A Translation Tuning HuDdle for Neurons.

In this issue of Molecular Cell, Tebaldi et al. (2018) identify the neuron-specific RNA-binding protein HuD as a regulator of global protein synthesis and translation enhancer of specific mTORC1-responsive transcripts. Importantly, the authors identify that the Y3 small non-coding RNA binds HuD to modulate translation and neurogenesis.

Management of the intraoperative loss of microsurgical needles: A literature review and clinical survey.

Data on the incidence, management, and consequences of retained microsurgical needles in plastic and reconstructive surgery remains sparse. Research suggests that a mobile C-arm x-ray has a low detection rate for needles of size 8-0 or smaller. By means of a literature review, and survey, we aimed to investigate the current practice employed in the event of the intraoperative loss of a microsurgical needle. A literature review was conducted investigating the incidence, current management strategies, and consequences of retained microsurgical needles. This informed the questions included in a survey investigating management strategies employed in the intra-operative loss of a microsurgical needle. Results from the literature review show an overall low detection rate of microsurgical needles on imaging. Of the forty responders who completed the survey, 80% did not use a mobile C-arm x-ray to locate a missing microsurgical needle. Of the 20% that had done so, x-ray had been unsuccessful in locating the needle in all cases. Portable x-ray has a definite role to play in locating needles of size 7-0 or larger. This study suggests that suture needles of size 8-0 or smaller cannot be reliably detected on x-ray. Regarding management of this event, one should consider the risk of harm to the patient if retained, against the risk of searching for the needle. Based on the results of this work as well as existing published data, we advise against obtaining intra-operative x-rays in the event of a lost needle size 8-0 and above. Appropriate documentation should be completed.

Preparing adults with intellectual disabilities for their future: How do support services staff view their role?

BACKGROUND: Person-centred service delivery underpins current approaches to working with individuals with intellectual disabilities. We investigated views of staff from a service organisation regarding their roles in creating desired futures for adults with intellectual disabilities. METHODS: Data were gathered from staff of a large organisation that provided a range of services to adults with intellectual disabilities. Respondents were asked to describe their role in assisting an individual with intellectual disability to meet their goals for the future. Responses were analysed using a text analysis programme. RESULTS: Two major themes were identified: 'Support for self-determination' and 'Business-as-usual'. These themes were not entirely separate but had some overlap. There were indications that staff experienced competing demands in their role(s). CONCLUSION: Although central to person-centred planning, staff who work with adults with intellectual disabilities may not see support of self-determination as a key factor in creating a desired future.

Gross motor function prediction using natural language processing in cerebral palsy.

AIM: To predict ambulatory status and Gross Motor Function Classification System (GMFCS) levels in patients with cerebral palsy (CP) by applying natural language processing (NLP) to electronic health record (EHR) clinical notes. METHOD: Individuals aged 8 to 26 years with a diagnosis of CP in the EHR between January 2009 and November 2020 (~12 years of data) were included in a cross-sectional retrospective cohort of 2483 patients. The cohort was divided into train-test and validation groups. Positive predictive value, sensitivity, specificity, and area under the receiver operating curve (AUC) were calculated for prediction of ambulatory status and GMFCS levels. RESULTS: The median age was 15 years (interquartile range 10-20 years) for the total cohort, with 56% being male and 75% White. The validation group resulted in 70% sensitivity, 88% specificity, 81% positive predictive value, and 0.89 AUC for predicting ambulatory status. NLP applied to the EHR differentiated between GMFCS levels I-II and III (15% sensitivity, 96% specificity, 46% positive predictive value, and 0.71 AUC); and IV and V (81% sensitivity, 51% specificity, 70% positive predictive value, and 0.75 AUC). INTERPRETATION: NLP applied to the EHR demonstrated excellent differentiation between ambulatory and non-ambulatory status, and good differentiation between GMFCS levels I-II and III, and IV and V. Clinical use of NLP may help to individualize functional characterization and management. WHAT THIS PAPER ADDS: Natural language processing (NLP) applied to the electronic health record (EHR) can predict ambulatory status in children with cerebral palsy (CP). NLP provides good prediction of Gross Motor Function Classification System level in children with CP using the EHR. NLP methods described could be integrated in an EHR system to provide real-time information.

Electronic health record and patterns of care for children with cerebral palsy.

AIM: To characterize the patterns of care of children with cerebral palsy (CP) in a tertiary healthcare system. METHOD: Electronic health record data from 2009 to 2019 were extracted for children with CP. Machine learning hierarchical clustering was used to identify clusters of care. The ratio of in-person to care coordination visits was calculated for each specialty. RESULTS: The sample included 6369 children with CP (55.7% males, 44.3% females, 76.2% white, 94.7% non-Hispanic; with a mean age of 8y 2mo [SD 5y 10mo; range 0-21y; median 7y 1mo]) at the time of diagnosis. A total of 3.7 million in-person visits and care coordination notes were identified across 34 specialties. The duration of care averaged 5 years 5 months with five specialty interactions and 21.8 in-person visits per year per child. Seven clusters of care were identified, including: musculoskeletal and function; neurological; high-frequency/urgent care services; procedures; comorbid diagnoses; development and behavioral; and primary care. Network analysis showed shared membership among several clusters. INTERPRETATION: Coordination of care is a central element for children with CP. Medical informatics, machine learning, and big data approaches provide unique insights into care delivery to inform approaches to improve outcomes for children with CP. What this paper adds Seven primary clusters of care were identified: musculoskeletal and function; neurological; high-frequency/urgent care services; procedures; comorbid diagnoses; development and behavioral; and primary care. The in-person to care coordination visit ratio was 1:5 overall for healthcare encounters. Most interactions with care teams occur outside of in-person visits. The ratio of in-person to care coordination activities differ by specialty.

Insights into the Molecular Basis of Genome Stability and Pristine Proteostasis in Naked Mole-Rats.

The naked mole-rat (Heterocephalus glaber) is the longest-lived rodent, with a maximal reported lifespan of 37 years. In addition to its long lifespan - which is much greater than predicted based on its small body size (longevity quotient of ~4.2) - naked mole-rats are also remarkably healthy well into old age. This is reflected in a striking resistance to tumorigenesis and minimal declines in cardiovascular, neurological and reproductive function in older animals. Over the past two decades, researchers have been investigating the molecular mechanisms regulating the extended life- and health- span of this animal, and since the sequencing and assembly of the naked mole-rat genome in 2011, progress has been rapid. Here, we summarize findings from published studies exploring the unique molecular biology of the naked mole-rat, with a focus on mechanisms and pathways contributing to genome stability and maintenance of proteostasis during aging. We also present new data from our laboratory relevant to the topic and discuss our findings in the context of the published literature.

Influenza and associated co-infections in critically ill immunosuppressed patients.

BACKGROUND: It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. METHODS: Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. RESULTS: Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90-1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. CONCLUSIONS: Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients.

Long-Term Outcome of Interdisciplinary Management of Patients with Duchenne Muscular Dystrophy Receiving Daily Glucocorticoid Treatment.

OBJECTIVE: To evaluate clinical outcomes and steroid side effects in a cohort of patients with Duchenne muscular dystrophy (DMD) treated with long-term daily glucocorticoid therapy. Although daily glucocorticoid therapy has been shown to extend ambulatory function in DMD, less frequent dosing is often used because of side effect concerns. STUDY DESIGN: Retrospective study of 97 patients with DMD aged 10 to <16 years treated with daily glucocorticoid (89% on deflazacort) for a mean of 8.5 years. Outcome measures were motor, pulmonary, and cardiac function, and scoliosis. Side effects were growth failure and weight gain, facial fullness, blood pressure, bone health, cataracts, gastrointestinal symptoms, behavior, hypertrichosis, and need for medication interventions. RESULTS: For 13- to 16-year-old patients, 40% could rise from the floor and 50% could perform the 30-foot run test. Forced vital capacity for the entire cohort was well preserved. Thirteen percent of younger (10- to <13-year-old) and 21% of older patients had findings of left ventricle systolic dysfunction. Six percent (all aged 16 years) developed scoliosis (Cobb angle >20 degrees). Eighty-six percent had normal weight velocities; 30% had no increased facial fullness; 72% had short stature; and 19% had asymptomatic cataracts. Asymptomatic spine compression deformities were noted in 76% and long bone fractures in 30%. One patient stopped glucocorticoid because of behavioral concerns. CONCLUSIONS: With evidence for improved outcomes and manageable side effects, we recommend use of daily glucocorticoid therapy for patients with DMD with anticipatory management of side effects and a coordinated interdisciplinary care approach.

Retro-Antegrade Technique in the Management of Severely Angulated Fourth and Fifth Metacarpal Neck Fractures: A Case Series.

Background: This study introduces a novel method for the management of closed metacarpal neck fractures. Kirschner wires (K-wire) are introduced in a retrograde and the wires withdrawn through skin proximally at the base of the metacarpal. The fracture is reduced using traction and the reduction is maintained by antegrade advancement of the K-wires. The aim of this study is to report the outcomes of this technique. Methods: A total of 36 patients with severely angulated closed metacarpal neck fractures underwent reduction and fixation using this novel method from January 2017 to December 2020 in centres in Ireland and Saudi Arabia. We performed a retrospective review of these patients' clinical data examining their outcomes. Results: Six months postoperatively, all fractures demonstrated bony union and correction of angulation. All patients exhibited excellent range of motion (ROM) with no significant impairment of hand function. Conclusions: The method detailed here is a simple, minimally invasive and reliable technique that has not previously been described. It is suitable for use in the management of closed metacarpal neck fractures of the fourth and fifth metacarpal, with dorsal angulation greater than 60°. Level of Evidence: Level IV (Therapeutic).

Beyond job placement: careers for refugees.

In this article, we highlight the Australian country context to advocate for career support that extends beyond initial job placement in a segmented labor market to strengthen refugees' skills and knowledge and future career development. We address systemic barriers while advocating for access to skilled career development practitioners, whose important expertise as members of multidisciplinary teams could enhance resettlement assistance. Strengthening the preparation of career development practitioners is essential for providing career support to refugees and for building capacity in the provision of resettlement services. We encourage debate within and between country contexts about ways to enhance refugees' career development.

Au-delà du placement: Carrières pour les réfugiés. Dans cet article, nous mettons en avant le contexte du pays australien pour plaider en faveur d'un soutien de carrière qui va au-delà l'insertion professionnelle initiale dans un marché du travail segmenté, afin de renforcer les compétences et les connaissances des réfugiées et leur futur développement de carrière. Nous abordons les obstacles systémiques tout en plaidant pour l'accès à des praticiennes qualifiées en développement de carrière, dont l'expertise importante en tant que membres d'équipes multidisciplinaires pourrait améliorer l'aide à la réinsertion. Le renforcement de la préparation des praticiennes en développement de carrière est essentiel pour fournir un soutien professionnel aux réfugiées et pour renforcer les capacités de prestation de services de réinsertion. Nous encourageons le débat au sein des contextes nationaux et entre eux sur les moyens d'améliorer le développement de carrière des réfugiées.

Más allá de la colocación: Carreras para refugiados. En este artículo destacamos el contexto del país australiano para abogar por un apoyo a la carrera profesional que vaya más allá de la colocación inicial en un mercado laboral segmentado para reforzar las habilidades y conocimientos de los refugiados y su futuro desarrollo profesional. Abordamos las barreras sistémicas a la vez que abogamos por el acceso a profesionales cualificados en desarrollo profesional, cuya importante experiencia como miembros de equipos multidisciplinares podría mejorar la asistencia al reasentamiento. Reforzar la preparación de los profesionales del desarrollo profesional es esencial para proporcionar apoyo profesional a los refugiados y para crear capacidad en la prestación de servicios de reasentamiento. Alentamos el debate dentro y entre los contextos nacionales sobre las formas de mejorar el desarrollo profesional de los refugiados.

The intersections of migration, app-based gig work, and career development: implications for career practice and research.

The incidence of app-based gig work is expanding rapidly in developed global north countries. Many app-based gig workers are migrants from developing global south countries searching for a better life in their resettlement countries. App-based gig work, however, is insecure, irregular and potentially precarious. Access to decent work is vital for migrants' integration after resettlement and also their career development. In the context of the decent work agenda, this article explores the intersections of migration, app-based gig work, and southern migrants' career development in the global north and considers the implications for career practice and research.

Las intersecciones de la migración, los conciertos basados en apps y el desarrollo de la carrera : implicaicones para la práctica de la carrera y la investigación. La incidencia de el trabajo musical basado en apps se está expandiendo rápidamente en los países del norte global desarrollado. Muchos migrantes músicos que trabajan a partir de las apps desde países del sur global en dsarrollo, buscando una vida mejor en los países de reasentamiento. El trabajo musical basado en apps es inseguro, irregular y potencialmente precario. El acceso al. Trabajo digno es vital para la integración de los migrantes tras su reasentameinteo y también para su desarrrollo de la carrera. En el contexto de la agenda sobre el trabajo digno, este artículo explora las intersecciones del trabajo musical basado en apps y el desarrollo de la carrera de los migrantes del sur en el norte global y considera las implicacions para la práctica de la carrera y la investigación.

Les intersections entre la migration, le travail de plateforme basé sur des applications et le développement de carrière: Implications pour la pratique et la recherche en matière de carrière. L'incidence des emplois de plateforme basés sur des applications se développe rapidement dans les pays développés du Nord. De nombreux travailleurs de ce type sont des migrants originaires de pays en développement du Sud à la recherche d'une vie meilleure dans leur pays de réinstallation. Cependant, le travail de plateforme basé sur des applications est peu sûr, irrégulier et potentiellement précaire. L'accès à un travail décent est vital pour l'intégration des migrants après leur réinstallation et pour le développement de leur carrière. Dans le contexte de l'agenda pour le travail décent, cet article explore les intersections entre la migration, le travail de plateforme basé sur les applications et l'évolution de carrière des migrants du Sud dans le Nord et examine les implications pour la pratique et la recherche en matière de carrière.

The naked truth: a comprehensive clarification and classification of current 'myths' in naked mole-rat biology.

The naked mole-rat (Heterocephalus glaber) has fascinated zoologists for at least half a century. It has also generated considerable biomedical interest not only because of its extraordinary longevity, but also because of unusual protective features (e.g. its tolerance of variable oxygen availability), which may be pertinent to several human disease states, including ischemia/reperfusion injury and neurodegeneration. A recent article entitled 'Surprisingly long survival of premature conclusions about naked mole-rat biology' described 28 'myths' which, those authors claimed, are a 'perpetuation of beautiful, but falsified, hypotheses' and impede our understanding of this enigmatic mammal. Here, we re-examine each of these 'myths' based on evidence published in the scientific literature. Following Braude et al., we argue that these 'myths' fall into four main categories: (i) 'myths' that would be better described as oversimplifications, some of which persist solely in the popular press; (ii) 'myths' that are based on incomplete understanding, where more evidence is clearly needed; (iii) 'myths' where the accumulation of evidence over the years has led to a revision in interpretation, but where there is no significant disagreement among scientists currently working in the field; (iv) 'myths' where there is a genuine difference in opinion among active researchers, based on alternative interpretations of the available evidence. The term 'myth' is particularly inappropriate when applied to competing, evidence-based hypotheses, which form part of the normal evolution of scientific knowledge. Here, we provide a comprehensive critical review of naked mole-rat biology and attempt to clarify some of these misconceptions.

Ribosomal 18 S RNA processing by the IGF-I-responsive WDR3 protein is integrated with p53 function in cancer cell proliferation.

Insulin-like growth factor-I (IGF-I) signaling is strongly associated with cell growth and regulates the rate of synthesis of the rRNA precursor, the first and the key stage of ribosome biogenesis. In a screen for mediators of IGF-I signaling in cancer, we recently identified several ribosome-related proteins, including NEP1 (nucleolar essential protein 1) and WDR3 (WD repeat 3), whose homologues in yeast function in ribosome processing. The WDR3 gene and its locus on chromosome 1p12-13 have previously been linked with malignancy. Here we show that IGF-I induces expression of WDR3 in transformed cells. WDR3 depletion causes defects in ribosome biogenesis by affecting 18 S rRNA processing and also causes a transient down-regulation of precursor rRNA levels with moderate repression of RNA polymerase I activity. Suppression of WDR3 in cells expressing functional p53 reduced proliferation and arrested cells in the G(1) phase of the cell cycle. This was associated with activation of p53 and sequestration of MDM2 by ribosomal protein L11. Cells lacking functional p53 did not undergo cell cycle arrest upon suppression of WDR3. Overall, the data indicate that WDR3 has an essential function in 40 S ribosomal subunit synthesis and in ribosomal stress signaling to p53-mediated regulation of cell cycle progression in cancer cells.

Aging through an epitranscriptomic lens.

The mechanistic causes of aging, the time-related decline in function and good health that leads to increased mortality, remain poorly understood. Here we propose that age-dependent alteration of the epitranscriptome, encompassing more than 150 chemically distinct post-transcriptional modifications or editing events, warrants exploration as an important modulator of aging. The epitranscriptome is a potent regulator of RNA function, diverse cellular processes and tissue regenerative capacity. To date, only a few studies link alterations in the epitranscriptome to molecular and physiological changes during aging; however, epitranscriptome dysfunction is associated with and underlies several age-associated pathologies, including cancer and neurodegenerative, cardiovascular and autoimmune diseases. For example, changes in RNA modifications (such as N6-methyladenosine and inosine) impact cardiac physiology and are linked to cardiac fibrosis. Although an uncharted research focus, mapping epitranscriptome alterations in the context of aging may elucidate novel predictors of both health and lifespan, and may identify therapeutic targets for attenuating aging and abrogating age-related diseases.

A case report of spontaneous mutation (C33>U) in the iron-responsive element of L-ferritin causing hyperferritinemia-cataract syndrome.

The hereditary hyperferritinemia cataract syndrome (HHCS) is an autosomal dominant disorder characterized by juvenile-onset cataracts and elevated serum ferritin levels. It is caused by mutation in the iron response element (IRE) within the 5'UTR of L-ferritin gene. The mutation results in a loss of post-transcriptional negative feedback exerted by the interaction between iron regulatory proteins 1, 2 (IRP1 and IRP2) and IRE, which leads to uncontrolled expression of L-ferritin. In this paper, we describe the molecular pathogenesis of non-hereditary hyperferritinemia cataract syndrome (non-H-HCS) in a patient with typical HHCS ocular lens morphology and high ferritin levels without obvious family history. Initial sequencing of the full-length L-ferritin cloned from genomic DNA demonstrated a mutation (C33>T) in the IRE of the affected patient but not in her unaffected family members. The mutation (C/T heterozygote) was also detected in cDNA derived from her blood mononuclear cells. Structure-prediction-modeling indicates that this mutation would significantly alter the secondary structure of the IRE, resulting in a loss of the interaction between IRP and IRE. By using IRP1/IRP2-human IgG1 Fc fusion proteins, we established a novel in vitro report system (modified ELISA) to verify impaired IRE/IRP binding. Both the C33>U and A40G mutations (the first identified mutation for HHCS) showed a dramatically decreased binding to IRP1/IRP2 protein, compared to the normal IRE RNA. Surprisingly, a decrease in L-ferritin mRNA levels was observed in the affected patient compared to controls suggesting a mechanism of transcriptional negative feedback by high intracellular L-ferritin protein levels not described heretofore. Taken together, spontaneous mutation in the IRE of L-ferritin may cause non-H-HCS by the same mechanism as HHCS. In addition, under abnormal circumstances, the protein level of L-ferritin may be principally controlled by post-transcriptional regulation rather than the transcriptional regulation. The successful establishment of an ELISA report system provides an alternative method to evaluate precisely the interaction between protein and RNA.

Community-Based Participatory Research: Engaging Youth to Provide Perspective on Risk and Protective Factors.

BACKGROUND: The Pennsylvania Youth Survey (PAYS) is administered biennially to adolescents; it covers knowledge, attitudes, and behaviors about risk and protective factors. PURPOSE: This study explored 8th, 10th, and 12th grade students' attitudes and beliefs about current trends regarding drugs, alcohol, and mental health. METHODS: We asked persons a series of questions in semi-structured focus groups (102 participants) while they were being presented with the PAYS data. RESULTS: Participants expressed significant insight on root causes of risk behaviors. They recommended a decreased emphasis on grades and class rank, and recommended addressing mental health stigma, educating about vaping and marijuana effects, and obtaining support from families, schools, and communities. CONCLUSION: Youth expressed interest in being an integral part of the planning and decision-making efforts that impact them. Our results support the Whole School, Community, and Child (WSCC) model.

The importance of cycle threshold values in interpreting molecular tests for SARS-CoV-2.

Using the Allplex™ 2019-nCoV assay (Seegene, South Korea), 285 samples were tested; 49 (17%) were positive for 3 genes, 4 (1.4%) samples were positive for 2 genes (all N gene and RdRP gene), 8 (3%) samples were positive for 1 gene (all N gene only), and 224 (78.5%) samples were negative.

The genetic architecture of the human cerebral cortex.

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

A single H/ACA small nucleolar RNA mediates tumor suppression downstream of oncogenic RAS.

Small nucleolar RNAs (snoRNAs) are a diverse group of non-coding RNAs that direct chemical modifications at specific residues on other RNA molecules, primarily on ribosomal RNA (rRNA). SnoRNAs are altered in several cancers; however, their role in cell homeostasis as well as in cellular transformation remains poorly explored. Here, we show that specific subsets of snoRNAs are differentially regulated during the earliest cellular response to oncogenic RASG12V expression. We describe a novel function for one H/ACA snoRNA, SNORA24, which guides two pseudouridine modifications within the small ribosomal subunit, in RAS-induced senescence in vivo. We find that in mouse models, loss of Snora24 cooperates with RASG12V to promote the development of liver cancer that closely resembles human steatohepatitic hepatocellular carcinoma (HCC). From a clinical perspective, we further show that human HCCs with low SNORA24 expression display increased lipid content and are associated with poor patient survival. We next asked whether ribosomes lacking SNORA24-guided pseudouridine modifications on 18S rRNA have alterations in their biophysical properties. Single-molecule Fluorescence Resonance Energy Transfer (FRET) analyses revealed that these ribosomes exhibit perturbations in aminoacyl-transfer RNA (aa-tRNA) selection and altered pre-translocation ribosome complex dynamics. Furthermore, we find that HCC cells lacking SNORA24-guided pseudouridine modifications have increased translational miscoding and stop codon readthrough frequencies. These findings highlight a role for specific snoRNAs in safeguarding against oncogenic insult and demonstrate a functional link between H/ACA snoRNAs regulated by RAS and the biophysical properties of ribosomes in cancer.