Digital Commons Network^™

Hif-2-Dependent Regulation Of Pthrp And Paraneoplastic Hypercalcemia In Aggressive Clear-Cell Renal Cell Carcinoma, Arijit Mal, Bingqing Xie, Zane Gray, Charlotte Small, Susmita G Ramanand, Yunpeng Gao, Vanina Toffessi Tcheuyap, Sashi Debnath, Alana Christie, Jeffrey Miyata, Brooklyn Jackson, Hua Zhong, Boning Gao, Jay Lohrey, Naim M Maalouf, Sangeetha M Reddy, John D Minna, Ivan Pedrosa, Xiankai Sun, Ram S Mani, Payal Kapur, James Brugarolas

Faculty, Staff and Student Publications

Renal cell carcinoma (RCC) patients with hypercalcemia (HC) have worse outcomes. HC often involves PTHrP, and the role of HIF-2 is incompletely understood. Leveraging RCC tumorgraft (TG) models of HC, which were characterized by tumor cell autonomous inflamatory/immune signatures, we show that HIF-2 inhibition with PT2399 frequently normalized calcium, downregulated circulating PTHrP and reduced HIF-2 binding to the PTHLH (PTHrP) promoter. Likely contributing to the selective induction of PTHrP in a subset of HIF-2-dependent tumors, the PTHLH locus was generally more accessible in TG(HC). However, PTHLH chromatin accessibility was grossly unaffected by PT2399, unlike elsewhere (including EPO locus in a …

Using Gnotobiotic Mice To Decipher Effects Of Gut Microbiome Repair In Undernourished Children On Tuft And Goblet Cell Function, Yi Wang, Hao-Wei Chang, Jiye Cheng, Daniel M Webber, Hannah M Lynn, Matthew C Hibberd, Clara Kao, Ishita Mostafa, Tahmeed Ahmed, Michael J Barratt, Jeffrey I Gordon

2020-Current year OA Pubs

Studies have implicated perturbations in the postnatal development of the gut microbiome as a contributing factor to childhood undernutrition. Compared to a standard ready-to-use supplementary food, a microbiome-directed complementary food (MDCF-2) designed to repair these perturbations produced superior improvements in ponderal and linear growth in clinical trials of Bangladeshi children with moderate acute malnutrition. Here, "reverse translation" experiments are performed where intact fecal microbiomes collected from trial participants before and at the end of treatment are introduced into female gnotobiotic mice just after delivery of their pups. Pups received diets designed to resemble those consumed by children in the trials …

Statistically Significant Association Does Not Imply Improvement In Prediction Of Clinical Outcomes, Shu Jiang, Bernard A Rosner, Graham A Colditz

2020-Current year OA Pubs

UNLABELLED: In the current landscape of clinical studies, the concept of statistically significant association is often mixed up with the expectation of improved prediction performance. We discuss the two concepts, association and prediction, and present the epidemiologic principles and statistical constructs that underlie the discrepancy between statistically significant associations and the rationale for their lack of impact on improving prediction in terms of discrimination. This issue is illustrated using an existing breast cancer dataset. The concept of statistically significant association should not be mixed up with the expectation of improved discrimination performance. Although some markers may not markedly improve discrimination, …

Fucosylated N-Glycan Landscape Of Triple-Negative Breast Cancer, Danielle A Scott, Souvik Seal, Laura Spruill, Jaclyn Dunne, Graham Colditz, Anand S Mehta, Richard R Drake, Marvella E Ford, Peggi M Angel

2020-Current year OA Pubs

UNLABELLED: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer lacking targeted therapies. Although aberrant N-glycosylation is a hallmark of malignancy, the specific roles of core-fucosylated (CF) and outer arm-fucosylated (OAF) N-glycans in TNBC progression and patient survival remain underexplored. This study utilized multiplexed glycomics by matrix-assisted laser desorption/ionization imaging mass spectrometry to spatially profile 348 N-glycans in 59 TNBC tumors with clinical characteristics including survival data. Spatial analysis revealed distinct localization patterns of CF and OAF isomers within tumor microenvironments. Strikingly, OAF glycans, but not CF, were strongly associated with tumor stage, with expression increasing from stage …

Engaging Ukrainian Tf-Cbt Therapists In A Practice Skills Course To Support Their Wellbeing, Elisabeth Pollio, Esther Deblinger, Beth Cooper, Maike Garbade, Julie P Harrison, Elisa Pfeiffer

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Background: Burnout and secondary traumatic stress (STS) are common among therapists working with trauma-exposed clients, which can negatively impact them professionally and personally. The shared trauma of war exposure may put therapists at greater risk. To help support their wellbeing, an eight-session course was offered to Ukrainian therapists following training in Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). This course involves therapists personally utilizing the PRACTICE skills taught to clients in TF-CBT for professional and personal benefit.

Objective: The objective was to gather preliminary evidence on the potential impact of implementing the course with Ukrainian therapists providing TF-CBT during a period of …

Single-Cell Landscape Of Sex-Specific Drivers Of Alzheimer's Disease., Yiyang Wu, Kyle J Travaglini, Mariano Gabitto, C Dirk Keene, Amy R Dunn, Catherine C Kaczorowski, Philip L De Jager, Vilas Menon, Julie A Schneider, David A Bennett, Logan Dumitrescu, Timothy J Hohman

Faculty Research 2025

INTRODUCTION: We investigated sex-specific gene expression associations with the neuropathology and cognitive manifestation of Alzheimer's disease (AD) leveraging single-nucleus transcriptomic datasets including 2.84 million nuclei from the dorsolateral prefrontal cortex (DLPFC).

METHODS: We delineated the full scope of sex-specific transcript associations, differential gene expression, signaling pathway, and cell-cell communication network changes in eight major DLPFC cell types.

RESULTS: Nine female-specific associations were identified and replicated, involving ADGRV1, OR3A3, IFI27L1, LYRM1, STAP2, TSTD2, PDYN, and TMEM50B. We observed the preponderance of protective female-specific associations in neurons. Sex-specific genes were enriched in the immune-, inflammation-, and damage-related stress-response pathways. Six ITGB1-mediated microglia-specific …

Telehealth And Virtual Supervision Practices For Health Professions Education In The Department Of Veterans Affairs, Nancy D. Harada, Kimberly Falco, Marjorie Bowman, John M. Byrne

Population and Public Health Sciences Faculty Publications

Background Telehealth and virtual supervision practices in health professions clinical education has grown rapidly, including in the Department of Veterans Affairs (VA) which oversees the largest interprofessional training effort in the United States. Telehealth is the provision of healthcare that is provided remotely through telecommunication technology, and virtual supervision is clinical supervision of health professions trainees (HPTs) that occurs through telecommunication technology. In this study we evaluate participation in telehealth and virtual supervision for physician, nursing, and associated health HPTs, and describe prevalent themes concerning HPT perceptions of telehealth and virtual supervision. Methods The survey study cohort included 10,865 HPTs …

Help-Seeking Among Early Adolescents Who Use Physical Peer Violence, Kelli Franco, Elizabeth Baumler, Leila Wood, Heidi Adams Rueda, Jeffrey R Temple

Faculty, Staff and Student Publications

Despite accumulating research on help-seeking among violence victims, little is known about help-seeking among youth who use violence. In a racially and ethnically diverse sample of early adolescents (N=2,676; 50.3% female; Mage=12.67), participants self-reported physical bullying, physical fighting, physical dating violence perpetration, and help-seeking intentions over the past year. T-tests and one-way ANOVAs examined help-seeking by sex and race, respectively. Prevalence and comparisons of help-seeking across youth with and without any violence were examined. Youth who used any physical peer violence (n=965) reported lower help-seeking intentions than their peers, and among violent youth, males reported …

Dual-Level Pattern Tree For Visual Field Improves Glaucoma Progression And Polygenic Risk Prediction, Luo Song, Lucy Q. Shen, Louis R. Pasquale, Michael V. Boland, Sarah R. Wellik, Carlos Gustavo De Moraes, Ayellet Segre, Janey L. Wiggs, Constance Turman, Jonathan S. Myers, Tobias Elze, Nazlee Zebardast, David S. Friedman, Jae H. Kang, Mengyu Wang

Wills Eye Hospital Papers

PURPOSE: To develop a dual-level pattern tree to characterize visual field (VF) loss subtypes that can be used to better predict glaucoma progression and glaucoma polygenic risk scores (PRSs).

METHODS: This study included 113,030 patients from three datasets, each used for a specific purpose: (1) model training, (2) progression forecasting, and (3) PRS correlations. We applied archetypal analysis to cluster 24-2 VFs into trunk patterns and their branch patterns. The Cox regression model was used to forecast VF progression using mean deviation (MD) slope, MD-fast slope, total deviation (TD) pointwise slope, and visual field index (VFI) slope. Multivariable regression analyses …

A Feasibility Study Of Sexual Organ-Dose Sparing Volumetric Modulated Arc Therapy In Female Low Rectal Cancer Patients Treated With Three-Dimensional Conformal Radiation Therapy, Margaret Downes, Victoria Olsen, Andre Williams, Rendi Sheu, Maria Thor, Lucy Greenwald, Vishruta Dumane, Kristin Hsieh, Ayesha Ali, Orly Morgan, Michael Buckstein, Deborah Marshall

Department of Radiation Oncology Faculty Papers

BACKGROUND: Sexual dysfunction is a significant toxicity of pelvic radiation therapy (RT) for female rectal cancer patients and may be more common with intensity-modulated techniques compared to three-dimensional conformal radiation therapy (3D-CRT). However, limited research has evaluated dose sparing of female sexual organs at risk (OARs), particularly erectile tissues that are critical for sexual function.

PURPOSE: This feasibility study aimed to demonstrate the practicality of contouring and sparing female sexual OARs in rectal cancer RT by generating sexual organ-sparing volumetric modulated arc therapy (SO-VMAT) plans from a small 3D-CRT cohort and comparing dose distributions to guide future planning.

METHODS: Nine …

Reading Ability Underlies The Composite Effect For Arabic Words, Rayan Kouzy, Zahra Hussain

School of Psychology

The composite effect, originally demonstrated for faces, has recently been shown to suggest holistic processing of words. The effect is associated with reading fluency in Latin script, but not in nonalphabetic Chinese script, suggesting that script properties influence its relationship with reading expertise. We measured the composite effect for Arabic, a visually complex alphabetic script that offers a useful contrast against Latin and Chinese. Arabic-English bilinguals (N = 24), and English-only readers (N = 22) completed a composite effect task, in which they judged whether the left or right halves of word pairs were the same or different. The unattended …

Dna Methylation Markers Of Insulin Resistance Surrogate Measures In The Atherosclerosis Risk In Communities (Aric) Study, Jeewoen Shin, Jan Bressler, Megan L Grove, Michael Brown, Elizabeth Selvin, James S Pankow, Myriam Fornage, Alanna C Morrison, Chloé Sarnowski

Faculty, Staff and Student Publications

Insulin resistance (IR) is a risk factor for cardiovascular diseases and type 2 diabetes. Associations between DNA methylation (DNAm) and IR have been less studied in African ancestry (AA) populations than those of European ancestry (EA). We aimed to identify associations between whole blood DNAm and IR in up to 1,811 AA and 964 EA participants from the Atherosclerosis Risk in Communities (ARIC) study. We quantified IR using three surrogate measures: the homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride-glucose index (TyG), and the triglyceride glucose-body mass index (TyG-BMI). We used ancestry-stratified linear regression models to conduct epigenome-wide association …

Association Of Epigenetic Age Acceleration And Mitochondrial Dna-Based Aging Metrics Provides Insights Into Mechanisms Of Aging-Related Diseases, Mengyao Wang, Yinan Zheng, Meng Lai, Emmanuel Saake, Xue Liu, Xiuqing Guo, Kent D Taylor, Tianxiao Huan, Roby Joehanes, Drew R Nannini, Kai Zhang, Nicole J Lake, Christina A Castellani, Stephen S Rich, Jerome I Rotter, Yongmei Liu, Laura M Raffield, April P Carson, Myriam Fornage, Jiantao Ma, Dan E Arking, Lifang Hou, Daniel Levy, Chunyu Liu

Faculty, Staff and Student Publications

Investigating the interplay between mitochondrial DNA (mtDNA) variations and epigenetic aging metrics may elucidate biological mechanisms associated with age-related diseases. We estimated epigenetic age acceleration (EAA) metrics from DNA methylation data and derived mtDNA metrics, including heteroplasmic variants and mtDNA copy number (mtDNA CN) from whole genome sequencing. Linear regressions and meta-analyses were conducted to assess associations between EAA and mtDNA metrics, adjusting for chronological age, self-identified sex, and other covariates in 6,316 participants (58% female, 41% non-White Americans). Mediation analysis was conducted to examine whether EAA mediated the relationship between mtDNA CN and metabolic traits. A higher burden of …

Where, How, And How Much? A Multicenter Cohort Study Of The Relationship Across Lupus Decision-Aid Modality, Place Of Administration, Interruption And Viewing Completeness, And Patient-Reported Outcomes, Jasvinder A Singh, Mark Beasley, Larry R Hearld

Faculty, Staff and Students Publications

Objective: We assessed whether shared decision-making (SDM) and patient acceptability, feasibility, and overall satisfaction with a computerized patient decision aid (PtDA) for patients with systemic lupus erythematosus (SLE) differs by PtDA setting, modality, and the viewing experience.

Methods: Patients with SLE were invited to view a self-administered computerized SLE PtDA during regular clinic visits at 15 rheumatology clinics in an implementation trial. Patients completed a survey that included SDM measures including the decision conflict scale (DCS), Preparation for Decision Making (PDM) scale, and CollaboRATE scale, and we measured perceived patient acceptability, feasibility, and satisfaction. Patients viewed the SLE PtDA in …

Sleep-Disordered Breathing Subtypes And Future Diet Quality In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Cecilia Castro-Diehl, Tianyi Huang, Alexis C Wood, Jerome I Rotter, Stephen S Rich, Tamar Sofer, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Objectives: Sleep-disordered breathing (SDB) and diet quality impact cardiometabolic disease, but few studies have examined if SDB influences diet quality. This study estimated the association between SDB subtypes (with and without sleepiness) and future diet quality in the Multi-Ethnic Study of Atherosclerosis.

Methods: Probable SDB was characterized by self-reported physician-diagnosed sleep apnea (PDSA) or habitual snoring and subtyped by presence or absence of sleepiness. A food frequency questionnaire measured diet 1.6 years before, and 7.8 years after SDB assessment. Diet quality was measured with the Alternate Healthy Eating Index-2010 (AHEI). Mean differences in AHEI at follow-up by SDB subtypes were …

Insights From A Survey Of School Nurses: Assessing The Challenges Of Constipation In Schools, Andrew S Chu, Eric H Chiou

Faculty, Staff and Students Publications

Objectives: School nurses are key responders to students with constipation, yet their experiences are underreported. This study surveyed their observations regarding constipation, identified barriers to student restroom access, and assessed educational needs.

Methods: In this descriptive, cross-sectional survey study, an anonymous online survey was distributed to school nurses participating in a virtual education series. The survey assessed nurse demographics, frequency of encounters with constipation and encopresis, school restroom policies, barriers to restroom use, accommodation requests, and training in constipation management.

Findings: Of 125 respondents, 95% encountered students with constipation at least monthly and 55% reported ≥ 6 encounters monthly. Commonly …

Comparative Value Of Echocardiography Vs. Right Heart Catheterization In Heart Failure With Preserved Ejection Fraction, Nathanael Tran, Mohammad Shaar, Hussein Al-Sudani, Ramy Sedhom, Hamza Akhtar, Kevin Bryan Lo, Gregg S. Pressman

Einstein Health Papers

BACKGROUND: Echocardiography and right heart catheterization (RHC) are useful in the evaluation of heart failure with preserved ejection fraction (HFpEF). We compared the two among decompensated HFpEF patients to determine their relative value in predicting all-cause mortality and a composite of cardiovascular (CV) death and heart failure (HF) readmission at 1 year.

METHODS: One hundred seventy-eight decompensated HFpEF patients who underwent both procedures and survived to hospital discharge were retrospectively identified. Hospital records and the National Death Index were queried to determine outcomes. Echocardiographic and invasive parameters were tested for significant associations with each outcome. Additionally, three predictive models were …

Middle Meningeal Artery Embolization Of Septated Chronic Subdural Hematomas, Juan Carlos Martinez-Gutierrez, Salvatore A D'Amato, Hussein A Zeineddine, Michael I Nahhas, Matthew J Kole, Hyun Woo Kim, Youngran Kim, Bryden H Dawes, Peng Roc Chen, Spiros L Blackburn, Sunil A Sheth, Gary Spiegel, Ching-Jen Chen, Ashutosh Mahapatra, Ryan S Kitagawa, Mark J Dannenbaum

Faculty, Staff and Student Publications

Introduction

Middle meningeal artery embolization (MMAE) has emerged as a promising new treatment for patients with chronic subdural hematomas (cSDH). Its efficacy, however, upon the subtype with a high rate of recurrence—septated cSDH—remains undetermined.

Methods

From our prospective registry of patients with cSDH treated with MMAE, we classified patients based on the presence or absence of septations. The primary outcome was the rate of recurrence of cSDH. Secondary outcomes included a reduction in cSDH thickness, midline shift, and rate of reoperation.

Results

Among 80 patients with 99 cSDHs, the median age was 68 years (IQR 59–77) with 20% females. Twenty-eight …

Healthcare Professionals’ Awareness Of And Barriers To Shared-Clinical-Decision-Making For Hpv Vaccination Among Adults 27–45 Years, Manali Desai, Shreela V Sharma, Joel Fokom Domgue, Onyema Chido-Amajuoyi, Robert Yu, Wenyaw Chan, Charles Darkoh, Sanjay Shete

Faculty, Staff and Student Publications

The Advisory Committee on Immunization Practices recommends human papillomavirus (HPV) vaccination for inadequately vaccinated adults aged 27–45 based on shared clinical decision-making (SCDM). However, little is known about awareness and barriers to SCDM among US healthcare providers (HCPs), especially in Texas, where HPV vaccination rates are below the national average. Between January and April 2021, we conducted a population-based cross-sectional survey (12% response rate) of HCPs licensed in Texas to assess the prevalence and factors associated with awareness of the SCDM recommendation. HCPs were asked if they were aware and if they foresaw any barriers in implementing SCDM for HPV …

A Qualitative Study Of Health Priorities Of People With Dementia And Care Partners In Emergency Department And Hospital Care In A Public Safety-Net Setting, Anita Chary, Sumin Yoon, Victor Lara, Annika Bhananker, Michelle Suh, Kei Ouchi, Maura Kennedy, Aanand D Naik

Faculty, Staff and Student Publications

Background: Over half of the people with dementia visit the emergency department (ED) each year. Little is known about how people with dementia and their care partners conceptualize or communicate about health outcome goals or care preferences during acute care episodes.

Participants and setting: We conducted interviews with 14 Hispanic people with dementia and 19 care partners recruited from a public safety net hospital system in the southeastern United States. Participants were community-dwelling and had recently visited the ED.

Methods: We used a qualitative study design informed by phenomenology and guided by the patient priorities care (PPC) framework. Interviews elicited …

Maternal Folic Acid Supplement Use, Folate Intake, And Preterm Birth Among Infants With Spina Bifida, Renata H Benjamin, Katherine L Ludorf, Rachel P Allred, Jenil R Patel, Wendy N Nembhard, Gary M Shaw, Suzan L Carmichael, Tania A Desrosiers, Eirini Nestoridi, Eva M Williford, A J Agopian

Faculty, Staff and Student Publications

Background: We sought to assess the extent to which folic acid supplementation and dietary folate intake are associated with preterm delivery among infants with spina bifida.

Methods: We conducted a retrospective population-based study using the National Birth Defects Prevention Study (NBDPS; 1999-2011) and the Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS; 2014-2019). We utilized robust Poisson regression to calculate the risk ratio (RR) and 95% confidence interval (CI) for the associations between preterm birth (< 37 weeks) and maternal use of folic acid-containing supplements, dietary folate intake quartile, and a combined variable accounting for supplementation and dietary folate status.

Results: Among 1199 infants with spina bifida (1011 in NBDPS, 188 in BD-STEPS), 217 (18.1%) were born preterm. There were no statistically significant associations …

Ddt Exposure Induces Microglial Activation And Disease-Associated Microglial Signatures: Relevance To Mechanisms Of Alzheimer’S Disease, Isha Mhatre-Winters, Aseel Eid, Nicole Blum, Yoonhee Han, Ferass M Sammoura, Long-Jun Wu, Jason R Richardson

The Brown Foundation: Institute of Molecular Medicine

Background: Alzheimer's disease (AD) is characterized by the presence of amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the primary metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were significantly higher in AD patients compared to age-matched controls and that DDT exposure worsened AD pathology in animal models.

Objective: Here, we investigated the effect of DDT on neuroinflammation in primary mouse microglia (PMG) and C57BL/6J mice.

Methods: DDT-induced inflammatory and disease-associated microglial (DAM) gene expression were determined in PMG by qPCR and immunocytochemistry, with and without pretreatment with the sodium channel antagonist tetrodotoxin (TTX). Furthermore, …

Short-Term Preeclampsia Prediction: Cutoff Variations For Sflt-1/Plgf In U.S. Patients With Or Without Hypertensive Disorders, Yaxin Li, Kristen Cagino, Jim Yee, Caroline Andy, Dajana Borova, Ayush Shah, Isla Racine, Tracy Grossman, Zhen Zhao

Student Papers, Posters & Projects

BACKGROUND: Preeclampsia (PE) is a complex disorder with significant maternal and fetal risks. The soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio shows promise as a diagnostic tool, but its adoption in the U.S. remains limited due to the lack of accessible testing platforms, U.S.-based studies, and evidence-based implementation guidelines.

PATIENTS/MATERIALS AND METHODS: We conducted a cohort study to evaluate the sFlt-1/PlGF ratio for predicting PE within two weeks among pregnant individuals ≥18 years, ≥20 weeks gestation. Serum samples were obtained from routine prenatal visits or triage evaluations. sFlt-1/PlGF ratios were measured using Roche Elecsys assays, and …

Understanding Dental Hygienists’ Knowledge, Attitudes, And Practices Regarding Hpv Vaccination, Paula M Cuccaro, Jihye Choi, Kawtar Zouaidi, Efrat K Gabay, Michael Mackert, Josefine Ortiz Wolfe

Faculty, Staff and Student Publications

The American Dental Association and American Academy of Pediatric Dentistry encourage oral health professionals to strongly recommend human papillomavirus (HPV) vaccination to prevent HPV-associated oropharyngeal cancer. This study examined oral health professionals' knowledge, attitudes, and practices regarding HPV vaccination. We used purposive sampling to recruit participants through state and national oral health societies and social media platforms. Flyers outlining eligibility criteria were distributed, and eligible participants completed an online survey. Primary measures included participants' HPV-related knowledge, attitudes, and practices, and willingness to receive HPV-related training and recommend HPV vaccination to patients, including parents of adolescents. Only responses from dental hygienists …

Proteogenomics In Cerebrospinal Fluid And Plasma Reveals New Biological Fingerprint Of Cerebral Small Vessel Disease, Ilana Caro, Daniel Western, Shinichi Namba, Na Sun, Shuji Kawaguchi, Yunye He, Masashi Fujita, Gennady Roshchupkin, Tim D'Aoust, Marie-Gabrielle Duperron, Muralidharan Sargurupremraj, Ami Tsuchida, Masaru Koido, Marziehsadat Ahmadi, Chengran Yang, Jigyasha Timsina, Laura Ibanez, Koichi Matsuda, Yutaka Suzuki, Yoshiya Oda, Akinori Kanai, Pouria Jandaghi, Markus Munter, Daniel Auld, Iana Astafeva, Raquel Puerta, Jerome I Rotter, Bruce M Psaty, Joshua C Bis, W T Longstreth, Thierry Couffinhal, Pablo García-González, Vanesa Pytel, Marta Marquié, Amanda Cano, Mercè Boada, Marc Joliot, Mark Lathrop, Quentin Le Grand, Lenore J Launer, Joanna M Wardlaw, Myriam Heiman, Agustin Ruiz, Paul M Matthews, Sudha Seshadri, Myriam Fornage, Hieab Adams, Aniket Mishra, David-Alexandre Trégouët, Yukinori Okada, Manolis Kellis, Philip L De Jager, Christophe Tzourio, Yoichiro Kamatani, Fumihiko Matsuda, Carlos Cruchaga, Stéphanie Debette

Faculty, Staff and Student Publications

Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific treatment, of which molecular mechanisms remain poorly understood. To identify potential biomarkers and therapeutic targets, we applied Mendelian randomization to examine over 2,500 proteins measured in plasma and, uniquely, cerebrospinal fluid, in relation to magnetic resonance imaging (MRI) markers of cSVD in more than 40,000 individuals. Here we show that 49 proteins are associated with MRI markers of cSVD, most prominently in cerebrospinal fluid. We highlight associations that are consistent across platforms and ancestries, and supported by complementary observational analyses, and we explore differences …

High-Risk Medications In Pediatric Dentistry: Patterns, Outcomes, And Clinical Implications, Yilei Liu, Kawtar Zouaidi, Colin C Hubbard, Muhammad F Walji, Matthew R Cooke, Donald B Rindal, Kristin N Ray, Elsbeth Kalenderian, Katie J Suda

Faculty, Staff and Student Publications

Background: High-risk medications such as opioids and benzodiazepines are frequently prescribed in pediatric dental care, yet their prescribing patterns and associated adverse outcomes remain poorly understood. The aim of this study was to determine the extent of such prescribing to pediatric patients and factors associated with adverse outcomes.

Methods: MarketScan data for patients younger than 18 years with a dental visit from 2014 through 2019 were analyzed. High-risk medications included benzodiazepines, barbiturates, and opioids. Composite outcomes included hospitalization, emergency department visit, or urgent care visit within 7 days after the dental visit. Opioid-attributable outcomes included opioid-related overdose within 7 days …

Does Reducing Videofluoroscopy Frame Rate Affect Dige/St Grades In Modified Barium Swallow Studies?, Shitong Mao, Carla L Warneke, Sheila N Buoy, Ariana J Sahli, Brinda Rao Korivi, Carly E A Barbon, Kristy K Brock, Katherine A Hutcheson

Faculty, Staff and Student Publications

Understanding the effects of reduced frame rates on the reliability of Modified Barium Swallow (MBS) ratings for swallowing safety and efficiency is essential for clinical practice. While previous research has examined frame rate (simulated pulse rates) implications concerning penetration, aspiration, and residue ratings, the impact on summary grading systems like the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) remains unclear. This study analyzed a total of 315 full MBS videos collected from 278 patients, and 76.25% of patients were diagnosed with head and neck cancer (mean age 62.51 years, SD 8.53; 12.23% female). We performed pairwise comparisons of DIGEST grades …

Tumor Intrinsic Mettl5 Modulates Atf4 Translation To Prevent T Cell-Induced Ferroptosis In Ovarian Cancer, Jiakai Hou, Cheng-Wei Ju, Nicholas A Egan, Yanjun Wei, Yunfei Wang, Minghao Dang, Tianyi Zhou, Leilei Shi, Ningbo Zheng, Si Chen, Ashley M Guerrero, Xiaofang Liang, Wanfu Wu, Areej Akhtar, Chitra Dhiman, Debanwita Roy Burman, Andro E Gerges, Mason D Flores, Han Li, Li-Sheng Zhang, Marleen Kok, Xiaobo Mao, Linghua Wang, Qin Feng, Yiwen Chen, Sanghoon Lee, Daniel J Mcgrail, Nidhi Sahni, Chuan He, Amir A Jazaeri, Weiyi Peng

Faculty, Staff and Student Publications

Poor clinical responses to immune checkpoint blockade (ICB) observed in ovarian cancer (OC) highlight an unmet need to understand the mechanisms driving immune evasion in this disease. To address this, an integrative analysis is conducted by combining in vitro genome‐wide immune screens, in vivo ICB screens, and clinical data mining, and METTL5 is identified as a crucial OC‐intrinsic factor that promotes immune resistance. Immunologically “cold” OC tumors and poor responders to ICB exhibit elevated METTL5 expression. Mechanistically, knocking out (KO) METTL5 in OC disrupts ATF4 translation by altering 18S rRNA m6A levels, leading to the downregulation of SLC7A11 and SLC3A2 …

Perceived Utility Of Genetic Carrier Screening In A Diverse Patient Population, Jack A Colleran, Meagan Choates, Syed Hashmi, Brittanie Shelton, Aranza Gonzalez Cendejas, Angela Haynes Burgess, Blair K Stevens

Faculty, Staff and Student Publications

Current reproductive guidelines call for offering expanded carrier screening (ECS) for genetic conditions. Currently available panels can include screening for carrier status of tens to hundreds of autosomal recessive and/or X-linked conditions. Clinical utility is based on alterations to reproductive decision-making, but study cohorts supporting the utility of ECS largely consist of individuals of European ancestry who are highly educated, of high income, and who often receive preconception counseling. There is a lack of research on the views of patients from diverse backgrounds. Therefore, we aimed to assess and compare perceptions of the utility of ECS and targeted carrier screening …

Clinical Outcomes Of Adult Patients With Newly Diagnosed Mixed Phenotype Acute Leukemia, Hannah Goulart, Farhad Ravandi, Nicholas J Short, Nitin Jain, Naval Daver, Tapan M Kadia, Courtney Dinardo, Gautam Borthakur, Koichi Takahashi, Naveen Pemmaraju, Fadi G Haddad, Guillermo Montalban Bravo, Yesid Alvarado, Ghayas C Issa, Alex Bataller, Sherry Pierce, Sanam Loghavi, Guilin Tang, Sa A Wang, Beenu Thakral, Elizabeth Shpall, Richard Champlin, Issa Khouri, Partow Kebriaei, Guillermo Garcia-Manero, Koji Sasaki, Elias J Jabbour, Jayastu Senapati

Faculty, Staff and Student Publications

Purpose: Mixed phenotype acute leukemia (MPAL) is a rare clinical entity with historically poor outcomes.

Methods: We conducted a retrospective analysis of adults 18 years and older with newly diagnosed B-cell (B/M) or T-cell/myeloid (T/M) MPAL treated at our institution between 2017 and 2024.

Results: We identified 42 patients (median age 70 years); 20 (48%) had B/M MPAL, and 22 (52%) had T/M MPAL; 57% of patients had adverse risk cytogenetics, and 41% had a TP53 mutation. Sixty-two percent of patients were treated with a hybrid regimen, and 45% of patients received intensive therapy. A composite complete remission (CRc; CR …