Preliminary Analysis Research Articles

Isolation of exogenous fungi from Notoginseng Radix et Rhizoma and preliminary analysis of toxigenic fungi

Isolation of exogenous fungi from Notoginseng Radix et Rhizoma and preliminary analysis of toxigenic fungi

Abstract 701: Preclinical data of a novel DNA-PK inhibitor in combination with radiation therapy shows promise in the treatment of established GBM and lung carcinoma cell lines

Abstract Radiation therapy (RT) is a cornerstone of oncologic therapy for the majority of solid malignancies, and unrepaired DNA double-strand breaks are responsible for radiation-induced cytotoxicity. RT-induced DNA lesions can be repaired by multiple mechanisms including homologous recombination (HR) and non-homologous end joining (NHEJ), and disruption of either of these pathways can enhance cytotoxicity. A key component of the NHEJ pathway is the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), and loss of kinase activity can significantly increase radiosensitivity. Herein we describe the results of our medicinal chemistry campaign to develop a potent and selective DNA-PKcs inhibitor, WNC0901. WNC0901 inhibits DNA-PKcs kinase activity in a cell free system with an IC50 of 0.071 nM and demonstrated at least 30-fold higher sensitivity than other family members (ATM, ATR, mTOR, PI3K). WNC0901 has limited aldehyde oxidase (AO) liability with a T1/2 >2000 min in liver cytosol and is stable for over 120 minutes in the presence and absence of an AO inhibitor. A preliminary pharmacokinetic analysis in wista han rat (IV=2mg/kg, PO=20mg/kg) demonstrated 116% apparent absolute oral bioavailability, 2.6 hour terminal half-life, 33.0 mL/min/kg clearance, and a 2.6% unbound brain-to-plasma partition coefficient (Kpuu). WNC0901 also had favorable pharmacokinetic properties in beagle dog (IV=2mg/kg, PO=20mg/kg) with moderate clearance (8.5 mL/min/kg), high apparent absolute oral bioavailability (131%) with good exposure (AUC=36092 h*ng/mL), moderate half-life (4.28 h), and low protein binding (74.3% fraction unbound). The volume of distribution was moderate in both species (Vss = 1.32 L/kg in wistar han rat and 1.87 L/kg in beagle dog). In cell culture, WNC0901 inhibited autophosphorylation of DNA-PKcs in HT29 cells irradiated with 10 Gy with an IC50 of 32.7 nM and robustly inhibited autophosphorylation in both U251 glioma and A549 lung cancer cell lines at 300 nM in combination with 5Gy. In a clonogenic assay, 5Gy irradiation (10% survival) combined with 100nM WNC0901 demonstrated modestly enhanced cell killing (1.5% survival), and maximal effects were seen at 300nM (0.04% survival, p<0.01). Similar radiosensitizing effects with 300 nM WNC0901 were seen in the A549 cell line (0.2% survival with combination compared to 19% with 5Gy alone, p<0.01). In summary, WNC0901 inhibits DNA-PK kinase activity and provides potent radiosensitization in a GBM and lung cancer cell line. Future studies will assess the combination of WNC0901 and RT in GBM patient-derived xenograft models in vivo. Citation Format: Ann C. Mladek, Danielle L. Burgenske, William F. Elmquist, Wei Zhong, Jann N. Sarkaria. Preclinical data of a novel DNA-PK inhibitor in combination with radiation therapy shows promise in the treatment of established GBM and lung carcinoma cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 701.

Abstract 6139: Genetic modifiers of KRAS-mutant colorectal cancer

Abstract Somatic driver mutations in KRAS are found in ~40% of colorectal cancers (CRCs) and are associated with worse outcomes. In the US, individuals of African ancestry with CRC are more likely to have tumors with KRAS mutations than individuals of European ancestry, even after considering differences in socioeconomic status and other risk factors. Germline variants can influence somatic mutation events and may provide a selective advantage such that a mutated cell is more likely to progress to a cancer. Germline variants have been found to associate with somatic mutations in a variety of tumors. Based on ancestry differences in KRAS tumor mutation frequency, we hypothesized that germline variants altering molecular pathways that support KRAS tumorigenesis will associate with KRAS-mutant status. To test this, we performed a two-step association study using KRAS mutation status as our phenotype in individuals with microsatellite stable CRC. First, we conducted a discovery analysis using genome-wide germline genotypes and somatic mutation data from 6,386 non-Hispanic White CRC patients from the Cancer Genome Atlas and the GECCO consortium, considering sex and tumor location as covariates. To select variants for additional study, we used in-silico tools, such as expression quantitative trait loci (eQTL), to predict how associated variants may alter gene expression and chromatin. After reviewing relevant genomic features, excluding SNVs with minor allele frequency <10% and pruning SNVs in linkage disequilibrium (r2>0.75), we identified candidate loci for a multi-ancestry independent validation analysis. In the discovery analysis, no variants met genome-wide significance thresholds (p-value <5x10-8), though 3 SNVs associated with KRAS mutation status with p-values <1x10-6 and 50 with p-values <1x10-5. Of these 50 SNVs, 21 met criteria for validation. We chose 80 additional SNVs (p-value <1x10-4) with predicted functional effect, for a total of 101 SNVs for analyses. In our preliminary validation analysis of 1,487 individuals grouped by self-reported race, no variants had a significant association in all populations. The rs726800 variant showed nominal association with KRAS mutation status (p-value=0.028) in self-reported non-Hispanic White individuals. This variant is within potential cis-regulatory distance of HS3ST3A1 and COX10-DT, both of which have been reported as cancer biomarkers. Nominal associations were identified in self-reported Black (n=7 SNVs) and Hispanic or Latino (n=3 SNVs) individuals, though both groups had limited sample sizes. Additional validation samples are being analyzed, as well as analysis with adjustment for genetic ancestry. Future functional studies of top candidate variants will add mechanistic insight. In summary, we identified germline SNVs that associate with KRAS somatic mutations in CRC and may inform the cellular context that supports development of colorectal tumors with KRAS mutations. Citation Format: Nijole P. Tjader, Johnny Ramroop, Tanish Gandhi, Peter T. Campbell, Andrew T. Chan, Steven Gallinger, Graham G. Giles, Marc J. Gunter, Tabitha A. Harrison, Michael Hoffmeister, Polly A. Newcomb, Shuji Ogino, Amanda I. Phipps, Conghui Qu, Robert E. Schoen, Andrew Pellatt, Michael O. Woods, Bethany Van Guelpen, Patrick Stevens, Heather Hampel, Ulrike Peters, Joseph P. McElroy, Amanda E. Toland. Genetic modifiers of KRAS-mutant colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6139.

Abstract 631: Functional genetics of APR-246 rescuable TP53 mutants

Abstract TP53, often referred to as the guardian of the genome, encodes for the p53 tumor suppressor protein, and is one of the most frequently mutated genes in human cancers. Some cancer sub-types, such as non-small cell lung carcinoma (NSCLC) and high grade serous carcinoma (HGSC), have high TP53 mutation rates reaching up to 56% and 96%, respectively. Given its multi-faceted role in human cancers, there have been several emerging therapeutic approaches targeting mutant p53. APR-246 is a small molecule drug currently in clinical trials for the functional rescue of p53 missense mutants, the most common type of p53 mutant protein, across various cancer types. APR-246 is proposed to bind mutant p53 and promote thermodynamic stabilization of the protein allowing it to regain wild-type-like conformation and consequentially regain WT-like functionality. However, there has yet to be a functional genomic screening of p53 mutants to systematically catalog which mutants are rescuable by APR-246. To address this critical gap, we have performed functional genetic screenings using a TP53 mutagenesis library. This pooled lentiviral library contains ~8,000 amino acid variants, spanning the entirety of the TP53 gene. Following stable transduction of this library into p53-null NSCLC and HGSOC cell lines, we performed functional screenings against sublethal doses of APR-246. Next-generation sequencing of the untreated and treated cell population allows for comparison of variant representation and determination of APR-246-sensitivity of p53 mutants. Preliminary statistical analysis of our screens has identified a pool of 117 “hit” mutants which are significantly depleted following treatment, indicative of APR-246-sensitivity. Two of these mutants, C242F and G266V, are non-functional, damaging mutations which occur in patients. Identifying p53 mutants that can be rescued by APR-246 will help identify which patients may benefit most from treatment with the drug. Citation Format: Anais Saunders, Caili Tong, Anthony N. Karnezis, Gary S. Leiserowitz, Jeremy R. Chein. Functional genetics of APR-246 rescuable TP53 mutants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 631.

Arceuthobium M.Bieb. (Viscaceae) parasitizing an angiosperm: the unique case of A. azoricum Hawksw. & Wiens in the Azores islands.

Arceuthobium azoricum Wiens & Hawksw. is a rare Azorean endemic epiphytic hemiparasite (mistletoe), that typically parasitizes branches of the gymnosperm Juniperus brevifolia (Hochst. ex Seub.) Antoine (Cupressaceae), also an Azorean endemic. Here we describe one population of A. azoricum, on Pico Island, parasitizing Erica azorica Hochst. ex Seub (Ericaceae) also an Azores endemic. Our molecular analysis (using nuclear ribosomal ITS) showed no differences between individuals parasitizing Erica and Juniperus. Moreover, a preliminary analysis showed no differences in morphological characters between accessions sampled from the different hosts. Given that this is the first bona fide record of Arceuthobium parasitizing an angiosperm, this population represents a unique host shifting event and its conservation is important because it may allow new insights into host recognition mechanisms in mistletoes. Immediate attention should be given to characterize this Pico Island population using appropriate molecular methods and additional morphological analyses.

Quick Extraction of Joint Surface Attitudes and Slope Preliminary Stability Analysis: A New Method Using Unmanned Aerial Vehicle 3D Photogrammetry and GIS Development

The present study proposes a preliminary analysis method for rock mass joint acquisition, analysis, and slope stability assessment based on unmanned aerial vehicle (UAV) photogrammetry to extract the joint surface attitude in Geographic Information Systems (GIS). The method effectively solves the difficulties associated with the above issues. By combining terrain-following photogrammetry (TFP) and perpendicular and slope surface photogrammetry (PSSP), the three-dimensional (3D) information can be efficiently obtained along the slope characteristics’ surface, which avoids the information loss involved in traditional single-lens aerial photography and the information redundancy of the five-eye aerial photography. Then, a semi-automatic geoprocessing tool was developed within the ArcGIS Pro 3.0 environment, using Python for the extraction of joint surfaces. Multi-point fitting was used to calculate the joint surface attitude. The corresponding attitude symbols are generated at the same time. Finally, the joint surface attitude information is used to perform stereographic projection and kinematic analysis. The former can determine the dominant joint group, and the latter can obtain the probability of four types of failure, including planar sliding, wedge sliding, flexural toppling, and direct toppling. The integrated stability evaluation method studied in this paper, which combines a 3D interpretation of UAV and GIS stereographic projection statistical analysis, has the advantages of being efficient and user-friendly, and requires minimal prior knowledge. The results can aid in the geological surveys of slopes and guide engineering practices.

Risk analysis of electrical power grids in India using best-worst method and grey causal modelling

PurposeThe study aims to identify the possible risk factors for electricity grids operational disruptions and to determine the most critical and influential risk indicators.Design/methodology/approachA multi-criteria decision-making best-worst method (BWM) is employed to quantitatively identify the most critical risk factors. The grey causal modeling (GCM) technique is employed to identify the causal and consequence factors and to effectively quantify them. The data used in this study consisted of two types – quantitative periodical data of critical factors taken from their respective government departments (e.g. Indian Meteorological Department, The Central Water Commission etc.) and the expert responses collected from professionals working in the Indian electric power sector.FindingsThe results of analysis for a case application in the Indian context shows that temperature dominates as the critical risk factor for electrical power grids, followed by humidity and crop production.Research limitations/implicationsThe study helps to understand the contribution of factors in electricity grids operational disruptions. Considering the cause consequences from the GCM causal analysis, rainfall, temperature and dam water levels are identified as the causal factors, while the crop production, stock prices, commodity prices are classified as the consequence factors. In practice, these causal factors can be controlled to reduce the overall effects.Practical implicationsFrom the results of the analysis, managers can use these outputs and compare the risk factors in electrical power grids for prioritization and subsequent considerations. It can assist the managers in efficient allocation of funds and manpower for building safeguards and creating risk management protocols based on the severity of the critical factor.Originality/valueThe research comprehensively analyses the risk factors of electrical power grids in India. Moreover, the study apprehends the cause-consequence pair of factors, which are having the maximum effect. Previous studies have been focused on identification of risk factors and preliminary analysis of their criticality using autoregression. This research paper takes it forward by using decision-making methods and causal analysis of the risk factors with blend of quantitative and expert response based data analysis to focus on the determination of the criticality of the risk factors for the Indian electric power grid.

Low-order modeling approach for the prediction of transverse combustion instabilities in multi-injector engines

AbstractThis paper addresses the prediction of spontaneous self-sustained transverse combustion instabilities in multi-injector engines using a multi-dimensional non-linear low-order Eulerian model. The approach utilizes a physically aware response function that directly links pressure oscillations to fuel mass flow rate, independent of external data. This enables accurate capture of the behavior of shear coaxial injectors that have been proven to show a peculiar dynamics of cyclic fuel accumulation and release in response to acoustic waves. A NASA test case is employed as a reference, and a comprehensive analysis is conducted to investigate the behavior of the model. Firstly, a preliminary analysis is performed within a quasi-one-dimensional framework for a reduced single-injector configuration. This analysis provides insights into the influence of key parameters on the instability onset. Subsequently, the full-scale geometry is considered in a multi-dimensional framework, and the low-order solver is employed to analyze the thermo-acoustic behavior of the engine. The model successfully captures the instability dynamics, including temporal evolution, dominant frequency, and mode shapes. Sensitivity analyses are conducted to examine the impact of the model free parameters on the unstable modes. Additionally, the effect of introducing baffles as damping devices within the combustion chamber is investigated. The results highlight the model predictive capabilities and its potential for guiding the design and optimization of liquid rocket engines.

An Upper Take on Doubler-Uppers

Against the background of comparatively insufficient, expressly dedicated studies on double particle verb person nominalisations, this paper offers a qualitative, cognitive-constructionist approach to the properties of doubler-upper nominalisations of particle verbs in English and a reappraisal of some of the available analyses thereof. On the assumption of the validity of the flexicon stance on the organisation of words in the human mind, and on the basis of a preliminary semantic analysis of 300 types of doubler-upper nouns extracted from two corpora and Urban Dictionary, it is claimed that there are no identifiable constraints on the possibility of double-er marking and no particular properties of particle verbs as bases to preclude double -er marking. A hypothesis is formulated that, despite their deviance, doubler-uppers strike the optimal balance between complexity and unity and appear to be the most natural and morphophonologically best-fitting pattern for particle verb -er nominalisation (at least in spoken discourse and the media).

Intravoxel incoherent motion assessment of liver fibrosis staging in MASLD.

Partial correlation analysis was performed to account for the interference of steatosis changes and inflammatory factors, to determine the true correlation between fibrosis and IVIM parameters (Dfast, Dslow, and F), and to evaluate the diagnostic efficacy of IVIM for liver fibrosis. A total of 106 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) examined by IVIM from November 2016 to November 2023 at our hospital were retrospectively included. Preliminary analysis of each IVIM parameter and correlations with pathological findings were performed using Spearman correlation analysis, and partial correlation analysis was used to exclude the interference of other pathological factors, thus yielding the true correlations between IVIM parameters (Dfast, Dslow, and F) and pathology. The diagnostic efficacy of IVIM parameters for diagnosing MASLDwas assessed via receiver operating characteristic (ROC) curve analysis. Spearman correlation analysis of all the IVIM parameters revealed correlations with steatosis, lobular inflammation, and ballooning. Partial correlation analysis indicated that Dfast was correlated with the pathological fibrosis stage (r = - 0.593, P < 0.001), Dslow was correlated with the pathological steatosis score (r = - 0.313, P < 0.05), and F was correlated with the pathological fibrosis stage and steatosis score (r = - 0.456 and 0.255, P < 0.001 and P < 0.05). In the diagnosis of hepatic fibrosis, significant hepatic fibrosis, advanced liver fibrosis and cirrhosis, Dfast achieved areas under the ROC curve of 0.763, 0.801, 0.853, and 0.897, respectively. The threshold values for diagnosing different fibrosis stages using Dfast (10-3 mm2/s) were 57.613, 54.587, 52.714, and 51.978, respectively. According to our partial correlation analysis, there was a moderate correlation between Dfast and F according to fibrosis stage, and Dfast was not influenced by inflammation or steatosis when diagnosing fibrosis in MASLD patients. A relatively close Dfast threshold is insufficient for accurately and noninvasively assessing various stages of MASLD fibrosis. In clinical practice, this approach can be considered an alternative method for the preliminary assessment of fibrosis in MASLD patients.

Exploring Roots of Profound Moments: An Empirical Study

The purpose of this qualitative study was to explore the components of a profound moment. We provisionally defined a profound moment as an experience that intentionally or unintentionally continues to surface in consciousness, has transformed an individual’s fundamental perspectives, and been integrated into an individual’s life. Participants who the researchers felt had experienced highly memorable moments and demonstrated an introspective personality were purposefully selected. Interviews were conducted using a semi-structured interpretive phenomenological approach; interviews were transcribed, coded, analyzed, and considered in the analysis. Results from preliminary analysis indicate components of profound moments include acceptance, permeation, humanity, and change.

Discovery of circulating blood biomarkers in patients with and without Modic changes of the lumbar spine: a preliminary analysis.

The following study aimed to determine the existence of blood biomarkers in symptomatic patients with or without lumbar Modic changes (MC). A cross-sectional sub-analyses of a prospective cohort was performed. Fasting blood samples were collected from patients with and without lumbar MC who had undergone spinal fusion or microdiscectomy. An 80-plex panel and CCL5/RANTES were used to assess preoperative plasma cytokine concentrations. Patient demographics and imaging phenotypes were also assessed. Thirty-one subjects were analysed (n = 18 no MC; n = 13 MC). No significant differences were found in age, sex, body mass index, smoking and alcohol history, and surgical procedure (i.e. fusion, decompression) between the two groups (p > 0.05). Several statistically significant blood biomarkers in MC patients were identified, including elevated levels of C-C Motif Chemokine Ligand 5 (CCL5, p = 0.0006), while Macrophage Migration Inhibitory Factor (MIF) was significantly lower (p = 0.009). Additionally, C-X-C Motif Chemokine Ligand 5 (CXCL5, p = 0.052), Pentraxin 3 (PTX3, p = 0.06) and Galectin-3 (Gal-3, p = 0.07) showed potential relevance. Moreover, MC patients exhibited significantly higher levels of disc degeneration (p = 0.0001) and displacement severity (p = 0.020). Based on multivariate analyses and controlling for disc degeneration/displacement, CCL5 (OR 1.02; 95% CI 1.002-1.033; p = 0.028) and MIF (OR 0.60; 95% CI 0.382-0.951; p = 0.030) were independently associated with MC patients. This "proof-of-concept" study is the first to identify specific and significantly circulating blood biomarkers associated with symptomatic patients with lumbar MC, independent of disc alterations of degeneration and/or bulges/herniations. Specifically, differences in CCL5 and MIF protein levels were significantly noted in MC patients compared to those without MC.

The Varieties of Agency in Human–Smart Device Relationships: The Four Agency Profiles

This paper investigates how users of smart devices attribute agency both to themselves and to their devices. Statistical analyses, tag cloud analysis, and sentiment analysis were applied on survey data collected from 587 participants. As a result of a preliminary factorial analysis, two independent constructs of agency emerged: (i) user agency and (ii) device agency. These two constructs received further support from a sentiment analysis and a tag cloud analysis conducted on the written responses provided in a survey. We also studied how user agency and device agency relate to various background variables, such as the user’s professional knowledge of smart devices. We present a new preliminary model, where the two agency constructs are used to conceptualize agency in human–smart device relationships in a matrix composed of a controller, collaborator, detached, and victim. Our model with the constructs of user agency and device agency fosters a richer understanding of the users’ experiences in their interactions with devices. The results could facilitate designing interfaces that better take into account the users’ views of their own capabilities as well as the capacities of their devices; the findings can assist in tackling challenges such as the feeling of lacking agency experienced by technologically savvy users.

A Novel Approach for Mixed-Methods Research Using Large Language Models: A Report Using Patients' Perspectives on Barriers to Arthroplasty.

Mixed-methods research is valuable in health care to gain insights into patient perceptions. However, analyzing textual data from interviews can be time-consuming and require multiple analysts for investigator triangulation. This study aims to explore a novel approach to investigator triangulation in mixed-methods research by employing a large language model (LLM) for analyzing data from patient interviews. This study compared the thematic analysis and survey generation performed by human investigators and ChatGPT-4, which uses GPT-4 as its backbone model, using data from an existing study that explored patient perceptions of barriers to arthroplasty. The human- and ChatGPT-4-generated themes and surveys were compared and evaluated based on their representation of salient themes from a predetermined topic guide. ChatGPT-4 generated analogous dominant themes and a comprehensive corresponding survey as the human investigators but in significantly less time. The survey questions generated by ChatGPT-4 were less precise than those developed by human investigators. The mixed-methods flowchart proposes integrating LLMs and human investigators as a supplementary tool for the preliminary thematic analysis of qualitative data and survey generation. By utilizing a combination of LLMs and human investigators through investigator triangulation, researchers may be able to conduct more efficient mixed-methods research to better understand patient perspectives. Ethical and qualitative implications of using LLMs should be considered.

Systematic Mendelian randomization reveals the causal roles of the microbiome on the risk of Parkinson's disease

Parkinsons Disease (PD) is a neurodegenerative disorder whose etiology is not fully understood. The human gut microbiome, a complex community of microorganisms residing in the digestive tract, has recently emerged as a potential factor influencing various health conditions, including neurodegenerative diseases. The causal involvement of the human gut microbiome in Parkinsons disease (PD) remains elusive, primarily due to the challenge of distinguishing causation from mere correlation, and the presence of contradictory findings in existing research. The relationship between the gut microbiome and PD was assessed using a two-sample Mendelian randomization (MR) approach. Assessing the impact of microbial traits using data from independent genome-wide association studies (GWAS) (comprising 2,259 samples) on PD within a cohort of 15,056 cases and 449,056 controls. We performed multiple sensitivity analyses to validate our findings. Preliminary MR analysis indicated that modifications in the bacterial composition of the Firmicutes and Proteobacteria phyla are associated with changes in PD risk. Additionally, bacteria in other genera also play a role in this causal association. We provide a comprehensive discussion of the results obtained from our MR analysis and highlight the distinctions between our study and prior research efforts.

Pediatrician perspectives on barriers and facilitators to discharge instruction comprehension and adherence for parents of children with medical complexity.

High rates of posthospitalization errors are observed in children with medical complexity (CMC). Poor parent comprehension of and adherence to complex discharge instructions can contribute to errors. Pediatrician views on common barriers and facilitators to parent comprehension and adherence are understudied. To examine pediatrician perspectives on barriers and facilitators experienced by parents in comprehension of and adherence to inpatient discharge instructions for CMC. We conducted a qualitative, descriptive study of attending pediatricians (n = 20) caring for CMC in inpatient settings (United States and Canada) and belonging to listservs for pediatric hospitalists/complex care providers. We used purposive/maximum variation sampling to ensure heterogeneity (e.g., hospital, region). A multidisciplinary team designed and piloted a semistructured interview guide with pediatricians who care for CMC. Team members conducted semistructured interviews via phone or video call. Interviews were audiorecorded and transcribed. We analyzed transcripts using content analysis; codes were derived a priori from a conceptual framework (based on the Pediatric Self-Management Model) and a preliminary transcript analysis. We applied codes and identified emerging themes. Pediatricians identified three themes as barriers and facilitators to discharge instruction comprehension and adherence: (1) regimen complexity, (2) access to the healthcare team (e.g., inpatient team, outpatient pediatrician, home nursing) and resources (e.g., medications, medical equipment), and (3) need for a family centered and health literacy-informed approach to discharge planning and education. Next steps include the assessment of parent perspectives on barriers and facilitators to discharge instruction comprehension and adherence for prents of CMC and the development of intervention strategies.

SPINAL ANATOMY AND BEYOND: INVESTIGATING DEGENERATIVE DISC DISEASE

Degenerative disc disease is a common manifestation in routine spine imaging; this finding is partly attributable to physiological aging and partly to a pathological condition, and sometimes, this distinction is simply not clear. The study's main objective is to find the spinal anatomy and investigate degenerative disc disease in spinal patients. This mixed-methods study was conducted in a public hospital in Karachi, Pakistan from March 2023 to September 2023. Fifty patients diagnosed with DDD are enrolled, with comprehensive clinical assessments conducted to evaluate symptomatology, functional impairment, and radiological findings. Additionally, advanced imaging modalities, including MRI and CT scans, elucidate structural changes within the spinal column. Preliminary analysis reveals a mean disc height loss of 3.2 mm (±0.8) across the study cohort, with significant variability observed among individual patients. Annular tears are prevalent in 70% of cases, predominantly localized to the lumbar spine. Furthermore, facet joint degeneration is evident in 85% of patients, with a mean grade of 2.4 (±0.6) on the Pfirrmann scale. Correlation analysis demonstrates a moderate positive correlation (r = 0.56, p &lt; 0.001) between disc height loss and severity of clinical symptoms. It is concluded that this study provides the complex pathology of degenerative disc disease (DDD) and its impact on spinal anatomy. Through a comprehensive investigation involving clinical assessments and advanced imaging techniques, we have elucidated the spectrum of degenerative changes within the intervertebral discs and facet joints.

Effect of duration of sodium valproate therapy on bone mineral density and vitamin D levels

ObjectiveThis study aimed to evaluate the impact of prolonged sodium valproate use on bone mineral density (BMD) and Vitamin D levels in pediatric epilepsy patients. MethodsIn a cross-sectional study conducted at the Epilepsy Clinic of Niloufer Hospital, Hyderabad, India, 50 pediatric patients (aged 4–10 years) were recruited. The cohort comprised 30 epilepsy patients on sodium valproate treatment (cases) and 20 healthy siblings without epilepsy or valproate use (controls). BMD was assessed using dual-energy X-ray absorptiometry to measure height-adjusted total body less head Z-scores (TBLH Z-scores), and serum 25-hydroxyvitamin D levels were measured. Statistical analysis included independent samples t-tests, Mann-Whitney U tests, and Pearson correlation, with a preliminary power analysis ensuring adequate sample size. ResultsCases exhibited significantly lower BMD TBLH Z-scores (Mean = -1.543) compared to controls (Mean = 0.515, p <.001) and reduced Vitamin D levels (Mean = 9.17 for cases vs. 27.80 for controls, p <.001). A negative correlation was observed between the duration of sodium valproate use and both BMD Z-scores (r = -0.626, p <.001) and Vitamin D levels (r = -0.707, p <.001). ConclusionsThe findings suggest a significant negative impact of prolonged sodium valproate use on both bone density and Vitamin D levels in pediatric patients. These results underscore the importance of monitoring and managing bone health in children receiving long-term sodium valproate therapy.

Abstract A030: The Montreal Cognitive Assessment (MoCA) administered virtually or via Duo APP in primary brain tumor patients: a preliminary analysis

Abstract Background: Primary brain tumor (PBT) patients experience cognitive dysfunction (CD) because of both their tumor and its treatment. Evaluating CD in PBT populations may inform patient outcomes and clinical management and allow exploration of biologic underpinnings associated with its occurrence. The Montreal Cognitive Assessment (MoCA) is a brief assessment of objective measures of cognition that evaluates 8 specific cognitive domains. Our group has previously reported the feasibility of MoCA, and this study includes using the newly developed MoCA Duo APP to evaluate and report the cognitive function of patients with PBT. Associations between total MoCA scores and clinical and demographic characteristics were explored. Methods: This cohort consisted of adult PBT patients (n=172) enrolled in the NCI-NOB Natural History Study (NCT02851706: PI T. Armstrong). Assessments were performed between February 2020 and July 2023 by MoCA certified assessors and administered in the clinic or via telehealth. MoCA scores range from 0 to 30 (normal cognition ≥ 26). Healthcare providers collected demographic and clinical characteristics, with Karnofsky performance status (KPS) scores categorized as poor (≤ 80) or good (≥ 90). Descriptive statistics, independent t-tests, one-way ANOVAs, and Pearson’s correlation were conducted using IBM SPSS Statistics software. Results: The majority of patients were male (58%), white (81%), had ≥12 years of education (87%), had high-grade (3/4) tumors (65%), and a good KPS score (68%). The mean MoCA score was 25 (median: 26; range: 6-30) with a mean completion time of 10.7 minutes (median: 10; range: 6.1-41.1). Forty-two percent (n=73) were classified as abnormal. The median scores were lowest in the visuospatial/executive (4/5; range: 0-5), abstraction (2/3; range: 0-3) and delayed recall (4/5; range: 0-5) domains. A univariate analysis identified lower MoCA scores in patients with high-grade tumors (p&amp;lt;0.001), poor KPS scores (p&amp;lt;0.001), who underwent two or more surgeries (p=0.004) or treatments (p=0.038), had recurrence (p=0.002), had progression on current imaging (p=0.017), and had current anticonvulsant (p=0.014) and corticosteroid use (p=0.036). Age at diagnosis (r=-0.157, p=0.021) and at visit (r=-0.193, p=0.005) had a weak negative correlation with MoCA scores. Conclusions: Our results indicate that patient age, tumor progression, treatment, and concomitant medications are associated with MoCA scores. Further analysis will evaluate tumor methylation status and blood-based biomarkers associated with occurrence to develop prediction models that can be evaluated in larger cohorts. Future investigations should compare MoCA scores to other forms of cognitive assessment, including patient-reported outcomes, incorporating multiple timepoints to monitor CD in patients throughout their treatment and survivorship care. Citation Format: McKenzie C. Kauss, Elizabeth Vera, Kimberly Reinhart, Hope Miller, Jaime Garcia, Morgan Johnson, Madhura V. Managoli, Maeve Pascoe, Kaitlynn Slattery, Alex R. Wollet, Mark R. Gilbert, Alvina Acquaye-Mallory, Terri S. Armstrong, Vivian A. Guedes. The Montreal Cognitive Assessment (MoCA) administered virtually or via Duo APP in primary brain tumor patients: a preliminary analysis [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr A030.

(039) Challenges in Transgender Care Through a Qualitative Lens: Provisional Results About Sexual Medicine Professionals´ Opinions

Abstract Introduction Transgender people’s health and healthcare have become one of the most important challenges in healthcare settings and policy making. The perspectives of transgender consumers are important to inform policymaking and the development of measures to diminish barriers to accessing and maintaining health care. However, the perspective of healthcare providers, namely clinicians, is less known and is important to take a comprehensive and collaborative stance to deliver the best healthcare. Objective To highlight the perspective of sexual medicine practitioners/sexologists involved in transgender healthcare on the challenges faced in providing transgender healthcare. Methods Following an initiative by the Portuguese Society for Clinical Sexology, we used a participatory research design involving experienced sexual medicine clinicians/sexologists and activists for transgender care to develop a study to collect sexologists' perceptions of the challenges they faced when providing health care to transgender people. After IRB approval, we used a cross-sectional qualitative design and disseminated an online survey among professional associations (e.g., the Portuguese Society of Andrology, Sexual Medicine and Reproduction). A total of 25 complete answers were collected from clinicians who act in transgender healthcare and whose professional background included: Clinical Psychology, Pediatric Psychiatry, Psychiatry, Endocrinology, Urology, Gynecology and Anesthesiology. Participants were, on average, 46 years old (SD = 12.38), had an average of 13 years (SD = 11.25) experience in Sexual Medicine/Clinical sexology and 11 years on average (SD = 10.38) of experience with transgender healthcare. Sociodemographic data was collected between January and June 2023, and four open questions were presented. The current study will report preliminary content analysis concerning the open question: “Which challenges have you encountered in your experience as a health professional acting clinically with transgender people?”. Results The preliminary content analysis revealed 6 main categories, each representing distinct and interrelated subcategories aggregating different codes. The main categories were: 1. Formal Institutional Challenges (e.g., lack of formal education concerning transgender care, lack of specific guidelines for primary care; long waiting lists); 2. Informal Institutional Challenges (e.g., lack of updated knowledge from other clinicians not directly involved in transgender care; non-responsiveness from colleagues, translating policies and international guidelines into practices); 3. Social Challenges (e.g., family stigma; social discrimination); 4. Patient’s Challenges (e.g., lack of compliance; hostility or negative expectations towards health professionals); 5. Personal limits (e.g., perseverative thinking about the timing and patients’ internalisation of information about surgery risks; feelings of strangeness towards non-binary bodies); 6. Clinical Challenges (e.g., presence of emotional disorders/psychopathology; establishing differential diagnosis). Conclusions The current preliminary and provisional results highlight that clinical sexologists involved in transgender healthcare face different challenges regarding their role. The interrelated themes and subthemes reveal that clinical sexologists acting in transgender care have a critical stance towards policy making, service management and the quality of professional education provided to clinicians. Stigmatisation by their colleagues towards transgender people is a focus of concern. Still, they also feel they experience patients’ hostility and clinical and ethical challenges when trying to provide the best standards of care with a lack of resources. Disclosure No.