Digital Commons Network^™

Practices In Single Ventricle Repairs: Insights From Computational Fluid Dynamics On Cavopulmonary Connections – A Scoping Review, Olivia K. Osuch

Student Works

Abstract: Single-ventricle congenital heart defects require complex surgical strategies, with computation fluid dynamics (CFD) playing a growing role in optimizing cavopulmonary connections. This scoping review examines CFD-derived insights into power loss, hepatic flow distribution (HFD), and wall shear stress (WSS) across different Fontan geometries.

Methods: A search of available peer-reviewed literature (1995-2024) identified studies using CFD models to analyze hemodynamic performance in second and third-stage single-ventricle repairs. Studies were categorized based on surgical stage, anatomical variations, modeling assumptions, and key outcomes such as power loss, HFD, and WSS.

Results: Of 30 included studies, 28 analyzed power loss, 24 evaluated HFD, …

Galectin-1 Inhibition As A Strategy For Malignant Peripheral Nerve Sheath Tumor Treatment, Hsiao-Chi Wang, Keila E Torres, Roger Xia, Marcio H Malogolowkin, Ssu-Wei Hsu, Ching-Hsien Chen, Tsung-Chieh Shih

Faculty, Staff and Student Publications

Neurofibromatosis type 1 (NF1) is an inherited disorder that predisposes individuals to malignant peripheral nerve sheath tumors (MPNSTs), a highly aggressive sarcoma with limited treatment options and poor prognosis. This study explores the potential of targeting the interaction between Galectin-1 and Ras as a novel therapeutic strategy for MPNSTs. Through molecular docking, we identified critical residues involved in the Galectin-1 and H-Ras interaction. We developed LLS30, a compound designed to target this Ras-binding pocket on Galectin-1, and tested its efficacy. LLS30 effectively disrupted the Galectin-1/Ras interaction, causing Ras delocalization from the plasma membrane and inhibiting Ras signaling. In vitro experiments …

Oral Decitabine Cedazuridine With And Without Venetoclax In Higher-Risk Myelodysplastic Syndromes Or Chronic Myelomonocytic Leukemia: A Propensity Score-Matched Study, Alex Bataller, Koji Sasaki, Samuel Urrutia, Guillermo Montalban-Bravo, Alexandre Bazinet, Kelly Chien, Danielle Hammond, Ian M Bouligny, Mahesh Swaminathan, Ghayas Issa, Nicholas Short, Naval Daver, Courtney D Dinardo, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gail J Roboz, Michael Savona, Elizabeth A Griffiths, James Mccloskey, Olatoyosi Odenike, Aram Oganesian, Harold N Keer, Mohammad Azab, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Hypomethylating agents (HMA) are indicated in the treatment of higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The combination of hypomethylating agents with venetoclax (Ven) has demonstrated promising results in these diseases, although randomized clinical trials are needed for validation. In this retrospective study, we compared two matched cohorts of patients with MDS or CMML: one receiving oral decitabine-cedazuridine (DEC-C, n = 73) and one receiving DEC-C and Ven (DEC-C-Ven, n = 51), in three contemporary clinical trials. The aim is to determine the impact of the addition of Ven to HMA in MDS and CMML. Individuals were matched …

Liver Tet1 Promotes Metabolic Dysfunction-Associated Steatotic Liver Disease, Hongze Chen, Muhammad Azhar Nisar, Joud Mulla, Xinjian Li, Kevin Cao, Shaolei Lu, Katsuya Nagaoka, Shang Wu, Peng Sheng Ting, Tung Sung Tseng, Hui Yi Lin, Xiao Ming Yin, Wenke Feng, Zhijin Wu, Zhixiang Cheng, William Mueller, Amalia Bay, Layla Schechner, Xuewei Bai, Chiung Kuei Huang

School of Public Health Faculty Publications

Global hepatic DNA methylation change has been linked to human patients with metabolic dysfunction-associated steatotic liver disease (MASLD). DNA demethylation is regulated by the TET family proteins, whose enzymatic activities require 2-oxoglutarate (2-OG) and iron that both are elevated in human MASLD patients. We aimed to investigate liver TET1 in MASLD progression. Depleting TET1 using two different strategies substantially alleviated MASLD progression. Knockout (KO) of TET1 slightly improved diet induced obesity and glucose homeostasis. Intriguingly, hepatic cholesterols, triglycerides, and CD36 were significantly decreased upon TET1 depletion. Consistently, liver specific TET1 KO led to improvement of MASLD progression. Mechanistically, TET1 promoted …

Limosilactobacillus Reuteri Promotes The Expression And Secretion Of Enteroendocrine- And Enterocyte-Derived Hormones, Sara C Di Rienzi, Heather A Danhof, Micah D Forshee, Ari Roberts, Robert A Britton

Faculty, Staff and Students Publications

Intestinal microbes can beneficially impact host physiology, prompting investigations into the therapeutic usage of such microbes in a range of diseases. For example, human intestinal microbe Limosilactobacillus reuteri strains ATCC PTA 6475 and DSM 17938 are being considered for use for intestinal ailments, including colic, infection, and inflammation, as well as for non-intestinal ailments, including osteoporosis, wound healing, and autism spectrum disorder. While many of their beneficial properties are attributed to suppressing inflammatory responses, we postulated that L. reuteri may also regulate intestinal hormones to affect physiology within and outside of the gut. To determine if L. reuteri secreted factors …

Uterine Pgrmc2 Deficiency Attenuates Endometrial Hyperplasia And Cancer And Prolongs Lifespan In A Pten Loss-Of-Function-Induced Cancer Model, Nicole C Kelp, Cindy A Pru, Sandeep Paudel, John P Lydon, J Julie Kim, John J Peluso, James K Pru

Faculty, Staff and Students Publications

The expression of members of the progesterone receptor membrane component (PGRMC) family, particularly PGRMC1, is elevated in diverse types of cancers, particularly those of the female reproductive system. While xenograft tumor studies using human transformed cell lines in immunocompromised mice have suggested that PGRMC1 enhances tumor growth and chemoresistance, the exact role of members of the PGRMC family in cancer development in vivo remains unclear. In this study, we examined the effect of deleting Pgrmc2 on the development of endometrial hyperplasia and cancer using a murine phosphatase and tensin homologue (Pten) conditional loss-of-function model. We previously established that …

Profiling Competitive Malaysian Archers: Musculoskeletal Injuries And Related Risk Factors, Ambusam Subramaniam, Fariza Zainudin Fairus, Mon Redee Sut Txi

Baltic Journal of Health and Physical Activity

Background: Archery requires precision, strength, stamina, and attention, yet musculoskeletal injury data is scarce. The study aimed to profile the musculoskeletal injuries and the associated risk factors among Malaysian archers. Methods: A cross-sectional approach was used to recruit 165 elite archers. The Standardized Nordic Questionnaire (SNQ), adapted risk factors questionnaire, Pittsburgh Sleep Quality Index (PSQI), and Depression Anxiety Stress Questionnaire (DASS-21) were used to screen participants. Results: Shoulder (drawing arm) (54.5%), shoulder (bow arm) (56.4%), upper back (38.8%), lower back (38.2%), and neck (37.6%) musculoskeletal injuries were common. The injuries were reported during training (85.5%), accumulation/overuse injuries (72.1%), and sudden …

Epigenetic Regulation And Tumor Suppressive Function Of Lncrna Ep300-As1 In Nasopharyngeal Carcinoma Through Activation Of Tfap2c Binding To Cst6: Implications For Diagnosis, Prognosis, And Therapy, Chengliang Xing, Shun Ding, Tingting Duan, Zhiqun Li, Jinren Yan, Yu Kuang, Qibing Liu, Zhonglin Mu

Integrated Health Sciences Faculty Research

The long non-coding RNA EP300-AS1 (lncRNA EP300-AS1), identified as a potential regulatory factor in various cancers, remains underexplored in nasopharyngeal carcinoma (NPC). This study investigated EP300-AS1’s regulatory mechanisms in NPC, particularly its interaction with transcription factor AP-2 Gamma (TFAP2C) and its effect on cystatin E/M (CST6) expression. Employing clinical samples and NPC cell lines, we conducted in vitro and in vivo xenograft experiments to assess the impacts of modulating EP300-AS1 expression. Techniques such as CCK8, migration, scratch, apoptosis assays, cell cycle analysis, immunoblotting, and fluorescence experiments elucidated EP300-AS1’s role in NPC. The interaction between EP300-AS1 and TFAP2C in regulating CST6 …

Real-World Impact Of Latanoprostene Bunod Ophthalmic Solution 0.024% In Glaucoma Therapy: A Narrative Review, W. Daniel Stamer, Thomas Chiu, Da-Wen Lu, Tsing Hong Wang, Prin Rojanapongpun, Ngamkae Ruangvaravate, Youn Hye Jo, Marlene R. Moster, Murray Fingeret, Nora Lee Cothran, Jessica Steen, Ian B. Gaddie, Ömür Uçakhan-Gündüz, Wesam S. Shalaby, Cindy M. L. Hutnik

Wills Eye Hospital Papers

Latanoprostene bunod ophthalmic solution (LBN) 0.024% is a topical nitric oxide (NO)-donating prostaglandin F2α (PGF2α) analog first approved in November 2017 for reduction of intraocular pressure (IOP) in patients with ocular hypertension (OHT) or open-angle glaucoma (OAG). This narrative review describes the unique mechanism of action of LBN and summarizes available real-world data. Upon instillation, LBN is metabolized into latanoprost acid and butanediol mononitrate, which is further reduced to NO and an inactive metabolite. Latanoprost acid increases aqueous humor outflow primarily through the uveoscleral (unconventional) pathway, whereas NO increases outflow through the trabecular (conventional) pathway. Eight studies were identified: 2 …

Sitc Strategic Vision: Prevention, Premalignant Immunity, Host And Environmental Factors, Sasha E Stanton, Kristin G Anderson, Tullia C Bruno, Christian M Capitini, Mary L Disis, Jennifer Mcquade, Laszlo Radvanyi, Claire Vanpouille-Box, Jennifer Wargo, Kelly J Baines, Megan M Y Hong, Adnan Rajeh, Raymond H Kim, Phillip Awadalla, Lauren K Hughes, Saman Maleki Vareki

Faculty, Staff and Student Publications

Cancer immunotherapy has improved the survival of a subset of patients by harnessing the power of the immune system to find and destroy malignant cells. The immune system also protects the host by destroying developing premalignant and malignant tumors. Advancing our knowledge of premalignant immunity and immune changes seen in lesions that develop into invasive cancer versus those that regress offers an exciting opportunity to leverage the immune system for immune prevention and immune interception of premalignancy. Understanding the immune environment of premalignant lesions and how chronic inflammation plays a central role in the evolution of premalignancy is essential for …

Cigarette Smoke Induces Angiogenic Activation In The Cancer Field Through Dysregulation Of An Endothelial Microrna, Asawari Korde, Anuradha Ramaswamy, Seth Anderson, Lei Jin, Jian-Ge Zhang, Buqu Hu, Walter V Velasco, Lixia Diao, Jing Wang, Margaret A Pisani, Maor Sauler, Daniel J Boffa, Jonathan T Puchalski, Xiting Yan, Seyed Javad Moghaddam, Shervin S Takyar

Faculty, Staff and Student Publications

Cigarette smoke (CS) creates a "cancer field" in the lung that promotes malignant transformation. The molecular changes within this field are not fully characterized. We examined the significance of microRNA-1 (miR-1) downregulation as one of these changes. We found that tumor miR-1 levels in three non-small cell lung cancer cohorts show inverse correlations with the smoking burden. Lung MiR-1 levels follow a spatial gradient, have prognostic significance, and correlate inversely with the molecular markers of injury. In CS-exposed lungs, miR-1 is specifically downregulated in the endothelium. Exposure to CS induces angiogenesis by selectively degrading mature miR-1 via a vascular endothelial …

Effects Of Prebiotic Phytocompound Administration In Gestational Diabetic Dams And Its Influence On Offspring Cognitive Outcomes, Gayathri Jagadeesan, Tushar K Das, Jennifer M Mendoza, Ghalya Alrousan, Maria P Blasco-Conesa, Parimelazhagan Thangaraj, Bhanu Priya Ganesh

Faculty, Staff and Student Publications

Gestational diabetes mellitus (GD)-induced gut dysbiosis in pregnant mothers may increase the risk of cognitive impairment and neurological disorders in both the mother and offspring as they age. Restoring gut balance could improve cognitive outcomes for both. Despite advancements in GD treatment, side effects have increased, and long-term neurocognitive impacts on offspring born to GD mothers remain underexplored. This study uses a GD mouse model, inducing pancreatic dysfunction in 3-month-old pregnant C57BL/6J mice with Streptozotocin. The efficacy and mechanism of the prebiotic phytocompound green leaf extract (

Assessing Cancer Therapeutic Efficacy In Vivo Using [2h7]Glucose Deuterium Metabolic Imaging, Mario C Chang, Vinay R Malut, Rohit Mahar, Anna Rushin, Marc A Mcleod, Geraldine L Pierre, Indu R Malut, Stephen J Staklinski, Max E Glanz, Mukundan Ragavan, Gaurav Sharma, Manoj Madheswaran, Arshee Badar, Aparna D Rao, Brian K Law, Michael S Kilberg, James H P Collins, Vikram D Kodibagkar, James A Bankson, Ralph J Deberardinis, Matthew E Merritt

Faculty, Staff and Student Publications

Metabolic imaging produces powerful visual assessments of organ function in vivo. Current techniques can be improved by safely increasing metabolic contrast. The gold standard, 2-[18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging, is limited by radioactive exposure and sparse assessment of metabolism beyond glucose uptake and retention. Deuterium magnetic resonance imaging (DMRI) with [6,6-2H2]glucose is nonradioactive, achieves tumor metabolic contrast, but can be improved by enriched contrast from deuterated water (HDO) based imaging. Here, we developed a DMRI protocol employing [2H7]glucose. Imaging 2H-signal and measuring HDO production in tumor-bearing mice detected differential glucose utilization across baseline tumors, tumors treated with vehicle control or …

Use Of Upadacitinib For Recalcitrant Oral Erosive Lichen Planus, Connor A. Sheehan, Nicholas D. Brownstone, Jason B. Lee, Sylvia Hsu

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Liver Transplantation In 3 Cholestatic Infants With History Of Covid Exposure, Shruti Sakhuja, Kalyani R Patel, Matthew Goss, Flor M Munoz, Garrett Wortham, Megan Crawford, John A Goss, Nhu Thao Galvan

Faculty, Staff and Students Publications

The COVID-19 pandemic presents several challenges during pregnancy including thromboembolic complications, direct placental infection, transplacental transmission, and systemic hyperinflammatory state. The liver is the second most commonly affected organ in SARS-CoV-2 infection after the lungs. Mechanisms of liver injury in COVID-19 patients can include: direct viral cytopathic effect, worsening of underlying liver disease, cytokine storm, hypoxic ischemic injury, and cholangiopathy leading to persistent marked cholestasis. Here we describe 3 infants at Texas Children's Hospital with perinatal SARS-CoV-2 exposure with persistent cholestasis and histologic evidence of extrahepatic biliary obstruction suggesting underlying biliary atresia (BA) with some atypical features possibly exacerbated by …

Characterization Of Hepatic Pathology During Azoxymethane-Induced Acute Liver Failure, Shadikchhya Maya Bhattarai, Ashwin Jhawer, Gabriel Frampton, Eleonora Troyanovskaya, Sharon Demorrow, Matthew Mcmillin

Faculty, Staff and Students Publications

Background: Acute liver failure (ALF) is a loss of liver function due to a severe hepatic insult. Studies utilizing the azoxymethane (AOM) mouse model of ALF, which also generates hepatic encephalopathy, have primarily focused on development of neurological deficits. However, the molecular processes that generate liver damage have not been fully characterized. Therefore, a more comprehensive characterization of the hepatic consequences of AOM toxicity is needed to better understand this disease model.

Aim: To identify molecular pathology contributing to hepatic injury during the progression of AOM-induced ALF.

Methods: C57BL/6 mice were injected with AOM to produce ALF and hepatic encephalopathy. …

Dock2 Deficiency And Gata2 Haploinsufficiency Can Underlie Critical Coronavirus Disease 2019 (Covid-19) Pneumonia, Sajjad Biglari, Leila Youssefian, Mohammad Amin Tabatabaiefar, Amir Hossein Saeidian, Bahareh Abtahi-Naeini, Erfan Khorram, Roya Sherkat, Atefeh Sohanforooshan Moghaddam, Fatemeh Mohaghegh, Maziyar Rahimi, Hamid Rahimi, Sharareh Babaei, Mohammad Shahrooei, Nikoo Mozafari, Shirin Zaresharifi, Fatemeh Vahidnezhad, Vida Homayouni, Lam C Tsoi, Johann E Gudjonsson, Hakon Hakonarson, Jean-Laurent Casanova, Emmanuelle Jouanguy, Vivien Béziat, Qian Zhang, Aurélie Cobat, Hassan Vahidnezhad

Faculty, Staff and Students Publications

The life-threatening coronavirus disease 2019 (COVID-19) affects about 1 in 1,000 healthy people under 50 without underlying conditions. Among patients with critical COVID-19 pneumonia, rare germline variants at genes controlling type I IFN immunity have been reported in up to 5% of patients. Causal etiologies in 80-85% of cases are still unknown. We analyzed two families with hypoxemic COVID-19 pneumonia for known single-gene inborn errors of immunity. In Family 1, two siblings with critical COVID-19 were homozygous for a DOCK2 variant, c.3624+5G>A. DOCK2 deficiency is a known T-cell disorder underlying severe viral diseases. The variant resulted in skipping exon …

Left Ventricular And Aortic Pressures Measured With Fluid-Filled And Solid-State Pressure Catheters: Similarities And Differences, Priscilla Machado, Ira Cohen, Brian Osler, Maureen E. Mcdonald, Cara Esposito, Marguerite Davis, David Fischman, Michael P. Savage, Praveen Mehrotra, Flemming Forsberg, Jaydev K. Dave

Division of Cardiology Faculty Papers

Objective: To compare left ventricular (LV) and aortic (AO) pressures obtained using fluid-filled and high-fidelity solid-state pressure catheters in subjects undergoing left heart catheterization.

Materials and Methods: Twenty subjects scheduled for a left heart catheterization were enrolled and 18 subjects completed this IRB-approved study. LV and AO pressures were obtained using fluid-filled pressure catheter (standard-of-care) and high-fidelity solid-state pressure catheter synchronously. Pressure tracings were analyzed to measure LV systolic (LVSP), LV minimum-diastolic (LVMDP), LV end-diastolic (LVEDP), AO systolic (AOSP), and AO diastolic (AODP) pressures. Isovolumic contraction and relaxation rates (peak ± dp/dt) were derived from the pressure waveforms. Repeated measures …

Management Of Parkinson's Disease Psychosis: First-Line Antipsychotic Selection And Rationale For Continuing, Combining, Or Switching, Stuart H. Isaacson, Henry Nasrallah, Rajesh Pahwa, Gustavo Alva, Daniel Kremens, Stephen M. Stahl

Department of Neurology Faculty Papers

INTRODUCTION: The past decade has seen a paradigm shift in the evaluation and management of Parkinson's disease psychosis (PDP), with the first approval of an antipsychotic in the US in 2016. An evidence-based review by the Movement Disorder Society found pimavanserin and clozapine to be clinically useful, (low-dose) quetiapine to be possibly useful, and all other antipsychotics to be avoided due to motor worsening. Clozapine and quetiapine use can be limited by provoking Parkinson's disease (PD) nonmotor symptoms of somnolence and hypotension. Quetiapine may also be limited by its risk in cognitive impairment. Pimavanserin is not associated with these symptoms. …

Mesenchymal Stem Cells Loaded In Injectable Alginate Hydrogels Promote Liver Growth And Attenuate Liver Fibrosis In Cirrhotic Rats, Dominic Karl M Bolinas, Allan John R Barcena, Archana Mishra, Marvin R Bernardino, Vincent Lin, Francisco M Heralde, Gouthami Chintalapani, Natalie W Fowlkes, Steven Y Huang, Marites P Melancon

Faculty, Staff and Student Publications

Cirrhosis, a marker of severe liver diseases, limits future liver remnant (FLR) growth, preventing many cancer patients from undergoing surgery. While portal vein blockade (PVB) techniques are used to stimulate liver regeneration, 20-30% of patients still fail to achieve the required growth. Although mesenchymal stem cell (MSC) therapy improves PVB, its efficacy is limited by poor cell retention. To address this, we utilized alginate hydrogels to deliver MSCs and improve their retention. MSCs were loaded in the hydrogel and injected intraportally in cirrhotic rats. Liver volume, weights, enzyme levels, and histology were monitored. Results showed that the hydrogel maintained 89.0 …

Effectiveness Of Intrapartum Azithromycin To Prevent Infections In Planned Vaginal Births In Low-Income And Middle-Income Countries: A Post-Hoc Analysis Of Data From A Multicentre, Randomised, Double-Blind Placebo-Controlled Trial, Waldemar A. Carlo, Alan T.N. Tita, Janet L. Moore, Musaku Mwenechanya, Elwyn Chomba, Jennifer J. Hemingway-Foday, Avinash Kavi, Mrityunjay C. Metgud, Shivaprasad S. Goudar, Richard J. Derman, Adrien Lokangaka, Antoinette Tshefu, Melissa Bauserman, Jackie K. Patterson, Poonam Shivkumar, Manju Waikar, Archana Patel, Patricia L. Hibberd, Paul Nyongesa, Fabian Esamai, Osayame Austine Ekhaguere, Sherri Bucher, Saleem Jessani, Shiyam Sunder Tikmani, Sarah Saleem, Robert L. Goldenberg, Sk Masum Billah, Ruth Lennox, Rashidul Haque, William Petri, Manolo Mazariegos, Nancy F. Krebs, Denise C. Babineau, Elizabeth M. Mcclure, Marion Koso-Thomas, A-Plus Trial Group

Global Health Articles

Background

In 2023, the Azithromycin Prevention in Labor Use (A-PLUS) trial showed intrapartum azithromycin reduces maternal sepsis or death in women with planned vaginal delivery in low-resource settings, but whether it reduces maternal infection is unknown. We aimed to evaluate the effectiveness of intrapartum azithromycin in reducing maternal infection.

Methods

We performed a post-hoc analysis of the multicentre, facility-based, randomised, double-blind, placebo-controlled A-PLUS trial. This trial compared prophylactic intrapartum single oral dose of 2 g azithromycin versus placebo on maternal morbidity and mortality in low-resource settings in southeast Asia and Africa from Sept 9, 2020, to Aug 18, 2022. The …

Cost-Effectiveness Of Intrapartum Azithromycin To Prevent Maternal Infection, Sepsis, Or Death In Low-Income And Middle-Income Countries: A Modelling Analysis Of Data From A Randomised, Multicentre, Placebo-Controlled Trial, Jackie K. Patterson, Simon Neuwahl, Sydney Kirsch, Janet L. Moore, Alan T.N. Tita, Waldemar A. Carlo, Adrien Lokangaka, Antoinette Tshefu, Musaku Mwenechanya, Elwyn Chomba, Avinash Kavi, Mrityunjay C. Metgud, Shivaprasad S. Goudar, Richard J. Derman, Poonam Shivkumar, Manju Waikar, Archana Patel, Patricia L. Hibberd, Paul Nyongesa, Fabian Esamai, Osa A. Ekhaguere, Sherri Bucher, Saleem Jessani, Shiyam S. Tikmani, Sarah Saleem, Blair J. Wylie, Robert L. Goldenberg, Sk Masum Billah, Ruth Lennox, Rashidul Haque, William A. Petri, Manolo Mazariegos, Nancy F. Krebs, Jennifer J. Hemingway-Foday, Denise Babineau, Marion Koso-Thomas, Elizabeth M. Mcclure, Melissa Bauserman

Global Health Articles

BACKGROUND: Sepsis is one of the leading causes of maternal mortality globally. In 2023, the Azithromycin Prevention in Labor Use (A-PLUS) trial showed intrapartum azithromycin for women planning a vaginal birth reduced the risk of maternal sepsis or death and infection. We aimed to evaluate the cost-effectiveness of intrapartum azithromycin for pregnant people planning a vaginal birth in low-income and middle-income countries (LMICs) using A-PLUS trial data.

METHODS: We compared the benefits and costs of intrapartum azithromycin versus standard care across 100 000 model simulations using data from the A-PLUS trial and a probabilistic decision tree model that included 24 …

Β-Catenin Drives The Foxc2-Mediated Epithelial-Mesenchymal Transition And Acquisition Of Stem Cell Properties, Maria Castaneda, Petra Den Hollander, Steve Werden, Esmeralda Ramirez-Peña, Suhas V Vasaikar, Nick A Kuburich, Claire Gould, Rama Soundararajan, Sendurai A Mani

Faculty, Staff and Student Publications

Background: Aggressive forms of breast cancer, such as triple-negative breast cancer (TNBC), are associated with an increase in cancer cells that exhibit stem cell properties. The activation of the epithelial-mesenchymal transition (EMT) program, mediated by the transcription factor FOXC2, generates these stem-like cells. FOXC2 is linked to poor prognoses across various cancer types and is notably upregulated in TNBC, where it establishes and sustains these stem-like cells within the tumor population.

Methods: Here, we decode the pathways regulating FOXC2 activation using EMT-enriched cell line models. Stemness was assessed using mammosphere assays and mesenchymal markers by western blot. Expression …

Combined Targeting Of Glioblastoma Stem Cells Of Different Cellular States Disrupts Malignant Progression, Chenfei Lu, Tao Kang, Junxia Zhang, Kailin Yang, Yang Liu, Kefan Song, Qiankun Lin, Deobrat Dixit, Ryan C Gimple, Qian Zhang, Zhumei Shi, Xiao Fan, Qiulian Wu, Daqi Li, Danyang Shan, Jiancheng Gao, Danling Gu, Hao You, Yangqing Li, Junlei Yang, Linjie Zhao, Zhixin Qiu, Hui Yang, Ningwei Zhao, Wei Gao, Weiwei Tao, Yingmei Lu, Yun Chen, Jing Ji, Zhe Zhu, Chunsheng Kang, Jianghong Man, Sameer Agnihotri, Qianghu Wang, Fan Lin, Xu Qian, Stephen C Mack, Zhibin Hu, Chaojun Li, Michael D Taylor, Ning Liu, Nu Zhang, Ming Lu, Yongping You, Jeremy N Rich, Wei Zhang, Xiuxing Wang

Faculty, Staff and Students Publications

Glioblastoma (GBM) is the most lethal primary brain tumor with intra-tumoral hierarchy of glioblastoma stem cells (GSCs). The heterogeneity of GSCs within GBM inevitably leads to treatment resistance and tumor recurrence. Molecular mechanisms of different cellular state GSCs remain unclear. Here, we find that classical (CL) and mesenchymal (MES) GSCs are enriched in reactive immune region and high CL-MES signature informs poor prognosis in GBM. Through integrated analyses of GSCs RNA sequencing and single-cell RNA sequencing datasets, we identify specific GSCs targets, including MEOX2 for the CL GSCs and SRGN for the MES GSCs. MEOX2-NOTCH and SRGN-NFκB axes play important …

Polycystic Ovarian Syndrome: A Clinical Review, Amanda Nettles

Lynchburg Journal of Medical Science

Polycystic ovarian syndrome (PCOS) is a pervasive condition that affects women all over the world. It presents with a wide variety of symptoms like menstrual irregularity, hyperandrogenism, and polycystic ovarian morphology. Although generally considered to be solely a reproductive disorder, PCOS impacts metabolic, psychological, and cardiovascular health, and increases the risk for those diagnosed for other complications. Although PCOS is relatively common, it remains greatly misunderstood, which makes diagnosing the condition even more complex. Risk factors taken into consideration include genetics, environment, and lifestyle. The pathophysiology of PCOS focuses on dysfunction of the hypothalamic-pituitary-ovarian axis, insulin resistance, and inflammation. There …

Common Misconceptions In Hormone Therapy (Ht) Treatment In Menopause, Miranda Zuhlke

Lynchburg Journal of Medical Science

ABSTRACT
The purpose of this review is to address the misconceptions surrounding Hormone Therapy (HT) in menopause largely surrounding the findings from Women’s Health Initiative (WHI). The review explores the history of HT, the risks and benefits, along with current guidelines for HT and non-hormonal options. A comprehensive search was conducted using electronic databases focusing on the effect of HT on breast cancer, cardiovascular health, bone health, and quality of life. Studies that analyzed the implications from the WHI were included as well as the North American Menopause Society (NAMS) current recommendations and guidelines for treatment options in menopause. Findings …

Testosterone Replacement Therapy In The Middle-Aged Male, Gina N. Demilt

Lynchburg Journal of Medical Science

The purpose of this review was to investigate the use of testosterone supplementation in the middle-aged male with a focus on the pathophysiology of testosterone throughout the lifespan, current supplementation options and their adverse effects, and the overall benefit of supplementing to enhance quality of life. A comprehensive search of electronic databases was conducted identifying studies that assessed clinical outcomes, pathophysiology, supplementation options, adverse effects and benefits of treatments. The findings suggested that testosterone levels naturally decline with age with most men developing symptoms of hypogonadism around age 60. Testosterone supplementation outside of current guidelines is not recommended, however men …

Comparing Testosterone Suppression In Intramuscular And Subcutaneous Leuprolide Acetate Formulations, Annalise Mcdonald, Kali Sullivan, Cara Cloghessy, Benjamin Sweigart, Brendan J. Connell

The Lahey Journal

Introduction

Androgen deprivation therapy (ADT) is commonly used to treat prostate cancer. Leuprolide acetate (LA) is a common ADT, manufactured as an intramuscular injection, Lupron® (LA-IM), and a subcutaneous injection, Eligard® (LA-SC) with the goal of testosterone < 50 ng/dL. We investigated for differences in testosterone suppression between the two formulations in patients with prostate cancer.

Methods

Clinical data was abstracted from our medical records system for patients with prostate cancer who started leuprolide acetate between January 2016 through March 2022 with a subsequent testosterone value checked. Primary endpoint was the proportion of subjects with testosterone levels < 50mg/dL, with secondary endpoints including the proportion of subject achieving testosterone levels < 20ng/dL and median testosterone levels.

Results

525 subjects were included. The LA-IM and LA-SC groups were balanced for age and race but the doses of leuprolide differed …

Aerosolized Transmissible Diseases Guidance Document, J. David Miller, John P. (Jack) Springston Jr., Cheryl L. Marcham, J. David Krause, Ling-Ling Hung, Wane A. Baker

Publications

Prior to COVID-19, pandemic influenza viruses have emerged four times in the previous one hundred years. This includes “Spanish” influenza (H1N1) in 1918, “Asian” influenza (H2N2) in 1957, “Hong Kong” influenza (H3N2) in 1968, and H1N1 “swine” influenza in 2009 (Saunders-Hastings & Krewski, 2016; Taubenberger, 2005). In early May 2024, the first reported human case of avian flu (H5N1) that had also infected cows in the US appeared in the literature (Uyeki et al., 2024). In late August 2024, OSHA released a hazard alert providing information for dairy workers on avian influenza in dairy cattle, together with personal protective equipment …

Rising Incidence Of Acute Hepatitis A Among Adults And Clinical Characteristics In A Tertiary Care Center Of Pakistan, Yumna Shahid, Amna Subhan Butt, Iqra Jamali, Faisal Wasim Ismail

Section of Gastroenterology

Background: For decades, hepatitis A virus (HAV) has been a leading cause of acute hepatitis among children and was less prevalent among adults. However, recently a paradigm shift has been observed in the epidemiology of HAV, as evident by cases of acute hepatitis due to HAV among adults.
Aim: To estimate frequency of HAV in acute viral hepatitis and compare characteristics in HAV and hepatitis E virus (HEV) infection.
Methods: This was a trend analysis conducted at Aga Khan University Hospital Karachi (Sindh, Pakistan) from February 2024 to May 2024. Individuals aged 18 years and older diagnosed with acute viral …