Preliminary Findings Research Articles

Assessment of myogenic potency in patient-derived fibroblasts with c.1289-2A>G Desmin mutation

Abstract Objectives The ultra-rare DES c.1289-2A>G mutation, resulting in a 48-base pair insertion in the Desmin tail domain, is associated with late-onset MFM1 (myofibrillar myopathy-1; OMIM number; 601419) and exhibits distinctive pathological features. Despite sustained expression and cytoskeletal integrity, muscle biopsies reveal dystrophic characteristics through an unidentified mechanism. A deeper understanding of the molecular mechanisms underlying Desmin-related MFM1 could enhance our perspective and comprehension of the disease’s pathophysiology. In this study, we aimed to investigate the pathological phenotype by assessing the myogenic potency of MyoD-induced patient-derived fibroblasts. Methods Following the immortalization and myoconversion of unaffected and patient-derived fibroblast cells, we analyzed the myogenic potency of the mutant and control groups on day 5 post-differentiation. This analysis involved staining cells with MF20 antibody and DAPI after MyoD induction. Results Employing six parameters to quantify extra nuclei and myotube properties, we unveil impaired myogenic differentiation in c.1289-2A>G mutant cells, as evidenced by a compromised fusion index and distinctive myogenic features. In summary, our preliminary findings indicate phenotypic abnormalities and suggest an association between the DES c.1289-2A>G mutation and delayed maturation and MFM in affected individuals. Conclusions Our results indicate a significant involvement of Desmin in the myogenic maturation of muscle cells. Further investigation is required to understand the changes in the transcriptome during the myoconversion of patient-derived fibroblasts.

Low dose exogenous melatonin plus evening dim light and time in bed scheduling advances circadian phase irrespective of measured or estimated dim light melatonin onset time: preliminary findings.

The purpose of the present study was to preliminarily evaluate whether knowing the dim light melatonin onset (DLMO) time is advantageous when treating delayed sleep-wake phase disorder (DSWPD) with low dose melatonin treatment plus behavioral interventions (i.e., evening dim light and time in bed (TIB) scheduling). In this randomized, controlled, double-blind trial, 40 adults with DSWPD were randomly assigned to 4 weeks of 0.5 mg timed to be administered either 3 hours before the DLMO (measured DLMO group, n = 20) or 5 hours before sleep onset time per actigraphy (estimated DLMO group, n = 20), in conjunction with behavioral interventions. The primary outcome was change in the DLMO (measured in-home). Secondary outcomes included sleep parameters per diary and actigraphy (sleep onset and offset times and total sleep time), Morningness-Eveningness Questionnaire (MEQ), Multidimensional Fatigue Inventory (MFI), PROMIS-Sleep Disturbance (SD), PROMIS-Sleep Related Impairment (SRI), and Pittsburgh Sleep Quality Index (PSQI). Mixed effects models tested for group differences in these outcome. After applying the Bonferroni correction for multiple comparisons (significant p-value set at ˂ .004), there were significant main effects for visit on all outcomes except PSQI and total sleep time per wrist actigraphy and diary. There were no group by visit interactions for any of the outcomes (p > .004). Scheduled low dose melatonin plus behavioral interventions may improve many circadian and sleep parameters regardless of whether melatonin administration is scheduled based on estimated or measured DLMO. A larger-scale trial is needed to confirm these preliminary findings. Clinicaltrials.gov Identifier: NCT03715465; Name: The Clinical Utility of Measuring the Circadian Clock in Treatment of Delayed Sleep-Wake Phase Disorder; URL: https://clinicaltrials.gov/study/NCT03715465.

Abstract A002: MALT1 as a regulator of tumor progression in H3K27-altered diffuse midline glioma

Abstract A002: MALT1 as a regulator of tumor progression in H3K27-altered diffuse midline glioma

Traces of Kinship Care: Preliminary Findings From Nansen Passport Holders’ Documents in the League of Nations and Arolsen Archives

This article offers a new perspective on a body of literature that has been growing since the modern concept of “statelessness” became a pressing concern of diplomats and the displaced alike more than a century ago: it studies the “voices” of the stateless as captured in the archival documents of the organizations designed to deal with refugees through the lens of family and kinship care. This will help us to gain an understanding of how stateless refugees and the officials, administrators and humanitarians who assisted them navigated and negotiated the kinds of care requested, needed, withheld, or provided, and that have been captured in the documents coming out of these processes. By positioning care as relational and embedded within historical documents, this contribution offers glimpses of the physical remnants of the processes that took shape between the various actors. From these explorations, it follows that the distinction between anonymous care, as provided by humanitarian or state organizations, and personal care may not have been so clear-cut: sometimes helpers and those being helped turn out both to be Nansen passport holders. The focus on family and kin moreover allows to move beyond the institutional focus on individuals and to understand statelessness and displacement as an experience of families and communities instead.

Abstract A017: An analysis of 13 independently performed assays to measure homologous recombination deficiency using 90 freshly extracted high grade serous ovarian tumors: findings from the friends of cancer research hrd harmonization project

Abstract A017: An analysis of 13 independently performed assays to measure homologous recombination deficiency using 90 freshly extracted high grade serous ovarian tumors: findings from the friends of cancer research hrd harmonization project

Abstract B083: Single-cell and spatial transcriptomic characterization of treatment resistance and immune dynamics in high-grade serous ovarian cancer

Abstract B083: Single-cell and spatial transcriptomic characterization of treatment resistance and immune dynamics in high-grade serous ovarian cancer

(161) Is there a Difference in Inflatable Penile Prosthesis Mechanical Failure and Infections Rates in Relation to Prostate Cancer Treatment Modality (Radiation Therapy vs Radical Prostatectomy)

Abstract Introduction Inflatable Penile Prosthesis (IPP) implantation as a treatment for ED has high satisfaction rates in the general population; however, there is limited literature on quantification of complication rates as stratified by ED etiology. Objective Our aim was to compare mechanical failure and infection rates in patients undergoing IPP implantation for ED following Radical Prostatectomy (RP) versus radiation therapy (RT) for prostate cancer. Methods A retrospective chart review from our institutional database was conducted to identify 405 patients who underwent IPP placement at our institution from 2015–2019, then selecting for those whose etiology of ED was following RP or RT. To prevent crossover confounding; patients with history of pelvic radiation or salvage radiotherapy were excluded from the RP group and patients with history of RP were excluded from the RT group. Data was obtained from 75 patients who met criteria for inclusion: 44 patients in the RP group and 31 patients in the RT group. Mechanical failure, infection rates, mean EDITS scores and additional survey questions were compared between the radiation and RP groups. Results Patient demographic information and IPP complication and satisfaction rates are listed below in Table 1 and Figure 1. There was a statistically significant difference in number of patients experiencing IPP complications, 19.4% (n=6) of patients in the RT cohort and 4.5% (n=2) in the RP cohort, respectively. There was no statistically significant difference found in stratified complications- infection rates, device erosion rates, mechanical failure rates, or device removal and/or replacement rates between the two groups. The RP cohort had a significantly higher mean Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire score versus the RT cohort, 91.58 to 76.02, respectively. Conclusions These preliminary findings, while requiring large-scale follow up, suggest that there is a higher rate of IPP related complications in patients with device placement following RT for prostate cancer versus RP. Disclosure No.

The relationship of pain intensity and opioid craving with delayed methadone dose: A preliminary study of individuals with opioid use disorder.

Despite a strong theoretical link between opioid craving and pain, little is known about the temporal relationship between pain and craving and the acute experience of pain in the context of methadone treatment. Using a cross-over design, the current study evaluated the time course of pain and craving and objective experience of pain as a function of the last methadone dose. Participants (n = 20) presented for the study in the morning and either received methadone dose as scheduled or delayed dose until the afternoon. During the 4-h study visit, participants completed a series of tasks, including repeated assessment of pain and craving at 0, +40, +70, +130, +160 and +240 min and a cold pressor test (CPT) at +15 and +220 min. Separate mixed model results demonstrated no effect of dosing condition on craving; however, there was a significant dosing condition by time interaction (F(5,209) = 3.38, P = .006) such that pain increased over time in the delayed methadone condition but decreased in time in the scheduled methadone condition. A mixed model predicting self-reported pain revealed a three-way interaction between dosing condition, craving and time (F(5,197) = 2.39, P = .039) explained by a positive association between craving and pain at each time point (except 240 min) in delayed condition (P-range = .004-.0001). A separate mixed model on CPT data indicated a significant condition by time interaction such that pain threshold decreased in the delayed, but not scheduled, condition (F(1,57) = 4.01, P = .050). These preliminary findings highlight the potential for increased risks after even a short delay in receiving a methadone dose.

(102) A Preliminary Analysis of Outcomes and Complication Rates for Patients Undergoing Inflatable Penile Prosthesis Implantation Following Intracavernosal Injection Therapy With or Without Concurrent Anticoagulation

Abstract Introduction Medications, namely antiplatelets (AP) and anticoagulation (AC), are effective at avoiding fatal vascular complications and prolonging the lives of our patients. As such, more and more men seeking treatment for erectile dysfunction (ED) also take blood thinners. This is an interaction we must better understand to provide safe, individualized care to our patients and minimize peri-operative morbidity. Currently, there is no published information on whether differences exist in the escalation of treatment for patients with erectile dysfunction and on AC. A previous study has demonstrated no statistically significant difference in complications between AC and non-AC groups while on ICI, despite there being a higher rate of absolute bleeding events for AC patients. Objective To compare outcomes and complication rates in patients undergoing IPP implantation following ICI therapy with or without concurrent anticoagulation. Methods A retrospective observational study was undertaken. Electronic patient records from January to September 2021 were reviewed. Included patients were those who had either currently or previously utilized ICI therapy for ED treatment. ICI therapy surveys and Erectile Dysfunction Inventory for Treatment Satisfaction (EDITS) questionnaire were obtained. 85 patients met the inclusion criteria; 43 concurrently using AC during ICI therapy and 42 with no AC use. Patients who were unable to completely stop their AC medications a week before surgery due to cardiovascular concerns or recommendations, underwent bridging with a shorter half life and reversible AC. Extra measures taken during the IPP for such patients, including meticulous hemostasis, compression dressing and drain insertion. Additional data regarding IPP implantation as well as any complications or infections experienced following IPP surgery which were compared between the AC and no AC groups. Results Patient demographics, IPP implantation information and subsequent complication rates are listed below in Table 1. There was no statistically significant difference in the rate of patients who underwent IPP placement between the AC and no AC cohorts. Moreover, there was also no statistically significant difference in median time from date of initial ICI usage to time of IPP placement as well as median time from IPP placement to last follow-up. Among the 12 total patients who underwent IPP placement, none experienced any complications, including infection, mechanical failure, device removal or revision at any time point up to last follow-up (longest was 18 months). No statistically significant differences in EDITS score between both groups was observed. Conclusions These preliminary findings, while requiring large-scale follow up, show that there is no statistically significant difference in rate of patients opting for IPP surgery following initiation of ICI therapy regardless of concomitant AC usage as well as the rate of complications following IPP implantation. Lastly, there is no drawbacks in performing such procedure in this specific cohort of patients, provided that all necessary measures are taken into consideration to minimize bleeding complications. Disclosure No.

Approaching tourism communication with empirical multimodality: exploratory analysis of Instagram and website photography through data-driven labeling

This paper reports the methods and results of the manual annotation of visual features in two corpora of tourism photography on travel boards' digital channels with a tailored tagging model based on the Grammar of Visual Design and adapted to tourism discourse. Computational analysis and statistical modeling show how the testing of theoretical assumptions through categorized data may lead to evidence-based interpretations of patterns of data clustering and to the detection of new communicative aims and conventions across digital media. Preliminary findings reveal indeed significant differences in the frequency of tag (co)patternings and use of visual strategies across channels that are related to the role and aim of each channel in the marketing funnel of persuasion and journey toward purchase (AIDA). Instagram imagery was demonstrated to foster a pre-consumption of the travel experience and emotionally charged reactions by representing perceptive and emotive expectations. While both channels play on postmodern tourists' desire for the uncontaminated, remote and the authentic, Instagram favors aerial views of pristine, aesthetically pleasant settings, often complemented with rear views of solitary individuals performing static processes of contemplation of natural wonders. This suggests a focus on attracting the attention and providing instant gratification of the senses by representing what stands in contrast to everyday life and traditional tourist experiences, both avoiding cognitive effort in a pervasive digital sphere with endless sources of information and encouraging further exploration on websites.

Exploring the readiness of hospice and oncology unit staff to offer spiritual support to patients: preliminary findings

Exploring the readiness of hospice and oncology unit staff to offer spiritual support to patients: preliminary findings

Hedges in interpreted and non-interpreted English: A cross-modal, corpus-based study

In this study, we adopt a monolingual, comparable, and cross-modal approach to investigate the use of hedges in interpreted and non-interpreted English speeches. To achieve this, we compile a corpus comprising speech data sourced from the interpreter-mediated Chinese government press conferences and the White House press conferences, respectively. Two research questions are formulated to guide our examination of hedging-related features in the corpus: (1) How does the use of hedges differ between interpreted English produced in different modes of interpreting (i.e., consecutive and simultaneous)? (2) How does the use of hedges in interpreted English differ from non-interpreted English? The results of our study show that interpreters, regardless of the consecutive and simultaneous mode, tend to employ significantly fewer hedges than spontaneous speakers of English. In addition, a vast majority of hedges in interpreted English stem from a relatively narrow range of core hedging devices. We posit that the underuse of hedges in interpreted English may be linked to constraints such as high cognitive pressure, rigid interactive structure, and source-language-related speech rhetoric conventions. Preliminary findings also suggest that the interpreting mode appears to exert little influence on the hedging patterns in the interpreters’ renditions. Potential factors underlying such a trend are briefly discussed.

Studi kasus pertumbuhan ikan lele (Clarias gariepinus) yang dibudidayakan oleh masyarakat Desa Oelbubuk, Desa Haumenibaki Di Kabupaten Timor Tengah Selatan

The African catfish (Clarias gariepinus) presents an opportunity for cultivation due to its rapid growth and high adaptability, making it a common choice for both industrial and household cultivation. This study aims to assess the growth and survival rates of African catfish (C. gariepinus) and compare these metrics between different groups. The research, spanning one month, will be conducted in two villages, Oelbubuk Village and Haumenibaki Village, located in the South Central Timor Regency. The methodology involves direct observation and sampling, with 100 catfish fry samples collected from each location, ranging in size from 5 to 9 cm. Parameters measured include growth in weight and absolute length, survival rates (SR), and water quality. Data collected will be analyzed descriptively and presented in tabular format. Preliminary findings indicate favorable growth and survival rates in Haumenibaki Village.
 
 Keywords: Survival rate, catfish and growth

Applying IROC Method in Patent Submission Evaluation in Indonesia: A Comparison with MAGIQ and AHP

This study applies the Improved Rank Order Centroid (IROC) to the Indonesian patent submission process within a Multi-Criteria Decision Making (MCDM) framework. The study evaluates four primary elements in patent assessment: "Patent Description," "Illustration," "Inventor's Ownership Statement," and "Rights Assignment Declaration." Preliminary findings indicate the importance of "Patent Description," followed by the other elements in descending order of significance. The evaluation also encompasses three applicant alternatives, with the Second Applicant emerging as the most favorable. The study further contrasts IROC outcomes with MAGIQ and AHP methodologies. While rank-based techniques like ROC and IROC generally produce similar weight distributions, the AHP method, which employs pairwise comparisons, often displays variations. The research underscores the potential of IROC in determining criterion weights, its comparison within the MAGIQ framework, and its validation through AHP. These insights aim to deepen our understanding of decision-making processes and analysis. The conclusion from comparing IROC results with MAGIQ and AHP indicates that the applicant rankings remain consistent. Therefore, further research is needed to understand the differences between evaluation methods and their impacts and explore the influence of cultural or regional factors in the patent submission process

Predicting likelihood of fraud among financial distressed firms in Malaysia using textual analysis

This research paper aims to analyze and predict fraud patterns among failed companies in Malaysia. The approach involves utilizing textual analysis on the management discussion and analysis (MD&A) section within the annual reports. The dataset is subjected to text clustering to group companies based on similar financial characteristics. This clustering process entails several steps, including data conversion, collation, and summarization into a structured format, followed by text pre-processing to cleanse the dataset. Notably, RapidMiner Studio software was utilized to extract data for the study. Subsequently, the documents are clustered using both the K-means and latent dirichlet allocation (LDA) methods. Upon examining a sample of 22 failed companies in the year 2020, the study reveals that financially distressed companies exhibit prominent financial negativity and utilize litigious financial terms within their MD&A sections. These linguistic traits are found to be closely associated with seven distinct characteristics of fraudulent firms. This preliminary findings provide compelling evidence that financial pressure may serve as a triggering factor for fraudulent activities within companies.

The Breakfast and Dressing Conflict Task: Preliminary Evidence of Its Validity to Measure Online Self-Awareness After Acquired Brain Injury.

Impaired self-awareness (SA) of deficits after an acquired brain injury (ABI) severely affects patients' independence in activities of daily living (ADLs). However, any assessment tool permits an exhaustive evaluation of SA in the context of ADLs. To study the validity of the Breakfast and Dressing Conflict Task (BD Conflict Task) to assess online SA (awareness of performance in the context of a given task) in patients with ABI; to study its interactions with offline SA (general awareness); and to test the validity of a simplified measure of performance monitoring, the ADL Conflict-Monitoring Index. Convergent validity and correlational study. Research laboratory, hospitals, and homes. Thirty patients with ABI and 28 neurologically healthy controls. Using the BD Conflict Task, measures of emergent awareness, self-regulation, anticipatory awareness, and self-evaluation were assessed and their convergent validity and relationship with offline SA were analyzed. The ADL Conflict-Monitoring Index was calculated, and its convergent validity was tested. The online SA variables of the BD Conflict Task showed convergent validity with traditional online SA measures. Offline SA correlated with emergent and anticipatory awareness in the Breakfast Task. The ADL Conflict-Monitoring Index proved to be a valid measure of patients' performance monitoring. These preliminary findings suggest that the BD Conflict Task is a valid tool to assess online SA in patients with ABI and provide further understanding of the online SA-offline SA interaction. Furthermore, the ADL Conflict-Monitoring Index may be a valid and easy-to-use monitoring measure in clinical settings. Plain-Language Summary: Patients with acquired brain injury (ABI) and reduced awareness of their cognitive deficits face problems performing activities of daily living (ADLs) and may show signs of unsafe behaviors. Being aware of one's own abilities involves anticipating problems before starting a task, detecting and correcting errors during the task, and evaluating performance afterward. This study provides preliminary validity for the Breakfast and Dressing Conflict Task, a new tool that assesses aspects of self-awareness simultaneously in the context of familiar and significant ADLs. Furthermore, the tool simplifies the assessment of detecting and correcting errors with an easy-to-use index, making it suitable for use in clinical settings.

Protective Effect of Nigella sativa Seed Extract and its Bioactive Compound Thymoquinone on Streptozotocin-induced Diabetic Rats.

The lack of a substantial breakthrough in the treatment of diabetes, a global issue, has led to an ongoing quest for herbs that contain bioactive elements with hypoglycemic properties. To investigate the potential protective effect of Nigella sativa seeds ethanol extract and its active ingredient, thymoquinone, on streptozotocin-induced diabetic rats. To induce diabetes, the male Wistar rats were administered an intraperitoneal injection of STZ at a dosage of 90mg/kg body weight in 0.9 percent normal saline after being fasted for 16 hours and made diabetic Group 1; 7 rats non-diabetic control (saline-treated), Group 2; 7 untreated diabetic rats, Group 3; 7 diabetic rats treated orally with N. sativa extract at a dose of 100mg/kg body weight, Group 4; 7 diabetic rats treated orally with thymoquinone at a dose of 10mg/kg body weight and Group 5; 7 diabetic rats treated orally with Metformin at a dose of 5mg/kg body weight. After the treatment of 28 days, all groups were examined for body weight and biochemical alterations. The results showed a significant decrease in blood glucose, urea, creatinine, uric acid, total protein, total cholesterol, low-density lipoprotein, and very low-density lipoprotein, while high-density lipoprotein was increased. Hepatic enzymes, alanine transaminase, aspartate aminotransferase, and alkaline phosphate were also normalized and significantly increased body weight. These preliminary findings demonstrate that the ethanol extract of N. sativa seeds and its active ingredient, thymoquinone have a protective effect against streptozotocin-induced diabetic rats. The present study opens new vistas for the use of N. sativa and its bioactive compound, thymoquinone, regarding its clinical application as a new nontoxic antidiabetic agent for managing diabetes mellitus.

Combined and sequential exposure to prenatal second hand smoke and postnatal maternal distress is associated with cingulo-opercular global efficiency and attention problems in school-age children

BackgroundPrenatal exposure to secondhand (environmental) tobacco smoke (SHS) is associated with adverse neurodevelopmental outcomes, including altered functional activation of cognitive control brain circuitry and increased attention problems in children. Exposure to SHS is more common among Black youth who are also disproportionately exposed to socioeconomic disadvantage and concomitant maternal distress. We examine the combined effects of exposure to prenatal SHS and postnatal maternal distress on the global efficiency (GE) of the brain's cingulo-opercular (CO) and fronto-parietal control (FP) networks in childhood, as well as associated attention problems. MethodsThirty-two children of non-smoking mothers followed in a prospective longitudinal birth cohort at the Columbia Center for Children's Environmental Health (CCCEH) completed magnetic resonance imaging (MRI) at ages 7–9 years old. GE scores were extracted from general connectivity data collected while children completed the Simon Spatial Incompatibility functional magnetic resonance imaging (fMRI) task. Prenatal SHS was measured using maternal urinary cotinine from the third trimester; postnatal maternal distress was assessed at child age 5 using the Psychiatric Epidemiology Research Interview (PERI-D). The Child Behavior Checklist (CBCL) measured Attention and Attention Deficit Hyperactivity Disorder (ADHD) problems at ages 7–9. Linear regressions examined the interaction between prenatal SHS and postnatal maternal distress on the GE of the CO or FP networks, as well as associations between exposure-related network alterations and attention problems. All models controlled for age, sex, maternal education at prenatal visit, race/ethnicity, global brain correlation, and mean head motion. ResultsThe prenatal SHS by postnatal maternal distress interaction term associated with the GE of the CO network (β = 0.673, Bu = 0.042, t(22) = 2.427, p = .024, D = 1.42, 95% CI [0.006, 0.079], but not the FP network (β = 0.138, Bu = 0.006, t(22) = 0.434, p = .668, 95% CI [−0.022, 0.033]). Higher GE of the CO network was associated with more attention problems (β = 0.472, Bu = 43.076, t(23) = 2.780, p = .011, D = 1.74, n = 31, 95% CI [11.024, 75.128], n = 31) and ADHD risk (β = 0.436, Bu = 21.961, t(29) = 2.567, p = .018, D = 1.81, 95% CI [4.219, 39.703], n = 30). ConclusionsThese preliminary findings suggest that sequential prenatal SHS exposure and postnatal maternal distress could alter the efficiency of the CO network and increase risk for downstream attention problems and ADHD. These findings are consistent with prior studies showing that prenatal SHS exposure is associated with altered function of brain regions that support cognitive control and with ADHD problems. Our model also identifies postnatal maternal distress as a significant moderator of this association. These data highlight the combined neurotoxic effects of exposure to prenatal SHS and postnatal maternal distress. Critically, such exposures are disproportionately distributed among youth from minoritized groups, pointing to potential pathways to known mental health disparities.

Abstract A009: Addressing obesity’s impact on the PTEN mutant endometrium

Abstract Obesity is a rising epidemic in the United States, with approximately 50% of adult women predicted to be obese by 2030. Obesity is a risk factor for endometrial hyperplasia (EH), which is characterized by the benign overgrowth of the endometrial epithelium and is considered a precursor lesion for endometrial cancer (EC). Somatic PTEN mutations are commonly observed in EH and EC, with PTEN loss being one of the earliest mutations observed in the progression to EC. Previous obesity work in our lab utilized high-fat diet (HFD)-induced obese WT mice and found that obesity affected different cell types within the endometrium, including non-tumor prone cells. Our preliminary findings suggest that 60% HFD prolongs the estrus stage of the estrus cycle in WT mice. The aims of this study are to determine the cell-specific effects of obesity on the endometrial epithelia carrying PTEN mutations. Female PTENfl/fl; Pax8Cre/+ mutant and Pax8Cre+/+ control mice on a C57BL/6J background were fed either a 60% HFD or it’s sucrose-matched control diet (CD) for a minimum of 22 weeks. Weekly mouse and food weights were collected. Mice were tested for glucose tolerance after being on diet for at least 4.5 months. Uterus and blood were collected at estrus stage. Uteri were processed for single-cell RNA seq. PTENfl/fl; Pax8Cre/+ mice on both the HFD and CD had a diminished weight gain compared to Pax8Cre+/+ mice on the same diet. HFD-treated mice exhibited hyperphagia, weighed significantly more than the CD mice, and demonstrated glucose intolerance. H&E staining of the adipose tissue and liver revealed adipocyte hypertrophy and fatty liver infiltration in HFD mice. IHC of PTENfl/fl; Pax8Cre/+ uteri confirmed epithelial-specific loss of PTEN and displayed endometrial hyperplasia. PTENfl/fl; Pax8Cre/+ uteri had an influx of Ly6G+ neutrophils invading the endometrial epithelium compared to the Pax8Cre+/+ mice. Strikingly in PTENfl/+; Pax8Cre/+ we observe clonal loss of PTEN immunoreactivity in a subset of endometrial glands with similar phenotypic features. We propose that obesity’s impact on non-tumor cell types within the endometrium will be shaped by early genetic mutations in tumor-prone epithelia. Citation Format: Hilary J. Skalski, Shannon K. Harkins, Amelia R. Arendt, Madison MacLachlan, Katelyn Becker, Marc Wegener, Marie Adams, Galen Hostetter, Ronald L. Chandler. Addressing obesity’s impact on the PTEN mutant endometrium [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A009.

The impact of active cytomegalovirus infection on donor-derived cell-free DNA testing in heart transplant recipients.

Little is known about the relationship between cytomegalovirus (CMV) infections and donor-derived cell-free DNA (dd-cfDNA) in heart transplant recipients. In our study, CMV and dd-cfDNA results were prospectively collected on single-organ heart transplant recipients. If the CMV study was positive, a CMV study with dd-cfDNA was repeated 1-3 months later. The primary aim was to compare dd-cfDNA between patients with positive and negative CMV results. Of 44 patients enrolled between August 2022 and April 2023, 12 tested positive for CMV infections, 25 were included as controls, and seven patients with a viral infection without CMV were excluded. Baseline characteristics did not differ significantly between CMV-positive and CMV-negative patients with the exception of a later median time post-transplant in the CMV-positive group (253 days vs. 120 days, p=.03). Dd-cfDNA levels were significantly higher in patients with CMV infections compared to those without (p<.001) with more patients in the CMV positive group showing dd-cfDNA results ≥.12% (75%vs. 8%, p<.001) and ≥.20% (58%vs. 8%, p=.002). Each 1 log10 copy/ml reduction in CMV viral load from visit 1 to visit 2 was associated with a.23% reduction in log10 dd-cfDNA (p=.002). Our findings suggest that active CMV infections may raise dd-cfDNA levels in patients following heart transplantation. Larger studies are needed to validate these preliminary findings.