Digital Commons Network^™

Sickle Cell Crisis-Induced Painless Bilateral Orbital Bone Infarction: A Case Report, Luke Farson, Marina Shenouda, Agni Kakouri, Ashkan Kashanchi, Clark Sitton, Timothy Mcculley, Ying Chen

Faculty, Staff and Student Publications

Introduction: Sickle cell disease is associated with painful vaso-occlusive crises, bone infarction, avascular necrosis, and osteomyelitis. Sickle cell orbitopathy is a rare manifestation with signs similar to periorbital cellulitis and has subtle radiologic features.

Case presentation: We report a case of a five-year-old girl with sickle cell who presented with bilateral orbital infarctions and subperiosteal hematomas, notably without periorbital pain, and was treated with antibiotics and steroids.

Conclusion: Physicians should be aware of this rare manifestation, especially in the pediatric population, as it can affect subsequent management.

Glaucoma Risk With Metformin And Sulfonylurea Therapies In Type 2 Diabetes: A Retrospective Cohort Study., Jared Lim, Jingru Zhou, Hulin Wu, Ziqi Liu, David A Lee

Faculty, Staff and Student Publications

Background: Research on metformin, sulfonylureas, and open-angle glaucoma risk in type 2 diabetes mellitus (T2DM) has yielded inconsistent findings. This study examined associations between hypoglycemic treatments and glaucoma diagnosis rates.

Methods: This retrospective cohort study analyzed electronic health records of newly diagnosed T2DM patients from the Merative™ Explorys® Therapeutic Dataset (2010-2022), comparing three groups: metformin monotherapy, sulfonylureas plus metformin combination, and untreated controls. Propensity score matching balanced demographics, glycemic control, body mass index, blood pressure, lipid levels, and comorbidities. Cox proportional hazards models calculated adjusted hazard ratios for incident glaucoma.

Results: After 1:1 propensity score matching, metformin monotherapy (N=100,387) showed …

Fostering Connection And Shame Resilience Through Self-Compassion: An Innovative Elective For Health Professions Learners, Gioconda Mojica, Peggy Hsieh, Andrew J Revell, Rex Marco

Faculty, Staff and Student Publications

Background: Shame is an emotional experience in health professions education, often contributing to burnout, isolation, and threats to professional identity. Self-compassion has been identified as a protective factor against shame. This study describes the development and evaluation of an elective designed to foster shame resilience and cultivate self-compassion among health professions students.

Methods: A 6-h elective, Fostering Connection and Shame Resilience Through Self-Compassion, was offered over 3 monthly 2-h sessions. Each session included a shared meal, abbreviated large-group conceptual learning, reflective writing, guided self-compassion practices, and small-group discussions. Participants completed the Self-Compassion Scale-Short Form (SCS-SF) at the beginning and …

Open Capsulorrhaphy With Capsular Shift And Open Coracohumeral Ligament Reconstruction For Chronic Recurrent Multidirectional Shoulder Instability, Anna E Sumpter, Christopher S Frey, Matthew T Provencher, Lance E Leclere

Faculty, Staff and Student Publications

Background: This case features the surgical reconstruction of the coracohumeral ligament (CHL) in conjunction with open capsulorrhaphy and capsular shift for the management of chronic, recurrent, multidirectional shoulder instability (MDI). While there is a paucity of existing literature examining the clinical outcomes of this technique, biomechanical studies have implied its potential to restore stability. This procedure may be of particular benefit to patients who have failed previous conservative management and/or attempts at surgical stabilization, as well as those with severe joint hyperlaxity or connective tissue disorders.

Indications: This patient failed extensive physical therapy, as well as previous arthroscopic labral repair …

Healthcare Utilization Following Implementation Of A Pediatric Social Needs Screening Program, Ashley Gibson, Kaleigh Riggs-Harpur, Midhat Jafry, Mallika Mathur, Yen-Chi Le, Sandra Mckay

Faculty, Staff and Student Publications

Objective: This study evaluated differences in healthcare utilization among a pediatric primary care population following implementation of a universal social needs screening and referral program. It was hypothesized that emergency, sick, and hospitalization visits would decrease post-implementation, with stable or increased preventive care.

Methods: A retrospective, observational study was conducted using electronic health record data from 2 cohorts at different time periods at a large academic pediatric primary care clinic. The pre-implementation group included patients with a well-child visit from 08/2021 to 07/2022; the post-implementation group included patients from 09/2022 to 08/2023. Healthcare utilization measures of emergency department visits, hospitalizations, …

Conduction Abnormalities After Tavi And Their Role In Patient Management: A Systematic Review, Ionuț Tudorancea, Irene Paula Popa, Mihai Ștefan Cristian Haba, Ștefan Popa, Viviana Onofrei, Dragomir Nicolae Șerban, Ionela Lăcrămioara Șerban, Irina Iuliana Costache-Enache, Radu Iliescu, Cătălin Loghin

Faculty, Staff and Student Publications

Objective: Transcatheter aortic valve implantation (TAVI) is associated with a relatively high incidence of permanent pacemaker implantation (PPM-I). We aimed to evaluate the existing literature on electrocardiographic (ECG) changes before and after TAVI, identify predictors for PPM-I, and suggest a standardized post-TAVI ECG monitoring protocol.

Methods: A systematic literature review was conducted across multiple databases, including PubMed, Web of Science, and JSTOR, to identify studies published between 2001 and 2024.

Results: From an initial pool of 24,170 records, 17 studies met the inclusion criteria. Pre-existing right bundle branch block and significant prolongation of ECG intervals were identified as strong predictors …

Risk Factors And Outcomes Of Reintubation Following Combined Heart-Lung Transplantation, Ye In Christopher Kwon, Michael Keller, Alan Lai, Brian Bao, Joshua Pei, Matthew Ambrosio, Jay Patel, Motaz Al-Yafi, Zachary Fitch, Josue Chery, Patricia Nicolato, Vigneshwar Kasirajan, Zubair A Hashmi

Faculty, Staff and Student Publications

Background: Unplanned reintubation after combined heart-lung transplantation (HLT) significantly affects morbidity and mortality, yet national data are limited. We evaluated the incidence, predictors, timing, and outcomes associated with reintubation after HLT.

Methods: We retrospectively reviewed adults undergoing primary HLT in the UNOS registry from January 2004 to September 2024. Patients were stratified by reintubation status (defined as re-established mechanical ventilation (MV) after initial extubation). Propensity matching (1:1) balanced recipient and donor characteristics. Multivariable logistic regression models identified independent risk factors.

Results: Among 609 adult HLT recipients, 165 (27.1%) required postoperative reintubation. After 1:1 propensity score matching, 146 patients who were …

Collision Tumors Involving Metastatic Carcinoma And Plasma Cell Myeloma: Report Of Two Cases, Ahmed A Ahmed, Muhammad Hassaan Khalid, Asad Ur Rehman, Nghia D Nguyen, Xinhai Robert Zhang

Faculty, Staff and Student Publications

Synchronous coexistence of plasma cell neoplasms (PCNs) and metastatic carcinoma is not a common phenomenon and poses a significant diagnostic challenge requiring meticulous histopathological and immunophenotypic analysis for accurate lineage assignment. We report two cases of collision tumors comprising PCN and metastatic lung carcinoma. Case 1 involved a 68-year-old male with metastatic non-small cell lung adenocarcinoma who developed intracranial lesions; resection revealed metastatic adenocarcinoma intermingled with clonal plasma cells. Case 2 was a 73-year-old woman with a lytic iliac crest lesion whose bone marrow and lesion biopsies showed diffuse infiltration by both carcinoma and atypical plasma cells. Comprehensive immunohistochemical profiling, …

“Do Everything” Versus Realistic Surgical Interventions: Navigating The Road To Shared Decision-Making In Trauma Surgery, Victoria E Wagner, Ashna S Karpe, Martin L Blakely, Lillian S Kao, Thaddeus J Puzio

Faculty, Staff and Student Publications

"DO EVERYTHING!!" How many times have you heard that phrase from a distressed family member? We routinely receive this desperate plea, and our knee-jerk reaction is to press on, push harder, be more aggressive. We, as acute care surgeons, have spent our lives learning a craft geared towards "doing everything" to heal patients so this response comes naturally. However, how do we respond to "do everything" when the probability of a meaningful recovery is extremely low or non-existent? These situations create moral tension for surgeons who must reconcile the desire to preserve life with the obligation to avoid harm, respect …

Blood Flow Regulates Metabolism In Hematopoietic Development, Pamela L Wenzel

Faculty, Staff and Student Publications

Blood flow modifies oxygen availability and biomechanical forces within the vasculature of the embryo as the hematopoietic system develops. The aorta-gonad-mesonephros (AGM) envelops the largest artery in the body and is a critical site for the emergence of hematopoietic stem cells (HSCs). Herein, I discuss the role of hypoxia-inducible factors (HIFs) and force as determinants of metabolism and fate determination. To address the effects of blood flow on hematopoietic development, I employ mouse embryo models and biomimetic culture. Real-time cell metabolic analyses show that oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) are altered by flow in cultures of …

Host Modulation Therapy In Periodontitis: From Established Therapies To Emerging Technologies, Aonjittra Phanrungsuwan, Jiaqi Huang, Neeraja Dharmaraj, Alejandra Cobos Perez, Omid Veiseh, Simon Young, Chun-Teh Lee

Faculty, Staff and Student Publications

Periodontitis is a biofilm-induced chronic inflammatory disease, characterized by gingival inflammation and alveolar bone loss. According to a national survey, approximately half of the U.S. adults are affected by periodontal disease. To effectively prevent and treat periodontitis, it is essential to address its underlying causes. The primary etiological factors include polymicrobial synergy and dysbiosis of the oral microbiota, and a dysregulated immune response. The standard therapeutic approach, mechanical removal of biofilm through debridement, sometimes demonstrates limited efficacy, particularly in cases of severe periodontitis, which may require adjunctive or additional therapy. Emerging evidence indicates that periodontal tissue destruction is initiated by …

Integrative Multi-Omics Profiling Identifies Infiltrative Hepatocellular Carcinoma As An Immunotherapy-Resistant Subtype With Distinct Molecular Features, Won Suk Lee, Seonjeong Woo, Sung Hwan Lee, Gae Hoon Jo, Ilhwan Kim, Hyeyeong Kim, Chansik An, Sanghoon Jung, Gwangil Kim, Haeyoun Kang, Beodeul Kang, Jung Sun Kim, Ho Yeong Lim, Incheon Kang, Hannah Yang, So Jung Kong, Dahyeon Son, Dong Jun Shin, Woo Young Kwon, Da-Yeon Lee, Ju-Seog Lee, Junho Park, Youngsoo Kim, Sohyun Hwang, Chan Kim, Hong Jae Chon

Faculty, Staff and Student Publications

Background/aims: Hepatocellular carcinoma (HCC) exhibits substantial morphological and biological heterogeneity. Clinical and molecular relevance of the infiltrative subtype remains poorly defined in the context of cancer immunotherapy. We aimed to evaluate the prognostic impact and molecular features of infiltrative HCC in patients treated with first-line atezolizumab plus bevacizumab (Ate/Bev).

Methods: We included 307 patients with advanced HCC treated with Ate/Bev and classified them into four gross morphological types based on imaging. Multi-omics profiling was conducted on tumor samples. Type IV infiltrative signature was derived and externally validated using five independent HCC cohorts, including IMbrave150.

Results: Infiltrative morphology, encompassing pure and …

Engineering Mutation Clones In Mammalian Cells With Crispr/Cas9, Zijun Huo, Jian Tu, Rachel Shoemaker, Dung-Fang Lee, Ruiying Zhao

Faculty, Staff and Student Publications

CRISPR, Clustered Regularly Interspaced Short Palindromic Repeat, as a powerful genome engineering system, has been widely accepted and employed in gene editing of a vast range of cell types. Compared to zinc finger nucleases (ZFNs) or transcription activator-like effector nucleases (TALENs), CRISPR shows a less complicated process and higher efficiency. With the development of different CRISPR systems, it can be used not only to knock out a gene but also to make precise modifications, activate or repress target genes with epigenetic modifications, and even for genome wide screening. Here we will describe the procedure of generating a stable cell line …

Uncertainty-Guided Test-Time Optimization For Personalizing Segmentation Models In Longitudinal Medical Imaging, Jaehee Chun, Austin Castelo, Mckell Woodland, Caleb O'Connor, Mais Al Taie, Mohamed Eltaher, Aashish Gupta, Bilel Daoud, Shanli Ding, Jeddy Bennett, Anirban Maitra, Matthew A Firpo, Kimberly Kirkwood, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

Background: Accurate and consistent image segmentation across longitudinal scans is essential in many clinical applications, including surveillance, treatment monitoring, and adaptive interventions. While personalized model adaptation using patient-specific prior scans has shown promise, current approaches typically rely on fixed training durations and lack mechanisms to determine optimal stopping points on a per-patient basis, particularly in the absence of validation labels.

Purpose: We propose an uncertainty-guided test-time optimization (TTO) framework that dynamically adjusts the personalization duration for each patient using a validation-free stopping criterion based on predictive uncertainty.

Methods: Our framework personalizes a generalized segmentation model using patient-specific prior imaging and …

Poly(A) Probe Hcr Rna-Fish Specifically Marks Pyriform Nurse Cells In The Brown Anole Lizard Ovary, Zoe B Griffin, Bonnie K Kircher, Richard R Behringer

Faculty, Staff and Student Publications

Hybridization chain reaction RNA-fluorescent in situ hybridization (HCR RNA-FISH) is a powerful and increasingly used method for visualizing gene expression in cells and tissues. A probe set against polyadenylated RNA (poly(A)) is often used as a positive control for RNA integrity and staining quality. While optimizing this technique in the ovary of the brown anole lizard (Anolis sagrei), we found that the poly(A) probe produced a strikingly specific and intense signal in pyriform cells, a specialized lizard-specific nurse cell type. This staining pattern was found in both whole-mount samples and paraffin sections, suggesting that poly(A) signal intensity can serve as …

Application Of The Lancet Commission Criteria For The Diagnosis Of Obesity To A Clinical Trials Population: The Leap Trial, Faith Anne N Heeren, Kathleen R Ruddiman, Courtney Simmons, Brian N White, Byron C Jaeger, Nicholas M Pajewski, Stephanie A Hooker, Deborah B Horn, Katy Martin-Fernandez, Kimberly A Gudzune, Caroline Blackwell Young, Jamy Ard, Kristina Henderson Lewis

Faculty, Staff and Student Publications

Objective: This study aimed to apply The Lancet Diabetes & Endocrinology criteria for diagnosing obesity among clinical trial participants and understand participants' characteristics by obesity status.

Methods: The criteria were operationalized and applied to baseline data from the Long-term Effectiveness of the Anti-obesity medication Phentermine (LEAP) trial (NCT05176626). Excess adiposity, organ and tissue dysfunction, and limitations to daily activities were assessed. We examined differences between participants with "no obesity," "pre-clinical obesity," and "clinical obesity."

Results: Among the 860 participants, 0.8% had no obesity (mean BMI 29.0 kg/m2 [SD 0.6]), 18.7% had pre-clinical obesity (mean BMI 35.2 kg/m2 [SD …

Physical Activity, Telomere Length, And Cardiometabolic Syndrome In Older Women: The Cardiovascular Health Study, Jeni Page, Melissa Richard, Elizabeth Lyons, Elizabeth Baumler, M Terese Verklan, Michelle C Odden, Elizabeth Lorenzo

Faculty, Staff and Student Publications

Background: Cardiometabolic syndrome (CMS) affects approximately 39% of US women and increases risk for cardiovascular disease, diabetes, and stroke. Telomere length, a biomarker of cellular aging, is associated with CMS and may be influenced by physical activity (PA), potentially mitigating telomere shortening. Black women have higher CMS prevalence compared to white women and may exhibit distinct telomere length dynamics influenced by interactions between CMS and PA.

Methods: Data were drawn from the Cardiovascular Health Study and included black and white women who provided data on PA, CMS risk factors, and telomere length (N = 417). Linear regression models examined the …

Genome-Wide Gene-Sleep Interaction Study Identifies Novel Lipid Loci In 732,564 Participants, Raymond Noordam, Wenyi Wang, Pavithra Nagarajan, Heming Wang, Michael R Brown, Amy R Bentley, Qin Hui, Aldi T Kraja, John L Morrison, Jeffrey R O'Connel, Songmi Lee, Karen Schwander, Traci M Bartz, Lisa De Las Fuentes, Mary F Feitosa, Xiuqing Guo, Xu Hanfei, Sarah E Harris, Zhijie Huang, Mart Kals, Christophe Lefevre, Massimo Mangino, Yuri Milaneschi, Peter J Van Der Most, Natasha L Pacheco, Nicholette D Palmer, Varun Rao, Rainer Rauramaa, Quan Sun, Yasuharu Tabara, Dina Vojinovic, Yujie Wang, Stefan Weiss, Qian Yang, Wei Zhao, Wanying Zhu, Md Abu Yusuf Ansari, Hugues Aschard, Pramod Anugu, Themistocles L Assimes, John Attia, Laura D Baker, Christie Ballantyne, Lydia Bazzano, Eric Boerwinkle, Brain Cade, Hung-Hsin Chen, Wei Chen, Yii-Der Ida Chen, Zekai Chen, Kelly Cho, Ileana De Anda-Duran, Latchezar Dimitrov, Anh Do, Todd Edwards, Tariq Faquih, Aroon Hingorani, Susan P Fisher-Hoch, J Michael Gaziano, Sina A Gharib, Ayush Giri, Mohsen Ghanbari, Hans Jörgen Grabe, Mariaelisa Graff, C Charles Gu, Jiang He, Sami Heikkinen, James Hixson, Yuk-Lam Ho, Michelle M Hood, Serena C Houghton, Carrie A Karvonen-Gutierrez, Takahisa Kawaguchi, Tuomas O Kilpeläinen, Pirjo Komulainen, Henry J Lin, Gregorio V Linchangco, Annemarie I Luik, Jintao Ma, James B Meigs, Joseph B Mccormick, Cristina Menni, Ilja M Nolte, Jill M Norris, Lauren E Petty, Hannah G Polikowsky, Laura M Raffield, Stephen S Rich, Renata L Riha, Thomas C Russ, Edward A Ruiz-Narvaez, Colleen M Sitlani, Jennifer A Smith, Harold Snieder, Tamar Sofer, Botong Shen, Jingxian Tang, Kent D Taylor, Maris Teder-Laving, Rima Triatin, Michael Y Tsai, Henry Völzke, Kenneth E Westerman, Rui Xia, Jie Yao, Kristin L Young, Ruiyuan Zhang, Alan B Zonderman, Xiaofeng Zhu, Jennifer E Below, Simon R Cox, Michelle Evans, Myriam Fornage, Ervin R Fox, Nora Franceschini, Sioban D Harlow, Elizabeth Holliday, M Arfan Ikram, Tanika Kelly, Timo A Lakka, Deborah A Lawlor, Changwei Li, Ching-Ti Liu, Reedik Mägi, Alisa K Manning, Fumihiko Matsuda, Alanna C Morrison, Matthias Nauck, Kari E North, Brenda Wjh Penninx, Michael A Province, Bruce M Psaty, Jerome I Rotter, Tim D Spector, Lynne E Wagenknecht, Ko Willems Van Dijk, Lifelines Cohort Study, Million Veteran Program, Cashell E Jaquish, Peter Wf Wilson, Patricia A Peyser, Patricia B Munroe, Paul S De Vries, W James Gauderman, Yan V Sun, Han Chen, Clint L Miller, Thomas W Winkler, Dabeeru C Rao, Susan Redline, Diana Van Heemst

Faculty, Staff and Student Publications

Background and aims: Deviations from the population mean in sleep duration have been associated with increased risk for developing dyslipidemia and atherosclerotic cardiovascular disease, but the mechanism of effect is poorly characterized. We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets.

Methods: We collected data from 55 cohorts with a combined sample size of 732,564 participants (87 % European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) …

Spatial Evolution In Temporal Dynamics Of Hemodynamic Response Function In Human Superior Colliculi With Ultra-High-Resolution Mri At 9.4t, Nooshin J Fesharaki, Artemy Vinogradov, David Ress, Jung Hwan Kim

Faculty, Staff and Student Publications

The superior colliculus (SC) plays a crucial role in multisensory integration, visual information processing, saccadic target selection, visual selective attention, and decision making. In particular, the SC has a key role in oculomotor coordination, following a rostro-caudal organization. The rostral SC, which corresponds to foveal representation, is linked to fixation, microsaccades, smooth pursuit, and vergence adjustments. In contrast, the caudal SC, representing more peripheral visual field, is associated with the large gaze shifts (saccades). However, evidence regarding whether this functional gradient is preserved in the human SC remains limited. In this study, we employed a sequence-following visual-motor task to specifically …

Alternative Polyadenylation Signatures Distinguish Maladaptive Right Ventricular Remodeling In Pulmonary Hypertension: Implications For Rna-Based Diagnostics And Therapeutics, Janani Subramaniam, Venkata Jonnakuti, Scott D Collum, Sandra Martineau, Kai-Lieh Huang, Sandra Breuils-Bonnet, Andrea L Frump, Bindu H Akkanti, Jayeshkumar A Patel, Manish K Patel, Ismael Salas De Armas, Isabella N Lefebvre, Rajko Radovancevic, Elvin Blanco, Eric J Wagner, Igor Gregoric, Sriram Nathan, Biswajit Kar, Steeve Provencher, Sebastien Bonnet, François Potus, Hari Krishna Yalamanchili, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Increased pulmonary vascular pressures due to vascular remodeling, elevated vascular resistance, and vasoconstriction characterize Pulmonary Arterial Hypertension (PAH). The narrowing of the pulmonary arteries and obstruction of blood flow increase the Right Ventricular (RV) afterload, forcing the RV to undergo structural and functional changes. While adaptive remodeling leads to RV compensation by maintaining function, maladaptive remodeling leads to RV decompensation, characterized by worsening function and eventual failure. At present, there is no effective treatment for these patients as therapies for left ventricular failure are ineffectual, and there are no therapies specifically targeting the RV. Therefore, there is a clear need …

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 …

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 …

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 …

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 …

Dcpr: A Deep Learning Framework For Circadian Phase Reconstruction, Xiao Han, Xiaochen Cen, Zhijin Li, Xiaobo Zhou, Zhiwei Ji

Faculty, Staff and Student Publications

Background: The circadian clock is an evolutionarily conserved system that orchestrates 24-h physiological rhythms through transcriptional and translational feedback loops. Mounting evidence suggests a bidirectional relationship between circadian rhythm alteration and disease progression, positioning the circadian clock as a potential therapeutic target. Due to the scarcity of high-resolution temporal omics data, it remains very challenging to elucidate the underlying regulatory mechanisms of the circadian system. As a practical alternative, public untimed transcriptomic datasets offer the potential to infer gene expression oscillations retrospectively. However, existing computational approaches for circadian phase estimation often suffer from limited predictive accuracy, reducing their ability to …

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 …

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 …

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 …