Medicine and Health Sciences Commons^™

Analysis Of Calr-Mutated Essential Thrombocythemia As A Distinct Disease Entity Compared With Jak2 V617f-Mutated And Triple-Negative Patients ​, Gökhan Sami̇ Aydin, Eli̇f Aksoy, İpek Yönal Hi̇ndi̇lerden, Aynur Dağlar Aday, Emi̇ne Gültürk, Meli̇ha Nalçaci, Fehmi̇ Hi̇ndi̇lerden

Turkish Journal of Medical Sciences

Background/aim: Calreticulin (CALR) mutations in essential thrombocythemia (ET) are associated with younger age, higher platelet counts, and lower thrombosis rates. The present study analyzes the demographic, laboratory, and clinical features of the CALR mutation and its prognostic impact.

Materials and methods: The clinical impact of CALR mutations was assessed in 391 ET patients.

Results: CALR-mutation patients were more commonly male than JAK2 V617F-positive and triple-negative patients. Age at diagnosis was similar across all groups, although patients with type 2 CALR mutations were younger than those with nontype 1/nontype 2 mutations. Compared with JAK2 V617F-positive patients, CALR-mutation patients had lower leukocyte …

Asthma Data In Türkiye Between 2016 And 2022: A Nationwide Descriptive And Observational Study Covering The Entire Adult Population, Kurtuluş Aksu, Gürgün Tuğçe Vural Solak, Nai̇m Ata, Mustafa Hami̇dullah Türkkani, Mustafa Mahi̇r Ülgü, Şuayi̇p Bi̇ri̇nci̇, Funda Aksu

Turkish Journal of Medical Sciences

Background/aim: Determining the current burden of asthma in countries is important in the diagnosis and follow-up of asthma patients and for the development of national health policies. Our study aimed to clarify the epidemiological and clinical data regarding asthmatic adults in Türkiye.

Materials and methods: The study was designed as a nationwide descriptive, observational cross-sectional study. Data on adult patients who were followed with the diagnosis of asthma in all public, private, and university hospitals in Türkiye between January 2016 and December 2022 were obtained from the e-Nabız database of the Ministry of Health and analyzed.

Results: The number of …

Comprehensive Profiling Of Gut Microbiota In Postmenopausal Osteoporosis ​, Gülsemi̇n Ertürk Çeli̇k, Sedat Yildiz, Münevver Aksoy Bektaş, Yaprak Engi̇n-Üstün

Turkish Journal of Medical Sciences

Background/aim: Osteoporosis is a multifactorial skeletal disease that predominantly affects postmenopausal women and is characterized by reduced bone mass and an increased risk of fractures. Growing evidence suggests that the gut microbiota plays a pivotal role in bone metabolism through immunological, endocrine, and metabolic pathways, forming the basis of the so-called gut– bone axis. This study aimed to characterize gut microbiota composition in postmenopausal women with osteoporosis compared with healthy controls.

Materials and methods: Forty postmenopausal women aged 55–65 years were classified into osteoporosis (n = 20) and healthy control (n = 20) groups based on dual-energy X-ray absorptiometry T-scores. …

Association Between Superstition Levels On Sports-Specific Success Motivation In Active Athletes: A Study In Ankara Province ​, Canan Sayin Temur

Turkish Journal of Medical Sciences

Background/aim: When athletes perceive themselves as strong, they may seek to maintain their motivation through the control of random external factors. The present study examines the effect of superstitions on sports-specific success motivation among active athletes.

Materials and methods: The research population consisted of licensed athletes in the athletics branch, while the sample comprised licensed and active athletes based in Ankara. A total of 408 athletes participated in the research, including 201 women, and 207 men. The participants completed a three-part questionnaire consisting of a Personal Information Form, the Motivation in Sports Scale, and the Superstitious Beliefs and Behaviors in …

Sun-Macerated Hypericum Perforatum Oleates In Fixed Oils: Analytical Characterization And Comparative Wound-Healing Activity, Ci̇han Çapar, Esra Akkol, Ayli̇n Yaba, Ayhan Parmaksiz, Engi̇n Sümer, Erdem Yeşi̇lada

Turkish Journal of Medical Sciences

Background/aim: Hypericum perforatum L. oleates prepared in fixed oils have long been used for wound management due to their anti-inflammatory, antibacterial, and tissue-regenerative properties. The bioactivity of these oleates is mainly attributed to hypericin, hyperforin, and pseudohypericin. This study aimed to comparatively evaluate the wound-healing potential of H. perforatum oleates prepared in different fixed oils, including Olea europaea L. (olive), Sesamum indicum L. (sesame), Helianthus annuus L. (sunflower), and Nigella sativa L. (black seed).Materials and methodsFixed oils were characterized by GC–MS, while oleuropein in olive oil and thymoquinone in black seed oil were quantified by HPLC, and sesamin and sesamol …

Red Cell Cryopreservation For Serologic Testing: Bulk Freezing With Polyvinylpyrrolidone (Pvp) ​, Di̇lek Gürlek Gökçebay, Willy Albert Flegel

Turkish Journal of Medical Sciences

Background/aim: Red cell cryopreservation is essential for immunohematology reference laboratories. Various cryopreservation methods maintain the structural integrity of red cells, such as bulk freezing with glycerol and droplet freezing with polyvinylpyrrolidone (PVP). In this paper, we provide a technical note with real-world data and report our experience with a modified PVP bulk-freezing method in a transfusion medicine setting.Materials and methods. Red cells were separated from whole blood samples and incubated for 1 h at room temperature with PVP with slow agitation or no agitation before freezing. Instead of using the established method of shock freezing droplets in liquid nitrogen, the …

Retinal Microvascular And Neuroretinal Structural Changes In Pulmonary Arterial Hypertension Assessed By Octa: A Comparative Study ​, Murat Erdağ, Tunahan Çalişkan, Hakan Yildirim, Tarik Kivrak, Mehmet Canleblebi̇ci̇, Ali̇ Dal, Mehmet Balbaba

Turkish Journal of Medical Sciences

Background/aim: Pulmonary arterial hypertension (PAH) is a progressive disorder with systemic vasculopathy, and noninvasive assessment remains challenging. The retina, sharing anatomical similarities with the cerebral microcirculation, is an accessible site for visualizing systemic vascular compromise. This study quantitatively evaluated retinal microvascular and neuroretinal structural changes in PAH patients compared to healthy controls using optical coherence tomography angiography (OCTA).

Materials and methods: In this single-center, cross-sectional case-control study, 40 patients with group 1 PAH and 38 healthy controls were enrolled. For statistical independence, only the right eye of each participant was analyzed (total: 78 eyes). All participants underwent high-resolution OCTA imaging. …

Prognostic Significance And Clinicopathological Associations Of Tumor Budding And Poorly Differentiated Clusters In Endometrioid Endometrial Carcinoma ​, Hani̇fe Seda Mavi̇li̇, Ömer Atmiş, Fatma Seher Pehli̇van, Fatma Sezen Çavdaroğlu Deveci̇, Ali̇ Riza Kandi̇loğlu

Turkish Journal of Medical Sciences

Background/aim: Tumor budding (TB) and poorly differentiated clusters (PDCs) are histopathological parameters that have been associated with poor prognosis in various malignancies, particularly colorectal carcinoma. Although numerous studies have demonstrated an association between the microcystic, elongated, and fragmented (MELF) pattern in endometrial carcinomas and lymphovascular invasion as well as lymph node metastasis, the literature regarding TB and PDCs in this context remains limited. This study aimed to investigate the potential associations of the MELF pattern, TB, and PDCs with overall survival, progression-free survival, and clinicopathological parameters in cases of endometrioid endometrial carcinoma (EEC).

Materials and methods: A total of 190 …

International Consensus On The Evaluation And Management Of Hypothalamic Hamartomas: Results From A Modified Delphi Survey, Nathan T Cohen, Xiaotong Li, Madison M Berl, Chima O Oluigbo, Hiroshi Shirozu, Samuel F Berkovic, Margaret Zacharin, Wirginia Maixner, Andreas Schulze-Bonhage, Kerstin Klotz, Nicola Specchio, Sarah Ferrand-Sorbets, Christine Bulteau, Alexis A Arzimanoglou, Jean Regis, J Helen Cross, Martin M Tisdall, Hanna Richardson, Arthur Cukiert, Cristine Cukiert, Julia Jacobs, Elizabeth J Donner, Phillip L Pearl, John F Kerrigan, Angus A Wilfong, Kevin C J Yuen, Dennis J Dlugos, Daniel Curry, Irfan Ali, John Ragheb, Lisa Soeby, Erica Webster, William D Gaillard

Faculty, Staff and Students Publications

Background and objectives: Hypothalamic hamartomas (HH) are rare brain lesions associated with epilepsy and numerous comorbidities. Worldwide treatment is varied. There is a paucity of high-quality evidence to guide treatment. This study aimed to establish expert consensus on the evaluation and management of HH.

Methods: A modified Delphi survey was designed by the Medical Advisory Board of Hope for Hypothalamic Hamartomas and was conducted among 17 International League Against Epilepsy level II epilepsy surgery centers. The survey included 257 questions in round 1 and 81 refined questions in round 2, covering domains of diagnosis, imaging, medical and surgical treatment, neuropsychological …

Global Impact Of Germline Structural Variation On The Cancer Proteome, Fengju Chen, Yiqun Zhang, Luis F Paulin, Darshan S Chandrashekar, Sooryanarayana Varambally, Fritz J Sedlazeck, Chad J Creighton

Faculty, Staff and Students Publications

Proteome and transcriptome data combined can help assess the relevance of non-coding germline variants. Here, we combine germline Structural Variants (SVs) with mass spectrometry-based proteomics on tumors from 1637 cancer patients spanning various tumor tissues of origin to determine the extent SV breakpoint patterns involve differential protein expression of nearby genes. Rare and singleton SVs disrupting protein expression of known cancer susceptibility genes collectively involve 6% of patients. About 24% of the hundreds of genes with SV-associated non-coding cis-regulatory alterations at the mRNA level are similarly associated at the protein level. Both rare and common SVs may associate with differential …

Dapk2 Regulates Pkm2 Phosphorylation At Threonine 45 To Facilitate Disturbed Flow-Induced Atherosclerosis, Shuai Guo, Long Xu, Yixin Chen, Yuan Zhao, Yuting Zhang, Runfa Yu, Kaixiang Cao, Litao Wang, Wenjia Ai, Jiang-Yun Luo, Lu Lu, Jun He, Yuan Zhou, Li Wang, Andrew H Baker, Yuqing Huo, Yiming Xu

Faculty, Staff and Students Publications

Background: Oscillatory shear stress (OSS), resulting from disturbed blood flow, is implicated in atherosclerotic plaque formation by incompletely understood mechanisms. This study aims to elucidate the involvement of death-associated protein kinase (DAPK) 2 in OSS-induced endothelial cell (EC) activation and atherosclerosis.

Methods: Publicly available resources, including genome-wide microarray, RNA sequencing, and single-cell RNA sequencing, were utilized to identify key OSS-sensitive regulatory factors. Techniques such as mass spectrometry, immunoprecipitation, proximity ligation assay, and RNA sequencing were employed to identify pyruvate kinase M2 (PKM2) as the binding protein of DAPK2 and determine the specific site of PKM2 phosphorylation by DAPK2. To assess …

Res-Mnd: Motor Neuron Disease Detection Using Res4net–Convolutional Block Attention Module ​, Shuriya Balusamy, Rakesh Sivalingam, Shobana Rooben, Sony Helen

Turkish Journal of Medical Sciences

Background/aim: Motor neuron diseases (MNDs) are progressive neurological disorders that cause muscle weakness and wasting as a result of ongoing neurodegeneration. MNDs require comprehensive diagnostic approaches that integrate clinical symptoms, laboratory findings, and multimodal imaging data.

Materials and methods: In this study, a novel residual network for motor neuron disease detection (RES-MND) framework is proposed for detecting MNDs using multimodal imaging data. Initially, the input multimodal images, including MRI, CT, PET, and DTI, are preprocessed using adaptive dynamic histogram equalization and the total variation bilateral filter. The preprocessed multimodal images are processed through Res4Net-CBAM for feature extraction to enhance image …

Role Of Novel Renal Biomarkers In Prognosticating Patients With Chronic Kidney Disease: A Prospective Cohort Study, Raghavan Padmanabhan, Kaviya Manoharan, Melina Sahay, Pooja Bhujangarao, Luxitaa Goenka, Solai Priya, Kumaraswamy Subramaniyan, Damal Kandadai Sriram, Melvin George

Turkish Journal of Medical Sciences

Background/aim: Several biomarkers have been assessed for the diagnosis of chronic kidney disease (CKD). However, limited data are available regarding their ability to predict mortality in CKD. The aim of this study was to assess the ability of lipocalin-2, receptor for advanced glycation end products (RAGE), tissue inhibitor of metalloproteinase 1 (TIMP-1), osteopontin, and trefoil factor 3 (TFF-3) in predicting the prognosis of patients with CKD.

Materials and methods: We included patients with CKD as defined by an estimated glomerular filtration rate of <60 mL/min/1.73 m2 of either sex who were above the age of 18 years. Patients with a history of acute-on-chronic kidney disease were excluded. The novel markers of interest were estimated from patients’ plasma samples using the multiplex enzyme-linked immunosorbent assay. These patients were followed for 1 year to assess mortality.

Results: The median (with interquartile range) plasma concentrations of lipocalin-2, RAGE, TIMP-1, osteopontin, and TFF-3 were 56.9 …

A Model Based On Dynamic Hematologic Parameters To Predict Short Term Clinical Events In Pediatric Acute Lymphoblastic Leukemia ​, Neryal Tahta, Sali̇h Gözmen, Sultan Okur Acar

Turkish Journal of Medical Sciences

Background/aim: Acute lymphoblastic leukemia (ALL) treatment is frequently complicated by infections, emergency visits, and therapy interruptions, yet early prediction of short-term clinical deterioration remains challenging. Traditional prognostic markers rely on static laboratory values, whereas dynamic hematologic fluctuations may provide earlier warning signals. This study presents and internally validates a clinically applicable prediction model based on dynamic hematologic parameters and clinician-documented symptoms for predicting short-term (7-day) clinical events in children with ALL.

Materials and methods: Included in this retrospective study were 44 pediatric ALL patients treated with Berlin-Frankfurt-Münster-based protocols between January 2023 and June 2025. Weekly observation units were created by …

Post-Exposure Prophylaxis For Hiv Among Healthcare Workers In Türkiye: A Descriptive, Multicenter Retrospective Study, Veysel Akca, İlkay Akbulut, Gül Ruhsar Yilmaz, Alper Tahmaz, Nefi̇se Öztoprak Çuvalci, İlknur Esen Yildiz, Mehmet Çabalak, Şeyma Topal, Özgür Günal, Bi̇rcan Kayaaslan, Fatma Eser, Tuba Damar Çakirca, Deni̇z Ölmez, Ali̇ye Baştuğ, Fi̇rdevs Aksoy, Hani̇fe Nur Karakoç Parlayan, Beyza Süllü, Damla Verendağ, Hatun Öztürk Çeri̇k, Mehmet Ali̇ Aşan, Ayhan Akbulut, Gülden Eser Karlidağ, Behi̇ce Kurtaran, Hüsnü Pullukçu, Turhan Togan

Turkish Journal of Medical Sciences

Background/aim: Post-exposure prophylaxis (PEP) for human immunodeficiency virus (HIV) plays a vital role in preventing transmission among healthcare workers following occupational exposure. Despite its clinical importance, epidemiological data regarding PEP implementation in Türkiye remain scarce. This study aimed to assess PEP practices, prophylactic treatment regimens, and follow-up outcomes among healthcare workers at risk of occupational HIV exposure.

Materials and methods: This retrospective, multicenter study was conducted between January 2020 and December 2024 across 16 healthcare facilities participating in the National HIV/AIDS Working Group. Healthcare workers aged 18 years and older who presented for evaluation following occupational exposure to HIV were …

Biomechanical Analysis Of Skeletal Open Bite Treatment Methods: A Comparative Finite Element Study ​, Ömer Faruk Sari, Muhammed Hi̇lmi̇ Buyukcavus

Turkish Journal of Medical Sciences

Background/aim: The biomechanical effects of zygomatic anchorage plates, vertical chin-caps, and occipital headgear on dentofacial structures in patients with skeletal anterior open bite malocclusion were compared using three-dimensional finite element analysis.

Materials and methods: Three-dimensional finite element models were constructed based on computed tomography data obtained from a patient with skeletal anterior open bite. Simulation models representing zygomatic anchorage-supported intrusion, vertical chin-cap, and occipital headgear were generated under fixed orthodontic conditions. In each scenario, a unilateral force of 200 g (1.96 N) was applied along clinically relevant force vectors. Stress distributions in craniofacial bones, sutural structures, teeth, roots, and temporomandibular …

Adoptive Cell Therapies For Glioblastoma: A Quest For Cures From Within, Jia-Shiun Leu, Xin Ge, Charles Robin Yu, Guang Peng, Jiyong Liang

The Brown Foundation: Institute of Molecular Medicine

Glioblastomas (GBMs) are the most aggressive form of brain cancer recalcitrant to both current standard-of-care and immune checkpoint therapies that benefit other cancer patients. Adoptive cell therapies (ACT) using patients' own immune cells have long been explored as a treatment strategy, including the historically studied lymphokine-activated killer (LAK) cells, the evolving chimeric antigen receptor (CAR) directed immune cells, the newly emerging tumor-infiltrating T lymphocyte (TIL) therapies, and others. Preclinical and clinical studies have shown promise but also highlighted significant challenges. In this review, we summarize these findings, highlight recent developments, discuss current limitations, and emphasize how ACT may benefit from …

Engineering Of Genetically Encoded Programmable Calcium Channel Inhibitory Binders, Xiaoxuan Liu, Sher Ali, Tien-Hung Lan, Decheng Wang, Brendan Mckee, Tatsuki Nonomura, Siyao Liu, Feng Zhao, Michael X Zhu, Yun Huang, Qing Deng, Guolin Ma, Yubin Zhou

Faculty, Staff and Student Publications

Store-operated Ca2+ release-activated Ca2+ (CRAC) channels, composed of STIM and ORAI, are essential for immune and developmental processes, and their dysregulation underlies channelopathies such as Stormorken syndrome. Here, we report the engineering of genetically encoded CRAC channel inhibitory binders (CRABs) derived from the ORAI C-terminal tail. Guided by deep mutational scanning, we optimize a membrane-anchored CRAB variant that potently inhibits Ca2+ influx and NFAT signaling, and rescues thrombocytopenia-like phenotypes in a zebrafish model of Stormorken syndrome. To enable tunable inhibition, we further design oligomeric, optogenetic (Opto-CRAB), and chemogenetic (Chemo-CRAB) variants, providing graded and real-time control of CRAC activity. Chemo-CRAB further …

Intouch Week Of April 13, 2026, New York Medical College

InTouch

• Avi Dennis, Named Director of Human Resources
• GSBMS Celebrates a Long‑Standing Tradition of Excellence in Scientific Discovery
• Inaugural Careers in Bloom Event Brings SHSP Students and Local Employers Together
• It Takes Trial and Error to Reach Discovery
• Raising Awareness and Strengthening Readiness

Acute Traumatic Aortic Injury: What The Radiologist Needs To Know, Kristina Ramirez-Garcia, Catalina Jaramillo, Emma Ferguson, Jason Au, Erika Odisio, Gustavo S Oderich, Daniel Ocazionez, Cihan Duran, Thanila Macedo

Faculty, Staff and Students Publications

Acute traumatic aortic injury (ATAI) is a rare but life-threatening consequence of blunt trauma that requires prompt diagnosis and accurate imaging assessment. This review presents an imaging-based approach to ATAI, with emphasis on computed tomography angiography (CTA) as the first-line modality for diagnosis, grading, treatment planning, and follow-up. CTA enables the detection of both direct and indirect signs while also allowing for the assessment of lesion severity, extent, and associated findings that may influence management. Familiarity with common mimics and anatomic variants improves diagnostic confidence and helps avoid false positive interpretations. Careful protocol optimization, including multiphasic acquisition, bolus timing, and …

"I Wasn't Broken": Addressing Stigma Associated With Dementia While Walking The Talk For Dementia, Kate Irving, Fernando Aguzzoli Peres, Walter D. Dawson, Jonathan Adrián Zegarra-Valdivia, Lingani Mbakile-Mahlanza, Sherril B. Gelmon

Institute on Aging Publications

INTRODUCTION:Walking the Talk for Dementia (WTD) convenes people from every continent and multiple perspectives, including people with lived experience, in a 40- km walk followed by a 2-day symposium. The aim is collective reflective dialogue about dementia stigma without the burden of professional hierarchies.

METHODS: Qualitative reflections during and immediately following the walk were analyzed using content analysis to identify common themes.

RESULTS: Three themes demonstrate an evolution of perspectives about dementia and stigma: “meeting the person not the label”, “a community in solidarity”, and “I wasn’t treated like I was broken, and I wasn’t broken.”

DISCUSSION: WTD created an …

Efficacy Of Glp-1 And Gip/Glp-1 Receptor Agonists On The Body Weight Management Of Obesity, Paige D. Timbrook

Seaver College Research And Scholarly Achievement Symposium

Obesity is a major epidemic across the United States, and weight loss through diet and physical activity alone is not sustainable. Treatment with tirzepatide and semaglutide have proven to be effective for obesity management in the short-term, but more research is needed to understand how certain types of medications impact weight loss over time. In this study, we recruited 42 adult participants with or without Type II diabetes who were 21 years and older, taking only one GLP-1 or GIP/GLP-1 receptor agonist at a time, had a beginning body mass index of 30 or greater or a beginning body mass …

The Role Of The "Indulgent Mindset" As A Modulator For Neuropsychiatric Biomarkers And Self-Reported Mental Wellbeing, Riva Ranier, Anika Anika, Sarah Simon, Ethan Chau, Emma Monte, Madison Retzloff, Johann Luna, Susan Helm

Seaver College Research And Scholarly Achievement Symposium

The Role of the "Indulgent Mindset" as a Modulator for Neuropsychiatric Biomarkers and Self-Reported Mental Wellbeing

Objective: Limited understanding persists regarding how an "indulgent mindset" about food shapes neuropsychiatric outcomes. Building on the "milkshake study" demonstrating that mindset modulates ghrelin response independent of nutritional content, this pilot study examines whether an indulgent mindset intervention affects neuropsychiatric biomarkers and mental wellbeing.

Methods: Women ages 19-65 (n=35; intervention n=17, control n=18) completed a 6-month randomized trial with baseline and post-intervention assessments including 3-day food diaries, mental wellbeing questionnaires, and comprehensive metabolomics (Iollo panel across mental health, metabolic health, gut microbiome, brain health, …

Atp Architect - Development Of A Metabolism Boardgame, Selene J. Welch, Micah Burk, Brooklyn Gilchrist, Emma Haase, Timothy T. Jones

SACAD: Scholarly Activities

Traditional metabolism instruction often leaves students struggling with pathway interconnectedness and metabolite flux. To foster systems thinking, we are developing an educational board game where students manipulate tokens to navigate physiological constraints and achieve target energy goals. Grounded in Design-Based Research (DBR), the game undergoes iterative refinement based on player feedback. The design utilizes constructivism by allowing students to "fail safely" and revise strategies in real-time, while leveraging embodied cognition to externalize abstract flux into the physical trading of resource tokens.

Powering Up Clinical Scholarship In Pain Management / Chronic Pain Fellowship, Evelyn Wang

HSLIC Faculty and Staff Instructional Resources

This presentation introduces chronic pain fellows to clinical scholarship pathways in pain management, highlighting core literature search strategies, evidence‐based resources, and HSLIC services that support research, publishing, and teaching in chronic pain care.

A Rare Case Of Cutaneous Extramedullary Hematopoiesis In Chronic Myeloid Leukemia, Bennett Christie-Nguyen, Hanadi El Achi, Levani Iashvili, Amer Wahed, Brenda Mai, Jacob Armstrong

Faculty, Staff and Student Publications

Cutaneous extramedullary hematopoiesis (CEH) is a rare manifestation of extramedullary hematopoiesis (EMH), a process typically associated with fetal development or myeloproliferative neoplasms. EMH most commonly involves the spleen, liver, and lymph nodes, with CEH being exceedingly rare in chronic myeloid leukemia (CML). Here, we present a 34-year-old Hispanic male with multiple bilateral lower extremity lesions, right buttock and leg pain, fatigue, and splenomegaly, who was found to have chronic-phase CML. Punch biopsy of one of the skin lesions demonstrated dermal infiltration by maturing hematopoietic elements, including granulocytes, megakaryocytes, and erythroid precursors, with fluorescence in situ hybridization (FISH) testing confirming a …

A Multidomain Peptide Hydrogel-Liposome Composite For Controlled Release Of A Cyclic Dinucleotide In Oral Cancer, Joseph W R Swain, Andrea H Molina, Gemalene M Sunga, Danielle Chew-Martinez, Neeraja Dharmaraj, Alejandra Cobos Perez, Arghadip Dey, Ephraim J Vázquez-Rosado, Simon Young, Jeffrey D Hartgerink

Faculty, Staff and Student Publications

While immunotherapy is a promising treatment strategy for cancer, the majority of head and neck squamous cell carcinoma (HNSCC) patients treated with single-agent immunotherapy do not respond. Therefore, researchers are investigating combination treatments with immunostimulatory molecules that can maximize anti-tumor responses. Cyclic dinucleotides (CDNs) are STING agonists that hold promise in combination approaches, but they require frequent intratumoral administration when used in both preclinical models of HNSCC and clinical trials. To reduce administration frequency, we have created a peptide hydrogel–liposome composite system, K2-Lip(CDN), for local and prolonged availability of CDN. We investigated the loading limits of cationic liposomes in both …

Therapeutic Potential Of Glp-1 Receptor Agonists For Smoking Cessation, Christian S Hendershot, W Kyle Simmons, Manish K Jha, Sherry A Mckee, Luba Yammine

Faculty, Staff and Student Publications

Glucagon-like peptide-1 (GLP-1) therapies are under investigation for a growing number of neuropsychiatric conditions, including substance use disorders. Cigarette smoking accounts for the largest proportion of substance use-related morbidity and mortality, in part reflecting increased risk for cardiometabolic disease among people who smoke. Given modest quit rates with approved smoking cessation therapies, medications with novel mechanisms of action are needed to expand the available monotherapy and combination treatment options. Treatments that prevent post-cessation weight gain could further reduce relapse and cardiometabolic risks following smoking cessation. Preclinical findings show that GLP-1 receptor agonists (GLP-1RA) modulate nicotine reward, reduce nicotine self-administration, and …

A Machine-Learning-Based Tool For Stroke Risk Prediction In Blunt Cerebrovascular Injury: Development And Preliminary Evaluation, Victoria Wagner, Joshua D Preston, Alejandro De Leon Castro, William F Mueller, Jonathan Nguyen, Manuel Garcia-Toca, Elizabeth R Benjamin, S Rob Todd, Jason D Sciarretta

Faculty, Staff and Student Publications

Purpose: Stroke risk correlates with the Biffl grading system in blunt cerebrovascular injury (BCVI). Although anti-thrombotic therapy is the mainstay of stroke prevention, no point-of-care clinical decision-support tool exists to guide timing for therapy. We sought to develop an interactive online calculator that incorporates patient-specific demographic and injury characteristics to estimate stroke risk and risk reduction with anti-thrombotic (AT) administration.

Methods: Data from BCVI patients (n = 1,197) at a Level I Trauma Center were retrospectively collected. Six machine learning methods were employed to predict stroke risk with and without AT therapy. Class imbalance was addressed using downsampling and/or class …

Loss Of Znrf3/Rnf43 Unleashes Egrfr In Cancer, Fei Yue, Amy T Ku, Payton D Stevens, Megan N Michalski, Weiyu Jiang, Jianghua Tu, Zhongcheng Shi, Yongchao Dou, Yi Wang, Xin-Hua Feng, Galen Hostetter, Xiangwei Wu, Shixia Huang, Noah F Shroyer, Bing Zhang, Bart O Williams, Qingyun Liu, Xia Lin, Yi Li

Faculty, Staff and Students Publications

ZNRF3 and RNF43 are closely related transmembrane E3 ubiquitin ligases with significant roles in development and cancer. Conventionally, their biological functions have been associated with regulating WNT signaling receptor ubiquitination and degradation. However, our proteogenomic studies have revealed EGFR as the protein most negatively correlated with ZNRF3/RNF43 mRNA levels in multiple human cancers. Through biochemical investigations, we demonstrate that ZNRF3/RNF43 interact with EGFR via their extracellular domains, leading to EGFR ubiquitination and subsequent degradation facilitated by the E3 ligase RING domain. Overexpression of ZNRF3 reduces EGFR levels and suppresses cancer cell growth in vitro and in vivo, whereas knockout of …