Digital Commons Network^™

Inducible Pou Class 2 Homeobox 3 Expression In Human Intestinal Organoids As A Model Of Human Tuft Cells, Carolyn Bomidi, Luqiong Wang, Hoa Nguyen-Phuc, Mary K Estes, Sarah E Blutt

Faculty, Staff and Students Publications

No abstract provided.

Sewers To Solutions: A Guide To Wastewater Pathogen Monitoring, Justin R Clark, Anthony W Maresso

Faculty, Staff and Students Publications

Wastewater-based epidemiology (WBE) is the analysis of wastewater to detect pathogen levels or activity for public health awareness or action. Pioneered in the 1940s, WBE underwent a resurgence during the COVID-19 pandemic, providing important information about number of cases, outbreaks, and seasonal impact. With advancements in detection technologies and growing interest in environmental surveillance, WBE is poised to become a standard practice in public health monitoring. Here, we provide an overview of the current state of the art of pathogen WBE, including methods of molecular detection, analysis of wastewater data, real-world applications and programs, public health interventions, and benefits and …

Editorial: Advances In Phage Applications: Deciphering Phage Biological And Ecological Mechanisms Through Metagenomics, Tasha M Santiago-Rodriguez, Gary A Toranzos

Faculty, Staff and Students Publications

No abstract provided.

Identification Of Cand1 As A Dna-Dependent Protein Kinase-Regulated Coactivator Of Androgen Receptor And The Arv7 Splice Variant, Ross A Hamilton, Basil Paul, Ping Yi, Kimal Rajapakshe, Anil K Panigrahi, Sandra L Grimm, Cristian Coarfa, Anna Malovannaya, Nancy L Weigel, David M Lonard, Charles E Foulds

Faculty, Staff and Students Publications

ARv7, the most prevalent androgen receptor (AR) variant in castration-resistant prostate cancer, lacks the ligand binding domain (LBD), rendering it resistant to LBD-targeted therapies. Identifying new therapeutic targets requires defining the coregulators and associated regulatory enzymes that govern AR and ARv7 transcriptional activity. Here, we have developed a cell-free DNA pulldown assay employing androgen response elements (AREs) to isolate and characterize the AR- and ARv7-associated coregulator complexes formed on DNA. Mass spectrometry analyses of ARE DNA pulldowns revealed previously unrecognized AR and ARv7 associating coregulators, such as cullin-associated NEDD8-dissociated protein 1 (CAND1), in addition to previously known coregulators. ARv7 showed …

Helicobacter Pylori And Cancer: What's The Link?, Elettra Merola, Giovanni Mario Pes, David Yates Graham, Maria Pina Dore

Faculty, Staff and Students Publications

Helicobacter pylori (H. pylori) is a human bacterial pathogen that causes one of the most common chronic bacterial infections worldwide. The microorganism has been classified by the International Agency for Research on Cancer as a Group I carcinogen. While the etiological link to gastric cancer is well established, the precise molecular and cellular mechanisms driving this transformation are highly complex and incompletely understood. Fundamentally, the infection results from the chronic presence of acute on chronic gastric mucosal inflammation. H. pylori pathogenicity is increased by bacterial virulence factors including the cytotoxin-associated gene A (CagA) and Vacuolating cytotoxin A (VacA) …

Psychometric Properties Of A Novel Affective Bias Task And Its Application In Clinical And Nonclinical Populations, Prathik Kalva, Kourtney Kanja, Brian A Metzger, Xiaoxu Fan, Brian Cui, Bailey Pascuzzi, John Magnotti, Madaline Mocchi, Raissa Mathura, Kelly R Bijanki

Faculty, Staff and Students Publications

To mitigate limitations in self-reported mood assessments, we introduce a novel affective bias task (ABT). The task quantifies instantaneous emotional state by leveraging the phenomenon of affective bias, in which people interpret external emotional stimuli in a manner consistent with their current emotional state. This study establishes task stability in measuring and tracking depressive symptoms in clinical and non-clinical populations. Initial assessment in a large non-clinical sample established normative ratings. Depressive symptoms were tracked relative to task performance in a non-clinical sample, as well as in a clinical cohort undergoing surgical evaluation for severe epilepsy. In both cohorts, a stronger …

Prevalence Of Clinically Relevant Nightmares And Their Differences By Sex And Diagnosis In Psychiatric Inpatients, Katrina A Rufino, Michelle A Patriquin, Courtney B Worley, Michael R Nadorff

Faculty, Staff and Students Publications

Nightmares have been shown to be associated with numerous forms of psychopathology, but the vast majority of this research has taken place in the general population and very little is known about their relation with psychopathology in those requiring inpatient hospitalization. In a sample of 1170 voluntarily admitted psychiatric inpatients, this study explores the frequency of reported nightmares in psychiatric inpatients with the aim of examining the prevalence of psychiatric diagnosis in those with and without clinically relevant nightmares. Participants completed the Disturbing Dream and Nightmare Severity Index (DDNSI) and the Structured Clinical Interview for DSM Disorders (SCID-5) at admission. …

Brain Death Versus Circulatory Death: How Functional Warm Ischemia And Cold Storage Impact Myocardial Membrane Repair In Human Donor Hearts, Shiyi Li, Rishav Bhattacharya, Abdussalam E Elsenousi, Katherine V Nordick, Adel M Hassan, Syed B Peer, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

This study compares myocardial injury responses in human donor hearts from donation after brain death (DBD) and donation after circulatory death (DCD), with a focus on myocardial membrane integrity, pyroptosis, and damage. Unlike DCD hearts, which are exposed to varying durations of functional warm ischemic time (fWIT), DBD hearts, which are never subjected to warm ischemia, served as controls. A total of 24 human hearts were procured, consisting of 6 from the DBD group and 18 from the DCD group. All procured hearts were placed in cold normal saline and stored for up to 6 h. Left ventricular biopsies were …

Mir-302 Regulates Pancreatic Progenitor Pool And Pancreatic Size, Ziyue Z Yang, Caroline G Snider, Ronald J Parchem

Faculty, Staff and Students Publications

Disruptions in pancreatic development can lead to health issues such as pancreatic agenesis and congenital diabetes mellitus. Understanding pancreatic organogenesis is critical for elucidating disease mechanisms and developing regenerative therapies. The pancreas consists of endocrine and exocrine cells, both of which are derived from multipotent progenitor cells (MPCs). MPC proliferation and differentiation are tightly controlled by multiple mechanisms, including post-transcriptional regulation by miRNAs. However, these regulatory factors are not fully understood. Here, we profiled miRNA expression in MPCs and identified that mir-302 was highly enriched during the earliest stages of pancreatic development. Loss of mir-302 resulted in reduced pancreatic size …

Causal Functional Mediation Analysis With An Application To Functional Magnetic Resonance Imaging Data, Yi Zhao, Xi Luo, Michael E Sobel, Martin A Lindquist, Brian S Caffo

Faculty, Staff and Student Publications

A primary goal of task-based functional magnetic resonance imaging (fMRI) studies is to quantify the effective connectivity between brain regions when stimuli are presented. Assessing the dynamics of effective connectivity has attracted increasing attention. Causal mediation analysis serves as a widely implemented tool aiming to delineate the mechanism between task stimuli and brain activations. However, the case, where the treatment, mediator, and outcome are continuous functions, has not been studied. Causal mediation analysis for functional data is considered. Semiparametric functional linear structural equation models are introduced and causal assumptions are discussed. The proposed models allow for the estimation of individual …

Intrathoracic Manifestations Of Hematologic Malignancies: A Narrative Review, Kshama Bhyravabhotla, Gregory Gaskey, Jeremy R Walder, Diwakar D Balachandran, Sujith V Cherian, Bilal Zafar, Lara Bashoura, Ajay Sheshadri, Saadia A Faiz

Faculty, Staff and Student Publications

Background and objective: Although the global incidence of hematologic malignancies is decreasing, the risk of developing these cancers is increasing due to increased lifespan and modern treatments including targeted therapy, chemotherapy, and radiation. Intrathoracic manifestations of hematologic malignancies may be the presenting sign leading to diagnosis or result from various treatment toxicity. The most common respiratory manifestation of hematologic malignancies is infectious, but up to half of pulmonary findings are from non-infectious etiologies. We aim to summarize the current literature on non-infectious intrathoracic manifestations of hematologic malignancies and their treatment.

Methods: We performed a literature review using PubMed Central and …

Netrin-1 Promotes Pancreatic Tumorigenesis And Innervation Through Neo1, Hiroki Kobayashi, Yosuke Ochiai, Junya Arai, Masahiro Hata, Feijing Wu, Masaki Sunagawa, Tadashi Iida, Taisuke Baba, Ermanno Malagola, Takayuki Tanaka, Zhengyu Jiang, Ruth A White, Xiaofei Zhi, Jin Qian, Quin T Waterbury, Ruhong Tu, Biyun Zheng, Yi Zeng, Hualong Zheng, Puran Zhang, Shuang Li, Leah B Zamechek, Jonathan S Labella, Takahiro Sugie, Atsushi Enomoto, Holger K Eltzschig, Carmine F Palermo, Iok In Christine Chio, Kenneth P Olive, Timothy C Wang

Faculty, Staff and Student Publications

Nerves can regulate tumorigenesis and cancer progression. However, clarification of the role of axon guidance molecules in tumorigenesis, innervation, and metastasis is required to better understand the tumor-promoting functions of nerves. Using murine KrasG12D-mutant pancreatic organoids, we screened axon guidance molecules and identified netrin-1 upregulation. Netrin-1 was also upregulated in vivo during pancreatic tumorigenesis in humans and mice. Mutant KRAS and β-adrenergic signaling upregulated netrin-1 and its receptor NEO1 in epithelial cells in part through the MAPK pathway. Ex vivo culture of celiac ganglia showed that netrin-1 promoted the axonogenesis of sympathetic neurons through nerve NEO1. In the Pdx1-Cre;LSL-KrasG12D/+ model, …

Speeding Up Interval Estimation For R2-Based Mediation Effect Of High-Dimensional Mediators Via Cross-Fitting, Zhichao Xu, Chunlin Li, Sunyi Chi, Tianzhong Yang, Peng Wei

Faculty, Staff and Student Publications

Mediation analysis is a useful tool in investigating how molecular phenotypes such as gene expression mediate the effect of exposure on health outcomes. However, commonly used mean-based total mediation effect measures may suffer from cancellation of component-wise mediation effects in opposite directions in the presence of high-dimensional omics mediators. To overcome this limitation, we recently proposed a variance-based R-squared total mediation effect measure that relies on the computationally intensive nonparametric bootstrap for confidence interval estimation. In the work described herein, we formulated a more efficient two-stage, cross-fitted estimation procedure for the R2 measure. To avoid potential bias, we performed …

Us Drug Policy Does Not Align With Experts’ Rankings Of Drug Harms: A Multi-Criteria Decision Analysis, Michael Broman, Alan K Davis, Stacey Armstrong, Adam Levin, Kaltum Ahmed, Gustavo A Angarita, Brooke J Arterberry, Cecilia Bergeria, Mitch Earleywine, Kathryn S Gex, Tom Gregoire, Jamey J Lister, David S Mathai, Nicky J Mehtani, Nathan Menke, Charles D Nichols, Hillary Shaub, Alayna P Tackett, Brandon Weiss, Nefize Yalin, Lawrence D Phillips

Faculty, Staff and Students Publications

Background: United States drug policy is primarily based on the Controlled Substances Act of 1970 and largely contradicts scientific evidence about how to mitigate drugs’ harms. Expert consensus on drug harms could inform policy that improves the health of people who use drugs while reducing negative societal impacts of drug use. Therefore, this study adapted and extended the relevant 2010 United Kingdom multi-criteria decision analysis, rating drug harms by criteria comprising health and social impacts to people who use drugs and their families, communities, and society.

Methods: Seventeen experts on drug use in the US, including three with lived experience …

Nutrition Support Adequacy In Children With Biliary Atresia After Liver Transplant, Nicole Knebusch, Manpreet Virk, Moreshwar S Desai, Marwa Mansour, Stacey Beer, Brittany Pearo, Kelby Fuller, Krupa Mysore, John Goss, Thomas Fogarty, Fernando Stein, Jorge A Coss-Bu

Faculty, Staff and Students Publications

No abstract provided.

An Integrated Platform For Concurrent Structural And Single-Nucleotide Variants Improves Copy-Number Detection And Reveals Pathogenic Alleles In Undiagnosed Mendelian Families, Haowei Du, Ming Yin Lun, Lidiia Gagarina, Jesse D Bengtsson, Christopher M Grochowski, Michele G Mehaffey, James Paul Hwang, Shalini N Jhangiani, Sravya V Bhamidipati, Donna M Muzny, M Cecilia Poli, Sebastian Ochoa, Ivan K Chinn, Anna Lindstrand, Jennifer E Posey, Richard A Gibbs, Pengfei Liu, James R Lupski, Claudia M B Carvalho

Faculty, Staff and Students Publications

Background: Copy number variation (CNV) is a class of genomic structural variation (SV) that contributes to genomic disorders and can significantly impact health. Short-read genome sequencing (sr-GS) enables genome-wide SV calling which has been shown to increase diagnosis in unsolved rare disease families. The growing number of large sequencing cohort projects with sr-GS data available requires open free analytical tools that provide visualization of CNV and SV integrated calls associated with gene annotation, proband-parent trio analysis to enable prioritization of de novo variants, B-allele frequency (BAF) plots to support CNV calls, parent of origin assessment and mosaicism detection.

Methods: To …

Gut Microbiome Metagenomics In Clinical Practice: Bridging The Gap Between Research And Precision Medicine, Henok Ayalew Tegegne, Tor C Savidge

Faculty, Staff and Students Publications

Gut microbiome metagenomics is emerging as a cornerstone of precision medicine, offering exceptional opportunities for improved diagnostics, risk stratification, and therapeutic development. Advances in high-throughput sequencing have uncovered robust microbial signatures linked to infectious, inflammatory, metabolic, and neoplastic diseases. Clinical applications now include pathogen detection, antimicrobial resistance profiling, microbiota-based therapies, and enterotype-guided patient stratification. However, translation into routine care is hindered by significant barriers including methodological variability, limited functional annotation, lack of bioinformatics standardization, and underrepresentation of global populations. This review synthesizes current translational strategies, emphasizing the need for hypothesis-driven designs, multi-omic integration, longitudinal and multi-center cohorts, and mechanistic validation. …

Novel Physical And Biological Applications Of Carbon Ion Radiotherapy, Danushka Seneviratne, Prapannajeet Biswal, Sunil Krishnan

The Brown Foundation: Institute of Molecular Medicine

Carbon ion radiation therapy (CIRT) is a high-LET radiotherapy, which distinguishes itself from traditional low-LET radiation, such as photons and protons, through its unique physical aspects, biological attributes, and the dramatically increased damage it causes within cellular DNA. Given its distinctive characteristics, it is expected to improve the therapeutic ratio of radiation treatments and enhance treatment outcomes in traditionally radiation-resistant tumor histologies. Despite these unique properties, much remains to be understood regarding the clinical use of CIRT before its full potential can be realized. In this review, we summarize the distinct advantages of CIRT with regard to its physical and …

Knowledge Of Cpr And Code Status Discussions In Traumatically Injured Older Adults: Does Health Literacy Matter, Mokunfayo O Fajemisin, Ashna S Karpe, Stephanie Martinez Ugarte, Gabrielle E Hatton, Krislynn Mueck, Lillian S Kao, Martin L Blakely, Gina H Khraish, Aanand Naik, Shreyans Sanghvi, Jessica L Lee, Thaddeus J Puzio

Faculty, Staff and Student Publications

Code Status Discussions (CSDs), CPR understanding, and health literacy is understudied in traumatically injured older adults. We hypothesized that traumatically injured older adults and their families would have limited understanding of CPR and code status, and that lower health literacy would be associated with reduced advance care planning knowledge. We surveyed injured adults ≥65 or their surrogates to assess baseline code status, health literacy, and CPR discussions. Univariate and multivariable analyses were conducted. Among 201 respondents 55% had low health literacy. Only 38% had discussions about CPR, and 21% were asked about code status during admission. Surrogates similarly overestimated CPR …

Invasive Candidiasis In Critically Ill Patients: Fundamental Concepts And Future Directions, María Alejandra Pérez, Wesley J Hoffmann, J Christian Pérez, Max W Adelman

Faculty, Staff and Student Publications

Topic importance: Invasive candidiasis (IC) is a common complication in patients in ICUs. IC can be divided into bloodstream infections (candidemia) and deep-seated infections. Candida infections are associated with high mortality and longer hospital stays. Moreover, the emergence of Candida auris and other species prone to cause ICU outbreaks highlights the importance of this pathogen.

Review findings: Candidemia represents about 20% of bloodstream infections in ICU patients, whereas intraabdominal candidiasis, the most common form of deep-seated infection, predominantly affects surgical ICU patients. Regarding species distribution, Candida albicans is the most common species; however, non-albicans species have become more prevalent in …

Mutational Analysis Of Human Norovirus Vp2 Elucidates Critical Molecular Interactions For Virus Assembly, Janam J Dave, Sue E Crawford, Robert L Atmar, Khalil Ettayebi, B V Venkataram Prasad, Mary K Estes

Faculty, Staff and Students Publications

Human noroviruses (HuNoVs) are the leading cause of viral gastroenteritis, with ≥80% of infections caused by the GII genogroup. HuNoVs are non-enveloped, with an icosahedral capsid composed of 90 dimers of the major capsid protein VP1, which encloses a minor structural protein, VP2, and a VPg-linked, positive-sense ssRNA genome. Although the atomic structure of the icosahedral capsid formed by VP1 is well characterized using crystallography and cryo-electron microscopy analyses of HuNoV virus-like particles, the structures and the localization of VP2 and VPg inside the capsid, how they are incorporated into the capsid, and whether this process requires interactions between them …

Black Bone Mri Morphometry For Mandibular Cortical Bone Measurement In Head And Neck Cancer Patients: Prospective Method Comparison With Ct, Lisanne V Van Dijk, Juan Ventura, Kareem A Wahid, Lin L Zhu, Brigid A Mcdonald, Sara Ahmed, Keith L Sanders, Sonja M Stieb, Lance Mccoy, Christina S Sharafi, Kathryn E Preston, Natalie A West, Sarah Mirbahaeddin, Dina M El-Habashy, Travis Salzillo, Samuel Mulder, Joly Fahim, Aubryane Dearmas, Mona Arbab, Yao Ding, Jihong Wang, Bastien Rigaud, Anando Sen, Mark Chambers, Katherine A Hutcheson, Kristy K Brock, Abdallah S R Mohamed, Stephen Y Lai, Clifton D Fuller

Faculty, Staff and Student Publications

Objectives: Determine the utility of low-flip angle "black bone" magnetic resonance imaging (MRI) for cortical mandibular bone assessment compared to computed tomography (CT).

Methods: Quantification of cortical mandibular bone width was performed per Hamada et al. at 15 cross-sectional interdentium locations on pretreatment black bone MRI and CT for 15 oropharyngeal cancer patients, with interobserver analyses on a subset of three patients by 11 observers. CT and MRI measurements were compared using Bland-Altman analysis, Lin's concordance, and Deming regression; interobserver variability was assessed with absolute variance and intraclass correlation coefficient (ICC).

Results: Bland Altman and Deming regression analyses showed CT …

Sex Differences In Bile Acid Homeostasis And Excretion Underlie The Disparity In Liver Cancer Incidence Between Males And Females, Megan E Patton, Sherwin Kelekar, Lauren J Taylor, Angela E Dean, Qianying Zuo, Rhishikesh N Thakare, Sung Hwan Lee, Emily C Gentry, Morgan Panitchpakdi, Pieter Dorrestein, Yazen Alnouti, Zeynep Madak-Erdogan, Ju-Seog Lee, Milton J Finegold, Sayeepriyadarshini Anakk

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC), the common liver cancer, exhibits higher incidence in males. Here, we report that mice lacking bile acid (BA) regulators, Farnesoid X Receptor (FXR also termed NR1H4) and Small Heterodimer Partner (SHP also termed NR0B2), recapitulate the sex difference in liver cancer risk. Since few therapeutic options are available, we focused on understanding the intrinsic protection afforded to female livers. Transcriptomic analysis in control and NR1H4 and NR0B2 double knockout livers identified female-specific changes in metabolism, including amino acids, lipids, and steroids. To assess translational relevance, we examined if transcriptomic signatures obtained from this murine HCC model correlate …

Non-Invasive Diagnosis Of Pulmonary Tuberculosis Using Face Mask Sampling: A Prospective Study In Adults, Dariusz Woelk, Lennard Meiwes, Nelly Ciobanu, Valeriu Crudu, Anna-Marya Comanac, Stela Kulcitkaia, Anca Vasiliu, Anna Maria Mandalakas, Christoph Lange, Thomas Theo Brehm, Dumitru Chesov

Faculty, Staff and Students Publications

Objectives: Sputum-based diagnostic methods for pulmonary tuberculosis (TB), including culture and nucleic acid amplification tests, provide high sensitivity and specificity. However, these methods rely on the patients' ability to produce sputum. In cases where sputum cannot be obtained, invasive procedures like bronchoscopy may become necessary. Our objective was to evaluate the diagnostic accuracy of face mask sampling (FMS) as a non-invasive alternative.

Methods: Adults with microbiologically confirmed pulmonary TB who had received fewer than three days of anti-TB therapy were recruited in Chişinău, Moldova. FMS was conducted and samples were analyzed on-site using Xpert MTB/RIF Ultra. Diagnostic performance was compared …

Retinal Vasculature In Schizophrenia Spectrum Disorder, Caroline Simon Sherman, Erik Gunnarsson, Nycole Hidalgo, Victoria Chen, Kevin Zhang, Shuo Chen, Hwiyoung Lee, Hugh O'Neill, L Elliot Hong, Osamah Saeedi

Faculty, Staff and Student Publications

The purpose of this research is to determine whether retinal vasculatures differ between participants with schizophrenia spectrum disorder (SSD) and controls. Ninety participants (51 SSD, mean age 35.8 ± 13.5, and 39 controls, mean age 35.5 ± 11.4) underwent 3 × 3 mm2 macular and 6 × 6 mm2 optic nerve head (ONH) optical coherence tomography angiography (OCTA) scans. En face macula and ONH region images were divided into quadrants, binarized, and then skeletonized. Skeletonized vessel densities were compared between our two groups. Additionally, the foveal avascular zone (FAZ) size and acircularity index were compared between the two groups. There …

Context Matching Is Not Reasoning When Performing Generalized Clinical Evaluation Of Generative Language Models, Andrew Wen, Qiuhao Lu, Yu-Neng Chuang, Guanchu Wang, Jiayi Yuan, Jiamu Zhang, Liwei Wang, Sunyang Fu, Kurt D Miller, Heling Jia, Steven D Bedrick, William R Hersh, Kirk E Roberts, Xia Hu, Hongfang Liu

Faculty, Staff and Student Publications

Current discussion surrounding the clinical capabilities of generative language models(GLMs) predominantly centers around multiple-choice question-answer(MCQA) benchmarks derived from clinical licensing examinations. While accepted for human examinees, characteristics unique to GLMs bring into question the validity of such benchmarks. Here, we validate five benchmarks using eight GLMs, ablating for parameter size and reasoning capabilities, validating via prompt permutation three key assumptions that underpin the generalizability of MCQA-based assessments: that knowledge is applied, not memorized, that semantic consistency will lead to consistent answers, and that situations with no answers can be recognized. While large models are more resilient to our perturbations compared …

Context Matching Is Not Reasoning When Performing Generalized Clinical Evaluation Of Generative Language Models, Andrew Wen, Qiuhao Lu, Yu-Neng Chuang, Guanchu Wang, Jiayi Yuan, Jiamu Zhang, Liwei Wang, Sunyang Fu, Kurt D Miller, Heling Jia, Steven D Bedrick, William R Hersh, Kirk E Roberts, Xia Hu, Hongfang Liu

Faculty, Staff and Student Publications

Current discussion surrounding the clinical capabilities of generative language models(GLMs) predominantly centers around multiple-choice question-answer(MCQA) benchmarks derived from clinical licensing examinations. While accepted for human examinees, characteristics unique to GLMs bring into question the validity of such benchmarks. Here, we validate five benchmarks using eight GLMs, ablating for parameter size and reasoning capabilities, validating via prompt permutation three key assumptions that underpin the generalizability of MCQA-based assessments: that knowledge is applied, not memorized, that semantic consistency will lead to consistent answers, and that situations with no answers can be recognized. While large models are more resilient to our perturbations compared …

Community And Academic Synergy For Cancer Survivorship Care Delivery Enhancement (Project Cascade): A Study Protocol For A Pragmatic, Stepped-Wedge, Cluster-Randomized Trial In Texas Primary Care Community Health Centers, Mary-Louise E Millett, Lauren Q Malthaner, Katharine Mccallister, Derek W Craig, Rebecca Eary, Melissa A Valerio-Shewmaker, L Aubree Shay, Suja S Rajan, Hilary Y Ma, Samiran Ghosh, Benjamin F Crabtree, Simon J Craddock Lee, Bijal A Balasubramanian

Faculty, Staff and Student Publications

Background: In the United States, over 18 million individuals are living with cancer. The majority of these cancer survivors also manage other chronic conditions and receive care from multiple specialists, including oncology, cardiology, and primary care clinicians. However, it remains unclear who holds primarily responsibility for coordinating their care across specialties. Because of its generalist nature, primary care is uniquely suited to deliver whole-person and coordinated care for all conditions for cancer survivors. However, primary care teams experience many challenges delivering high-quality survivorship care. While integrating care for all conditions including cancer is a core principle of high-quality primary care, …

Amino Acid Signaling In Skeletal Muscle Is Blunted By Prematurity In A Piglet Model, Antonio C Ramos Dos Santos, Agus Suryawan, Ki Beom Jang, Rosemarie D Parada, Mahmoud A Mohammad, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

Background: Preterm (PT) infants are at increased risk for reduced postnatal lean mass accretion. We established that the feeding-induced stimulation of protein synthesis in skeletal muscle is blunted in piglets born PT compared with those born at term.

Objectives: We evaluated the extent to which key components of the amino acid-sensing pathways that regulate mechanistic target of rapamycin complex 1 (mTORC1) activation contribute to anabolic resistance in skeletal muscle of piglets born PT compared with those born term.

Methods: Piglets delivered by cesarean section 10 d PT (n = 23) or at term (n = 22) were administered total parenteral …

A Spatiotemporal Model Of Cxcl10 As A Master Regulator Of Immune Evasion And Metastasis In Osteosarcoma, Benjamin B Gyau, Tsz-Kwong Man

Faculty, Staff and Students Publications

The C-X-C motif chemokine ligand 10 (CXCL10) is implicated in the progression of osteosarcoma (OS), the most aggressive pediatric bone malignancy. However, its role often presents a profound clinical paradox: although high circulating levels are strongly linked to poor prognosis, its canonical function is to recruit anti-tumor immune cells. This review unravels these contrasting roles by proposing a novel spatiotemporal model. We argue that in the early stages, immune-evading OS cells initiate the formation of a pre-metastatic niche (PMN) in the lungs, creating a localized inflammatory environment that becomes the primary source of elevated circulating CXCL10. As the disease progresses, …