Digital Commons Network^™

Environmental Justice: A Missing Core Tenet Of Global Health, Redeat Workneh, Merhawit Abadi, Krystle Perez, Sharla Rent, Elliott Mark Weiss, Stephanie Kukora, Olivia Brandon, Gal Barbut, Sahar Rahiem, Shaphil Wallie, Joseph Mhango, Benjamin C Shayo, Friday Saidi, Gesit Metaferia, Mahlet Abayneh, Gregory C Valentine

Faculty, Staff and Students Publications

No abstract provided.

Echocardiographic Image Collection And Evaluation In Infants With Chd: Lessons Learned From The Imaging Core Lab For The Residual Lesion Score Study, Jami C Levine, Steven Colan, Felicia Trachtenberg, Edward Marcus, Matthew Ferguson, Anitha Parthiban, Carolyn Taylor, Andreea Dragulescu, Benjamin Goot, Ronald V Lacro, Carol Mcfarland, Shanthi Narasimhan, Matthew O'Connor, Marcus Schamberger, Shubhika Srivistava, Michael Taylor, Meena Nathan

Faculty, Staff and Students Publications

Many factors affect patient outcome after congenital heart surgery, including the complexity of the heart disease, pre-operative status, patient specific factors (prematurity, nutritional status and/or presence of comorbid conditions or genetic syndromes), and post-operative residual lesions. The Residual Lesion Score is a novel tool for assessing whether specific residual cardiac lesions after surgery have a measurable impact on outcome. The goal is to understand which residual lesions can be tolerated and which should be addressed prior to leaving the operating room. The Residual Lesion Score study is a large multicentre prospective study designed to evaluate the association of Residual Lesion …

Environmental Justice: A Missing Core Tenet Of Global Health, Redeat Workneh, Merhawit Abadi, Krystle Perez, Sharla Rent, Elliott Mark Weiss, Stephanie Kukora, Olivia Brandon, Gal Barbut, Sahar Rahiem, Shaphil Wallie, Joseph Mhango, Benjamin C Shayo, Friday Saidi, Gesit Metaferia, Mahlet Abayneh, Gregory C Valentine

Faculty, Staff and Students Publications

No abstract provided.

Advances In Pediatric Acute Kidney Injury Pharmacology And Nutrition: A Report From The 26th Acute Disease Quality Initiative (Adqi) Consensus Conference, Molly Wong Vega, Michelle C Starr, Patrick D Brophy, Prasad Devarajan, Danielle E Soranno, Ayse Akcan-Arikan, Rajit Basu, Stuart L Goldstein, Jennifer R Charlton, Erin Barreto

Faculty, Staff and Students Publications

BACKGROUND: In the past decade, there have been substantial advances in our understanding of pediatric AKI. Despite this progress, large gaps remain in our understanding of pharmacology and nutritional therapy in pediatric AKI.

METHODS: During the 26th Acute Disease Quality Initiative (ADQI) Consensus Conference, a multidisciplinary group of experts reviewed the evidence and used a modified Delphi process to achieve consensus on recommendations for gaps and advances in care for pharmacologic and nutritional management of pediatric AKI. The current evidence as well as gaps and opportunities were discussed, and recommendations were summarized.

RESULTS: Two consensus statements were developed. (1) High-value, …

Targeting Glutamine Dependence With Drp-104 Inhibits Proliferation And Tumor Growth Of Castration-Resistant Prostate Cancer, David Moon, J Spencer Hauck, Xue Jiang, Holly Quang, Lingfan Xu, Fan Zhang, Xia Gao, Robert Wild, Jeffrey I Everitt, Everardo Macias, Yiping He, Jiaoti Huang

Faculty, Staff and Students Publications

BACKGROUND: Prostate cancer (PCa) continues to be one of the leading causes of cancer deaths in men. While androgen deprivation therapy is initially effective, castration-resistant PCa (CRPC) often recurs and has limited treatment options. Our previous study identified glutamine metabolism to be critical for CRPC growth. The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) blocks both carbon and nitrogen pathways but has dose-limiting toxicity. The prodrug DRP-104 is expected to be preferentially converted to DON in tumor cells to inhibit glutamine utilization with minimal toxicity. However, CRPC cells' susceptibility to DRP-104 remains unclear.

METHODS: Human PCa cell lines (LNCaP, LAPC4, C4-2/MDVR, PC-3, 22RV1, …

Increased Plasma Branched Short-Chain Fatty Acids And Improved Glucose Homeostasis: The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Arianne Aslamy, Alexis C Wood, Elizabeth T Jensen, Alain G Bertoni, Patricia A Sheridan, Kari E Wong, Gautam Ramesh, Jerome I Rotter, Yii-Der I Chen, Mark O Goodarzi

Faculty, Staff and Students Publications

Short-chain fatty acids (SCFAs) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched SCFAs (BSCFAs; isobutyrate, isovalerate, and methylbutyrate) is largely unknown. In a cohort of 219 non-Hispanic White participants and 126 African American participants, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, and lipid traits, and other SCFAs. We observed a bimodal distribution of …

Diabetes Study Of Children Of Diverse Ethnicity And Race: Study Design, Maria J Redondo, Kylie K Harrall, Deborah H Glueck, Mustafa Tosur, Serife Uysal, Andrew Muir, Elizabeth G Atkinson, Melanie R Shapiro, Liping Yu, William E Winter, Michael Weedon, Todd M Brusko, Richard Oram, Kendra Vehik, William Hagopian, Mark A Atkinson, Dana Dabelea, Discover Study Group

Faculty, Staff and Students Publications

AIMS: Determining diabetes type in children has become increasingly difficult due to an overlap in typical characteristics between type 1 diabetes (T1D) and type 2 diabetes (T2D). The Diabetes Study in Children of Diverse Ethnicity and Race (DISCOVER) programme is a National Institutes of Health (NIH)-supported multicenter, prospective, observational study that enrols children and adolescents with non-secondary diabetes. The primary aim of the study was to develop improved models to differentiate between T1D and T2D in diverse youth.

MATERIALS AND METHODS: The proposed models will evaluate the utility of three existing T1D genetic risk scores in combination with data on …

Frequency Of Treatment Failure Of Utis In Children With Congenital Urinary Tract Anomalies, Catherine S Forster, Alexis C Wood, Stephanie Davis-Rodriguez, Pearl W Chang, Sanyukta Desai, Michael Tchou, John M Morrison, Jamie D Mudd, Brittany D Casey, Victor Trevisanut, Rana F Hamdy, Vijaya Vemulakonda, Patrick W Brady, Sowdhamini S Wallace, Uti In Children With Cakut Study Group

Faculty, Staff and Students Publications

OBJECTIVES: Children with certain congenital anomalies of the kidney and urinary tract and neurogenic bladder (CAKUT/NGB) are at higher risk of treatment failure for urinary tract infections (UTIs) than children with normal genitourinary anatomy, but the literature describing treatment and outcomes is limited. The objectives of this study were to describe the rate of treatment failure in children with CAKUT/NGB and compare duration of antibiotics between those with and without treatment failure.

METHODS: Multicenter retrospective cohort of children 0 to 17 years old with CAKUT/NGB who presented to the emergency department with fever or hypothermia and were diagnosed with UTI …

Psychosocial Moderators Of Polygenic Risk Scores Of Inflammatory Biomarkers In Relation To Grimage, Amanda J F Tamman, Dora Koller, Sheila Nagamatsu, Brenda Cabrera-Mendoza, Chadi Abdallah, John H Krystal, Joel Gelernter, Janitza L Montalvo-Ortiz, Renato Polimanti, Robert H Pietrzak

Faculty, Staff and Students Publications

GrimAge acceleration has previously predicted age-related morbidities and mortality. In the current study, we sought to examine how GrimAge is associated with genetic predisposition for systemic inflammation and whether psychosocial factors moderate this association. Military veterans from the National Health and Resilience in Veterans study, which surveyed a nationally representative sample of European American male veterans, provided saliva samples for genotyping (N = 1135). We derived polygenic risk scores (PRS) from the UK Biobank as markers of genetic predisposition to inflammation. Results revealed that PRS for three inflammatory PRS markers—HDL (lower), apolipoprotein B (lower), and gamma-glutamyl transferase (higher)—were associated …

Ketamine For Pain In Sickle Cell Disease Reduces Opioid Usage, Christina O Onyebuchi, Corrie E Chumpitazi, Jennifer L Placencia, Andrea N Jackson, Jennifer L Jones, Laura Torres, Venée N Tubman

Faculty, Staff and Students Publications

CONTEXT: Pain attributable to sickle cell disease (SCD) is often unpredictable, recurrent, and requires complex treatments. Subanesthetic ketamine infusion has been studied in other diseases and disorders, but there is still limited data on its efficacy in pain management for SCD.

OBJECTIVES: The primary objective is to determine if subanesthetic ketamine infusion reduces pain scores and opioid requirements in hospitalized pediatric patients with SCD.

RESULTS: Forty-six admissions among 22 patients between February 2018 and December 2019 were analyzed. We observed decrease in pain scores within 24 hours of ketamine initiation in 34 of 46 admissions (mean pain score per patient …

Mitochondrial Involvement In Sarcopenia, Charles Affourtit, Jane E. Carré

School of Biomedical Sciences

Sarcopenia lowers the quality-of-life for millions of people across the world, as accelerated loss of skeletal muscle mass and function contributes to both age- and disease-related frailty. Physical activity remains the only proven therapy for sarcopenia to date, but alternatives are much sought after to manage this progressive muscle disorder in individuals who are unable to exercise. Mitochondria have been widely implicated in the etiology of sarcopenia and are increasingly suggested as attractive therapeutic targets to help restore the perturbed balance between protein synthesis and breakdown that underpins skeletal muscle atrophy. Reviewing current literature, we note that mitochondrial bioenergetic changes …

Altered Larval Activation Response Associated With Multidrug Resistance In The Canine Hookworm Ancylostoma Caninum, Elise L Mckean, Emilia Grill, Young-Jun Choi, Makedonka Mitreva, Damien M O'Halloran, John M Hawdon

2020-Current year OA Pubs

Parasitic gastrointestinal nematodes pose significant health risks to humans, livestock, and companion animals, and their control relies heavily on the use of anthelmintic drugs. Overuse of these drugs has led to the emergence of resistant nematode populations. Herein, a naturally occurring isolate (referred to as BCR) of the dog hookworm,

Biomarker-Directed Targeted Therapy Plus Durvalumab In Advanced Non-Small-Cell Lung Cancer: A Phase 2 Umbrella Trial, Benjamin Besse, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of …

The Conceptual Definition Of Sarcopenia: Delphi Consensus From The Global Leadership Initiative In Sarcopenia (Glis), Ben Kirk, Ellen F Binder, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists.

OBJECTIVE: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia.

DESIGN: The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of …

Contemporary Report Of Surgical Outcomes After Single-Stage Total Pancreatectomy: A 10-Year Experience, Nitzan Zohar, Luke Kowal, David Moskal, Francesca Ponzini, George Sun, Ryan J. Lamm, John Williamson, Avinoam Nevler, Harish Lavu, Warren R. Maley, Charles J. Yeo, Wilbur B. Bowne

Department of Surgery Faculty Papers

BACKGROUND: Surgeons rarely perform elective total pancreatectomy (TP). Our study seeks to report surgical outcomes in a contemporary series of single-stage (SS) TP patients.

METHODS: Between the years 2013 to 2023 we conducted a retrospective review of 60 consecutive patients who underwent SSTP. Demographics, pathology, treatment-related variables, and survival were recorded and analyzed.

RESULTS: SSTP consisted of 3% (60/1859) of elective pancreas resections conducted. Patient median age was 68 years. Ninety percent of these patients (n = 54) underwent SSTP for pancreatic ductal adenocarcinoma (PDAC). Conversion from a planned partial pancreatectomy to TP occurred intraoperatively in 31 (52%) patients. Fifty-nine …

Reply To Ayoub-Charette Et Al Lack Of Biological Plausibility And Major Methodological Issues Cast Doubt On The Association Between Aspartame And Autism Comment On "Fowler Et Al Daily Early-Life Exposures To Diet Soda And Aspartame Are Associated With Autism In Males: A Case-Control Study, Sharon Parten Fowler, David Gimeno Ruiz De Porras, Michael D Swartz, Paula Stigler Granados, Lynne Parsons Heilbrun, Raymond F Palmer

Faculty, Staff and Student Publications

Thank you for the opportunity to respond to the concerns raised by Ayoub-Charette et al [...].

Experience With A Hybrid Recruitment Approach Of Patient-Facing Web Portal Screening And Subsequent Phone And Medical Record Review For A Neurosurgical Intervention Trial For Chronic Ischemic Stroke Disability (Pisces Iii), Brad J Kolls, Keith W Muir, Sean I Savitz, Lawrence R Wechsler, Julie G Pilitsis, Scott Rahimi, Richard L Beckman, Vincent Holmes, Peng R Chen, David S Albers, Daniel T Laskowitz

Faculty, Staff and Student Publications

BACKGROUND: Recruitment of participants is the greatest risk to completion of most clinical trials, with 20-40% of trials failing to reach the targeted enrollment. This is particularly true of trials of central nervous system (CNS) therapies such as intervention for chronic stroke. The PISCES III trial was an invasive trial of stereotactically guided intracerebral injection of CTX0E03, a fetal derived neural stem cell line, in patients with chronic disability due to ischemic stroke. We report on the experience using a novel hybrid recruitment approach of a patient-facing portal to self-identify and perform an initial screen for general trial eligibility (tier …

Improving Safety And Preventing Falls Using An Evidence-Based, Front-Line Staff Huddling Practice: Protocol For A Pragmatic Trial To Increase Quality Of Care In State Veterans Homes, Princess Nash, Valerie Clark, Eleanor Mcconnell, Whitney Mills, Robert Morgan, Camilla Pimentel, Katherine Ritchey, Cari Levy, A Lynn Snow, Christine Hartmann

Faculty, Staff and Student Publications

Introduction: Falls in nursing homes are a major cause for decreases in residents' quality of life and overall health. This study aims to reduce resident falls by implementing the LOCK Falls Programme, an evidence-based quality improvement intervention. The LOCK Falls Programme involves the entire front-line care team in (1) focusing on evidence of positive change, (2) collecting data through systematic observation and (3) facilitating communication and coordination of care through the practice of front-line staff huddles.

Methods and analysis: The study protocol describes a mixed-methods, 4-year hybrid (type 2) effectiveness-implementation study in State Veterans Homes in the USA. The study …

Polyaminer-Bulk Is A Deep Learning-Based Algorithm That Decodes Alternative Polyadenylation Dynamics From Bulk Rna-Seq Data, Venkata Soumith Jonnakuti, Eric J Wagner, Mirjana Maletić-Savatić, Zhandong Liu, Hari Krishna Yalamanchili

Faculty, Staff and Students Publications

Alternative polyadenylation (APA) is a key post-transcriptional regulatory mechanism; yet, its regulation and impact on human diseases remain understudied. Existing bulk RNA sequencing (RNA-seq)-based APA methods predominantly rely on predefined annotations, severely impacting their ability to decode novel tissue- and disease-specific APA changes. Furthermore, they only account for the most proximal and distal cleavage and polyadenylation sites (C/PASs). Deconvoluting overlapping C/PASs and the inherent noisy 3' UTR coverage in bulk RNA-seq data pose additional challenges. To overcome these limitations, we introduce PolyAMiner-Bulk, an attention-based deep learning algorithm that accurately recapitulates C/PAS sequence grammar, resolves overlapping C/PASs, captures non-proximal-to-distal APA changes, …

Association Of Lifestyle Intervention With Risk For Cardiovascular Events Differs By Level Of Glycated Hemoglobin, Michael P Bancks, Scott J Pilla, Ashok Balasubramanyam, Hsin-Chieh Yeh, Karen C Johnson, Joseph Rigdon, Lynne E Wagenknecht, Mark A Espeland

Faculty, Staff and Students Publications

Purpose: We reevaluated the Action for Health in Diabetes (Look AHEAD) intensive lifestyle intervention (ILI) to assess whether the effect of ILI on cardiovascular disease (CVD) prevention differed by baseline glycated hemoglobin (HbA1c).

Methods: Look AHEAD randomized 5145 adults, aged 45 to 76 years with type 2 diabetes and overweight/obesity to ILI or a diabetes support and education (DSE) control group for a median of 9.6 years. ILI focused on achieving weight loss through decreased caloric intake and increased physical activity. We assessed the parent trial's primary composite CVD outcome. We evaluated additive and multiplicative heterogeneity of the intervention on …

Association Of Risk Factors And Comorbidities With Chronic Pain In The Elderly Population., Neil Mookerjee, Nicole Schmalbach, Gianna Antinori, Subhadra Thampi, Dylan Windle-Puente, Amy Gilligan, Ha Huy, Megha Andrews, Angela Sun, Roshni Gandhi, William Benedict, Austin Chang, Ben Sanders, Justin Nguyen, Maanika Reddy Keesara, Janet Aliev, Aneri Patel, Isaiah Hughes, Ian Millstein, Krystal Hunter, Satyajeet Roy

Cooper Medical School of Rowan University Departmental Research

INTRODUCTION/OBJECTIVE: Chronic pain disorders affect about 20% of adults in the United States, and it disproportionately affects individuals living in the neighborhoods of extreme socioeconomic disadvantage. In many instances, chronic pain has been noted to arise from an aggregation of multiple risk factors and events. Therefore, it is of importance to recognize the modifiable risk factors. The aim of this study was to investigate the comorbid medical conditions and risk factors associated with chronic pain disorders in patients aged 65 years and older.

METHODS: Our team retrospectively reviewed medical records of elderly patients (65 years and older) who were evaluated …

Sodium Oligomannate Alters Gut Microbiota, Reduces Cerebral Amyloidosis And Reactive Microglia In A Sex-Specific Manner, Megan E Bosch, Choonghee Lee, Aishwarya Nambiar, Samira Parhizkar, Marie L Laury, David M Holtzman, Et Al.

2020-Current year OA Pubs

It has recently become well-established that there is a connection between Alzheimer's disease pathology and gut microbiome dysbiosis. We have previously demonstrated that antibiotic-mediated gut microbiota perturbations lead to attenuation of Aβ deposition, phosphorylated tau accumulation, and disease-associated glial cell phenotypes in a sex-dependent manner. In this regard, we were intrigued by the finding that a marine-derived oligosaccharide, GV-971, was reported to alter gut microbiota and reduce Aβ amyloidosis in the 5XFAD mouse model that were treated at a point when Aβ burden was near plateau levels. Utilizing comparable methodologies, but with distinct technical and temporal features, we now report …

A Small Molecule With Big Impact: Mrtx1133 Targets The Krasg12d Mutation In Pancreatic Cancer, Daoyan Wei, Liang Wang, Xiangsheng Zuo, Anirban Maitra, Robert S Bresalier

Faculty, Staff and Student Publications

KRAS mutations drive oncogenic alterations in numerous cancers, particularly in human pancreatic ductal adenocarcinoma (PDAC). About 93% of PDACs have KRAS mutations, with G12D (∼42% of cases) and G12V (∼32% of cases) being the most common. The recent approval of sotorasib (AMG510), a small-molecule, covalent, and selective KRASG12C inhibitor, for treating patients with non-small cell lung cancer represents a breakthrough in KRAS targeted therapy. However, there is a need to develop other much-needed KRAS-mutant inhibitors for PDAC therapy. Notably, Mirati Therapeutics recently developed MRTX1133, a small-molecule, noncovalent, and selective KRASG12D inhibitor through extensive structure-based drug design. MRTX1133 has demonstrated potent …

Cpsf3 Inhibition Blocks Pancreatic Cancer Cell Proliferation Through Disruption Of Core Histone Mrna Processing, Abdulrahman A Alahmari, Aditi H Chaubey, Venkata S Jonnakuti, Arwen A Tisdale, Carla D Schwarz, Abigail C Cornwell, Kathryn E Maraszek, Emily J Paterson, Minsuh Kim, Swati Venkat, Eduardo Cortes Gomez, Jianmin Wang, Katerina V Gurova, Hari Krishna Yalamanchili, Michael E Feigin

Duncan NRI Faculty and Staff Publications

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited effective treatment options, potentiating the importance of uncovering novel drug targets. Here, we target cleavage and polyadenylation specificity factor 3 (CPSF3), the 3′ endonuclease that catalyzes mRNA cleavage during polyadenylation and histone mRNA processing. We find that CPSF3 is highly expressed in PDAC and is associated with poor prognosis. CPSF3 knockdown blocks PDAC cell proliferation and colony formation in vitro and tumor growth in vivo. Chemical inhibition of CPSF3 by the small molecule JTE-607 also attenuates PDAC cell proliferation and colony formation, while it has no effect on cell proliferation …

Cpsf3 Inhibition Blocks Pancreatic Cancer Cell Proliferation Through Disruption Of Core Histone Mrna Processing, Abdulrahman A Alahmari, Aditi H Chaubey, Venkata S Jonnakuti, Arwen A Tisdale, Carla D Schwarz, Abigail C Cornwell, Kathryn E Maraszek, Emily J Paterson, Minsuh Kim, Swati Venkat, Eduardo Cortes Gomez, Jianmin Wang, Katerina V Gurova, Hari Krishna Yalamanchili, Michael E Feigin

Faculty, Staff and Students Publications

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited effective treatment options, potentiating the importance of uncovering novel drug targets. Here, we target cleavage and polyadenylation specificity factor 3 (CPSF3), the 3′ endonuclease that catalyzes mRNA cleavage during polyadenylation and histone mRNA processing. We find that CPSF3 is highly expressed in PDAC and is associated with poor prognosis. CPSF3 knockdown blocks PDAC cell proliferation and colony formation in vitro and tumor growth in vivo. Chemical inhibition of CPSF3 by the small molecule JTE-607 also attenuates PDAC cell proliferation and colony formation, while it has no effect on cell proliferation …

Yersiniabactin Is A Quorum-Sensing Autoinducer And Siderophore In Uropathogenic Escherichia Coli, James R Heffernan, John A Wildenthal, Hung Tran, George L Katumba, William H Mccoy, Jeffrey P Henderson

2020-Current year OA Pubs

Siderophores are secreted ferric ion chelators used to obtain iron in nutrient-limited environmental niches, including human hosts. While all

Protecting Human And Animal Health: The Road From Animal Models To New Approach Methods, Barbara L F Kaplan, Alan M Hoberman, William Slikker, Mary Alice Smith, Emanuela Corsini, Thomas B Knudsen, M Sue Marty, Sonya K Sobrian, Suzanne C Fitzpatrick, Marcia H Ratner, Donna L Mendrick

Faculty, Staff and Student Publications

Animals and animal models have been invaluable for our current understanding of human and animal biology, including physiology, pharmacology, biochemistry, and disease pathology. However, there are increasing concerns with continued use of animals in basic biomedical, pharmacological, and regulatory research to provide safety assessments for drugs and chemicals. There are concerns that animals do not provide sufficient information on toxicity and/or efficacy to protect the target population, so scientists are utilizing the principles of replacement, reduction, and refinement (the 3Rs) and increasing the development and application of new approach methods (NAMs). NAMs are any technology, methodology, approach, or assay used …

Study Protocol For Clinical Trial Of The Fit Families Multicomponent Obesity Intervention For African American Adolescents And Their Caregivers: Next Step From The Orbit Initiative, Phillippe B Cunningham, Sylvie Naar, James R Roberts, Jennifer Powell, David M Ledgerwood, Jeff Randall, Brian E Lozano, Colleen A Halliday, Mohan Madisetti, Samiran Ghosh

Faculty, Staff and Student Publications

INTRODUCTION: This study will test the effectiveness of FIT Families (FIT), a multicomponent family-based behavioural intervention, against a credible attention control condition, Home-Based Family Support (HBFS). This protocol paper describes the design of a randomised clinical trial testing the efficacy of the FIT intervention. The protocol will assess the efficacy of FIT to improve health status in African American adolescents with obesity (AAAO) and their primary caregivers on primary (percent body fat) and secondary (physical activity, metabolic control, weight loss) outcomes and its cost-effectiveness.

METHODS: 180 youth/caregiver dyads are randomised into FIT or HBFS, stratified by age, gender and baseline …

Phase I Study Of Mtorc1/2 Inhibitor Sapanisertib (Cb-228/Tak-228) In Combination With Metformin In Patients With Mtor/Akt/Pi3k Pathway Alterations And Advanced Solid Malignancies, Vivek Subbiah, Niamh Coleman, Sarina A Piha-Paul, Apostolia M Tsimberidou, Filip Janku, Jordi Rodon, Shubham Pant, Ecaterina E Ileana Dumbrava, Siqing Fu, David S Hong, Shizhen Zhang, Ming Sun, Yunfang Jiang, Jason Roszik, Juhee Song, Ying Yuan, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

BACKGROUND: Sapanisertib (CB-228/TAK-228) is a potent, selective ATP-competitive, dual inhibitor of mTORC1/2. Metformin is thought to inhibit the mTOR pathway through upstream activation of 5'-AMP-activated protein kinase (AMPK) suggesting combination therapy may enhance antitumor activity of sapanisertib. We report preliminary safety, tolerability, and efficacy from the dose-escalation study of sapanisertib in combination with metformin in patients with advanced solid tumors.

METHODS: Patients with advanced metastatic solid tumors resistant or refractory to standard treatment, with and without mTOR/AKT/PI3K pathway alterations, received sapanisertib 3 or 4 mg daily together with metformin once to three times daily (500-1,500 mg). All patients underwent 14-day …

Development And Validation Of Parent-Reported Gastrointestinal Health Scale In Mecp2 Duplication Syndrome, Davut Pehlivan, Sukru Aras, Daniel G Glaze, Muharrem Ak, Bernhard Suter, Kathleen J Motil

Faculty, Staff and Students Publications

BACKGROUND/AIMS: We aimed to develop a validated patient-reported Gastrointestinal Health Scale (GHS) specific to MECP2 Duplication Syndrome (MDS) to be used in clinical trials.

METHODS: MDS parents completed a Gastrointestinal Health Questionnaire (GHQ) to investigate the most relevant and important items associated with gastrointestinal problems in MECP2-related disorders. Item reduction was executed according to EORTC guidelines. We performed reliability and validity studies for the finalized scale.

RESULTS: A total of 106 surveys were eligible for item reduction and validation processes. The initial 55 items were reduced to 38 items based on parent responses, expert opinion, and initial confirmatory factor analysis …