Life Sciences Commons^™

Agricultural Groundcover Update January 2024, Justin Laycock

Natural resources published reports

Summary

• About 94% of the grainbelt had adequate (more than 50%) vegetative groundcover to prevent wind erosion in January 2024.
• In the northern half of the grainbelt, a larger-than-average area has 51–60% groundcover, which is expected to decrease to below 50% over the coming months.
• Just under 6% of the grainbelt (855,000 ha) had less than 50% groundcover, which is inadequate to prevent wind erosion. West Midlands Ag Soil Zone had the highest risk of wind erosion and 14.5% of this farmland had inadequate groundcover.
• Less than 0.5% of the grainbelt had a high to very high risk of wind …

Antimicrobial Tolerance In Salmonella: Contributions To Survival And Persistence In Processing Environments, Tomi Obe, Aaron S. Kiess, Ramakrishna Nannapaneni

Poultry Science Faculty Publications and Presentations

Salmonella remains a top bacterial pathogen implicated in several food-borne outbreaks, despite the use of antimicrobials and sanitizers during production and processing. While these chemicals have been effective, Salmonella has shown the ability to survive and persist in poultry processing environments. This can be credited to its microbial ability to adapt and develop/acquire tolerance and/or resistance to different antimicrobial agents including oxidizers, acids (organic and inorganic), phenols, and surfactants. Moreover, there are several factors in processing environments that can limit the efficacy of these antimicrobials, thus allowing survival and persistence. This mini-review examines the antimicrobial activity of common disinfectants/sanitizers used …

Effects Of Environmental Enrichments On Welfare And Hepatic Metabolic Regulation Of Broiler Chickens, Seong W. Kang, Karen D. Christensen, Michael T. Kidd, Sara K. Orlowski

Poultry Science Faculty Publications and Presentations

The aims of this study were to find suitable environmental enrichment (EE) and evaluate the combined effect of two EEs, variable light intensity (VL) lighting program and EH, on mental health and hepatic metabolic regulation in commercial broilers. To find the advantageous EEs for broilers, three different EEs (board, hut, and ramp) were tested in trial 1. EEs were placed and the engagement of birds to EEs, dustbathing behavior, and daily physical activity were observed. Birds treated with huts showed higher engagement than the board- or ramp-treated birds (p < 0.05). The results of dustbathing behavior and daily physical activity indicated that the environmental hut (EH) is the most favorable enrichment for broilers. In the second trial, to test the effect of EHs on mental health and hepatic metabolic conditions, the brain and liver were sampled from the four treatment birds (20 lx_Con, 20 lx_Hut, VL_Con and VL_Hut) on day 42. The lower expression of TPH2 (tryptophan hydroxylase 2) of VL_Hut birds than those of VL_Con and 20 lx_Hut treated birds suggests the combining effect of EHs with the VL lighting program on the central serotonergic homeostasis of broilers. Reduced expressions of TH (tyrosine hydroxylase), GR (glucocorticoid receptor), BDNF (brain-derived neurotrophic factor) of VL_Hut treated birds compared to those of VL_Con and 20 lx_Hut birds suggest lower stress, stress susceptibility, and chronic social stress in VL_Hut treated birds. The expression of CPT1A (carnitine palmitoyl transferase 1) increased over three-fold in the liver of VL_Con birds compared to 20 lx_Con birds (p < 0.05). EHs treatment in VL birds (VL_Hut) significantly decreased CPT1A but not in 20 lx birds (20 lx_Hut). The expression of ACCα (acetyl-CoA carboxylase alpha) was significantly decreased in VL_Con birds compared to 20 lx_Con birds. There was no significant difference in the hepatic FBPase (fructose-1,6-bisphosphatase), GR, and 11β-HSD1 (11 β-hydroxysteroid dehydrogenease-1) expression between 20 lx_Con and VL_Con birds, but EHs significantly stimulated GR in 20 lx_Hut birds, and stimulated FBPase and 11β-HSD1 expression in the VL_Hut birds compared to 20 lx_Con birds, suggesting that the VL lighting program reduced fatty acid synthesis and increased fatty acid β-oxidation in the broilers’ liver and VL_Hut improved the hepatic de novo glucose production. Taken together, the results suggest that the stimulated voluntary activity by EHs in the light-enriched broiler house improved mental health and hepatic metabolic function of broilers and may indicate that the improved hepatic metabolic function contributes to efficient nutritional support for broilers.

Us Public Opinion About The Safety Of Gene Editing In The Agriculture And Medical Fields And The Amount Of Evidence Needed To Improve Opinions, Brandon R. Mcfadden, Joy N. Rumble, Kathryn A. Stofer, Kevin M. Folta

Agricultural Economics and Agribusiness Faculty Publications and Presentations

Introduction: Implementation of gene editing in agriculture and medicine hinges on public acceptance. The objectives of this study were to explore U.S. public opinion about gene editing in agricultural and medical fields and to provide more insight into the relationship between opinions about the safety of gene editing and the potential impact of evidence to improve opinions about safety.

Methods: Data were from two samples of U.S. respondents: 1,442 respondents in 2021 and 3,125 respondents in 2022. Survey respondents provided their opinions about the safety of gene editing in the agricultural and medical fields and answered questions about the number …

Ras/Mapk Signaling Mediates Adipose Tissue Control Of Ovarian Germline Survival And Ovulation In Drosophila Melanogaster, Tancia Bradshaw, Chad Simmons, Rachael Ott, Alissa Richmond Armstrong

Faculty Publications

From insects to humans, oogenesis is tightly linked to nutritional input, yet little is known about how whole organism physiology matches dietary changes with oocyte development. Considering that diet-induced adipose tissue dysfunction is associated with an increased risk for fertility problems, and other obesity-associated pathophysiologies, it is critical to decipher the cellular and molecular mechanisms linking adipose nutrient sensing to remote control of the ovary and other tissues. Our previous studies in Drosophila melanogaster have shown that amino acid sensing, via the amino acid response pathway and mTOR-mediated signaling function within adipocytes to control germline stem cell maintenance and ovulation, …

The Divided Self: Internal Conflict In Literature, Philosophy, Psychology, And Neuroscience, Yulia Greyman

Dissertations, Theses, and Capstone Projects

This thematic project examines the notion of self-division, particularly in terms of the conflict between cognition and metacognition, across the fields of philosophy, psychology, and, most recently, the cognitive and neurosciences. The project offers a historic overview of models of self-division, as well as analyses of the various problems presented in theoretical models to date. This work explores how self-division has been depicted in the literary works of Edgar Allan Poe, Don DeLillo, and Mary Shelley. It examines the ways in which artistic renderings alternately assimilate, resist, and/or critique dominant philosophical, psychological, and scientific discourses about the self and its …

Adaptive Evolution Of Surface Proteins In Microbial Pathogens: Lyme Disease Pathogens (Borreliella Sp.) And Human Immunodeficiency Virus Type 1 (Hiv-1), Li Li

Dissertations, Theses, and Capstone Projects

Cell and virion surface proteins are key to the survival and adaptation of microbial pathogens by enabling them to evade host immune responses and to persist in diverse environments. Pathogens respond to host immune pressures with genetic changes in surface proteins through mechanisms including point mutations, recombination, gene duplication and loss, and lateral gene transfer, resulting in novel antigenic variants and antigenic diversity. This continuous adaptation helps pathogens evade host immunity, leading to chronic infections and recurrent disease outbreaks. Understanding these mechanisms is vital for developing effective strategies to combat infectious diseases.

This dissertation comprises three chapters exploring the adaptive …

The Effect Of Alpha Binaural Beats On Virtual Reality Experiences, Andronikki C. Gerohristodoulos

Dissertations, Theses, and Capstone Projects

Visually induced motion sickness (VIMS), a subset of motion sickness, has been a long-term obstacle preventing comfortable experiences in virtual reality (VR). There is a growing body of research showing that binaural beats (BBs) have been effective to influence aspects of cognition. The goal of this experiment was to investigate the possible effects of attending to BBs and any changes to the severity of VIMS symptoms following immersion in a virtual reality environment (VRE). To validate our hypothesis a repeated-measures, between-subjects experiment was designed (n=16) and an alpha (10Hz) frequency BB and a control audio were created. Participants were split …

Deep Learning-Based H-Score Quantification Of Immunohistochemistry-Stained Images, Zhuoyu Wen, Danni Luo, Shidan Wang, Ruichen Rong, Bret M Evers, Yisheng Fang, Shengjie Yang, Zifan Gu, Emily N Arner, Cheryl M Lewis, Luisa M Solis Soto, Junya Fujimoto, Carmen Behrens, Ignacio I Wistuba, Donghan M Yang, Rolf A Brekken, Kathryn A O'Donnell, Yang Xie, Guanghua Xiao

Faculty, Staff and Student Publications

Immunohistochemistry (IHC) is a well-established and commonly used staining method for clinical diagnosis and biomedical research. In most IHC images, the target protein is conjugated with a specific antibody and stained using diaminobenzidine (DAB), resulting in a brown coloration, whereas hematoxylin serves as a blue counterstain for cell nuclei. The protein expression level is quantified through the H-score, calculated from DAB staining intensity within the target cell region. Traditionally, this process requires evaluation by 2 expert pathologists, which is both time consuming and subjective. To enhance the efficiency and accuracy of this process, we have developed an automatic algorithm for …

Phase I Study Of Sapanisertib (Cb-228/Tak-228/Mln0128) In Combination With Ziv-Aflibercept In Patients With Advanced Solid Tumors, Niamh Coleman, Bettzy Stephen, Siqing Fu, Daniel Karp, Vivek Subbiah, Sarina A Piha-Paul, Senait N Fessahaye, Fengying Ouyang, Bulent Yilmaz, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

BACKGROUND: Sapanisertib is a potent ATP-competitive, dual inhibitor of mTORC1/2. Ziv-aflibercept is a recombinant fusion protein comprising human VEGF receptor extracellular domains fused to human immunoglobulin G1. HIF-1α inhibition in combination with anti-angiogenic therapy is a promising anti-tumor strategy. This Phase 1 dose-escalation/expansion study assessed safety/ tolerability of sapanisertib in combination with ziv-aflibercept in advanced solid tumors.

METHODS: Fifty-five patients with heavily pre-treated advanced metastatic solid tumors resistant or refractory to standard treatment received treatment on a range of dose levels.

RESULTS: Fifty-five patients were enrolled and treated across a range of dose levels. Forty were female (73%), median age …

Safety And Efficacy Of A New High-Dose Regimen Of Panobinostat, Gemcitabine, Busulfan, And Melphalan For 1st Or 2nd Salvage Asct For Refractory/Relapsed Or High-Risk Myeloma: Matched-Pair Comparisons With Concurrent Control Cohorts, Yago Nieto, Zixi Yang, Benigno C Valdez, Suprateek Kundu, Qaiser Bashir, Samer Srour

Faculty, Staff and Student Publications

Improvement of autologous stem-cell transplantation (ASCT) for myeloma is needed. Building on our prior work, we prospectively evaluated panobinostat and gemcitabine/busulfan/melphalan (GemBuMel) with ASCT in this population. Patients aged 18-65 years with relapsed/refractory or high-risk myeloma and adequate end-organ function were eligible. Treatment included panobinostat (20 mg/day, days -9 to -2) and GemBuMel (days -8 to -2). Patients were enrolled in 1st (ASCT-1) or 2nd ASCT (ASCT-2) cohorts. We compared their outcomes with all our other concurrent ASCT patients who met eligibility criteria but received melphalan or BuMel off study, matched for age, prior therapy lines, high-risk cytogenetics, and response …

The Biology Of Hope: Inflammatory And Neuroendocrine Profiles In Ovarian Cancer Patients, Susan K Lutgendorf, Rachel M Telles, Brendan Whitney, Premal H Thaker, George M Slavich, Frank J Penedo, Steven W Cole, Anil K Sood, Benjamin W Corn

Faculty, Staff and Student Publications

INTRODUCTION: Although the concept of hope is highly relevant for cancer patients, little is known about its association with cancer-relevant biomarkers. Here we examined how hope was related to diurnal cortisol and interleukin-6 (IL-6), a pro-inflammatory cytokine previously associated with tumor biology and survival in ovarian cancer. Secondly, we examined whether hope and hopelessness are distinctly associated with these biomarkers.

METHOD: Participants were 292 high-grade ovarian cancer patients who completed surveys and provided saliva samples 4x/daily for 3 days pre-surgery to assess diurnal cortisol. Blood (pre-surgery) and ascites were assessed for IL-6. Hope and hopelessness were assessed using standardized survey …

Pluripotency Of A Founding Field: Rebranding Developmental Biology, Crystal D Rogers, Chris Amemiya, Swathi Arur, Leslie Babonis, Michael Barresi, Richard Behringer, Dominique Bergmann, Ben Blackman, C Titus Brown, Bill Browne, Jasmin Camacho, Chiswili Yves Chabu, Ida Chow, Ondine Cleaver, Jonah Cool, Megan Y Dennis, Alexandra Jazz Dickinson, Stefano Di Talia, Margaret Frank, Stewart Gillmor, Eric S Haag, Iswar Hariharan, Richard Harland, Aman Husbands, Loydie Jerome-Majewska, Kristen Koenig, Carole Labonne, Michael Layden, Chris Lowe, Madhav Mani, Megan Martik, Katelyn Mckown, Cecilia Moens, Christian Mosimann, Joyce Onyenedum, Robert Reed, Ajna Rivera, Dan Rokhsar, Loic Royer, Flora Rutaganira, Rachel Shahan, Neelima Sinha, Billie Swalla, Jaimie M Van Norman, Daniel E Wagner, Athula Wikramanayake, Sophia Zebell, Siobhán M Brady

Faculty, Staff and Student Publications

The field of developmental biology has declined in prominence in recent decades, with off-shoots from the field becoming more fashionable and highly funded. This has created inequity in discovery and opportunity, partly due to the perception that the field is antiquated or not cutting edge. A 'think tank' of scientists from multiple developmental biology-related disciplines came together to define specific challenges in the field that may have inhibited innovation, and to provide tangible solutions to some of the issues facing developmental biology. The community suggestions include a call to the community to help 'rebrand' the field, alongside proposals for additional …

Correction: Il-1Α Mediates Innate And Acquired Resistance To Immunotherapy In Melanoma, Shubhra Singh, Zhilan Xiao, Karishma Bavisi, Jason Roszik, Brenda D Melendez, Mark J Cantwell, Greg Lizee, Patrick Hwu, Sattva S Neelapu, Willem W Overwijk, Manisha Singh

Faculty, Staff and Student Publications

No abstract provided.

Deep Learning-Based Automatic Segmentation Of Cardiac Substructures For Lung Cancers, Xinru Chen, Raymond P Mumme, Kelsey L Corrigan, Yuki Mukai-Sasaki, Efstratios Koutroumpakis, Callistus M Nguyen, Kai Huang, Cenji Yu, Ting Xu, Aji Daniel, Peter A Balter, Xiaodong Zhang, Joshua S Niedzielski, Sanjay S Shete, Anita Deswal, Laurence E Court, Zhongxing Liao, Jinzhong Yang

Faculty, Staff and Student Publications

Purpose: Accurate and comprehensive segmentation of cardiac substructures is crucial for minimizing the risk of radiation-induced heart disease in lung cancer radiotherapy. We sought to develop and validate deep learning-based auto-segmentation models for cardiac substructures.

Materials and methods: Nineteen cardiac substructures (whole heart, 4 heart chambers, 6 great vessels, 4 valves, and 4 coronary arteries) in 100 patients treated for non-small cell lung cancer were manually delineated by two radiation oncologists. The valves and coronary arteries were delineated as planning risk volumes. An nnU-Net auto-segmentation model was trained, validated, and tested on this dataset with a split ratio of 75:5:20. …

Phase 2 Study Of Inotuzumab Ozogamicin For Measurable Residual Disease In Acute Lymphoblastic Leukemia In Remission, Elias Jabbour, Fadi G Haddad, Nicholas J Short, Jayastu Senapati, Nitin Jain, Jeffrey Jorgensen, Yesid Alvarado, Xuemei Wang, Courtney Dinardo, Lucia Masarova, Tapan Kadia, Rebecca S Garris, Farhad Ravandi, Hagop Kantarjian

Faculty, Staff and Student Publications

The detection of measurable residual disease (MRD) is the strongest predictor of relapse in acute lymphoblastic leukemia (ALL). Using inotuzumab ozogamicin in the setting of MRD may improve outcomes. Patients with ALL in first complete remission (CR1) or beyond (CR2+) with MRD ≥ 1 × 10-4 were enrolled in this phase 2 trial. Inotuzumab was administered at 0.6 mg/m2 on day 1 and 0.3 mg/m2 on day 8 of cycle 1, then at 0.3 mg/m2 on days 1 and 8 of cycles 2-6. Twenty-six consecutive patients with a median age of 46 years (range, 19-70 years) were treated. Nineteen (73%) …

Azithromycin Reduces Hemoglobin-Induced Innate Neuroimmune Activation, Chirayu D Pandya, Hemendra J Vekaria, Miriam Zamorano, Amanda L Trout, Rodney M Ritzel, Christopher Bolden, John C Gensel, Brandon A Miller

Faculty, Staff and Student Publications

Neonatal intraventricular hemorrhage (IVH) releases blood products into the lateral ventricles and brain parenchyma. There are currently no medical treatments for IVH and surgery is used to treat a delayed effect of IVH, post-hemorrhagic hydrocephalus. However, surgery is not a cure for intrinsic brain injury from IVH, and is performed in a subacute time frame. Like many neurological diseases and injuries, innate immune activation is implicated in the pathogenesis of IVH. Innate immune activation is a pharmaceutically targetable mechanism to reduce brain injury and post-hemorrhagic hydrocephalus after IVH. Here, we tested the macrolide antibiotic azithromycin, which has immunomodulatory properties, to …

Mediators Of Necroptosis: From Cell Death To Metabolic Regulation, Xiaoqin Wu, Laura E Nagy, Jérémie Gautheron

Faculty, Staff and Student Publications

Necroptosis, a programmed cell death mechanism distinct from apoptosis, has garnered attention for its role in various pathological conditions. While initially recognized for its involvement in cell death, recent research has revealed that key necroptotic mediators, including receptor-interacting protein kinases (RIPKs) and mixed lineage kinase domain-like protein (MLKL), possess additional functions that go beyond inducing cell demise. These functions encompass influencing critical aspects of metabolic regulation, such as energy metabolism, glucose homeostasis, and lipid metabolism. Dysregulated necroptosis has been implicated in metabolic diseases, including obesity, diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD), contributing to chronic …

Development Of Resistance To Type Ii Jak2 Inhibitors In Mpn Depends On Axl Kinase And Is Targetable, Tamara Codilupi, Jakub Szybinski, Stefanie Arunasalam, Sarah Jungius, Andrew C Dunbar, Sime Brkic, Lenka Vokalova, Julie L Yang, Katarzyna Buczak, Nilabh Ghosh, Jakob R Passweg, Alicia Rovo, Anne Angelillo-Scherrer, Dmitry Pankov, Stefan Dirnhofer, Ross L Levine, Richard Koche, Sara C Meyer

Faculty, Staff and Student Publications

PURPOSE: Myeloproliferative neoplasms (MPN) dysregulate JAK2 signaling. Because clinical JAK2 inhibitors have limited disease-modifying effects, type II JAK2 inhibitors such as CHZ868 stabilizing inactive JAK2 and reducing MPN clones, gain interest. We studied whether MPN cells escape from type ll inhibition.

EXPERIMENTAL DESIGN: MPN cells were continuously exposed to CHZ868. We used phosphoproteomic analyses and ATAC/RNA sequencing to characterize acquired resistance to type II JAK2 inhibition, and targeted candidate mediators in MPN cells and mice.

RESULTS: MPN cells showed increased IC50 and reduced apoptosis upon CHZ868 reflecting acquired resistance to JAK2 inhibition. Among >2,500 differential phospho-sites, MAPK pathway activation was …

Association Between Circulating Inflammatory Markers And Adult Cancer Risk: A Mendelian Randomization Analysis, James Yarmolinsky, Jamie W Robinson, Daniela Mariosa, Ville Karhunen, Jian Huang, Neil Murphy, Emmanouil Bouras, Karl Smith-Byrne, Sarah J Lewis, Tessel E Galesloot, Lambertus A Kiemeney, Sita Vermeulen, Paul Martin, Demetrius Albanes, Lifang Hou, Polly A Newcomb, Emily White, Alicja Wolk, Anna H Wu, Loïc Le Marchand, Amanda I Phipps, Daniel D Buchanan, International Lung Cancer Consortium, Practical Consortium, Sizheng Steven Zhao, Dipender Gill, Stephen J Chanock, Mark P Purdue, George Davey Smith, Paul Brennan, Karl-Heinz Herzig, Marjo-Riitta Järvelin, Chris I Amos, Rayjean J Hung, Abbas Dehghan, Mattias Johansson, Marc J Gunter, Kostas K Tsilidis, Richard M Martin

Faculty, Staff and Student Publications

BACKGROUND: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.

METHODS: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were …

Anatomy Of The Female Reproductive Tract Organs Of The Brown Anole (Anolis Sagrei), Bonnie K Kircher, Edward L Stanley, Richard R Behringer

Faculty, Staff and Student Publications

Female reproduction in squamate reptiles (lizards and snakes) is highly diverse and mode of reproduction, clutch size, and reproductive tract morphology all vary widely across this group of ~11,000 species. Recently, CRISPR genome editing techniques that require manipulation of the female reproductive anatomy have been developed in this group, making a more complete understanding of this anatomy essential. We describe the adult female reproductive anatomy of the model reptile the brown anole (Anolis sagrei). We show that the brown anole female reproductive tract has three distinct anterior-to-posterior regions, the infundibulum, the glandular uterus, and the nonglandular uterus. The infundibulum has …

Txnrd1 Drives The Innate Immune Response In Senescent Cells With Implications For Age-Associated Inflammation, Xue Hao, Bo Zhao, Martina Towers, Liping Liao, Edgar Luzete Monteiro, Christina Freeman, Hsin-Yao Tang, Aaron Havas, Andrew V Kossenkov, Shelley L Berger, Peter D Adams, David W Speicher, David Schultz, Ronen Marmorstein, Kenneth S Zaret, Rugang Zhang

Faculty, Staff and Student Publications

Sterile inflammation, also known as 'inflammaging', is a hallmark of tissue aging. Cellular senescence contributes to tissue aging, in part, through the secretion of proinflammatory factors collectively known as the senescence-associated secretory phenotype (SASP). The genetic variability of thioredoxin reductase 1 (TXNRD1) is associated with aging and age-associated phenotypes such as late-life survival, activity of daily living and physical performance in old age. TXNRD1's role in regulating tissue aging has been attributed to its enzymatic role in cellular redox regulation. Here, we show that TXNRD1 drives the SASP and inflammaging through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) …

Sionx Coating Regulates Mesenchymal Stem Cell Antioxidant Capacity Via Nuclear Erythroid Factor 2 Activity Under Toxic Oxidative Stress Conditions, Neelam Ahuja, Kamal Awad, Su Yang, He Dong, Antonios Mikos, Simon Young, Venu Varanasi

Faculty, Staff and Student Publications

Healing in compromised and complicated bone defects is often prolonged and delayed due to the lack of bioactivity of the fixation device, secondary infections, and associated oxidative stress. Here, we propose amorphous silicon oxynitride (SiONx) as a coating for the fixation devices to improve both bioactivity and bacteriostatic activity and reduce oxidative stress. We aimed to study the effect of increasing the N/O ratio in the SiONx to fine-tune the cellular activity and the antioxidant effect via the NRF2 pathway under oxidative stress conditions. The in vitro studies involved using human mesenchymal stem cells (MSCs) to examine the effect of …

Lfsproshiny: An Interactive R/Shiny App For Prediction And Visualization Of Cancer Risks In Families With Deleterious Germline Tp53 Mutations, Nam H Nguyen, Elissa B Dodd-Eaton, Gang Peng, Jessica L Corredor, Wenwei Jiao, Banu K Arun

Faculty, Staff and Student Publications

Purpose: LFSPRO is an R library that implements risk prediction models for Li-Fraumeni syndrome (LFS), a genetic disorder characterized by deleterious germline mutations in the TP53 gene. To facilitate the use of these models in clinics, we developed LFSPROShiny, an interactive R/Shiny interface of LFSPRO that allows genetic counselors (GCs) to perform risk predictions without any programming components and further visualize the risk profiles of their patients to aid the decision-making process.

Methods: LFSPROShiny implements two models that have been validated on multiple LFS patient cohorts: a competing risk model that predicts cancer-specific risks for the first primary and a …

Minimal Information For Studies Of Extracellular Vesicles (Misev2023): From Basic To Advanced Approaches, Joshua A Welsh, Deborah C I Goberdhan, Lorraine O'Driscoll, Edit I Buzas, Cherie Blenkiron, Houjian Cai, Tom A P Driedonks, Uta Erdbrügger, Juan M Falcon-Perez, Qing-Ling Fu, Andrew F Hill, Metka Lenassi, Sai Kiang Lim, Mỹ G Mahoney, Sujata Mohanty, Andreas Möller, Rienk Nieuwland, Takahiro Ochiya, Susmita Sahoo, Ana C Torrecilhas, Lei Zheng, Andries Zijlstra, Sarah Abuelreich, Reem Bagabas, Paolo Bergese, Esther M Bridges, Marco Brucale, Dylan Burger, Randy P Carney, Emanuele Cocucci, Rossella Crescitelli, Edveena Hanser, Adrian L Harris, Norman J Haughey, An Hendrix, Alexander R Ivanov, Tijana Jovanovic-Talisman, Nicole A Kruh-Garcia, Vroniqa Ku'ulei-Lyn Faustino, Diego Kyburz, Cecilia Lässer, Kathleen M Lennon, Jan Lötvall, Adam L Maddox, Elena S Martens-Uzunova, Rachel R Mizenko, Lauren A Newman, Andrea Ridolfi, Eva Rohde, Tatu Rojalin, Andrew Rowland, Andras Saftics, Ursula S Sandau, Julie A Saugstad, Faezeh Shekari, Simon Swift, Dmitry Ter-Ovanesyan, Juan P Tosar, Zivile Useckaite, Francesco Valle, Zoltan Varga, Edwin Van Der Pol, Martijn J C Van Herwijnen, Marca H M Wauben, Ann M Wehman, Sarah Williams, Andrea Zendrini, Alan J Zimmerman, Clotilde Théry, Kenneth W Witwer

Faculty, Staff and Student Publications

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional …

Neurologic Morbidity And Functional Independence In Adult Survivors Of Childhood Cancer, Stefanie C Vuotto, Mingjuan Wang, M Fatih Okcu, Daniel C Bowers, Nicole J Ullrich, Chenghong Li, Rebecca M Howell, Todd M Gibson, Wendy M Leisenring, Kevin C Oeffinger, Leslie L Robison, Gregory T Armstrong, Kevin R Krull, Tara M Brinkman

Faculty, Staff and Student Publications

OBJECTIVE: To examine associations between neurologic late effects and attainment of independence in adult survivors of childhood cancer treated with central nervous system (CNS)-directed therapies.

METHODS: A total of 7881 survivors treated with cranial radiation therapy (n = 4051; CRT) and/or intrathecal methotrexate (n = 4193; IT MTX) ([CNS-treated]; median age [range] = 25.5 years [18-48]; time since diagnosis = 17.7 years [6.8-30.2]) and 8039 without CNS-directed therapy reported neurologic conditions including stroke, seizure, neurosensory deficits, focal neurologic dysfunction, and migraines/severe headaches. Functional independence was assessed using latent class analysis with multiple indicators (independent living, assistance with routine and personal …

Absence Of Btk, Bcl2, And Plcg2 Mutations In Chronic Lymphocytic Leukemia Relapsing After First-Line Treatment With Fixed-Duration Ibrutinib Plus Venetoclax, Nitin Jain, Lisa J Croner, John N Allan, Tanya Siddiqi, Alessandra Tedeschi, Karl Eckert, Anwesha Mukherjee, James P Dean, Edith Szafer-Glusman, John F Seymour

Faculty, Staff and Student Publications

Purpose: Mutations in BTK, PLCG2, and BCL2 have been reported in patients with progressive disease (PD) on continuous single-agent BTK or BCL2 inhibitor treatment. We tested for these mutations in samples from patients with PD after completion of first-line treatment with fixed-duration ibrutinib plus venetoclax for chronic lymphocytic leukemia (CLL) in the phase II CAPTIVATE study.

Patients and methods: A total of 191 patients completed fixed-duration ibrutinib plus venetoclax (three cycles of ibrutinib then 12-13 cycles of ibrutinib plus venetoclax). Genomic risk features [del(11q), del(13q), del(17p), trisomy 12, complex karyotype, unmutated IGHV, TP53 mutated] and mutations in genes recurrently mutated …

Genomic Staging Of Multifocal Lung Squamous Cell Carcinomas Is Independent Of The Comprehensive Morphologic Assessment, Sanja Dacic, Xuanye Cao, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridion, Sabina Berezowska, Jin-Haeng Chung, Lin Dongmei, David Hwang, Mari Mino-Kenudson, Yuko Minami, Mauro Papotti, Natasha Rekhtman, Anja C Roden, Erik Thunnissen, Ming-Sound Tsao, Yasushi Yatabe, Akihiko Yoshida, Linghua Wang, Douglas J Hartman, Jacob A Jerome, Humam Kadara, Teh-Ying Chou, Ignacio I Wistuba

Faculty, Staff and Student Publications

Introduction: Morphologic and molecular data for staging of multifocal lung squamous cell carcinomas (LSCCs) are limited. In this study, whole exome sequencing (WES) was used as the gold standard to determine whether multifocal LSCC represented separate primary lung cancers (SPLCs) or intrapulmonary metastases (IPMs). Genomic profiles were compared with the comprehensive morphologic assessment.

Methods: WES was performed on 20 tumor pairs of multifocal LSCC and matched normal lymph nodes using the Illumina NovaSeq6000 S4-Xp (Illumina, San Diego, CA). WES clonal and subclonal analysis data were compared with histologic assessment by 16 thoracic pathologists. In addition, the immune gene profiling of …

Aleukemic Chronic Myeloid Leukemia Without Neutrophilia And Thrombocytosis: A Report From The Bcr::Abl1 Pathology Group, Daniel Rivera, Wei Cui, Juehua Gao, Deniz Peker, Qian-Yun Zhang, Lianqun Qiu, Zhihong Hu, Koji Sasaki, Aileen Y Hu, Shuyu E, Meng Liu, Hong Fang, Wei Wang, Guilin Tang, Jane F Apperley, Andreas Hochhaus, Jorge E Cortes, Joseph D Khoury, L Jeffrey Medeiros, Elias Jabbour, Shimin Hu

Faculty, Staff and Student Publications

Chronic myeloid leukemia (CML) is characterized by leukocytosis with left-shifted neutrophilia, basophilia, eosinophilia, and variable thrombocytosis. However, extremely rare cases of patients with CML without significant leukocytosis and thrombocytosis (aleukemic phase [ALP] CML, or CML-ALP) have been reported. Due to its rarity and limited awareness, there remains a significant knowledge gap concerning the pathologic diagnosis, disease progression, and optimal patient management and outcomes. In this multi-institutional study, we investigated 31 patients with CML-ALP. Over half (54.8%) of patients had a history of or concurrent hematopoietic or nonhematopoietic malignancies. At time of diagnosis of CML-ALP, approximately 26.7% of patients exhibited neutrophilia, …

Glucose Metabolism In Posterior Cingulate Cortex Has Supplementary Value To Predict The Progression Of Cognitively Unimpaired To Dementia Due To Alzheimer’S Disease: An Exploratory Study Of 18f-Fdg-Pet, Qi Zhang, Chunqiu Fan, Luyao Wang, Taoran Li, Min Wang, Jiehui Jiang

Faculty, Staff and Student Publications

Amyloid-β (Aβ) and tau are important biomarkers to predict the progression of cognitively unimpaired (CU) to dementia due to Alzheimer's disease (AD), according to the diagnosis framework from the US National Institute on Aging and the Alzheimer's Association (NIA-AA). However, it is clinically difficult to predict those subjects who were already with Aβ positive (A +) or tau positive (T +). As a typical characteristic of neurodegeneration in the diagnosis framework, the hypometabolism of the posterior cingulate cortex (PCC) has significant clinical value in the early prediction and prevention of AD. In this paper, we proposed the glucose metabolism in …