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Articles 6091 - 6120 of 46070
Full-Text Articles in Entire DC Network
Navigating The Future Of Polygenic Risk Scores: Insights From Child And Adolescent Psychiatrists, Page M Trotter, Amanda R Merner, Lauren A Ginn, Abigail C Martinez, Ana L Battaglino, Kaitlynn P Craig, Jason Bach, Katherine J Freedberg, Takahiro Soda, Eric A Storch, Gabriel Lázaro-Muñoz, Stacey Pereira
Navigating The Future Of Polygenic Risk Scores: Insights From Child And Adolescent Psychiatrists, Page M Trotter, Amanda R Merner, Lauren A Ginn, Abigail C Martinez, Ana L Battaglino, Kaitlynn P Craig, Jason Bach, Katherine J Freedberg, Takahiro Soda, Eric A Storch, Gabriel Lázaro-Muñoz, Stacey Pereira
Center for Medical Ethics and Health Policy Staff Publications
Polygenic risk scores (PRS) are a method of calculating genetic risk for polygenic, or multi-gene, disorders. These scores have potential impacts in the realm of child and adolescent psychiatry, given the high prevalence of psychiatric disorders among youth. However, there are concerns about PRS implementation among key stakeholders, namely child and adolescent psychiatrists (CAP). We conducted interviews with 29 U.S.-based CAP to investigate clinician attitudes toward the use of PRS. The data herein correspond to a future scenario we provided CAP in which PRS are accurate and portable to patients of different racial and ethnic backgrounds. We found that CAP …
Detection Of Chromosomal Mosaicism- The Importance Of Karyotyping And Fish, Allison Kalinousky, Jennifer L. Roberts, Madeeha Alikhan, John Herriges, Lei Zhang, Elena Repnikova
Detection Of Chromosomal Mosaicism- The Importance Of Karyotyping And Fish, Allison Kalinousky, Jennifer L. Roberts, Madeeha Alikhan, John Herriges, Lei Zhang, Elena Repnikova
Research Days
This project evaluates the prevalence of chromosomal mosaicism in constitutional samples using conventional cytogenetic techniques evaluated at Children's Mercy Hospital during a 20-year period.
Effects Of Genetic Polymorphisms On The Oct1 And Oct2-Mediated Uptake Of Atenolol, Mollie Margaret Walton Md, Jonathan Wagner Do, Ceclia E. Villanueva Phd, Bruno Hagenbuch Phd
Effects Of Genetic Polymorphisms On The Oct1 And Oct2-Mediated Uptake Of Atenolol, Mollie Margaret Walton Md, Jonathan Wagner Do, Ceclia E. Villanueva Phd, Bruno Hagenbuch Phd
Research Days
This project characterizes the role of OCT1 and OCT2 on cellular uptake of atenolol and tests the hypothesis that OCT1 and OCT2 proteins with genetic polymorphisms, when expressed in vitro, will result in altered cellular uptake of atenolol relative to the reference genotype. This approach utilizes transiently transfected OCT1 and OCT2 cell assays to perform time-dependent atenolol uptake experiments to generate kinetics information. The goal is to provide a better understanding of polymorphisms associated with OCT1 and OCT2 expression and function as a means to individualize pharmacologic therapy for atenolol.
Roles Of Class Iii Phosphatidylinositol 3-Kinase, Vps34, In Phagocytosis, Autophagy, And Endocytosis In Retinal Pigmented Epithelium, Feng He, Ralph M Nichols, Melina A Agosto, Theodore G Wensel
Roles Of Class Iii Phosphatidylinositol 3-Kinase, Vps34, In Phagocytosis, Autophagy, And Endocytosis In Retinal Pigmented Epithelium, Feng He, Ralph M Nichols, Melina A Agosto, Theodore G Wensel
Faculty, Staff and Students Publications
Phosphatidylinositol-3-phosphate (PI(3)P) is important for multiple functions of retinal pigmented epithelial (RPE) cells, but its functions in RPE have not been studied. In RPE from mouse eyes and in cultured human RPE cells, PI(3)P-enriched membranes include endosomes, the trans-Golgi network, phagosomes, and autophagophores. Mouse RPE cells lacking activity of the PI-3 kinase, Vps34, lack detectable PI(3)P and die prematurely. Phagosomes containing rod discs accumulate, as do membrane aggregates positive for autophagosome markers. These autophagy-related membranes recruit LC3/Atg8 without Vps34, but phagosomes do not. Vps34 loss leads to accumulation of lysosomes which do not fuse with phagosomes or membranes with …
Science Tikkun: A Bioscience Pandemic Framework In A Hebrew Tradition Of Global Repair, Peter Hotez
Science Tikkun: A Bioscience Pandemic Framework In A Hebrew Tradition Of Global Repair, Peter Hotez
Center for Medical Ethics and Health Policy Staff Publications
Over the past decade we have seen a steady increase in dangerous pandemic threats. They include two major Ebola epidemics and cholera in Africa; dengue, Zika, yellow fever in the Americas; a COVID-19 pandemic; and H5N1 in Texas. This is happening because of a confluence of modern forces including urbanization, deforestation, and climate change. Yet as pandemics emerge on a crowded and warming planet, anti-science disinformation and antisemitism impede our response. Science tikkun is an overarching framework for repair and redress. It honors the legacy of Maimonides, Teilhard de Chardin, and others who have sought reconciliation between science and religion.
Monoclonal Antibodies Targeting Candida Disrupt Biofilms And Inhibit Growth Across Global Clinical Isolates, Jonothan Rosario-Colon, Karen Eberle, Hong Xin
Monoclonal Antibodies Targeting Candida Disrupt Biofilms And Inhibit Growth Across Global Clinical Isolates, Jonothan Rosario-Colon, Karen Eberle, Hong Xin
School of Graduate Studies Faculty Publications
Candida species are a major cause of severe fungal infections, particularly in immunocompromised individuals and hospitalized patients. Among these, Candida auris stands out as an emerging “superbug”, responsible for life-threatening bloodstream infections with mortality rates up to 60%. This multidrug-resistant, hospital-acquired pathogen has been declared a serious global health threat, complicating effective treatment and increasing mortality risks. Our research has identified universal monoclonal antibodies (mAbs) targeting Candida albicans cell wall epitopes, which are highly homologous to those in other pathogenic Candida species, including C. auris. Passive transfer of mAbs—C3.1 (anti-β-1,2-mannotriose) and 9F2 (anti-phosphoglycerate kinase 1)—significantly extended survival and improved fungal …
High Kynu Expression Is Associated With Poor Prognosis, Keap1/Stk11 Mutations, And Immunosuppressive Metabolism In Patient-Derived But Not Murine Lung Adenocarcinomas, Ling Cai, Thomas J Rogers, Reza Mousavi Jafarabad, Hieu Vu, Chendong Yang, Nicole Novaresi, Ana Galán-Cobo, Luc Girard, Edwin J Ostrin, Johannes F Fahrmann, Jiyeon Kim, John V Heymach, Kathryn A O'Donnell, Guanghua Xiao, Yang Xie, Ralph J Deberardinis, John D Minna
High Kynu Expression Is Associated With Poor Prognosis, Keap1/Stk11 Mutations, And Immunosuppressive Metabolism In Patient-Derived But Not Murine Lung Adenocarcinomas, Ling Cai, Thomas J Rogers, Reza Mousavi Jafarabad, Hieu Vu, Chendong Yang, Nicole Novaresi, Ana Galán-Cobo, Luc Girard, Edwin J Ostrin, Johannes F Fahrmann, Jiyeon Kim, John V Heymach, Kathryn A O'Donnell, Guanghua Xiao, Yang Xie, Ralph J Deberardinis, John D Minna
Faculty, Staff and Student Publications
Background/Objectives: We aimed to discover genes with bimodal expression linked to patient outcomes, to reveal underlying oncogenotypes and identify new therapeutic insights in lung adenocarcinoma (LUAD).
Methods: We performed meta-analysis to screen LUAD datasets for prognostic genes with bimodal expression patterns. Kynureninase (KYNU), a key enzyme in tryptophan catabolism, emerged as a top candidate. We then examined its relationship with LUAD mutations, metabolic alterations, immune microenvironment states, and expression patterns in human and mouse models using bulk and single-cell transcriptomics, metabolomics, and preclinical model datasets. Pan-cancer prognostic associations were also assessed.
Results: Model-based clustering of KYNU expression outperformed median-based dichotomization …
Novel Rpl30 Variant In Diamond Blackfan Anemia Demonstrates Early Impact On Erythroid Differentiation With Downregulated Gata1-Hsp70, Alexandra Prosser-Dombrowski, Irina Pushel, Jacqelyn Nemechek, Priyanka Kumar, Jay L. Vivian, Jennifer Gerton, John M. Perry
Novel Rpl30 Variant In Diamond Blackfan Anemia Demonstrates Early Impact On Erythroid Differentiation With Downregulated Gata1-Hsp70, Alexandra Prosser-Dombrowski, Irina Pushel, Jacqelyn Nemechek, Priyanka Kumar, Jay L. Vivian, Jennifer Gerton, John M. Perry
Research Days
Background: Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome caused by ribosomal protein gene mutations leading to apoptosis of erythroid progenitors. We identified a novel heterozygous variant (c.167+769C>T) in the noncoding region of RPL30 in a patient diagnosed with DBA.
Objectives/Goal: We hypothesized that this variant stunts erythroid differentiation at the proerythroblast stage and is pathogenic for DBA.
Methods/Design: We developed an induced pluripotent stem cell (iPSC) model with a wild type (WT) and three CRISPR-Cas9 edited RPL30 mutant clones. iPSCs were differentiated into hematopoietic stem cells, which were assessed by flow cytometry and single cell …
Duration Of Labor And Umbilical Artery Acidosis In Critical Congenital Heart Disease, Sarah Gwazdacz Md, Teresa Nguyen Bs, Mary Donofrio Md, Faap, Facc, Fase, Timothy Bennett Md, Amanda Mcintosh Md, Faap, Facc.
Duration Of Labor And Umbilical Artery Acidosis In Critical Congenital Heart Disease, Sarah Gwazdacz Md, Teresa Nguyen Bs, Mary Donofrio Md, Faap, Facc, Fase, Timothy Bennett Md, Amanda Mcintosh Md, Faap, Facc.
Research Days
Standard delivery protocols for most prenatally diagnosed CCHD is induction of labor at 39 weeks with aims of a vaginal delivery (VD) near a tertiary care center. There is no benefit to planned Cesarean delivery (CD) over VD for most infants with CCHD. However, longer durations of labor (DOL) in CCHD have been described as a risk factor for umbilical artery (UA) acidosis. We aim to describe the relationship between DOL and UA pH and neonatal outcomes in those with prenatally diagnosed CCHD.
Retrospective chart review of prenatally diagnosed with CCHD born at Children’s Mercy from 2012 – 2023. Inclusion …
Inpatient Thrombophilia Workup After Acute Vte: The Tests That Don’T Pay It Forward, Eliakim Munda, Bs, Ruben Rhoades, Md, Ms
Inpatient Thrombophilia Workup After Acute Vte: The Tests That Don’T Pay It Forward, Eliakim Munda, Bs, Ruben Rhoades, Md, Ms
Health Equity and Quality Improvement (HEQI) Summit
Background
- Venous thromboembolism is a complex multifactorial disease that is influenced by genetic, environmental and behavioral risk factors.
- Testing for inherited thrombophilia is commonly performed after a VTE event to help identify underlying genetic risk factors and assess the risk of recurrence.
- Despite clinical guidelines advising against thrombophilia testing in patients with acute VTE, these tests continue to be ordered even though lab results are unlikely to alter treatment decisions
Problem Statement
- At TJUH, activity and genetic assays are frequently ordered for patients with acute VTE during admission, increasing the likelihood of false- positive results that may lead to unnecessary …
Pcsk-9 Inhibitors Treatment: The Cardiovascular Disparity, Julia Lees, Seana-Pierre Williams, Tahir Razzaq, Michael B. Roberts
Pcsk-9 Inhibitors Treatment: The Cardiovascular Disparity, Julia Lees, Seana-Pierre Williams, Tahir Razzaq, Michael B. Roberts
The Journal of Integrated Primary Care
Introduction: According to the Center for Disease Control and Prevention (CDC) and American Heart Association (AHA), cardiovascular disease is the leading cause of death in the United States. This phenomenon disproportionally affects the African American population, who have a 31% higher mortality rate than non-Hispanic Caucasian individuals. A retrospective review of PCSK-9 medication use, specifically in a patient population that had minimal representation in the large, landmark clinical trials, can lead to better understanding about the therapeutic potential in cardiovascular disease reduction and patient outcomes attributed to medication use. Education regarding this novel drug class, medication access and patient support, …
Literature Review Of Stiff Person Syndrome, Mustafa Ansari, Adam Davis, Donald Penney
Literature Review Of Stiff Person Syndrome, Mustafa Ansari, Adam Davis, Donald Penney
The Journal of Integrated Primary Care
Background: Stiff Person Syndrome (SPS) is a rare, debilitating autoimmune neurological disorder characterized by progressive muscle rigidity, painful spasms, and gait disturbances. It is strongly associated with autoantibodies against glutamic acid decarboxylase (GAD), leading to impaired GABAergic neurotransmission. SPS exists on a spectrum, with both classical and paraneoplastic variants, the latter often linked to malignancies such as breast cancer.
Methods: This review synthesizes current literature on the pathophysiology, clinical presentation, diagnostic criteria, and treatment modalities of SPS. We examine emerging therapies, including immunomodulatory approaches and antibody-targeted interventions, to address the heterogeneity of disease progression and treatment response.
Results: SPS remains …
Movement Disorders In Relapsing And Progressive Ms: A Comprehensive Prospective Evaluation Of A Large Real-Life Cohort, Hannah Kelly, Rongyi Sun, Mohamed Elkasaby, Alexander Wang, Hesham Abboud
Movement Disorders In Relapsing And Progressive Ms: A Comprehensive Prospective Evaluation Of A Large Real-Life Cohort, Hannah Kelly, Rongyi Sun, Mohamed Elkasaby, Alexander Wang, Hesham Abboud
Faculty Scholarship
Background: Recent studies suggest that movement disorders are common in early MS. However, the frequency and clinical characteristics of movement disorders at all stages of MS remain unknown. Objectives: To evaluate the frequency, clinical characteristics, and anatomical generators of movement disorders in relapsing and progressive MS. Methods: We conducted a prospective study of adult MS patients from 2016 to 2022 at a neuroimmunology clinic. Patients were evaluated for demyelination-related movement disorders via a survey and focused examination. We classified movement disorders based on phenomenology and identified anatomic correlates according to lesion locations and relation to relapses. Findings were compared between …
Adults' Intention To Take An Arthritis Prescription Drug Based On Drug Advertisements, Amanda Radola
Adults' Intention To Take An Arthritis Prescription Drug Based On Drug Advertisements, Amanda Radola
Seton Hall University Dissertations and Theses (ETDs)
Direct-to-Consumer Prescription Advertising (DTCPA) has rapidly expanded, particularly via social media, but research on its influence on individual decisions regarding prescribed medications remains limited. This gap is notable among chronic disease patients, such as those with arthritis, which affected over 58.5 million U.S. adults as of 2015 and is projected to rise to 78.4 million by 2040 (Barbour et al., 2017; Hootman et al., 2016). Social media discussions show significant activity following television ads for arthritis drugs (Curtis et al., 2017). However, few studies explore how DTCPA impacts patient intentions to take advertised arthritis medications. This study employed a novel …
Identifying Key Factors Associated With Assistive Technology Availability For Dementia Care Using Machine Learning, Wai Hang Kwok, Syed Afaq Ali Shah, Guanjin Wang
Identifying Key Factors Associated With Assistive Technology Availability For Dementia Care Using Machine Learning, Wai Hang Kwok, Syed Afaq Ali Shah, Guanjin Wang
Research outputs 2022 to 2026
This study explores the factors influencing the availability of assistive technology for people with dementia through the application of machine learning. The analysis identified key factors, including carer support, protective legislation, and access to reimbursable products from the WHO Global Health Observatory. A random forest model with high accuracy emphasises the importance of targeted resources and policies in improving dementia care infrastructure.
Mapping Pain Management In Maine Participant Flyer, Ling Cao
Mapping Pain Management In Maine Participant Flyer, Ling Cao
Maine Pain Registry
Flyer calling for participation in UNE project Mapping Pain Management in Maine.
Peripheral Neuroimmune Mechanisms Of Chronic Back Pain, Aleyah Esther Goins
Peripheral Neuroimmune Mechanisms Of Chronic Back Pain, Aleyah Esther Goins
Biomedical Sciences ETDs
Chronic back pain (CBP) affects 1 in 10 people worldwide, reducing mobility, productivity, and quality of life. Despite its prevalence, non-addictive treatments remain limited due to an incomplete understanding of chronic pain mechanisms. This dissertation examines peripheral neuroimmune interactions in CBP using a urokinase-type plasminogen activator (uPA)-induced mouse model (uPA-CBP). uPA, a pro-inflammatory serine protease, was injected into the L2/L3 lumbar spinous ligament, inducing prolonged mechanical and cold hypersensitivity. Flow cytometry of dorsal root ganglia (DRG) showed increased CD45+CD11b+ myeloid cells in males and CD45+CD3+CD4+ lymphocytes in females. DRG neurons from male uPA-CBP mice exhibited heightened action potential firing. Pharmacological …
Diagnostic Considerations For Gastrointestinal Stromal Tumors With Altered Immunophenotype Following Imatinib Treatment: A Case Report And Literature Review, Jihuan Chen, Liz M. Yang, Jonathan Somma, Yujun Gan, Zengying Wu, Zhiyan Fu
Diagnostic Considerations For Gastrointestinal Stromal Tumors With Altered Immunophenotype Following Imatinib Treatment: A Case Report And Literature Review, Jihuan Chen, Liz M. Yang, Jonathan Somma, Yujun Gan, Zengying Wu, Zhiyan Fu
School of Medicine Faculty Publications
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract and have a high rate of recurrence and metastasis. Using an immunohistochemical (IHC) panel including KIT/CD117 and DOG1 allows for accurate diagnosis in more than 98% of cases. However, after tyrosine kinase inhibitor treatment, some cases can exhibit histologic dedifferentiation and loss of KIT/CD117 and DOG1 expression that may cause difficulty in confirming recurrent or persistent disease. We present such a case of an Imatinib treated, CD117 and DOG1 dual negative, metastatic GIST to the liver in a 55-year-old female which required molecular analysis to confirm …
St6galnac-I Regulates Tumor Cell Sialylation Via Nectin2/Muc5ac-Mediated Immunosuppression And Angiogenesis In Non-Small Cell Lung Cancer, Muthamil Iniyan Appadurai, Sanjib Chaudhary, Ashu Shah, Gopalakrishnan Natarajan, Zahraa W. Alsafwani, Parvez Khan, Dhananjay D. Shinde, Subodh M. Lele, Lynette M. Smith, Mohd W. Nasser, Surinder K. Batra, Apar Kishor Ganti, Imayavaramban Lakshmanan
St6galnac-I Regulates Tumor Cell Sialylation Via Nectin2/Muc5ac-Mediated Immunosuppression And Angiogenesis In Non-Small Cell Lung Cancer, Muthamil Iniyan Appadurai, Sanjib Chaudhary, Ashu Shah, Gopalakrishnan Natarajan, Zahraa W. Alsafwani, Parvez Khan, Dhananjay D. Shinde, Subodh M. Lele, Lynette M. Smith, Mohd W. Nasser, Surinder K. Batra, Apar Kishor Ganti, Imayavaramban Lakshmanan
Journal Articles: Biochemistry & Molecular Biology
Glycosylation controls immune evasion, tumor progression, and metastasis. However, how tumor cell sialylation regulates immune evasion remains poorly characterized. ST6GalNAc-I, a sialyltransferase that conjugates sialic acid to the glycans in glycoproteins, was overexpressed in an aggressive-type KPA (KrasG12D/+ Trp53R172H/+ Ad-Cre) lung adenocarcinoma (LUAD) model and patient samples. Proteomic and biochemical analysis indicated that ST6GalNAc-I mediated NECTIN2 sialylation in LUAD cells. ST6GalNAc-I-deficient tumor cells cocultured with T cells were more susceptible to T cell-mediated tumor cell killing, indicating a key role for NECTIN2 in T cell dysfunction. Mice injected with St6galnac-I-knockdown syngeneic cells showed reduced lung tumor incidence and Nectin2/Tigit-associated immunosuppression. …
Clinical Benefit Analysis Of Modified Motion Management Protocols, Dyanne S. Macalinao
Clinical Benefit Analysis Of Modified Motion Management Protocols, Dyanne S. Macalinao
UNLV Theses, Dissertations, Professional Papers, and Capstones
Radiation therapy is crucial for treating cancer, using ionizing radiation to target and destroy cancer cells. This radiation is produced by machines like linear accelerators or through natural radioactive decay. Radiation therapy treatment planning involves prescribing doses and contouring target areas. However, managing tumors that move with breathing, such as in the lungs, remains a major challenge. Tumor motion exceeding 5 mm, as outlined in the AAPM’s Task Group 76, can compromise treatment accuracy, risking underdosing the tumor and overdosing healthy tissue. This issue is especially critical in high dose treatments like stereotactic body radiation therapy (SBRT). TG-76 provides different …
Effects Of Altered Somatosensory Input On Gait Kinetics And Kinematics Via Different Footwear In Individuals With Chronic Post-Stroke Hemiparesis, Daniela Casillas, Lesley Ruiz
Effects Of Altered Somatosensory Input On Gait Kinetics And Kinematics Via Different Footwear In Individuals With Chronic Post-Stroke Hemiparesis, Daniela Casillas, Lesley Ruiz
UNLV Theses, Dissertations, Professional Papers, and Capstones
Purpose/Hypothesis: Individuals with post-stroke hemiparesis walk with significant asymmetries, leading to slow, effortful walking, and a high risk of falls. One contributing factor is altered sensation on the plantar surface. Studies examining altered somatosensory input via insoles, vibration and other tactile stimuli observed improvements in hemiparesis gait. This study investigates whether altering somatosensory input through different footwear can affect kinetics, kinematics and muscle activity during walking post-stroke. We hypothesized the barefoot conditions would have increased dorsiflexion (heel-strike, swing), increased plantarflexion during toe-off, increased muscle activity and kinetics, compared to memory foam conditions.
Participants: 13 individuals with chronic post-stroke hemiparesis (4F/9M, …
Long-Term Efficacy Of Pembrolizumab And The Clinical Utility Of Ctdna In Locally Advanced Dmmr/Msi-H Solid Tumors, Michael Lapelusa, Wei Qiao, Bryan Iorgulescu, Francis San Lucas, Keyur Patel, Deepak Bhamidipati, Jane Varkey Thomas, Nancy You, Wai Chin Foo, Dipen Maru, Selvi Thirumurthi, Van Morris, Scott Kopetz, Michael Overman, Kaysia Ludford
Long-Term Efficacy Of Pembrolizumab And The Clinical Utility Of Ctdna In Locally Advanced Dmmr/Msi-H Solid Tumors, Michael Lapelusa, Wei Qiao, Bryan Iorgulescu, Francis San Lucas, Keyur Patel, Deepak Bhamidipati, Jane Varkey Thomas, Nancy You, Wai Chin Foo, Dipen Maru, Selvi Thirumurthi, Van Morris, Scott Kopetz, Michael Overman, Kaysia Ludford
Faculty, Staff and Student Publications
Neoadjuvant immunotherapy can induce pathologic complete response (pCR) in patients with localized deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) tumors. The long-term outcomes of these patients are unknown, as is the clinical utility of measuring circulating tumor DNA (ctDNA). Follow-up was evaluated in patients enrolled in a phase II trial (NCT04082572) that evaluated the efficacy and safety of pembrolizumab in patients with localized dMMR/MSI-H tumors. The primary outcomes of this trial have previously been reported. 3-year EFS and OS rates were 80% (95% CI: 66% - 93%) and 94% (95% CI: 86% - 100%). Patients without detectable ctDNA after pembrolizumab had …
Ubiquitin-Conjugating Enzyme Ube2n Modulates Proteostasis In Immunoproteasome-Positive Acute Myeloid Leukemia, Chiharu Ishikawa, Laura Barreyro, Avery M Sampson, Kathleen M Hueneman, Kwangmin Choi, Sophia Y Philbrook, Issac Choi, Lyndsey C Bolanos, Mark Wunderlich, Andrew G Volk, Stephanie S Watowich, Kenneth D Greis, Daniel T Starczynowski
Ubiquitin-Conjugating Enzyme Ube2n Modulates Proteostasis In Immunoproteasome-Positive Acute Myeloid Leukemia, Chiharu Ishikawa, Laura Barreyro, Avery M Sampson, Kathleen M Hueneman, Kwangmin Choi, Sophia Y Philbrook, Issac Choi, Lyndsey C Bolanos, Mark Wunderlich, Andrew G Volk, Stephanie S Watowich, Kenneth D Greis, Daniel T Starczynowski
Faculty, Staff and Student Publications
Altered protein homeostasis through proteasomal degradation of ubiquitinated proteins is a hallmark of many cancers. Ubiquitination, coordinated by E1, E2, and E3 enzymes, involves up to 40 E2-conjugating enzymes in humans to specify substrates and ubiquitin linkages. In a screen for E2 dependencies in acute myeloid leukemia (AML), ubiquitin conjugating enzyme E2 N (UBE2N) emerged as the top candidate. To investigate UBE2N's role in AML, we characterized an enzymatically defective mouse model of UBE2N, revealing UBE2N's requirement in AML without an impact on normal hematopoiesis. Unlike other E2s, which mediate lysine-48 (K48) polyubiquitination and degradation of proteins, UBE2N primarily synthesizes …
G-Quadruplex Stabilizer Cx-5461 Effectively Combines With Radiotherapy To Target Α-Thalassemia/Mental Retardation X-Linked-Deficient Malignant Glioma, Sharvari Dharmaiah, Prit Benny Malgulwar, William E Johnson, Brandon A Chen, Vladislav Sharin, Benjamin T Whitfield, Christian Alvarez, Vasudev Tadimeti, Ahsan S Farooqi, Jason T Huse
G-Quadruplex Stabilizer Cx-5461 Effectively Combines With Radiotherapy To Target Α-Thalassemia/Mental Retardation X-Linked-Deficient Malignant Glioma, Sharvari Dharmaiah, Prit Benny Malgulwar, William E Johnson, Brandon A Chen, Vladislav Sharin, Benjamin T Whitfield, Christian Alvarez, Vasudev Tadimeti, Ahsan S Farooqi, Jason T Huse
Faculty, Staff and Student Publications
Background: Inactivation of α-thalassemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures, enhancing replication stress and genomic instability. Building on earlier work, we evaluated the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in ATRX-deficient preclinical glioma models.
Methods: Using the G4 stabilizer CX-5461, we treated patient-derived glioma stem cells (GSCs) in vitro and GSC flank and intracranial murine xenografts in vivo to evaluate efficacy as both a single agent and in combination with ionizing radiation (IR), the …
Development And Validation Of A Clinical Risk Model For Postoperative Outcome In Newly Diagnosed Glioblastoma: A Report Of The Rano Resect Group, Philipp Karschnia, Jacob S Young, Gilbert C Youssef, Antonio Dono, Levin Häni, Tommaso Sciortino, Francesco Bruno, Stephanie T Juenger, Nico Teske, Jorg Dietrich, Michael Weller, Michael A Vogelbaum, Martin Van Den Bent, Juergen Beck, Niklas Thon, Jasper K W Gerritsen, Shawn Hervey-Jumper, Daniel P Cahill, Susan M Chang, Roberta Rudà, Lorenzo Bello, Oliver Schnell, Yoshua Esquenazi, Maximilian I Ruge, Stefan J Grau, Raymond Y Huang, Patrick Y Wen, Mitchel S Berger, Annette M Molinaro, Joerg-Christian Tonn
Development And Validation Of A Clinical Risk Model For Postoperative Outcome In Newly Diagnosed Glioblastoma: A Report Of The Rano Resect Group, Philipp Karschnia, Jacob S Young, Gilbert C Youssef, Antonio Dono, Levin Häni, Tommaso Sciortino, Francesco Bruno, Stephanie T Juenger, Nico Teske, Jorg Dietrich, Michael Weller, Michael A Vogelbaum, Martin Van Den Bent, Juergen Beck, Niklas Thon, Jasper K W Gerritsen, Shawn Hervey-Jumper, Daniel P Cahill, Susan M Chang, Roberta Rudà, Lorenzo Bello, Oliver Schnell, Yoshua Esquenazi, Maximilian I Ruge, Stefan J Grau, Raymond Y Huang, Patrick Y Wen, Mitchel S Berger, Annette M Molinaro, Joerg-Christian Tonn
Faculty, Staff and Student Publications
Background: Following surgery, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aimed (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool.
Methods: The response assessment in neuro-oncology (RANO) resect group retrospectively compiled an international, seven-center training cohort of patients with newly diagnosed glioblastoma. The combined associations of residual tumor with molecular or clinical factors and survival were analyzed, and recursive partitioning analysis was performed for risk modeling. The resulting model …
Assessing The Effects Of Streptozotocin-Induced Hyperglycemia On Amyloid Beta Accumulation And Cognitive Behavior In A Mouse Model Of Alzheimer’S Disease-Related Pathology, Andrew Adonay Ortiz
Assessing The Effects Of Streptozotocin-Induced Hyperglycemia On Amyloid Beta Accumulation And Cognitive Behavior In A Mouse Model Of Alzheimer’S Disease-Related Pathology, Andrew Adonay Ortiz
UNLV Theses, Dissertations, Professional Papers, and Capstones
Alzheimer’s disease (AD) is an irreversible and devastating neurodegenerative disease characterized by progressive synaptic, dendritic, glial, and neuronal loss, collectively leading to impairments in learning, memory, and deterioration of cognitive and behavioral functions. AD is the most common form of dementia accounting for 60-80% of all cases. AD affects approximately 7 million Americans and is the 6th leading cause of death in the US. Furthermore, by 2050, the US is projected to spend over $1.1 trillion on AD-related treatments. Pathological hallmarks of AD include beta-amyloid (Aβ) plaques, intracellular neurofibrillary tangles (NFTs), and chronic neuroinflammation, which can promote and exacerbate both …
The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons Of The Transcriptomic Landscapes Across Mouse Models, Ling Cai, Fangjiang Wu, Qinbo Zhou, Ying Gao, Bo Yao, Ralph J Deberardinis, George K Acquaah-Mensah, Vassilis Aidinis, Jennifer E Beane, Shyam Biswal, Ting Chen, Carla P Concepcion-Crisol, Barbara M Grüner, Deshui Jia, Robert A Jones, Jonathan M Kurie, Min Gyu Lee, Per Lindahl, Yonathan Lissanu, Corina Lorz, David Macpherson, Rosanna Martinelli, Pawel K Mazur, Sarah A Mazzilli, Shinji Mii, Herwig P Moll, Roger A Moorehead, Edward E Morrisey, Sheng Rong Ng, Matthew G Oser, Arun R Pandiri, Charles A Powell, Giorgio Ramadori, Mirentxu Santos, Eric L Snyder, Rocio Sotillo, Kang-Yi Su, Tetsuro Taki, Kekoa Taparra, Phuoc T Tran, Yifeng Xia, J Edward Van Veen, Monte M Winslow, Guanghua Xiao, Charles M Rudin, Trudy G Oliver, Yang Xie, John D Minna
The Lung Cancer Autochthonous Model Gene Expression Database Enables Cross-Study Comparisons Of The Transcriptomic Landscapes Across Mouse Models, Ling Cai, Fangjiang Wu, Qinbo Zhou, Ying Gao, Bo Yao, Ralph J Deberardinis, George K Acquaah-Mensah, Vassilis Aidinis, Jennifer E Beane, Shyam Biswal, Ting Chen, Carla P Concepcion-Crisol, Barbara M Grüner, Deshui Jia, Robert A Jones, Jonathan M Kurie, Min Gyu Lee, Per Lindahl, Yonathan Lissanu, Corina Lorz, David Macpherson, Rosanna Martinelli, Pawel K Mazur, Sarah A Mazzilli, Shinji Mii, Herwig P Moll, Roger A Moorehead, Edward E Morrisey, Sheng Rong Ng, Matthew G Oser, Arun R Pandiri, Charles A Powell, Giorgio Ramadori, Mirentxu Santos, Eric L Snyder, Rocio Sotillo, Kang-Yi Su, Tetsuro Taki, Kekoa Taparra, Phuoc T Tran, Yifeng Xia, J Edward Van Veen, Monte M Winslow, Guanghua Xiao, Charles M Rudin, Trudy G Oliver, Yang Xie, John D Minna
Faculty, Staff and Student Publications
Lung cancer, the leading cause of cancer mortality, exhibits diverse histological subtypes and genetic complexities. Numerous preclinical mouse models have been developed to study lung cancer, but data from these models are disparate, siloed, and difficult to compare in a centralized fashion. In this study, we established the Lung Cancer Autochthonous Model Gene Expression Database (LCAMGDB), an extensive repository of 1,354 samples from 77 transcriptomic datasets covering 974 samples from genetically engineered mouse models (GEMMs), 368 samples from carcinogen-induced models, and 12 samples from a spontaneous model. Meticulous curation and collaboration with data depositors produced a robust and comprehensive database, …
Investigating The Influence Of Environmental Stressors To Exopolysaccharide Production In Soil Cyanobacteria: Genomic And Physiological Perspectives, Benjy Sedano-Herrera
Investigating The Influence Of Environmental Stressors To Exopolysaccharide Production In Soil Cyanobacteria: Genomic And Physiological Perspectives, Benjy Sedano-Herrera
UNLV Theses, Dissertations, Professional Papers, and Capstones
Cyanobacteria are photosynthetic microbes with essential roles in Earth’s ecosystems. The secretion of long–chain polysaccharides, known as exopolysaccharides (EPS), is a key trait facilitating cyanobacterial adaptation to diverse ecosystems. Genomics studies have shown that aquatic cyanobacteria harbor multiple gene copies encoding EPS export proteins, likely conferring a selective advantage in lakes or oceans. In addition, physiological experiments showed that nutrient limitation in aquatic habitats influences EPS production, affecting cyanobacterial fitness. However, whether terrestrial cyanobacteria also harbor multiple EPS-related genes and how nutrient limitation impacts their EPS production is not well understood.In the first chapter of my thesis, we investigated the …
Core Temperature While Swimming In Warm Open Water With And Without A Wetsuit, Katsiaryna Afanasyeva
Core Temperature While Swimming In Warm Open Water With And Without A Wetsuit, Katsiaryna Afanasyeva
UNLV Theses, Dissertations, Professional Papers, and Capstones
Triathlon is a popular sport which attract participants from all over the world. In general, triathlon is a safe sport with risk of death being about 1.74 deaths per 100,000 participants (Harris et al., 2017). The swimming portion of the race can be dangerous, posing particular risks due to open water conditions and the physical demands of the event. This study investigated the effects of wetsuit use on core temperature in warm open-water swimming (27.9–28.3°C). Four experienced triathletes (2 males, 2 females; age 49.50 ± 7.83 years) completed two 700-meter open-water swims at a submaximal pace—once wearing their personal full-sleeve …
Patterns In Antibiotic Susceptibility Before And After Covid-19, Jessica Freely
Patterns In Antibiotic Susceptibility Before And After Covid-19, Jessica Freely
UNLV Theses, Dissertations, Professional Papers, and Capstones
The COVID-19 pandemic led to a surge in antibiotic use, despite the viral nature of the disease. This widespread and often unnecessary use of antibiotics poses a serious threat on global health by accelerating the development of antibiotic resistance. Healthcare professionals utilize strategies, including Antibiotic Stewardship Programs (ASPs) and the use of antibiograms to mitigate the growing threat of antibiotic resistance. Antibiograms are tools used in healthcare settings to summarize and track bacterial susceptibility to various antibiotics. They provide clinicians critical information to guide selection of effective antibiotic treatment and monitor resistance trends overtime. The Centers for Disease Control and …