Medicine and Health Sciences Commons^™

Oculomics Analysis In Multiple Sclerosis: Current Ophthalmic Clinical And Imaging Biomarkers, Alex Suh, Gilad Hampel, Aditya Vinjamuri, Joshua Ong, Sharif Amit Kamran, Ethan Waisberg, Phani Paladugu, Nasif Zaman, Prithul Sarker, Alireza Tavakkoli, Andrew G Lee

Faculty, Staff and Student Publications

Multiple Sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. Early recognition and treatment are important for preventing or minimizing the long-term effects of the disease. Current gold standard modalities of diagnosis (e.g., CSF and MRI) are invasive and expensive in nature, warranting alternative methods of detection and screening. Oculomics, the interdisciplinary combination of ophthalmology, genetics, and bioinformatics to study the molecular basis of eye diseases, has seen rapid development through various technologies that detect structural, functional, and visual changes in the eye. Ophthalmic biomarkers (e.g., tear composition, …

Social Determinants Of Health And Surgical Desirability Of Outcome Ranking In Older Veterans, Michael A Jacobs, Yubo Gao, Susanne Schmidt, Paula K Shireman, Michael Mader, Carly A Duncan, Leslie R M Hausmann, Karyn B Stitzenberg, Lillian S Kao, Mary Vaughan Sarrazin, Daniel E Hall

Faculty, Staff and Student Publications

Importance: Evaluating how social determinants of health (SDOH) influence veteran outcomes is crucial, particularly for quality improvement.

Objective: To measure associations between SDOH, care fragmentation, and surgical outcomes using a Desirability of Outcome Ranking (DOOR).

Design, setting, and participants: This was a cohort study of US veterans using data from the Veterans Affairs (VA) Surgical Quality Improvement Program (VASQIP; 2013-2019) limited to patients aged 65 years or older with inpatient stays between 2 and 30 days, merged with multiple data sources, including Medicare. Race and ethnicity data were retrieved from VASQIP, Medicare and Medicaid beneficiary summary files, the Veterans Health …

Targeting The Epidermal Growth Factor Receptor Pathway In Chemotherapy-Resistant Triple-Negative Breast Cancer: A Phase Ii Study, Clinton Yam, Miral Patel, Holly A Hill, Ryan Sun, Roland L Bassett, Elisabeth Kong, Senthil Damodaran, Kimberly B Koenig, Sausan Abouharb, Sadia Saleem, Ajit K Bisen, Rashmi K Murthy, David L Ramirez, Gaiane M Rauch, Beatriz E Adrada, Rosalind P Candelaria, Xiaoping Wang, Elizabeth A Mittendorf, Alastair M Thompson, Jason B White, Elizabeth E Ravenberg, Alyson R Clayborn, Qing-Qing Ding, Daniel J Booser, Oluchi Oke, Abenaa M Brewster, Gabriel N Hortobagyi, Nuhad K Ibrahim, Jennifer K Litton, Vicente Valero, Banu K Arun, Debu Tripathy, Jeffrey T Chang, Ken Chen, Anil Korkut, Stacy L Moulder, Lei Huo, Bora Lim, Naoto T Ueno

Faculty, Staff and Student Publications

Purpose: Epidermal growth factor receptor (EGFR) pathway activation causes chemotherapy resistance, and inhibition of the EGFR pathway sensitizes triple-negative breast cancer (TNBC) cells to chemotherapy in preclinical models. Given the high prevalence of EGFR overexpression in TNBC, we conducted a single-arm phase II study of panitumumab (anti-EGFR monoclonal antibody), carboplatin, and paclitaxel as the second phase of neoadjuvant therapy (NAT) in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02593175).

Patients and methods: Patients with early-stage, AC-resistant TNBC, defined as disease progression or ≤80% reduction in tumor volume after four cycles of AC, were eligible for this study and …

Integrated Safety And Efficacy Analyses Of Phase 3 Trials Of A Microbiome Therapeutic For Recurrent Cdi, Colleen S Kraft, Matthew Sims, Michael Silverman, Thomas J Louie, Paul Feuerstadt, Edward S Huang, Sahil Khanna, Charles S Berenson, Elaine E L Wang, Stuart H Cohen, Louis Korman, Christine Lee, Colleen R Kelly, Alberto Odio, Paul P Cook, Bret Lashner, Mayur Ramesh, Princy Kumar, Ananya De, Asli Memisoglu, David A Lombardi, Brooke R Hasson, Barbara H Mcgovern, Lisa Von Moltke, Darrell S Pardi, Ecospor Iii And Ecospor Iv Investigators

Faculty, Staff and Students Publications

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI.

OBJECTIVE, DESIGN, AND PATIENTS: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities.

METHODS: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest …

Detection Of Mosaic And Population-Level Structural Variants With Sniffles2, Moritz Smolka, Luis F Paulin, Christopher M Grochowski, Dominic W Horner, Medhat Mahmoud, Sairam Behera, Ester Kalef-Ezra, Mira Gandhi, Karl Hong, Davut Pehlivan, Sonja W Scholz, Claudia M B Carvalho, Christos Proukakis, Fritz J Sedlazeck

Faculty, Staff and Students Publications

Calling structural variations (SVs) is technically challenging, but using long reads remains the most accurate way to identify complex genomic alterations. Here we present Sniffles2, which improves over current methods by implementing a repeat aware clustering coupled with a fast consensus sequence and coverage-adaptive filtering. Sniffles2 is 11.8 times faster and 29% more accurate than state-of-the-art SV callers across different coverages (5-50×), sequencing technologies (ONT and HiFi) and SV types. Furthermore, Sniffles2 solves the problem of family-level to population-level SV calling to produce fully genotyped VCF files. Across 11 probands, we accurately identified causative SVs around MECP2, including highly complex …

Distinct Landscape And Clinical Implications Of Therapy-Related Clonal Hematopoiesis, Koichi Takahashi, Daisuke Nakada, Margaret Goodell

Faculty, Staff and Student Publications

Therapy-related clonal hematopoiesis (t-CH) is defined as clonal hematopoiesis detected in individuals previously treated with chemotherapy and/or radiation therapy. With the increased use of genetic analysis in oncological care, the detection of t-CH among cancer patients is becoming increasingly common. t-CH arises through the selective bottleneck imposed by chemotherapies and potentially through direct mutagenesis from chemotherapies, resulting in a distinct mutational landscape enriched with mutations in DNA damage-response pathway genes such as TP53, PPM1D, and CHEK2. Emerging evidence sheds light on the mechanisms of t-CH development and potential strategies to mitigate its emergence. Due to its unique characteristics that predominantly …

A Method For Rapid And Reliable Quantification Of Vegf-Cell Binding Activity, Prabuddha Waduge, Avinash Kaur, Wei Li

Faculty, Staff and Students Publications

Vascular endothelial growth factor (VEGF) is a pleiotropic growth factor that binds a broad spectrum of cell types and regulates diverse cellular processes, including angiogenesis, growth and survival. However, it is technically difficult to quantify VEGF-cell binding activity because of reversible nature of ligand-receptor interactions. Here we used T7 bacteriophage display to quantify and compare binding activity of three human VEGF-A (hVEGF) isoforms, including hVEGF111, 165 and 206. All three isoforms bound equally well to immobilized aflibercept, a decoy VEGF receptor. hVEGF111-Phage exhibited minimal binding to immobilized heparan sulfate, whereas hVEGF206-Phage and hVEGF165-Phage had the highest and intermediate binding to …

Behavioral Screening Reveals A Conserved Residue In Y-Box Rna-Binding Protein Required For Associative Learning And Memory In C Elegans, Ashley N Hayden, Katie L Brandel, Edward W Pietryk, Paul R Merlau, Priyadharshini Vijayakumar, Emily J Leptich, Elizabeth S Gaytan, Meredith I Williams, Connie W Ni, Hsiao-Tuan Chao, Jill A Rosenfeld, Rachel N Arey

Faculty, Staff and Students Publications

RNA-binding proteins (RBPs) regulate translation and plasticity which are required for memory. RBP dysfunction has been linked to a range of neurological disorders where cognitive impairments are a key symptom. However, of the 2,000 RBPs in the human genome, many are uncharacterized with regards to neurological phenotypes. To address this, we used the model organism C. elegans to assess the role of 20 conserved RBPs in memory. We identified eight previously uncharacterized memory regulators, three of which are in the C. elegans Y-Box (CEY) RBP family. Of these, we determined that cey-1 is the closest ortholog to the mammalian Y-Box …

A Mouse Model For Conditional Expression Of Activated Β-Catenin In Epidermal Keratinocytes, Vineet K Maurya, Yan Ying, John P Lydon

Faculty, Staff and Students Publications

We report the generation and characterization of the K5: CAT bigenic mouse in which the constitutively activated form of β-catenin (ΔN89 β-catenin) is conditionally expressed in cytokeratin-5 (K5) positive epidermal keratinocytes. Following short-term doxycycline intake during the telogen resting phase, the adult K5: CAT bigenic develops enlarged pilosebaceous units that expand deep into the dermis, an expansion usually observed during the anagen growth phase. Prolonged doxycycline treatment results in significant thickening and folding of the K5: CAT epidermis. During this persistent induction period, there is clear evidence of increased keratinocyte proliferation, particularly in the epidermal basal cell layer and the …

Perineuronal Nets’ Role In Metabolism, Nan Zhang, Beite Song, Peng Bai, Li Du, Lulu Chen, Yong Xu, Tianshu Zeng

Faculty, Staff and Students Publications

Perineuronal nets (PNNs), specialized extracellular matrix (ECM) structures that envelop neurons, have recently been recognized as key players in the regulation of metabolism. This review explores the growing body of knowledge concerning PNNs and their role in metabolic control, drawing insights from recent research and relevant studies. The pivotal role of PNNs in the context of energy balance and whole body blood glucose is examined. This review also highlights novel findings, including the effects of astroglia, microglia, sex and gonadal hormones, nutritional regulation, circadian rhythms, and age on PNNs dynamics. These findings illuminate the complex and multifaceted role of PNNs …

Rotavirus Vaccine Effectiveness Against Severe Acute Gastroenteritis: 2009-2022, Alpha Oumar Diallo, Mary E Wikswo, Iddrisu Sulemana, Leila C Sahni, Julie A Boom, Sasirekha Ramani, Rangaraj Selvarangan, Mary E Moffatt, Christopher J Harrison, Natasha Halasa, James Chappell, Laura Stewart, Mary Allen Staat, Elizabeth Schlaudecker, Christina Quigley, Eileen J Klein, Janet A Englund, Danielle M Zerr, Geoffrey A Weinberg, Peter G Szilagyi, Christina Albertin, Samantha H Johnston, John V Williams, Marian G Michaels, Robert W Hickey, Aaron T Curns, Michelle Honeywood, Slavica Mijatovic-Rustempasic, Mathew D Esona, Michael D Bowen, Umesh D Parashar, Rashi Gautam, Sara A Mirza, Jacqueline E Tate

Faculty, Staff and Students Publications

Background: Rotavirus was the leading cause of acute gastroenteritis among US children until vaccine introduction in 2006, after which, substantial declines in severe rotavirus disease occurred. We evaluated rotavirus vaccine effectiveness (VE) over 13 years (2009-2022).

Methods: We analyzed data from the New Vaccine Surveillance Network using a test-negative case-control design to estimate rotavirus VE against laboratory-confirmed rotavirus infections among children seeking care for acute gastroenteritis (≥3 diarrhea or ≥1 vomiting episodes within 24 hours) in the emergency department (ED) or hospital. Case-patients and control-patients were children whose stool specimens tested rotavirus positive or negative, respectively, by enzyme immunoassay or …

Linkage Between Fuz And Gpr161 Genes Regulates Sonic Hedgehog Signaling During Mouse Neural Tube Development, Sung-Eun Kim, Hyun-Yi Kim, Bogdan J Wlodarczyk, Richard H Finnell

Faculty, Staff and Students Publications

Sonic hedgehog (Shh) signaling regulates embryonic morphogenesis utilizing the primary cilium, the cell's antenna, which acts as a signaling hub. Fuz, an effector of planar cell polarity signaling, regulates Shh signaling by facilitating cilia formation, and the G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling. The range of phenotypic malformations observed in mice bearing mutations in either of the genes encoding these proteins is similar; however, their functional relationship has not been previously explored. This study identified the genetic and biochemical linkage between Fuz and Gpr161 in mouse neural tube development. Fuz was found to be …

High Fat, High Sucrose Diet Promotes Increased Expression Of Ace2 Receptor In The Siv-Infected Host: Implications For Sars-Cov-2 Infection, Elizabeth C. Delery, Danielle E. Levitt, Angela M. Amedee, Patricia E. Molina, Liz Simon

School of Graduate Studies Faculty Publications

Introduction: People with pre-existing conditions, including metabolic comorbidities, are at greater risk for complications of SARS-CoV-2 infection and expression of machinery required for viral entry into host cells may be a contributing factor. This study tested the hypothesis that high fat, high sucrose diet (HFSD) and alcohol use increase expression of angiotensin converting enzyme 2 (ACE2) receptor and transmembrane serine protease 2 (TMPRSS2) in tissues isolated from simian immunodeficiency virus (SIV) infected macaques, the most clinically relevant model for the study of HIV. Methods: Biospecimens obtained from a longitudinal study of SIV-infected, antiretroviral therapy (ART)-treated female rhesus macaques (Macaca mulatta) …

Artificial Fruit Ripening Agents And Their Impact On Health Of The University Students In Lahore, Muhammad Ahsan, Faraz Ahmad, Faiza Usman, Shamaila Habib, Imran Shahid, Sohail Abbas, Sajida Munir

Journal of Bioresource Management

To evaluate the impact of chemicals used in artificial fruit ripening and to create an approach for raising public awareness of the risks associated with artificial fruit ripening. It was a cross-sectional and observational study, in which data was gathered from 900 university students by convenient sampling technique in Lahore. The duration of research was from May 2021 to Dec 2021. The adverse reactions caused due to different fruits were recorded on a questionnaire. Candidates included in this research were, aged between 18 years to 28 years and healthy, whereas unhealthy were excluded. Out of 900 participants, 247 (27.4 %) …

Hormone Replacement Therapy And Risk Of Pancreatic Cancer In Postmenopausal Women: Evidence From The Us National Inpatient Sample 2008–2018, Lei Liu, Xinyu Wang, Dekai Guo, Ruirui Ma, Haibing Gong, Congjun Wang

Faculty, Staff and Student Publications

BACKGROUND: Pancreatic cancer is a serious, usually fatal disease and one of the most aggressive malignancies. Research into whether hormone replacement therapy (HRT) might protect against pancreatic cancer has yielded mixed results. This study aimed to investigate the potential association between HRT and the risk of pancreatic cancer in postmenopausal women.

METHODS: This population-based, retrospective study extracted data from the US National Inpatient Sample (NIS) 2008-2018. Hospitalized females aged ≥55 years were eligible for inclusion. Associations between HRT, other study variables, and pancreatic cancer diagnosis were determined using univariate and multivariable regression analyses.

RESULTS: After 1:4 matching by age, data …

Impact Of Essential Genes On The Success Of Genome Editing Experiments Generating 3313 New Genetically Engineered Mouse Lines, Hillary Elrick, Kevin A Peterson, Brandon J Willis, Denise G Lanza, Elif F Acar, Edward J Ryder, Lydia Teboul, Petr Kasparek, Marie-Christine Birling, David J Adams, Allan Bradley, Robert E Braun, Steve D Brown, Adam Caulder, Gemma F Codner, Francesco J Demayo, Mary E Dickinson, Brendan Doe, Graham Duddy, Marina Gertsenstein, Leslie O Goodwin, Yann Hérault, Lauri G Lintott, K C Kent Lloyd, Isabel Lorenzo, Matthew Mackenzie, Ann-Marie Mallon, Colin Mckerlie, Helen Parkinson, Ramiro Ramirez-Solis, John R Seavitt, Radislav Sedlacek, William C Skarnes, Damien Smedley, Sara Wells, Jacqueline K White, Joshua A Wood, International Mouse Phenotyping Consortium, Stephen A Murray, Jason D Heaney, Lauryl M J Nutter

Faculty, Staff and Students Publications

The International Mouse Phenotyping Consortium (IMPC) systematically produces and phenotypes mouse lines with presumptive null mutations to provide insight into gene function. The IMPC now uses the programmable RNA-guided nuclease Cas9 for its increased capacity and flexibility to efficiently generate null alleles in the C57BL/6N strain. In addition to being a valuable novel and accessible research resource, the production of 3313 knockout mouse lines using comparable protocols provides a rich dataset to analyze experimental and biological variables affecting in vivo gene engineering with Cas9. Mouse line production has two critical steps - generation of founders with the desired allele and …

Single-Cell Transcriptomes And Chromatin Accessibility Of Endothelial Cells Unravel Transcription Factors Associated With Dysregulated Angiogenesis In Systemic Sclerosis, Mengqi Huang, Tracy Tabib, Dinesh Khanna, Shervin Assassi, Robyn Domsic, Robert Lafyatis

Faculty, Staff and Student Publications

Objectives: Vasculopathy emerges early in systemic sclerosis (SSc) and links to endothelial cell (EC) injury and angiogenesis. Understanding EC transcriptomes and epigenomes is crucial for unravelling the mechanisms involved.

Methods: Transcriptomes and chromatin accessibility were assessed by single-cell RNA sequencing and single-nucleus transposase-accessible chromatin sequencing. Immunofluorescent staining of skin and proteomics assay were employed to confirm the altered SSc EC phenotypes. Gain-of-function assay was used to evaluate the effects of ETS transcription factors on human dermal ECs (hDECs).

Results: Both control and SSc ECs shared transcriptomic signatures of vascular linages (arterial, capillary and venous ECs) and lymphatic ECs. Arterial ECs …

Reconstructing Oral Cavity Tumor Evolution Through Brush Biopsy, Evit John, Tom Lesluyes, Toby M Baker, Maxime Tarabichi, Ann Gillenwater, Jennifer R Wang, Peter Van Loo, Xiao Zhao

Faculty, Staff and Student Publications

Oral potentially malignant disorders (OPMDs) with genomic alterations have a heightened risk of evolving into oral squamous cell carcinoma (OSCC). Currently, genomic data are typically obtained through invasive tissue biopsy. However, brush biopsy is a non-invasive method that has been utilized for identifying dysplastic cells in OPMD but its effectiveness in reflecting the genomic landscape of OPMDs remains uncertain. This pilot study investigates the potential of brush biopsy samples in accurately reconstructing the genomic profile and tumor evolution in a patient with both OPMD and OSCC. We analyzed single nucleotide variants (SNVs), copy number aberrations (CNAs), and subclonal architectures in …

Effects Of White Matter Hyperintensity Burden On Functional Outcome After Mild Versus Moderate-To-Severe Ischemic Stroke, Dong-Seok Gwak, Wi-Sun Ryu, Dawid Schellingerhout, Jinyong Chung, Hang-Rai Kim, Sang-Wuk Jeong, Beom Joon Kim, Joon-Tae Kim, Keun-Sik Hong, Jong-Moo Park, Man-Seok Park, Kang-Ho Choi, Tai Hwan Park, Kyungbok Lee, Sang-Soon Park, Kyusik Kang, Yong-Jin Cho, Hong-Kyun Park, Byung-Chul Lee, Kyung-Ho Yu, Mi-Sun Oh, Soo Joo Lee, Jae Guk Kim, Jae-Kwan Cha, Dae-Hyun Kim, Jun Lee, Moon-Ku Han, Ji Sung Lee, Hee-Joon Bae, Dong-Eog Kim

Faculty, Staff and Student Publications

It is uncertain whether the prognostic power of white matter hyperintensity (WMH) on post-stroke outcomes is modulated as a function of initial neurological severity, a critical determinant of outcome after stroke. This multi-center MRI study tested if higher WMH quintiles were associated with 3-month poor functional outcome (modified Rankin Scale ≥ 3) for mild versus moderate-to-severe ischemic stroke. Mild and moderate-to-severe stroke were defined as admission National Institute of Health Stroke Scale scores of 1-4 and ≥ 5, respectively. Mean age of the enrolled patients (n = 8918) was 67.2 ± 12.6 years and 60.1% male. The association between WMH …

Nanopore Signal Deviations From Pseudouridine Modifications In Rna Are Sequence-Specific: Quantification Requires Dedicated Synthetic Controls, Amr Makhamreh, Sepideh Tavakoli, Ali Fallahi, Xinqi Kang, Howard Gamper, Mohammad Nabizadehmashhadtoroghi, Miten Jain, Ya-Ming Hou, Sara H Rouhanifard, Meni Wanunu

Department of Biochemistry and Molecular Biology Faculty Papers

Chemical modifications to mRNA respond dynamically to environmental cues and are important modulators of gene expression. Nanopore direct RNA sequencing has been applied for assessing the presence of pseudouridine (ψ) modifications through basecalling errors and signal analysis. These approaches strongly depend on the sequence context around the modification, and the occupancies derived from these measurements are not quantitative. In this work, we combine direct RNA sequencing of synthetic RNAs bearing site-specific modifications and supervised machine learning models (ModQuant) to achieve near-analytical, site-specific ψ quantification. Our models demonstrate that the ionic current signal features important for accurate ψ classification are sequence …

A Framework For Human Evaluation Of Large Language Models In Healthcare Derived From Literature Review, Thomas Yu Chow Tam, Sonish Sivarajkumar, Sumit Kapoor, Alisa V Stolyar, Katelyn Polanska, Karleigh R Mccarthy, Hunter Osterhoudt, Xizhi Wu, Shyam Visweswaran, Sunyang Fu, Piyush Mathur, Giovanni E Cacciamani, Cong Sun, Yifan Peng, Yanshan Wang

Faculty, Staff and Student Publications

With generative artificial intelligence (GenAI), particularly large language models (LLMs), continuing to make inroads in healthcare, assessing LLMs with human evaluations is essential to assuring safety and effectiveness. This study reviews existing literature on human evaluation methodologies for LLMs in healthcare across various medical specialties and addresses factors such as evaluation dimensions, sample types and sizes, selection, and recruitment of evaluators, frameworks and metrics, evaluation process, and statistical analysis type. Our literature review of 142 studies shows gaps in reliability, generalizability, and applicability of current human evaluation practices. To overcome such significant obstacles to healthcare LLM developments and deployments, we …

Broad Applicability Of The Goldspire™ Platform For The Treatment Of Solid Tumors, Jenny Zilberberg, Christopher Uhl, Charles B Scott, David W. Andrews, Mark A Exley

Department of Neurosurgery Faculty Papers

Goldspire™ is a personalized immunotherapy platform that combines whole tumor-derived cells with antisense oligonucleotide (IMV-001) against Insulin-Like Growth Factor-1 Receptor (IGF-1R) in biodiffusion chambers (BDCs; 0.1 μm pore). BDCs are exposed to 5-6 Gy and implanted at abdominal sites for ∼48 h to deliver an antigenic payload and immunostimulatory factors to train the immune system. Lead product IGV-001 was evaluated in newly diagnosed glioblastoma (ndGBM) patients in Phase 1a and 1b trials (NCT02507583). A Phase 2b study (NCT04485949) recently completed enrollment. Preventative treatment with tumor-specific products manufactured with Goldspire limited tumor progression and extended overall survival in mice challenged with …

Molecular Targets For Breast Cancer Therapy, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

"Breast cancer is by far the most common cancer in women, and for a while, it surpassed lung cancer as the most diagnosed cancer, regardless of gender, in 2020 [1]. Chemotherapy and hormone therapy are still the first line of treatment, despite extensive research in molecularly targeted drugs. Therefore, triple negative breast cancer (TNBC) is still known as the most challenging type for treatment due to the limited identified targets. Inherent and acquired resistance are still major hurdles in breast cancer therapy, which further highlights the importance of identifying new molecular targets in this battle. The inherent resistance of unresponsive …

The Association Between Sampling And Survival In Patients With Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy And Pancreaticoduodenectomy, Mehran Taherian, Matthew H G Katz, Laura R Prakash, Dongguang Wei, Yi Tat Tong, Zongshan Lai, Deyali Chatterjee, Hua Wang, Michael Kim, Ching-Wei D Tzeng, Naruhiko Ikoma, Robert A Wolff, Dan Zhao, Eugene J Koay, Anirban Maitra, Huamin Wang

Faculty, Staff and Student Publications

Adequate sampling is essential to an accurate pathologic evaluation of pancreatectomy specimens resected for pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT). However, limited data are available for the association between the sampling and survival in these patients. We examined the association of the entire submission of the tumor (ESOT) and the entire submission of the pancreas (ESOP) with disease-free survival (DFS) and overall survival (OS), as well as their correlations with clinicopathologic features, for 627 patients with PDAC who received NAT and pancreaticoduodenectomy. We demonstrated that both ESOT and ESOP were associated with lower ypT, less frequent perineural invasion, …

A Systematic Review On The Techniques, Long-Term Outcomes, And Complications Of Partial Breast Irradiation After Breast-Conserving Surgery For Early-Stage Breast Cancer, Jing Ning, Guanghui Cheng, Ning Wu

Faculty, Staff and Student Publications

To evaluate the efficacy and safety of four techniques of partial breast irradiation (PBI) including interstitial brachytherapy (ISBT), balloon-based brachytherapy (BBT), Intraoperative radiotherapy (IORT) and three-dimensional conformal radiotherapy (3DCRT) in the treatment for early-stage breast cancer patients after breast-conserving surgery. A systematic search was performed according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines using the PubMed, Embase, Cochrane Library and Web of Science databases. The inclusion criteria were clinical trials and observational studies that reported on outcome measures of principal PBI techniques. The methodological quality of the included research data was assessed using bias risk …

Efficacy And Safety Of Glp-1 Analog Ecnoglutide In Adults With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial, Dalong Zhu, Weimin Wang, Guoyu Tong, Guoqing Ma, Jianhua Ma, Jie Han, Xin Zhang, Yang Liu, Shenglian Gan, Hong Qin, Qing Zheng, Jing Ning, Zhiyi Zhu, Mengying Guo, Yue Bu, Yao Li, Catherine L Jones, Martijn Fenaux, Mohammed K Junaidi, Susan Xu, Hai Pan

Faculty, Staff and Student Publications

Glucagon-like peptide-1 (GLP-1) analogs are important therapeutics for type 2 diabetes and obesity. Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog. We conducted a Phase 2, randomized, double-blind, placebo-controlled study enrolling 145 adults with T2DM. Participants were randomized to 0.4, 0.8, or 1.2 mg ecnoglutide or placebo as once-weekly injections for 20 weeks. The primary objective was to evaluate the efficacy of ecnoglutide, as measured by HbA1c change from baseline at Week 20. Secondary endpoints included body weight, glucose and lipid parameters, as well as safety. We show that, at end of treatment, the 0.4, 0.8, and 1.2 mg groups …

Inorganic Pyrophosphate Plasma Levels In Patients With Ggcx-Associated Pxe-Like Phenotypes, Qiaoli Li, Catherine Troutman, Mary Peckiconis, Tamara Wurst, Sharon Terry

Department of Biochemistry and Molecular Biology Faculty Papers

ntroduction: Pseudoxanthoma elasticum (PXE) is an autosomal recessive ectopic calcification disorder clinically affecting the skin, eyes, and vascular system. Most cases of PXE are caused by inactivating pathogenic variants in the ABCC6 gene encoding a hepatic transmembrane efflux transporter, which facilitates the extracellular release of ATP, the precursor of inorganic pyrophosphate (PPi), a potent endogenous inhibitor of calcification. Pathogenic variants in GGCX, encoding γ-glutamyl carboxylase required for activation of vitamin K-dependent coagulation factors as well as matrix Gla protein (MGP) and Gla-rich protein (GRP), two inhibitors of ectopic calcification, have also been reported to cause cutaneous changes like those seen …

Mtap And P16 Ihc As Markers For Cdkn2a/B Loss In Meningiomas, Hanim I Ozkizilkaya, Anjali Vinocha, Antonio Dono, Oluwaseun Basit Ogunbona, Gokce A Toruner, Phyu P Aung, Carlos Kamiya Matsuoka, Yoshua Esquenazi, Franco Demonte, Leomar Y Ballester

Faculty, Staff and Student Publications

Background: Homozygous cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) loss is one of the parameters that support the designation of meningiomas as Central Nervous System (CNS) WHO grade 3 tumors. Evaluation of CDKN2A/B by sequencing or Fluorescence in situ hybridization (FISH) is costly and not always readily accessible. An immunohistochemistry (IHC)-based marker for the evaluation of CDKN2A/B loss would provide faster results at a lower cost.

Methods: This retrospective study included patients diagnosed with meningioma at our institution between 2016 and 2019. Archival tumor tissue was used for analysis. MTAP immunohistochemistry (IHC) was performed at various dilutions (1:1200, 1:400, 1:200, 1:100) using …

Use Of Web-Based Decision Support To Improve Informed Choice For Chemoprevention: A Qualitative Analysis Of Pre-Implementation Interviews (Swog S1904), Alissa M Michel, Haeseung Yi, Jacquelyn Amenta, Nicole Collins, Anna Vaynrub, Subiksha Umakanth, Garnet Anderson, Katie Arnold, Cynthia Law, Sandhya Pruthi, Ana Sandoval-Leon, Rachel Shirley, Maria Grosse Perdekamp, Sarah Colonna, Stacy Krisher, Tari King, Lisa D Yee, Tarah J Ballinger, Christa Braun-Inglis, Debra A Mangino, Kari Wisinski, Claudia A Deyoung, Masey Ross, Justin Floyd, Andrea Kaster, Lindi Vanderwalde, Thomas J Saphner, Corrine Zarwan, Shelly Lo, Cathy Graham, Alison Conlin, Kathleen Yost, Doreen Agnese, Cheryl Jernigan, Dawn L Hershman, Marian L Neuhouser, Banu Arun, Katherine D Crew, Rita Kukafka

Faculty, Staff and Student Publications

Background: Women with high-risk breast lesions, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have a 4- to tenfold increased risk of breast cancer compared to women with non-proliferative breast disease. Despite high-quality data supporting chemoprevention, uptake remains low. Interventions are needed to break down barriers.

Methods: The parent trial, MiCHOICE, is a cluster randomized controlled trial evaluating the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. For this pre-implementation analysis, 25 providers participated in semi-structured interviews prior to accessing decision support tools. …

"Not A Cookie Cutter Situation": How Neurodivergent Students Experience Group Work In Their Stem Courses, Sophia Salvatore, Claudia White, Stephen Podowitz

College of Life Sciences Faculty Papers

Background: Although group work is increasingly used in STEM courses and may lead to improved academic outcomes, there is evidence that some implementations of group work may lead to unintended barriers for certain students’ learning. Despite the growing number of neurodivergent undergraduate students, there is limited research on neurodivergent students’ experiences with group work in STEM courses. To address this knowledge gap, the current research investigated the experiences of 22 neurodivergent undergraduate students with group work in STEM courses at a range of institution types and in a variety of STEM disciplines. Participants shared experiences with in-class and out-of-class group …