Medicine and Health Sciences Commons^™

Quiescent Oxphos-High Triple-Negative Breast Cancer Cells That Persist After Chemotherapy Depend On Bcl-Xl For Survival, Slawomir Andrzejewski, Marie Winter, Leandro Encarnacao Garcia, Olusiji Akinrinmade, Francisco Madeira Marques, Emmanouil Zacharioudakis, Anna Skwarska, Julio Aguirre-Ghiso, Marina Konopleva, Guangrong Zheng, Susan A Fineberg, Daohong Zhou, Evripidis Gavathiotis, Tao Wang, Eugen Dhimolea

Faculty, Staff and Student Publications

The persistent residual tumor cells that survive after chemotherapy are a major cause of treatment failure, but their survival mechanisms remain largely elusive. These cancer cells are typically characterized by a quiescent state with suppressed activity of MYC and MTOR. We observed that the MYC-suppressed persistent triple-negative breast cancer (TNBC) cells are metabolically flexible and can upregulate mitochondrial oxidative phosphorylation (OXPHOS) genes and respiratory function ("OXPHOS-high" cell state) in response to DNA-damaging anthracyclines such as doxorubicin, but not to taxanes. The elevated biomass and respiratory function of mitochondria in OXPHOS-high persistent cancer cells were associated with mitochondrial elongation and remodeling, …

Interoperability As A Catalyst For Digital Health And Therapeutics: A Scoping Review Of Emerging Technologies And Standards (2015–2025), Kola Adegoke, Abimbola Adegoke, Deborah Dawodu, Akorede Adekoya, Ayoola Bayowa

Health & Biomedical Sciences Faculty Publications

Background: Interoperability is fundamental for advancing digital health and digital therapeutics, particularly with the integration of technologies such as artificial intelligence (AI), blockchain, and federated learning. Low- and middle-income countries (LMICs), where digital infrastructure remains fragmented, face specific challenges in implementing standardized and scalable systems. Methods: This scoping review was conducted using the Arksey and O’Malley framework, refined by Levac et al., and the Joanna Briggs Institute guidelines. Five databases (PubMed, Scopus, IEEE Xplore, ACM Digital Library, and Google Scholar) were searched for peer-reviewed English language studies published between 2015 and 2025. We identified 255 potentially eligible articles and selected …

Mechanistic Study Of Pexidartinib-Induced Toxicity In Human Hepatic Cells, Si Chen, Yuxi Li, Xilin Li, Nan Mei, Xiaobo He, Matthew S Bryant, Xuan Qin, Feng Li, Lei Guo

Faculty, Staff and Students Publications

Pexidartinib, a tyrosine kinase inhibitor, was approved by the U.S. Food and Drug Administration in 2019 for treating adult patients with symptomatic tenosynovial giant cell tumors. Because of its hepatotoxicity risks, pexidartinib received a boxed warning; however, mechanistic studies on this hepatotoxicity remain limited. In this study, we demonstrate that pexidartinib decreases cell viability in primary human hepatocytes and hepatic HepG2 cells. A 24-h treatment with pexidartinib led to apoptosis in HepG2 cells, as evidenced by increased caspase 3/7 activity and the induction of cleaved PARP and γ-H2A.X. Pexidartinib-induced endoplasmic reticulum (ER) stress was observed at early time points of …

One-Sided Matching Portal (Osmp): A Tool To Facilitate Rare Disease Patient Matchmaking., Matthew Osmond, E Magda Price, Orion J. Buske, Mackenzie Frew, Madeline Couse, Taila Hartley, Conor Klamann, Hannah G B H Le, Jenny Xu, Delvin So, Anjali Jain, Kevin Lu, Kevin Mo, Hannah Wyllie, Erika Wall, Hannah G. Driver, Warren A. Cheung, Ana S A Cohen, Emily G. Farrow, Isabelle Thiffault, Care Rare Canada Consortium, Andrei L. Turinsky, Tomi Pastinen, Michael Brudno, Kym M. Boycott

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Genomic matchmaking-the process of identifying individuals with overlapping phenotypes and rare variants in the same gene-is an important tool facilitating gene discoveries for unsolved rare genetic disease (RGD) patients. Current approaches are two-sided, meaning both patients being matched must have the same candidate gene flagged. This limits the number of RGD patients eligible for matchmaking. One-sided matchmaking, in which a gene of interest is queried in the genome-wide sequencing data of RGD patients, would make matchmaking possible for previously undiscoverable individuals. However, platforms and workflows for this approach have not been well established.

RESULT: We released a beta version …

Complications Of Ovarian Metastases From Well-Differentiated Small Bowel Neuroendocrine Neoplasms: A Focus On Bowel And Ureteral Obstruction, Sydney J. Wellens, Nicholas J. Skill, Kevin M. Sullivan, Mary A. Maluccio, Kristen E. Limbach

School of Medicine Faculty Publications

Ovarian metastasis from small bowel neuroendocrine neoplasms (SBNENs) was traditionally considered rare, but more recent series have suggested a higher prevalence. This case series seeks to examine the features and outcomes of patients with neuroendocrine ovarian metastases (NOM). Female patients with histologically confirmed well-differentiated SBNENs were identified using a prospectively maintained database (2014–2024). The electronic medical record was reviewed for details of diagnosis, histopathology, biomarkers, and outcomes among patients with and without NOM. 175 patients met inclusion criteria. 35 patients (20 %) had ovarian metastasis; for this group, 31.4 % had small bowel obstruction only, 5.7 % had ureteral obstruction …

Higher Mortality Following Sars-Cov-2 Infection In Rural Versus Urban Dwellers Persists For Two Years Post-Infection, A. Jerrod Anzalone, Michael T. Vest, Makayla E. Schissel, Bradley Price, William B. Hillegass, Ronald Horswell, San Chu, Clifford J. Rosen, Lucio Miele, Susan L. Santangelo, Gordon S. Smith, Sally L. Hodder, Christopher G. Chute

School of Medicine Faculty Publications

Previous studies demonstrated higher short-term mortality among rural compared with urban residents infected with SARS-CoV-2. However, whether this difference persists remains uncertain. This retrospective cohort study analyzed two-year post-COVID-19 mortality by rurality using the National Clinical Cohort Collaborative COVID-19 Enclave, a United States-based longitudinal electronic health record repository. We analyzed mortality among patients infected with SARS-CoV-2 between April 2020 and December 2022, with follow-up until December 2024. Patients were categorized into urban, urban-adjacent rural (UAR), and nonurban-adjacent rural (NAR) groups based on residential ZIP Code. Mortality differences were assessed using Kaplan-Meier analysis and weighted multivariable Cox regression, with weights derived …

A Case Of Granuloma Annulare Mimicking Candidal Intertrigo In The Groin, Scotty Smith, Patrice Perche, Leonard Gately

School of Medicine Faculty Publications

Granuloma annulare (GA) is a benign, non-infectious granulomatous skin condition of uncertain etiology, often presenting as annular erythematous plaques. While commonly localized to the hands and feet, GA has multiple clinical variants and can mimic other dermatologic conditions, leading to diagnostic challenges. We report a rare case of GA localized to the inguinal region in a 55-year-old female initially treated empirically for candidal intertrigo without improvement. Biopsy demonstrated interstitial histiocytic infiltrates dissecting between collagen bundles with increased dermal mucin, confirming a diagnosis of interstitial GA. The patient was subsequently treated with triamcinolone 0.1% ointment and hydroxychloroquine 200 mg twice daily …

Clinical Utility Of Diffusion Tensor Imaging In Sport-Related Concussion: A Systematic Review, Shiv Patil, Rithvik Kata, Serhat Aydin, Mert Karabacak, Konstantinos Margetis, Sotirios Bisdas

Student Papers, Posters & Projects

OBJECTIVE: Sport-related concussion (SRC) is a prevalent form of traumatic brain injury that is associated with long-term neurological and psychiatric impairment, particularly among athletes with a history of repetitive concussions. The biological variability of SRC's impact on the brain, as well as a lack of objective biomarkers to diagnose and prognosticate concussion, has prompted interest in advanced neuroimaging methods such as diffusion tensor imaging (DTI). By measuring disruptions in water diffusivity due to head trauma, DTI can detect alterations in white matter integrity that are not visualized by conventional imaging methods. This systematic review aims to synthesize major trends and …

Neighborhood Social Cohesion Associated With Chronic Liver Disease Prevalence And All-Cause Mortality, Tiange P. Zhang, Jennifer L. Dodge, Divya Ayyala-Somayajula, Norah A. Terrault

Division of Gastroenterology and Hepatology Faculty Papers

Background and Aims: Neighborhood social cohesion (NSC)—the degree of trust and solidarity within a community—may influence health through multiple pathways including shaping healthy norms, perception of safety, and stress. Whether NSC influences chronic liver disease (CLD) prevalence and associated mortality in the United States is unknown. Methods: Using 172,047 adults from the 2013–2018 National Health Interview Survey with linkage to National Death Index mortality data, NSC was measured using questions on help availability, accountability, trustworthiness, and connectedness among neighbors, with composite scores (4–16) categorized as minimal (4–7), low (8–10), moderate (11–13), and high (14–16). Logistic and Cox regression tested the …

Diverse Presentations Of Aphasia: A Comparative Analysis Of Polysynthetic And Analytic Languages Through Kanien'keha (Mohawk) And English Morphology And Syntax, Halle L. Elder

The Downtown Review: An Interdisciplinary Journal Written and Peer-Reviewed by Mandel Honors College Students at Cleveland State University

This paper looks to compare two linguistically diverse languages, English and Kanien'keha, a native American language commonly known as Mohawk. The comparison will revolve around the morphology and syntax typologies of these two languages. In addition to the morphological and syntactic comparison, I will discuss how aphasia presents itself in different language typologies, placing this comparison onto English and Kanien'keha. The research questions I look to answer are: How does word formation and sentence structure differ between English and Kanien'kéha? Does aphasia present differently in analytic and polysynthetic languages like English and Kanien'kéha? The morphological data and syntactic data are …

Successful Therapeutic Response Of Intravenous Immunoglobulin In Guillain-Barre Syndrome With Onset More Than Two Weeks: A Case Report, Ezra Immanuelly Pribadi, Fauna Herawati, Valentinus Besin, Marisca Evalina Gondokesumo

Chulalongkorn Medical Journal

Guillain-Barré Syndrome (GBS), with a global incidence of 1–2 cases per 100,000 population annually, remains the most common cause of acute flaccid paralysis. Standard treatment includes plasma exchange within 4 weeks or intravenous immunoglobulin (IVIg) within 2 weeks of symptom onset. However, IVIg may still benefit selected late-presenting cases. Here, we report a case a 17-year-old male presented with progressive bilateral limb weakness and paresthesia that began approximately 3 weeks before admission. He also experienced a brief syncope episode and defecation syncope, indicating possible autonomic involvement. On hospital day 3, after shared decision-making, the family opted for IVIg over plasma …

A Rare Variation In The Branching Pattern Of The Axillary Artery, Preethi Umanath, Sutha Selvaraj

Chulalongkorn Medical Journal

ABSTRACT:

BACKGROUND: This study aims to elucidate a previously unreported rare variation in the branching pattern of the third part of the axillary artery.

Results and discussion: During the routine dissection of a male cadaver, it was observed that the third part branches of the left axillary artery, specifically the anterior and posterior circumflex humeral arteries, were completely absent. To compensate for the missing branches, an unusual ascending branch emerged from the arteria profunda brachii (a branch of the brachial artery). This branch later divided into two: the deltoid branch, which accompanied the axillary nerve, entered in to …

Morphological And Biological Properties Of Platelet Rich Fibrin Membrane Producing From Different Centrifugation Protocols, Vannarut Satitpitakul Md, Sarisa Tangkhunchaisaeng

Chulalongkorn Medical Journal

Background: Platelet-rich fibrin (PRF) membranes represent a promising tool for corneal epithelial disease treatment, though a standardized protocol remains unestablished. Objective: This study aimed to evaluate the morphological and biological properties of Platelet-Rich Fibrin (PRF) membranes producing from different centrifugation protocols Methods: Four distinct low speed centrifugation protocols (100g/5min, 200g/5min, 100g/10min, and 200g/10min) were established for PRF production from 3 healthy volunteers. We assessed fibrin and membrane dimensions, white blood cell and platelet concentrations, kinetic release of growth factors (TGF-, PDGF-BB, VEGF, IGF-1), and inflammatory cytokines (IL-6, IL-1, TNF-). In vitro degradation and bacterial contamination were also examined. Results: All …

The Impact Of G6pd Deficiency On Liver Damage And Disease Progression In Hepatocellular Carcinoma: A Cross-Sectional Study In Thailand, Watcharapong Jugnam-Ang, Phatchayanat Tansakul, Makamas Chanda, Poonlarp Cheepsunthorn, Pisit Tangkijvanich, Chalisa L. Cheepsunthorn Ph.D.

Chulalongkorn Medical Journal

Background. Glucose 6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway, producing reduced nicotinamide adenine dinucleotide phosphate (NADPH) to support redox homeostasis and cancer cell proliferation. While G6PD deficiency has been linked to reduced cancer risk, its impact on hepatocellular carcinoma (HCC) remains unclear.

Objectives. This study investigates the prevalence of G6PD deficiency in HCC patients and its association with clinical parameters across disease stages.

Methods. A cross-sectional study analyzed G6PD activity and clinical data from 174 HCC patients, 100 hepatitis B virus (HBV)-infected patients, and 154 healthy controls. Peripheral blood G6PD activity was measured, and …

Investigating The Organs At Risk (Oar) Received Dose During Prostate Cancer Therapy Using Intensity Modulated Radiation Therapy (Imrt) And 3d Conformal Radiotherapy (3dcrt): A Comparison Study, Talib Abdulwahid, Hussein Mraity, Mustafa Al-Aseebee, Zeyad Al-Dulaimi, Ali Abid Abojassim

Chulalongkorn Medical Journal

Radiotherapy domain is known to impose undesired risk of radiation to normal tissue surrounding the tumor. So, the treatment planning systems are developing with time to introduce a perfect treatment. Organs at risks surrounding prostate tumors are sensitive to high doses of radiation. This study is aimed at comparing the efficiency of the three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT) techniques during the treatment of prostate cancer. A cross-sectional study was performed in Middel Euphrate Csancer Center, Najaf , Iraq. A 25 patients with prostate tumor were enrolled. They underwent CT scans from imaging then treated with x-ray …

Effectiveness Of Vitamin D3 In Facilitating The Therapeutic Progression Of Healing Diabetic Foot Ulcers, Fatemeh Nouri, Sara Aghaei, Gülüzar Özbolat, Yusuf Döğüş, Mahdi Mirhamidi, Reza Rahimi Barghani, Amin Daemi

Chulalongkorn Medical Journal

Background: Today’s, diabetes and its complications have afflicted a large population all over the world, so that it is estimated that its prevalence in all age groups will reach from 2.8% in 2000 to 4.4% in 2030. It is well known that vitamin D may cause rapid wound healing and anti-inflammatory.

Objective: Regarding the importance of the quality of life of diabetic patients and the improvement of chronic diabetic foot ulcers, this paper aims to investigate the efficacy of vitamin D3 on the healing of diabetic foot ulcers. The present research is conducted as a randomized controlled trial.

Methods: …

Non-Invasive Way For Detection Of Neonatal Jaundice Using Gbr, Priti V. Bhagat, Mukesh Raghuwanshi, Ashutosh D. Bagde

Chulalongkorn Medical Journal

Background: Neonatal jaundice is a common condition in newborns due to excess levels of bilirubin. The traditional method for bilirubin testing is invasive, i.e., through blood tests only, which is painful to infants. Therefore, this study uses machine learning algorithms to develop a non-invasive way to detect neonatal jaundice.

Objectives: Design a computer-aided support system to detect neonatal jaundice using machine learning algorithm.

Methods: The gradient-boosting regression model is used to predict the bilirubin level. Gradient Boosting is a robust boosting algorithm that combines several weak learners into strong learners, in which each new model is trained to minimize the …

The Comparison Of Radiation Attenuation Correction Techniques For Relative Renal Function In Renal Cortical Scintigraphy, Benchamat Phromphao, Sorasak Wanitchanan, Trai Chairat, Thunyaluk Sawatnatee, Tanawat Sontrapornpol

Chulalongkorn Medical Journal

Background: Renal cortical scintigraphy using Tc-99m Dimercaptosuccinic acid (Tc-99m DMSA) is the detection of cortical abnormalities. In addition, relative renal function (RRF) is performed by DMSA scintigraphy and estimated from the radiopharmaceutical uptake in both kidneys with radiation attenuation correction. Generally, attenuation correction is calculated from mathematic methods with kidney depth correction for an accurate renal function value.

Objective: The purpose of this research was to study the correlation of the RRF with radiation attenuation correction by geometric mean (GM) method and kidney depth correction by Beer-Lambert law equation.

Methods: Researchers studied in the spherical phantom, kidney phantom and patient’s …

Periodontal Status In Patients With Chronic Skin Diseases: A Pilot Study, Hao Nguyen, Thuy Nguyen, Thuy Vo, Huong Duong, Hoa Ho, Nhi Pham, Nguyen Pham, Nam Huynh

Chulalongkorn Medical Journal

Background: Many skin diseases, especially those that also involve the oral mucosa lesions might play an important role in the etiopathogenesis of oral health and mucocutaneous inflammation. The presence of these oral sores may make it more difficult to maintain good oral hygiene, which increases plaque accumulation and raises the risk of developing periodontal disease.

Objectives: This study aimed to evaluate and compare the periodontal status of chronic skin disease (CSD) patients with healthy controls.

Methods: 109 patients and 37 healthy subjects were included in this study. Parameters evaluated included bleeding on probing index (BOP), periodontal pocket depths (PPD), clinical …

Treatment Of Biopsy-Proven Laryngeal Squamous Cell Carcinoma In Situ, Praneet C. Kaki, Aman M. Patel, Lily Huang, Gavin Turner, Afash Haleem, Jason A. Brant, Robert M. Brody, Ryan M. Carey

SKMC Student Presentations and Publications

OBJECTIVE: To investigate the impact of clinical surveillance, primary radiotherapy, and primary surgery on overall survival (OS) in laryngeal carcinoma in situ (Cis).

METHODS: The 2006-2020 National Cancer Database was queried for adults with a biopsy-proven diagnosis of laryngeal Cis. Multivariable binary logistic and Cox proportional hazards regression models were implemented.

RESULTS: Of 3567 unique patients satisfying inclusion criteria, 514 (14.4%) underwent clinical surveillance, 1074 (30.1%) underwent primary radiotherapy, and 1979 (55.5%) underwent primary surgery. Receiving treatment at an academic/research facility was associated with higher odds of undergoing primary surgery compared to primary radiotherapy. Among 646 patients undergoing primary surgery …

Genomic Insights Into A Diarrheal Outbreak In Bangladesh Reveal Novel Etec Lineages And Expansion Of Cs23 Colonization Factor, Sadia Isfat Ara Rahman, James M Fleckenstein, Et Al.

2020-Current year OA Pubs

Enterotoxigenic

Estimated Waste Generation From 1 Million Basic Metabolic Panels: A Multisite U.S. Study, Seema Khattri Bhandari, Kwaku Twum, Erving T Laryea, Yaqing Du, Raeshun T Glover, Rachel G Brackbill, William Butler, Khushbu Patel, Christopher W Farnsworth, Christina C Pierre, Steven W Cotten, Joesph R Wiencek

2020-Current year OA Pubs

OBJECTIVES: Clinical laboratory operations consume large amounts of electricity and water and generate considerable quantities of solid waste. In this study, we quantified and compared the estimated solid waste produced from performing one million basic metabolic panels (BMPs) across five major high-throughput chemistry analyzer systems commonly used in the United States. Additionally, we estimated the carbon emissions associated with the electricity and water usage of each analyzer to better understand their environmental impact.

METHODS: Five academic medical centers each using a different clinical chemistry analyzer system, collected their respective annual vendor purchase data (January 2022-December 2022). Consumables including reagent cartridges, …

Performance Evaluation Of A Commercial Multiplex Pathogen Panel For Detection Of Bacteria In Sputum Specimens From Non-Icu Patients With Suspected Lower Respiratory Tract Infection, Madeline Gemoules, Tristan T Timbrook, Elizabeth Neuner, Rebekah E Dumm, Tamara Krekel

2020-Current year OA Pubs

Rapid diagnostic testing can improve pathogen detection and lead to targeted antibiotics. The BioFire FilmArray Pneumonia Panel (BFPP) is a multiplex PCR that has displayed strong concordance with traditional microbiologic techniques. However, most existing literature focuses on deep respiratory specimens, and there is sparse literature on performance in sputum specimens. This retrospective, single-center study included adult patients between 1 September 2022 and 31 August 2024 who had collection of a BFPP with standard of care (SOC) culture from a sputum specimen on a non-intensive care unit (ICU) floor or in the emergency department if admitted to a non-ICU floor. Out …

Factors Associated With Corrective Actions, Remediation, And Employment Termination Of Emergency Physicians, Lyndsay Tyler, Yachana Bhakta, Michael Gottlieb, Chadd K. Kraus, Terry Kowalenko, Yvette Calderon, Samuel M. Keim, Diane L. Gorgas, Deborah B. Diercks, Lewis S. Nelson

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Medical professionalism is fundamental to the delivery of high-quality patient care. There is a paucity of data to describe behaviors associated with negative professional and employment outcomes. This study examines common factors leading to corrective actions, remediation, and termination of emergency physicians (EPs).

METHODS: This was a cross-sectional survey sent to academic chairs in emergency medicine to identify factors for corrective actions, remediation, or termination of EPs. Survey items were piloted and response process validity gathered prior to administration. Data are reported as descriptive statistics.

RESULTS: 60 of 167 (36 %) members of the Association of Academic Chairs in …

Fate Mapping Of Peripherally-Derived Macrophages After Traumatic Brain Injury In Mice Reveals A Long-Lasting Population With A Distinct Transcriptomic Signature, Maria Serena Paladini, Benjamin A Yang, Kristof A Torkenczy, Elma S Frias, Xi Feng, Karen Krukowski, Rene Sit, Maurizio Morri, Wendy Lam, Valentina Pedoia, Stefka Tyanova, Marco Colonna, Amber L Nolan, Susanna Rosi

2020-Current year OA Pubs

Traumatic brain injury (TBI) is an environmental risk factor for dementia and long-term neurological deficits, posing a significant public health challenge. TBI-induced neuroinflammation involves both brain-resident microglia and peripheral monocyte-derived macrophages (MDMs). Previous research has shown that MDMs contribute to the development of long-term memory deficits, yet their long-term behavior following brain infiltration remains unclear. To address this, our study uses two complementary fate-mapping mouse lines, CCR2-creERT2 and Ms4a3-cre, for precise and lasting tracking of MDMs in vivo. Here we show that MDMs persist in the brain for at least 8 months post-TBI in both male and female mice. MDMs …

Implementation Mapping To Identify Best Practices For Implementing Population-Wide Genomic Screening Programs: Protocol For The Focus (Facilitating The Implementation Of Population-Wide Genomic Screening) Study, Megan Roberts, Jarrod Marable, Kimberly Foss, Cason Whitcomb, Deborah Cragun, Adam Buchanan, Miranda Hallquist, Nathaniel Baker, Rebecca Bosch, Derek W Craig, Ingrid Wagner, Maria Fernandez, Chanita Hughes-Halbert, Caitlin Allen

Faculty, Staff and Student Publications

Background: Population-wide genomic screening (PGS) for genetic conditions such as hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia presents opportunities to reduce morbidity and mortality among the 1%-2% of the population at elevated risk for these serious, preventable diseases. With decreasing sequencing costs and growing support from national bodies, there are increasing numbers of PGS programs in the United States. However, guidelines and strategies to support implementation are limited, especially regarding equitable access to PGS. Contextual factors, such as organizational structures and processes, impact PGS implementation, often failing to benefit underrepresented populations. To address these challenges, we …

Enhanced Piezo1 Function Contributes To The Pathogenesis Of Sickle Cell Disease, Luis O Romero, Manisha Bade, Laila Elsherif, Jada D Williams, Xiangmei Kong, Adebowale Adebiyi, Kenneth I Ataga, Shang Ma, Julio F Cordero-Morales, Valeria Vásquez

Faculty, Staff and Student Publications

Sickle cell disease (SCD), an inherited blood disorder caused by a mutation in the β-globin gene, is characterized by sickle erythrocytes that are prone to hemolysis, leading to anemia and vaso-occlusion crises. In sickle erythrocytes, hemoglobin aggregation is followed by altered cation permeability and subsequent dehydration. Interventions that restore cation permeability can decrease hemolysis and ameliorate the symptoms associated with SCD. PIEZO1 is a nonselective mechanosensitive cation channel that regulates erythrocyte volume. Gain-of-function (GOF) mutations in PIEZO1 cause hemolytic anemia by increasing cation permeability, leading to erythrocyte dehydration in humans and mice. Although PIEZO1 plays a key role in erythrocyte …

A Soft-Stiff Patterned Bioengineering Model Reveals Kinase Pathways Driving Directional Cell Migration In Pulmonary Arterial Hypertension, Tamanna Islam, Jacob Hooper, Xiaojun Zhang, Clarissa Garcia, Md Mahedi Hasan, David H Drewry, Mohammad Anwar Hossain, Taslim A Al-Hilal

Faculty, Staff and Student Publications

Directional cell migration by pulmonary arterial cells (PACs) is one of the important features of diseases involving arterial remodeling, such as pulmonary arterial hypertension (PAH), a disease that is often characterized by reduced arterial compliance and increased extracellular matrix (ECM) stiffening. However, there are no therapeutics that can halt the directional cell migration of PACs in PAH. The inability to identify drug targets or drugs against the directional cell migration during PAH pathogenesis stems from an incomplete understanding of the process and a lack of effective translational models for screening of candidate small molecules. Here, for the first time, we …

Advances In Fret Methodologies For Probing Molecular Interactions, Geetika Verma, Vasanthi Jayaraman

Faculty, Staff and Student Publications

Förster resonance energy transfer (FRET) has evolved into a powerful, quantitative approach for probing biomolecular structure, dynamics, and interactions. This research highlight brings together recent studies in Biophysical Journal that push the boundaries of traditional FRET. These innovations expand the spatial and temporal resolution of FRET, enabling its application to increasingly complex biological systems.

Multicenter Stroke Preclinical Assessment Network Analysis Of Cardiovascular Risk Factor Subgroups Treated With The Poly(Adp-Ribose) Polymerase Inhibitor Veliparib, Raymond C Koehler, Karni Bedirian, Mu-Hsun Chen, Yanrong Shi, Suyi Cao, Brooklyn D Avery, Senthilkumar S Karuppagounder, Kazi Akhter, Adnan Bibic, Valina L Dawson, Ted M Dawson, Márcio A Diniz, Jessica Lamb, Karisma A Nagarkatti, Anjali Chauhan, Jaroslaw Aronowski, Louise D Mccullough, Andreia Lopes De Morais, Xuyan Jin, Cenk Ayata, Mariia Kumskova, Rakesh B Patel, Anil K Chauhan, Enrique C Leira, Pradip K Kamat, Mohammad B Khan, Krishnan M Dhandapani, David C Hess, Ligia S B Boisserand, Basavaraju G Sanganahalli, Lauren H Sansing, Patrick D Lyden

Faculty, Staff and Student Publications

Background: The Stroke Preclinical Assessment Network tested 6 therapeutic interventions initiated at the time of reperfusion after focal ischemic stroke in young mice, aging mice, obese mice, and spontaneously hypertensive rats. This randomized, controlled trial was conducted across 6 sites with concealed treatment and blinded neurobehavior assessments. The trial had an adaptive design with preset levels of efficacy and futility interrogated after each of 4 stages. The primary outcome was turning preference on the corner test at 1 month. The PARP (poly(ADP-ribose) polymerase) inhibitor, veliparib, was considered futile after the second stage when pooling all animal models (n=231 …