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Articles 6841 - 6870 of 21765

Full-Text Articles in Medicine and Health Sciences

Real-World Experience Of Patients With Multiple Myeloma Receiving Ide-Cel After A Prior Bcma-Targeted Therapy, Christopher J Ferreri, Michelle A T Hildebrandt, Hamza Hashmi, Leyla O Shune, Joseph P Mcguirk, Douglas W Sborov, Charlotte B Wagner, M Hakan Kocoglu, Aaron Rapoport, Shebli Atrash, Peter M Voorhees, Jack Khouri, Danai Dima, Aimaz Afrough, Gurbakhash Kaur, Larry D Anderson, Gary Simmons, James A Davis, Nilesh Kalariya, Lauren C Peres, Yi Lin, Murali Janakiram, Omar Nadeem, Melissa Alsina, Frederick L Locke, Surbhi Sidana, Doris K Hansen, Krina K Patel, Omar Alexis Castaneda Puglianini Aug 2023

Real-World Experience Of Patients With Multiple Myeloma Receiving Ide-Cel After A Prior Bcma-Targeted Therapy, Christopher J Ferreri, Michelle A T Hildebrandt, Hamza Hashmi, Leyla O Shune, Joseph P Mcguirk, Douglas W Sborov, Charlotte B Wagner, M Hakan Kocoglu, Aaron Rapoport, Shebli Atrash, Peter M Voorhees, Jack Khouri, Danai Dima, Aimaz Afrough, Gurbakhash Kaur, Larry D Anderson, Gary Simmons, James A Davis, Nilesh Kalariya, Lauren C Peres, Yi Lin, Murali Janakiram, Omar Nadeem, Melissa Alsina, Frederick L Locke, Surbhi Sidana, Doris K Hansen, Krina K Patel, Omar Alexis Castaneda Puglianini

Faculty, Staff and Student Publications

Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior …


A De Novo Missense Variant In Ezh1 Associated With Developmental Delay Exhibits Functional Deficits In Drosophila Melanogaster, Sharayu V Jangam, Lauren C Briere, Kristy L Jay, Jonathan C Andrews, Melissa A Walker, Lance H Rodan, Frances A High, Undiagnosed Diseases Network, Shinya Yamamoto, David A Sweetser, Michael F Wangler Aug 2023

A De Novo Missense Variant In Ezh1 Associated With Developmental Delay Exhibits Functional Deficits In Drosophila Melanogaster, Sharayu V Jangam, Lauren C Briere, Kristy L Jay, Jonathan C Andrews, Melissa A Walker, Lance H Rodan, Frances A High, Undiagnosed Diseases Network, Shinya Yamamoto, David A Sweetser, Michael F Wangler

Faculty, Staff and Students Publications

EZH1, a polycomb repressive complex-2 component, is involved in a myriad of cellular processes. EZH1 represses transcription of downstream target genes through histone 3 lysine27 (H3K27) trimethylation (H3K27me3). Genetic variants in histone modifiers have been associated with developmental disorders, while EZH1 has not yet been linked to any human disease. However, the paralog EZH2 is associated with Weaver syndrome. Here we report a previously undiagnosed individual with a novel neurodevelopmental phenotype identified to have a de novo missense variant in EZH1 through exome sequencing. The individual presented in infancy with neurodevelopmental delay and hypotonia and was later noted to have …


Evaluation Of The Virulence Potential Of Avian Pathogenic Escherichia Coli Isolated From Broiler Breeders With Colibacillosis In Mississippi, Jiddu Joseph Aug 2023

Evaluation Of The Virulence Potential Of Avian Pathogenic Escherichia Coli Isolated From Broiler Breeders With Colibacillosis In Mississippi, Jiddu Joseph

Theses and Dissertations

Avian pathogenic Escherichia coli (APEC) is a bacterium that is responsible for colibacillosis in birds. However, information about broiler breeder APEC isolates is limited, but the data is critical due to the transfer of this bacteria down the production pyramid to progenies resulting in high mortality. Therefore, we evaluated the phenotypic virulence characteristics of 28 isolates using embryo lethality and day-old chick challenge assays. Also, the in vitro adhesion and invasion potential of selected nine isolates were identified. Results showed more than 1/3rd of the isolates were highly virulent and the virulence increased as the number of virulence-associated genes …


Effectiveness Of Intervention Studies Based On Diet And/Or Physical Activity In Treatment, Prevention, And Management Of Diabetes Among South Asians: A Systematic Review, Ishaan Arora Aug 2023

Effectiveness Of Intervention Studies Based On Diet And/Or Physical Activity In Treatment, Prevention, And Management Of Diabetes Among South Asians: A Systematic Review, Ishaan Arora

Theses and Dissertations

The purpose of this study was to describe diet and/or physical activity-based interventions and their control in cardiometabolic risk factors of diabetes for the South Asian (SA) population. A systematic review was conducted in accordance with the PRISMA guidelines. Seventeen randomized control trials meeting the inclusion criteria were included for analysis. Interventions with type-2 diabetic SA showed significant improvements in HbA1c% (4/5 studies), fasting blood glucose (3/4 studies), and postprandial glucose (2/2 studies). Interventions with at-risk/prediabetic and non-diabetic SA showed a modest change in overall outcomes, with significant change reported for post-prandial insulin (3/4 studies), BMI and weight (2/4 studies), …


Adherence To A Gluten-Free Diet And Depression, And Nutrient Distribution In Participants With Celiac Disease, Mohammad K. Shushari Aug 2023

Adherence To A Gluten-Free Diet And Depression, And Nutrient Distribution In Participants With Celiac Disease, Mohammad K. Shushari

Theses and Dissertations

Celiac disease (CD), an autoimmune disorder affecting millions of Americans, poses significant obstacles leading to a normal life. With no known cure, adherence to a strict glutenfree diet (GFD) is essential. However, the cost and limited availability of gluten-free alternatives can burden individuals with CD. Additionally, factors such as socioeconomic status, nutrient deficiencies, and the nature of the disease may contribute to mental health issues. This study aimed to investigate the influence of adherence to a GFD on depression in CD patients. The prevalence of depression among individuals with CD from diverse backgrounds was examined, along with the analysis of …


Metabolic Adaptation Of Staphylococcus Aureus Pathogenesis And Therapeutic Approach In Diabetic Foot Ulcers., Carol L. Baker Aug 2023

Metabolic Adaptation Of Staphylococcus Aureus Pathogenesis And Therapeutic Approach In Diabetic Foot Ulcers., Carol L. Baker

Theses and Dissertations

37.3 million Americans (11.2% of the US population) currently have Type 2 diabetes mellitus (T2DM) with over 1.5 million new cases being diagnosed each year. The multifactorial etiology of the patient having neuropathy, overweight/obesity, foot deformities, ischemia, and infection leads to a condition called diabetic foot ulcer (DFU). One in six patients with a DFU will require amputation with infected DFUs have a 155-fold increased risk of amputation. Staphylococcus aureus is the most common bacteria isolated from severe DFU infections that require amputation. Interestingly, diabetics are more heavily colonized with S. aureus compared to non-diabetics suggesting a unique advantageous adaptation …


Sars-Cov-2 Infection In Unvaccinated High-Risk Pregnant Women In The Bronx, Ny, Usa Is Associated With Decreased Apgar Scores And Placental Villous Infarcts, Sandra E. Reznik, Patricia M. Vuguin, Alexa Cohen, Rasha Khoury, Olivier Loudig, Ridin Balakrishnan, Susan A. Fineberg, Francine Hughes, Malini Harigopal, Maureen J. Charron Aug 2023

Sars-Cov-2 Infection In Unvaccinated High-Risk Pregnant Women In The Bronx, Ny, Usa Is Associated With Decreased Apgar Scores And Placental Villous Infarcts, Sandra E. Reznik, Patricia M. Vuguin, Alexa Cohen, Rasha Khoury, Olivier Loudig, Ridin Balakrishnan, Susan A. Fineberg, Francine Hughes, Malini Harigopal, Maureen J. Charron

School of Medicine Faculty Publications

Babies born to severe acute respiratory syndrome corona virus-2 (SARS-CoV-2)-infected mothers are at greater risk for perinatal morbidity and more likely to receive a neurodevelopmental diagnosis in the first year of life. However, the effect of maternal infection on placental function and neonatal outcomes varies depending upon the patient population. We set out to test our hypothesis that maternal SARS-CoV-2 infection in our underserved, socioeconomically disadvantaged, mostly unvaccinated, predominantly African American and Latina population in the Bronx, NY would have effects evident at birth. Under IRB approval, 56 SARS-CoV-2-positive patients infected during the “first wave” of the pandemic with alpha …


Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke Aug 2023

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …


Csf1r Regulates Schizophrenia-Related Stress Response And Vascular Association Of Microglia/Macrophages, Ling Yan, Yanli Li, Fengmei Fan, Mengzhuang Gou, Fangling Xuan, Wei Feng, Keerthana Chithanathan, Wei Li, Junchao Huang, Hongna Li, Wenjin Chen, Baopeng Tian, Zhiren Wang, Shuping Tan, Alexander Zharkovsky, L Elliot Hong, Yunlong Tan, Li Tian Aug 2023

Csf1r Regulates Schizophrenia-Related Stress Response And Vascular Association Of Microglia/Macrophages, Ling Yan, Yanli Li, Fengmei Fan, Mengzhuang Gou, Fangling Xuan, Wei Feng, Keerthana Chithanathan, Wei Li, Junchao Huang, Hongna Li, Wenjin Chen, Baopeng Tian, Zhiren Wang, Shuping Tan, Alexander Zharkovsky, L Elliot Hong, Yunlong Tan, Li Tian

Faculty, Staff and Student Publications

BACKGROUND: Microglia are known to regulate stress and anxiety in both humans and animal models. Psychosocial stress is the most common risk factor for the development of schizophrenia. However, how microglia/brain macrophages contribute to schizophrenia is not well established. We hypothesized that effector molecules expressed in microglia/macrophages were involved in schizophrenia via regulating stress susceptibility.

METHODS: We recruited a cohort of first episode schizophrenia (FES) patients (n = 51) and age- and sex-paired healthy controls (HCs) (n = 46) with evaluated stress perception. We performed blood RNA-sequencing (RNA-seq) and brain magnetic resonance imaging, and measured plasma level of colony stimulating …


Spatial Transcriptomics Of Intraductal Papillary Mucinous Neoplasms Of The Pancreas Identifies Nkx6-2 As A Driver Of Gastric Differentiation And Indolent Biological Potential, Marta Sans, Yuki Makino, Jimin Min, Kimal I Rajapakshe, Michele Yip-Schneider, C Max Schmidt, Mark W Hurd, Jared K Burks, Javier A Gomez, Fredrik I Thege, Johannes F Fahrmann, Robert A Wolff, Michael P Kim, Paola A Guerrero, Anirban Maitra Aug 2023

Spatial Transcriptomics Of Intraductal Papillary Mucinous Neoplasms Of The Pancreas Identifies Nkx6-2 As A Driver Of Gastric Differentiation And Indolent Biological Potential, Marta Sans, Yuki Makino, Jimin Min, Kimal I Rajapakshe, Michele Yip-Schneider, C Max Schmidt, Mark W Hurd, Jared K Burks, Javier A Gomez, Fredrik I Thege, Johannes F Fahrmann, Robert A Wolff, Michael P Kim, Paola A Guerrero, Anirban Maitra

Faculty, Staff and Student Publications

Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas are bona fide precursor lesions of pancreatic ductal adenocarcinoma (PDAC). The most common subtype of IPMNs harbor a gastric foveolar-type epithelium, and these low-grade mucinous neoplasms are harbingers of IPMNs with high-grade dysplasia and cancer. The molecular underpinning of gastric differentiation in IPMNs is unknown, although identifying drivers of this indolent phenotype might enable opportunities for intercepting progression to high-grade IPMN and cancer. We conducted spatial transcriptomics on a cohort of IPMNs, followed by orthogonal and cross species validation studies, which established the transcription factor NKX6-2 as a key determinant of gastric …


The Co-Delivery Of Adenovirus-Based Immune Checkpoint Vaccine Elicits A Potent Anti-Tumor Effect In Renal Carcinoma, Nan Jiang, Yanyan Zheng, Jiage Ding, Jiawei Wang, Fei Zhu, Meng Wang, Navid Sobhani, Praveen Neeli, Gang Wang, Hailong Li, Junnian Zheng, Dafei Chai Aug 2023

The Co-Delivery Of Adenovirus-Based Immune Checkpoint Vaccine Elicits A Potent Anti-Tumor Effect In Renal Carcinoma, Nan Jiang, Yanyan Zheng, Jiage Ding, Jiawei Wang, Fei Zhu, Meng Wang, Navid Sobhani, Praveen Neeli, Gang Wang, Hailong Li, Junnian Zheng, Dafei Chai

Faculty, Staff and Students Publications

Immune-based checkpoint therapy has made significant progress in cancer treatment, but its therapeutic effect is limited. A replication-defective adenovirus (Ad) vaccine encoding tumor antigen carbonic anhydrase IX (CAIX) combined with Ad-encoding immune checkpoint PD-L1 was developed to treat renal carcinoma. Three tumor models, subcutaneous, lung metastasis and orthotopic tumor were established, and Ad vaccines were used to immunize them and evaluate the vaccine's therapeutic effect. Compared to the single Ad vaccine group, the subcutaneous tumor growth was significantly reduced in Ad-CAIX/Ad-PD-L1 combination group. Co-immunization of Ad-CAIX/Ad-PD-L1 enhanced the induction and maturation of CD11c


Transmission Of Yellow Fever Vaccine Virus Through Blood Transfusion And Organ Transplantation In The Usa In 2021: Report Of An Investigation, Carolyn V. Gould, Rebecca J. Free, Julu Bhatnagar, Raymond A. Soto, Tricia L. Royer, Warren R. Maley, Sean Moss, Matthew A. Berk, Rebecca Craig-Shapiro, Rosy Priya L. Kodiyanplakkal, Lars F. Westblade, Thangamani Muthukumar, Yoram A. Puius, Amresh Raina, Azam Hadi, Kymberly A. Gyure, Danielle Trief, Marcus Pereira, Matthew J. Kuehnert, Vennus Ballen, Debra A. Kessler, Kimberly Dailey, Charles Omura, Thuy Doan, Steve Miller, Michael R. Wilson, Jennifer A. Lehman, Jana M. Ritter, Elizabeth Lee, Luciana Silva-Flannery, Sarah Reagan-Steiner, Jason O. Velez, Janeen J. Laven, Kelly A. Fitzpatrick, Amanda Panella, Emily H. Davis, Holly R. Hughes, Aaron C. Brault, Kirsten St George, Amy B. Dean, Joel Ackelsberg, Sridhar V. Basavaraju, Charles Y. Chiu, J. Erin Staples Aug 2023

Transmission Of Yellow Fever Vaccine Virus Through Blood Transfusion And Organ Transplantation In The Usa In 2021: Report Of An Investigation, Carolyn V. Gould, Rebecca J. Free, Julu Bhatnagar, Raymond A. Soto, Tricia L. Royer, Warren R. Maley, Sean Moss, Matthew A. Berk, Rebecca Craig-Shapiro, Rosy Priya L. Kodiyanplakkal, Lars F. Westblade, Thangamani Muthukumar, Yoram A. Puius, Amresh Raina, Azam Hadi, Kymberly A. Gyure, Danielle Trief, Marcus Pereira, Matthew J. Kuehnert, Vennus Ballen, Debra A. Kessler, Kimberly Dailey, Charles Omura, Thuy Doan, Steve Miller, Michael R. Wilson, Jennifer A. Lehman, Jana M. Ritter, Elizabeth Lee, Luciana Silva-Flannery, Sarah Reagan-Steiner, Jason O. Velez, Janeen J. Laven, Kelly A. Fitzpatrick, Amanda Panella, Emily H. Davis, Holly R. Hughes, Aaron C. Brault, Kirsten St George, Amy B. Dean, Joel Ackelsberg, Sridhar V. Basavaraju, Charles Y. Chiu, J. Erin Staples

Department of Medicine Faculty Papers

BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients.

METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by …


Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu Aug 2023

Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu

School of Medicine Faculty Publications

Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used …


Two Structurally Defined Aβ Polymorphs Promote Different Pathological Changes In Susceptible Mice, Ruben Gomez-Gutierrez, Ujjayini Ghosh, Wai-Ming Yau, Nazaret Gamez, Katherine Do, Carlos Kramm, Hamid Shirani, Laura Vegas-Gomez, Jonathan Schulz, Ines Moreno-Gonzalez, Antonia Gutierrez, K Peter R Nilsson, Robert Tycko, Claudio Soto, Rodrigo Morales Aug 2023

Two Structurally Defined Aβ Polymorphs Promote Different Pathological Changes In Susceptible Mice, Ruben Gomez-Gutierrez, Ujjayini Ghosh, Wai-Ming Yau, Nazaret Gamez, Katherine Do, Carlos Kramm, Hamid Shirani, Laura Vegas-Gomez, Jonathan Schulz, Ines Moreno-Gonzalez, Antonia Gutierrez, K Peter R Nilsson, Robert Tycko, Claudio Soto, Rodrigo Morales

Faculty, Staff and Student Publications

Misfolded Aβ is involved in the progression of Alzheimer's disease (AD). However, the role of its polymorphic variants or conformational strains in AD pathogenesis is not fully understood. Here, we study the seeding properties of two structurally defined synthetic misfolded Aβ strains (termed 2F and 3F) using in vitro and in vivo assays. We show that 2F and 3F strains differ in their biochemical properties, including resistance to proteolysis, binding to strain-specific dyes, and in vitro seeding. Injection of these strains into a transgenic mouse model produces different pathological features, namely different rates of aggregation, formation of different plaque types, …


Mavs Signaling Is Required For Preventing Persistent Chikungunya Heart Infection And Chronic Vascular Tissue Inflammation, Maria G Noval, Sophie N Spector, Eric Bartnicki, Franco Izzo, Navneet Narula, Stephen T Yeung, Payal Damani-Yokota, M Zahidunnabi Dewan, Valeria Mezzano, Bruno A Rodriguez-Rodriguez, Cynthia Loomis, Kamal M Khanna, Kenneth A Stapleford Aug 2023

Mavs Signaling Is Required For Preventing Persistent Chikungunya Heart Infection And Chronic Vascular Tissue Inflammation, Maria G Noval, Sophie N Spector, Eric Bartnicki, Franco Izzo, Navneet Narula, Stephen T Yeung, Payal Damani-Yokota, M Zahidunnabi Dewan, Valeria Mezzano, Bruno A Rodriguez-Rodriguez, Cynthia Loomis, Kamal M Khanna, Kenneth A Stapleford

Faculty, Staff and Student Publications

Chikungunya virus (CHIKV) infection has been associated with severe cardiac manifestations, yet, how CHIKV infection leads to heart disease remains unknown. Here, we leveraged both mouse models and human primary cardiac cells to define the mechanisms of CHIKV heart infection. Using an immunocompetent mouse model of CHIKV infection as well as human primary cardiac cells, we demonstrate that CHIKV directly infects and actively replicates in cardiac fibroblasts. In immunocompetent mice, CHIKV is cleared from cardiac tissue without significant damage through the induction of a local type I interferon response from both infected and non-infected cardiac cells. Using mice deficient in …


Persistence To Anti-Cgrp Monoclonal Antibodies And Onabotulinumtoxina Among Patients With Migraine: A Retrospective Cohort Study, Larry Charleston, Brian Talon, Christine Sullivan, Carlton Anderson, Steven Kymes, Stephane A. Regnier, Seema Soni-Brahmbhatt, Stephanie J. Nahas Aug 2023

Persistence To Anti-Cgrp Monoclonal Antibodies And Onabotulinumtoxina Among Patients With Migraine: A Retrospective Cohort Study, Larry Charleston, Brian Talon, Christine Sullivan, Carlton Anderson, Steven Kymes, Stephane A. Regnier, Seema Soni-Brahmbhatt, Stephanie J. Nahas

Department of Jefferson Headache Center Papers and Presentations

BACKGROUND: To date, real-world evidence on persistence to anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) or onabotulinumtoxinA have excluded eptinezumab. This retrospective cohort study was performed to compare treatment persistency among patients with migraine on anti-CGRP mAbs (erenumab, fremanezumab, galcanezumab, or eptinezumab) or onabotulinumtoxinA.

METHODS: This retrospective study used IQVIA PharmMetrics data. Adult patients with migraine treated with an anti-CGRP mAb or onabotulinumtoxinA who had 12 months of continuous insurance enrollment before starting treatment were included. A "most recent treatment episode" analysis was used in which the most recent episode was defined as the latest treatment period with the same …


Probing Conformational Landscapes Of Binding And Allostery In The Sars-Cov-2 Omicron Variant Complexes Using Microsecond Atomistic Simulations And Perturbation-Based Profiling Approaches: Hidden Role Of Omicron Mutations As Modulators Of Allosteric Signaling And Epistatic Relationships, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao Aug 2023

Probing Conformational Landscapes Of Binding And Allostery In The Sars-Cov-2 Omicron Variant Complexes Using Microsecond Atomistic Simulations And Perturbation-Based Profiling Approaches: Hidden Role Of Omicron Mutations As Modulators Of Allosteric Signaling And Epistatic Relationships, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

In this study, we systematically examine the conformational dynamics, binding and allosteric communications in the Omicron BA.1, BA.2, BA.3 and BA.4/BA.5 spike protein complexes with the ACE2 host receptor using molecular dynamics simulations and perturbation-based network profiling approaches. Microsecond atomistic simulations provided a detailed characterization of the conformational landscapes and revealed the increased thermodynamic stabilization of the BA.2 variant which can be contrasted with the BA.4/BA.5 variants inducing a significant mobility of the complexes. Using the dynamics-based mutational scanning of spike residues, we identified structural stability and binding affinity hotspots in the Omicron complexes. Perturbation response scanning and network-based mutational …


Dietary Intake During A Pragmatic Cluster-Randomized Weight Loss Trial In An Underserved Population In Primary Care, John W. Apolzan, Corby K. Martin, Robert L. Newton, Candice A. Myers, Connie L. Arnold, Terry C. Davis, William D. Johnson, Dachuan Zhang, Christoph Höchsmann, Vivian A. Fonseca, Kara D. Denstel, Emily F. Mire, Benjamin F. Springgate, Carl J. Lavie, Peter T. Katzmarzyk, Phillip Brantley, Ronald Horswell, Tina K. Thethi, Jonathan Gugel, Eboni Price-Haywood, Kathleen B. Kennedy, Daniel F. Sarpong Aug 2023

Dietary Intake During A Pragmatic Cluster-Randomized Weight Loss Trial In An Underserved Population In Primary Care, John W. Apolzan, Corby K. Martin, Robert L. Newton, Candice A. Myers, Connie L. Arnold, Terry C. Davis, William D. Johnson, Dachuan Zhang, Christoph Höchsmann, Vivian A. Fonseca, Kara D. Denstel, Emily F. Mire, Benjamin F. Springgate, Carl J. Lavie, Peter T. Katzmarzyk, Phillip Brantley, Ronald Horswell, Tina K. Thethi, Jonathan Gugel, Eboni Price-Haywood, Kathleen B. Kennedy, Daniel F. Sarpong

School of Medicine Faculty Publications

Background: Currently there are limited data as to whether dietary intake can be improved during pragmatic weight loss interventions in primary care in underserved individuals. Methods: Patients with obesity were recruited into the PROPEL trial, which randomized 18 clinics to either an intensive lifestyle intervention (ILI) or usual care (UC). At baseline and months 6, 12, and 24, fruit and vegetable (F/V) intake and fat intake was determined. Outcomes were analyzed by repeated-measures linear mixed-effects multilevel models and regression models, which included random cluster (clinic) effects. Secondary analyses examined the effects of race, sex, age, and food security status. Results: …


Skp2-Mediated Mlkl Degradation Confers Cisplatin-Resistant In Non-Small Cell Lung Cancer Cells, Huiling Zhou, Li Zhou, Qing Guan, Xuyang Hou, Cong Wang, Lijun Liu, Jian Wang, Xinfang Yu, Wei Li, Haidan Liu Aug 2023

Skp2-Mediated Mlkl Degradation Confers Cisplatin-Resistant In Non-Small Cell Lung Cancer Cells, Huiling Zhou, Li Zhou, Qing Guan, Xuyang Hou, Cong Wang, Lijun Liu, Jian Wang, Xinfang Yu, Wei Li, Haidan Liu

Faculty, Staff and Students Publications

Non-small cell lung cancer (NSCLC) is the most prevalent type of cancer and the leading cause of cancer-related death. Chemotherapeutic resistance is a major obstacle in treating NSCLC patients. Here, we discovered that the E3 ligase Skp2 is overexpressed, accompanied by the downregulation of necroptosis-related regulator MLKL in human NSCLC tissues and cell lines. Knockdown of Skp2 inhibited viability, anchorage-independent growth, and in vivo tumor development of NSCLC cells. We also found that the Skp2 protein is negatively correlated with MLKL in NSCLC tissues. Moreover, Skp2 is increased and accompanied by an upregulation of MLKL ubiquitination and degradation in cisplatin-resistant …


Use Of Electronic Health Record Reminders To Improve Primary Care Providers’ Colorectal Cancer Screening Recommendations., Terra Renee Schrembs Aug 2023

Use Of Electronic Health Record Reminders To Improve Primary Care Providers’ Colorectal Cancer Screening Recommendations., Terra Renee Schrembs

Doctor of Nursing Practice Papers

Background: Colorectal cancer (CRC) is the third most common worldwide cause of cancer morbidity and mortality. CRC mortality is preventable through regular screening. Electronic health record (EHR) reminders for providers can increase providers’ CRC screening recommendations and lead to earlier CRC diagnosis. According to the National Cancer Institute’s Screening and Risk Factors Report for Kentucky by County 2008-2010, 62.7% of adults in a rural Kentucky county aged 50-75 had completed a home based FOBT in the past two years or have ever had a colorectal endoscopy.

Purpose: The purpose of this DNP project was to implement and evaluate an …


Causal Inference Methods For Estimation Of Survival And General Health Status Measures Of Alzheimer’S Disease Patients, Ehsan Yaghmaei Aug 2023

Causal Inference Methods For Estimation Of Survival And General Health Status Measures Of Alzheimer’S Disease Patients, Ehsan Yaghmaei

Computational and Data Sciences (PhD) Dissertations

Identifying optimal treatment options with respect to survival of Alzheimer's disease patients is crucially important and previously uninvestigated research question. Our objective was to estimate the causal effects of the most prevalent classes of Alzheimer’s disease drugs, Donepezil and Memantine, and their combined use on Survival and General Health Status Measures of Alzheimer's disease patients for the first five years after initial diagnosis. We carried out a thorough causal inference study using doubly robust estimators, nonparametric bootstrap confidence intervals, Bonferroni corrections for multiple comparisons and analyzing one of the largest high-quality medical databases containing millions of de-identified electronic health records …


From Myzocytosis To Cytostomal Nutrient Uptake And Transport By Intracellular Plasmodium Species, T. Y. Sam-Yellowe Aug 2023

From Myzocytosis To Cytostomal Nutrient Uptake And Transport By Intracellular Plasmodium Species, T. Y. Sam-Yellowe

Biological, Geological, and Environmental Faculty Publications

No abstract provided.


Enhancing Adherence To Best Practice Guidelines Related To Pressure Injury Prevention In The Operating Room At A Children's Hospital During Comprehensive Dental Procedures., Alyce Bailey Seaver Aug 2023

Enhancing Adherence To Best Practice Guidelines Related To Pressure Injury Prevention In The Operating Room At A Children's Hospital During Comprehensive Dental Procedures., Alyce Bailey Seaver

Doctor of Nursing Practice Papers

Background: 1,600,000 patients develop a hospital-acquired pressure injury every year, and 23% of these originate during surgery. Research has demonstrated that the incidence of hospital-acquired pressure injuries developing during surgery has risen over the past 5 years. This rise has been attributed to nurse circulators exhibiting poor knowledge regarding best practices for intraoperative patient positioning and intraoperative documentation that does not follow standards of care.

Purpose: This quality improvement project aimed to enhance circulator knowledge on best practices for intraoperative patient positioning and improve documentation of intraoperative patient positioning in the electronic medical record to comply with standards of …


Clinical And Environmental Factors Affecting The Survival Outcomes Among Stage 1a Tn0m0 First Primary Non-Small Cell Lung Carcinoma Patients In The United States., Naiya Patel Aug 2023

Clinical And Environmental Factors Affecting The Survival Outcomes Among Stage 1a Tn0m0 First Primary Non-Small Cell Lung Carcinoma Patients In The United States., Naiya Patel

Electronic Theses and Dissertations

Background: Lung cancer is the second leading cause of death in the United States (U.S.). The most prevalent histological type of lung cancer is Non-Small Cell Lung Cancer (NSCLC), which has an overall five years survival of 5% if left untreated. Therefore, early treatment of NSCLC is vital to improve overall survival (OS) outcomes. Several factors affect survival outcomes, which can be categorized as modifiable or non-modifiable. The difference in timely receipt of guideline-concordant treatment affects the survival outcomes of patients with stage 1A NSCLC. This dissertation explored factors that affect treatment and survival outcomes among stage 1A NSCLC patients …


Aurka Inhibition-Based Combination Therapy Approaches In Glioblastoma., Muge Sak Aug 2023

Aurka Inhibition-Based Combination Therapy Approaches In Glioblastoma., Muge Sak

Electronic Theses and Dissertations

Glioblastoma is the most common and aggressive central nervous system tumor in adults with a 6% survival rate. Decades of research for improving life expectancy and quality of life have been ineffective. The discovery of better treatment strategies is urgent to improve the survival rates for glioblastoma patients. Aurora Kinase A is a regulator of tumor progression and is overexpressed in glioblastoma. We used a specific Aurora Kinase A inhibitor alisertib in combination with DNA-damaging platinum agent carboplatin or brain-penetrating taxane TPI 287. We investigated the efficacy of these combinations in treating in vitro and in vivo tissue culture models …


Effect Of Body Mass Index Percentile On Complicated Appendicitis, Postoperative Complications And Health Service Utilization Among Pediatric Patients In The United States, Nutan Hebballi Aug 2023

Effect Of Body Mass Index Percentile On Complicated Appendicitis, Postoperative Complications And Health Service Utilization Among Pediatric Patients In The United States, Nutan Hebballi

Dissertations and Theses (Open Access)

While overweight and obesity have been extensively studied for complicated appendicitis, postoperative complications, and health service utilization, the effects of being underweight are unknown. This dissertation assesses the associations between the body mass index (BMI) spectrum with complicated appendicitis, postoperative complications, and healthcare service utilization in pediatric patients.  A retrospective review of pediatric patients who underwent appendectomy surgery (01/01/2016-12/31/2020) was conducted using the National Surgical Quality Improvement Program database. Computed age and gender-specific BMI percentiles were categorized into underweight, normal weight, overweight and obese. The 30-day postoperative complications were grouped into minor, major, and any. Healthcare service utilizations were compared …


Neuroimaging Manifestatations In Covid-19 And Its Sequelae, Abhigna M, Vikram Patil Aug 2023

Neuroimaging Manifestatations In Covid-19 And Its Sequelae, Abhigna M, Vikram Patil

Digital Journal of Clinical Medicine

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a novel pathogenic virus in late 2019, infecting millions of people with severe pulmonary infections. It spread worldwide in a short time and became a pandemic, after which the World Health Organization (WHO) declared it a public health emergency. Central nervous system involvement by COVID-19 is already an established entity in the literature. The aim of this study was to evaluate in detail the acute and delayed neurological manifestations of COVID -19.

RESULTS: COVID-19 infection can cause various neurologic manifestations and imaging findings. The most common neuroradiological abnormality is cerebrovascular …


Investigation Of Orthohantavirus Genetics In Rodent Reservoirs And Clinical Samples, Samuel Melvin Goodfellow Aug 2023

Investigation Of Orthohantavirus Genetics In Rodent Reservoirs And Clinical Samples, Samuel Melvin Goodfellow

Biomedical Sciences ETDs

Orthohantaviruses are negative-sense, single stranded RNA viruses with trisegmented genomes that can cause severe disease in humans and are carried by several host reservoirs throughout the world. In the United States, Sin Nombre orthohantavirus (SNV) is the primary cause of hantavirus cardiopulmonary syndrome (HCPS) with a fatality rate of ~36% and the highest cases occuring in the southwest region. The primary SNV host reservoir is thought to be the western deer mouse, Peromyscus maniculatus, however it has been shown that other rodents can carry different orthohantaviruses. We designed a pan-orthohantavirus detection tool to survey several small mammal populations throughout New …


Early Career Special Education Teacher Lived Experiences During Covid-19, Sydney Parks Aug 2023

Early Career Special Education Teacher Lived Experiences During Covid-19, Sydney Parks

Graduate Student Dissertations, Theses, Capstones, and Portfolios

The stories and lived experiences of Early Career Special Education Teachers must be shared. This study provides more information on the beginning lived experiences of Special Education Teachers during COVID-19. The researcher conducted a qualitative narrative design to further investigate burnout and self-efficacy among Early Career Special Education Teachers. The researcher conducted an open-ended question interview that allowed participants to relive their experience teaching during COVID-19. The conclusion of this study is that Special Education Teachers love their job but seek more financial security, administrative support and guidance, recognition.


Lipid Droplet Biogenesis And Functions In Health And Disease, Armella Zadoorian, Ximing Du, Hongyuan Yang Aug 2023

Lipid Droplet Biogenesis And Functions In Health And Disease, Armella Zadoorian, Ximing Du, Hongyuan Yang

Faculty, Staff and Student Publications

Ubiquitous yet unique, lipid droplets are intracellular organelles that are increasingly being recognized for their versatility beyond energy storage. Advances uncovering the intricacies of their biogenesis and the diversity of their physiological and pathological roles have yielded new insights into lipid droplet biology. Despite these insights, the mechanisms governing the biogenesis and functions of lipid droplets remain incompletely understood. Moreover, the causal relationship between the biogenesis and function of lipid droplets and human diseases is poorly resolved. Here, we provide an update on the current understanding of the biogenesis and functions of lipid droplets in health and disease, highlighting a …