Digital Commons Network^™

Silent Messengers In The Nano-World: Harnessing Extracellular Vesicles As Theranostic Tools For Neonatal Surgical Conditions, Augusto Zani

2020-Current year OA Pubs

Extracellular vesicles (EVs) are lipid bilayer-enclosed nanoparticles secreted by all cells that mediate intercellular communication by transferring proteins, lipids, and nucleic acids. Among their cargo, microRNAs are key post-transcriptional regulators of organogenesis. In fetal lung development, EV-mediated signaling is essential for the coordination of epithelial, mesenchymal, endothelial, and immune cells. In congenital diaphragmatic hernia (CDH), disruption of these interactions leads to pulmonary hypoplasia and pulmonary hypertension, the primary causes of morbidity and mortality. Amniotic fluid stem cell-derived EVs (AFSC-EVs) have emerged as a promising cell-free therapy to restore this impaired communication. In rodent, rabbit, and human models of pulmonary hypoplasia, …

Evaluating The Effectiveness Of Escalating To Weekly Adalimumab Dosing For The Treatment Of Noninfectious Uveitis: A Multicenter Study, Shani Pillar, Akshay Thomas, Lynn M Hassman, Howard Chen, Sapna Gangaputra, Laura J Kopplin, Kelly Boyd, Kareem Moussa, Derek C Pham, Keren Chen, Nicholas J Jackson, Edmund Tsui

2020-Current year OA Pubs

PURPOSE: To evaluate the effectiveness of adalimumab dosage escalation in patients with noninfectious uveitis that is controlled inadequately with standard dosing.

DESIGN: Multicenter retrospective interventional case series.

PARTICIPANTS: Patients with noninfectious uveitis receiving active standard biweekly adalimumab dosing who underwent treatment escalation to weekly adalimumab dosing at 6 tertiary referral centers.

METHODS: Demographic data and clinical findings were assessed at the time of adalimumab dosage escalation and 6 months later. Mixed-model analysis was performed to analyze clinical outcomes and to assess predictive factors of success.

MAIN OUTCOME MEASURES: Treatment success composite criteria included: (1) disease quiescence (≤ 0.5+ anterior chamber …

Leveraging The Pedsnet Clinical Research Network And Electronic Health Record Data To Enhance Efficiency Of Trial Enrollment For A Rare Pediatric Rheumatic Disease, Pamela F Weiss, Levon Utidjian, Mitchell Maltenfort, Hanieh Razzaghi, Timothy G Brandon, Cassandra Muir, Cora Sears, Edward J Oberle, Jennifer Cooper, Kevin Baszis, Mary B Toth, Esi M Morgan, Christopher B Forrest

2020-Current year OA Pubs

BACKGROUND: We evaluated the PEDSnet clinical research network for study enrollment of juvenile spondyloarthritis, a rare rheumatic disease that includes enthesitis-related arthritis (ERA) and psoriatic arthritis (PsA). METHODS: An electronic health record (EHR)-based typology was developed by an interdisciplinary team to query EHR data for a spectrum of pediatric rheumatic diseases (2009–2023) from 8 PEDSnet centers. The prevalence, characteristics and drug exposures for juvenile spondyloarthritis was explored to gauge feasibility of leveraging the network for study enrollment. Next, the typology was adapted to identify subjects for a clinical trial; the efficiency of EHR typology query was compared to standard screening …

Sequential Platinum And Parp Inhibition Enhances Pd1 Immunotherapy Efficacy In Murine Brca2 Mutated Pancreatic Cancer, John C Mcvey, Max M Wattenberg, Heather Coho, Kayjana Infante, Kelly Markowitz, Devora Delman, Cynthia Clendenin, Emma E Furth, Rashmi Tondon, Ben Z Stanger, Robert H Vonderheide, Kim A Reiss, Gregory L Beatty

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDAC) is a challenging malignancy to treat, but emerging evidence suggests that specific subtypes may respond more favorably to certain therapies. BRCA-mutated PDAC represents a distinct subtype that is particularly sensitive to DNA-damaging therapies. The current standard of care for advanced BRCA-mutated PDAC involves induction platinum-based chemotherapy followed by maintenance therapy with a poly (ADP-ribose) polymerase inhibitor (PARPi). However, the randomized phase III POLO trial, upon which this standard is based, did not demonstrate an improved overall survival in patients who received olaparib compared to those who received placebo, highlighting the need for new therapeutic approaches. Additionally, …

Human Chorionic Gonadotropin Decreases Cerebral Cystic Encephalomalacia And Parvalbumin Interneuron Degeneration In A Pro-Inflammatory Model Of Mouse Neonatal Hypoxia-Ischemia, Benjamin Miller, Alexander Crider, Bhooma Aravamuthan, Rafael Galindo

2020-Current year OA Pubs

Human chorionic gonadotropin (hCG) is an immunoregulatory and neurotrophic glycoprotein of potential clinical utility in the neonate at risk for cerebral injury. However, hCG has not been demonstrated to affect the pro-degenerative actions of inflammation in neonatal brain injury. Here we utilize a neonatal mouse model of mild hypoxia-ischemia (HI) combined with intraperitoneal administration of lipopolysaccharide (LPS) to evaluate the neuroprotective actions of hCG in the setting of systemic inflammation. Intraperitoneal treatment with hCG significantly decreased tissue loss and cystic degeneration in the hippocampus and cerebral cortex of term-equivalent neonatal mice exposed to LPS and HI. Noting that parvalbumin immunoreactive …

Novel R Shiny Tool For Survival Analysis With Time-Varying Covariate In Oncology Studies: Overcoming Biases And Enhancing Collaboration, Yimei Li, Yang Qiao, Fei Gao, Jordan Gauthier, Qiang Ed Zhang, Jenna Voutsinas, Wendy Leisenring, Ted Gooley, Corinne Summers, Alexandre Hirayama, Cameron Turtle, Rebecca Gardner, Jarcy Zee, Qian Vicky Wu

Wills Eye Hospital Papers

PURPOSE: Our study is motivated by evaluating the role of hematopoietic cell transplantation (HCT) after chimeric antigen receptor T-cell (CAR-T) therapy for ALL, a debated topic. Because patients may receive HCT at different times after CAR-T infusion or never, HCT post-CAR-T should be considered as a time-varying covariate (TVC).

METHODS: Standard Cox models and Kaplan-Meier (KM) curves (naïve method) assume that TVC status is known and fixed at baseline, which can yield biased estimates. Landmark analysis is a popular alternative but depends on a chosen landmark time. Time-dependent (TD) Cox model is better suited for TVC although visualizing survival curves …

Partial Versus Full Revision In Cementless Single-Stage Exchange For Hip Periprosthetic Joint Infection: A Multicenter Comparative Study With 10-Year Survivorship Analysis, Wenbo Mu, Atthakorn Jarusriwanna, Boyong Xu, Scot A. Brown, Xiaogang Zhang, Alexander Dawes, Javad Parvizi Md, Li Cao

Rothman Institute Papers

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most challenging complications following total hip arthroplasty (THA). Traditional management typically involves full revision to ensure comprehensive infection eradication. However, for patients with well-fixed implants, partial revision in a single-stage cementless approach may provide a viable alternative, potentially preserving bone stock and reducing operative time. The relative efficacy of this approach compared with full revision remains to be fully explored. This multicenter study aims to determine whether partial revision in cementless single-stage exchange surgery offers comparable infection control outcomes to full revision for select patients with well-fixed implants.

METHODS: We conducted …

Downregulation Of Slc40a1 Leads To Iron Accumulation In Fibrotic Lung Fibroblasts, Quanjin Dang, Chaoqun Huang, Yurong Liang, Akshaya Surendran, Dharanya Muthiah, Kishore Vaddadi, Sankha Hewawasam, Tingting W Mills, Lin Liu

Faculty, Staff and Student Publications

Iron is an essential nutrient for almost all organisms. However, excess iron generates reactive oxygen species and causes tissue injuries. Iron is implicated in idiopathic pulmonary fibrosis (IPF). In this study, we examined iron accumulation in fibrotic lung fibroblasts and the underlying mechanisms. We hypothesize that the downregulation of Solute Carrier Family 40 Member 1 (SLC40A1) results in iron accumulation in lung fibroblasts of IPF patients. Using a Prussian Blue iron staining, we found that iron accumulated in the fibrotic region of the lungs from IPF patients and bleomycin- and asbestos-induced lung fibrosis mice. Iron was partially co-localized with the …

The Origin Of Hepatocellular Carcinoma Depends On Metabolic Zonation, Jason Guo, Roger Liang, Andrew Chung, Zhijie Li, Boyuan Li, Eric Chen, Lin Li, Jingjing Wang, Meng-Hsiung Hsieh, Ivy Xiangyi Fang, Benjamin Kroger, Yunguan Wang, Min Zhu, Xiongzhao Ren, Greg Mannino, Yuemeng Jia, Yonglong Wei, Stephen Moore, Daniel J Siegwart, Stephen S Chung, Zixi Wang, Tripti Sharma, Suman Komjeti, Yi Han, Purva Gopal, Guanghua Xiao, Tao Wang, Hao Zhu

Faculty, Staff and Student Publications

The origin of cancer is poorly understood because premalignant cells are rarely followed in their native environments. Although the spatial compartmentalization of metabolic functions is critical for proper liver function, it is unknown whether cancers arise from some zones but not others and whether there are metabolic determinants of cancer risk. Zone-specific, mosaic introduction of Ctnnb1 (catenin beta 1) and Arid2 (AT-rich interaction domain 2) mutations, commonly co-mutated genes in hepatocellular carcinoma (HCC), in mouse models showed that position and metabolic context determine clone fates. Ctnnb1/Arid2-driven cancers were much more likely to arise in zone 3. The …

Establishing T1 And Ecv Mapping Based Nomogram Differentiate Acute Ischemic And Nonischemic Myocardial Injury: A Proof-Of-Concept Study, Yanping Su, Kan Liu, Et Al.

2020-Current year OA Pubs

OBJECTIVES: To develop and validate a nomogram based on T1 and extracellular volume fraction (ECV) mapping derived from cardiovascular magnetic resonance (CMR) for differentiating ischemic from nonischemic cardiomyopathies during the acute phase.

METHODS: This retrospective study included patients who underwent CMR at the Fifth Affiliated Hospital of Wenzhou Medical University (internal dataset) and the Fifth Affiliated Hospital of Sun Yat-sen University (external dataset). Patients were assigned to a training set (n = 73), a test set (n = 30), an internal validation set (n = 28), and an external validation set (n = 16). Six multivariable logistic regression models were …

Olutasidenib In Recurrent/Relapsed Locally Advanced Or Metastatic Idh1-Mutated Chondrosarcoma: Phase 1b/2 Trial, Robin L Jones, Roman Groisberg, Jean-Yves Blay, Howard Colman, Macarena De La Fuente, Patricia Roxburgh, Mwe Mwe Chao, Hua Tian, Florence Duffaud, Rastislav Bahleda, Brian A Van Tine

2020-Current year OA Pubs

Chondrosarcomas are rare cartilaginous neoplasms with limited treatment options. Isocitrate dehydrogenase 1/2 (mIDH1/2) mutations occur in 65% of chondrosarcomas. Here we report safety and efficacy of olutasidenib, an mIDH1 inhibitor, evaluated in patients with locally advanced or metastatic mIDH1 chondrosarcoma (Clinicaltrials.gov identifier: NCT03684811). The primary endpoint was objective response rate by tumor evaluation; secondary endpoints included adverse events, progression-free and overall survival. Patients received olutasidenib 150 mg twice daily. Twenty-three patients were enrolled; 16 were diagnosed with conventional chondrosarcoma (cCS). Median age was 57 (range, 30-71) years. In 21 response-evaluable patients, 11 (52%) had stable disease, 8 (38%) had progressive …

Designing Inclusive Newborn Sequencing Research: Insights From Parents In Underrepresented Communities, Maya C Del Rosario, Sheyenne A Walmsley, Barbara W Harrison, Crystal T Stephens, Bethany Zettler, Greysha Rivera-Cruz, Priyal Agrawal, Amy Brower, Stephanie Chigbu, Kurt D Christensen, Casie A Genetti, Richetta Givens, Nina B Gold, Inez V Reeves, Isabella Schichter, Habib Shariat, Sandra Simon, Hadley Stevens Smith, Melissa Uveges, Robert C Green, Ingrid A Holm, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Background: It is essential that studies of genomic sequencing (GS) in newborns and children include individuals from under-represented racial and ethnic groups (URG) to ensure future applications are equitably implemented. We conducted interviews with parents from URG to better understand their perspectives on GS research, develop strategies to reduce barriers to enrollment, and facilitate research participation.

Methods: Semi-structured interviews with 50 parents from URG.

Results: Nearly all parents said they would be interested in participating in an infant GS study. Parents were interested in participating in GS research for reasons including clinical utility, personal utility, and/or family health benefits. Deterrents …

Mast Cells Promote Pathology And Susceptibility In Tuberculosis, Ananya Gupta, Vibha Taneja, Javier Rangel-Moreno, Nilofer Naqvi, Abhimanyu, Yun Tao, Mushtaq Ahmed, Kuldeep Singh Chauhan, Daniela Trejo-Ponce De Leon, Gustavo Ramírez-Martínez, Luis Jiménez-Alvarez, Cesar Luna-Rivero, Joaquin Zuniga, Deepak Kaushal, Shabaana A Khader

2020-Current year OA Pubs

Tuberculosis (TB), caused by the bacterium

Defining The Heterogeneous Molecular Landscape Of Lung Cancer Cell Responses To Epigenetic Inhibition, Chuwei Lin, Catherine M Sniezek, Christopher D Mcgann, Rashmi Karki, Ross M Giglio, Benjamin A Garcia, José L Mcfaline-Figueroa, Devin K Schweppe

2020-Current year OA Pubs

Epigenetic inhibitors exhibit powerful antiproliferative and anticancer activities. However, cellular responses to small-molecule epigenetic inhibition are heterogeneous and dependent on factors such as the genetic background and metabolic state of cells, as well as on-/off-target engagement of individual small-molecule compounds. The molecular study of the extent of this heterogeneity often measures changes in a single cell line. To more comprehensively profile the effects of small-molecule perturbations and their influence on heterogeneous cellular responses, we present a molecular resource based on the quantification of chromatin, proteome, and transcriptome remodeling due to histone deacetylase inhibitors (HDACi) in non-isogenic cell lines. Through quantitative …

Epidermal Growth Factor Receptor Regulates Beclin-1 In Hyperoxic Acute Lung Injury., Zachary M Harris, Asawari Korde, Johad Khoury, Edward P Manning, Gail Stanley, Yosep Shin, Kennedy Mitchell, Alexa Von Der Schulenburg, Ying Sun, Buqu Hu, Hyeon Jun Shin, John Joerns, Brian Clark, Lindsey Placek, Derya Unutmaz, Aigul Moldobaeva, Lokesh Sharma, Maor Sauler, Govindarajan Rajagopalan, Xuchen Zhang, He Wang, Mahboobe Ghaedi, Min-Jong Kang, Jonathan L Koff

Faculty Research 2026

BACKGROUND: While delivery of supplemental oxygen is a life-saving therapy, exposure to high oxygen, called hyperoxia, leads to increased intensive care unit mortality. Hyperoxia induces oxidant-mediated acute lung injury (ALI) and pulmonary cell death, called hyperoxic ALI (HALI). Elucidating molecular mechanisms in HALI could identify therapeutic targets in ALI.

METHODS: In the current study, we examined in vivo effects of HALI on Beclin-1 (BCN1), which regulates autophagy, and modulation of BCN1 by epidermal growth factor receptor (EGFR). Effects of HALI on BCN1 and autophagy were examined in mice with genetically decreased EGFR (EGFR

RESULTS: In WT, HALI led to increased …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Expression Spectrum Of Te-Driven Transcripts In Human Adult Tissues, Benpeng Miao, Xinlong Luo, Amina Ademovic, Yushan Yang, Tao P Wu, Bo A Zhang

2020-Current year OA Pubs

BACKGROUND: Transposable elements (TEs) are vital components of eukaryotic genomes and have played a critical role in genome evolution. Although most TEs are silenced in the mammalian genome, increasing evidence suggests that certain TEs are actively involved in gene regulation during early developmental stages. However, the extent to which human TEs drive gene transcription in adult tissues remains largely unexplored. RESULTS: In this study, we systematically analyze 17,329 human transcriptomes to investigate how TEs influence gene transcription across 47 adult tissues. Our findings reveal that TE-driven transcripts are broadly expressed in human tissues, contributing to both housekeeping functions and tissue-specific …

Dual Roles Of Trpv2 In The Innate Immune Response To Cytosolic Dna: Arresting Dormant And Boosting Activated Sting, Chen Cheng, Hsiang-Ting Lu, Shan Li, Zhongsheng You

2020-Current year OA Pubs

The cGAS/STING-dependent innate immune pathway is central in the cellular response to cytosolic DNA derived from viral infections, genotoxic stress, or mitochondrial defects. While efficient activation of the pathway is crucial for defending against pathogens and cancer, maintaining its dormancy without stimuli is equally important to avoid autoimmunity. However, the precise control of the cGAS/STING pathway remains poorly understood. Here, we report that the ion channel TRPV2 regulates both the dormancy and activation of STING. TRPV2 associates with STING and suppresses spontaneous STING activation in the absence of cytoDNA but dissociates from STING and promotes its activation by releasing Ca

Ablation Of Cd38 In Multiple Myeloma Cells Leads To An Aggressive Phenotype In A Mouse Xenograft Model, Michael R Dyer, Alex Zheleznyak, Erin N Teubner, Julie L Prior, Brad Manion, Zhenghan Jing, Amit K Sharma, Junwei Du, Rui Tang, Mark A Fiala, John F Dipersio, Deborah Veis, Julie O'Neal, Mikhail Y Berezin, Monica Shokeen

2020-Current year OA Pubs

Multiple myeloma (MM) is a plasma cell malignancy characterized by bone pain and end-organ failure. A major challenge in treating MM is therapeutic resistance. CD38-targeted immunotherapies, such as daratumumab, have significantly improved outcomes; however, variable responses, resistance, and relapse remain vital challenges. We hypothesized that loss of CD38 drives a more aggressive phenotype and resistance to therapy. To test this, we developed a CD38 knockout (KO) clone of a human MM cell line and evaluated it in immunodeficient mice. Mice with CD38 KO tumors exhibited an increased tumor burden and reduced survival compared with those with CD38 wild-type (WT) tumors. …

Biomarkers Of Response To Neoadjuvant Palbociclib Plus Anastrozole In Endocrine-Resistant Estrogen Receptor-Positive/Her2-Negative Breast Cancer: A Phase 2 Trial, Tim Kong, Alex Mabry, Maureen Highkin, Jeremy Hoog, Zhanfang Guo, Adrian Gonzales-Gonzales, Shana Thomas, Yingduo Song, Feng Gao, Mateusz Opyrchal, Lindsay Peterson, Foluso Ademuyiwa, Julie Margenthaler, Rebecca Aft, Katherine Glover-Collins, Leslie Nehring, Yu Tao, Souzan Sanati, Ian S Hagemann, Fouad Boulos, Li Ding, Stephen T Oh, Ron Bose, Jason D Weber, Jingqin Luo, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

CDK4/6 inhibitors (CDK4/6i) improve outcomes for estrogen receptor (ER) positive/HER2-negative breast cancers (BCs), yet intrinsic and acquired resistance exist. Here, we evaluated anastrozole in combination with palbociclib (ANA/PAL) in the NeoPalAna Endocrine-Resistant cohort (NCT01723774). Thirty-four patients with clinical stage II/III ER + /HER2- BCs resistant to standard neoadjuvant endocrine therapy (on-treatment Ki67 > 10%) received neoadjuvant ANA/PAL, with serial biopsies analyzed. The primary endpoint, complete cell cycle arrest (CCCA; Ki67

Nutrition Assistance Programs And Pediatric Weight Outcomes: A Systematic Review, Dan Ferris, Genevieve Davison, Tyler Frank, Amanda Gilbert, Fanice Thomas, Sydney Rothman, Kim Lipsey, Sarah Moreland-Russell

2020-Current year OA Pubs

BACKGROUND/OBJECTIVES: Food insecurity and pediatric obesity have increased concurrently in the U.S., raising questions about the role of Federal Nutrition Assistance Programs (FNAPs) in shaping weight outcomes. This systematic review examined evidence on relationships between FNAP participation and pediatric weight outcomes.

METHODS: Six databases were searched for U.S.-based, peer-reviewed studies published through July 2024 that assessed FNAP participation and pediatric weight outcomes.

RESULTS: Seventy-five studies met the inclusion criteria, and no consistent pattern indicated that any single FNAP or program type (educational setting-based or direct financial support) reliably reduced or increased childhood overweight or obesity risk. Twenty studies found statistically …

Impact Of Social Vulnerability On Glycemic Control And Diabetes Technology Use In Youth With Type 1 Diabetes, Nicholas R Banull, Melanie Bryan, Stephen I Stone, Hope Shimony, Amanda Ingram, Ana María Arbeláez

2020-Current year OA Pubs

BACKGROUND: Diabetes technology has been shown to improve glycemic control in people with type 1 diabetes (T1DM). Despite their benefits, these technologies are used less frequently by youth from lower socioeconomic backgrounds and racial minorities worldwide. This study aimed to examine the relationship between social vulnerability, disparities in diabetes technology use, and glycemic control in youth with T1DM. METHODS: This retrospective billing code analysis included 1,460 patients with T1DM, aged ≤ 23 years old, who were seen at a large academic diabetes center in the Midwest between January 2020 and April 2022, before the expansion of insurance coverage for diabetes …

Women With Moderate Anaemia Prior To Conception Benefited Most From Nutrition Interventions: A Secondary Analysis Of The Women First Preconception Maternal Nutrition Trial, Sumera Aziz Ali, Ka Kahe, Jeanine Genkinger, Linda Valeri, Sarah Saleem, Saleem Jessani, Robert Goldenberg, Jamie Westcott, Jennifer Kemp, Ana Garces, Lester Figueroa, Shivaprasad Goudar, Sangappa Dhaded, Richard Derman, Antoinette Tshefu Kitoto, Adrien Lokangaka, Melissa Bauserman, Elizabeth Mcclure, Marion Koso-Thomas, Louise Kuhn, Nancy Krebs

Global Health Articles

INTRODUCTION: The Women First (WF) Preconception Maternal Nutrition trial found greater benefits of small-quantity lipid-based nutrient supplements (SQ-LNS) for intrauterine growth among anaemic versus non-anaemic women at preconception. We investigated whether the benefits of SQ-LNS in improving markers of intrauterine growth occurred evenly across the mild to moderate spectrum of pre-pregnancy anaemia.

METHODS: We analysed WF data (n=2443 maternal-newborn dyads) from Pakistan, India, Guatemala and the Democratic Republic of Congo. Women received SQ-LNS either ≥3 months preconception through pregnancy (Arm 1); starting in the late first trimester (Arm 2); or not at all (Arm 3: control), with all supplementations discontinued …

Multilevel Analysis Of The Food And Physical Activity Environment And Adult Obesity Across U.S. Counties And States, Ann Mary Abraham, Michael D Swartz, Alexandra E Van Den Berg, Stephen H Linder

Faculty, Staff and Student Publications

Adult obesity rates have risen steadily across the United States over the past decade, with more than 40% of adults affected. Persistent geographic and demographic disparities exist in obesity prevalence across the nation. While prior research has examined individual or environmental associated factors of obesity, limited studies have addressed both physical activity and food environments across the nation using multilevel approaches. This cross-sectional ecological study (2014-2024) used a two-level random intercept model to assess the association between county- and state-level factors and adult obesity prevalence across over 3000 U.S. counties nested within 51 states. County-level associated factors included food insecurity, …

Creative Arts To Enhance Cervical Cancer Awareness Using Art-Based Messages From A Nigerian Crowdsourcing Open Call: Qualitative Thematic Analysis, Abdulhammed O Babatunde, Olufunto A Olusanya, Peter Kalulu, Temitope Ojo, Onyekachukwu Anikamadu, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cervical cancer is a leading cause of cancer deaths among women in Nigeria, yet awareness is low. Historically, art has served as a medium for processing emotions and sharing experiences, which can be effective in promoting health and behavior change.

OBJECTIVE: This study aimed to examine art submissions and social media engagement from a Nigerian crowdsourcing open call to inform co-designed strategies for cervical cancer prevention among women.

METHODS: This study reported following the SRQR (Standard Reporting for Qualitative Research) guideline. From October to November 2023, we launched an open call for art on social media, inviting adult women …

Intestinal Epithelial Tlr5 Signaling Promotes Barrier-Supportive Macrophages, Ming-Ting Tsai, Ryann Callaghan, Charles Ng, Lisette Peres-Tintin, Dean B Matthews, Nikketa Stanford, Karuna Ganesh, Mary K Estes, Gretchen E Diehl

Faculty, Staff and Students Publications

Intestinal macrophages are essential for epithelial barrier repair. In homeostasis, macrophages are continuously replenished by recruitment of circulating CCR2+ monocytes into the intestinal lamina propria. This requires the commensal microbiota, however, the specific microbial factors and downstream host pathways that coordinate macrophage replenishment are inadequately understood. Here, we show that colonization with an E. coli isolate increased CCR2+ macrophages in the intestine and ameliorated pathology in a colitis model. Using human colonic organoids, we showed E. coli colonization induced CCL2 secretion by intestinal epithelial stem cells which promoted monocyte migration. In vivo, protection was abolished in the absence of epithelial …

Tead-Independent Mechanisms Of Yap Function In Cardiomyocyte Cell Cycle Reentry, Bing Xie, Jeffrey Steimle, Vaibhav Deshmukh, Lin Liu, Chang-Ru Tsai, Todd R Heallen, Wyatt Paltzer, Yuka Morikawa, Fansen Meng, Jun Wang, James F Martin

Faculty, Staff and Students Publications

Adult mammalian hearts exhibit limited regenerative capacity because of the restricted renewal of cardiomyocytes. Recent studies reveal that mammalian hearts exhibit transient regenerative potential within a short time frame after birth, suggesting a regulatory mechanism that prevents adult hearts from initiating a regenerative response to cardiac injury. Here, we discovered that an active form of YAP, named YAP6SA, which is not inhibited by the Hippo signaling pathway and does not interact with TEADs, induces cardiomyocyte cell cycle reentry. In addition, YAP6SA interacts with scaffold protein MPDZ to regulate Rho GTPases and promote cell cycle progression in cardiomyocytes (CMs). Importantly, YAP6SA …

Fyn-Saracatinib Complex Structure Reveals An Active State-Like Conformation, Hai Minh Ta, Banumathi Sankaran, Eric D Roush, Josephine C Ferreon, Allan Chris M Ferreon, Choel Kim

Faculty, Staff and Students Publications

Fyn is a Src-family tyrosine kinase implicated in synaptic dysfunction and neuroinflammation across multiple neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Saracatinib (AZD0530) is a potent Src-family inhibitor that has been explored as a repurposed therapeutic; however, its clinical utility is limited by poor kinase selectivity caused by high sequence conservation within Src-family ATP-binding sites. Here, we combine surface plasmon resonance (SPR) and X-ray crystallography to define saracatinib recognition by the Fyn kinase domain (KD). SPR single-cycle kinetics shows that saracatinib binds the isolated Fyn KD and full-length Fyn with low-nanomolar affinity, whereas dasatinib binds with subnanomolar …

A Universal Of Human Social Cognition: Children From 17 Communities Process Gaze In Similar Ways, Manuel Bohn, Julia Christin Prein, Agnes Ayikoru, Florian M. Bednarski, Ardain Dzabatou, Michael C. Frank, Annette M.E. Henderson, Joan Isabella, Josefine Kalbitz, Patricia Kanngiesser, Dilara Keşşafoğlu, Bahar Köymen, Maira V. Manrique-Hernandez, Shirley Magazi, Lizbeth Mújica-Manrique, Julia Ohlendorf, Damilola Olaoba, Wesley R. Pieters, Sarah Pope-Caldwell, Katie Slocombe, Robert Z. Sparks, Jahnavi Sunderarajan, Wilson Vieira, Zhen Zhang, Yufei Zong, Roman Stengelin, Daniel B.M. Haun

School of Psychology

Theoretical accounts typically assume that key features of human socio-cognitive development are universal. This paper reports a large-scale cross-cultural study (17 communities, diverse ethnicities, N = 1,377, 709 female, mean = 5.50 years, -collected March 2022 to January 2024) on gaze following in early childhood. To test for universality, cognitive processing signatures were derived from a computational model treating gaze following as social vector estimation. Results showed substantial variation between communities and individuals. Yet, the processing signature was found in all communities. Individual differences in performance were related to children's familiarity with the data-collection device but not opportunities for social …