Medical Specialties Commons^™

Health Literacy And Cumulative Social Disadvantage Are Associated With Survival And Transplant In Patients With Hepatocellular Carcinoma: A Prospective Study, Lauren D Nephew, Susan M Rawl, Allie Carter, Nicole Garcia, Patrick O Monahan, John Holden, Marwan Ghabril, Eleazar Montalvan-Sanchez, Kavish Patidar, Archita P Desai, Eric Orman, Naga Chalasani

Faculty, Staff and Students Publications

OBJECTIVE: To investigate how individual social determinants of health (SDOH) and cumulative social disadvantage (CSD) affect survival and receipt of liver transplant (LT) in patients with hepatocellular carcinoma (HCC).

METHODS: We enrolled 139 adult patients from two Indianapolis hospital systems between June 2019 and April 2022. Structured questionnaires collected SDOH and social risk factor data. We compared SDOH and CSD by race, gender and disease aetiology, assigning one point per adverse SDOH. Multivariable competing risk survival analysis assessed associations between SDOH, CSD, survival and LT receipt.

RESULTS: Black patients experienced higher CSD than white patients in the cohort (5.4±2.5 vs …

Pulse Oximetry Accuracy In Children With Dark Skin Tones: Relevance To Acute Lower Respiratory Infection Care In Low- And Middle-Income Countries, Shubhada Hooli, Tim Colbourn, Manish I Shah, Kristy Murray, Anna Mandalakas, Eric D Mccollum

Faculty, Staff and Students Publications

Acute lower respiratory infections (ALRI) are the leading post-neonatal cause of death in children under 5 years old. There is a high prevalence of pediatric ALRI-related hypoxemia in low- and middle-income countries. The WHO defines clinically meaningful hypoxemia in children as a SpO2 (peripheral oxygen saturation) < 90%. Multiple studies put this convention into question and found SpO2 of 90% to 92% to be associated with child ALRI mortality. An evolving body of evidence suggests that pulse oximeters systematically overestimate oxygen saturation in individuals with dark skin tones. We conducted a narrative review of pediatric studies evaluating pulse oximeter accuracy in children without COVID-19. Four studies, one prospective, examined pulse oximeter accuracy in children of varying ages with dark skin tones. All studies had limitations that affect their generalizability. There is evidence that certain pulse oximeters may overestimate oxygen saturation in children with dark skin tones. Further prospective research is urgently needed to identify affected populations and clinical implications. Despite recognized challenges, we strongly urge continued and expanded use of pulse oximetry as its use will save lives.

Neuron-Glial Interactions: Implications For Plasticity, Behavior, And Cognition, Mauricio Rangel-Gomez, Cristina M Alberini, Benjamin Deneen, Gabrielle T Drummond, Tiina Manninen, Mriganka Sur, Aleksandra Vicentic

Faculty, Staff and Students Publications

The traditional view of glial cells as mere supportive tissue has shifted, due to advances in technology and theoretical conceptualization, to include a diversity of other functions, such as regulation of complex behaviors. Astrocytes, the most abundant glial cells in the central nervous system (CNS), have been shown to modulate synaptic functions through gliotransmitter-mediated neurotransmitter reuptake, influencing neuronal signaling and behavioral functions. Contemporary studies further highlight astrocytes' involvement in complex cognitive functions. For instance, inhibiting astrocytes in the hippocampus can lead to memory deficits, suggesting their integral role in memory processes. Moreover, astrocytic calcium activity and astrocyte-neuron metabolic coupling have …

Novel Ox40 And 4–1bb Derived Spacers Enhance Cd30 Car Activity And Safety In Cd30 Positive Lymphoma Models, Lindsay Kua, Chee Hoe Ng, Jin Wei Tan, Hwee Ching Tan, Cheah Chen Seh, Fiona Wong, Richard Ong, Cliona M Rooney, Joel Tan, Qingfeng Chen, Ivan D Horak, Kar Wai Tan, Lionel Low

Faculty, Staff and Students Publications

The chimeric antigen receptor (CAR) derived from the CD30 specific murine antibody, HRS-3, has produced promising clinical efficacy with a favorable safety profile in the treatment of relapsed or refractory CD30-positive lymphomas. However, persistence of the autologous CAR-T cells was brief, and many patients relapsed a year after treatment. The lack of persistence may be attributed to the use of a wild-type immunoglobulin (Ig)G1 spacer that can associate with Fc receptors. We first identified the cysteine-rich domain (CRD) 5 of CD30 as the primary binding epitope of HRS-3 and armed with this insight, attempted to improve the HRS-3 CAR functionality …

Clinical Outcome-Guided Deep Temporal Clustering For Disease Progression Subtyping, Dulin Wang, Xiaotian Ma, Paul E Schulz, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

Objective: Complex diseases exhibit heterogeneous progression patterns, necessitating effective capture and clustering of longitudinal changes to identify disease subtypes for personalized treatments. However, existing studies often fail to design clustering-specific representations or neglect clinical outcomes, thereby limiting the interpretability and clinical utility.

Method: We design a unified framework for subtyping longitudinal progressive diseases. We focus on effectively integrating all data from disease progressions and improving patient representation for downstream clustering. Specifically, we propose a clinical Outcome-Guided Deep Temporal Clustering (OG-DTC) that generates representations informed by clustering and clinical outcomes. A GRU-based seq2seq architecture captures the temporal dynamics, and the model …

Sex Differences In Metabolic Adaptation In Infants With Cyanotic Congenital Heart Disease, Tina O Findley, Ana Carolina Palei, Kyung Serk Cho, Zhongming Zhao, Caleb Shi, Gouri Mahajan, Antonio Francesco Corno, Jorge Salazar, Louise Mccullough

Faculty, Staff and Student Publications

BACKGROUND: Female infants with congenital heart disease (CHD) face significantly higher postoperative mortality rates after adjusting for cardiac complexity. Sex differences in metabolic adaptation to cardiac stressors may be an early contributor to cardiac dysfunction. In adult diseases, hypoxic/ischemic cardiomyocytes undergo a cardioprotective metabolic shift from oxidative phosphorylation to glycolysis which appears to be regulated in a sexually dimorphic manner. We hypothesize sex differences in cardiac metabolism are present in cyanotic CHD and detectable as early as the infant period.

METHODS: RNA sequencing was performed on blood samples (cyanotic CHD cases, n = 11; controls, n = 11) and analyzed …

A Nurse-Driven Screening Process To Increase Icu Palliative Care Utilization, Sara L. Stock

Doctor of Nursing Practice Final Project Abstract

Purpose

A scholarly project aimed to increase palliative care by 25% for intensive care unit patients in eight weeks by integrating nurse-driven screening process into multidisciplinary rounds.

Background

Palliative care provides valuable mental, emotional, and spiritual support for patients and families. These benefits are available to any patient with a disease process causing symptoms affecting quality of life. Palliative care is falsely equated with hospice care, leading to further delay. The original referral model relied only on intensivist identification of eligibility The project was implemented in a 20-bed medical and surgical ICU in a community hospital in the Houston area. …

Improving Adherence Amongst Post-Stroke Patients In The Outpatient Setting, Olivea Adetu

Doctor of Nursing Practice Final Project Abstract

PURPOSE

This quality improvement (QI) project aimed to enhance medication adherence and follow-up rates through structured, personalized phone calls to recently discharged post-stroke patients. The project was implemented at an outpatient neuroscience clinic in Greater Houston.

BACKGROUND

Low medication adherence and poor attendance at the first neurology follow-up appointment among post-stroke patients contribute to increased morbidity and higher risk of recurrent stroke. Despite receiving discharge instructions, many patients do not consistently take their prescribed medications or attend their initial neurology visit.

METHODOLOGY

Guided by the Plan-Do-Study-Act (PDSA) cycle, this project engaged a medical assistant to call recently discharged stroke patients …

Mr-Linac-Guided Stereotactic Radiotherapy For Ct-Indiscernible Intravascular Renal Cell Carcinoma Tumours, Mihir D Shanker, Zhiqian Henry Yu, Jinzhong Yang, Surena Matin, Matthew T Campbell, Pavlos Msaouel, Nizar Tannir, Surendra Prajapati, Yao Ding, Belinda Lee, Angela Sobremonte, Chad Tang

Faculty, Staff and Student Publications

Inferior vena cava tumour thrombus (IVC‐TT) is a life‐threatening complication of advanced renal cell carcinoma (RCC) occurring in 10%–25% of patients with RCC with one third of patients having concurrent distant metastatic disease. ¹ , ² Surgical resection in the form of radical nephrectomy and caval thrombectomy is the established option for obtaining local control of the disease and is associated with long‐term oncologic control; however, only 50% of patients are operative candidates at time of diagnosis. ³ , ⁴ Untreated RCC IVC‐TT has a poor natural history, with a median survival of 5 months with a 1‐year disease‐specific survival …

Physical Exercise-Related Manifestations Of Long Covid: A Systematic Review And Meta-Analysis, Chen Zheng, Jun-Jie Chen, Zi-Han Dai, Ke-Wen Wan, Feng-Hua Sun, Jun-Hao Huang, Xiang-Ke Chen

Faculty, Staff and Student Publications

OBJECTIVE: This study aims to systematically assess physical exercise-related symptoms of post-acute sequelae of SARS-CoV-2 infection (PASC or long COVID) in coronavirus disease 2019 (COVID-19) survivors.

METHODS: Eight databases were systematically searched on March 03, 2024. Original studies that compared physical exercise-related parameters measured by exercise testing between COVID-19 survivors who recovered from SARS-CoV-2 infection over 3 months and non-COVID-19 controls were included. A random-effects model was utilized to determine the mean differences (MDs) or standardized MDs in the meta-analysis.

RESULTS: A total of 40 studies with 6241 COVID-19 survivors were included. The 6-min walk test, maximal oxygen consumption (VO …

Medical Students’ Self-Perceived Knowledge And Clinical Comfort With Genetics In Pakistan, Maheen Arshad, Angela Trepanier, S Shahrukh Hashmi, Rizwan Naeem, Saqib Mehmood, Myla Ashfaq

Faculty, Staff and Student Publications

Pakistan has a high rate of genetic disorders and neonatal mortality concurrent with noted lack of genetic counselors and geneticists. To meet the needs of the patient population, the responsibility of providing clinical genetic services falls on general and specialty physicians. However, their education regarding these essential services is not standardized in medical school curricula nor has it ever been evaluated. The purpose of this work is to describe the self-perceived knowledge, clinical comfort, and perspectives of Pakistani medical students toward their medical genetics' education. A web-based survey was distributed electronically to medical schools around the country. The survey comprised …

Pre-Diagnosis Tea And Coffee Consumption And Survival After A Diagnosis Of Ovarian Cancer: Results From The Ovarian Cancer Association Consortium, Christina M Nagle, Torukiri I Ibiebele, Elisa V Bandera, Daniel Cramer, Jennifer A Doherty, Graham G Giles, Marc T Goodman, Gillian E Hanley, Holly R Harris, Allan Jensen, Susanne K Kjaer, Alice W Lee, Roger L Milne, Bo Qin, Jean Richardson, Naoko Sasamoto, Weiva Sieh, Kathryn L Terry, Linda Titus, Britton Trabert, Nicolas Wentzensen, Anna H Wu, Andrew Berchuck, Malcolm Pike, Celeste Leigh Pearce, Penelope M Webb

Faculty, Staff and Student Publications

BACKGROUND: Tea and coffee are the most frequently consumed beverages in the world. Green tea in particular contains compounds with potential anti-cancer effects, but its association with survival after ovarian cancer is uncertain.

METHODS: We investigated the associations between tea and coffee consumption before diagnosis and survival using data from 10 studies in the Ovarian Cancer Association Consortium. Data on tea (green, black, herbal), coffee and caffeine intake were available for up to 5724 women. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI).

RESULTS: Compared with women who did not drink …

Molecular Architecture And Functional Dynamics Of The Pre-Incision Complex In Nucleotide Excision Repair, Jina Yu, Chunli Yan, Tanmoy Paul, Lucas Brewer, Susan E Tsutakawa, Chi-Lin Tsai, Samir M Hamdan, John A Tainer, Ivaylo Ivanov

Faculty, Staff and Student Publications

Nucleotide excision repair (NER) is vital for genome integrity. Yet, our understanding of the complex NER protein machinery remains incomplete. Combining cryo-EM and XL-MS data with AlphaFold2 predictions, we build an integrative model of the NER pre-incision complex(PInC). Here TFIIH serves as a molecular ruler, defining the DNA bubble size and precisely positioning the XPG and XPF nucleases for incision. Using simulations and graph theoretical analyses, we unveil PInC's assembly, global motions, and partitioning into dynamic communities. Remarkably, XPG caps XPD's DNA-binding groove and bridges both junctions of the DNA bubble, suggesting a novel coordination mechanism of PInC's dual incision. …

Superior Antitumor Immune Response Achieved With Proton Over Photon Immunoradiotherapy Is Amplified By The Nanoradioenhancer Nbtxr3, Yun Hu, Sébastien Paris, Narayan Sahoo, Qi Wang, Qianxia Wang, Hampartsoum B Barsoumian, Ailing Huang, Jordan Da Silva, Célia Bienassis, Claudia S Kettlun Leyton, Tiffany A Voss, Fatemeh Masrorpour, Thomas Riad, Carola Leuschner, Nahum Puebla-Osorio, Saumil Gandhi, Quynh-Nhu Nguyen, Jing Wang, Maria Angelica Cortez, James W Welsh

Faculty, Staff and Student Publications

Recent findings suggest that immunoradiotherapy (IRT), combining photon radiotherapy (XRT) or proton radiotherapy (PRT) with immune checkpoint blockade, can enhance systemic tumor control. However, the comparative efficacy of XRT and PRT in IRT remains understudied. To address this, we compared outcomes between XRT + αPD1 and PRT + αPD1 in murine αPD1-resistant lung cancer (344SQR). We also assessed the impact of the nanoparticle radioenhancer NBTXR3 on both XRT + αPD1 and PRT + αPD1 for tumor control and examined the tumor immune microenvironment using single-cell RNA sequencing (scRNAseq). Additionally, mice cured by NBTXR3 + PRT + αPD1 were rechallenged with …

Preventive Treatment With A Cd73 Small Molecule Inhibitor Enhances Immune Surveillance In K-Ras Mutant Pancreatic Intraepithelial Neoplasia, Lincoln N Strickland, Wendao Liu, Usama Hussein, Nicolette Mardik, Xian Chen, Tingting Mills, Lana A Vornik, Michelle I Savage, Shizuko Sei, John Clifford, Holger K Eltzschig, Powel H Brown, Zhongming Zhao, Florencia Mcallister, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Immunoprevention is an emerging consideration for solid tumors, including pancreatic ductal adenocarcinoma (PDAC). We and others have shown that Kras mutations in genetic models of spontaneous pancreatic intraepithelial neoplasia (PanIN), which is a precursor to PDAC, results in CD73 expression in the neoplastic epithelium and some populations of infiltrating immune cells, including macrophages and CD8 T cells. CD73 is an ecto-enzyme that converts extracellular adenosine monophosphate to adenosine, a critical immune inhibitory molecule in PDAC. We hypothesized inhibition of CD73 would reduce the incidence of PanIN formation and alter the immune microenvironment. To test our hypothesis, we used the KrasG12D; …

Dcis Knowledge Of Women Choosing Between Active Surveillance And Surgery For Low-Risk Dcis, E G Engelhardt, R S J M Schmitz, M A Gerritsma, C M T Sondermeijer, E Verschuur, J H E Houtzager, R Griffioen, N Bijker, R M Mann, V Retèl, F H Van Duijnhoven, J Wesseling, E M A Bleiker

Faculty, Staff and Student Publications

BACKGROUND: Ductal carcinoma in situ (DCIS) can progress to invasive breast cancer (IBC), but often never will. As we cannot predict accurately which DCIS-lesions will or will not progress to IBC, almost all women with DCIS undergo breast-conserving surgery supplemented with radiotherapy, or even mastectomy. In some countries, endocrine treatment is prescribed as well. This implies many women with non-progressive DCIS undergo overtreatment. To reduce this, the LORD patient preference trial (LORD-PPT) tests whether mammographic active surveillance (AS) is safe by giving women with low-risk DCIS a choice between treatment and AS. For this, sufficient knowledge about DCIS is crucial. …

Pulmonary Vascular Manifestations Of Hereditary Haemorrhagic Telangiectasia, Sarah Cullivan, Barry Kevane, Brian Mccullagh, Terry M O'Connor, Robin Condliffe, Sean Gaine

Children’s Nutrition Research Center Staff Publications

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant, multisystem disorder that manifests with a spectrum of disease including cardiopulmonary complications. HHT is characterised by aberrant signalling via the transforming growth factor β (TGFβ) pathway, with loss of vascular integrity, angiogenesis and vascular dysplasia. The disease has an estimated prevalence of 1 in 5000 persons and the penetrance increases with increasing age. HHT commonly presents with epistaxis and telangiectasia, while visceral arteriovenous malformations are not uncommon. Mutations in the ENG, ACVRL1 and MADH4 genes account for 97% of all HHT cases, and it is recommended that genetic tests are used in …

Benefits Of Calorie Restriction In Mice Are Mediated Via Energy Imbalance, Not Absolute Energy Or Protein Intake, Daniel L Smith, Sharon E Mitchell, Maria S Johnson, Victoria K Gibbs, Stephanie Dickinson, Beate Henschel, Rui Li, Kathryn A Kaiser, Daniella E Chusyd, Andrew W Brown, David B Allison, John R Speakman, Tim R Nagy

Children’s Nutrition Research Center Staff Publications

Caloric restriction (CR) results in reduced energy and protein intake, raising questions about protein restriction's contribution to CR longevity benefits. We kept ad libitum (AL)-fed male C57BL/6J mice at 27°C (AL27) and pair-fed (PF) mice at 22°C (22(PF27)). The 22(PF27) group was fed to match AL27 while restricted for calories due to cold-induced metabolism. The 22(PF27) mice had significantly lower body weight, lean mass, fat mass, leptin, IGF-1, and TNF-α levels than AL27 mice (p< 0.001 for all). Manipulations over ~11 weeks resulted in significant differences in body temperature, physical activity, and expression of key genes linked to hunger in the hypothalamus. Survival was significantly greater in 22(PF27) compared to AL27 overall (p< 0.001). CR in the context of equivalent energy and protein intake resulted in hormonal, metabolic, and physiological benefits and extended longevity. Hence, energy imbalance, rather than low energy or protein intake per se, mediates the benefits of CR.

Clonal Hematopoiesis Of Indeterminate Potential Is Associated With Reduced Risk Of Cognitive Impairment In Patients With Chronic Kidney Disease, Cissy Xiao, Manjula Kurella Tamura, Yang Pan, Varun Rao, Celestin Missikpode, Caitlyn Vlasschaert, Tetsushi Nakao, Xiao Sun, Changwei Li, Zhijie Huang, Amanda Anderson, Md Mesbah Uddin, Do-Kyun Kim, Jonathan Taliercio, Rajat Deo, Zeenat Bhat, Dawei Xie, Panduranga Rao, Jing Chen, James P Lash, Jiang He, Pradeep Natarajan, James E Hixson, Kristine Yaffe, Tanika N Kelly, Cric Study Investigators

Faculty, Staff and Student Publications

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown.

Methods: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean.

Results: Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted …

Lps-Induced Whole-Blood Cytokine Production And Depressive Symptoms In Dementia Spousal Caregivers: The Moderating Effect Of Childhood Trauma, Daniel L Argueta, Kelly N Brice, E Lydia Wu-Chung, Michelle A Chen, Vincent D Lai, Jensine Paoletti-Hatcher, Bryan T Denny, Charles Green, Luis D Medina, Paul Schulz, Jennifer Stinson, Cobi Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Dementia spousal caregivers are at risk for adverse mental and physical health outcomes. Caregiver burden, anticipatory grief, and proinflammatory cytokine production may contribute to depressive symptoms among caregivers. People who report childhood trauma are more likely to have exaggerated stress responses that may also contribute to depressive symptoms in adulthood. This study aimed to test whether the relationship between whole-blood cytokine production and depressive symptoms is strongest in caregivers who report high levels of childhood trauma.

Methods: A sample of 103 dementia spousal caregivers provided self-report data on demographics, health information, caregiver burden, anticipatory grief, and depressive symptoms. We also …

Development And Clinical Implementation Of A Digital Workflow Utilizing 3d-Printed Oral Stents For Patients With Head And Neck Cancer Receiving Radiotherapy, Rance Tino, Millicent A Roach, Gabriela D Fuentes, Anshuman Agrawal, Mohamed Zaid, Dylan J Cooper, Nimit Bajaj, Ruitao Lin, Lianchun Xiao, Lauren L Mayo, Lee R Wiederhold, Shalin J Shah, Molly K Tate, Gregory M Chronowski, Jay P Reddy, Megan Mezera, Justin M Mann, Mark Augspurger, Adegbenga O Otun, Mark S Chambers, Eugene J Koay

Faculty, Staff and Student Publications

Objectives: We describe the development of 3D-printed stents using our digital workflow and their effects on patients enrolled in the lead-in phase of a multi-center, randomized Phase-II trial.

Materials and methods: Digital dental models were created for patients using intraoral scanning. Digital processes were implemented to develop the mouth-opening, tongue-depressing, and tongue-lateralizing stents using stereolithography. Time spent and material 3D-printing costs were measured. Physicians assessed mucositis using the Oral Mucositis Assessment Scale (OMAS) and collected MD Anderson Symptom Inventory (MDASI) reports and adverse events (AEs) from patients at various time points (TPs). OMAS and MDASI results were evaluated using paired …

Pparγ/Etv2 Axis Regulates Endothelial-To-Mesenchymal Transition In Pulmonary Hypertension, Dong Hun Lee, Minseong Kim, Sarah S Chang, Raham Lee, Andrew J Jang, Juyoung Kim, Jing Ma, Michael J Passineau, Raymond L Benza, Harry Karmouty-Quintana, Wilbur A Lam, Benjamin T Kopp, Roy L Sutliff, C Michael Hart, Changwon Park, Bum-Yong Kang

Faculty, Staff and Student Publications

Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells. Etv2 +/- mice spontaneously developed PH and right …

The Five Homologous Ciar-Controlled Ccn Srnas Of Streptococcus Pneumoniae Modulate Zn-Resistance, Nicholas R De Lay, Nidhi Verma, Dhriti Sinha, Abigail Garrett, Maximillian K Osterberg, Daisy Porter, Spencer Reiling, David P Giedroc, Malcolm E Winkler

Faculty, Staff and Student Publications

Zinc is a vital transition metal for all bacteria; however, elevated intracellular free Zn levels can result in mis-metalation of Mn-dependent enzymes. For Mn-centric bacteria such as Streptococcus pneumoniae that primarily use Mn instead of Fe as an enzyme cofactor, Zn is particularly toxic at high concentrations. Here, we report our identification and characterization of the function of the five homologous, CiaRH-regulated Ccn sRNAs in controlling S. pneumoniae virulence and metal homeostasis. We show that deletion of all five ccn genes (ccnA, ccnB, ccnC, ccnD, and ccnE) from S. pneumoniae strains D39 (serotype 2) and TIGR4 (serotype 4) causes Zn …

Phenotypic Diversity Of Type Iii Secretion System Activity In Enteropathogenic Escherichia Coli Clinical Isolates, Carmen A Contreras, Tracy H Hazen, Carmen Guadarrama, Ramón Cervantes-Rivera, Theresa J Ochoa, Pablo Vinuesa, David A Rasko, Jose L Puente

Faculty, Staff and Student Publications

Introduction. Enteropathogenic Escherichia coli (EPEC) strains pose a significant threat as a leading cause of severe childhood diarrhoea in developing nations. EPEC pathogenicity relies on the type III secretion system (T3SS) encoded by the locus of enterocyte effacement (LEE), facilitating the secretion and translocation of bacterial effector proteins.

Gap Statement. While the regulatory roles of PerC (plasmid-encoded regulator) and GrlA (global regulator of LEE-activator) in ler expression and LEE gene activation are well-documented in the EPEC prototype strain E2348/69, understanding the variability in LEE gene expression control mechanisms among clinical EPEC isolates remains an area requiring further investigation.

Aim. This …

Genomic Biomarkers To Predict Response To Atezolizumab Plus Bevacizumab Immunotherapy In Hepatocellular Carcinoma: Insights From The Imbrave150 Trial, Sun Young Yim, Sung Hwan Lee, Seung-Woo Baek, Bohwa Sohn, Yun Seong Jeong, Sang-Hee Kang, Kena Park, Hyewon Park, Sunyoung S Lee, Ahmed O Kaseb, Young Nyun Park, Sun-Hee Leem, Michael A Curran, Ji Hoon Kim, Ju-Seog Lee

Faculty, Staff and Student Publications

Background/aims: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge.

Methods: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full …

Feasibility Of Quantitative Relaxometry For Prostate Target Localization And Response Assessment In Magnetic Resonance-Guided Online Adaptive Stereotactic Body Radiotherapy, Ergys Subashi, Eve Locastro, Sarah Burleson, Aditya Apte, Michael Zelefsky, Neelam Tyagi

Faculty, Staff and Student Publications

Purpose: Multiparametric magnetic resonance imaging (MRI) is known to provide predictors for malignancy and treatment outcome. The inclusion of these datasets in workflows for online adaptive planning remains under investigation. We demonstrate the feasibility of longitudinal relaxometry in online MR-guided adaptive stereotactic body radiotherapy (SBRT) to the prostate and dominant intra-prostatic lesion (DIL).

Methods: Fifty patients with intermediate-risk prostate cancer were included in the study. The clinical target volume (CTV) was defined as the prostate gland plus 1 cm of seminal vesicles. The gross tumor volume (GTV) was defined as the DIL identified on multiparametric MRI. Online adaptive radiotherapy was …

Small-Molecule Ccr4 Antagonists In Cutaneous T-Cell Lymphoma, José S Enriquez, Xiaohong Wang, Loka Reddy Velatooru, Wei Han, Pedram Bijani, Xiao Ni

Faculty, Staff and Student Publications

Mycosis fungoides (MF) and Sézary syndrome (SS) are two most common types of cutaneous T-cell lymphoma (CTCL). Despite advances in understanding the pathogenesis of MF and SS, effective treatments remain limited. CC chemokine receptor-4 (CCR4) is highly expressed on CTCL cells and serves as a great therapeutic target. Mogamulizumab, an FDA-approved anti-CCR4 antibody, has shown efficacy in treating MF/SS; however, its side effects have raised concerns, underscoring the need for more effective and less toxic CCR4-targeted therapies. Although small-molecule CCR4 antagonists have been studied in other diseases involving CCR4⁺ Th2 cells and regulatory T cells, their effects in CTCL …

Evaluating Dynamic And Predictive Discrimination For Recurrent Event Models: Use Of A Time-Dependent C-Index, Jian Wang, Xinyang Jiang, Jing Ning

Faculty, Staff and Student Publications

Interest in analyzing recurrent event data has increased over the past few decades. One essential aspect of a risk prediction model for recurrent event data is to accurately distinguish individuals with different risks of developing a recurrent event. Although the concordance index (C-index) effectively evaluates the overall discriminative ability of a regression model for recurrent event data, a local measure is also desirable to capture dynamic performance of the regression model over time. Therefore, in this study, we propose a time-dependent C-index measure for inferring the model's discriminative ability locally. We formulated the C-index as a function of time using …

Mhc Hammer Reveals Genetic And Non-Genetic Hla Disruption In Cancer Evolution, Clare Puttick, Thomas P Jones, Michelle M Leung, Felipe Galvez-Cancino, Jiali Liu, Manuel Varas-Godoy, Andrew Rowan, Oriol Pich, Carlos Martinez-Ruiz, Robert Bentham, Krijn K Dijkstra, James R M Black, Rachel Rosenthal, Nnennaya Kanu, Kevin Litchfield, Roberto Salgado, David A Moore, Peter Van Loo, Mariam Jamal-Hanjani, Sergio A Quezada, Tracerx Consortium, Charles Swanton, Nicholas Mcgranahan

Faculty, Staff and Student Publications

Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue. In lung TRACERx and lung and breast TCGA cohorts, 61% of lung adenocarcinoma (LUAD), 76% of lung squamous cell carcinoma (LUSC) and 35% of estrogen receptor-positive (ER+) cancers harbored class I HLA transcriptional repression, while HLA tumor-enriched alternative splicing occurred in 31%, 11% …

Biomarker Trajectory For Earlier Detection Of Lung Cancer, Ehsan Irajizad, Johannes F Fahrmann, Iakovos Toumazis, Jody Vykoukal, Jennifer B Dennison, Yu Shen, Kim-Anh Do, Edwin J Ostrin, Ziding Feng, Samir Hanash

Faculty, Staff and Student Publications

Background: To determine whether an algorithm based on repeated measurements of a panel of four circulating protein biomarkers (4 MP) for lung cancer risk assessment results in improved performance over a single time measurement.

Methods: We conducted data analysis of the 4 MP consisting of the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment in pre-diagnostic sera from 2483 ever-smoker participants (389 cases and 2094 randomly selected non-cases) in the Prostate, Lung, Colorectal, Ovarian (PLCO) Study who had at least two sequential blood collections over 6 years. A parametric empirical Bayes (PEB) algorithm, which …