TMC function, dysfunction, and restoration in mouse vestibular organs.

Tmc1 and Tmc2 are essential pore-forming subunits of mechanosensory transduction channels localized to the tips of stereovilli in auditory and vestibular hair cells of the inner ear. To investigate expression and function of Tmc1 and Tmc2 in vestibular organs, we used quantitative polymerase chain reaction (qPCR), fluorescence in situ hybridization - hairpin chain reaction (FISH-HCR), immunostaining, FM1-43 uptake and we measured vestibular evoked potentials (VsEPs) and vestibular ocular reflexes (VORs). We found that Tmc1 and Tmc2 showed dynamic developmental changes, differences in regional expression patterns, and overall expression levels which differed between the utricle and saccule. These underlying changes contributed to unanticipated phenotypic loss of VsEPs and VORs in Tmc1 KO mice. In contrast, Tmc2 KO mice retained VsEPs despite the loss of the calcium buffering protein calretinin, a characteristic biomarker of mature striolar calyx-only afferents. Lastly, we found that neonatal Tmc1 gene replacement therapy is sufficient to restore VsEP in Tmc1 KO mice for up to six months post-injection.

Identification of skewed X chromosome inactivation using exome and transcriptome sequencing in patients with suspected rare genetic disease.

BACKGROUND: X-chromosome inactivation (XCI) is an epigenetic process that occurs during early development in mammalian females by randomly silencing one of two copies of the X chromosome in each cell. The preferential inactivation of either the maternal or paternal copy of the X chromosome in a majority of cells results in a skewed or non-random pattern of X inactivation and is observed in over 25% of adult females. Identifying skewed X inactivation is of clinical significance in patients with suspected rare genetic diseases due to the possibility of biased expression of disease-causing genes present on the active X chromosome. The current clinical test for the detection of skewed XCI relies on the methylation status of the methylation-sensitive restriction enzyme (Hpall) binding site present in proximity of short tandem polymorphic repeats on the androgen receptor (AR) gene. This approach using one locus results in uninformative or inconclusive data for 10-20% of tests. Further, recent studies have shown inconsistency between methylation of the AR locus and the state of inactivation of the X chromosome. Herein, we develop a method for estimating X inactivation status, using exome and transcriptome sequencing data derived from blood in 227 female samples. We built a reference model for evaluation of XCI in 135 females from the GTEx consortium. We tested and validated the model on 11 female individuals with different types of undiagnosed rare genetic disorders who were clinically tested for X-skew using the AR gene assay and compared results to our outlier-based analysis technique. RESULTS: In comparison to the AR clinical test for identification of X inactivation, our method was concordant with the AR method in 9 samples, discordant in 1, and provided a measure of X inactivation in 1 sample with uninformative clinical results. We applied this method on an additional 81 females presenting to the clinic with phenotypes consistent with different hereditary disorders without a known genetic diagnosis. CONCLUSIONS: This study presents the use of transcriptome and exome sequencing data to provide an accurate and complete estimation of X-inactivation and skew status in a cohort of female patients with different types of suspected rare genetic disease.

Vorinostat, temozolomide or bevacizumab with irradiation and maintenance BEV/TMZ in pediatric high-grade glioma: A Children's Oncology Group Study.

Background: Outcomes for children with high-grade gliomas (HGG) remain poor. This multicenter phase II trial evaluated whether concurrent use of vorinostat or bevacizumab with focal radiotherapy (RT) improved 1-year event-free survival (EFS) compared to temozolomide in children with newly diagnosed HGG who received maintenance temozolomide and bevacizumab. Methods: Patients ≥ 3 and < 22 years with localized, non-brainstem HGG were randomized to receive RT (dose 54-59.4Gy) with vorinostat, temozolomide, or bevacizumab followed by 12 cycles of bevacizumab and temozolomide maintenance therapy. Results: Among 90 patients randomized, the 1-year EFS for concurrent bevacizumab, vorinostat, or temozolomide with RT was 43.8% (±8.8%), 41.4% (±9.2%), and 59.3% (±9.5%), respectively, with no significant difference among treatment arms. Three- and five-year EFS for the entire cohort was 14.8% and 13.4%, respectively, with no significant EFS difference among the chemoradiotherapy arms. IDH mutations were associated with more favorable EFS (P = .03), whereas H3.3 K27M mutations (P = .0045) and alterations in PIK3CA or PTEN (P = .025) were associated with worse outcomes. Patients with telomerase- and alternative lengthening of telomeres (ALT)-negative tumors (n = 4) had an EFS of 100%, significantly greater than those with ALT or telomerase, or both (P = .002). While there was no difference in outcomes based on TERT expression, high TERC expression was associated with inferior survival independent of the telomere maintenance mechanism (P = .0012). Conclusions: Chemoradiotherapy with vorinostat or bevacizumab is not superior to temozolomide in children with newly diagnosed HGG. Patients with telomerase- and ALT-negative tumors had higher EFS suggesting that, if reproduced, mechanism of telomere maintenance should be considered in molecular-risk stratification in future studies.

Seminal cell-free DNA as a potential marker for in vitro fertility of Nellore bulls.

PURPOSE: This study aimed to identify a marker for freezability and in vitro fertility of sperm samples before freezing. METHODS: Semen was collected from nine Nelore bulls; half of the ejaculate was used for seminal plasma cell-free DNA (cfDNA) quantification, and the other half was cryopreserved. Evaluation of sperm movement using computer-assisted semen analysis and plasma membrane integrity and stability, acrosomal integrity, apoptosis, and mitochondrial potential using flow cytometry were performed on fresh and frozen/thawed semen at 0, 3, 6, and 12 h after thawing. Frozen/thawed sperm was also used for in vitro embryo production. cfDNA was extracted from each bull, and the total DNA and number of cell-free mitochondrial DNA (cfmtDNA) copies were quantified. Semen from each animal was used for IVF, and cleavage, blastocyst formation, and cell counts were evaluated. RESULTS: Two groups were formed and compared based on the concentrations of cfDNA and cfmDNA present: low-cfDNA and high-cfDNA and low-cfmtDNA and high-cfmtDNA. Up to 12 h post-thawing, there were no differences between the groups in the majority of the sperm parameters evaluated. Cleavage, day 6 and 7 blastocyst rates, and the number of cells were higher in the high cfDNA group than in the low cfDNA group. Similar results were observed for cfmtDNA, except for the number of cells, which was similar between the groups. CONCLUSION: The concentration of cfDNA and the relative number of copies of cfmtDNA in seminal plasma cannot predict the freezability of semen but can be used to predict in vitro embryo production.

Semiautomated approach focused on new genomic information results in time and effort-efficient reannotation of negative exome data.

Most rare disease patients (75-50%) undergoing genomic sequencing remain unsolved, often due to lack of information about variants identified. Data review over time can leverage novel information regarding disease-causing variants and genes, increasing this diagnostic yield. However, time and resource constraints have limited reanalysis of genetic data in clinical laboratories setting. We developed RENEW, (REannotation of NEgative WES/WGS) an automated reannotation procedure that uses relevant new information in on-line genomic databases to enable rapid review of genomic findings. We tested RENEW in an unselected cohort of 1066 undiagnosed cases with a broad spectrum of phenotypes from the Mayo Clinic Center for Individualized Medicine using new information in ClinVar, HGMD and OMIM between the date of previous analysis/testing and April of 2022. 5741 variants prioritized by RENEW were rapidly reviewed by variant interpretation specialists. Mean analysis time was approximately 20 s per variant (32 h total time). Reviewed cases were classified as: 879 (93.0%) undiagnosed, 63 (6.6%) putatively diagnosed, and 4 (0.4%) definitively diagnosed. New strategies are needed to enable efficient review of genomic findings in unsolved cases. We report on a fast and practical approach to address this need and improve overall diagnostic success in patient testing through a recurrent reannotation process.

Food webs in isolation: The food-web structure of a freshwater reservoir with armoured shores in a former coastal bay area.

Many shallow coastal bays have been closed off from the sea to mitigate the risk of flooding, resulting in coastal reservoir lakes with artificial armoured shorelines. Often these enclosed ecosystems show a persistent decline in biodiversity and ecosystem services, which is likely reflected in their food-web structure. We therefore hypothesize that the food webs of coastal reservoir lakes with armoured shorelines (1) consist of relatively few species with a low food-web connectance and short food chains, and (2) are mainly fuelled by autochthonous organic matter produced in the pelagic zone. To investigate these two hypotheses, we used stable-isotope analysis to determine the food-web structure of lake Markermeer (The Netherlands), a large reservoir lake with armoured shorelines in a former coastal bay area. Contrary to expectation, connectance of the food web in lake Markermeer was comparable to other lakes, while food-chain length was in the higher range. However, the trophic links revealed that numerous macroinvertebrates and fish species in this constructed lake exhibited omnivorous feeding behaviour. Furthermore, in line with our second hypothesis, primary consumers heavily relied on pelagically derived organic matter, while benthic primary production exerted only a minor and seasonal influence on higher trophic levels. Stable-isotope values and the C:N ratio of sediment organic matter in the lake also aligned more closely with phytoplankton than with benthic primary producers. Moreover, terrestrial subsidies of organic matter were virtually absent in lake Markermeer. These findings support the notion that isolation of the lake through shore armouring and the lack of littoral habitats in combination with persistent resuspension of sediments have affected the food web. We argue that restoration initiatives should prioritize the establishment of land-water transition zones, thereby enhancing habitat diversity, benthic primary production, and the inflow of external organic matter while preserving pelagic primary production.

CRISPR/Cas9 deletion of MIR155HG in human T cells reduces incidence and severity of acute GVHD in a xenogeneic model.

ABSTRACT: Acute graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT). Using preclinical mouse models of disease, previous work in our laboratory has linked microRNA-155 (miR-155) to the development of acute GVHD. Transplantation of donor T cells from miR-155 host gene (MIR155HG) knockout mice prevented acute GVHD in multiple murine models of disease while maintaining critical graft-versus-leukemia (GVL) response, necessary for relapse prevention. In this study, we used clustered, regularly interspaced, short palindromic repeats (CRISPR)/Cas9 genome editing to delete miR-155 in primary T cells (MIR155HGΔexon3) from human donors, resulting in stable and sustained reduction in expression of miR-155. Using the xenogeneic model of acute GVHD, we show that NOD/SCID/IL2rγnull (NSG) mice receiving MIR155HGΔexon3 human T cells provide protection from lethal acute GVHD compared with mice that received human T cells with intact miR-155. MIR155HGΔexon3 human T cells persist in the recipients displaying decreased proliferation potential, reduced pathogenic T helper-1 cell population, and infiltration into GVHD target organs, such as the liver and skin. Importantly, MIR155HGΔexon3 human T cells retain GVL response significantly improving survival in an in vivo model of xeno-GVL. Altogether, we show that CRISPR/Cas9-mediated deletion of MIR155HG in primary human donor T cells is an innovative approach to generate allogeneic donor T cells that provide protection from lethal GVHD while maintaining robust antileukemic response.

Changes in Sexuality and Sexual Dysfunction over Time in the First Two Years after Treatment of Head and Neck Cancer.

The aim of this study was to investigate changes in sexuality and sexual dysfunction in head and neck cancer (HNC) patients in the first two years after treatment, in relation to the type of treatment. Data were used of 588 HNC patients participating in the prospective NETherlands Quality of life and Biomedical Cohort Study (NET-QUBIC) from diagnosis to 3, 6, 12 and 24 months after treatment. Primary outcome measures were the International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI). The total scores of the IIEF and FSFI were dichotomized into sexual (dys)function. In men, type of treatment was significantly associated with change in erectile function, orgasm, satisfaction with intercourse, and overall satisfaction. In women, type of treatment was significantly associated with change in desire, arousal, and orgasm. There were significant differences between treatment groups in change in dysfunctional sexuality. A deterioration in sexuality and sexual dysfunction from baseline to 3 months after treatment was observed especially in patients treated with chemoradiation. Changes in sexuality and sexual dysfunction in HNC patients were related to treatment, with an acute negative effect of chemoradiation. This effect on the various domains of sexuality seems to differ between men and women.

Effect of interprofessional and intraprofessional clinical collaboration on patient related outcomes in multimorbid older patients - a retrospective cohort study on the Intensive Collaboration Ward.

BACKGROUND: The management and care of older patients with multiple health problems is demanding and complex. Interprofessional and intraprofessional collaboration has the potential to improve both the efficiency and the quality of care for these patients. However, it has proven difficult to demonstrate the efficacy of this approach in terms of objective patient-related outcomes. Recently, a care model with interprofessional and intraprofessional care was started, the Intensive Collaboration Ward (ICW). This ward combines interprofessional care and intraprofessional care for older patients with multiple health problems. The aim of this study was to evaluate the effects of ICW care in older patients with multiple health problems. METHODS: This retrospective cohort study evaluated the effects on patients outcomes. This was done by comparing patients of the new model, the ICW (ICW group), to a historical cohort of comparable patients who would have been eligible for the ICW (control group). Outcomes were medical consultations, allied health professional consultations, radiological procedures, waiting time for radiological procedures, change in primary treating specialty, length of hospital stay, readmission rate, and mortality rate. Linear and logistic regression analyses were performed, adjusted for baseline differences. RESULTS: The ICW group required significantly fewer medical consultations than the control group. Calls to specialists from the emergency room decreased significantly, but there was no change in in-person consultations on the ER. 51% of control patients had ≥ 1 in-hospital consultation compared to 21% of ICW patients (p < 0.05). Patients in the ICW group received significantly more consultations with allied health professionals and more often had a change in primary treating specialty. CONCLUSIONS: Interprofessional and intraprofessional clinical collaboration on the ICW reduced in-hospital consultations and increased allied health professionals' consultations. This approach may decrease fragmentation of care and provide more integrated, efficient and patient centered care. This may improve the overall care of older patients with multiple health problems.

Differential consumption of alcohol, caffeine, and caffeinated alcohol by adolescent rats, and effects on post-adolescent gene expression signatures in the nucleus accumbens and orbitofrontal cortex.

Caffeinated alcoholic beverages (CABs) are widely consumed despite little known about their behavioral and biological effects. Furthermore, CABs are also popular among adolescents, a particularly vulnerable and maturing demographic. In this preliminary study, we compared levels of daily adolescent voluntary consumption of caffeine (0.03%), alcohol (10%), caffeinated alcohol (0.03% + 10%), or vehicle and evaluated the effects of this on mRNA expression in brain regions associated with addiction and known to be affected by each drug. Beginning on postnatal day 30, rats were allowed unrestricted access to gelatin combined with one, both, or neither drug for twenty days. Compared to vehicle-consuming animals, consumption of gelatin was significantly attenuated when alcohol was included. The addition of caffeine to alcohol increased alcohol consumption in the early days of access compared to alcohol alone; however, after two weeks, alcohol consumption between these groups reached comparable levels. Compared to animals consuming caffeine alone, combining caffeine with alcohol significantly reduced caffeine intake. Targeted mRNA analysis of tissue collected from the nucleus accumbens and orbitofrontal cortex after the consumption period identified unique patterns of differentially expressed genes between treatment groups, across a broad array of neurotransmitter systems. Of particular note were genes related to a number of solute transporters and serotonergic functions. This preliminary work suggests unique pharmacological and behavioral effects from consuming caffeinated alcohol during adolescence. Since CABs are widely consumed by adolescents, these results suggest that more research into the pharmacological and behavioral effects elicited by CABs is warranted.

An unusual presentation of Pseudomonas citronellolis bacteraemia and Campylobacter gastroenteritis infection in a human - a case report and literature review.

Introduction: Pseudomonas citronellolis is an unusual pathogen in humans and has not been extensively described in the scientific literature. Herein, we present a case of bacteremia and septic shock due to Pseudomonas citronellolis following Campylobacter species gastroenteritis in a patient with immunosuppression. Case Presentation: An 80-year-old man with myeloproliferative disorder on ruxolitinib presented with several days of worsening abdominal pain, which rapidly developed into septic shock with multi-organ failure and explosive diarrhea. Gram-negative bacilli observed on Gram staining of his blood culture broth were later identified as Pseudomonas citronellolis and Bacteroides thetaiotaomicron . Repeated abdominal imaging revealed no evidence of intestinal perforation or megacolon. In addition, stool PCR was positive for Campylobacter species. His clinical course improved after 14 days of meropenem with complete resolution of his symptoms and organ failure. Conclusion: P. citronellolis is a rare infection in humans. We postulate that Janus Associated Kinase (JAK) inhibition in myeloproliferative disorders heightened this patient's risk of bacterial translocation and severe illness in the setting of Campylobacter gastroenteritis. P. citronellolis may be identified more frequently as a pathogen in humans as more advanced diagnostic technologies become increasingly available in clinical microbiology.

Cumulus-oocyte complexes from sows show differences in lipid metabolism compared to cumulus-oocyte complexes from prepubertal gilts during in vitro maturation.

This study aimed to evaluate the effects of donor age on lipid metabolism during in vitro maturation (IVM) of pigs cumulus-oocyte complexes (COCs). We evaluated transcript levels of genes, the percentage of ooplasm occupied by lipid droplets (LD) and evaluated DNA methylation in COCs from sows and prepubertal gilts. Transcript levels of six genes (ACACA, ACSS2, FASN, FABP3, SLC27A4, PLIN2), which were analyzed in cumulus cells (CCs), increased after 44 h of IVM in the sow group. In the gilt group, only FASN expression increased, while NR3C1 expression decreased after IVM. The measurement of LD in oocytes showed an accumulation of lipids in sow oocytes during IVM, while gilt oocytes showed a decrease in LD. FABP3 and NR3C1 methylation patterns exhibited a demethylation pattern in CCs and oocytes from gilts and sows and showed statistical differences between groups. CCs from sows had a better capacity to change transcription levels of the major genes involved in lipid metabolism during IVM than CCs from gilts. This difference may be involved in accumulation of lipids, acquisition of competence, and maturation of enclosed oocytes. Our results contribute to a better understanding of mechanisms involved in lipid metabolism and acquisition of competence in porcine COCs.

DNA methylation profile of single in vitro matured bovine oocytes.

Somatic cell nuclear transfer (SCNT) is commercially used despite incomplete nuclear reprogramming of the somatic cell nucleus by the enucleated oocyte compromising its efficiency. Oocyte selection is a key factor in increasing this efficiency as its cytoplasm reprograms the differentiated cell. In this study, we adapted a methodology to characterize epialleles in potential epigenetic markers in single in vitro matured oocytes. Characterization of the regions that control the expression of imprinted genes, X-chromosome inactivation, and satellite I DNA (IGF2, ICR-H19, XIST, RepA, and SAT1) showed methylated and unmethylated alleles in the imprinted genes IGF2 and ICR-H19 while XIST-DMR1 and RepA showed hypermethylated alleles. There was great variation in methylation patterns for candidate regions which may be related to oocyte quality. Moreover, the identification of different epialleles in the same oocyte suggests that, at least for those loci, the epigenome of the metaphase plate and polar body is different. The single-cell bisulfite polymerase chain reaction technique can be used to improve the precision of selecting the best oocytes for SCNT procedures, thereby increasing its efficiency.

Apremilast and narrowband ultraviolet B combination therapy suppresses Th17 axis and promotes melanogenesis in vitiligo skin: a randomized, split-body, pilot study in skin types IV-VI.

Improved repigmentation of generalized vitiligo in skin types IV-VI has been reported in clinical response to combined therapy with apremilast and narrowband (NB)-UVB; however, tissue responses to combined therapy versus NB-UVB monotherapy have not been elucidated. We compared the change from baseline in cellular and molecular markers in vitiligo skin after combined therapy versus NB-UVB monotherapy. We assessed lesional and nonlesional skin samples from enrolled subjects and evaluated for immune infiltrates, inflammatory, and melanogenesis-related markers which were compared across different treatment groups. Combined therapy resulted in significant reduction of CD8+T cells and CD11c+ dendritic cells, downregulation of PDE4B and Th17-related markers, and upregulation of melanogenesis markers. This study was limited to small sample size, skin types IV-VI, and high dropout rate. Our molecular findings support the clinical analysis that apremilast may potentiate NB-UVB in repigmentation of generalized vitiligo in skin types IV-VI.

Exploring clinical learning experiences of novice physiotherapy students in a hospital setting.

BACKGROUND: Exposure to clinical practice experiences ensures undergraduate physiotherapy students meet the clinical competencies required to graduate as autonomous practitioners. Much of the research literature has investigated the clinical experiences of medical students. While recent studies have explored physiotherapy students' experiences with simulation, few have explored their perspectives of a clinical placement in a hospital setting at the early learning stage of a four-year programme. OBJECTIVE: To explore the perspectives of novice undergraduate physiotherapy students on a clinical placement in a real hospital setting. METHODS: Fifteen Year 3 undergraduate physiotherapy students participated in semi-structured interviews midway through a three-week tertiary care clinical placement. Interviews were transcribed, coded and analyzed using thematic analysis. RESULTS: Three main themes emerged: 1) student attributes affecting placement experience; 2) impact of the educator on student experience; and 3) effects of the clinical environment on student experiences. CONCLUSION: The real clinical environment promotes a rich learning experience for students, while the clinical educator is pivotal to guiding student learning through provision of resources and feedback. Provision of early orientation and timely clarification of expectations is important to alleviate anxiety and allow students to prepare themselves.

Comorbidity Burden in a Cohort of Adolescent and Young Adult Patients Diagnosed with Central Nervous System Tumors and Sarcomas.

Purpose: Adolescent and young adult (AYA) oncology patients experience unique biological, behavioral, and socioeconomic challenges, for which provision of care must be tailored. AYAs with central nervous system (CNS) tumors and sarcomas represent a vulnerable population with worse outcomes and potential for serious sequelae from intense multimodal therapy. Comorbidity burden impacts treatment tolerance, adherence, and efficacy, yet has been understudied among these high-risk AYA patients. Methods: Utilizing a validated AYA oncology comorbidity index, we (1) measured comorbid conditions present at diagnosis in AYA-aged patients with CNS tumors and sarcomas and (2) compared baseline comorbidity burden across ascending AYA age groups (15-19, 20-29, and 30-39 years) and with pediatric patients (10-14 years). Results: The cohort included 131 AYAs and 50 pediatric patients. Mean comorbidity score significantly differed between pediatric (0.8) and AYA (1.7) patients, and across ascending age subgroups (0.8 [10-14] < 1.2 [15-19] < 1.7 [20-29] < 2.5 [30-39]). AYAs were significantly more likely than pediatric patients to have ≥2 or ≥3 comorbidities (47% vs. 18%, 24% vs. 6%), with increasing prevalence across ascending age subgroups. Frequency of overweight/obese status, smoking/substance use, obstetric/gynecologic conditions, and cardiovascular comorbidities increased with age. In multivariate analyses adjusting for sex, tumor type, and race, age remained a significant predictor of comorbidity score. Conclusions: AYAs with CNS tumors or sarcomas have a high burden of baseline comorbidities, which increase with age at diagnosis, conferring susceptibility to treatment-related toxicity and mortality. Improving the prognosis for AYAs requires appropriate identification of pre-existing comorbidities and tailoring therapeutic and supportive care accordingly.

Dialectic narratives, hostile actors, and Earth's resources in Saskatchewan, Canada.

This paper uses networks of action situations (NAS) together with actor network theory (ANT) to identify the decisions that were made in Saskatchewan regarding power production and explore what future choices are available in the context of climate change. A theoretical and methodological contribution to NAS literature is made with focus on interconnected human and non-human objects (carbon, hydro, and uranium) or 'actants' and the development of discourses supporting or opposing their development. Actants provide the nodes of focus, while discourses explain the development of actants and their links. Identification and explanation of the emergence and recession of actants on the Saskatchewan landscape are analyzed with diagnostics of telecoupled systems, polycentric governance, and flows of faction situations. Focus group and survey data are used to identify future pathways and imaginaries of power production and the actants of carbon, hydro and uranium. Actants of carbon (coal) and hydro are possibly kept alive with carbon capture and storage and import of hydro-electricity from the distant action situation in a neighboring province (if the necessary infrastructure is built). While actants of renewables are strongly emerging, uranium currently mined on the Saskatchewan landscape is receiving strong support by government due to the possibility of small modular reactors (SMRs). This expanded theoretical conception of NAS illustrates distant action situations impact on local narratives and decision-making and dynamics of polycentric governance that are neither top down nor collaborative. Supplementary Information: The online version contains supplementary material available at 10.1007/s11625-022-01214-y.

Immunohistochemical assessment and clinical, histopathologic, and molecular correlates of membranous somatostatin type-2A receptor expression in high-risk pediatric central nervous system tumors.

Introduction: 177Lu-DOTATATE, a radionuclide therapy that binds somatostatin type-2A receptors (SST2A), has demonstrated efficacy in neuroendocrine tumors and evidence of central nervous system (CNS) penetration, supporting potential expansion within pediatric neuro-oncology. Understanding the prevalence of SST2A expression across pediatric CNS tumors is essential to identify patients who may benefit from somatostatin receptor-targeted therapy and to further elucidate the oncogenic role of SST2A. Methods: SST2A immunohistochemistry (IHC) was performed on tumor specimens and interpreted by an experienced pathologist (blinded), utilizing semi-quantitative scoring of membranous expression within viable tumor. Immunoreactive cell percentage was visually scored as 0 (none), 1 (<10%), 2 (10-50%), 3 (51-80%), or 4 (>80%). Staining intensity was scored as 0 (none), 1 (weak), 2 (moderate), or 3 (strong). Combined scores for each specimen were calculated by multiplying percent immunoreactivity and staining intensity values (Range: 0-12). Results: A total of 120 tumor samples from 114 patients were analyzed. Significant differences in SST2A IHC scores were observed across histopathologic diagnoses, with consistently high scores in medulloblastoma (mean ± SD: 7.5 ± 3.6 [n=38]) and meningioma (5.7 ± 3.4 [n=15]), compared to minimal or absent expression in ATRT (0.3 ± 0.6 [n=3]), ETMR (1.0 ± 0 [n=3]), ependymoma (grades I-III; 0.2 ± 0.7 [n=27]), and high-grade glioma (grades III-IV; 0.4 ± 0.7 [n=23]). Pineoblastoma (3.8 ± 1.5 [n=4]) and other embryonal tumors (2.0 ± 4.0 [n=7]) exhibited intermediate, variable expression. Among medulloblastomas, SST2A IHC scores were higher in non-SHH (8.5 ± 3.1) than SHH (5.0 ± 3.3) molecular subgroups (p=0.033). In a subset of paired primary and recurrent specimens from four patients, SST2A IHC scores remained largely unchanged. Discussion: High membranous SST2A expression was demonstrated in medulloblastoma, meningioma, and some rarer embryonal tumors with potential diagnostic, biologic, and therapeutic implications. Somatostatin receptor-targeted therapy such as 177Lu-DOTATATE deserves further investigation in these highly SST2A-expressing pediatric CNS tumors.