A Highly Transparent Photo-Electro-Thermal Film with Broadband Selectivity for All-Day Anti-/De-Icing.

A photo- and electro-thermal film can convert sunlight and electricity into heat to solve icing problems. Combination of them provides an efficient strategy for all-day anti-/de-icing. However, only opaque surfaces have been reported, due to the mutual exclusiveness between photon absorption and transmission. Herein, a highly transparent and scalable solution-processed photo-electro-thermal film is reported, which exhibits an ultra-broadband selective spectrum to separate the visible light from sunlight and a countertrend suppress of emission in longer wavelength. It absorbs ≈ 85% of invisible sunlight (ultraviolet and near-infrared) for light-heat conversion, meanwhile maintains luminous transmittance > 70%. The reflection of mid-infrared leads to low emissivity (0.41), which further preserves heat on the surface for anti-/de-icing purpose. This ultra-broadband selectivity enables temperature elevation > 40 °C under 1-sun illumination and the mutual support between photo-thermal and electro-thermal effects contributes to > 50% saving of electrical consumption under weak solar exposure (0.4-sun) for maintaining unfrozen surfaces at -35 °C environment. The reverberation from photo-electro-thermal and super-hydrophobic effects illustrates a lubricating removal of grown ice in short time (< 120 s). The self-cleaning ability and the durability under mechanical, electrical, optical, and thermal stresses render the film stable for long-term usage in all-day anti-/de-icing applications.

Altered Vaginal Microbiota Composition Correlates With Human Papillomavirus and Mucosal Immune Responses in Women With Symptomatic Cervical Ectopy.

Cervical ectopy is a benign condition of the lower genital tract that is frequently detected in women of reproductive age. Although cervical ectopy is regarded as a physiological condition, some women experience symptoms such as leucorrhoea, persistent bleeding and recurrent vaginal infections that require medical intervention. Cervical ectopy has not been linked to cervical cancer, but it is thought to facilitate the acquisition of sexually transmitted diseases (STDs), like Human Papillomavirus (HPV) infection, as it provides a favorable microenvironment for virus infection and dissemination. We and others have described the presence of oncogenic HPV types in women with symptomatic cervical ectopy. The relevance of this finding and the impact of symptomatic cervical ectopy on the cervicovaginal microenvironment (vaginal microbiota, immune and inflammatory responses) are currently unknown. To shed some light into the interplay between HPV, the vaginal microbiota and mucosal immune and inflammatory responses in the context of this condition, we enrolled 156 women with symptomatic cervical ectopy and determined the presence of HPV using a type-specific multiplex genotyping assay. Overall, HPV was detected in 54.48% women, oncogenic HPV types were found in more than 90% of HPV-positive cases. The most prevalent HPV types were HPV16 (29.4%), HPV31 (21.17%) and HPV18 (15.29%). Next, we evaluated the vaginal microbial composition and diversity by 16S rDNA sequencing, and quantified levels of cytokines and chemokines by flow cytometry using bead-based multiplex assays in a sub-cohort of 63 women. IL-21 and CXCL9 were significantly upregulated in HPV-positive women (p=0.0002 and p=0.013, respectively). Women with symptomatic cervical ectopy and HPV infection had increased diversity (p<0.001), and their vaginal microbiota was enriched in bacterial vaginosis-associated anaerobes (Sneathia, Shuttleworthia, Prevotella, and Atopobium) and depleted in Lactobacillus spp. Furthermore, the vaginal microbiota of women with symptomatic cervical ectopy and HPV infection correlated with vaginal inflammation (IL-1ß, rho=0.56, p=0.0004) and increased mucosal homeostatic response (IL-22, rho=0.60, p=0.0001). Taken together, our results suggest that HPV infection and dysbiotic vaginal communities could favor a vaginal microenvironment that might delay the recovery of the cervical epithelium in women with symptomatic cervical ectopy and favor STDs acquisition.

Drivers of insect consumption across human populations.

Discussions regarding entomophagy in humans have been typically led by entomologists. While anthropologists devote much time to understanding diverse human subsistence practices, historical and cultural variation in insect consumption remains largely unexplained. This review explores the relation between variable ecologies, subsistence strategies, and social norms on insect consumption patterns across past and contemporary human populations. Ecological factors, such as the nutritional contribution of edible insects relative to those of other foraged or farmed resources available, may help explain variation in their consumption. Additionally, our evolved social learning strategies may help propagate social norms that prohibit or prioritize the consumption of some or all edible insects, independent of their profitability. By adopting a behavioral ecological and cultural evolutionary approach, this review aims to resolve current debates on insect consumption and provide directions for future research.

Relación entre obesidad y enfermedades crónicas no transmisibles e infecciosas / Relationship between obesity and chronic non-communicable and infectious diseases

Introducción: la obesidad aumenta el riesgo a padecer de enfermedades crónicas no transmisibles (ECNT) y afecta el curso de enfermedades de origen infeccioso. Objetivo: examinar la literatura sobre cómo influye la obesidad en la gravedad del cuadro clínico de algunas de las enfermedades no transmisibles y transmisibles de mayor impacto en el Perú. Métodos: investigación documental. Se hace un análisis de contenidos de artículos y documentos de estudios desarrollados en diversos contextos asociados a la presencia de obesidad junto con infecciones o ECNT y en base de datos. Resultados: la condición de obesidad alcanzada por malos hábitos de consumo y baja actividad física, es la principal responsable del elevado índice de las ECNT y por consecuente de las tasas de mortalidad. Conclusiones: el exceso de peso afecta al sistema inmunológico, contribuyendo específicamente en los fenómenos exacerbados de respuesta inflamatoria sistémica, determinada por el aumento de secreción de adipocitoquinas, que predispone al organismo a desarrollar y contraer ECNT y enfermedades infecciosas. (AU)

Introduction: Obesity increases the risk of chronic non-communicable diseases (NCDs) and affects the course of diseases of infectious origin. Objective: Reviewing the literature on how obesity influences the severity of the clinical picture of some of the non-communicable and communicable diseases of greatest impact in Peru. Methods:Documentary research, from studies developed in various contexts associated with the presence of obesity along with infections or NCDs. Results: The condition of obesity reached by bad consumption habits and low physical activity is the main responsible for the high rate of NCDs, consequently, mortality. Conclusions: Excess weight affects the immune system, contributing specifically to exacerbated phenomena of a systemic inflammatory response, determined by increased secretion of adipocytokines, which predisposes the body to develop and contract NCDs and infectious diseases. (AU)

Knowledge, practices and perceptions regarding oral health preventive measures among Mexican dental students: a cross-sectional survey study.

Although oral diseases are mostly preventable, they remain a global public health problem. Thus, there is a need for trained personnel to actively intervene in promoting oral health, to prevent and timeously detect oral diseases, and, in turn, to provide comprehensive quality healthcare. The main objective of the study was to evaluate the knowledge, practices and perceptions regarding oral health preventive measures amongst undergraduate dental students. This cross-sectional study was conducted between the period October 2017 and January 2018. The subjects included were undergraduate students of the dental science program at the School of Dentistry, in Leon Guanajuato, Mexico. A validated questionnaire was used to identify knowledge of preventive dentistry and the frequency of oral health preventive actions in the dental school clinics. Besides, perception towards prevention in dentistry was assessed. A total of N=232 undergraduate students participated of whom 65.9% (N=153) were women. More than half of the students 59.5%, (N=138) rated their knowledge on the prevention of oral diseases as good, followed by 32.8% (N=75) of students who rated it as regular. 49% (N=97) of the students performed frequently preventive treatments in their daily clinical practice. 90% (N=217) think that the main reason of low practice of prevention in dentistry is the lack of commitment of the dentist. 72.8% (N=169) mention that there should be professionals dedicated exclusively to preventive dentistry. Students of second grade demonstrated better prevention knowledge and tended to engage more frequently in preventive activities (p<0.05). In conclusion, our study found that, second-year students perform preventive practices more frequently and these practices decrease as their studies progress. It should be sought to create positive attitudes towards prevention not only in the year in preventive dentistry, but also throughout the entire career. This enables students to become trained professionals that can deliver preventive services to their patients.

Results from the Survey of Antibiotic Resistance (SOAR) 2015-17 in Latin America (Argentina, Chile and Costa Rica): data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

OBJECTIVES: To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates from community-acquired respiratory tract infections (CA-RTIs) collected in 2015-17 from Argentina, Chile and Costa Rica. METHODS: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: A total of 170 S. pneumoniae and 218 H. influenzae isolates were collected at five centres in Argentina, Chile and Costa Rica in 2015-17. Small S. pneumoniae isolate numbers from Costa Rica (n = 2) meant that these could only be included in the penicillin susceptibility analysis; they were excluded from further country analyses. Around one-third of pneumococcal isolates from Argentina and two-thirds from Chile were non-susceptible to penicillin by CLSI oral or EUCAST low-dose IV breakpoints, but most (≥89%) were susceptible by CLSI IV or EUCAST high-dose breakpoints. Amongst pneumococci from Argentina, about 80% or more were susceptible to most other antibiotics except cefaclor (all breakpoints), cefixime (PK/PD breakpoints), cefuroxime (EUCAST breakpoints) and trimethoprim/sulfamethoxazole (CLSI and PK/PD breakpoints). S. pneumoniae isolates from Chile showed significantly lower susceptibility (P < 0.05) using CLSI breakpoints compared with those from Argentina for many of the antibiotics tested. Among isolates of H. influenzae from Latin America, more than 90% were susceptible to amoxicillin/clavulanic acid (high dose), cefixime, cefpodoxime, ceftriaxone and fluoroquinolones, irrespective of the breakpoints used. The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. CONCLUSIONS: Antibiotic susceptibility of H. influenzae isolates was generally high in the Latin American countries studied; however, susceptibility profiles varied for S. pneumoniae by country and depending on the breakpoints used, especially for cefaclor. These factors are important in decision making for empirical therapy of bacterial infections.

Basal-Type Breast Cancer Stem Cells Over-Express Chromosomal Passenger Complex Proteins.

(1) Aim: In the present paper we analyzed the transcriptome of CSCs (Cancer Stem Cells), in order to find defining molecular processes of breast cancer. (2) Methods: We performed RNA-Seq from CSCs isolated from the basal cell line MDA-MB-468. Enriched processes and networks were studied using the IPA (Ingenuity Pathway Analysis) tool. Validation was performed with qRT-PCR and the analysis of relevant genes was evaluated by overexpression, flow cytometry and in vivo zebrafish studies. Finally, the clinical relevance of these results was assessed using reported cohorts. (3) Results: We found that CSCs presented marked differences from the non-CSCs, including enrichment in transduction cascades related to stemness, cellular growth, proliferation and apoptosis. Interestingly, CSCs overexpressed a module of co-regulated Chromosomal Passenger Proteins including BIRC5 (survivin), INCENP and AURKB. Overexpression of BIRC5 increased the number of CSCs, as assessed by in vitro and in vivo zebrafish xenotransplant analyses. Analysis of previously published cohorts showed that this co-regulated module was not only overexpressed in basal breast tumors but also associated with relapse-free and overall survival in these patients. (4) Conclusions: These results underline the importance of Cancer Stem Cells in breast cancer progression and point toward the possible use of chromosomal passenger proteins as prognostic factors.

Progesterone signaling during pregnancy in the lab opossum, Monodelphis domestica.

To investigate subtle pregnancy-associated changes in the lab opossum, Monodelphis domestica, an induced ovulator, we compared pregnant with non-pregnant and pseudopregnant animals with regard to serum P4 levels and progesterone receptor (PR) expression. Using video-verified, time-mated lab opossums as sources of biological material, we compared ovaries, uteri and sera obtained on odd-numbered days of the 14.5-day pregnancy in this animal. Females that mated successfully but did not produce embryos were classified as pseudopregnant. P4 levels differed significantly between pregnant (N = 21) and either non-pregnant (N = 3) or pseudopregnant (N = 3) opossums, but not between the non-pregnant and pseudopregnant groups. A significant decline in serum P4 occurred between pregnancy days 3 and 5, coinciding with an elevated probability of pregnancy failure between days 5 and 9. PR was detected in the nuclei of uterine-gland epithelial cells on pregnancy days 5 and 7 as well as variably in the corpora lutea (CL) of animals on pregnancy days 3-11. PR expression in the CL suggests that P4 may be autostimulatory in lab opossums and that certain levels of this steroid are required during normal pregnancy. The significant day-3 drop in P4 may explain why pregnancy failure in this polyovular metatherian is likeliest to occur between days 5 and 9, an interval during which the extended period of blastocyst morphogenesis and expansion occurs. Taken together, these results suggest that P4 may have unrecognized signaling roles not only in pregnancy but perhaps embryonic development as well in the lab opossum.

Somatic innervation contributes to the release of bulbourethral gland secretion in male rats.

BACKGROUND: In male rats, the bulbourethral glands (Bu-Gs) are the unique accessory sexual glands surrounded by striated musculature. However, until now the role of this musculature was unknown. OBJECTIVES: (i) To characterize the Bu-Gs striated muscular layer in male rats and determine its innervation and response to genital stimulation. (ii) To reveal the role of the Bu-Gs striated musculature in the release of glandular secretion. (iii) To elucidate the effect of bilateral ablation of the Bu-Gs on copulatory behavior and seminal fluid characteristics. MATERIALS AND METHODS: Adult Wistar male rats were allocated in three experiments: in Experiment 1, the Bu-Gs striated musculature, innervation and reflex activity were determined by gross anatomy and histological and electrophysiological techniques; electromyographic activity of the Bu-Gs striated musculature was evoked with genital stimulation. In Experiment 2, Bu-Gs were analyzed after copulatory behavior of intact or animals with unilateral transected motor branch of the sacral plexus (MBSP). In Experiment 3, copulatory behavior and spermatobioscopy of males with bilateral ablation of the Bu-Gs or sham surgery were analyzed. RESULTS: The Bu-Gs striated fibers discharged in response to mechanostimulation of the prepuce, glans, and penile-urethra. Innervation of the Bu-Gs striated musculature originated from the MBSP; this nerve also innervates striated penile muscles. Unilateral transection of the MBSP significantly decreased the secretion from the ipsilateral Bu-G to the nerve transection. Bilateral ablation of Bu-Gs did not affect seminal plug formation but decreased semen viscosity. DISCUSSION AND CONCLUSION: The Bu-Gs striated musculature contributes to expel glandular secretion during sexual intercourse. The somatic control of Bu-Gs secretion is additional to the reported autonomic innervation supplied by the cavernosus nerve, which may underlie the synthesis of secretion as well as contraction of Bu-Gs smooth muscle.

Betaxanthins and antioxidant capacity in Stenocereus pruinosus: Stability and use in food.

Betalains are important pigments for the food, pharmaceutical, and cosmetics industry. In the yellow Stenocereus pruinosus fruits (pitayas), total betalain concentration, Folin-Ciocalteu reduction capacity, and antiradical capacity per dry weight were 2345.9µgg-1, 7.3mg gallic acid equivalentsg-1, and 48.8µmol Trolox equivalentg-1, respectively. The stability of betaxanthins, which represent 89% of total betalains in yellow pitayas, was evaluated over a range of pH, temperature, as well as in the presence of food additives. Maximum stability was observed at pH6.6, and addition of ascorbic acid increased the half-life 1.8 times. Thermal stability at pH6.48±0.05 was also evaluated from 50°C to 80°C, over which the activation energy for betaxanthin degradation was determined to be 66.2kJmol-1. Model gelatin gummies and beverages were then prepared with pitaya juice or pulp, and pigment retention and color parameters were investigated during storage under various conditions. To match the yellow color of commercial products, gummies were supplemented with 4.6% w/w juice or pulp, and beverages were supplemented with 5% w/v juice, achieving H° values of 69.0-86.2° and 64.6-87.1°, respectively. Results indicate that betaxanthins were more stable in gummies than in beverages, and that pigment retention increased when products were stored in the dark or at low temperatures. Also, different changes in color during storage were observed between gummies and beverages.

Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia.

This corrects the article DOI: 10.1038/mp.2017.42.

Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia.

Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide single-nucleotide polymorphism (SNP) and neuroimaging data from 1750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (false discovery rate=10%). In particular, intracranial volume and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross-disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder.

Hepatitis B surface antibodies in medical students from a public university in Puebla, Mexico.

Although preventable with vaccination, Hepatitis B virus (HBV) infection is a major health concern, with ∼400 million people at risk of developing the chronic form of the disease worldwide. The anti-HBV vaccine consists of a recombinant HBV surface antigen (HBsAg), which induces specific anti-HBs antibodies and confers 95% protection for >20 y. The aim of the present study was to analyze the response to HBV vaccination by measuring anti-HBs antibodies in serum samples from medical students of a public university in Puebla, Mexico. HBV infection markers HBsAg and anti-HBs, were also determined. A total of 201 students were included and vaccination coverage was found at 54%. Overall seropositivity for HBsAg, anti-HBc and anti-HBs determined by ELISA was 0.5%, 1.0% and 47%, respectively. Protective levels of anti-HBs >10 mIU/mL were found in 93.2% of subjects vaccinated with 2 or 3 doses and in 40% of those vaccinated with a single dose; while only 4.8% of unvaccinated subjects were anti-HBs positive. The response to the HBV vaccine was different in each participant, despite similar vaccination scheme. A history of blood transfusion/organ transplant or more than 2 sexual partners was significantly associated with anti-HBc positivity, OR = 399 (p = 0.010) and OR = 19.9 (p = 0.044), respectively. HBV immunization coverage was low in our sample compared with reports from countries with similar HBV prevalence, but anti-HBs in vaccinated individuals were in the expected range. It is important to promote HBV vaccination and awareness among medical students, due to their exposure risk.

Neuroanatomic and behavioral correlates of urinary dysfunction induced by vaginal distension in rats.

The aim of the present study was to use a model of simulated human childbirth in rats to determine the damage to genitourinary structures and behavioral signs of urinary dysfunction induced by vaginal distension (VD) in female rats. In experiment 1, the length of the genitourinary tract and the nerves associated with it were measured immediately after simulated human delivery induced by VD or sham (SH) procedures. Electroneurograms of the dorsal nerve of the clitoris (DNC) were also recorded. In experiment 2, histological characteristics of the bladder and major pelvic ganglion of VD and SH rats were evaluated. In experiment 3, urinary parameters were determined in conscious animals during 6 h of dark and 6 h of light before and 3 days after VD or SH procedures. VD significantly increased distal vagina width (P < 0.001) and the length of the motor branch of the sacral plexus (P < 0.05), DNC (P < 0.05), and vesical nerves (P < 0.01) and decreased DNC frequency and amplitude of firing. VD occluded the pelvic urethra, inducing urinary retention, hematomas in the bladder, and thinness of the epithelial (P < 0.05) and detrusor (P < 0.01) layers of the bladder. Major pelvic ganglion parameters were not modified after VD. Rats dripped urine in unusual places to void, without the stereotyped behavior of micturition after VD. The neuroanatomic injuries after VD occur alongside behavioral signs of urinary incontinence as determined by a new behavioral tool for assessing micturition in conscious animals.

Advances in the knowledge of breast cancer stem cells. A review.

Much effort has been made by researchers to elucidate the complex biology of breast cancer stem cells (BCSCs), a small subset of breast tumor cells that display stem cell properties, drive tumor initiation, and growth. In recent years, it has been suggested that BCSCs could be responsible for the process of metastasis and the development of drug resistance. These findings make the need to find the distinguishing blend of markers that can recognize only BCSCs of the utmost importance in order to be able to design new targeted therapies. This review will summarize BCSCs' main features as well as the cell surface markers that are currently used to identify them.

Tissue inhibitor of metalloproteinases-4 (TIMP-4) regulates stemness in cervical cancer cells.

Tissue inhibitor of metalloproteinase-4 (TIMP-4) belongs to a family of extracellular matrix (ECM) metalloproteinases inhibitors that are overexpressed in several cancers. However, the role of TIMP-4 during carcinogenesis is poorly understood. To evaluate TIMP-4 functions in carcinogenesis, stably transfected cells overexpressing this tissue inhibitor were used. Xenograft tumor growth, stem cell enrichment, colony formation, and gene regulation were investigated. Microarrays and in silico analysis were carried out to elucidate TIMP-4 molecular mechanisms. In the present report, we show that in nude mice, cervical cancer cells that overexpress TIMP-4 formed tumors faster than control cell-derived tumors. Furthermore, in vivo limiting dilution assays showed that fewer TIMP-4 overexpressing cells are needed for tumor formation. In vitro analyses demonstrated that TIMP-4 overexpression or exposure to human recombinant TIMP-4 (hrTIMP4) caused an enrichment of the tumor progenitor cell (TPC) population. Accordingly, genome-wide expression and signaling pathway analyses showed that hrTIMP-4 modulated cell survival, cell proliferation, inflammation, and epithelial-mesenchymal transition (EMT) signaling networks. Notably, NFκB signaling pathway appeared to be globally activated upon hrTIMP-4 treatment. Overall, this report provides the first example that TIMP-4 regulates carcinogenesis through enriching the TPC population in cervical cancer cells. Understanding TIMP-4 effects on tumorigenesis may provide clues for future therapies design. © 2015 Wiley Periodicals, Inc.

BioAssay Research Database (BARD): chemical biology and probe-development enabled by structured metadata and result types.

BARD, the BioAssay Research Database (https://bard.nih.gov/) is a public database and suite of tools developed to provide access to bioassay data produced by the NIH Molecular Libraries Program (MLP). Data from 631 MLP projects were migrated to a new structured vocabulary designed to capture bioassay data in a formalized manner, with particular emphasis placed on the description of assay protocols. New data can be submitted to BARD with a user-friendly set of tools that assist in the creation of appropriately formatted datasets and assay definitions. Data published through the BARD application program interface (API) can be accessed by researchers using web-based query tools or a desktop client. Third-party developers wishing to create new tools can use the API to produce stand-alone tools or new plug-ins that can be integrated into BARD. The entire BARD suite of tools therefore supports three classes of researcher: those who wish to publish data, those who wish to mine data for testable hypotheses, and those in the developer community who wish to build tools that leverage this carefully curated chemical biology resource.

The genomic landscape of pediatric Ewing sarcoma.

UNLABELLED: Pediatric Ewing sarcoma is characterized by the expression of chimeric fusions of EWS and ETS family transcription factors, representing a paradigm for studying cancers driven by transcription factor rearrangements. In this study, we describe the somatic landscape of pediatric Ewing sarcoma. These tumors are among the most genetically normal cancers characterized to date, with only EWS-ETS rearrangements identified in the majority of tumors. STAG2 loss, however, is present in more than 15% of Ewing sarcoma tumors; occurs by point mutation, rearrangement, and likely nongenetic mechanisms; and is associated with disease dissemination. Perhaps the most striking finding is the paucity of mutations in immediately targetable signal transduction pathways, highlighting the need for new therapeutic approaches to target EWS-ETS fusions in this disease. SIGNIFICANCE: We performed next-generation sequencing of Ewing sarcoma, a pediatric cancer involving bone, characterized by expression of EWS-ETS fusions. We found remarkably few mutations. However, we discovered that loss of STAG2 expression occurs in 15% of tumors and is associated with metastatic disease, suggesting a potential genetic vulnerability in Ewing sarcoma.