Medicine and Health Sciences Commons^™

Neutralizing Antibody Immune Correlates In Covail Trial Recipients Of An Mrna Second Covid-19 Vaccine Boost, Bo Zhang, Youyi Fong, Lauren Dang, Jonathan Fintzi, Shiyu Chen, Jing Wang, Nadine G Rouphael, Angela R Branche, David J Diemert, Ann R Falsey, Daniel S Graciaa, Lindsey R Baden, Sharon E Frey, Jennifer A Whitaker, Susan J Little, Satoshi Kamidani, Emmanuel B Walter, Richard M Novak, Richard Rupp, Lisa A Jackson, Chenchen Yu, Craig A Magaret, Cindy Molitor, Bhavesh Borate, Sydney Busch, David Benkeser, Antonia Netzl, Derek J Smith, Tara M Babu, Angelica C Kottkamp, Anne F Luetkemeyer, Lilly C Immergluck, Rachel M Presti, Martín Bäcker, Patricia L Winokur, Siham M Mahgoub, Paul A Goepfert, Dahlene N Fusco, Robert L Atmar, Christine M Posavad, Jinjian Mu, Mat Makowski, Mamodikoe K Makhene, Seema U Nayak, Paul C Roberts, Peter B Gilbert, Dean Follmann

Faculty, Staff and Students Publications

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ("COVID-19") and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. …

Targeting Trpc Channels For Control Of Arthritis-Induced Bone Erosion, Suravi Ray, Jamie L Mccall, Jin Bin Tian, Jaepyo Jeon, Aidan Douglas, Kendall Tyler, Siyao Liu, Kendyl Berry, Brady Nicewarner, Casey Hall, Klaus Groschner, Bernadett Bacsa, Werner Geldenhuys, Michael X Zhu, Harry C Blair, John B Barnett, Jonathan Soboloff

Faculty, Staff and Student Publications

Arthritis leads to bone erosion due to an imbalance between osteoclast and osteoblast function. Our prior investigations revealed that the Ca2+-selective ion channel, Orai1, is critical for osteoclast maturation. Here, we show that the small-molecule ELP-004 preferentially inhibits transient receptor potential canonical (TRPC) channels. While ELP-004 minimally affected physiological RANKL-induced osteoclast maturation in murine bone marrow- and spleen-derived myeloid cells (BMSMCs) and human PBMC-derived cells, it potently interfered with osteoclast maturation driven by TNFα or LTB4. The contribution of TRPC channels to osteoclastogenesis was examined using BMSMCs derived from TRPC4-/- or TRPC(1-7)-/- mice, again revealing preferential interference with osteoclastogenesis driven …

Exosomal Galectin-3 Promotes Peritoneal Metastases In Gastric Adenocarcinoma Via Microenvironment Alterations, Yibo Fan, Shumei Song, Melissa Pool Pizzi, Gengyi Zou, Jody V Vykoukal, Katsuhiro Yoshimura, Jiankang Jin, George A Calin, Rebecca E Waters, Qiong Gan, Linghua Wang, Samir Hanash, Shilpa S Dhar, Jaffer A Ajani

Faculty, Staff and Student Publications

Peritoneal carcinomatosis (PC) in gastric adenocarcinoma (GAC) is the most common metastatic site and leads to a short median survival. Exosomes have been shown to remodel the microenvironment, facilitating tumor metastases. However, the functional component in GAC cell-derived exosomes that remodel the landscape in the peritoneal cavity remains unclear. To address this, we performed in-depth proteomic profiling of ascites-derived exosomes from patients with PC, and we found that Galectin-3 was highly enriched in exosomes derived from malignant ascites. exosomal Galectin-3 was the crucial regulator of PC. Blockage of exosomal Galectin-3 significantly inhibited tumor metastases and prolonged overall survival. Exosomal Galectin-3 …

Dysregulated Klf4 Expression Plays A Pivotal Role In The Pathogenesis Of Pancreatic Intraductal Papillary Mucinous Neoplasms, Xiangsheng Zuo, Liang Wang, Yi Liu, Huamin Wang, Margarete Hafley, Mihai Gagea, Ru Chen, Yun Xiong, Sheng Pan, Imad Shureiqi, Robert S Bresalier, Daoyan Wei

Faculty, Staff and Student Publications

No abstract provided.

Light-Dark Shift Promotes Colon Carcinogenesis Through Accelerated Colon Aging, Deepak Sharma, Phillip A Engen, Abu Osman, Darbaz Adnan, Maliha Shaikh, Mostafa K Abdel-Reheem, Ankur Naqib, Stefan J Green, Bruce Hamaker, Christopher B Forsyth, Lin Cheng, Ali Keshavarzian, Khashayarsha Khazaie, Faraz Bishehsari

Faculty, Staff and Student Publications

Colorectal cancer (CRC) is the third most common cancer worldwide, with rising prevalence among younger adults. Several lifestyle factors, particularly disruptions in circadian rhythms by light-dark (LD) shifts, are known to increase CRC risk. Epidemiological studies previously showed LD-shifts are associated with increased risk of CRC. To explore the mechanisms and interactions between LD-shift and intestinal aging, we investigated how the combination of LD-shifts and aging impacts colon carcinogenesis development. Our data showed that LD-shifts and aging increased colon tumorigenesis. Notably, LD-shift accelerated intestinal aging by altering aging-related pathways, such as intestinal barrier damage, accompanied by dysbiotic changes in the …

Clinical And Molecular Characteristics Of Patients With Brain Metastasis Secondary To Pancreatic Ductal Adenocarcinoma, Mahmoud Yousef, Mark W Hurd, Abdelrahman Yousef, Ethan B Ludmir, Ashwathy B Pillai, Jennifer Peterson, Eugene J Koay, Sali Albarouki, Ching-Wei Tzeng, Rebecca Snyder, Matthew H G Katz, Huamin Wang, Michael J Overman, Anirban Maitra, Shubham Pant, Brandon G Smaglo, Robert A Wolff, James Yao, John P Shen, Dan Zhao

Faculty, Staff and Student Publications

Background: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Secondary brain metastasis (Br-M) occurs in less than 1% of patients. Clinical characteristics and molecular alterations have not been characterized in this rare patients' subset.

Materials and methods: The Foundry software platform was used to retrospectively query electronic health records for patients with Br-M secondary to PDAC from 2005 to 2023; clinical, molecular, and overall survival (OS) data were analyzed.

Results: Br-M was diagnosed in 44 patients with PDAC. Median follow-up was 78 months; median OS from initial PDAC diagnosis was 47 months. Median duration from PDAC diagnosis …

Pooled Safety Analysis And Management Of Sotorasib-Related Adverse Events In Kras G12c-Mutated Advanced Non-Small Cell Lung Cancer, Ferdinandos Skoulidis, Bob T Li, Maximilian Hochmair, Ramaswamy Govindan, Mark Vincent, Anthonie J Van Der Wekken, Noemi Reguart Aransay, Kenneth J O'Byrne, Nicolas Girard, Frank Griesinger, Makoto Nishio, Simon Häfliger, Colin Lindsay, Niels Reinmuth, Astrid Paulus, Pavlos Papakotoulas, Sang-We Kim, Carlos Gil Ferreira, Giulia Pasello, Michael Duruisseaux, Spyridon Gennatas, Anastasios Dimou, Bhakti Mehta, William Kormany, Chidozie Nduka, Brooke E Sylvester, Christine Ardito-Abraham, Yang Wang, Adrianus Johannes De Langen

Faculty, Staff and Student Publications

Introduction: We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks.

Methods: Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0. Adverse events were deemed sotorasib-related per investigator causality assessment.

Results: In the pooled population (n = 549), TRAEs were reported in 388 (70.7%) patients (grade 1: 124 [22.6%]; grade 2: 117 [21.3%]; …

Comparison Of Sampling And Culture Methods For The Recovery Of Yeast From Hospital Surfaces, Allison R Eberly, Alyssa M Valencia, Kate Peacock, David Mcdonald, Tiffany Hink, Carleigh Samuels, Lucy Vogt, Yao-Peng Xue, Maggie Newberry, Caroline A O'Neil, Gautam Dantas, Jennie H Kwon

2020-Current year OA Pubs

OBJECTIVE: To compare the recovery of yeast from hospital surfaces from two different collection methods: Eswab moistened with molecular water, and premoistened stick-mounted sponge.

DESIGN: Comparison of collection methods for the recovery of yeast in the hospital environment.

SETTING: This study took place at intensive care units of a large academic medical center.

Evolution Of The Umbilical Cord Blood Proteome Across Gestational Development, Leena B Mithal, Nicola Lancki, Ted Ling-Hu, Young Ah Goo, Sebastian Otero, Nathaniel J Rhodes, Byoung-Kyu Cho, William A Grobman, Judd F Hultquist, Denise Scholtens, Karen K Mestan, Patrick C Seed

2020-Current year OA Pubs

Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth. In this study, we comprehensively characterized the cord blood proteome of infants born between 25 to 42 weeks using untargeted mass spectrometry and functional enrichment analysis. We determined that the cord blood proteome at birth varies significantly across gestational development. …

Neutralizing Antibody Immune Correlates In Covail Trial Recipients Of An Mrna Second Covid-19 Vaccine Boost, Bo Zhang, Rachel M Presti, Et Al.

2020-Current year OA Pubs

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ("COVID-19") and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. …

Germline Predisposition In Multiple Myeloma, Fernanda Martins Rodrigues, Yize Li, Erik Storrs, Michael C Wendl, Reyka G Jayasinghe, Mark Fiala, John F Dipersio, Ravi Vij, Li Ding, Et Al.

2020-Current year OA Pubs

We present a study of rare germline predisposition variants in 954 unrelated individuals with multiple myeloma (MM) and 82 MM families. Using a candidate gene approach, we identified such variants across all age groups in 9.1% of sporadic and 18% of familial cases. Implicated genes included genes suggested in other MM risk studies as potential risk genes (

Barcoded Sars-Cov-2 Viruses Define The Impact Of Duration And Route Of Exposure On The Transmission Bottleneck In A Hamster Model, Reed Trende, Tamarand L Darling, Tianyu Gan, David Wang, Adrianus C M Boon

2020-Current year OA Pubs

The transmission bottleneck, defined as the number of viruses shed from one host to infect another, is an important determinant of the rate of virus evolution and the level of immunity required to protect against virus transmission. Despite its importance, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission bottleneck remains poorly characterized. We adapted a SARS-CoV-2 reverse genetics system to generate a pool of >200 isogenic SARS-CoV-2 viruses harboring specific 6-nucleotide barcodes, infected donor hamsters with this pool, and exposed contact hamsters to paired infected donors, varying the duration and route of exposure. Following exposure, the nasal turbinates, trachea, …

Recommendations For Interdisciplinary Research Collaboration For Early Career Dissemination And Implementation Researchers: A Multi-Phase Study, Hannah G Lane, Sallie D Allgood, Julie Schexnayder, Hayden B Bosworth, Ana A Baumann, Allison A Lewinski

2020-Current year OA Pubs

INTRODUCTION: Dissemination and implementation (D&I) scientists are key members of collaborative, interdisciplinary clinical and translational research teams. Yet, early career D&I researchers (ECRs) have few guidelines for cultivating productive research collaborations. We developed recommendations for ECRs in D&I when serving as collaborators or co-investigators.

METHODS: We employed a consensus-building approach: (1) group discussions to identify 3 areas of interest: "Marketing yourself" (describing your value to non-D&I collaborators), "Collaboration considerations

RESULTS: Forty-four D&I researchers completed the first survey, 12 of whom attended one of three focus groups. Twenty-nine D&I researchers completed the second survey (

CONCLUSIONS: Research collaborations are essential in …

Mission Success: Mastering Muscle Function Through Humanoid Analysis, Amber M. Chelette

Educational Practices in Kinesiology

Knowledge of muscle function and human movement are essential skills of all kinesiology students. In the humanoid activity, teams are challenged to determine whether a muscle is essential to the successful development of a humanoid being sent to Mars. This activity provides a significant learning experience regarding muscle anatomy, function, and movement analysis. The humanoid activity is intended for use in a face-to-face upper-level kinesiology anatomy or movement analysis course and best implemented with class sizes of 20-30 students. The total time commitment is approximately 45 minutes.

Class Iii Phosphatidylinositol-3 Kinase/Vacuolar Protein Sorting 34 In Cardiovascular Health And Disease, Yuanjun Shen, Jason Gleghorn

Pharmacy Faculty Scholarship

Phosphatidylinositol-3 kinases (PI3Ks) play a critical role in maintaining cardiovascular health and the development of cardiovascular diseases (CVDs). Specifically, vacuolar Protein Sorting 34 (VPS34) or PIK3C3, the only member of Class III PI3K, plays an important role in CVD progression. The main function of VPS34 is inducing the production of phosphatidylinositol 3-phosphate, which, together with other essential structural and regulatory proteins in forming VPS34 complexes, further regulates the mammalian target of rapamycin activation, autophagy, and endocytosis. VPS34 is found to have crucial functions in the cardiovascular system, including dictating the proliferation and survival of vascular smooth muscle cells and cardiomyocytes …

Process Evaluation Of The Hockey Fans In Training Lifestyle Intervention (For Men With Overweight Or Obesity)., Wendy M Blunt, Marisa L Kfrerer, Dawn P. Gill, Katie J Shillington, Brendan Riggin, Jennifer D Irwin, Brooke Bliss, Robert J Petrella

Department of Medicine Publications

BACKGROUND: Despite the proven relationship between lifestyle and morbidity and mortality, rates of chronic disease (e.g. obesity) continue to rise in paradox to the myriad of studies supporting lifestyle behaviour change. Men have been less likely to seek out preventative care or lifestyle programs, putting them at risk. In response, Hockey Fans In Training (Hockey FIT) was developed as a group-based, lifestyle intervention leveraging the draw of hockey fandom to engage middle-aged men with overweight or obesity in lifestyle change. Encouraging pilot study results informed the optimization and delivery of the intervention through a cluster randomized controlled trial in 42 …

Priority Competencies For Designated Education Officers In The Veterans Health Administration, Duane R. Bidwell, Anita Samuel, Ronald M. Cervero, Steven J. Durning, Sherri L. Stephan, Erin L. Patel, Marjorie A. Bowman, Holly S. Meyer

Population and Public Health Sciences Faculty Publications

Designated Education Officers (DEOs) at Veteran Health Administration (VHA) hospitals are senior educational leaders tasked with oversight of all clinical training at a particular facility. They prioritize dozens of tasks and responsibilities each day, from educational policy and strategy to staff management, financial planning, onboarding of trainees, and facility planning and management. Clarifying priority competencies for the role can help executives recruit, appoint, and evaluate capable personnel and promote effective, efficient performance. Using a federally developed method of competency analysis, researchers consulted a panel of subject-matter experts to identify priority competencies for DEOs, using data from a 2013 study that …

Practicing And Assessing Skills Of Interpreting Culture And Sensitivity Reports, Lana Gettman

Faculty Research ​and Publications

No abstract provided.

Medical School Watercooler Newsletter - January 16, 2025, Lindsay Hughes

Watercooler Newsletter

This is the Thursday, January 16, 2025 edition of the Frederick P. Whiddon College of Medicine at the University of South Alabama.

Contents include:

• Whiddon College of Medicine celebrates new doctoral graduates
• Medical student presents at international pediatric neurosurgery meeting
• Internal medicine residents improve nonverbal skills in unique way
• Neurosurgery department makes impact at Congress of Neurological Surgeons Meeting 
• Staff earn research administration credentials 
• Military students match early in residency programs

Improving The Clinical Diagnostic Criteria For Genetically Confirmed Adult-Onset Huntington Disease: Considering Nonmotor Presentations, Ciaran M. Considine, Clare M. Eddy, Samuel A. Frank, Sandra K. Kostyk, Mayke Oosterloo, Annie Killoran, Erin Furr Stimming, Matthias Dose, Travis Cruickshank, Thomas D. Bird, Louise Vetter, Astri Arnesen, James Valvano, Herwig W. Lange, Daniel O. Claassen

Research outputs 2022 to 2026

BackgroundHuntington disease (HD) is a genetic neurodegenerative disorder. Given the focus on motor manifestations, nonmotor symptoms are frequently underappreciated in clinical evaluations, despite frequently contributing to primary functional impairment.Recent FindingsA diagnosis of motor-onset as the definition of manifest symptoms misrepresents the complex nature of HD presentation. Despite recent attempt to integrate nonmotor diagnostic criteria, practical guidelines are necessary to inform clinical diagnosis. We propose an HD diagnostic framework and staging system that prioritizes genetic testing, integrates motor and nonmotor symptom considerations in the determination of clinical disease onset and severity, and acknowledges the secondary role of clinically indicated diagnostic assessments, …

Hiv Associated Epigenetic Trends And Chronic Diseases: Insights Into The Hidden Burden Of Chronic Infection, Courtney G. Wallace, Zachary Capriotti, Zachary Klase

Kimmel Cancer Center Faculty Papers

Human Immunodeficiency Virus (HIV) remains a major health challenge despite dramatic advances in treatment and prevention. People living with HIV (PLWH) continue to experience high rates of non-AIDS comorbidities, including cardiovascular, renal, pulmonary, oncologic, and neurocognitive disorders. These conditions persist under viral suppression, underscoring the lasting biological impact of infection. Epigenetic dysregulation has emerged as a key driver of these outcomes. HIV integration, viral proteins, chronic inflammation, and ART exposure have all been reported to alter DNA methylation, histone modifications, transcription factor networks, and noncoding RNA regulation. These changes extend beyond infected cells, reprogramming uninfected immune and tissue compartments. Long-lived …

Keeping Kids Safe At Meals: Preventing And Responding To Choking, Mia Dustin, Savannah Daines, Stacy Bevan, Palak Gupta, Mateja R. Savoie-Roskos

All Current Publications

Introducing solid foods is an exciting developmental milestone, but it can also raise concerns about choking for parents and caregivers. Choking occurs when an object, such as food or a toy, blocks a child’s airway and prevents air from moving in and out of the lungs. This fact sheet offers practical guidance on how to prevent food-related choking, recognize the signs of a choking emergency, and what to do if a child is choking.

Assessment, Decision, Adaptation, Production, Topical Experts-Integration, Training, And Testing (Adapt-Itt) Framework To Tailor Evidence-Based Posttraumatic Stress Disorder Treatment For People With Hiv To Enhance Engagement And Adherence: Qualitative Results From A Feasibility Randomized Controlled Trial, Cristina M. Lopez, Angela D. Moreland, Stephanie Amaya, Erin Bisca, Christin Mujica, Tayler Wilson, Nathaniel Baker, Lauren Richey, Allison Ross Eckard, Patricia A. Resick, Steven A. Safren, Carla Kmett Danielson

School of Medicine Faculty Publications

BACKGROUND: Individuals with co-occurring posttraumatic stress disorder (PTSD) and HIV are at high-risk for negative HIV-related outcomes, including low adherence to antiretroviral therapy, faster disease progression, more hospitalizations, and almost twice the rate of death. Despite high rates of PTSD in persons with HIV (PWH) and poor HIV-related health outcomes associated with PTSD, an effective evidence-based treatment for PTSD symptoms in PWH does not exist. OBJECTIVE: This study aimed to describe the adaptation and theater testing of an evidence-based intervention designed for people with co-occurring PTSD and HIV. METHODS: The Assessment, Decision, Adaptation, Production, Topical experts-integration, Training, and Testing (ADAPT-ITT) …

Racial Disparities Of Type 2 Diabetes Through Exercise: The Multi-Ethnic Study Of Atherosclerosis, Tong Xia, Roch A. Nianogo, Qingzhao Yu, Tamara Horwich, Preethi Srikanthan, Kosuke Inoue, Matthew Allison, Zuo-Feng Zhang, Karol E. Watson, Liwei Chen

School of Public Health Faculty Publications

Introduction: Persistent racial and ethnic disparities exist for Type 2 diabetes in the U.S. Racial and ethnic minorities have a higher risk of Type 2 diabetes, and studies suggest that they engage in less exercise than White population. This study examined whether and to what degree racial differences in Type 2 diabetes were explained by exercise. Methods: Adults aged 45–84 years without Type 2 diabetes at baseline (2000–2002) were included from the Multi-Ethnic Study of Atherosclerosis cohort and followed through 2020. Associations between race and Type 2 diabetes were examined using multivariable Cox proportional hazard regression. The effects of exercise …

A Yeast-Based Oral Therapeutic Delivers Immune Checkpoint Inhibitors To Reduce Intestinal Tumor Burden, Olivia N Rebeck, Miranda J Wallace, Jerome Prusa, Jie Ning, Esse M Evbuomwan, Sunaina Rengarajan, Lemoyne Habimana-Griffin, Suryang Kwak, David Zahrah, Jason Tung, James Liao, Bejan Mahmud, Skye R S Fishbein, Erick S Ramirez Tovar, Rehan Mehta, Bin Wang, Mark G Gorelik, Gautam Dantas, Et Al.

2020-Current year OA Pubs

Engineered probiotics are an emerging platform for in situ delivery of therapeutics to the gut. Herein, we developed an orally administered, yeast-based therapeutic delivery system to deliver next-generation immune checkpoint inhibitor (ICI) proteins directly to gastrointestinal tumors. We engineered Saccharomyces cerevisiae var. boulardii (Sb), a probiotic yeast with high genetic tractability and innate anticancer activity, to secrete "miniature" antibody variants that target programmed death ligand 1 (Sb_haPD-1). When tested in an ICI-refractory colorectal cancer (CRC) mouse model, Sb_haPD-1 significantly reduced intestinal tumor burden and resulted in significant shifts to the immune cell profile and microbiome composition. This oral therapeutic platform …

Atrial Fibrillation Recurrence Risk After Catheter Ablation In Patients With Rheumatoid Arthritis: A Systematic Review And Meta-Analysis, Pongprueth Rujirachun, Phuuwadith Wattanachayakul, Svita Taveeamornrat, Patompong Ungprasert, Nithi Tokavanich, Krit Jongnarangsin

Einstein Health Papers

BACKGROUND: The association between rheumatoid arthritis (RA) and the risk of developing atrial fibrillation (AF) is well-established. However, data on the impact of RA on AF recurrence postcatheter ablation (CA) remain unclear. This current study aimed to assess the impact of RA on AF recurrence after catheter-based pulmonary vein isolation.

METHODS: Potentially eligible studies were identified from Medline and EMBASE databases from inception to December 20, 2023. Eligible study must consist of two cohorts of patients with and without RA who underwent catheter ablation for AF. Pooled risk ratio (RR) and 95% CI were calculated using Dersimonian and Laird's random-effect, …

Expansion Of Genotypic And Phenotypic Findings In Adamts18-Related Ocular Pathology, Ari August, Rebecca Procopio, Christopher Rapuano, Jose Pulido

Wills Eye Hospital Papers

Purpose: ADAMTS18-related ocular pathology is rare with few described cases. Features include distinctive facies, refractive error, anterior segment dysgenesis, and retinal dystrophy. Previous patients were found to have ho- mozygous variants in ADAMTS18. Here, we present a patient with compound heterozygous ADAMTS18-related pathology and its associated findings. Observations: A 37-year-old male with a history of bilateral congenital nasolacrimal duct obstruction, dry eye syndrome, mild myopia, and accommodative esotropia presented to the Retina Service. He was found to have multiple features of anterior segment dysgenesis and retinal dystrophy, some of which have not been previously reported in association with ADAMTS18 variants. …

Transcription Factor Runx1 Regulates Coagulation Factor Xiii-A (F13a1): Decreased Platelet-Megakaryocyte F13a1 Expression And Clot Contraction In Runx1 Haplodeficiency, Fabiola Del Carpio-Cano, Natthapol Songdej, Liying Guan, Guangfen Mao, Lawrence E. Goldfinger, Jeremy G.T. Wurtzel, Kiwon Lee, Michele P. Lambert, Mortimer Poncz, A. Koneti Rao

Cardeza Foundation for Hematologic Research

BACKGROUND: Germline RUNX1 haplodeficiency (RHD) is associated with thrombocy- topenia, platelet dysfunction, and predisposition to myeloid malignancies. Platelet expression profiling of an RHD patient showed decreased F13A1, encoding for the A subunit of factor (F)XIII, a transglutaminase that cross-links fibrin and induces clot stabilization. FXIII-A is synthesized by hematopoietic cells, megakaryocytes, and monocytes.

OBJECTIVES: o understand RUNX1 regulation of F13A1 expression in platelets/mega- karyocytes and the mechanisms and consequences of decreased F13A1 in RHD.

METHODS: We performed studies in platelets, human erythroleukemia (HEL) cells, and human CD34+ cell-derived megakaryocytes including on clot contraction in cells following small inhibitor RNA knockdown …

Exploring The Pathogen Profiles Of Ancient Feces, Drew Capone, David Holcomb, Amanda Lai, Karl Reinhard, Joe Brown

Karl Reinhard Publications

Analysis of ancient desiccated feces – termed paleofeces or coprolites – can unlock insights into the lives of ancient people. We collected desiccated feces from caves in the Rio Zape Valley in Mexico (725-920 CE). First, we extracted DNA with methods previously optimized for paleofeces. Then, we applied highly sensitive modern molecular tools (i.e., PCR pre-amplification followed by multi-parallel qPCR) to assess the presence of 30 enteric pathogens. We detected ≥1 pathogen associated gene in each of the ten samples and a mean of 3.9 pathogens per sample. The targets detected included Blastocystis spp. (n=7), atypical enteropathogenic E. coli (n=7), …

Discontiguous Recurrences Of Idh-Wildtype Glioblastoma Share A Common Origin With The Initial Tumor And Are Frequently Hypermutated, Malcolm F Mcdonald, Sricharan Gopakumar, Tareq A Juratli, Ilker Y Eyüpoglu, Ganesh Rao, Jacob J Mandel, Ali Jalali

Faculty, Staff and Students Publications

Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences. In our institutional database, we identified 22 patients with targeted exome sequencing of pairs of initial and recurrent IDH-wildtype glioblastoma. Recurrences were classified as contiguous or discontiguous based on the presence or absence of T2 FLAIR signal connection to the initial site of disease on MRI. Exome analysis revealed shared driver and passenger mutations between discontiguous recurrences …