Digital Commons Network^™

Peripheral Blood Biomarkers For Rheumatoid Arthritis-Associated Interstitial Lung Disease, Brent A. Luedders

Theses & Dissertations

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a common extra-articular complication of rheumatoid arthritis (RA). Measuring peripheral blood biomarkers represents an appealing strategy to inform the screening and prediction of RA-ILD. In these studies, I aimed to further characterize the associations of peripheral blood biomarkers with prevalent and incident RA-ILD. First, I evaluated the associations of matrix metalloproteinases (MMPs) with RA-ILD among a multicenter cohort of RA U.S. Veteran patients (n = 2,312). Higher concentrations of MMP-7 and MMP-9 were independently associated with both prevalent and incident RA-ILD, including a nearly four-fold increased odds of prevalent RA-ILD (adjusted odds ratio …

Beyond Precision: Ambiomic Survivorship In Childhood And Aya Cancer., Juan Antonio Ortega-García, Omar Shakeel, Nicole Wood, Antonio Pérez-Martínez, Jose Luís Fuster-Soler, Mark D. Miller

Manuscripts, Articles, Book Chapters and Other Papers

Background: Survival among children and adolescents and young adults (AYA) with cancer has improved substantially over recent decades; however, dominant survivorship models remain reactive-activated post-treatment and anchored to static exposure- and organ-based screening. This design underuses the anticipatory window at diagnosis and overlooks environmental and social determinants that modulate outcomes across the life course. Methods: We narratively reviewed international frameworks including the Children's Oncology Group (COG), the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG), the Pan-European Network for Care of Survivors after Childhood and Adolescent Cancer (PanCare) and the National Comprehensive Cancer Network (NCCN), and synthesized evidence …

A Comparison Of Tenecteplase To Alteplase For Treatment Of Acute Ischemic Stroke Using Epic Cosmos Database, Marco Gonzalez Castellon

Theses & Dissertations

Ischemic stroke is highly prevalent and an important cause of morbidity, mortality, and long-term disability in the in the United States. The incidence and prevalence of stroke is expected to increase in the next few years due to several factors including aging of the U. S. population, improved treatment, and socioeconomic factors. In 1996, the FDA approved rtPA for the treatment of ischemic stroke patients. Patients had a greater likelihood of recovering successfully. However, rtPA has significant limitations, such as an elevated risk of intracranial hemorrhage, administration difficulties, and limited effectiveness. In March 2025, the FDA approved the use of …

Protocol For Nucleo-Cytoplasmic Fractionation Of Mammalian Cells To Study Protein Translocation Via Immunoblotting, Adhikarimayum Lakhikumar Sharma, Eddy Zhu, Rithika Padyala, Kavya Parikh, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Studying protein translocation is essential for understanding protein function and regulatory mechanisms, including the activity of transcription factors. Here, we present a protocol for isolating high-quality cytoplasmic and nuclear protein fractions from mammalian cells. We describe steps for separating cytoplasmic proteins, washing nuclei, and extracting nuclear proteins. We then detail procedures for quantifying proteins and analyzing their distribution by immunoblotting within a single immunoblot. This protocol is applicable to both suspension and adherent cell types. For complete details on the use and execution of this protocol, please refer to Sharma et al.

The Effect Of Glp-1 Receptor Agonists On Reoperation Following Anterior Cervical Discectomy And Fusion, Nicholas C. Bank, Daniel Whittingslow, Sam Duggan, Joshua L. Morningstar, Douglas S. Weinberg

Student Papers, Posters & Projects

BACKGROUND: Pseudarthrosis remains a significant complication of ACDF, contributing to patient morbidity and increased healthcare costs. Glucagon-like peptide-1 receptor agonists (GLP-1RA), widely prescribed for diabetes and obesity, have been shown to reduced odds of pseudoarthrosis after ACDF. However, it remains unclear whether these reductions meaningfully translate to reduced odds of subsequent cervical surgery.

METHODS: The TriNetX United States Collaborative Network was queried for patients who underwent single- or multi-level ACDF between 2013-2023. Patients with perioperative GLP-1RA use and propensity-score-matched controls without GLP-1RA use were compared for subsequent rates of pseudoarthrosis and cervical reoperation at 6-, 12-, and 24-month intervals. Odds …

P-15 Peptide Enhanced Bone Graft Improves Time To Fusion In Transforaminal Lumbar Interbody Fusion: A Randomized, Controlled, Investigational Device Exemption Study, James S. Harrop, Michael P. Steinmetz, John E. O'Toole, Christopher D Chaput, Rick C. Sasso, K. Brandon Strenge, Greg Maislin, Jeffrey P. Mullin, Thomas B. Freeman, Anthony Guanciale, Howard Lantner, Michael E. Janssen, David G. Schwartz, John M. Small, Wellington K. Hsu, Paul M. Arnold

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Prospective, multicenter, single-blind, randomized, and controlled pivotal study.

OBJECTIVE: Compare time-to-fusion in patients treated with P-15L (PearlMatrix TM P-15 peptide enhanced bone graft) versus local autograft over 24 months and evaluate changes in pain and quality of life at 24 months relative to baseline.

SUMMARY OF BACKGROUND DATA: P-15L, an FDA-designated breakthrough device, is a composite bone graft with P-15, a 15-amino acid polypeptide that promotes cellular adhesion, proliferation, and differentiation to support bone formation.

METHODS: Patients (22-80 y) with degenerative disc disease were randomized to the investigational (P-15L) or control (local autograft) group during single-level transforaminal lumbar …

Metabolomic Profiling Reveals Brain Lipid Alterations In Pex7-Deficient Models Of Rhizomelic Chondrodysplasia Punctata, Riya Sankhe, Meredith I Williams, Wedad Fallatah, Laura Mackay, Mary Layne Brown, Pranjali Bhagwat, Sarah H Elsea, Nancy Braverman, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Rhizomelic chondrodysplasia punctata type 1 (RCDP1) is a peroxisomal disorder characterized by skeletal shortening, intellectual disability, seizures, cataracts, and reduced lifespans. RCDP1 is caused by biallelic loss-of-function variants in PEX7, which encodes a protein required for importing select enzymes into the peroxisome matrix, including those essential for ether lipid synthesis (e.g., plasmalogens) and the branched-chain fatty acid catabolism. Plasmalogen deficiency is a hallmark of RCDP1 and other peroxisomal disorders, including RCDP types 2-5 (RCDP2-5) and Zellweger spectrum disorders (ZSD). Here, we performed comprehensive metabolomic profiling of clinical samples from RCDP patients and Pex7-deficient mouse models. We identified profound …

Daily Intake Of A Lycopene-Rich Juice Is Associated With Reductions In Inflammatory Markers But Not Increases In Skin Carotenoids In A Pilot Study Among Participants With Obesity, Stephanie B Jilcott Pitts, Qiang Wu, Melissa N Laska, Elizabeth Gates, Megumi H Seese, Katelyn E Senkus, Santiago Carrero Longlax, Alexandra Portillo-Varela, Andrew R Dinardo, Nancy E Moran

Faculty, Staff and Students Publications

Background

Obesity is associated with systemic inflammation, increasing chronic disease risk. Carotenoids possess anti-inflammatory properties, yet the short-term impact of carotenoid-rich juice intake on inflammation in individuals with obesity remains unclear. Therefore, the purpose of this paper was to examine: (1) participant adherence to a 3-week lycopene-rich juice intervention; (2) variance and effect sizes of responses to the dietary intervention; (3) changes in skin and plasma carotenoids, and inflammatory markers among adults with obesity.

Methods

Twenty-five participants with body mass index (BMI) > 30 kg/m2 were recruited and completed the study. Participants drank 4 ounces (118.3 mL) of study-provided tomato juice, …

Adaptive Neuromodulation Dialogues: Navigating Current Challenges And Emerging Innovations In Neuromodulation System Development, Frederik Lampert, Matthew R Baker, Michael A Jensen, Amir H Ayyoubi, Christian Bentler, Jessica L Bowersock, Rosana Esteller, Jeffrey A Herron, Graham W Johnson, Daryl R Kipke, Christopher K Kovach, Vaclav Kremen, Filip Mivalt, Joseph S Neimat, Theoden I Netoff, Enrico Opri, Alexander Rockhill, Joshua M Rosenow, Kristin K Sellers, Nathan P Staff, Chandra Prakash Swamy, Ashwin Viswanathan, Gerwin Schalk, Timothy Denison, Dora Hermes, Nuri F Ince, Peter Brunner, Gregory A Worrell, Kai J Miller

Faculty, Staff and Students Publications

Adaptive neuromodulation systems and implantable brain-computer interfaces have made notable strides in recent years, translating experimental prototypes into clinical applications and garnering substantial attention from the public. This surge in interest is accompanied by increased scrutiny related to the safety, efficacy, and ethical implications of these systems, all of which must be directly addressed as we introduce new neurotechnologies. In response, we have synthesized the insights resulting from discussions between groups of experts in the field and summarized them into five key domains essential to therapeutic device development: (1) analyzing current landscape of neuromodulation devices and translational platforms (2) identifying …

Assessing Education And Training Of Developmental Screening Tools Among Residents In A Southern Academic Medical Center, Paige Seabrook, Dustin E. Sarver, Susan Buttross

Journal of Public Health in the Deep South

Background: Developmental disabilities are highly common. Early identification of developmental disabilities is critical, but many practitioners, including those in Southern U.S. states like Mississippi, do not utilize developmental screening tools.

Purpose: We aimed to identify modifiable targets within resident training experiences and their correlates using a quality improvement approach to serve as a baseline for intervention efforts.

Methods: Medical residents (N = 57) in pediatrics (n = 26), combined medicine-pediatrics (n = 12), and family medicine (n = 19) completed a survey assessing training, attitudes, practices, and perceived barriers regarding using screening tools. Perceived barriers were …

Factors Influencing The Choice Of Neurology As A Specialty Among Medical Students And Physicians In Saudi Arabia: A Cross-Sectional Study, Muhannad A. Alahmadi, Moath M. Alomairi, Aseel O. Banasir, Omar Babateen

Saudi Toxicology Journal

Neurological disorders represent a substantial global health burden and contribute to the rising demand for neurologists. In Saudi Arabia, the shortage of neurologists underscores the importance of understanding how medical students and physicians perceive neurology as a career. This study aimed to explore the level of interest in neurology and identify factors influencing specialty selection. This cross-sectional study was conducted between November and December 2024 among undergraduate medical students and medical graduates (residents, fellows, specialists, and consultants) in Saudi Arabia. First-year students and those without prior exposure to neurology were excluded. Data were collected through a structured online questionnaire distributed …

Status Of Training In The Use Of Lumen-Apposing Metal Stents For Therapeutic Endoscopic Ultrasound During Advanced Endoscopy Fellowship: A Survey Questionnaire, Yasi Xiao, Maham Hayat, Abdul S. Mohammed, Abdullah Abbasi, Sagar Pathak, Saurabh Chandan, Daryl Ramai, Deepanshu Jain, Muhammad K. Hasan, Mustafa A. Arain, Kambiz K. Kadkhodayan, Natalie Cosgrove, Dennis Yang

Division of Gastroenterology and Hepatology Faculty Papers

Background and Aims The lumen-apposing metal stent (LAMS) has revolutionized endoscopic ultrasound (EUS). However, there is a paucity of data on the optimal approaches to training on the use of LAMSs. This survey study aimed to evaluate the status of training in LAMSs among advanced endoscopy fellowship (AEF) trainees. Methods AEF (academic year 2023-2024) trainees were invited to complete a 15-question survey on LAMS training. The questions included the following domains: demographics, exposure to LAMSs before AEF, number of observed and hands-on participation using LAMSs for EUS-guided pancreatic fluid collection drainage (EUS-PFCD), choledochoduodenostomy (EUS-CD), gallbladder drainage (EUS-GBD), and gastrojejunostomy (EUS-GJ) …

Transposable Element-Derived Mir-28-5p And Mir-708-5p: Exploring Potential Roles In Lung Cancer, Sergiu Chira, Cornelia Braicu, Stefan Strilciuc, George A Calin, Ioana Berindan-Neagoe

Faculty, Staff and Student Publications

Background: Transposable elements are normally silenced by epigenetic mechanisms; however, during malignant transformation, epigenetic alterations enable transposons to produce functional molecules like miRNAs. Among these, LINE-2 (L2) elements can generate miRNAs capable of regulating key genes, including tumor suppressors. Two L2-derived miRNAs, miR-28 and miR-708, have been linked to lung cancer, yet the mechanisms underlying their dysregulation remain poorly understood. Our study reveals how genomic context contributes to aberrant gene expression through comprehensive bioinformatic analyses.

Methods: Using bioinformatics analysis, we evaluated the expression of miR-28 and miR-708 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets from TCGA. …

Life-Threatening Bradycardia In Anti-Nmda-Receptor Encephalitis And A Novel Use For Permanent Pacing, Sarah Tucker, Abhijit Das, Andres Jimenez, Areeba Basit, Yike Jiang, Emily A Smitherman, Heather Van Mater, Taylor Howard, Alexander J Sandweiss, Kristen S Fisher

Faculty, Staff and Students Publications

Background: Pediatric anti-NMDA receptor encephalitis (pNMDARE) is an autoantibody-mediated disorder that can cause severe autonomic dysfunction, including symptomatic bradycardia and asystole. Dysautonomia can last for years, making it very challenging to manage.

Objective: To describe outcomes of 5 pNMDARE patients with life-threatening bradycardic and/or asystolic events who were managed with permanent or semi-permanent pacemaker implantation.

Methods: We performed a retrospective chart review of 5 patients from multiple institutions. We included patients with a diagnosis of pNMDARE (confirmed by positive cerebrospinal fluid and/or serum anti-NMDAR antibodies) who had a permanent or semi-permanent pacemaker placed due to symptomatic bradycardia, sinus pauses, and/or …

Mechanistic And Functional Characterization Of Abtb2 As A Novel Target For Pancreatic Cancer Therapy, Nan Lyu, Olamide T Olaoba, Qiongling Wang, Harinarayanan Janakiraman, Xinjian Liu, Ernest Ramsay Camp, Kun Cheng, Eric T Kimchi, Yi Miao, Kevin F Staveley-O'Carroll, Guangfu Li

Faculty, Staff and Students Publications

BTB/POZ domain-containing proteins are increasingly recognized for their context-dependent roles in cancer, acting as either tumor suppressors or oncogenic drivers depending on the cancer type. Among them, the function of ankyrin repeat and BTB domain-containing protein 2 (ABTB2) in pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy, has remained unexplored. In this study, we employed comprehensive functional genomics approaches—siRNA/shRNA knockdown, CRISPR-Cas9 knockout, plasmid-based overexpression, and a Cre-LoxP transgenic mouse model—to systemically modulate ABTB2 expression in human and murine PDAC cell lines, as well as in the KPC mouse model of PDAC. Our gain- and loss-of-function studies revealed that ABTB2 plays …

Intimate Partner Violence And Brain Injury In Women: Understanding Prevalence, Symptomatology, And Consequences, Jacob T. Perez

Undergraduate Research Symposium

Intimate partner violence (IPV) refers to physical, sexual, or psychological harm caused by a current or former partner. While IPV can affect anyone, women are particularly vulnerable and disproportionately affected. Physical IPV often includes experiences of repeated trauma to the head, face, and neck, including strangulation. These injuries can result in a range of consequences, including comorbid conditions such as depression, PTSD, anxiety, and cognitive impairments, along with neurological effects like reduced brain connectivity and white matter integrity. Common brain injuries associated with IPV include traumatic brain injury (TBI), which results from blunt force trauma; subconcussive/repetitive blows, caused by head …

The Impact Of Exercise On Albuminuria And Kidney Function In The 2nd And 3rd Trimesters Of Physiological Pregnancy, Wojciech Wołyniec, Andrzej Kochanowicz, Jan Mieszkowski, Łukasz Radzimiński, Marcin Renke, Anna Szumilewicz

Baltic Journal of Health and Physical Activity

Background: Physical activity is an important part of healthy lifestyle and should be continued during low-risk pregnancy. Several studies have suggested that most pregnant women had no contraindications to perform exercises. The aim of the study was to assess the acute effect of an exercise test up to refusal and a chronic impact of an 8-week HIIT program on albuminuria and kidney function in the 2nd and 3rd trimester of pregnancy. Material and Methods: A group of 36 pregnant women was studied. At the beginning of the study, all participants had normal kidney function and albuminuria at rest. Nineteen women …

Postoperative Anaemia: The Unseen Challenge In Cardiac Surgery, Matthew A. Warner, Jacob Raphael

Department of Anesthesiology Faculty Papers

Postoperative anaemia is an overlooked complication of cardiac surgery that is associated with adverse clinical outcomes. Although small clinical trials suggest that postoperative treatment with i.v. iron improves haemoglobin recovery and reduces transfusion utilisation, appropriately powered randomised controlled trials are necessary to definitively evaluate the efficacy of treatment on clinical outcomes of importance to patients, clinicians, and healthcare systems. A comprehensive approach to perioperative anaemia management demands a renewed focus on both prevention and treatment to improve patient outcomes.

Surgical Revision In The Presence Of An S. Aureus Infection Increases Virulence Factor Expression And Activates A Multi-Tissue Inflammatory Response, Carly J. Smith, Arianna J. Moniodes, Amanda R. Watkins, Autumn G. Melvage, Thomas P. Thompson, Eirene Choi, Abigail A. Lucas, Brendan F. Gilmore, Thomas P. Schaer, Noreen J. Hickok, Theresa A. Freeman

Department of Orthopaedic Surgery Faculty Papers

Replacing implanted medical hardware due to infection often requires one or more revision surgeries. Each surgery triggers a tissue injury response and disrupts the established bacterial biofilm. However, the complex tissue response to reinjury and biofilm disturbance is not well understood. Our results show that with an existing infection, immunological niches such as the bone marrow, lymph nodes, and circulating blood further upregulate pro-inflammatory programs in response to revision. Rather than reducing bacterial burden, this heightened inflammation provokes virulence factor expression and tissue damage, including bone osteolysis and muscle fibrosis. While muscle fibrosis appears transient and begins resolving by 14 …

Osteoprogenitor Cells From Non-Regenerative Bone Show Greater Resistance To Cellular Stress Than Those From Regenerative Bone, Joshua Broussard, Sylvia Culpepper, Tyrel Long, Alexander J. Trostle, Robert J. Tower, Mimi C. Sammarco, Jennifer Simkin

School of Medicine Faculty Publications

INTRODUCTION: Bone regeneration following injury depends on osteoprogenitor cells derived predominantly from the periosteum. Incomplete regeneration has been attributed to both cell-extrinsic factors (e.g., environment, inflammation, mechanical instability) and cell-intrinsic factors (e.g., impaired proliferation or differentiation of stem cells). In the digit amputation mouse model, amputation through the third phalanx (P3) supports complete regeneration, while amputation through the second phalanx (P2) results in callus formation and scarring. Periosteal cells are known to be the major contributing cell source for repair and regeneration. Yet the healing outcomes of P2 and P3 amputations are significantly different. This study tests whether P2 and …

Urinothorax And Empyema: Presentation Of An Unusual Complication Of A Rare Condition, Nolan Fox, Nicholas Fox, Shourjo Chakravorty, Neeraj Sinha

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

A 68-year-old male with a history of metastatic bladder cancer and urinary obstruction presented with intractable hiccups and chest pain is presented in this case. He was found to have a unilateral pleural effusion in addition to ipsilateral renal metastasis abutting the diaphragm. Imaging revealed empyema. Thoracentesis revealed positive cultures and a lack of malignant cells on cytology. Comorbid urinary obstruction and urinary tract infection suggested the rare diagnosis of an infected urinothorax. Thoracentesis also revealed pleural fluid creatinine greater than serum creatinine, meeting the most specific diagnostic criteria for urinothorax and establishing the diagnosis. Treatment aimed at evacuating the …

Esophageal Gastrointestinal Stromal Tumor With, Bradley Kruithoff, Lauren Beard, David Liebner, Swati Satturwar, Matthew Lamb

Oncology Articles

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms typically involving the upper gastrointestinal tract. Most GISTs are driven by activating mutations in the KIT or PDGFRA genes, which are primary molecular markers for diagnosis and treatment. In addition, CD117 and DOG1 (discovered on GIST 1) are important immunohistochemical diagnostic markers of GISTs. Esophageal GISTs are exceptionally rare, and those driven by BRAF gene fusions are even more uncommon. This report describes a 69-year-old woman who underwent surgical resection of an esophageal GIST harboring an MKRN1-BRAF gene fusion, offering insight into future treatment and surveillance strategies.

Physical Performance Differences Between Top And First League Female Football Players: Insights From Locomotion Metrics, Mariola Gepfert, Artur Gołaś, Miłosz Drozd, Katarzyna Strońska-Grabień, Piotr Sawicki, Ewelina Lulińska

Baltic Journal of Health and Physical Activity

Background: This study aims to compare locomotion metrics between Poland’s Top League and First League at the team level using 10 Hz GPS. Methods: Team-level match data (autumn round) were analysed. The following metrics were computed: total distance, high-speed running (HSR: 19–23 km·h⁻¹ [5.28–6.39 m·s⁻¹]), sprinting (> 23 km·h⁻¹ [> 6.39 m·s⁻¹]), accelerations and decelerations at two thresholds (> 3.0 and > 4.0 m·s⁻²), and Player Load (arbitrary units, tri-axial accelerometry). Between-league differences were tested with Mann–Whitney U; rank-biserial effect sizes were reported. Results: Top League teams covered more sprint and HSR distance and performed more ACC/DEC at both thresholds (all …

Adjudicated Cardiovascular Events In Patients With Covid-19: Association With Vaccination Status And Changes Over Time, Behnood Bikdeli, Darsiya Krishnathasan, Antoine Bejjani, Candrika D. Khairani, Nada Hamade, Umberto Campia, Julia Davies, Nicole Porio, Ali Assi, Andre Armero, Anthony Tristani, Marcos D. Ortiz-Rios, Victor Nauffal, Zaid I. Almarzooq, Eric Q. Wei, Bridget Mcgonagle, Mariana Pfeferman, Sina Rashedi, Alyssa Sato, Giovanni Scimeca, Valeria Zuluaga-Sánchez, Mehrdad Zarghami, Aditya Achanta, Sirus Jesudasen, Bruce C. Tiu, Geno J. Merli, Orly Leiva, John Fanikos, Aditya M. Sharma, Samantha M. Rizzo, Ruth B. Morrison, Alec Vishnevsky, Shiavax J. Rao, Sivan Naveh, Abdelghani El Rafei, James Welker, Marc P. Bonaca, Brett J. Carroll, Samuel Z. Goldhaber, Zhou Lan, Gregory Piazza, The Corona-Vte Network Investigators

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Patients with COVID-19 are at risk of thrombotic and cardiovascular complications. Existing risk estimates derive from early COVID-19 experiences. More recent event rates, temporal trends, and the association between vaccination status and cardiovascular outcomes remain unclear.

METHODS: The CORONA-VTE Network (COVID-19 Registry to Assess Frequency, Risk Factors, Management, and Outcomes of Arterial and Venous Thromboembolic Complications) multicenter registry included patients with COVID-19 from March 2020 to February 2024. A composite of venous and arterial thrombotic events and a composite of adjudicated cardiovascular events were assessed at 90 days after COVID-19 diagnosis. Time-to-first-event analyses were stratified by inpatients and outpatients …

Traumatic And Incidental Diaphragmatic Hernias In Adults: A Case Series Highlighting Diagnostic Challenges, Surgical Management, And Postoperative Outcomes, Prajwal Chandrashekhara, Chanchal Raj Chhallani, Preethi Hiremath

Manipal Journal of Medical Sciences

Background:
Diaphragmatic hernia (DH) in adults, although uncommon, presents a significant clinical challenge due to its variable symptoms and potential for life-threatening complications. The condition can be either traumatic or congenital, and in some cases, it may be found incidentally during imaging for unrelated conditions. This case series aims to highlight the diverse clinical presentations, diagnostic challenges, surgical management strategies, and postoperative outcomes associated with diaphragmatic hernias in adults.

Methods:
We present four cases of diaphragmatic hernias diagnosed in adult patients, including both traumatic and incidental findings. Case 1 involves a 26-year-old male with a traumatic diaphragmatic hernia following a …

Beyond The Ordinary: A Case Report On A Giant Choledochal Cyst, Isha Saxena, Naresh Kumar J, Pareekshith Raghupal, Santosh Rai, Jayateertha Joshi

Manipal Journal of Medical Sciences

Choledochal cysts are rare congenital abnormalities of the biliary tract (1), with an incidence of 1:1000 births in the Asian population, with a female predominance. They usually appear within the first decade of life, presenting with symptoms like abdominal pain, jaundice, and a palpable abdominal mass. Todani et al. (2) classified them into five types. Common diagnostic techniques include ultrasound, CT, MRCP and ERCP. This case report presents a 14-year-old female with a giant type 1 choledochal cyst, successfully managed with cholecystectomy and Roux-en-Y jejunostomy.

Vesicle-Mediated Mitochondrial Clearance Presents An Actionable Metabolic Vulnerability In Triple-Negative Breast Cancer, Jody Vykoukal, Yihui Chen, Mingxin Zuo, Riccardo Ballarò, Monica J Hong, Hansini Krishna, Daniela B Rodriquez-Perera, Hiroyuki Katayama, Ehsan Irajizad, Ranran Wu, Ricardo A León-Letelier, Jennifer B Dennison, Angelica M Gutierrez, Adriana Paulucci-Holthauzen, Timothy C Thompson, Leona Rusling, Yining Cai, Fu Chung Hsiao, Soyoung Park, Banu Arun, Samir Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

Selective autophagy of mitochondria is known to promote cancer cell survival and progression, including in triple-negative breast cancer (TNBC). Here, we apply an integrated multi-omics approach together with functional experimental analyses to investigate metabolic adaptations that support mitochondrial quality control in TNBC. We detail a mitochondrial quality control mechanism, complementary to mitophagy, that is enabled by a program of heightened extracellular sphingomyelin salvaging in TNBC coupled with extracellular vesicle-mediated intracellular clearance of mitochondrial damage. Targeting of this onco-metabolic pathway via repurposing of eliglustat, a selective small molecule inhibitor of glucosylceramide synthase, results in ceramide-mediated compensatory mitophagy and cancer cell death …

Accurate Imputation Of Pathway-Specific Gene Expression In Spatial Transcriptomics With Pasta, Ruoxing Li, Peng Yang, Mauro Di Pilato, Jianjun Zhang, Christopher R Flowers, Lulu Shang, Ziyi Li

Faculty, Staff and Student Publications

Mapping the entire transcriptome at single-cell resolution under its natural spatial context is essential for investigating the oncogenesis and progression of diseases. The recently emerged targeted in-situ technologies retain the spatial organization of cells at high resolution, although they remain limited in the number of genes that can be simultaneously measured. To overcome this obstacle, numerous computational methods have been developed to predict unmeasured gene expression in spatial transcriptomics data by leveraging scRNA-seq data. Most of these methods focus on the expression of individual genes and usually generate highly variable predictions. In this study, we introduce PASTA (PAthway-oriented Spatial gene …

Lung Adenocarcinoma Surfaceome Remodeling With Egfr Inhibitors Uncovers Placental Alkaline Phosphatase As A Target For Combination Therapy, Yihui Chen, Rongzhang Dou, Monica J Hong, Hanwen Xu, Jody Vykoukal, Ricardo A León-Letelier, Yining Cai, Soyoung Park, Ehsan Irajizad, Fu Chung Hsiao, Jennifer B Dennison, Edwin J Ostrin, Johannes F Fahrmann, Hiroyuki Katayama, Samir M Hanash

Faculty, Staff and Student Publications

Treatment of lung adenocarcinomas (LUADs) that exhibit activated epidermal growth factor receptor (EGFR) with EGFR tyrosine kinase inhibitors (TKIs) has limited efficacy. Assessment of the impact of EGFR TKI on the LUAD surfaceome remodeling reveals potential therapeutic targets. We identify placental type alkaline phosphatase (ALPP), which has restricted expression in normal tissues, among upregulated surface proteins following EGFR TKI treatment of both TKI sensitive as well as resistant cells. EGF treatment represses ALPP expression, whereas EGFR TKIs upregulate its expression through dephosphorylation and activation of FoxO3a, a transcriptional regulator that binds to the promoter region of ALPP. The combination of …

Flawed Design And Selection Bias In Critical Care Randomized Controlled Trials (Rcts): The Patient Safety Risk Of The "Rct Mimic"., Lawrence A Lynn

Ambulatory and Primary Care Articles

Over three decades, randomized controlled trials (RCTs) for critical care syndromes such as acute respiratory distress syndrome (ARDS), sepsis, and community acquired pneumonia (CAP) have repeatedly produced non-reproducible results, at times leading to high-impact reversals of global protocols when later studies revealed harm. These trials enroll patients using expert-derived threshold sets intended to define the syndrome. This analytic review presents the first historical and formal methodological review and mathematical analysis of such RCT using causal symbolic modeling (cSM), directed acyclic graphs (DAGs), and do-calculus. The review includes landmark publications, task-force threshold sets, and case examples, including the 2025 REMAP-CAP corticosteroid …