neuronal differentiation and maturation.

Background: Bryant-Li-Bhoj neurodevelopmental syndrome (BLBS) is neurogenetic disorder caused by variants in H3-3A and H3-3B, the two genes that encode the histone H3.3 protein. Ninety-nine percent of individuals with BLBS show developmental delay/intellectual disability, but the mechanism by which variants in H3.3 result in these phenotypes is not yet understood. As a result, only palliative interventions are available to individuals living with BLBS. Methods: Here, we investigate how one BLBS-causative variant, H3-3B p.Leu48Arg (L48R), affects neurodevelopment using an induced pluripotent stem cell (iPSC) model differentiated to 2D neural progenitor cells (NPCs), 2D forebrain neurons (FBNs), and 3D dorsal forebrain organoids (DFBOs). We employ a multi-omic approach in the 2D models to quantify the resulting changes in gene expression and chromatin accessibility. We used immunofluorescence (IF) staining to define the identities of cells in the 3D DFBOs. Results: In the 2D systems, we found dysregulation of both gene expression and chromatin accessibility of genes important for neuronal fate, maturation, and function in H3.3 L48R compared to control. Our work in 3D organoids corroborates these findings, demonstrating altered proportions of radial glia and mature neuronal cells. Conclusions: These data provide the first mechanistic insights into the pathogenesis of BLBS from a human-derived model of neurodevelopment, which suggest that the L48R increases H3-3B expression, resulting in the hyper-deposition of H3.3 into the nucleosome which underlies changes in gene expression and chromatin accessibility. Functionally, this causes dysregulation of cell adhesion, neurotransmission, and the balance between excitatory and inhibitory signaling. These results are a crucial step towards preclinical development and testing of targeted therapies for this and related disorders.

Whole-genome analysis of plasma fibrinogen reveals population-differentiated genetic regulators with putative liver roles.

Genetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole genome sequencing (WGS) data provides better coverage of the genome and better representation of non-European variants. To better understand the genetic landscape regulating plasma fibrinogen levels, we meta-analyzed WGS data from the NHLBI's Trans-Omics for Precision Medicine (TOPMed) program (n=32,572), with array-based genotype data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (n=131,340) imputed to the TOPMed or Haplotype Reference Consortium panel. We identified 18 loci that have not been identified in prior genetic studies of fibrinogen. Of these, four are driven by common variants of small effect with reported MAF at least 10 percentage points higher in African populations. Three signals (SERPINA1, ZFP36L2, and TLR10) contain predicted deleterious missense variants. Two loci, SOCS3 and HPN, each harbor two conditionally distinct, non-coding variants. The gene region encoding the fibrinogen protein chain subunits (FGG;FGB;FGA), contains 7 distinct signals, including one novel signal driven by rs28577061, a variant common in African ancestry populations but extremely rare in Europeans (MAFAFR=0.180; MAFEUR=0.008). Through phenome-wide association studies in the VA Million Veteran Program, we found associations between fibrinogen polygenic risk scores and thrombotic and inflammatory disease phenotypes, including an association with gout. Our findings demonstrate the utility of WGS to augment genetic discovery in diverse populations and offer new insights for putative mechanisms of fibrinogen regulation.

Health-economic burden attributable to novel serotypes in candidate 24- and 31-valent pneumococcal conjugate vaccines.

INTRODUCTION: Next-generation pneumococcal vaccines currently in clinical trials include 24- and 31-valent pneumococcal conjugate vaccines (PCV24, PCV31), which aim to prevent upper-respiratory carriage and disease involving the targeted serotypes. We aimed to estimate the comprehensive health-economic burden associated with acute respiratory infections (ARIs) and invasive pneumococcal disease (IPD) attributable to PCV24- and PCV31-additional (non-PCV20) serotypes in the United States. MATERIAL AND METHODS: We multiplied all-cause incidence rate estimates for acute otitis media (AOM), sinusitis, and non-bacteremic pneumonia by estimates of the proportions of each of these conditions attributable to pneumococci and the proportions of pneumococcal infections involving PCV24- and PCV31-additional serotypes. We estimated serotype-specific IPD incidence rates using US Active Bacterial Core surveillance data. We accounted for direct medical and non-medical costs associated with each condition to estimate resulting health-economic burden. Non-medical costs included missed work and lost quality-adjusted life years due to death and disability. RESULTS: The health-economic burden of PCV24-additional serotypes totaled $1.3 ($1.1-1.7) billion annually in medical and non-medical costs, comprised of $0.9 ($0.7-1.2) billion due to ARIs and $0.4 ($0.3-0.5) billion due to IPD. For PCV31-additional serotypes, medical and non-medical costs totaled $7.5 ($6.6-8.6) billion annually, with $5.5 ($4.7-6.6) billion due to ARIs and $1.9 ($1.8-2.1) billion due to IPD. The largest single driver of costs was non-bacteremic pneumonia, particularly in adults aged 50-64 and ≥65 years. CONCLUSIONS: Additional serotypes in PCV24 and PCV31, especially those included in PCV31, account for substantial health-economic burden in the United States.

Progress on the development of Class A GPCR-biased ligands.

Class A G protein-coupled receptors (GPCRs) continue to garner interest for their essential roles in cell signalling and their importance as drug targets. Although numerous drugs in the clinic target these receptors, over 60% GPCRs remain unexploited. Moreover, the adverse effects triggered by the available unbiased GPCR modulators, limit their use and therapeutic value. In this context, the elucidation of biased signalling has opened up new pharmacological avenues holding promise for safer therapeutics. Functionally selective ligands favour receptor conformations facilitating the recruitment of specific effectors and the modulation of the associated pathways. This review surveys the current drug discovery landscape of GPCR-biased modulators with a focus on recent advances. Understanding the biological effects of this preferential coupling is at different stages depending on the Class A GPCR family. Therefore, with a focus on individual GPCR families, we present a compilation of the functionally selective modulators reported over the past few years. In doing so, we dissect their therapeutic relevance, molecular determinants and potential clinical applications.

Geographic variation in first lower extremity amputations related to diabetes and/or peripheral arterial disease.

BACKGROUND: To assess trends of first cases of lower extremity amputations (LEA) related to diabetes and/or peripheral arterial disease (PAD), according to areas of residency and neighbourhood material/social deprivation quintiles, in the province of Quebec, Canada. METHODS: Using the Quebec Integrated Chronic Disease Surveillance System, we calculated crude and age-standardized annual incidence rates of first LEA (total, minor and major) among adults ≥40 years with diabetes and/or PAD between fiscal years 2006 to 2019. Area of residency was compiled in three categories: 1) Montreal/other census metropolitan areas (CMAs), 2) midsize agglomerations (10,000 to 100,000 inhabitants), and 3) small towns/rural areas (<10,000 inhabitants). We also stratified by neighbourhood material/social deprivation quintiles. One-year and 5-year all-cause mortality after first LEA was compared between areas of residency. RESULTS: Among the 10,275 individuals who had a first LEA, age-standardized LEA rates remained stable between 2006 and 2019, while major LEA declined in all geographical areas whereas minor LEA increased (31.6%) in small towns/rural areas. In 2019, age-standardized LEA rates were higher in midsize agglomerations and small towns/rural areas compared with CMAs. Age-standardized LEA rates in 2019 were higher among the most deprived quintile compared with the most privileged quintile, for both material/social deprivation. No difference was observed in mortality after first LEA between areas of residency. CONCLUSION: There are health disparities in the burden of diabetes and PAD related first LEA in the province of Quebec. In order to improve preventive care and reduce the burden of LEA, targeted actions should be taken among the most deprived groups and rural settings.

Exploring the feasibility and acceptability of community paramedicine programs in achieving vaccination equity: a qualitative study.

BACKGROUND: Mobile Integrated Health-Community Paramedicine (MIH-CP) is a novel approach that may reduce the rural-urban disparity in vaccination uptake in the United States. MIH-CP providers, as physician extenders, offer clinical follow-up and wrap-around services in homes and communities, uniquely positioning them as trusted messengers and vaccine providers. This study explores stakeholder perspectives on feasibility and acceptability of community paramedicine vaccination programs. METHODS: We conducted semi-structured qualitative interviews with leaders of paramedicine agencies with MIH-CP, without MIH-CP, and state/regional leaders in Indiana. Interviews were audio recorded, transcribed verbatim, and analyzed using content analysis. RESULTS: We interviewed 24 individuals who represented EMS organizations with MIH-CP programs (MIH-CP; n = 10), EMS organizations without MIH-CP programs (non-MIH-CP; n = 9), and state/regional administrators (SRA; n = 5). Overall, the sample included professionals with an average of 19.6 years in the field (range: 1-42 years). Approximately 75% (n = 14) were male, and all identified as non-Hispanic white. MIH-CPs reported they initiated a vaccine program to reach underserved areas, operating as a health department extension. Some MIH-CPs integrated existing services, such as food banks, with vaccine clinics, while other MIH-CPs focused on providing vaccinations as standalone initiatives. Key barriers to vaccination program initiation included funding and vaccinations being a low priority for MIH-CP programs. However, participants reported support for vaccine programs, particularly as they provided an opportunity to alleviate health disparities and improve community health. MIH-CPs reported low vaccine hesitancy in the community when community paramedics administered vaccines. Non-CP agencies expressed interest in launching vaccine programs if there is clear guidance, sustainable funding, and adequate personnel. CONCLUSIONS: Our study provides important context on the feasibility and acceptability of implementing an MIH-CP program. Findings offer valuable insights into reducing health disparities seen in vaccine uptake through community paramedics, a novel and innovative approach to reduce health disparities in rural communities.

A robust brain network for sustained attention from adolescence to adulthood that predicts later substance use.

Substance use, including cigarettes and cannabis, is associated with poorer sustained attention in late adolescence and early adulthood. Previous studies were predominantly cross-sectional or under-powered and could not indicate if impairment in sustained attention was a predictor of substance use or a marker of the inclination to engage in such behavior. This study explored the relationship between sustained attention and substance use across a longitudinal span from ages 14 to 23 in over 1000 participants. Behaviors and brain connectivity associated with diminished sustained attention at age 14 predicted subsequent increases in cannabis and cigarette smoking, establishing sustained attention as a robust biomarker for vulnerability to substance use. Individual differences in network strength relevant to sustained attention were preserved across developmental stages and sustained attention networks generalized to participants in an external dataset. In summary, brain networks of sustained attention are robust, consistent, and able to predict aspects of later substance use.

Erratum. Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes. Diabetes Care 2024;47:1276-1298.

In the article cited above, incorrect affiliation information was given for author Linda A. DiMeglio. The correct affiliation for Linda A. DiMeglio is Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN. The online version of the article (https://doi.org/10.2337/dci24-0042) has been updated to correct the error.

NUS so fast: the social and ecological implications of a rapidly developing indigenous food economy in the Cape Town area.

The modern global food system is highly unsustainable, shaped by industrialisation and corporate consolidation, with negative repercussions on the environment and biodiversity as well as human health. This paper looks at the burgeoning economy in neglected and underutilised species (NUS) in the Western Cape, South Africa, as a potential innovation that could make the local food system more socially and ecologically resilient. Although, at present, NUS are only marginally included in the local food system and policy discussions, NUS increasingly appear in the high-end food industry, driven by international gastronomic trends. These species hold potential as climate resilient, nutritionally dense, and socially and culturally significant foods in the region, but they also carry ecological and social risks. We critically examine the fledgling NUS economy in the Cape Town area to unpack the motivations and challenges associated with the potentially transformative inclusion of these foods into the local food system. We demonstrate that the main risks associated with NUS are negative ecological repercussions, privatisation of the NUS economy, and the reproduction and further entrenchment of unequal power and race dynamics in the region. To mitigate these risks and actualise the related benefits associated with NUS, engagement with the ecological, social, and political context of NUS needs to be significantly deepened. This is particularly true for those working in the high-end food industry, who appear to be driving the NUS economy, and will require education around sustainability and Traditional Ecological Knowledge (TEK), as well as a foregrounding awareness of power dynamics.

An international study presenting a federated learning AI platform for pediatric brain tumors.

While multiple factors impact disease, artificial intelligence (AI) studies in medicine often use small, non-diverse patient cohorts due to data sharing and privacy issues. Federated learning (FL) has emerged as a solution, enabling training across hospitals without direct data sharing. Here, we present FL-PedBrain, an FL platform for pediatric posterior fossa brain tumors, and evaluate its performance on a diverse, realistic, multi-center cohort. Pediatric brain tumors were targeted due to the scarcity of such datasets, even in tertiary care hospitals. Our platform orchestrates federated training for joint tumor classification and segmentation across 19 international sites. FL-PedBrain exhibits less than a 1.5% decrease in classification and a 3% reduction in segmentation performance compared to centralized data training. FL boosts segmentation performance by 20 to 30% on three external, out-of-network sites. Finally, we explore the sources of data heterogeneity and examine FL robustness in real-world scenarios with data imbalances.

Ex vivo comparison of one-layer versus two-layer closures in end-to-end anastomoses in normal equine descending colon.

OBJECTIVE: The aim of the study was to evaluate time to closure, bursting pressures and luminal diameters of a single and double-layer end-to-end anastomoses in normal equine descending colon. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Eight adult horses. METHODS: Four segments of descending colon from each horse were randomly assigned to a control (n = 8, CON), one-layer (n = 12, group 1; continuous Lembert pattern), or two-layer group (n = 12, group 2; simple continuous oversewn with Cushing pattern). Anastomoses were performed, and time to closure and luminal diameter were measured. Bursting pressures were determined, and location of failure was recorded. Mixed analysis of variance (ANOVA) was employed. RESULTS: Mean time to completion was decreased (p = .003) in group 1 (18.6 min ± 22.8 s) compared with group 2 (21.35 min ± 22.8 s). Luminal diameter was reduced (p < .0001) in group 2 (47 ± 2.46 mm) compared to group 1 (65 ± 2.77 mm). Location of failure was remote to the anastomosis in all but one segment; therefore, differences in anastomotic bursting pressures could not be determined. CONCLUSION: Two-layer closures resulted in significant luminal reduction and took longer to complete than one-layer anastomoses. CLINICAL SIGNIFICANCE: Use of one-layer closures may be advantageous primarily with respect to luminal diameter.

Geographical location, cigarette risk perceptions, and current smoking among older US adults.

INTRODUCTION: Cigarette smoking and smoking-related lung disease are more common in rural (vs urban) areas of the United States (US). This study examined relationships between geographical location, cigarette risk perceptions, and current smoking among older adults who are at greatest risk of developing smoking-related lung disease. METHODS: The study was a secondary data analysis of 12126 respondents aged ≥40 years from Wave 5 of the Population Assessment of Tobacco and Health Study. Weighted descriptive statistics and Poisson regressions assessed current smoking (vs never or former) as a function of geographical location in a stepwise fashion, first unadjusted, then adjusting for sociodemographic characteristics, and finally for both sociodemographic characteristics and cigarette risk perceptions (4-item scale), in three separate models. Sensitivity analyses examined whether individual risk perceptions items had a greater impact on the association between geographical location and current smoking. RESULTS: Current smoking was more common among rural (20.6%) than urban (17.6%) residents. The risk ratio (RR) for rural (vs urban) residence on current smoking decreased from 1.17 (95% CI: 1.03-1.32) to 1.14 (95% CI: 1.01-1.29) to 1.08 (95% CI: 0.96-1.21) across the stepwise models. Lower cigarette risk perceptions confounded the rural-current smoking association and was an independent risk factor for smoking (adjusted RR, ARR=2.15; 95% CI: 1.94-2.18). In sensitivity analyses, believing that cigarettes are very or extremely (vs somewhat, slightly, or not at all) harmful to health and agreeing (vs not agreeing) that secondhand smoke causes lung disease in people who do not smoke, confounded the rural-current smoking association whereas beliefs about smoking causing lung cancer or lung disease in people who smoke did not. CONCLUSIONS: Lower cigarette risk perceptions among rural residents confounded the positive association between rural residence and current smoking. Results from sensitivity analyses highlight potential targets for communication campaigns aimed at promoting more accurate perceptions of the harmful health consequences of cigarette smoking.

Skin Carotenoids are Related to Cognitive Abilities among Toddlers.

BACKGROUND: Carotenoids are antioxidant pigments that deposit in human tissues (e.g., skin, macula, and brain) upon dietary consumption. The health implications of skin carotenoids, which reflect overall dietary carotenoid consumption, have not been adequately studied in younger populations. OBJECTIVE: This work aimed to examine links between skin carotenoids and cognitive, language, and motor skills among toddlers. A secondary aim explored relationships between skin carotenoids and neurophysiological outcomes of sensory memory (i.e., mismatch negativity [MMN]) and the functional integrity of the visual pathway (i.e., visual evoked potentials [VEPs]). METHODS: Toddlers 12-18 months (n = 45) participated in a cross-sectional study. Skin carotenoids were measured with reflection spectroscopy via the Veggie MeterTM. Cognitive, language, and motor skills were measured using the Bayley Scale of Infant and Toddler Development IV Screening Test (BSID-IV). MMN and VEPs were collected with an auditory oddball task and a pattern reversal task, respectively, using electroencephalography. Analyses adjusted for age, household income, highest level of parental education, and total carotenoid intake (mg/1000kCal). RESULTS: Regression modelling revealed that skin carotenoids significantly related to cognition (R2 = 0.57, p = 0.04) and not to any other BSID-IV subsets. Neither MMN nor VEP outcomes significantly related to skin carotenoids. CONCLUSIONS: Greater skin carotenoids were selectively related to cognition, indicating that carotenoids may play a role in cognition in toddlers. Additional research is needed to understand links between skin carotenoids and specific domains of cognitive function and brain health in early life. CLINICAL TRIAL REGISTRY: N/A.

Existing evidence on the effects of climate variability and climate change on ungulates in North America: a systematic map.

BACKGROUND: Climate is an important driver of ungulate life-histories, population dynamics, and migratory behaviors. Climate conditions can directly impact ungulates via changes in the costs of thermoregulation and locomotion, or indirectly, via changes in habitat and forage availability, predation, and species interactions. Many studies have documented the effects of climate variability and climate change on North America's ungulates, recording impacts to population demographics, physiology, foraging behavior, migratory patterns, and more. However, ungulate responses are not uniform and vary by species and geography. Here, we present a systematic map describing the abundance and distribution of evidence on the effects of climate variability and climate change on native ungulates in North America. METHODS: We searched for all evidence documenting or projecting how climate variability and climate change affect the 15 ungulate species native to the U.S., Canada, Mexico, and Greenland. We searched Web of Science, Scopus, and the websites of 62 wildlife management agencies to identify relevant academic and grey literature. We screened English-language documents for inclusion at both the title and abstract and full-text levels. Data from all articles that passed full-text review were extracted and coded in a database. We identified knowledge clusters and gaps related to the species, locations, climate variables, and outcome variables measured in the literature. REVIEW FINDINGS: We identified a total of 674 relevant articles published from 1947 until September 2020. Caribou (Rangifer tarandus), elk (Cervus canadensis), and white-tailed deer (Odocoileus virginianus) were the most frequently studied species. Geographically, more research has been conducted in the western U.S. and western Canada, though a notable concentration of research is also located in the Great Lakes region. Nearly 75% more articles examined the effects of precipitation on ungulates compared to temperature, with variables related to snow being the most commonly measured climate variables. Most studies examined the effects of climate on ungulate population demographics, habitat and forage, and physiology and condition, with far fewer examining the effects on disturbances, migratory behavior, and seasonal range and corridor habitat. CONCLUSIONS: The effects of climate change, and its interactions with stressors such as land-use change, predation, and disease, is of increasing concern to wildlife managers. With its broad scope, this systematic map can help ungulate managers identify relevant climate impacts and prepare for future changes to the populations they manage. Decisions regarding population control measures, supplemental feeding, translocation, and the application of habitat treatments are just some of the management decisions that can be informed by an improved understanding of climate impacts. This systematic map also identified several gaps in the literature that would benefit from additional research, including climate effects on ungulate migratory patterns, on species that are relatively understudied yet known to be sensitive to changes in climate, such as pronghorn (Antilocapra americana) and mountain goats (Oreamnos americanus), and on ungulates in the eastern U.S. and Mexico.

Diagnostic and Therapeutic Implications of a FUS::TFCP2 Fusion and ALK Activation in a Metastatic Rhabdomyosarcoma.

The identification of gene fusions in rare sarcoma subtypes can have diagnostic, prognostic, and therapeutic impacts for advanced cancer patients. Here, we present a case of a 31-year-old male with a lytic lesion of the left mandible initially diagnosed as an osteosarcoma but found to have a TFCP2 fusion and ALK alteration, redefining the diagnosis and providing rationale for a novel treatment strategy. Histologically, the tumor displayed hypercellular, spindled to epithelioid neoplasm and nuclear pleomorphism, while immunohistochemistry showed diffuse SATB2 and focal desmin staining. Whole genome and transcriptome analysis revealed a FUS::TFCP2 fusion, the defining alteration of a rare molecularly characterized subtype of soft tissue sarcoma termed intraosseous rhabdomyosarcoma. An internal ALK deletion and extremely high ALK RNA expression were also identified, suggesting potential benefit of an ALK inhibitor. This patient displayed a rapid and dramatic clinical and radiographic response to an ALK inhibitor, alectinib. Unfortunately, the response was short-lived, likely due to the advanced stage and aggressiveness of the disease. This report describes genome and transcriptome characterization of an intraosseous rhabdomyosarcoma, few of which exist in the literature, as well as providing evidence that inhibition of ALK may be a rational treatment strategy for patients with this exceedingly rare soft tissue sarcoma subtype characterized by TFCP2 fusions and ALK activation.