Life Sciences Commons^™

Methods To Reduce Nitrogen And Carbon Losses From Finishing Beef Cattle, Hanna K. Cronk

Department of Animal Science: Dissertations, Theses, and Student Research

A finishing experiment evaluated the effect of incremental supplemental rumen-protected lysine on beef cattle performance. All cattle were fed the same diet of high moisture corn, dried rolled corn, modified distillers grains plus solubles, corn silage, and supplement with inclusion levels of lysine ranging from 0 to 7 grams/day, in 1 g increments. Dry matter intake (P ≤ 0.04) and ADG (P ≤ 0.04) decreased linearly as supplemental lysine increased in the diet with no effect on final carcass adjusted feed efficiency (P ≥ 0.34). In the initial 64 days of the experiment, increasing lysine in the …

The Evaluation Of Encapsulated Megasphaera Elsdenii In An Accelerated Beef Step-Up Program And An Acidosis Challenge Model And The Evaluation Of Ramp Versus A Traditional Forage Grain Adaptation Strategy On Methane And Respired Carbon Dioxide, Cindy D. Mansfield

Department of Animal Science: Dissertations, Theses, and Student Research

A metabolism experiment (Exp 1) was conducted to evaluate daily feeding of encapsulated Megasphaera elsdenii (M. elsdenii) NCIMB 41125 along with a one-time drench of 1×10¹¹ CFU of M. elsdenii on dry matter intake (DMI), in-vitro lactate utilization, volatile fatty acid (VFA), and lactate concentration. Treatments consisted of steers which were fed no M. elsdenii (CONTROL), steers drenched with the commercial dose 1×10¹¹ CFU of M. elsdenii (LactiproNXT) on d 1 of the experiment and received no other M. elsdenii (DRENCH), and steers drenched with a commercial dose of LactiproNXT on d …

Impact Of Physical Activity Levels On College Student Depression, Anxiety, And Stress, Sophia R. Sullivan Almquist

Celebrating Scholarship and Creativity Day (2018-)

A moderate to high prevalence of depression, anxiety, and stress have been found in undergraduate students. Physical activity has been shown to decrease anxiety, depression, and stress. Examining the impacts of physical activity on the mental health of college students might show to be beneficial. PURPOSE: To assess if self-reported physical activity levels impact depression, anxiety, and stress levels in college students. METHODS: A total of 92 college students from private institutions in central Minnesota completed an online survey. The survey collected demographics including age, gender, height, weight, and year in school. The International Physical Activity Questionnaire (IPAQ) was used …

A New Method For Reducing Salmonella In Poultry Meat, Regis Yizerwe

Honors Program: Senior Projects (Public)

An important approach to decreasing the transmission of Salmonella into the food chain is to treat raw chicken after processing. This can be, and has been done, by using antibiotics and chemical disinfectants. Using antibiotics is not a viable option due to the issue of antimicrobial resistance. Although some chemical disinfectants have been used effectively, they are restricted due to the amounts that can be used safely, the acceptance of their use and resistance to implementation in various parts of the world. This study has revealed that using a naturally occurring saponin–Quillaja Saponaria– in small concentrations under certain conditions of …

Self-Selected Pacing Strategy And Lactate Response In Individual Medley Time Trials, Claire Galloway

Undergraduate Theses and Capstone Projects

The 200 and 400-yard individual medley (IM; 200 IM and 400 IM, respectively) are two swimming events that challenge swimmers' versatility. Each of these events has different physiological requirements, where the 200 IM is viewed as an anaerobic event and the 400 IM as an aerobic event. Additionally, the IMs require performance in all four competitive stroke disciplines in a specific order (butterfly, backstroke, breaststroke, and freestyle), with each stroke requiring a different magnitude of intensity, efficiency, and speed. Purpose: To study the different pacing strategies and corresponding blood lactate response during the 200 IM and 400 IM in National …

Silk Production In Mature And Penultimate Female Dolomedes Scriptus, Dylan J. Haley

Undergraduate Theses and Capstone Projects

Male Dolomedes scriptus are able to determine female maturity status by silk alone, as demonstrated by increased courtship in the presence of silk from mature females (Roach and Benson, unpublished). However, the mechanism by which the males determine female maturity status is unknown. It is possible that there are pheromonal signals indicating reproductive status. Specifically, I test whether mature female D. scriptus produce a different amount of silk than penultimate females, particularly if mature females produce more than immatures. If mature D. scriptus females produce more silk than penultimate females, male D. scriptus may determine maturity status of females via …

The Effect Of Joint Versus Soft Tissue Flossing On Overall Performance In The Lower Extremities, Emily Bray

Undergraduate Theses and Capstone Projects

Effective warm-up routines result in a reduction in muscle soreness post-exercise, a lessened risk of injury, and an enhanced performance output ability. Existing research has shown promising effects of muscle tissue flossing, a novel method of warming up in which a latex band is used to apply pressure to a specific area in the body. The purpose of this study was to determine how active college students respond to flossing applied to both a joint as well as soft tissue in the lower extremities, focusing on the ankle joint and calf muscle. Floss bands were applied bilaterally for each of …

Current Treatment Strategies And Risk Stratification For Oral Carcinoma, Issa Mohamad, Mica D E Glaun, Kumar Prabhash, Ahmed Busheri, Stephen Y Lai, Vanita Noronha, Ali Hosni

Faculty, Staff and Student Publications

Management of oral cavity squamous cell carcinoma (OSCC) involves a multidisciplinary team approach. Surgery is ideally the primary treatment option for nonmetastatic OSCC, and less invasive curative surgical approaches are preferred in early-stage disease to minimize surgical-related morbidity. For patients at high risk of recurrence, adjuvant treatment using radiation therapy or chemoradiation is often used. Systemic therapy may also be used in the neoadjuvant setting (for advanced-stage disease with the intent of mandibular preservation) or in the palliative setting (for nonsalvageable locoregional recurrence and/or distant metastases). Patient involvement in treatment decision is the key for patient-driven management, particularly in clinical …

Genomic And Transcriptomic Analysis Of Checkpoint Blockade Response In Advanced Non-Small Cell Lung Cancer, Arvind Ravi, Matthew D Hellmann, Monica B Arniella, Mark Holton, Samuel S Freeman, Vivek Naranbhai, Chip Stewart, Ignaty Leshchiner, Jaegil Kim, Yo Akiyama, Aaron T Griffin, Natalie I Vokes, Mustafa Sakhi, Vashine Kamesan, Hira Rizvi, Biagio Ricciuti, Patrick M Forde, Valsamo Anagnostou, Jonathan W Riess, Don L Gibbons, Nathan A Pennell, Vamsidhar Velcheti, Subba R Digumarthy, Mari Mino-Kenudson, Andrea Califano, John V Heymach, Roy S Herbst, Julie R Brahmer, Kurt A Schalper, Victor E Velculescu, Brian S Henick, Naiyer Rizvi, Pasi A Jänne, Mark M Awad, Andrew Chow, Benjamin D Greenbaum, Marta Luksza, Alice T Shaw, Jedd Wolchok, Nir Hacohen, Gad Getz, Justin F Gainor

Faculty, Staff and Student Publications

Anti-PD-1/PD-L1 agents have transformed the treatment landscape of advanced non-small cell lung cancer (NSCLC). To expand our understanding of the molecular features underlying response to checkpoint inhibitors in NSCLC, we describe here the first joint analysis of the Stand Up To Cancer-Mark Foundation cohort, a resource of whole exome and/or RNA sequencing from 393 patients with NSCLC treated with anti-PD-(L)1 therapy, along with matched clinical response annotation. We identify a number of associations between molecular features and outcome, including (1) favorable (for example, ATM altered) and unfavorable (for example, TERT amplified) genomic subgroups, (2) a prominent association between expression of …

One Immune System Plays Many Parts: The Dynamic Role Of The Immune System In Chronic Pain And Opioid Pharmacology, Sanam Mustafa, Juliana E Bajic, Benjamin Barry, Samuel Evans, Kariel R Siemens, Mark R Hutchinson, Peter M Grace

Faculty, Staff and Student Publications

The transition from acute to chronic pain is an ongoing major problem for individuals, society and healthcare systems around the world. It is clear chronic pain is a complex multidimensional biological challenge plagued with difficulties in pain management, specifically opioid use. In recent years the role of the immune system in chronic pain and opioid pharmacology has come to the forefront. As a highly dynamic and versatile network of cells, tissues and organs, the immune system is perfectly positioned at the microscale level to alter nociception and drive structural adaptations that underpin chronic pain and opioid use. In this review, …

Development And Validation Of A Patient-Reported Outcome Measure To Assess Symptom Burden After Chimeric Antigen Receptor T-Cell Therapy, Xin Shelley Wang, Samer A Srour, Tito Mendoza, Meagan Whisenant, Ishwaria Subbiah, Elizabeth Gonzalez, Mona Kamal, Shu-En Shen, Charles Cleeland, Partow Kebriaei, Katayoun Rezvani, Sattva Neelapu, Sairah Ahmed, Elizabeth Shpall

Faculty, Staff and Student Publications

This cross-sectional study aimed to develop and validate a patient-reported outcomes (PROs) assessment tool to assess symptom burden and daily functioning in patients after chimeric antigen receptor (CAR) T-cell therapy, the MD Anderson Symptom Inventory (MDASI-CAR). The items were generated based on literature review, content elicitation interviews with patients, and clinician's review. The patients completed the MDASI core and module, single-item quality-of-life (QoL) measure and Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29). The psychometric validation analysis was based on the acceptability after item reduction process. The final 10 MDASI-CAR module items included tremors, fever/chills, headache, balance, dizziness, attention, difficulty speaking, coughing, …

Neural Network Based Ensemble Model To Predict Radiation Induced Lymphopenia After Concurrent Chemo-Radiotherapy For Non-Small Cell Lung Cancer From Two Institutions, Yejin Kim, Ibrahim Chamseddine, Yeona Cho, Jin Sung Kim, Radhe Mohan, Nadya Shusharina, Harald Paganetti, Steven Lin, Hong In Yoon, Seungryong Cho, Clemens Grassberger

Faculty, Staff and Student Publications

The use of adjuvant Immune Checkpoint Inhibitors (ICI) after concurrent chemo-radiation therapy (CCRT) has become the standard of care for locally advanced non-small cell lung cancer (LA-NSCLC). However, prolonged radiotherapy regimens are known to cause radiation-induced lymphopenia (RIL), a long-neglected toxicity that has been shown to correlate with response to ICIs and survival of patients treated with adjuvant ICI after CCRT. In this study, we aim to develop a novel neural network (NN) approach that integrates patient characteristics, treatment related variables, and differential dose volume histograms (dDVH) of lung and heart to predict the incidence of RIL at the end …

Aapm Task Group Report 305: Guidance For Standardization Of Vendor-Neutral Reject Analysis In Radiography, Kevin Little, Ingrid Reiser, Bruce Apgar, Poonam Dalal, Jaydev Dave, Ryan Fisher, Katie Hulme, Mary Ellen Jafari, Emily Marshall, Stephen Meyer, Quentin Moore, Nicole Murphy, Thomas Nishino, Katelyn Nye, Kevin O'Donnell, John Sabol, Adrian Sanchez, William Sensakovic, Lawrence Tarbox, Robert Uzenoff, Alisa Walz-Flannigan, Charles Willis, Jie Zhang

Faculty, Staff and Student Publications

Reject rate analysis is considered an integral part of a diagnostic radiography quality control (QC) program. A rejected image is a patient radiograph that was not presented to a radiologist for diagnosis and that contributes unnecessary radiation dose to the patient. Reject rates that are either too high or too low may suggest systemic department shortcomings in QC mechanisms. Due to the lack of standardization, reject data often cannot be easily compared between radiography systems from different vendors. The purpose of this report is to provide guidance to help standardize data elements that are required for comprehensive reject analysis and …

Sarcoidosis And Airway Disease After Immune Checkpoint Inhibitor Therapy: Case Study And Review Of The Literature, Felipe Soto, Luis F Torre-Sada, Frank E Mott, Sang T Kim, Roza Nurieva, Vickie R Shannon, Saadia A Faiz, Roberto F Casal, Mehmet Altan, Julie Lin, Ajay Sheshadri

Faculty, Staff and Student Publications

Pulmonary toxicity from immune checkpoint inhibitor therapy is typically a severe and potentially fatal complication, but these observations are driven by the most common toxicity, pneumonitis. Rarer pulmonary immune related adverse events, like airway disease and sarcoidosis, may have a more benign course. In this case report, we present a patient in whom therapy with the PD-1 inhibitor pembrolizumab resulted in severe eosinophilic asthma and sarcoidosis. This is the first case showing that anti-IL-5 inhibition may be safe in patients who develop eosinophilic asthma after ICI therapy. We further show that sarcoidosis does not necessarily require treatment cessation. This case …

Prospective Study Of Perioperative Circulating Tumor Dna Dynamics In Patients Undergoing Hepatectomy For Colorectal Liver Metastases, Timothy E Newhook, Michael J Overman, Yun Shin Chun, Arvind Dasari, Ching-Wei D Tzeng, Hop S Tran Cao, Victoria Raymond, Christine Parseghian, Benny Johnson, Yujiro Nishioka, Yoshikuni Kawaguchi, Abhineet Uppal, Timothy J Vreeland, Ariel Jaimovich, Elsa M Arvide, Jenilette V Cristo, Steven H Wei, Kanwal P Raghav, Van K Morris, Jeffrey E Lee, Scott Kopetz, Jean-Nicolas Vauthey

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate the association of perioperative ctDNA dynamics on outcomes after hepatectomy for CLM.

SUMMARY BACKGROUND DATA: Prognostication is imprecise for patients undergoing hepatectomy for CLM, and ctDNA is a promising biomarker. However, clinical implications of perioperative ctDNA dynamics are not well established.

METHODS: Patients underwent curative-intent hepatectomy after preoperative chemotherapy for CLM (2013-2017) with paired prehepatectomy/postoperative ctDNA analyses via plasma-only assay. Positivity was determined using a proprietary variant classifier. Primary endpoint was recurrence-free survival (RFS). Median follow-up was 55 months.

RESULTS: Forty-eight patients were included. ctDNA was detected before and after surgery (ctDNA+/+) in 14 (29%), before but …

National Brain Tumour Registry Of China (Nbtrc) Statistical Report Of Primary Brain Tumours Diagnosed In China In Years 2019–2020, Dan Xiao, Changxiang Yan, Deling Li, Tianshu Xi, Xianzhi Liu, Dan Zhu, Guodong Huang, Jianguo Xu, Zhengwen He, Anhua Wu, Chiyuan Ma, Jiang Long, Kai Shu, Hongming Ji, Ning Wang, Gang Chen, Jiankai Yang, Hui Ma, Zhiyong Li, Xiaochuan Sun, Yan Qu, Zhixiong Liu, Xiaofan Jiang, Chunlei Tian, Shilei Ni, Renya Zhan, Liwen Chen, Ming Ge, Maode Wang, Xiaobing Jiang, Geng Guo, Zhenmin Han, Chuan Zhang, Tingrong Zhang, Changwu Dou, Liangzhao Chu, Pengcheng Wang, Junfei Shao, Xiyue Wu, Ju Yu, Yu Wang, Nan Wu, Rui Zhang, Mingming Zhang, Yong Hong, Jianzhong Gao, Yunqian Li, Yawen Pan, Bing Zhao, Nan Ji, Guangliang Shan, Chirag B Patel, Wang Jia, Liwei Zhang

Faculty, Staff and Student Publications

BACKGROUND: The lack of a well-designed brain tumour registry with standardized pathological diagnoses in underdeveloped countries hinders the ability to compare epidemiologic data across the globe. The National Brain Tumour Registry of China (NBTRC), created in January 2018, is the first multi-hospital-based brain tumour registry in China. Patient data reported to the NBTRC in years 2019-2020 were assessed.

METHODS: Tumour pathology was based on the 2016 World Health Organization (WHO) classification of tumours of the central nervous system and ICD-O-3. The anatomical site was coded per the Surveillance, Epidemiology, and End Results (SEER) solid tumour module (version of July 2019). …

P53 And Ovarian Carcinoma Survival: An Ovarian Tumor Tissue Analysis Consortium Study, Martin Köbel, Eun-Young Kang, Ashley Weir, Peter F Rambau, Cheng-Han Lee, Gregg S Nelson, Prafull Ghatage, Nicola S Meagher, Marjorie J Riggan, Jennifer Alsop, Michael S Anglesio, Matthias W Beckmann, Christiani Bisinotto, Michelle Boisen, Jessica Boros, Alison H Brand, Angela Brooks-Wilson, Michael E Carney, Penny Coulson, Madeleine Courtney-Brooks, Kara L Cushing-Haugen, Cezary Cybulski, Suha Deen, Mona A El-Bahrawy, Esther Elishaev, Ramona Erber, Sian Fereday, Aocs Group, Anna Fischer, Simon A Gayther, Arantzazu Barquin-Garcia, Aleksandra Gentry-Maharaj, C Blake Gilks, Helena Gronwald, Marcel Grube, Paul R Harnett, Holly R Harris, Andreas D Hartkopf, Arndt Hartmann, Alexander Hein, Joy Hendley, Brenda Y Hernandez, Yajue Huang, Anna Jakubowska, Mercedes Jimenez-Linan, Michael E Jones, Catherine J Kennedy, Tomasz Kluz, Jennifer M Koziak, Jaime Lesnock, Jenny Lester, Jan Lubiński, Teri A Longacre, Maria Lycke, Constantina Mateoiu, Bryan M Mccauley, Valerie Mcguire, Britta Ney, Alexander Olawaiye, Sandra Orsulic, Ana Osorio, Luis Paz-Ares, Teresa Ramón Y Cajal, Joseph H Rothstein, Matthias Ruebner, Minouk J Schoemaker, Mitul Shah, Raghwa Sharma, Mark E Sherman, Yurii B Shvetsov, Naveena Singh, Helen Steed, Sarah J Storr, Aline Talhouk, Nadia Traficante, Chen Wang, Alice S Whittemore, Martin Widschwendter, Lynne R Wilkens, Stacey J Winham, Javier Benitez, Andrew Berchuck, David D Bowtell, Francisco J Candido Dos Reis, Ian Campbell, Linda S Cook, Anna Defazio, Jennifer A Doherty, Peter A Fasching, Renée T Fortner, María J García, Marc T Goodman, Ellen L Goode, Jacek Gronwald, David G Huntsman, Beth Y Karlan, Linda E Kelemen, Stefan Kommoss, Nhu D Le, Stewart G Martin, Usha Menon, Francesmary Modugno, Paul Dp Pharoah, Joellen M Schildkraut, Weiva Sieh, Annette Staebler, Karin Sundfeldt, Anthony J Swerdlow, Susan J Ramus, James D Brenton

Faculty, Staff and Student Publications

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were …

Cone-Beam Ct Sampling Incompleteness: Analytical And Empirical Studies Of Emerging Systems And Source-Detector Orbits, Pengwei Wu, Aina Tersol, Rolf Clackdoyle, John M Boone, Jeffrey H Siewerdsen

Faculty, Staff and Student Publications

PURPOSE: Motivated by emerging cone-beam computed tomography (CBCT) systems and scan orbits, we aim to quantitatively assess the completeness of data for 3D image reconstruction-in turn, related to "cone-beam artifacts." Fundamental principles of cone-beam sampling incompleteness are considered with respect to an analytical figure-of-merit [FOM, denoted

APPROACH:A previously proposed analytical FOM [tan ( ψmin ) , defined as the minimum angle between a point in the 3D image reconstruction and the x-ray source over the scan orbit] was analyzed for a variety of CBCT geometries. A physical test phantom was configured with parallel disk pairs (perpendicular to the z-axis) …

A Model For Gastrointestinal Tract Motility In A 4d Imaging Phantom Of Human Anatomy, Ergys Subashi, Paul Segars, Harini Veeraraghavan, Joseph Deasy, Neelam Tyagi

Faculty, Staff and Student Publications

BACKGROUND: Gastrointestinal (GI) tract motility is one of the main sources for intra/inter-fraction variability and uncertainty in radiation therapy for abdominal targets. Models for GI motility can improve the assessment of delivered dose and contribute to the development, testing, and validation of deformable image registration (DIR) and dose-accumulation algorithms.

PURPOSE: To implement GI tract motion in the 4D extended cardiac-torso (XCAT) digital phantom of human anatomy.

MATERIALS AND METHODS: Motility modes that exhibit large amplitude changes in the diameter of the GI tract and may persist over timescales comparable to online adaptive planning and radiotherapy delivery were identified based on …

Philadelphia-Like Genetic Rearrangements In Adults With B-Cell All: Refractoriness To Chemotherapy And Response To Tyrosine Kinase Inhibitor In Abl Class Rearrangements, Jayastu Senapati, Elias Jabbour, Marina Konopleva, Nicholas J Short, Guilin Tang, Naval Daver, Partow Kebriaei, Tapan Kadia, Naveen Pemmaraju, Koichi Takahashi, Courtney Dinardo, Koji Sasaki, Gautam Borthakur, Beenu Thakral, Rashmi Kanagal-Shamanna, Keyur Patel, Farhad Ravandi, Kathryn Roberts, Charles Mullighan, Hagop Kantarjian, Nitin Jain

Faculty, Staff and Student Publications

PURPOSE: Philadelphia-like (Ph-like) B-cell ALL is a high-risk subtype of B-cell ALL that shares a gene expression profile with Ph-positive ALL, but without a

PATIENTS AND METHODS: We performed a retrospective review of patients with B-cell ALL treated at MD Anderson Cancer Center to identify recurrent genetic fusions commonly seen in Ph-like ALL and focus on patients treated with TKI.

RESULTS: We identified 23 patients with recurrent genetic fusions commonly seen in Ph-like ALL; 14 had

CONCLUSION: Understanding the genomics of B-cell ALL is important for disease prognostication and for precise treatment planning. Besides conventional cytogenetics and directed FISH testing, …

Critical Role Of The Ventral Temporal Lobe In Naming, Kathryn M Snyder, Kiefer J Forseth, Cristian Donos, Patrick S Rollo, Simon Fischer-Baum, Joshua Breier, Nitin Tandon

Faculty, Staff and Student Publications

OBJECTIVE: Lexical retrieval deficits are characteristic of a variety of different neurological disorders. However, the exact substrates responsible for this are not known. We studied a large cohort of patients undergoing surgery in the dominant temporal lobe for medically intractable epilepsy (n = 95) to localize brain regions that were associated with anomia.

METHODS: We performed a multivariate voxel-based lesion-symptom mapping analysis to correlate surgical lesions within the temporal lobe with changes in naming ability. Additionally, we used a surface-based mixed-effects multilevel analysis to estimate group-level broadband gamma activity during naming across a subset of patients with electrocorticographic recordings and …

Barriers To Colonoscopy In Uk Colorectal Cancer Screening Programmes: Qualitative Interviews With Ethnic Minority Groups, Robert S Kerrison, Natalie Gil, Elizabeth Travis, Robyn Jones, Katriina L Whitaker, Colin Rees, Stephen Duffy, Christian Von Wagner

Faculty, Staff and Student Publications

OBJECTIVE: People from ethnic minority backgrounds are less likely to attend colonoscopy, following faecal immunochemical test screening, and are more likely to be diagnosed with colorectal cancer at an advanced stage as a result. The aim of this research was to explore the barriers and facilitators to attending colonoscopy, perceived by ethnic minority groups living in the United Kingdom.

METHODS: Semi-structured online and telephone interviews were conducted with thirty men and women of Black-African (n = 5), Black-Caribbean (n = 5), South Asian (n = 10) and White British (n = 10) descent. Participants were eligible for screening, but had …

Targeting Pd-L2-Rgmb Overcomes Microbiome-Related Immunotherapy Resistance, Joon Seok Park, Francesca S Gazzaniga, Meng Wu, Amalia K Luthens, Jacob Gillis, Wen Zheng, Martin W Lafleur, Sarah B Johnson, Golnaz Morad, Elizabeth M Park, Yifan Zhou, Stephanie S Watowich, Jennifer A Wargo, Gordon J Freeman, Dennis L Kasper, Arlene H Sharpe

Faculty, Staff and Student Publications

The gut microbiota is a crucial regulator of anti-tumour immunity during immune checkpoint inhibitor therapy. Several bacteria that promote an anti-tumour response to immune checkpoint inhibitors have been identified in mice1-6. Moreover, transplantation of faecal specimens from responders can improve the efficacy of anti-PD-1 therapy in patients with melanoma7,8. However, the increased efficacy from faecal transplants is variable and how gut bacteria promote anti-tumour immunity remains unclear. Here we show that the gut microbiome downregulates PD-L2 expression and its binding partner repulsive guidance molecule b (RGMb) to promote anti-tumour immunity and identify bacterial species that mediate this effect. PD-L1 and …

Mincle-Gsdmd-Mediated Release Of Il-1Β Small Extracellular Vesicles From Hepatic Macrophages In Ethanol-Induced Liver Injury, Quanri Zhang, Weiwei Liu, Katarzyna Bulek, Han Wang, Megan R Mcmullen, Xiaoqin Wu, Nicole Welch, Renliang Zhang, Jaividhya Dasarathy, Srinivasan Dasarathy, Laura E Nagy, Xiaoxia Li

Faculty, Staff and Student Publications

BACKGROUND: Macrophage-inducible C-type lectin (Mincle) is expressed on hepatic macrophages and senses ethanol (EtOH)-induced danger signals released from dying hepatocytes and promotes IL-1β production. However, it remains unclear what and how EtOH-induced Mincle ligands activate downstream signaling events to mediate IL-1β release and contribute to alcohol-associated liver disease (ALD). In this study, we investigated the association of circulating β-glucosylceramide (β-GluCer), an endogenous Mincle ligand, with severity of ALD and examined the mechanism by which β-GluCer engages Mincle on hepatic macrophages to release IL-1β in the absence of cell death and exacerbates ALD.

METHOD AND RESULTS: Concentrations of β-GluCer were increased …

Fully Human Monoclonal Antibody Targeting Activated Adam10 On Colorectal Cancer Cells, Nayanendu Saha, Du-San Baek, Rachelle P Mendoza, Dorothea Robev, Yan Xu, Yehuda Goldgur, M Jason De La Cruz, Elisa De Stanchina, Peter W Janes, Kai Xu, Dimiter S Dimitrov, Dimitar B Nikolov

Faculty, Staff and Student Publications

Metastasis and chemoresistance in colorectal cancer are mediated by certain poorly differentiated cancer cells, known as cancer stem cells, that are maintained by Notch downstream signaling initiated upon Notch cleavage by the metalloprotease ADAM10. It has been shown that ADAM10 overexpression correlates with aberrant signaling from Notch, erbBs, and other receptors, as well as a more aggressive metastatic phenotype, in a range of cancers including colon, gastric, prostate, breast, ovarian, uterine, and leukemia. ADAM10 inhibition, therefore, stands out as an important and new approach to deter the progression of advanced CRC. For targeting the ADAM10 substrate-binding region, which is located …

Redox Phospholipidomics Discovers Pro-Ferroptotic Death Signals In A375 Melanoma Cells In Vitro And In Vivo, Yulia Y Tyurina, Alexandr A Kapralov, Vladimir A Tyurin, Galina Shurin, Andrew A Amoscato, Dhivyaa Rajasundaram, Hua Tian, Yuri L Bunimovich, Yulia Nefedova, William G Herrick, Ralph E Parchment, James H Doroshow, Hulya Bayir, Apurva K Srivastava, Valerian E Kagan

Faculty, Staff and Student Publications

Growing cancer cells effectively evade most programs of regulated cell death, particularly apoptosis. This necessitates a search for alternative therapeutic modalities to cause cancer cell's demise, among them - ferroptosis. One of the obstacles to using pro-ferroptotic agents to treat cancer is the lack of adequate biomarkers of ferroptosis. Ferroptosis is accompanied by peroxidation of polyunsaturated species of phosphatidylethanolamine (PE) to hydroperoxy- (-OOH) derivatives, which act as death signals. We demonstrate that RSL3-induced death of A375 melanoma cells in vitro was fully preventable by ferrostatin-1, suggesting their high susceptibility to ferroptosis. Treatment of A375 cells with RSL3 caused a significant …

Predictors Of Perceived Functional Status In Early Systemic Sclerosis: A Prospective Longitudinal Study Of An Early Disease Cohort, Julia Chernis, Maryam Buni, Sarah Kazzaz, Jun Ying, Marka Lyons, Shervin Assassi, Maureen Mayes

Faculty, Staff and Student Publications

OBJECTIVE: The modified Health Assessment Questionnaire (M-HAQ) is a well-established patient-reported outcome measure in systemic sclerosis (SSc) studies that reflects how a patient functions in several categories of activities of daily living. This study analyzed clinical, demographic, and socioeconomic factors that predict M-HAQ scores over time.

METHODS: This study included 388 patients with baseline M-HAQ scores from the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) early disease cohort with a mean disease duration of 2.5 years, mean follow-up time of 3.9 years, and median follow-up of 7.2 years. A total of 1,950 M-HAQ measurements were analyzed. Baseline disease characteristics …

Author Correction: Comprehensive Molecular Characterization Of Mitochondrial Genomes In Human Cancers, Yuan Yuan, Young Seok Ju, Youngwook Kim, Jun Li, Yumeng Wang, Christopher J Yoon, Yang Yang, Inigo Martincorena, Chad J Creighton, John N Weinstein, Yanxun Xu, Leng Han, Hyung-Lae Kim, Hidewaki Nakagawa, Keunchil Park, Peter J Campbell, Han Liang

Faculty, Staff and Student Publications

No abstract provided.

National Cancer Control Plan Of The Korea: Current Status And The Fourth Plan (2021-2025), Kyu-Tae Han, Jae Kwan Jun, Jeong-Soo Im

Faculty, Staff and Student Publications

Cancer management has become a major policy goal for the government of the Korea. As such, the government introduced the National Cancer Control Plan (NCCP) to reduce the individual and social burdens caused by cancer and to promote national health. During the past 25 years, 3 phases of the NCCP have been completed. During this time, the NCCP has changed significantly in all aspects of cancer control from prevention to survival. The targets for cancer control are increasing, and although some blind spots remain, new demands are emerging. The government initiated the fourth NCCP in March 2021, with the vision …

Monte Carlo-Derived 99m Tc Uptake Quantification With Commercial Planar Mbi: Absolute Tumor Activity, Benjamin P Lopez, Srinivas Cheenu Kappadath

Faculty, Staff and Student Publications

BACKGROUND: Molecular breast imaging (MBI) of 99mTc-sestamibi is an emerging adjunct qualitative tool in the detection and diagnosis of breast cancer.

PURPOSE: This work outlines the development and performance evaluation of a methodology to absolutely quantify tumor 99mTc activity uptake using a commercially available dual-headed MBI system by implementing corrections for background, scatter, attenuation, and detector characteristics.

METHODS: A validated Monte Carlo application of a commercial MBI system was used to simulate over 7000 unique acquisitions of spherical and ellipsoidal tumors in breast tissue. Tumor absolute activity was calculated following background, scatter, and attenuation corrections of tumor region of interest …