Urinary Biomarkers for Lupus Nephritis: A Systems Biology Approach.

Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disorder. Kidney involvement, termed lupus nephritis (LN), is seen in 40-60% of patients with systemic lupus erythematosus (SLE). After the diagnosis, serial measurement of proteinuria is the most common method of monitoring treatment response and progression. However, present treatments for LN-corticosteroids and immunosuppressants-target inflammation, not proteinuria. Furthermore, subclinical renal inflammation can persist despite improving proteinuria. Serial kidney biopsies-the gold standard for disease monitoring-are also not feasible due to their inherent risk of complications. Biomarkers that reflect the underlying renal inflammatory process and better predict LN progression and treatment response are urgently needed. Urinary biomarkers are particularly relevant as they can be measured non-invasively and may better reflect the compartmentalized renal response in LN, unlike serum studies that are non-specific to the kidney. The past decade has overseen a boom in applying cutting-edge technologies to dissect the pathogenesis of diseases at the molecular and cellular levels. Using these technologies in LN is beginning to reveal novel disease biomarkers and therapeutic targets for LN, potentially improving patient outcomes if successfully translated to clinical practice.

Tailoring magnetic Sn-MOFs for efficient amoxicillin antibiotic removal through process optimization.

This study investigated the efficacy of magnetic Sn metal-organic frameworks (MSn-MOFs) in removing the insecticide amoxicillin (AMX) from aqueous solutions. Our thorough experimental investigation showed that MSn-MOFs were an incredibly effective adsorbent for removing AMX. Several methods were used to characterize the material. BET investigation of the data displayed a significant surface area of 880 m2 g-1 and a strong magnetic force of 89.26 emu g-1. To identify the point of zero charge, surface characterization was carried out and the value was 7.5. This shows that the adsorbent carries a positive and negative charge below and above this position, respectively. Moreover, the impact of pH on adsorption equilibrium was explored. The results of kinetic models to explore the adsorption of AMX on MSn-MOFs supported the pseudo-second-order, and the adsorption complied well with the Langmuir isotherm. The results revealed that the overall adsorption mechanism may entail chemisorption via an endothermic spontaneous process with MSn-MOFs. The precise modes by which MSn-MOFs and AMX interacted may involve pore filling, H-bonding, π-π interaction, or electrostatic interaction. Determining the nature of this interaction is essential in understanding the adsorption behavior of the MOFs and optimize the adsorbent design for real-world applications. The use of the MSn-MOF adsorbent provides a straightforward yet efficient method for the filtration of water and treatment of industrial effluents. The results showed 2.75 mmol g-1 as the maximum capacity for adsorption at pH = 6. Additional tests were conducted to assess the adsorbent regeneration, and even after more than six cycles, the results demonstrated a high level of efficiency. The adsorption results were enhanced by the application of the Box-Behnken design.

Physical functioning in patients with end-stage knee osteoarthritis: A cross-sectional study in Jordan using self-reported questionnaire and performance-based tests.

BACKGROUND: Knee osteoarthritis (OA) is a debilitating condition that leads to functional limitations. Self-reported questionnaires and performance-based tests are tools commonly used for measuring physical function. OBJECTIVES: (1) To evaluate the impact of end-stage knee OA on functional outcomes and examine the association between self-reported and performance-based measures of function in patients with end-stage knee osteoarthritis awaiting total knee arthroplasty (2) To explore the interrelationships among pain, strength, and overall physical function in this patient population. METHODS: In this cross-sectional analysis, 33 patients with end-stage knee OA were recruited and completed the knee Outcome Survey-Activities of Daily Living Scale (KOS-ADLS) and executed performance-based tests including the Timed Up and Go, the 30-second chair stand test, and the Stair Climbing Test. Knee pain, and isometric hip and knee strength were evaluated. RESULTS: Patients perceived deficits in their physical functionwith a score of 35/100 on the KOS-ADLS and demonstrated functional limitations in all performed tasks. KOS-ADLs was weakly associated with TUG and 30s-CST (r=-0.301, p= 0.047, and r= 0.39, p= 0.014. respectively). Knee pain was linked with the KOS-ADL score and GRS score (r=-0.406, p= 0.010; r=-0.343, p= 0.027; respectively), while the strength of the affected side was correlated with the performed (p=< 0.001) and reported function outcomes (p= 0.007). CONCLUSION: Participants exhibit declines in both perceived and executed functional abilities. Self-reported and performance-based functional measures are weakly correlated within our study group, highlighting the importance of incorporating both measures in clinical practice for a comprehensive evaluation of physical function. Pain was linked to subjective aspect of physical function, while strength was connected to perceived and performed functional capacity. Implementing a tailored rehabilitation program targeting muscle weakness and pain holds the potential to mitigate functional decline in individuals awaiting total knee arthroplasty (TKA).

Intravenous fluid rate of 250 mL/h versus 125 mL/h in nulliparous women: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Evidence regarding the type and rate of intravenous (IV) fluid administration during labor is still inconclusive and the studies assessing the impact of IV fluids had mixed results. OBJECTIVES: To evaluate the effects of IV fluids at an infusion rate of 250 mL/h as compared with 125 mL/h on labor outcomes in nulliparous women. SEARCH STRATEGY: We searched six databases for relevant studies through a search strategy containing the relevant keywords "IV hydration", "IV fluids", and "labor" from the inception of these databases to May 1, 2023, without any applied restrictions. SELECTION CRITERIA: Search results were imported to Covidence for screening of eligible articles for this review. Randomized controlled trials (RCTs) assessing the impact of IV fluids at 250 mL/h on the outcomes of labor in nulliparous women at term (>37 weeks) as compared with 125 mL/h were included only. DATA COLLECTION AND ANALYSIS: Data regarding the characteristics of included studies, participant's baseline characteristics, and concerned outcomes were collected in an Excel spreadsheet and all the concerned outcomes were pooled as risk ratios (RR) or mean difference (MD) with 95% confidence interval (CI) in the meta-analysis models using RevMan 5.4. MAIN RESULTS: Pooled data from 11 RCTs with 1815 patients showed that 250 mL/h infusion rate had a significant reduction in cesarean section rate (RR 0.70, 95% CI 0.56-0.88, P = 0.002), the first stage of labor duration (MD -46.97, 95% CI -81.79 to -12.14, P = 0.008), the second stage of labor duration (MD -2.69, 95% CI -4.34 to -1.05, P = 0.001), prolonged labor incidence (RR 0.72, 95% CI 0.58-0.89, P = 0.003), as compared with 125 mL/h. Also, the vaginal delivery rate (RR 1.07, 95% CI 1.02-1.12, P = 0.009) was higher with a 250 mL/h infusion rate. CONCLUSION: IV fluids at an infusion rate of 250 mL/h during labor in nulliparous women decreased the cesarean delivery rate, increased the vaginal delivery rate, shortened the first and second-stage labor duration, decreased the incidence of prolonged labor as compared with 125 mL/h. These findings suggest enhanced labor progression and a lower risk of labor complications with higher infusion rates. However, future research involving a more diverse population and exploring the potential benefits of combining IV infusion rates with other interventions, such as adding dextrose or less restrictive oral intake during labor, is needed.

Clinical Impact of CDK4/6 Inhibitors in De Novo or PR- or Very Elderly Post-Menopausal ER+/HER2- Advanced Breast Cancers.

The CDK4/6 inhibitors significantly increase progression-free survival (PFS) in ER+/HER2- advanced breast cancer patients. In clinical trials, overall survival (OS) improvement has been demonstrated for ribociclib and abemaciclib but not for palbociclib. We undertook a real-world evaluation of PFS and OS in 227 post-menopausal patients who received first-line CDK4/6 inhibitors. There is no significant difference in median PFS (27.5 months vs. 25.7 months, p = 0.3) or median OS (49.5 months vs. 50.2 months, p = 0.67) in patients who received either palbociclib or ribociclib, respectively. De novo disease is significantly associated with prolonged median PFS and median OS compared with recurrence disease (47.1 months vs. 20.3 months (p = 0.0002) and 77.4 months vs. 37.3 months (p = 0.0003), respectively). PR- tumours have significantly reduced median PFS and OS compared with PR+ disease (19.2 months vs. 38 months (p = 0.003) and 34.3 months vs. 62.6 months (p = 0.02), respectively). In the very elderly (>80 years), median PFS and OS are significantly shorter compared with patients who are 65 years or below (14.5 months vs. 30.2 months (p = 0.01), and 77.4 months vs. 29.6 months (p = 0.009), respectively) in the palbociclib group. Our data suggest that the benefit in the very elderly is limited, and PR+/de novo disease obtains the maximum survival benefit.

Bispecific Antibodies in Hematological Malignancies: A Scoping Review.

Bispecific T-cell engagers (BiTEs) and bispecific antibodies (BiAbs) have revolutionized the treatment landscape of hematological malignancies. By directing T cells towards specific tumor antigens, BiTEs and BiAbs facilitate the T-cell-mediated lysis of neoplastic cells. The success of blinatumomab, a CD19xCD3 BiTE, in acute lymphoblastic leukemia spearheaded the expansive development of BiTEs/BiAbs in the context of hematological neoplasms. Nearly a decade later, numerous BiTEs/BiAbs targeting a range of tumor-associated antigens have transpired in the treatment of multiple myeloma, non-Hodgkin's lymphoma, acute myelogenous leukemia, and acute lymphoblastic leukemia. However, despite their generally favorable safety profiles, particular toxicities such as infections, cytokine release syndrome, myelosuppression, and neurotoxicity after BiAb/BiTE therapy raise valid concerns. Moreover, target antigen loss and the immunosuppressive microenvironment of hematological neoplasms facilitate resistance towards BiTEs/BiAbs. This review aims to highlight the most recent evidence from clinical trials evaluating the safety and efficacy of BiAbs/BiTEs. Additionally, the review will provide mechanistic insights into the limitations of BiAbs whilst outlining practical applications and strategies to overcome these limitations.

The Long and Winding Road: 25 Years of the National Advanced Driving Simulator.

The National Advanced Driving Simulator is a high-fidelity motion-base simulator owned by the National Highway Transportation Safety Administration and managed and operated by the University of Iowa. Its 25-year history has intersected with some of the most significant developments in automotive history, such as advanced driver assistance systems like stability control and collision warning systems, and highly automated vehicles. The simulator is an application of immersive virtual reality that uses multiprojection instead of head-mounted displays. A large-excursion motion system provides realistic acceleration and rotation cues to the driver. Due to its level of immersion and realism, drivers respond to events in the simulator the same way they would in their own vehicle. We document the history and technology behind this national facility.

Three-dimensional catheter tip force sensing using multi-core fiber Bragg gratings.

Awareness of catheter tip interaction forces is a crucial aspect during cardiac ablation procedures. The most important contact forces are the ones that originate between the catheter tip and the beating cardiac tissue. Clinical studies have shown that effective ablation occurs when contact forces are in the proximity of 0.2 N. Lower contact forces lead to ineffective ablation, while higher contact forces may result in complications such as cardiac perforation. Accurate and high resolution force sensing is therefore indispensable in such critical situations. Accordingly, this work presents the development of a unique and novel catheter tip force sensor utilizing a multi-core fiber with inscribed fiber Bragg gratings. A customizable helical compression spring is designed to serve as the flexural component relaying external forces to the multi-core fiber. The limited number of components, simple construction, and compact nature of the sensor makes it an appealing solution towards clinical translation. An elaborated approach is proposed for the design and dimensioning of the necessary sensor components. The approach also presents a unique method to decouple longitudinal and lateral force measurements. A force sensor prototype and a dedicated calibration setup are developed to experimentally validate the theoretical performance. Results show that the proposed force sensor exhibits 7.4 mN longitudinal resolution, 0.8 mN lateral resolution, 0.72 mN mean longitudinal error, 0.96 mN mean lateral error, a high repeatability, and excellent decoupling between longitudinal and lateral forces.

OLDER ADULTS' SUBJECTIVE WELL-BEING EXPERIENCING THE EXERGAME "I AM DOLPHIN".

The objective of this study was to understand older adults' perceptions of the connections between an exergame intervention, "I Am Dolphin," and their subjective well-being. Researchers conducted three focus groups with 14 older adults who participated in the exergame feasibility study. The semi-structured focus groups were transcribed, coded, and analysed using deductive and inductive techniques. Three themes were constructed related to playing the exergame and participants' subjective well-being: 1) elevated mood (through scheduled activity, immersion, and socialization), 2) feelings of achievement (especially following frustration and competition), and 3) perceived cognitive or physical changes. These findings will help researchers better understand how exergames may relate to the well-being of older adults. Future investigators could use these findings to create and implement new exergame interventions.

Bringing High-Dose Neurorestorative Behavioral Training Into the Acute Stroke Unit.

ABSTRACT: Stroke remains common and is a leading cause of adult disability. While there have been enormous system changes for the diagnosis and delivery of hyperacute stroke treatments at comprehensive stroke centers, few advances have been made in those same centers for treatments focused on behavioral recovery and brain repair. Specifically, during the early hospital period, there is a paucity of approaches available for reduction of impairment beyond what is expected from spontaneous biological recovery. Thus, patients in the early stroke recovery period are not receiving the kind of training needed, at the requisite intensity and dose, to exploit a potential critical period of heightened brain plasticity that could maximize true recovery instead of just compensation. Here, we describe an ongoing pilot program to reconfigure the acute stroke unit experience to allow for a new emphasis on brain repair. More specifically, we have introduced a novel room-based video-gaming intervention; restorative neuroanimation, into the acute stroke hospital setting. This new intervention provides the opportunity for an extra hour(s) of high-intensity neurorestorative behavioral treatment that is complementary to conventional rehabilitation. To accomplish this, system redesign was required to insert this new treatment into the patient day, to properly stratify patients behaviorally and physiologically for the treatment, to optimize the digital therapeutic approach itself, and to maintain the impairment reduction after discharge.

Discovery of novel (N-aryl-4-methylpiperidinyl)pyrazoles: a new class of potent lepidopteran insecticides.

BACKGROUND: Insects of the order Lepidoptera are among the most destructive global pests, causing billions of dollars in damage annually. A new class of N-arylpyrazole-4-methylpiperidines with potent activity on lepidopteran species has been discovered. RESULTS: In a high-throughput insecticide screen compound 1 was identified to possess modest activity on the lepidopteran insect Plutella xylostella. Optimization of 1 to compound 42 resulted in a compound with excellent activity on Spodoptera exigua, Spodoptera frugiperda, and Helicoverpa zea with median lethal concentrations values of 2.8, 1.4, and 12.5 ppm respectively. Although the mode of action remains unknown, these compounds do not appear to work by many of the known biochemical mechanisms of insect control. CONCLUSION: N-Arylpyrazole-4-methylpiperidines represent a new class of insecticides with excellent activity on a broad spectrum of lepidopteran pests. Studies to date indicate the potential for a novel mode of action; however, the target site is unknown at present. © 2023 Society of Chemical Industry.

Older Adults and Three-Dimensional Exergaming: Motivators and Barriers to Participation and Retention.

Background: Cognitive and physical activity are important for daily functioning. However, limited research exists on the motivators and barriers associated with older adults participating and adhering to exergame studies that promote physical and cognitive activity. Our objective was to examine older adults' motivators and barriers to joining and completing a three-dimensional exergame study. Methods: Fourteen older adults who participated in the exergame study contributed to one of three focus group discussions. Inductive and deductive methods were used to analyze the qualitative data. Results: Motivators for joining were generativity, peer referrals, self-improvement, and curiosity. Accomplishment, immersion, and exercise were motivators for retention. Participants also cited the structured schedule and adaptive difficulty features as motivators for retention. Barriers to participation included frustration due to lack of level advancement and fatigue/pain during gameplay. Some (n = 3) reported camera tracking issues as a barrier. Unanticipated gender-based trends arose when examining perceptions of the study team's role and motivators for retention. Conclusion: These findings will inform future research strategies for participant recruitment, enrollment, and retention, in addition to providing insights into the design of motivating, enjoyable, and sustainable exergames for older adults.

SARS-CoV-2 epitopes inform future vaccination strategies.

All currently approved COVID-19 vaccines utilize the spike protein as their immunogen. SARS-CoV-2 variants of concern (VOCs) contain mutations in the spike protein, enabling them to escape infection- and vaccination-induced immune responses to cause reinfection. New vaccines are hence being researched intensively. Studying SARS-CoV-2 epitopes is essential for vaccine design, as identifying targets of broadly neutralizing antibody responses and immunodominant T-cell epitopes reveal candidates for inclusion in next-generation COVID-19 vaccines. We summarize the major studies which have reported on SARS-CoV-2 antibody and T-cell epitopes thus far. These results suggest that a future of pan-coronavirus vaccines, which not only protect against SARS-CoV-2 but numerous other coronaviruses, may be possible. The T-cell epitopes of SARS-CoV-2 have gotten less attention than neutralizing antibody epitopes but may provide new strategies to control SARS-CoV-2 infection. T-cells target many SARS-CoV-2 antigens other than spike, recognizing numerous epitopes within these antigens, thereby limiting the chance of immune escape by VOCs that mainly possess spike protein mutations. Therefore, augmenting vaccination-induced T-cell responses against SARS-CoV-2 may provide adequate protection despite broad antibody escape by VOCs.

Unmasking of Brugada syndrome by lamotrigine in a patient with pre-existing epilepsy: A case report with review of the literature.

Brugada syndrome is an inherited cardiac channelopathy arising from mutations in voltage-gated cardiac sodium channels. Idiopathic epilepsy portrays a coalescent underlying pathophysiological mechanism pertaining to the premature excitation of neuronal voltage-gated ion channels resulting in the disruption of presynaptic neurons and the unregulated release of excitatory neurotransmitters. The coexistence of epilepsy and Brugada syndrome may be explained by mutations in voltage-gated ion channels, which are coexpressed in cardiac and neural tissue. Moreover, the incidence of sudden unexpected death in epilepsy has been associated with malignant cardiac arrhythmias in the presence of mutations in voltage-gated ion channels. Lamotrigine is an antiepileptic drug that inhibits neuronal voltage-gated sodium channels, thus stabilizing neural impulse propagation and controlling seizure activity in the brain. However, lamotrigine has been shown to inhibit cardiac voltage-gated sodium channels resulting in a potential arrhythmogenic effect and the ability to unmask Brugada syndrome in genetically susceptible individuals. We are reporting a case of a 27-year-old male patient with a background of presumed idiopathic epilepsy who was initiated on lamotrigine therapy resulting in the unmasking of Brugada syndrome and the onset of syncopal episodes. This case provides further evidence for the arrhythmogenic capacity of lamotrigine and highlights the relationship between epilepsy and Brugada syndrome. In this report, we aim to review the current literature regarding the associations between epilepsy and Brugada syndrome and the impact of lamotrigine therapy on such patients.

The Molecular Landscape of Medulloblastoma in Teenagers and Young Adults.

Medulloblastoma (MB) is a childhood malignant brain tumour but also occurs in teenagers and young adults (TYA). Considering that MB is heterogeneous, this study aimed to define the molecular landscape of MBs in TYAs. We collated more than 2000 MB samples that included 287 TYA patients (13-24 years). We performed computational analyses consisting of genome-wide methylation and transcriptomic profiles and developed a prognostics model for the TYAs with MB. We identified that TYAs predominantly comprised of Group 4 (40%) and Sonic Hedgehog (SHH)-activated (33%) tumours, with Wingless-type (WNT, 17%) and Group 3 (10%) being less common. TYAs with SHH tumours displayed significantly more gene expression alterations, whereas no gene was detected in the Group 4 tumours. Across MB subgroups, we identified unique and shared sets of TYA-specific differentially methylated probes and DNA-binding motifs. Finally, a 22-gene signature stratified TYA patients into high- and low-risk groups, and the prognostic significance of these risk groups persisted in multivariable regression models (P = 0.001). This study is an important step toward delineating the molecular landscape of TYAs with MB. The emergence of novel genes and pathways may provide a basis for improved clinical management of TYA with MB.

FBG-Based Estimation of External Forces Along Flexible Instrument Bodies.

A variety of medical treatment and diagnostic procedures rely on flexible instruments such as catheters and endoscopes to navigate through tortuous and soft anatomies like the vasculature. Knowledge of the interaction forces between these flexible instruments and patient anatomy is extremely valuable. This can aid interventionalists in having improved awareness and decision-making abilities, efficient navigation, and increased procedural safety. In many applications, force interactions are inherently distributed. While knowledge of their locations and magnitudes is highly important, retrieving this information from instruments with conventional dimensions is far from trivial. Robust and reliable methods have not yet been found for this purpose. In this work, we present two new approaches to estimate the location, magnitude, and number of external point and distributed forces applied to flexible and elastic instrument bodies. Both methods employ the knowledge of the instrument's curvature profile. The former is based on piecewise polynomial-based curvature segmentation, whereas the latter on model-based parameter estimation. The proposed methods make use of Cosserat rod theory to model the instrument and provide force estimates at rates over 30 Hz. Experiments on a Nitinol rod embedded with a multi-core fiber, inscribed with fiber Bragg gratings, illustrate the feasibility of the proposed methods with mean force error reaching 7.3% of the maximum applied force, for the point load case. Furthermore, simulations of a rod subjected to two distributed loads with varying magnitudes and locations show a mean force estimation error of 1.6% of the maximum applied force.

Laboratory markers predictive of fulminant Clostridioides difficile infection refractory to fluid resuscitation.

BACKGROUND: Old age, leucocytosis, hypoalbuminemia, and elevated creatinine have been identified as risk factors for fulminant Clostridioides difficile infection (CDI). High ATLAS scores have also been linked to fatal disease. The affiliated studies, however, involved patients prescribed metronidazole - a regimen no longer standard of care. The variables were thus reassessed in patients prescribed optimal therapy. METHODS: Adults hospitalized with CDI at University of Kentucky Medical Center were retrospectively reviewed. Enrolled subjects were separated according to disease classification i.e. non-severe/severe versus fulminant CDI. Fulminant patients were further subdivided into hypotensive persons responsive to fluid resuscitation, and those with sequent shock, ileus, or megacolon. Following partition, the cohorts underwent correlation analysis. FINDINGS: Forty-five subjects had non-severe/severe disease. Thirteen fulminant CDI patients responded to fluid resuscitation. Seventeen fulminant CDI patients developed shock, ileus, or megacolon. Median WBC counts, albumin values, and ATLAS scores varied among the cohorts. Although WBC counts were similar among the fulminant subsets, declining albumin values and increasing ATLAS scores mirrored disease worsening. Logistic regression revealed albumin values < 20 g/L (odds ratio [OR] 3.91) and ATLAS scores ≥ 6 (OR 5.03) to predict critical illness in hypotensive persons. CONCLUSION: Median WBC counts, albumin values, and ATLAS scores differed in patients separated by CDI severity. A notable variance in albumin values and ATLAS scores between fluid responsive fulminant disease and critical illness was moreover seen. The finding suggests hypoalbuminemia and high ATLAS scores in hypotensive CDI patients may herald shock, ileus, or megacolon.

Acylative Dynamic Kinetic Resolution of Secondary Alcohols: Tandem Catalysis by HyperBTM and Bäckvall's Ruthenium Complex.

Non-enzymatic dynamic kinetic resolution (DKR) of secondary alcohols by enantioselective acylation using an isothiourea-derived HyperBTM catalyst and racemization of slowly reacting alcohol by Bäckvall's ruthenium complex is reported. The DKR approach features high enantioselectivities (up to 99:1), employs easy-to-handle crystalline 4-nitrophenyl isobutyrate as the acylating reagent, and proceeds at room temperature and under an ambient atmosphere. The stereoinduction model featuring cation-π system interactions between the acylated HyperBTM catalyst and π electrons of an alcohol aryl subunit has been elaborated by DFT calculations.

Integrative molecular characterization of pediatric spinal ependymoma: the UK Children's Cancer and Leukaemia Group study.

BACKGROUND: Pediatric spinal ependymomas (SP-EPNs) are rare primary central nervous system tumors with heterogeneous clinical course. Considering that ependymomas in children are biologically distinct from their adult counterparts, this study aimed to define the molecular landscape of SP-EPNs in children. METHODS: In this retrospective study, we have collected tumor samples from 27 SP-EPN patients younger than 18 years and carried out the histological review, DNA methylation, and gene expression profiling. RESULTS: Unsupervised analyses with methylation profiles revealed 2 subgroups where all grade I tumors (n = 11) were in Group 1, but the grade II/III tumors split into 2 groups (n = 7 in Group 1 and n = 9 in Group 2). The Heidelberg classifier assigned Group 1 tumors as spinal myxopapillary ependymomas (SP-MPEs), 5 Group 2 tumors as SP-EPNs, and failed to classify 4 Group 2 tumors. Copy numbers derived from DNA methylation arrays revealed subgroup-specific genetic alterations and showed that SP-EPN tumors lack MYCN amplification. Gene expression profiling revealed distinct transcriptomic signatures, including overexpression of genes involved in oxidative phosphorylation in SP-MPEs that were validated by Western blot analysis. We discovered widespread decreases in DNA methylation at enhancer regions that are associated with the expression of oncogenic signaling pathways in SP-MPEs. Furthermore, transcription factor motifs for master regulators, including HNF1B, PAX3, and ZIC3, were significantly overrepresented in probes specific to distal regulatory regions in SP-MPEs. CONCLUSION: Our findings show substantial heterogeneity in pediatric SP-EPN and uncover novel enhancers and transcriptional pathways specific to the SP-MPE subgroup, providing a foundation for future therapeutic strategies.