Medicine and Health Sciences Commons^™

Eco-Microbiology: Discovering Biochemical Enhancers Of Pet Biodegradation By Piscinibacter Sakaiensis, Felipe-Andrés Piedra, Miguel A Salazar, Sara Abouelniaj, Raayed Rahman, Justin C Clark, Yimo Han, Zhao Wang, Anthony Maresso

Faculty, Staff and Students Publications

The scale of plastic pollution boggles the mind. Nearly 400 megatons of virgin plastics are produced annually, with an environmental release rate of 80%, and plastic waste, including microplastics and nanoplastics, is associated with a plethora of problems. The naturally evolved abilities of plastic-degrading microbes offer a starting point for generating sustainable and eco-centric solutions to plastic pollution-a field of endeavor we term eco-microbiology. Here, we developed an iterative discovery procedure coupling faster polyethylene terephthalate (PET)-dependent bioactivity screens with longer-term PET biodegradation assays to find biochemical boosters of PET consumption by the bacterium Piscinibacter sakaiensis. We discovered multiple hits …

Emerging Clostridioides Difficile Ribotypes Have Divergent Metabolic Phenotypes, Firas S Midani, Heather A Danhof, Nathanael Mathew, Colleen K Ardis, Kevin W Garey, Jennifer K Spinler, Robert A Britton

Faculty, Staff and Students Publications

Clostridioides difficile is a gram-positive spore-forming pathogen that commonly causes diarrheal infections in the developed world. Although C. difficile is a genetically diverse species, certain ribotypes are overrepresented in human infections, and it is unclear if metabolic adaptations are essential for the emergence of these epidemic ribotypes. To identify ribotype-specific metabolic differences, we therefore tested carbon substrate utilization by 88 C. difficile isolates and looked for differences in growth between 22 ribotypes. As expected, C. difficile was capable of growing on a variety of carbon substrates. Further, C. difficile strains clustered by phylogenetic relationship and displayed ribotype-specific and clade-specific …

Best Practices For Imaging Of Transcatheter Valve Failure: An Update From The Heart Valve Collaboratory, Omar K Khalique, Syed Zaid, Gilbert H L Tang, Mohamed Abdel-Wahab, Miriama Akodad, Vinayak N Bapat, Jeroen J Bax, Daniel J Blackman, Philipp Blanke, Sabine Bleiziffer, Davide Capodanno, Joao L Cavalcante, Lakshmi P Dasi, Ole De Backer, Matthiew De Beuel, Alison Duncan, Marc R Dweck, Miho Fukui, Aakriti Gupta, Kentaro Hayashida, Howard C Herrmann, Tsuyoshi Kaneko, Nicole Karam, Jaffar M Khan, Jan Kovac, Uri Landes, Jonathon A Leipsic, Martin B Leon, Michael J Mack, Mahesh V Madhavan, Moody M Makar, Raj R Makkar, Mouaz Al Mallah, David Meier, Thomas Modine, Atsushi Okada, Roosha K Parikh, Radoslaw Parma, Dhairya Patel, Philippe Pibarot, Bernard Prendergast, Nishath Quader, Michael J Reardon, Toby Rogers, Lucy M Safi, Stephanie L Sellers, Sabah Skaf, Giuseppe Tarantini, Didier Tchetche, Nicolas Van Mieghem, Dee Dee Wang, John G Webb, Stephan Windecker, Steven J Yakubov, Victoria Delgado, Rebecca T Hahn, Hasan Jilaihawi

Faculty, Staff and Students Publications

This updated Heart Valve Collaboratory framework addresses the growing concern for transcatheter valve failure (TVF) following transcatheter aortic valve replacement (TAVR). With the increasing volume of redo-TAV and surgical TAV explantation, there is a critical need for standardized pathways and protocols for evaluating TVF using echocardiography and cardiac computed tomography (CT) angiography. This document clarifies prior definitions of bioprosthetic valve deterioration and bioprosthetic valve failure in a practical, imaging directed context for TAVR. It discusses various imaging modalities for diagnosing TVF, including echocardiography, cardiac CT angiography, cardiac magnetic resonance, and positron emission tomography/CT. Recommendations are provided on the systematic imaging …

Health System, Community-Based, Or Usual Dementia Care For Persons With Dementia And Caregivers: The D-Care Randomized Clinical Trial, David B Reuben, Thomas M Gill, Alan Stevens, Jeff Williamson, Elena Volpi, Maya Lichtenstein, Lee A Jennings, Rebecca Galloway, Jenny Summapund, Katy Araujo, David Bass, Lisa Weitzman, Zaldy S Tan, Leslie Evertson, Mia Yang, Katherine Currie, Aval-Na'ree S Green, Sybila Godoy, Sitara Abraham, Jordan Reese, Rafael Samper-Ternent, Roxana M Hirst, Pamela Borek, Peter Charpentier, Can Meng, James Dziura, Yunshan Xu, Eleni A Skokos, Zili He, Sherry Aiudi, Peter Peduzzi, Erich J Greene, D-Care Study

Faculty, Staff and Student Publications

Importance: The effectiveness of different approaches to dementia care is unknown.

Objective: To determine the effectiveness of health system-based, community-based dementia care, and usual care for persons with dementia and for caregiver outcomes.

Design, setting, and participants: Randomized clinical trial of community-dwelling persons living with dementia and their caregivers conducted at 4 sites in the US (enrollment June 2019-January 2023; final follow-up, August 2023).

Interventions: Participants were randomized 7:7:1 to health system-based care provided by an advanced practice dementia care specialist (n = 1016); community-based care provided by a social worker, nurse, or licensed therapist care consultant (n = 1016); …

Icos-Expressing Car-T Cells Mediate Durable Eradication Of Triple-Negative Breast Cancer And Metastasis, Shelley Herbrich, Mehdi Chaib, Padmanee Sharma

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) remains one of the most aggressive and therapeutically challenging breast cancer subtypes. In their recent study, Cao et al introduced a B7H3-specific chimeric antigen receptor (CAR)-T cell with constitutive inducible co-stimulator (ICOS) expression (ICOS-B7H3-CAR-T), which demonstrated eradication of TNBC, including metastases, in preclinical models. These CAR-T cells exploit the expression of ICOS ligand on TNBC cells, enhancing antitumor cytotoxicity through ICOS signaling. Compared with conventional B7H3-CAR-T cells, the ICOS-B7H3-CAR-T cells exhibited superior antitumor efficacy, increased cytokine secretion, and prolonged survival in xenograft murine models. This study highlights ICOS as a promising co-stimulatory molecule for improving CAR-T …

High-Dimensional Analysis Of Injured Patients Reveals Distinct Circulating Proteomic Profiles In Plasma Vs. Whole Blood Resuscitation, Hamed Moheimani, Xuejing Sun, Mehves Ozel, Jennifer L Darby, Erika P Ong, Tunde Oyebamiji, Upendra K Kar, Mark H Yazer, Matthew D Neal, Francis X Guyette, Stephen R Wisniewski, Bryan A Cotton, Jeremy W Cannon, Martin A Schreiber, Ernest E Moore, Nicholas Namias, Joseph P Minei, Christopher D Barrett, Jishnu Das, Jason L Sperry, Timothy R Billiar

Faculty, Staff and Student Publications

Early blood product resuscitation is often essential for optimal trauma care. However, the effects of different products on the underlying trauma-induced coagulopathy and immune dysfunction are not well described. Here, we use high-dimensional analysis and causal modeling in a longitudinal study to explore the circulating proteomic response to plasma as a distinct component versus low-titer O whole blood (LTOWB), which contains plasma. We highlight the differential impacts of plasma and LTOWB on immune mediator levels and the distinct capacity of plasma to modulate coagulation by elevating fibrinogen and factor XIII and reducing platelet factor 4. A higher proportion of plasma …

Mathematical Modeling To Address Questions In Breast Cancer Screening: An Overview Of The Breast Cancer Models Of The Cancer Intervention And Surveillance Modeling Network, Oguzhan Alagoz, Jennifer L Caswell-Jin, Harry J De Koning, Hui Huang, Xuelin Huang, Sandra J Lee, Yisheng Li, Sylvia K Plevritis, Swarnavo Sarkar, Clyde B Schechter, Natasha K Stout, Amy Trentham-Dietz, Nicolien Van Ravesteyn, Kathryn P Lowry

Faculty, Staff and Student Publications

The National Cancer Institute-funded Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer mathematical models have been increasingly utilized by policymakers to address breast cancer screening policy decisions and influence clinical practice. These well-established and validated models have a successful track record of use in collaborations spanning over 2 decades. While mathematical modeling is a valuable approach to translate short-term screening performance data into long-term breast cancer outcomes, it is inherently complex and requires numerous inputs to approximate the impacts of breast cancer screening. This review article describes the 6 independently developed CISNET breast cancer models, with a particular focus …

Near-Infrared Fluorescence Imaging With An Met-Targeting Probe For Biopsy Site Selection In Patients With Oral Potentially Malignant Disorders, Jingbo Wang, Xuemin Shen, Qifan Ma, Lin Yang, Xiaoyu Zhou, Luting Wang, Junqi Cui, Chunye Zhang, Guojun Li, Neil Gross, Siyi Li, Ruimin Huang, Changyou Zhan, Zhen Cheng, Kun Wang, Jie Tian, Ying Yuan, Xiaofeng Tao

Faculty, Staff and Student Publications

Accurate detection of malignant transformation in oral potentially malignant disorders (OPMDs) is crucial for guiding effective treatment and improving patient management. This study evaluates the potential of MET-binding peptide-indocyanine green (cMBP-ICG), a mesenchymal-epithelial transition factor (MET)-targeted near-infrared fluorescence imaging (NIRFI) probe, for biopsy site selection in OPMDs. Preclinical results demonstrate the superior accuracy of NIRFI-assisted biopsy over conventional oral examination (COE)-based biopsy in detecting high-grade dysplasia (HGD) or squamous cell carcinoma (SCC) and reducing missed detection rates. In a clinical trial with 50 patients, NIRFI-assisted biopsy achieves significantly higher diagnostic accuracy compared to COE-based biopsy (91% vs. 72%, p = …

Framework For Kidney Health Follow-Up Among Neonates With Critical Cardiac Disease: A Report From The Neonatal Kidney Health Consensus Workshop, Stephen M Gorga, Tara Beck, Paulomi Chaudhry, Marissa J Defreitas, Dana Y Fuhrman, Catherine Joseph, Catherine D Krawczeski, David M Kwiatkowski, Michelle C Starr, Matthew W Harer, Jennifer R Charlton, David J Askenazi, David T Selewski, Katja M Gist

Faculty, Staff and Students Publications

Acute kidney injury is common among neonates with critical cardiac disease. Risk factors and associations with kidney-related outcomes are heterogeneous and distinct from other neonates. As survival of children with critical cardiac disease increases to adulthood, the burden of chronic kidney disease is increasing. Thirty percent to 50% of adults with congenital heart disease have impaired kidney function, even in the absence of prior kidney injury episodes. This may be related to the current standardized acute kidney injury criteria, which may not fully capture clinically meaningful kidney injury and long-term kidney health risks. An improved understanding of which neonates with …

The Autophagy Protein Atg14 Safeguards Against Unscheduled Pyroptosis Activation To Enable Embryo Transport During Early Pregnancy, Pooja Popli, Arin K Oestreich, Vineet K Maurya, Marina N Rowen, Yong Zhang, Michael J Holtzman, Ramya Masand, John P Lydon, Shizuo Akira, Kelle Moley, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Recurrent pregnancy loss, characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition to embryo quality and endometrial function, proper oviduct function is also essential for successful pregnancy establishment. Therefore, structural abnormalities or inflammation resulting from infection in the oviduct may impede the transport of embryos to the endometrium, thereby increasing the risk of miscarriage. However, our understanding of the biological processes that preserve the oviductal cellular structure and functional integrity is limited. Here, we report that autophagy-related protein ATG14 plays a crucial role in maintaining the cellular integrity of the oviduct by …

Guanine Nucleotide Biosynthesis Blockade Impairs Mll Complex Formation And Sensitizes Leukemias To Menin Inhibition, Xiangguo Shi, Minhua Li, Zian Liu, Jonathan Tiessen, Yuan Li, Jing Zhou, Yudan Zhu, Swetha Mahesula, Qing Ding, Lin Tan, Mengdie Feng, Yuki Kageyama, Yusuke Hara, Jacob J Tao, Xuan Luo, Kathryn A Patras, Philip L Lorenzi, Suming Huang, Alexandra M Stevens, Koichi Takahashi, Ghayas C Issa, Md Abul Hassan Samee, Michalis Agathocleous, Daisuke Nakada

Faculty, Staff and Student Publications

Targeting the dependency of MLL-rearranged (MLLr) leukemias on menin with small molecule inhibitors has opened new therapeutic strategies for these poor-prognosis diseases. However, the rapid development of menin inhibitor resistance calls for combinatory strategies to improve responses and prevent resistance. Here we show that leukemia stem cells (LSCs) of MLLr acute myeloid leukemia (AML) exhibit enhanced guanine nucleotide biosynthesis, the inhibition of which leads to myeloid differentiation and sensitization to menin inhibitors. Mechanistically, targeting inosine monophosphate dehydrogenase 2 (IMPDH2) reduces guanine nucleotides and rRNA transcription, leading to reduced protein expression of LEDGF and menin. Consequently, the formation and chromatin binding …

Diverse Ancestral Representation Improves Genetic Intolerance Metrics, Alexander L Han, Chloe F Sands, Dorota Matelska, Jessica C Butts, Vida Ravanmehr, Fengyuan Hu, Esmeralda Villavicencio Gonzalez, Nicholas Katsanis, Carlos D Bustamante, Quanli Wang, Slavé Petrovski, Dimitrios Vitsios, Ryan S Dhindsa

Duncan NRI Faculty and Staff Publications

The unprecedented scale of genomic databases has revolutionized our ability to identify regions in the human genome intolerant to variation—regions often implicated in disease. However, these datasets remain constrained by limited ancestral diversity. Here, we analyze whole-exome sequencing data from 460,551 UK Biobank and 125,748 Genome Aggregation Database (gnomAD) participants across multiple ancestries to test several key intolerance metrics, including the Residual Variance Intolerance Score (RVIS), Missense Tolerance Ratio (MTR), and Loss-of-Function Observed/Expected ratio (LOF O/E). We demonstrate that increasing ancestral representation, rather than sample size alone, critically drives their performance. Scores trained on variation observed in African and Admixed …

Author Correction: Generation Of A Tree Shrew Breast Cancer Model Using Lentivirus Expressing Pik3ca-H1047r, Li Zeng, Hong-Yan Zhang, Chuan-Yu Yang, Zhuo Cheng, Qiu-Yun Jiang, Yao Luo, Yi Li, Fu-Bing Li, Ce-Shi Chen

Faculty, Staff and Students Publications

No abstract provided.

Phase I Trial Of Tti-101, A First-In-Class Oral Inhibitor Of Stat3, In Patients With Advanced Solid Tumors, Apostolia M Tsimberidou, David J Vining, Sukeshi P Arora, Sofia De Achaval, Jeffrey Larson, John Kauh, Carrie Cartwright, Rony Avritscher, Imran Alibhai, David J Tweardy, Ahmed O Kaseb

Faculty, Staff and Student Publications

Purpose: Signal transducer and activator of transcription 3 is a transcription factor that is essential for the survival and immune sequestration of cancer cells. We conducted a phase I study of TTI-101, a first-in-class, selective small-molecule inhibitor of signal transducer and activator of transcription 3, in patients with advanced metastatic cancer.

Patients and methods: Patients were treated with TTI-101 orally twice daily in 28-day cycles at four dose levels (DL): 3.2 (DL1), 6.4 (DL2), 12.8 (DL3), and 25.6 (DL4) mg/kg/day ("3+3" design). Three TTI-101 formulations were used in a stepwise manner (NCT03195699).

Results: Sixty-four patients were treated (median …

Correction: Ellsworth, M.; Ostrosky-Zeichner, L. Isavuconazole: Mechanism Of Action, Clinical Efficacy, And Resistance, Misti Ellsworth, Luis Ostrosky-Zeichner

Faculty, Staff and Student Publications

In the original article [1], in Section 6.3, “Treatment groups received caspofungin 750 mg IV on day 1” should be “70 mg” instead of “750 mg”. We made a mistake in the process of writing. The corrected paragraph is as follows:

“Treatment groups received caspofungin 70 mg IV on day 1 followed by 50 mg IV daily or 200 mg of isavuconazole IV q8h on days 1–2 followed by 200 mg once daily.”

The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated.

Neural Correlates Of Opioid-Induced Risk-Taking Behavior In The Prelimbic Prefrontal Cortex, Cana B Quave, Andres M Vasquez, Guillermo Aquino-Miranda, Milagros Marín, Esha P Bora, Chinenye L Chidomere, Xu O Zhang, Douglas S Engelke, Fabricio H Do-Monte

Faculty, Staff and Student Publications

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of …

An Exosome-Based Liquid Biopsy Predicts Depth Of Response And Survival Outcomes To Cetuximab And Panitumumab In Metastatic Colorectal Cancer: The Exonerate Study, Caiming Xu, Alessandro Mannucci, Francis Esposito, Helena Oliveres, Vicente Alonso-Orduña, Alfonso Yubero, Carlos Fernández-Martos, Antonieta Salud, Javier Gallego, Marta Martín-Richard, Julen Fernández-Plana, Mónica Guillot, Jorge Aparicio, Marwan Fakih, Scott Kopetz, Jaime Feliu, Joan Maurel, Ajay Goel

Faculty, Staff and Student Publications

Purpose: The EXOsome and cell-free miRNAs of anti-EGFR ResistAnce (EXONERATE) study was an open-label, biomarker interventional study designed to develop, test, and validate a liquid biopsy predictive of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) for first-line EGFR inhibitors in metastatic colorectal cancer (mCRC).

Patients and methods: Patients with newly diagnosed RAS wild-type, chemotherapy-naïve mCRC, both right- and left-sided, were enrolled in two nationwide trials to receive cetuximab or panitumumab along with chemotherapy. The primary endpoint was 12-month PFS, which was hierarchically tested in left- and right-sided mCRCs to predict PFS, OS, and ORR.

Results: Genome-wide …

Impact Of Co-Mutations And Transcriptional Signatures In Non-Small Cell Lung Cancer Patients Treated With Adagrasib In The Krystal-1 Trial, Marcelo V Negrao, Alvaro G Paula, David Molkentine, Laura Hover, Monique Nilsson, Natalie Vokes, Lars Engstrom, Andrew Calinisan, David M Briere, Laura Waters, Jill Hallin, Lixia Diao, Mehmet Altan, George R Blumenschein, Ferdinandos Skoulidis, Jing Wang, Scott E Kopetz, David S Hong, Don L Gibbons, Peter Olson, James G Christensen, John V Heymach

Faculty, Staff and Student Publications

Purpose: KRAS inhibitors are revolutionizing the treatment of non-small cell lung cancer (NSCLC), but clinico-genomic determinants of treatment efficacy warrant continued exploration.

Experimental design: Patients with advanced KRASG12C-mutant NSCLC treated with adagrasib [KRYSTAL-1 (NCT03785249)] were included in the analysis. Pretreatment next-generation sequencing data were collected per protocol. HTG EdgeSeq Transcriptome Panel was used for gene expression profiling. Clinical endpoints included objective response, progression-free survival (PFS), and overall survival (OS). KRASG12C-mutant NSCLC cell lines and xenograft models were used for sensitivity analyses and combination drug screens.

Results: KEAP1 MUT and STK11MUT were associated with shorter survival to adagrasib [KEAP1: …

Association Of Messenger Rna Coronavirus Disease 2019 (Covid-19) Vaccination And Reductions In Post Covid Conditions Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection In A Us Prospective Cohort Of Essential Workers, Josephine Mak, Sana Khan, Amadea Britton, Spencer Rose, Lisa Gwynn, Katherine D Ellingson, Jennifer Meece, Leora R Feldstein, Harmony Tyner, Laura J Edwards, Matthew S Thiese, Allison Naleway, Manjusha Gaglani, Natasha Solle, Jefferey L Burgess, Julie Mayo Lamberte, Meghan Shea, Taryn Hunt-Smith, Alberto Caban-Martinez, Cynthia Porter, Ryan Wiegand, Ramona Rai, Kurt T Hegmann, James Hollister, Ashley Fowlkes, Meredith Wesley, Andrew L Philips, Patrick Rivers, Robin Bloodworth, Gabriella Newes-Adeyi, Lauren E W Olsho, Sarang K Yoon, Sharon Saydah, Karen Lutrick

Center for Medical Ethics and Health Policy Staff Publications

Background: Data are limited on whether vaccination reduces post COVID conditions (PCCs) risk after less severe nonhospitalized coronavirus disease 2019 (COVID-19). This study assessed whether COVID-19 vaccination protected against PCCs in persons with mild initial infections during Delta and Omicron variant predominance.

Methods: This study utilized a case-control design, nested within the HEROES-RECOVER cohort. Participants aged ≥18 years with test-confirmed severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) between 28 June 2021 and 14 September 2022 were surveyed for PCCs, defined by symptoms lasting >4 weeks after initial infection. Cases self-reported PCCs and controls self-reported no PCCs. The exposure was …

Ca-125 As A Biomarker In Renal Medullary Carcinoma: Integrated Molecular Profiling, Functional Characterization, And Prospective Clinical Validation, Sandra L Grimm, Menuka Karki, Kyle A Blum, Jean-Philippe Bertocchio, Rong He, Durga N Tripathi, Niki M Zacharias, Justin M Lebenthal, Rahul A Sheth, Priya Rao, Giannicola Genovese, Zhen Lu, Robert C Bast, Davis R Ingram, Rossana Lazcano, Khalida M Wani, Wei-Lien Wang, Alexander J Lazar, Nizar M Tannir, Cheryl L Walker, Cristian Coarfa, Pavlos Msaouel

Faculty, Staff and Student Publications

Purpose: Renal medullary carcinoma (RMC) is a highly aggressive malignancy defined by the loss of the SMARCB1 tumor suppressor. It mainly affects young individuals of African descent with sickle cell trait, and it is resistant to conventional therapies used for other renal cell carcinomas. This study aimed to identify potential biomarkers for early detection and disease monitoring of RMC.

Experimental design: Integrated profiling of primary untreated RMC tumor tissues and paired adjacent kidney controls was performed using RNA sequencing and histone chromatin immunoprecipitation sequencing. The expression of serum cancer antigen 125 (CA-125), was prospectively evaluated in 47 patients with RMC. …

Genetic Associations With C-Peptide Levels Before Type 1 Diabetes Diagnosis In At-Risk Relatives, Taylor M Triolo, Hemang M Parikh, Mustafa Tosur, Lauric A Ferrat, Lu You, Peter A Gottlieb, Richard A Oram, Suna Onengut-Gumuscu, Jeffrey P Krischer, Stephen S Rich, Andrea K Steck, Maria J Redondo

Children’s Nutrition Research Center Staff Publications

Objective: We sought to determine whether the type 1 diabetes genetic risk score-2 (T1D-GRS2) and single nucleotide polymorphisms are associated with C-peptide preservation before type 1 diabetes diagnosis.

Methods: We conducted a retrospective analysis of 713 autoantibody-positive participants who developed type 1 diabetes in the TrialNet Pathway to Prevention Study who had T1DExomeChip data. We evaluated the relationships of 16 known single nucleotide polymorphisms and T1D-GRS2 with area under the curve (AUC) C-peptide levels during oral glucose tolerance tests conducted in the 9 months before diagnosis.

Results: Higher T1D-GRS2 was associated with lower C-peptide AUC in the 9 months before …

Exploring Profiles Of Fathers Integrating Food And Physical Activity Parenting Practices, John A Jimenez-Garcia, Louise C Mâsse, Robert L Newton, Salma M Musaad, Alicia Beltran, Teresia M O'Connor

Children’s Nutrition Research Center Staff Publications

Objective: This study aims to identify fathers' profiles integrating food parenting practices (FPP) and physical activity parenting practices (PAPP).

Design: We analysed cross-sectional data. The fathers completed the reduced FPP and PAPP item banks and socio-demographic and family dynamics (co-parenting and household responsibility) questionnaires. We identified fathers' profiles via latent profile analysis. We explored the influence of social determinants, child characteristics and family dynamics on fathers' profiles using multinomial logistic regression.

Setting: Online survey in the USA.

Participants: Fathers of 5-11-year-old children.

Results: We analysed data from 606 fathers (age = 38 ± 8·0; Hispanic = 37·5 %). Most fathers …

The Role Of Genetics In Human Oral Health: A Systematic-Narrative Review, Anita Joy-Thomas, Zarna Lalwani, Leticia Guajardo, John Valenza, Walid D Fakhouri

Faculty, Staff and Student Publications

Background/Objectives: An individual's genetic makeup influences their organ development, orofacial structures, and overall health. Though many studies have been conducted to determine the inheritance of oral diseases and conditions, there is a lack of comprehensive research classifying these disorders based on the genetic and environmental etiology.

Methods: This systematic review aimed to analyze the existing body of literature using the PubMed and Cochrane databases and answer the following question: "What evidence exists supporting the role of genetic factors in oral conditions?" This systematic-narrative review methodically categorizes oral diseases and conditions based on their genetic or environmental linkages. Each …

Extensive Epigenomic Dysregulation Is A Hallmark Of Homologous Recombination Deficiency In Triple-Negative Breast Cancer, Youdinghuan Chen, Lucas A Salas, Jonathan D Marotti, Nicole P Jenkins, Chao Cheng, Todd W Miller, Arminja N Kettenbach, Brock C Christensen

Faculty, Staff and Students Publications

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with substantial disease heterogeneity, limited treatment options, and dismal clinical outcomes. Some TNBCs display homologous recombination deficiency (HRD), a phenotype with elevated genomic burden and worse prognosis if left untreated but chemotherapeutic sensitivity. While the molecular landscape of TNBC is distinct from other breast cancer subtypes, the TNBC-specific link between HRD and epigenome-wide methylation has not been established. This study reports two independent cohorts of TNBC tumors (n = 32 and n = 58) with HRD and epigenomic landscapes measured by the Multiplex Ligation-dependent Probe Amplification assay and the …

Inflammation And Gut Barrier Function-Related Genes And Colorectal Cancer Risk In Western European Populations, Hannah B Mandle, Mazda Jenab, Marc J Gunter, Anne Tjønneland, Anja Olsen, Christina C Dahm, Jie Zhang, Pierre-Emmanuel Sugier, Joseph Rothwell, Gianluca Severi, Rudolf Kaaks, Verena A Katzke, Matthias B Schulze, Giovanna Masala, Sabina Sieri, Salvatore Panico, Carlotta Sacerdote, Catalina Bonet, Maria-Jose Sánchez, Pilar Amiano, José María Huerta, Marcela Guevara, Richard Palmqvist, Thyra Löwenmark, Aurora Perez-Cornago, Elisabete Weiderpass, Alicia K Heath, Amanda J Cross, Paolo Vineis, David J Hughes, Veronika Fedirko

Faculty, Staff and Student Publications

Gut barrier dysfunction and related inflammation are known to be associated with the development and progression of colorectal cancer (CRC). We investigated associations of 292 single-nucleotide polymorphisms (SNPs) from 27 genes related to endotoxins/lipopolysaccharide (LPS) sensing and tolerance, mucin synthesis, inflammation, and Crohn's disease with colon and rectal cancer risks. Incident CRC cases (N = 1374; colon = 871, rectum = 503) were matched 1:1 to controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. Previously measured serum concentrations of gut barrier function and inflammation biomarkers (flagellin/LPS-specific immunoglobulins and C-reactive protein [CRP]) were available for a sub-set …

Adding Metastasis-Directed Therapy To Standard-Of-Care Systemic Therapy For Oligometastatic Breast Cancer (Extend): A Multicenter, Randomized Phase 2 Trial, Jay P Reddy, Alexander D Sherry, Bryan Fellman, Suyu Liu, Tharakeswara Bathala, Cara Haymaker, Lorenzo Cohen, Benjamin D Smith, David Ramirez, Simona F Shaitelman, Stephen G Chun, Marina Medina-Rosales, Mediget Teshome, Abenaa Brewster, Carlos H Barcenas, Alexandre Reuben, Amol J Ghia, Ethan B Ludmir, Daniel Weed, Shalin J Shah, Melissa P Mitchell, Wendy A Woodward, Daniel R Gomez, Chad Tang

Faculty, Staff and Student Publications

PURPOSE: Prior evidence suggests a progression-free survival (PFS) benefit from adding metastasis-directed therapy (MDT) to standard-of-care (SOC) systemic therapy for patients with some oligometastatic solid tumors. Randomized trials testing this hypothesis in breast cancer have yet to be published. We sought to determine whether adding MDT to SOC systemic therapy improves PFS in oligometastatic breast cancer.

METHODS AND MATERIALS: External Beam Radiation to Eliminate Nominal Metastatic Disease is a multicenter phase 2 randomized basket trial testing the addition of MDT to SOC systemic therapy in patients with ≤5 metastases (NCT03599765). Patients were randomly assigned 1:1 to MDT (definitive local treatment …

Investigation Of Dynamic Regulation Of Tfeb Nuclear Shuttling By Microfluidics And Quantitative Modelling, Iacopo Ruolo, Sara Napolitano, Lorena Postiglione, Gennaro Napolitano, Andrea Ballabio, Diego Di Bernardo

Duncan NRI Faculty and Staff Publications

Transcription Factor EB (TFEB) controls lysosomal biogenesis and autophagy in response to nutritional status and other stress factors. Although its regulation by nuclear translocation is known to involve a complex network of well-studied regulatory processes, the precise contribution of each of these mechanisms is unclear. Using microfluidics technology and real-time imaging coupled with mathematical modelling, we explored the dynamic regulation of TFEB under different conditions. We found that TFEB nuclear translocation upon nutrient deprivation happens in two phases: a fast one characterised by a transient boost in TFEB dephosphorylation dependent on transient calcium release mediated by mucolipin 1 (MCOLN1) followed …

Superior Preclinical Efficacy Of Co-Treatment With Brg1/Brm And Flt3 Inhibitor Against Aml Cells With Flt3 Mutations, Warren Fiskus, Christopher P Mill, Jessica Piel, Mike Collins, Murphy Hentemann, Branko Cuglievan, Christine E Birdwell, Kaberi Das, Hanxi Hou, John A Davis, Antrix Jain, Anna Malovannaya, Tapan M Kadia, Naval Daver, Koji Sasaki, Koichi Takahashi, Danielle Hammond, Patrick K Reville, Lauren B Flores, Sanam Loghavi, Xiaoping Su, Courtney D Dinardo, Kapil N Bhalla

Faculty, Staff and Student Publications

Although treatment with standard frontline therapies, including a FLT3 inhibitor (FLT3i) reduces AML burden and achieves clinical remissions, most patients with AML with FLT3 mutation relapse due to therapy-resistant stem/progenitor cells. The core ATPases, BRG1 (SMARCA4) and BRM (SMARCA2) of the canonical (c) BAF (BRG1/BRM-associated factor) complex is a dependency in AML cells, including those harboring FLT3 mutations. We have previously reported that treatment with FHD-286, a BRG1/BRM ATPases inhibitor, induces differentiation and loss of viability of AML stem/progenitor cells. Findings of present studies demonstrate that treatment with FHD-286 induces lethality in AML cells, regardless of sensitivity or resistance to …

Precision Phenotyping For Curating Research Cohorts Of Patients With Unexplained Post-Acute Sequelae Of Covid-19, Alaleh Azhir, Jonas Hügel, Jiazi Tian, Jingya Cheng, Ingrid V Bassett, Douglas S Bell, Elmer V Bernstam, Maha R Farhat, Darren W Henderson, Emily S Lau, Michele Morris, Yevgeniy R Semenov, Virginia A Triant, Shyam Visweswaran, Zachary H Strasser, Jeffrey G Klann, Shawn N Murphy, Hossein Estiri

Faculty, Staff and Student Publications

BACKGROUND: Scalable identification of patients with post-acute sequelae of COVID-19 (PASC) is challenging due to a lack of reproducible precision phenotyping algorithms, which has led to suboptimal accuracy, demographic biases, and underestimation of the PASC.

METHODS: In a retrospective case-control study, we developed a precision phenotyping algorithm for identifying cohorts of patients with PASC. We used longitudinal electronic health records data from over 295,000 patients from 14 hospitals and 20 community health centers in Massachusetts. The algorithm employs an attention mechanism to simultaneously exclude sequelae that prior conditions can explain and include infection-associated chronic conditions. We performed independent chart reviews …

Body Composition And Its Outcomes And Management In Multiple Sclerosis: Narrative Review, Ariel Kidwell-Chandler, Justin Jackson, Brenda Jeng, Stephanie L Silveira, Lara A Pilutti, Paul R Hibbing, Robert W Motl

Faculty, Staff and Student Publications

Background: There is emerging interest in obesity and its prevalence, outcomes, and management in people with multiple sclerosis (MS). Body mass index (BMI) is the traditional marker of obesity in MS, whereas body composition, inclusive of specific body tissue compartments (e.g., fat, bone, and muscle), is often overlooked despite its relevance.

Objective: This narrative review (a) underscored the use and utility of dual-energy X-ray absorptiometry (DEXA) as an accurate and reliable measure of body composition; (b) thematically analyzed and synthesized the current evidence regarding body composition (using DEXA); and (c) determined gaps to be addressed in future research. Methods: …