Investigative Techniques Commons^™

Reliability And Spatial Consistency Of Mr Diffusion Tensor Imaging Measures Along The Cerebral Perivascular Space, Enchao Qiu, Joga Chaganti, Phillip Phan, M. Alizadeh, Devon Middleton, Kiran Talekar, Prabath Mondel, Scott H. Faro, Feroze Mohamed, Hsiangkuo Yuan

Department of Radiology Faculty Papers

BACKGROUND AND PURPOSE: Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) has emerged as a promising noninvasive method for evaluating water motion that may reflect glymphatic system function. However, the reliability of DTI-ALPS measurements across different region-of-interest (ROI) selection methods remains underinvestigated. This study aimed to assess the interrater reliability among three neuroradiologists in native space and compare DTI-ALPS indices derived from ROIs placed in subjects' native space versus standardized Montreal Neurological Institute (MNI) space.

METHODS: DTI-ALPS indices from 16 healthy subjects were calculated from both left and right hemispheres using two ROI placement approaches: (1) native space ROIs …

Development Of Emerin Mrna Lipid Nanoparticles To Rescue Myogenic Differentiation., Nicholas Marano, Liza Elif Guner, Rachel S Riley, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Emery-Dreifuss muscular dystrophy 1 (EDMD1) arises from mutations in EMD. Most EDMD1 patients lack detectable emerin expression. They experience symptoms such as skeletal muscle wasting, joint contractures, and cardiac conduction defects. Currently, physicians rely on treating patient symptoms without addressing the underlying cause-lack of functional emerin protein. Thus, there is a need for therapeutic approaches that restore emerin protein expression to improve patient outcomes. One way would be to deliver emerin mRNA or protein directly to affected tissues to restore tissue homeostasis. Here, we evaluated the utility of lipid nanoparticles (LNPs) to deliver emerin mRNA to diseased cells. LNPs …

Discontinuation Rates And Predictors Of Medical Cannabis Cessation For Chronic Musculoskeletal Pain, Mohammad Khak, Sina Ramtin, Juliet Chung, Asif M. Ilyas, Ari Greis

Rothman Institute Papers

Medical cannabis (MC) is increasingly used as a treatment for chronic musculoskeletal pain, but there is limited data on factors influencing its discontinuation. This study aims to investigate the rates of MC discontinuation and explore factors influencing it in patients with chronic musculoskeletal pain. A retrospective analysis was conducted on 78 patients certified for medical cannabis over a 2 year period. Patient demographics, pain origin, and Global Physical Health (GPH) and Global Mental Health (GMH) scores were collected before intervention. Discontinuation rates were measured at three-month and one-year follow-up. Statistical analyses, including Fisher's Exact Test and two-sample t-tests, were performed …

Feasibility And Preliminary Efficacy Of A Lymphedema And Fibrosis Self-Management Program For Head And Neck Cancer Survivors: A Pilot Randomized Controlled Trial, Jie Deng, Barbara Murphy, Lucy Andersen, Erin Mcmenamin, John Lukens, Joy Cohn, Karthik Rajasekaran, Ryan Quinn, Bryan Spinelli, Alexander Lin

Department of Physical Therapy Faculty Papers

OBJECTIVES: Survivors of head and neck cancer (HNC) are at high risk for developing lymphedema and fibrosis (LEF). Once diagnosed with LEF, survivors must engage in a lifelong program of self-care to minimize long-term adverse effects. However, evidence-based LEF self-management (SM) programs are lacking. To fill this void, we developed and pilot-tested a LEF-SM program for HNC survivors.

MATERIALS AND METHODS: The LEF-SM Program was developed using the Information-Motivation-Behavioral Skills model of health behavior change as a framework. The program was pilot tested in a three-group randomized controlled trial evaluating feasibility and preliminary efficacy. Fifty-nine participants were randomized to: Usual …

The Effect Of Hcv On Methadone Dose During Pregnancy, Sarah Boudova, Neel S. Iyer, Danielle M. Tholey, Jonathan M. Fenkel, Rupsa C. Boelig

Department of Obstetrics and Gynecology Faculty Papers

Pregnancy is a time of high patient motivation to initiate treatment for opioid use disorder (OUD). Hepatic drug metabolism can be altered by pregnancy and hepatitis C virus (HCV) infection. We aimed to examine the impact of HCV during pregnancy on methadone dosing. Retrospective chart review of all pregnant patients with OUD admitted for initiation of methadone from 1/2020-6/2022. Associations were examined using Student's T-tests, chi-squared tests, Fisher's exact tests and univariate and multivariate linear regression. We identified 191 pregnancies initiated on methadone, of which 188 were screened for HCV. 111 (59.0%) were HCV Antibody (Ab)+, of whom 108 were …

Quantile Index Predictors Using R Package Hyper.Gam, Tingting Zhan, Misung Yi, Inna Chervoneva

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

MOTIVATION: Evaluation of single-cell protein expression from immunohistochemistry images is used increasingly in biomedical research. Many proteins are used solely for phenotyping cells in the tumor microenvironment. Other proteins with meaningfully quantitative expression levels provide so-called functional protein biomarkers. There is still a limited number of methods and software tools available for utilizing the entire distributions of single-cell expression levels.

RESULTS: We present the R package hyper.gam, providing a supervised learning framework for deriving biomarkers based on single-cell distribution quantiles. The single-cell data are first converted into sample quantile functions, which are then used as predictors in scalar-on-function regression models …

Elevated Nr2f1 Underlies The Persistence Of Invasive Disease After Treatment Of Braf-Mutant Melanoma, Manoela Tiago, Timothy J. Purwin, Casey D. Stefanski, Renaira Oliveira Da Silva, Mitchell E. Fane, Yash Chhabra, Jelan I. Haj, Jessica L. F. Teh, Rama Kadamb, Weijia Cai, Sheera Rosenbaum, Vivian Chua, Nir Hacohen, Michael A. Davies, Jessie Villanueva, Inna Chervoneva, Ashani T. Weeraratna, Dan A. Erkes, Claudia Capparelli, Julio A. Aguirre-Ghiso, Andrew E. Aplin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite the success of targeted inhibitors in cutaneous melanoma, therapeutic responses are limited by the aged tumor microenvironment and drug-tolerant residual cells. Given the similarities between drug tolerance and cellular dormancy, we studied the dormancy marker, nuclear receptor subfamily 2 group F member 1 (NR2F1), in response to BRAF-V600E inhibitors (BRAFi) plus MEK inhibitors (MEKi) in BRAF-mutant melanoma models. Transcriptomic analysis of melanoma patient samples treated with BRAFi + MEKi showed increased NR2F1. NR2F1 was highly expressed in the drug-tolerant invasive cell state of minimal residual disease in patient-derived and mouse-derived xenografts on BRAFi + MEKi. NR2F1 over-expression was sufficient …

Effects Of Maackia Amurensis Seed Lectin (Masl) On Oscc Cell Morphology, Pdpn Expression, Growth, And Motility In A Phase 1 Clinical Trial, Ariel C Yin, Cayla J Holdcraft, Tyler J Hellmig, Eamonn J Brace, David I Suster, Alan J Shienbaum, Dylan Roden, Evelyne Kalyoussef, Ghayoour Mir, Eugenio Capitle, Soly Baredes, Rabie M Shanti, Mika K Kaneko, Yukinari Kato, Hisataka Kobayashi, Aki Furusawa, Mahnaz Fatahzadeh, Gary S Goldberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Podoplanin (PDPN) has emerged as a functionally relevant biomarker and chemotherapeutic target expressed by OSCC cells. PDPN signaling can directly increase tumor cell invasion and metastasis, and also inhibit host lymphocyte activation and immune response. Accordingly, antibodies and Maackia amurensis seed lectin (MASL) can target the PDPN receptor to inhibit OSCC cell migration and viability. However, the effects of MASL on OSCC cells in oral cancer patients has not yet been reported.

METHODS: We conducted a Phase 1 human clinical trial to examine the effects of a single 100 mg oral dose of MASL on OSCC cell morphology, PDPN …

Utility Of The Us Preventive Services Task Force For Preeclampsia Risk Assessment And Aspirin Prophylaxis, Thomas Mcelrath, Arun Jeyabalan, Arkady Khodursky, Alison Moe, Manfred Lee, Maneesh Jain, Laura Goetzl, Elizabeth Sutton, Pamela Simmons, George Saade, Antonio Saad, Luis Pacheco, Esther Park-Hwang, Antonina Frolova, Ebony Carter, Ai-Ris Collier, Daniel Kiefer, Vincenzo Berghella, Rupsa Boelig, Michal Elovitz, Cynthia Gyamfi-Bannerman, Joseph Biggio, Kara Rood, William Grobman, Carrie Haverty, Morten Rasmussen

Department of Obstetrics and Gynecology Faculty Papers

IMPORTANCE: The US Preventive Services Task Force (USPSTF) guidelines on preeclampsia risk assessment and aspirin prophylaxis (AP) have not been evaluated for clinical utility.

OBJECTIVE: To evaluate which characteristics in the USPSTF guidelines identify risk status and the association of preeclampsia risk with AP recommendations.

DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study enrolled from July 2020 to March 2023 with data analysis performed from October to December 2024. Enrollment occurred at 11 centers throughout the US or via direct-to-participant recruitment. Pregnant participants aged 18 years or older with a singleton pregnancy less than 22 weeks' gestation were selected via …

Risk Factors For In-Stent Stenosis After Flow-Diverter Implantation For Intracranial Aneurysm: A Single Center Analysis Of 161 Consecutive Patients, Rabab Alshahrani, Spyridon Karadimas, Mohammed Ali Alvi, Patrick Joseph Nicholson, Timo Krings

Department of Neurosurgery Faculty Papers

INTRODUCTION: Flow diverters (FD) are used for the treatment of intracranial aneurysms, by redirecting flow and serving as a scaffold for endothelial coverage of the aneurysm ostium. However, in-stent stenosis has been observed in some patients treated with these devices, the cause of which and the epidemiology remaining elusive. In the current study we aimed to elucidate potential factors leading to higher degree of in-stent stenosis including gender, location, and type of FD.

METHODS: The authors queried their institutional Electronic Health Record (EHR) for all patients undergoing FD for intracranial saccular aneurysms. We excluded cases where an FD was performed …

Integrase-Deficient Lentiviral Vector As A Platform For Efficient Crispr/Cas9-Mediated Gene Editing For Mucopolysaccharidosis Iva, Fnu Nidhi, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disorder causing systemic skeletal dysplasia due to a deficiency of N-acetyl-galactosamine-6-sulfate sulfatase (GALNS) enzyme activity, leading to the impaired degradation and accumulation of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate. While treatments such as enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) are available, they have significant limitations regarding efficacy in skeletal tissues and long-term safety, highlighting the need for more effective therapies. We evaluated a novel gene therapy approach using a dual Integrase-deficient lentiviral vector (IDLV) to deliver an expression cassette that includes human GALNS cDNA and Cas9 sgRNA, …

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Seeking Into Cell-Free Therapies For Bone-Affected Lysosomal Storage Disorders, Andrés Felipe Leal, Harry Pachajoa, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Lysosomal storage disorders (LSDs) constitute a group of monogenic systemic diseases resulting from deficiencies in specific lysosomal enzymes that cause the intralysosomal accumulation of non- or partially degraded substrates, leading to lysosomal dysfunction. In some cases of LSDs, the bone is more severely affected, thus producing skeletal manifestations in patients. Current therapies, such as enzyme replacement therapy (ERT) and gene therapy (GT), show limited efficacy in correcting skeletal abnormalities. Increasing evidence suggests that microenvironmental disturbances also contribute significantly to disease pathogenesis. Therefore, therapeutic strategies targeting lysosomal dysfunction and microenvironmental dysregulation are needed. Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) are emerging as …

Pilot Survey Of Attitudes Toward Xenotransplantation Among Nursing Students In London, Uk., Daniel Rodger, Luz A. Padilla, Daniel J. Hurst, David K C Cooper, Gilberto Buzzi, Antonio Ríos

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Solid organ xenotransplantation has been approved for clinical trials in the United States. Because of the role of nurses in patient decision-making, it is important to understand the attitudes of the future nursing workforce toward xenotransplantation. This pilot study aimed to investigate the attitudes of adult nursing students toward xenotransplantation.

METHODS: A cross-sectional survey design was used. The online pilot survey was completed by 33 undergraduate adult nursing students at one university in London, England. A minority of the hospitals that students may have had a clinical placement in had a transplant unit. The protocol for this study was …

Validation Of Established Thyroid Ultrasound Volume Norms In A Chernobyl Cohort, Lydia B. Zablotska, Robert J. Mcconnell, Aleksandr V. Rozhko, Patrick O'Kane, Vasilina Yauseyenka, Mark P. Little, Victor Minenko, Vladimir Drozdovitch, Tamara Moskvicheva, Maureen Hatch, Tamara Yeudachkova, Kiyohiko Mabuchi, Elizabeth K. Cahoon

Department of Radiology Faculty Papers

OBJECTIVE: To establish thyroid ultrasound volume norms appropriate for studies of diffuse goiter in a cohort of children and adolescents from an iodine-deficient population exposed to 131I by the Chernobyl fallout.

METHODS: A cohort of 11,970 Belarusians aged ≤18 years at the time of the 1986 Chernobyl accident with individual thyroid radiation dose estimates was screened 10-18 years later. From these, a low-dose subset of 2,392 with no thyroid diseases was selected to construct age- and sex-specific normative values for thyroid ultrasound volume, compared to Belarusian Ministry of Health (MOH) norms and existing WHO and European standards.

RESULTS: Cohort-specific values …

Individualized Functional And Structural Language Lateralities In Temporal Lobe Epilepsy And Their Impact On Memory, Ankeeta Ankeeta, Qirui Zhang, Sam Sharifzadeh Javidi, Shilpi Modi, Michael R. Sperling, Joseph I. Tracy

Department of Neurology Faculty Papers

The basis and impact of functional asymmetries in the brain, particularly language lateralization, are not fully understood, and the relationship between functional and structural asymmetries remains largely untested. This study investigated the degree to which asymmetries in hemispheric language laterality are concordant with asymmetries in gray matter (GM) structure and whether the hemispheric organization of memory is influenced by functional language asymmetries. Structural and functional MR data was acquired from 261 individuals, including those with unilateral temporal lobe epilepsy (LTLE = 96, RTLE = 69) and matched with healthy participants (HPs = 96). Functional language laterality indices (LIs) were calculated …

Comparison Of Open And Laparo-Endoscopic Repair Techniques For Patients With Bilateral Inguinal Hernias, Divyansh Agarwal, Tina Bharani, Nora Fullington, Lauren Ott, Kortney Hodgson, Daelyn Mcclain, Kaela Blake, Michael Reinhorn

Department of Surgery Faculty Papers

INTRODUCTION: For primary bilateral inguinal hernias, international guidelines favor a laparoscopic posterior mesh repair due to relatively lower risk of acute and chronic pain, faster recovery, and favorable biomechanical properties compared to open anterior approaches (Lichtenstein, plug and patch, etc.). However, studies comparing open mesh-based bilateral inguinal hernia repairs to bilateral laparoscopic and robotic mesh-based approaches are limited. The Abdominal Core Health Quality Collaborative (ACHQC) registry includes longitudinal data on bilateral inguinal hernia repairs performed via open as well as laparo-endoscopic approaches. We hypothesize that outcomes for bilateral inguinal hernia repair are similar between open and laparo-endoscopic approaches in the …

Long-Term Non-Conditional And Conditional Metastasis Of Uveal Melanoma By Tumor Size Category In 8034 Patients, Rolika Bansal, Hidayet Sener, Jerry A. Shields, Carol L. Shields

Wills Eye Hospital Papers

PURPOSE: To estimate metastasis of patients with uveal melanoma (UM) based on tumor size categories classified by ultrasonographic thickness as small (0.0-3.0 mm), medium (3.1-8.0 mm), or large (≥8.1 mm) using both non-conditional and conditional analyses.

DESIGN: Retrospective analysis.

METHODS: A retrospective study of 8034 cases over 35-years at a single ocular oncology referral center evaluated the primary endpoint of cumulative incidence of metastasis at 5-, 10-, 15-, 20-, 25- and 30-years using non-conditional and conditional analysis at 3-years, 5-years, and 10-years of metastasis-free survival.

RESULTS: The mean thicknesses for small, medium, and large UMs were 2.5 mm, 5.0 mm, …

Colorectal Cancer And The Risk Of Mortality Among Individuals With Suicidal Ideation, Srikanta Banerjee, Jagdish Khubchandani, Stanley Nkemjika

Department of Psychiatry and Human Behavior Faculty Papers

Suicide is a major public health problem that has grown at alarming rates in the last two decades. Colorectal cancer (CRC) is one of the most common causes of cancer deaths in the United States in both males and females. However, the influence of suicidal ideation (SI) on the association between CRC and risk of mortality has not been well examined.

METHODS: For this study, the 2005-2018 National Health and Nutrition Examination Survey (NHANES), a nationally representative survey of United States adults aged 20 years or older, was utilized. CRC survivorship was determined from self-reported data on CRC, and mortality …

A Smart Pill Bottle And Text Messaging Intervention For Promoting Medication Adherence In Patients With Chronic Myeloid Leukemia: A Pilot Study Of Txt4 Tki, Kuang-Yi Wen, Neil Palmisiano, Rita Smith, Rachel Slamon, Gina Keiffer, Christian Fidler, Margaret Kasner, Lindsay Wilde, Md

Department of Medical Oncology Faculty Papers

BACKGROUND: Patients undergoing tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) often face challenges with adherence, despite the efficacy of the treatment. Theory-guided and evidence-informed interventions addressing psychosocial and adherence barriers are critical for promoting adherence. Using a mixed-method approach, the pilot study developed and evaluated the feasibility and potential impact of an intervention "txt4TKI," to support medication and symptom management among CML patients undergoing TKI therapy.

METHODS: Guided by the Necessity and Concerns framework, the study comprised two phases: Phase 1 involved qualitative patient needs assessment interviews informing intervention design. Phase 2 was a single-arm pilot study …

Tacrolimus Dosing In Liver Transplant Recipients Using Phenotypic Personalized Medicine: A Phase 2 Randomized Clinical Trial, Jeffrey Khong, Megan Lee, Curtis Warren, Un Kim, Sergio Duarte, Kenneth Andreoni, Sunaina Shrestha, Mark Johnson, Narendra Battula, Danielle Mckimmy, Thiago Beduschi, Ji-Hyun Lee, Derek Li, Chih-Ming Ho, Ali Zarrinpar

Department of Surgery Faculty Papers

Tacrolimus is the most commonly used immunosuppression drug after solid organ transplantation; however, its dosing is challenging due to substantial inter-individual variability, often resulting in blood levels that deviate from the target therapeutic range. We explored whether a dynamically customized, phenotypic-outcome-guided drug dosing method could improve maintenance of drug trough levels within pre-determined target ranges, focusing on tacrolimus immediately after liver transplantation. This single-center, partially blinded, completed clinical trial involved 62 adults undergoing liver transplantation, block randomized into parallel groups: standard-of-care (SOC) clinician-determined or Phenotypic Personalized Medicine (PPM)-guided tacrolimus dosing. The primary outcome was percentage of post-transplant days with large …

Causes Of Death Among Us Medical Residents, Nicholas A. Yaghmour, William E. Bynum, Frederic W. Hafferty, Karen D. Könings, Thomas Richter, Timothy P. Brigham, Thomas J. Nasca

Division of Nephrology Faculty Papers

IMPORTANCE: From 2000 to 2014, the leading causes of medical resident death in the United States were neoplastic diseases and suicide.

OBJECTIVE: To examine whether US medical resident rates of death have changed since 2014 and whether causes of resident death differ by specialty.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, residents and fellows who were enrolled in Accreditation Council for Graduate Medical Education (ACGME)-accredited training programs and who died from January 2015 to December 2021 were submitted to the National Death Index to obtain causes of death. These decedents were compared with residents and fellows who died between …

Normative Variability In Retinal Nerve Fiber Layer Thickness: Does It Matter Where The Peaks Are?, Sowjanya Gowrisankaran, Ashkan Abbasi, Xubo Song, Joel Schuman, Gadi Wollstein, Bhavna Antony, Hiroshi Ishikawa

Wills Eye Hospital Papers

PURPOSE: Retinal nerve fiber layer thickness (RNFLT), a glaucoma biomarker, has a wide normative range affecting its sensitivity and specificity for abnormality detection. The interindividual RNFLT peak location variability contribution to this wide normative range has not been directly evaluated. The purpose of this study is to assess the effect of RNFLT peak normalization (PN) on normative variability.

METHODS: Circumpapillary RNFLT profiles at 1.7 mm radius from the optic nerve head (ONH) were re-sampled from optical coherence tomography (OCT) volumes (Cirrus HD-OCT, 200 × 200) obtained from one eye of 83 healthy individuals. Fovea-ONH axis (FOA) was calculated from corresponding …

Physical Activity Measurement Reactivity Among Midlife Adults With Elevated Risk For Cardiovascular Disease: Protocol For Coordinated Analyses Across Six Studies., Kiri Baga, Gabrielle M Salvatore, Iris Bercovitz, Amanda L Folk, Ria Singh, Laura M König, Meghan L Butryn, Jacqueline A Mogle, Danielle Arigo

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of death in the United States, and adults aged 40-60 years with specific health conditions are at particularly elevated risk for developing CVD. Physical activity (PA) is a key cardioprotective behavior and many interventions exist to promote PA in this group. Effective promotion requires accurate assessment of PA behavior; as PA is often estimated by averaging across multiple days, a threat to accurate assessment is measurement reactivity, or an atypical increase in PA behavior at the start of measurement periods that may bias conclusions. Evidence for PA measurement reactivity is equivocal, though …

Plasma Proteomic Biomarkers Of Physical Frailty In Heart Failure: A Propensity Score Matched Discovery-Based Pilot Study, Quin Denfeld, Noelle Pavlovic, Christopher Lee, Jon Jacobs, Mary Roberts Davis, Samantha Powell, Marina Gritsenko, Susan Joseph, Beth Habecker

Division of Cardiology Faculty Papers

BACKGROUND: Physical frailty is highly prevalent in heart failure (HF), but we lack an understanding of the underlying pathophysiology. Proteomic evaluation of plasma samples may elucidate potential mechanisms and biomarkers of physical frailty in HF.

OBJECTIVES: We aimed to identify plasma proteomic biomarkers that are differentially expressed between physically frail and non-physically frail adults with HF.

METHODS: This was a secondary analysis of a subset of data and plasma samples from a study of frailty among patients with New York Heart Association (NYHA) Functional Classification I-IV HF. Physical frailty was measured using the Frailty Phenotype Criteria. Propensity score matching was …

Molecular Subtyping Of Hypertensive Disorders Of Pregnancy, Michal Elovitz, Elaine Gee, Nathaniel Delaney-Busch, Alison Moe, Mitsu Reddy, Arkady Khodursky, Johnny La, Ilma Abbas, Kay Mekaru, Hunter Collins, Farooq Siddiqui, Rory Nolan, Rupsa Boelig, Daniel Kiefer, Pamela Simmons, George Saade, Antonio Saad, Ebony Carter, Thomas Mcelrath, Stephen Quake, Mark Depristo, Carrie Haverty, Manfred Lee, Eugeni Namsaraev, Vincenzo Berghella, Ai-Ris Collier, Antonia Frolova, Esther Park-Hwang, Luis Pacheco, Elizabeth Sutton, Maneesh Jain, Kara Rood, William A Grobman, Joseph Biggio, Cynthia Gyamfi-Bannerman, Arun Jeyabalan, Morten Rasmussen

Department of Obstetrics and Gynecology Faculty Papers

Hypertensive disorders of pregnancy (HDP), including preeclampsia, affect 1 in 6 pregnancies, are major contributors to maternal morbidity and mortality, yet lack precision medicine strategies. Analyzing transcriptomic data from a prospectively-collected diverse cohort (n = 9102), this study reveals distinct RNA subtypes in maternal blood, reclassifying clinical HDP phenotypes like early/late-onset preeclampsia. The placental gene PAPPA2 strongly predicts the most severe forms of preeclampsia in individuals without pre-existing high risk factors, months before symptoms, and its overexpression correlates with earlier delivery in a dose-dependent manner. Further, molecular subtypes characterized by immune genes are upregulated in less severe forms of HDP. …

Larotrectinib Compared With Real-World Non-Tropomyosin Receptor Kinase Inhibitor Therapies In Patients With Tropomyosin Receptor Kinase Fusion Cancer, Marcia S. Brose, C. Benedikt Westphalen, Xiaoyun Pan, Vadim Bernard-Gauthier, Milena Kurtinecz, Helen Guo, Virginie Aris, Neil R. Brett, Abdelali Majdi, Vivek Subbiah, Nathan A. Pennell, Kenneth L. Kehl, Alexander Drilon

Kimmel Cancer Center Faculty Papers

PURPOSE: Neurotrophic tyrosine receptor kinase gene fusions are oncogenic drivers of various solid tumors. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor approved for patients with TRK fusion cancer on the basis of single-arm trials. This study was a matched comparative effectiveness study of larotrectinib in clinical trials versus standard of care (SOC) in the real-world (RW) setting.

METHODS: Adult patients with advanced/metastatic TRK fusion non-small cell lung cancer, colorectal cancer, soft tissue sarcoma, thyroid cancer, or salivary gland carcinoma were included. Deduplicated data from RW patients were from US and ex-US data sources. Patients in the larotrectinib …

Evaluating Artifact-Free Four-Dimensional Computer Tomography With 16 Cm Detector Array, Inhwan Yeo, Wei Nie, Jiajin Fan, Mindy Joo, Michael Correa, Qianyi Xu

Department of Radiation Oncology Faculty Papers

PURPOSE: To evaluate a 16 cm-array axial four-dimensional computer tomography (4DCT) in comparison with a 4 cm-array 4DCT in the presence of respiration irregularity.

METHOD: Ten traces of lung tumor motion from CyberKnife treatments were imported to move the lung cylinder, containing a spherical target, of a phantom. Images were acquired for the lung that moved to each of the 10-positions/phases (1) step-wisely by nominal helical scan at each movement (ground truth), (2) continuously by 4D scan with the 16 cm array, and (3) the same with the 4 cm array, involving table shift. Irregularities, consisting of baseline shift and/or …

Effect Of Testosterone Treatment During Puberty In Boys With Klinefelter Syndrome (The Tipy Study): Protocol For A Nationwide Randomised, Double-Blinded, Placebo-Controlled Study, Ida Dyhr Caspersen, Andrés Felipe Østergaard Fritzbøger, Jørgen Holm Petersen, Niels Birkebæk, Ann-Margrethe Rønholt Christensen, Anders Jørgen Schou, Kurt Kristensen, Judith L. Ross, Shanlee Davis, Gary Butler, Sophie Van Rijn, Anders Juul, Lise Aksglaede

Department of Pediatrics Faculty Papers

INTRODUCTION: Klinefelter syndrome (KS) is a genetic condition characterised by the presence of an extra X chromosome in males (47,XXY). KS is associated with various phenotypic characteristics in adult life, including infertility, hypogonadism and increased risk of type II diabetes, cardiovascular disease and osteoporosis. Additionally, individuals with KS often experience mental health challenges and functional impairments that significantly impact their quality of life. Currently, testosterone replacement therapy (TRT) in adolescence is considered the first-line treatment by some physicians for patients with KS and biochemical signs of hypogonadism. However, comprehensive evidence on its effectiveness in preventing typical phenotypic traits associated with …

Prodrug Activation In Malaria Parasites Mediated By An Imported Erythrocyte Esterase, Acylpeptide Hydrolase (Apeh), Sesh A. Sundararaman, Justin J. Miller, Ellora C. Daley, Kelsey A. O'Brien, Paulina Kasak, Abigail M. Daniels, Rachel L. Edwards, Kenneth M. Heidel, Darean A. Bague, Madeleine A. Wilson, Andrew J. Koelper, Elexi C. Kourtoglou, Alex D. White, Sloan A. August, Georgia A. Apple, Regis W. Rouamba, Anthony J. Durand, John J. Esteb, Florian L. Muller, R. Jeremy Johnson, Geoffrey C. Hoops, Cynthia S. Dowd, Audrey R. Odom John

College of Health Professions Faculty Papers

The continued emergence of antimalarial drug resistance highlights the need to develop new antimalarial therapies. Unfortunately, new drug development is often hampered by undesirable drug-like properties of lead compounds. Prodrug approaches temporarily mask undesirable compound features, improving bioavailability and target penetration. We have found that lipophilic diester prodrugs of phosphonic acid antibiotics, such as fosmidomycin (Fsm), exhibit significantly higher antimalarial potency than their parent compounds [R.L. Edwards et al., Sci. Rep. 7, 8400 (2017)]. However, the activating enzymes for these prodrugs were unknown. Here, we show that an erythrocyte enzyme, acylpeptide hydrolase (APEH), is the major activating enzyme of multiple …

Vdac2 And Bak Scarcity In Liver Mitochondria Enables Targeting Hepatocarcinoma While Sparing Hepatocytes, Shamim Naghdi, Piyush Mishra, Soumya S. Roy, David Weaver, Ludivine Walter, Erika Davies, Anil N. Antony, Xuena Lin, Gisela Moehren, Mark A. Feitelson, Christopher A. Reed, Tullia Lindsten, Craig B. Thompson, Hien T. Dang, Jan B. Hoek, Erik S. Knudsen, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Differences between normal tissues and invading tumors that allow tumor targeting while saving normal tissue are much sought after. Here we show that scarcity of VDAC2, and the consequent lack of Bak recruitment to mitochondria, renders hepatocyte mitochondria resistant to permeabilization by truncated Bid (tBid), a Bcl-2 Homology 3 (BH3)-only, Bcl-2 family protein. Increased VDAC2 and Bak is found in most human liver cancers and mitochondria from tumors and hepatic cancer cell lines exhibit VDAC2- and Bak-dependent tBid sensitivity. Exploring potential therapeutic targeting, we find that combinations of activators of the tBid pathway with inhibitors of the Bcl-2 family proteins …