Digital Commons Network^™

Toward Clinical-Grade Evaluation Of Large Language Models, Amy C Moreno, Danielle S Bitterman

Faculty, Staff and Student Publications

No abstract provided.

Safety And Efficacy Of Ibrutinib In Combination With Rituximab And Lenalidomide In Previously Untreated Follicular And Marginal Zone Lymphoma: An Open Label, Phase 2 Study, Max J Gordon, Lei Feng, Paolo Strati, Hun Ju Lee, Fredrick B Hagemeister, Jason R Westin, Felipe Samaniego, Mario L Marques-Piubelli, Francisco Vega Vazquez, Edwin R Parra Cuentas, Luisa M Solis-Soto, Wencai Ma, Jing Wang, Linda Claret, Barbara Averill, Karina Ibanez, Luis E Fayad, Christopher R Flowers, Michael R Green, R Eric Davis, Sattva S Neelapu, Nathan H Fowler, Loretta J Nastoupil

Faculty, Staff and Student Publications

Background: Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non-Hodgkin lymphomas (iNHL). Median survival for iNHL is approximately 20 years. Because standard treatments are not curative, patients often receive multiple lines of therapy with associated toxicity-rationally designed, combination therapies with curative potential are needed. The immunomodulatory drug lenalidomide was evaluated in combination with rituximab for the frontline treatment of FL in the phase 3 RELEVANCE study. Ibrutinib, an oral Bruton tyrosine kinase inhibitor, is active in NHL and was evaluated in combination with lenalidomide, rituximab, and ibrutinib (IRR) in a phase 1 study.

Methods: The authors conducted an …

A Journey In Science: Molecular Vaccines For Global Child Health In Troubled Times Of Anti-Science, Peter J Hotez

Faculty, Staff and Students Publications

My scientific life in translational medicine runs in two parallel, yet often converging paths. The first, is four-decade-long commitment to develop new vaccines for parasitic and neglected tropical diseases, as well as pandemic threats. This includes a vaccine for human hookworm infection that I began as an MD-PhD student in New York City in the 1980s, and a new low-cost COVID vaccine that reached almost 100 million people in low- and middle-income countries. Alongside this life in scientific research, is one in public engagement for vaccine and neglected disease diplomacy to ensure that people who live in extreme poverty can …

Tissue-Resident Memory T Cell Signatures From Single-Cell Analysis Associated With Better Melanoma Prognosis, Chongming Jiang, Cheng-Chi Chao, Jianrong Li, Xin Ge, Aidan Shen, Vadim Jucaud, Chao Cheng, Xiling Shen

Faculty, Staff and Students Publications

Tissue-resident memory T cells (TRM) are a specialized T cell population residing in peripheral tissues. The presence and potential impact of TRM in the tumor immune microenvironment (TIME) remain to be elucidated. Here, we systematically investigated the relationship between TRM and melanoma TIME based on multiple clinical single-cell RNA-seq datasets and developed signatures indicative of TRM infiltration. TRM infiltration is associated with longer overall survival and abundance of T cells, NK cells, M1 macrophages, and memory B cells in the TIME. A 22-gene TRM–derived risk score was further developed to effectively classify patients into low- and high-risk categories, distinguishing overall …

Characterization Of Flavonoids With Potent And Subtype-Selective Actions On Estrogen Receptors Alpha And Beta, Michael J Bolt, Jessica Oceguera, Pankaj K Singh, Kazem Safari, Derek H Abbott, Kaley A Neugebauer, Maureen G Mancini, Daniel A Gorelick, Fabio Stossi, Michael A Mancini

Faculty, Staff and Students Publications

The initial step in estrogen-regulated transcription is the binding of a ligand to its cognate receptors, named estrogen receptors (ERα and ERβ). Phytochemicals present in foods and environment can compete with endogenous hormones to alter physiological responses. We screened 224 flavonoids in our engineered biosensor ERα and ERβ PRL-array cell lines to characterize their activity on several steps of the estrogen signaling pathway. We identified 83 and 96 flavonoids that can activate ERα or ERβ, respectively. While most act on both receptors, many appear to be subtype-selective, including potent flavonoids that activate ER at sub-micromolar concentrations. We employed an orthogonal …

Β-Actin G342d As A Cause Of Nk Cell Deficiency Impairing Lytic Synapse Termination, Abigail E Reed, Jackeline Peraza, Frederique Van Den Haak, Evelyn R Hernandez, Richard A Gibbs, Ivan K Chinn, James R Lupski, Enrica Marchi, Ran Reshef, Bachir Alobeid, Emily M Mace, Jordan S Orange

Faculty, Staff and Students Publications

Natural killer (NK) cell deficiency (NKD) occurs when an individual’s major clinical immunodeficiency derives from abnormal NK cells and is associated with several genetic etiologies. Three categories of β actin-related diseases with over 60 ACTB (β actin) variants have previously been identified, none with a distinct NK cell phenotype. An individual with mild developmental delay, macrothrombocytopenia, susceptibility to infections, molluscum, and EBV-associated lymphoma had functional NK cell deficiency for over a decade. A de novo ACTB variant encoding G342D β actin was identified and was consistent with the individual’s developmental and platelet phenotype. This novel variant also was found to …

Hematologic Dnmt3a Reduction And High-Fat Diet Synergize To Promote Weight Gain And Tissue Inflammation, Jaime M Reyes, Ayala Tovy, Linda Zhang, Angelina S Bortoletto, Carina Rosas, Chun-Wei Chen, Sarah M Waldvogel, Anna G Guzman, Rogelio Aguilar, Sinjini Gupta, Ling Liu, Matthew T Buckley, Kalyani R Patel, Andrea N Marcogliese, Yumei Li, Choladda V Curry, Thomas A Rando, Anne Brunet, Ronald J Parchem, Rachel E Rau, Margaret A Goodell

Faculty, Staff and Students Publications

During aging, blood cell production becomes dominated by a limited number of variant hematopoietic stem cell (HSC) clones. Differentiated progeny of variant HSCs are thought to mediate the detrimental effects of such clonal hematopoiesis on organismal health, but the mechanisms are poorly understood. While somatic mutations in DNA methyltransferase 3A (DNMT3A) frequently drive clonal dominance, the aging milieu also likely contributes. Here, we examined in mice the interaction between high-fat diet (HFD) and reduced DNMT3A in hematopoietic cells; strikingly, this combination led to weight gain. HFD amplified pro-inflammatory pathways and upregulated inflammation-associated genes in mutant cells along a pro-myeloid trajectory. …

Single Cell Atlas Of Human Gastric Muscle Immune Cells And Macrophage-Driven Changes In Idiopathic Gastroparesis, Lakshmikanth L Chikkamenahalli, Erik Jessen, Cheryl E Bernard, W K Eddie Ip, Margaret Breen-Lyles, Gianluca Cipriani, Suraj R Pullapantula, Ying Li, Shefaa Alasfoor, Laura Wilson, Kenneth L Koch, Braden Kuo, Robert J Shulman, Bruno P Chumpitazi, Travis J Mckenzie, Todd A Kellogg, James Tonascia, Frank A Hamilton, Irene Sarosiek, Richard Mccallum, Henry P Parkman, Pankaj J Pasricha, Thomas L Abell, Gianrico Farrugia, Surendra Dasari, Madhusudan Grover, Niddk Gastroparesis Clinical Research Consortium (Gpcrc)

Faculty, Staff and Students Publications

Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with the enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45+ cells obtained from the gastric tissue of 20 subjects. We demonstrate 11 immune cell clusters with T cells being most abundant followed by myeloid cells. The proportions of cells belonging to the 11 clusters were similar between IG and controls. However, 9/11 clusters showed 578-11,429 differentially expressed genes. In IG, MM had decreased expression of tissue-protective and microglial …

A Comparative Analysis Of Tonebp Conditional Knockout Mouse Models Reveals Inter-Dependency Between Compartments Of The Intervertebral Disc, Greig Couasnay, Haley Garcia, Florent Elefteriou

Faculty, Staff and Students Publications

Interactions between notochord and sclerotome are required for normal embryonic spine patterning, but whether the postnatal derivatives of these tissues also require interactions for postnatal intervertebral disc (IVD) growth and maintenance is less established. We report here the comparative analysis of four conditional knockout mice deficient for TonEBP, a transcription factor known to allow cells to adapt to changes in extracellular osmotic pressure, in specific compartments of the IVD. We show that TonEBP deletion in nucleus pulposus (NP) cells does not affect their survival or aggrecan expression, but promoted cell proliferation in the NP and in adjacent vertebral growth plates …

Dolutegravir-Induced Neural Tube Defects In Mice Are Folate Responsive, Gabriel L Tukeman, Hui Wei, Ying L Lin, Bogdan J Wlodarczyk, Richard H Finnell, Robert M Cabrera

Faculty, Staff and Students Publications

Objectives: In 2018, the Botswana Tsepamo Study reported a nine-fold increased risk of neural tube defects in infants whose mothers were treated with dolutegravir (DTG) from the time of conception. As maternal folate supplementation and status is a well known modifier of neural tube defect (NTD) risk, we sought to evaluate birth outcomes in mice fed normal and low folic acid diets treated with DTG during pregnancy.

Design: DTG was evaluated for developmental toxicity using pregnant mice fed normal or low folic acid diet.

Methods: CD-1 mice were provided diet with normal (3 mg/kg) or low (0.3 mg/kg) folic acid. …

The Relationship Between Adverse Childhood Experiences And Juvenile Offender Typology, Aliza Beth Lipman

Dissertations and Theses

Approximately 1 in 5 girls and in 20 boys in the United States are victims of child sexual assault every year. Child sexual assault can lead to multiple negative short term and long-term impacts affecting general health, mental health, interpersonal relationships, socio-economic status, criminal behavior and more. Prevention research focuses on a thorough understanding of the perpetrators of assault and the context surrounding offenses in order to reduce and prevent assault. Within this research, juvenile offenders are perceived as a single homogenous group whereas adult offenders are consistently specified based on offender and offense characteristics. The exploration of the relationship …

Effect Of Neutralizing Monoclonal Antibody Treatment On Early Trajectories Of Virologic And Immunologic Biomarkers In Patients Hospitalized With Covid-19, Tomas O Jensen, Greg A Grandits, Mamta K Jain, Thomas A Murray, Birgit Grund, Kathryn Shaw-Saliba, Michael A Matthay, Mahsa Abassi, Magdalena Ardelt, Jason V Baker, Peter Chen, Robin L Dewar, Anna L Goodman, Timothy J Hatlen, Helene C Highbarger, Mark Holodniy, Perrine Lallemand, Sylvain Laverdure, Bradley G Leshnower, David Looney, Charalampos D Moschopoulos, Henry Mugerwa, Daniel D Murray, Eleftherios Mylonakis, Stephanie Nagy-Agren, M Tauseef Rehman, Adam Rupert, Randy A Stevens, Stuart Turville, Amy Weintrob, Katherine Wick, Jens Lundgren, Emily R Ko, Activ-3/Tico Study Group

Faculty, Staff and Student Publications

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood.

METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models.

RESULTS: Analysis included 2149 participants enrolled between …

Outpatient Covid-19 Convalescent Plasma Recipient Antibody Thresholds Correlated To Reduced Hospitalizations Within A Randomized Trial, Han-Sol Park, Anna Yin, Caelan Barranta, John S Lee, Christopher A Caputo, Jaiprasath Sachithanandham, Maggie Li, Steve Yoon, Ioannis Sitaras, Anne Jedlicka, Yolanda Eby, Malathi Ram, Reinaldo E Fernandez, Owen R Baker, Aarthi G Shenoy, Giselle S Mosnaim, Yuriko Fukuta, Bela Patel, Sonya L Heath, Adam C Levine, Barry R Meisenberg, Emily S Spivak, Shweta Anjan, Moises A Huaman, Janis E Blair, Judith S Currier, James H Paxton, Jonathan M Gerber, Joann R Petrini, Patrick B Broderick, William Rausch, Marie Elena Cordisco, Jean Hammel, Benjamin Greenblatt, Valerie C Cluzet, Daniel Cruser, Kevin Oei, Matthew Abinante, Laura L Hammitt, Catherine G Sutcliffe, Donald N Forthal, Martin S Zand, Edward R Cachay, Jay S Raval, Seble G Kassaye, Christi E Marshall, Anusha Yarava, Karen Lane, Nichol A Mcbee, Amy L Gawad, Nicky Karlen, Atika Singh, Daniel E Ford, Douglas A Jabs, Lawrence J Appel, David M Shade, Bryan Lau, Stephan Ehrhardt, Sheriza N Baksh, Janna R Shapiro, Jiangda Ou, Yu Bin Na, Maria D Knoll, Elysse Ornelas-Gatdula, Netzahualcoyotl Arroyo-Curras, Thomas J Gniadek, Patrizio Caturegli, Jinke Wu, Nelson Ndahiro, Michael J Betenbaugh, Alyssa Ziman, Daniel F Hanley, Arturo Casadevall, Shmuel Shoham, Evan M Bloch, Kelly A Gebo, Aaron Ar Tobian, Oliver Laeyendecker, Andrew Pekosz, Sabra L Klein, David J Sullivan

Faculty, Staff and Students Publications

BACKGROUND

COVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.

METHODS

This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization–equivalent anti–Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors …

Label-Aware Distance Mitigates Temporal And Spatial Variability For Clustering And Visualization Of Single-Cell Gene Expression Data, Shaoheng Liang, Jinzhuang Dou, Ramiz Iqbal, Ken Chen

Faculty, Staff and Student Publications

Clustering and visualization are essential parts of single-cell gene expression data analysis. The Euclidean distance used in most distance-based methods is not optimal. The batch effect, i.e., the variability among samples gathered from different times, tissues, and patients, introduces large between-group distance and obscures the true identities of cells. To solve this problem, we introduce Label-Aware Distance (LAD), a metric using temporal/spatial locality of the batch effect to control for such factors. We validate LAD on simulated data as well as apply it to a mouse retina development dataset and a lung dataset. We also found the utility of our …

Btn1a1 Is A Novel Immune Checkpoint Mutually Exclusive To Pd-L1, Young-Seung Kim, Seung-Hoon Lee, Andrew H Park, Chunai Wu, Bong-Ki Hong, Hyunjin Jung, Steven H Lin, Stephen S Yoo

Faculty, Staff and Student Publications

BACKGROUND: While Programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) blockade is a potent antitumor treatment strategy, it is effective in only limited subsets of patients with cancer, emphasizing the need for the identification of additional immune checkpoints. Butyrophilin 1A1 (BTN1A1) has been reported to exhibit potential immunoregulatory activity, but its ability to function as an immune checkpoint remains to be systematically assessed, and the mechanisms underlying such activity have yet to be characterized.

METHODS: BTN1A1 expression was evaluated in primary tumor tissue samples, and its ability to suppress T-cell activation and T cell-dependent tumor clearance was examined. …

Lifestyle Medicine For The Prevention And Treatment Of Pancreatitis And Pancreatic Cancer, Sruthi Kapliyil Subramanian, Bhaumik Brahmbhatt, Jennifer M Bailey-Lundberg, Nirav C Thosani, Pritesh Mutha

Faculty, Staff and Student Publications

The incidence of pancreatitis and pancreatic cancer is on the upswing in the USA. These conditions often lead to higher healthcare costs due to the complex nature of diagnosis and the need for specialized medical interventions, surgical procedures, and prolonged medical management. The economic ramification encompasses direct healthcare expenses and indirect costs related to productivity losses, disability, and potential long-term care requirements. Increasing evidence underscores the importance of a healthy lifestyle in preventing and managing these conditions. Lifestyle medicine employs evidence-based interventions to promote health through six key pillars: embracing a whole-food, plant-predominant dietary pattern; regular physical activity; ensuring restorative …

Utility Of Peripheral Protein Biomarkers For The Prediction Of Incident Interstitial Features: A Multicentre Retrospective Cohort Study, Samuel Ash, Tracy J Doyle, Bina Choi, Ruben San Jose Estepar, Victor Castro, Nicholas Enzer, Ravi Kalhan, Gabrielle Liu, Russell Bowler, David O Wilson, Raul San Jose Estepar, Ivan O Rosas, George R Washko

Faculty, Staff and Students Publications

INTRODUCTION/RATIONALE: Protein biomarkers may help enable the prediction of incident interstitial features on chest CT.

METHODS: We identified which protein biomarkers in a cohort of smokers (COPDGene) differed between those with and without objectively measured interstitial features at baseline using a univariate screen (t-test false discovery rate, FDR p

RESULTS: In COPDGene, 1305 biomarkers were available and 20 differed between those with and without interstitial features at baseline. Of these, 11 were associated with feature progression over a mean of 5.5 years of follow-up, and of these 4 were available in PLuSS, (angiopoietin-2, matrix metalloproteinase 7, macrophage inflammatory protein 1 …

Effect Of Neutralizing Monoclonal Antibody Treatment On Early Trajectories Of Virologic And Immunologic Biomarkers In Patients Hospitalized With Covid-19, Tomas O Jensen, Greg A Grandits, Mamta K Jain, Thomas A Murray, Birgit Grund, Kathryn Shaw-Saliba, Michael A Matthay, Mahsa Abassi, Magdalena Ardelt, Jason V Baker, Peter Chen, Robin L Dewar, Anna L Goodman, Timothy J Hatlen, Helene C Highbarger, Mark Holodniy, Perrine Lallemand, Sylvain Laverdure, Bradley G Leshnower, David Looney, Charalampos D Moschopoulos, Henry Mugerwa, Daniel D Murray, Eleftherios Mylonakis, Stephanie Nagy-Agren, M Tauseef Rehman, Adam Rupert, Randy A Stevens, Stuart Turville, Amy Weintrob, Katherine Wick, Jens Lundgren, Emily R Ko

Faculty, Staff and Student Publications

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood.

METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models.

RESULTS: Analysis included 2149 participants enrolled between …

A Novel Spatiotemporal Graph Convolutional Network Framework For Functional Connectivity Biomarkers Identification Of Alzheimer’S Disease, Ying Zhang, Le Xue, Shuoyan Zhang, Jiacheng Yang, Qi Zhang, Min Wang, Luyao Wang, Mingkai Zhang, Jiehui Jiang, Yunxia Li

Faculty, Staff and Student Publications

BACKGROUND: Functional connectivity (FC) biomarkers play a crucial role in the early diagnosis and mechanistic study of Alzheimer's disease (AD). However, the identification of effective FC biomarkers remains challenging. In this study, we introduce a novel approach, the spatiotemporal graph convolutional network (ST-GCN) combined with the gradient-based class activation mapping (Grad-CAM) model (STGC-GCAM), to effectively identify FC biomarkers for AD.

METHODS: This multi-center cross-racial retrospective study involved 2,272 participants, including 1,105 cognitively normal (CN) subjects, 790 mild cognitive impairment (MCI) individuals, and 377 AD patients. All participants underwent functional magnetic resonance imaging (fMRI) and T1-weighted MRI scans. In this study, …

Microcurrent-Mediated Modulation Of Myofibroblasts For Cardiac Repair And Regeneration, Dipthi Bachamanda Somesh, Karsten Jürchott, Thomas Giesel, Thomas Töllner, Alexander Prehn, Jan-Peter Richters, Dragana Kosevic, J. Eduardo Rame, Peter Göttel, Johannes Müller

Division of Cardiology Faculty Papers

Cardiovascular diseases are a significant cause of illness and death worldwide, often resulting in myofibroblast differentiation, pathological remodeling, and fibrosis, characterized by excessive extracellular matrix protein deposition. Treatment options for cardiac fibrosis that can effectively target myofibroblast activation and ECM deposition are limited, necessitating an unmet need for new therapeutic approaches. In recent years, microcurrent therapy has demonstrated promising therapeutic effects, showcasing its translational potential in cardiac care. This study therefore sought to investigate the effects of microcurrent therapy on cardiac myofibroblasts, aiming to unravel its potential as a treatment for cardiac fibrosis and heart failure. The experimental design involved …

Viral Epitope Scanning Reveals Correlation Between Seasonal Hcovs And Sars-Cov-2 Antibody Responses Among Cancer And Non-Cancer Patients, Salum J. Lidenge, Dicle Yalcin, Sydney J. Bennett, Owen Ngalamika, Brenda B. Kweyamba, Chacha J. Mwita, For Yue Tso, Julius Mwaiselage, John T. West, Charles Wood

School of Medicine Faculty Publications

Seasonal coronaviruses (HCoVs) are known to contribute to cross-reactive antibody (Ab) responses against SARS-CoV-2. While these responses are predictable due to the high homology between SARS-CoV-2 and other CoVs, the impact of these responses on susceptibility to SARS-CoV-2 infection in cancer patients is unclear. To investigate the influence of prior HCoV infection on anti-SARS-CoV-2 Ab responses among COVID-19 asymptomatic individuals with cancer and controls without cancers, we utilized the VirScan technology in which phage immunoprecipitation and sequencing (PhIP-seq) of longitudinal plasma samples was performed to investigate high-resolution (i.e., epitope level) humoral CoV responses. Despite testing positive for anti-SARS-CoV-2 Ab in …

Genomic Evolution Shapes Prostate Cancer Disease Type, Dan J Woodcock, Atef Sahli, Ruxandra Teslo, Vinayak Bhandari, Andreas J Gruber, Aleksandra Ziubroniewicz, Gunes Gundem, Yaobo Xu, Adam Butler, Ezequiel Anokian, Bernard J Pope, Chol-Hee Jung, Maxime Tarabichi, Stefan C Dentro, J Henry R Farmery, Cruk Icgc Prostate Group, Peter Van Loo, Anne Y Warren, Vincent Gnanapragasam, Freddie C Hamdy, G Steven Bova, Christopher S Foster, David E Neal, Yong-Jie Lu, Zsofia Kote-Jarai, Michael Fraser, Robert G Bristow, Paul C Boutros, Anthony J Costello, Niall M Corcoran, Christopher M Hovens, Charlie E Massie, Andy G Lynch, Daniel S Brewer, Rosalind A Eeles, Colin S Cooper, David C Wedge

Faculty, Staff and Student Publications

The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype …

Cytoplasmic Genome Contributions To Domestication And Improvement Of Modern Maize, Shuai Cao, Huanhuan Zhang, Yang Liu, Yi Sun, Z Jeffrey Chen

Faculty, Staff and Student Publications

Background: Studies on maize evolution and domestication are largely limited to the nuclear genomes, and the contribution of cytoplasmic genomes to selection and domestication of modern maize remains elusive. Maize cytoplasmic genomes have been classified into fertile (NA and NB) and cytoplasmic-nuclear male-sterility (CMS-S, CMS-C, and CMS-T) groups, but their contributions to modern maize breeding have not been systematically investigated.

Results: Here we report co-selection and convergent evolution between nuclear and cytoplasmic genomes by analyzing whole genome sequencing data of 630 maize accessions modern maize and its relatives, including 24 fully assembled mitochondrial and chloroplast genomes. We show that the …

Adaptive Changes In Young Football Players Working In A Modified Tactical Periodization Model Based On The Example Of Endurance., Marta Szymanek-Pilarczyk, Michał Jakub Nowak, Jacek Wąsik

Baltic Journal of Health and Physical Activity

Introduction: Adequate endurance is a critical element of success in football, both at professional and amateur levels. Therefore, this study aimed to assess the effectiveness of training based on a modified wave (repeating) periodization model on the endurance of players aged 12–16 at the RKS Raków Academy in 2018–2022.

Material and Method: The analysis involved football players aged 12 to 16 with 4–8 years of training experience, involved in a program called "wave periodization". Two tests were performed each year, one in June (Test A) and the other one in December (Test B). Maximal Aerobic Speed (MAS) and Velocity Intermittent …

Novel Lipid Mediator 7s,14r-Docosahexaenoic Acid: Biogenesis And Harnessing Mesenchymal Stem Cells To Ameliorate Diabetic Mellitus And Retinal Pericyte Loss, Yan Lu, Haibin Tian, Hongying Peng, Quansheng Wang, Bruce A. Bunnell, Nicolas G. Bazan, Song Hong

School of Medicine Faculty Publications

Introduction: Stem cells can be used to treat diabetic mellitus and complications. ω3-docosahexaenoic acid (DHA) derived lipid mediators are inflammation-resolving and protective. This study found novel DHA-derived 7S,14R-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-docosahexaenoic acid (7S,14R-diHDHA), a maresin-1 stereoisomer biosynthesized by leukocytes and related enzymes. Moreover, 7S,14R-diHDHA can enhance mesenchymal stem cell (MSC) functions in the amelioration of diabetic mellitus and retinal pericyte loss in diabetic db/db mice. Methods: MSCs treated with 7S,14R-diHDHA were delivered into db/db mice i.v. every 5 days for 35 days. Results: Blood glucose levels in diabetic mice were lowered by 7S,14R-diHDHA-treated MSCs compared to control and untreated MSC groups, accompanied by …

Limonene Exerts Anti-Inflammatory Effect On Lps-Induced Jejunal Injury In Mice By Inhibiting Nf-Κb/Ap-1 Pathway, Sarmed H. Kathem, Yasameen Sh. Nasrawi, Shihab H. Mutlag, Surya M. Nauli

Pharmacy Faculty Articles and Research

The human gastrointestinal system is a complex ecosystem crucial for well-being. During sepsis-induced gut injury, the integrity of the intestinal barrier can be compromised. Lipopolysaccharide (LPS), an endotoxin from Gram-negative bacteria, disrupts the intestinal barrier, contributing to inflammation and various dysfunctions. The current study explores the protective effects of limonene, a natural compound with diverse biological properties, against LPS-induced jejunal injury in mice. Oral administration of limonene at dosages of 100 and 200 mg/kg was used in the LPS mouse model. The Murine Sepsis Score (MSS) was utilized to evaluate the severity of sepsis, while serum levels of urea and …

Landscape Of Pharmacogenetic Variants Associated With Non-Insulin Antidiabetic Drugs In The Indian Population, Ambily Sivadas, S Sahana, Bani Jolly, Rahul C Bhoyar, Abhinav Jain, Disha Sharma, Mohamed Imran, Vigneshwar Senthivel, Mohit Kumar Divakar, Anushree Mishra, Arpita Mukhopadhyay, Greg Gibson, Km Venkat Narayan, Sridhar Sivasubbu, Vinod Scaria, Anura V Kurpad

Faculty, Staff and Student Publications

INTRODUCTION: Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants.

RESEARCH DESIGN AND METHODS: We mined 1029 Indian whole genomes for PGx variants, drug-drug interaction (DDI) and drug-drug-gene interactions (DDGI) associated with …

Author Correction: Hypomorphic Brca2 And Rad51c Double Mutant Mice Display Fanconi Anemia, Cancer And Polygenic Replication Stress, Karl-Heinz Tomaszowski, Sunetra Roy, Carolina Guerrero, Poojan Shukla, Caezaan Keshvani, Yue Chen, Martina Ott, Xiaogang Wu, Jianhua Zhang, Courtney D Dinardo, Detlev Schindler, Katharina Schlacher

Faculty, Staff and Student Publications

No abstract provided.

A Biogeographical Appraisal Of The Threatened South East Africa Montane Archipelago Ecoregion, Julian Bayliss, Gabriela B Bittencourt-Silva, William R Branch, Carl Bruessow, Steve Collins, T Colin E Congdon, Werner Conradie, Michael Curran, Savel R Daniels, Iain Darbyshire, Harith Farooq, Lincoln Fishpool, Geoffrey Grantham, Zacharia Magombo, Hermenegildo Matimele, Ara Monadjem, Jose Monteiro, Jo Osborne, Justin Saunders, Paul Smith, Claire N Spottiswoode, Peter J Taylor, Jonathan Timberlake, Krystal A Tolley, Érica Tovela, Philip J Platts

Faculty, Staff and Student Publications

Recent biological surveys of ancient inselbergs in southern Malawi and northern Mozambique have led to the discovery and description of many species new to science, and overlapping centres of endemism across multiple taxa. Combining these endemic taxa with data on geology and climate, we propose the 'South East Africa Montane Archipelago' (SEAMA) as a distinct ecoregion of global biological importance. The ecoregion encompasses 30 granitic inselbergs reaching > 1000 m above sea level, hosting the largest (Mt Mabu) and smallest (Mt Lico) mid-elevation rainforests in southern Africa, as well as biologically unique montane grasslands. Endemic taxa include 127 plants, 45 vertebrates …

Evaluation Of Treatment Parameters For Focused-Extracorporeal Shock Wave Therapy In Knee Osteoarthritis Patients With Bone Marrow Lesions: A Pilot Study, Hani Al-Abbad, Jacqueline E Reznik, Erik Biros, Bruce Paulik, Rob Will, Samuel Gane, Penny Moss, Anthony Wright

Faculty, Staff and Student Publications

OBJECTIVES: To evaluate the effect of different dosage parameters of focused-extracorporeal shock wave therapy on pain and physical function in knee osteoarthritis patients with bone marrow lesions. In addition, to investigate pathophysiological changes based on imaging and biomarker measures.

METHODS: Using a single-case experimental design, a total of 12 participants were randomly allocated in 4 equal groups of 3 to receive different dosages of focused-extracorporeal shock wave therapy. Each group received either 4 or 6 sessions of 1500 or 3000 shocks over 4 or 6 weekly sessions. Participants underwent repeated measurements during the baseline, intervention, and post-intervention phases for Western …