Medical Specialties Commons^™

Intraprocedural Versus Initial Follow-Up Minimal Ablative Margin Assessment After Colorectal Liver Metastasis Thermal Ablation: Which One Better Predicts Local Outcomes?, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Bryan M Fellman, Aaron K Jones, Joshua D Kuban, Steven Y Huang, Zeyad A Metwalli, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Objectives: The aim of this study was to investigate the prognostic value of 3-dimensional minimal ablative margin (MAM) quantified by intraprocedural versus initial follow-up computed tomography (CT) in predicting local tumor progression (LTP) after colorectal liver metastasis (CLM) thermal ablation.

Materials and methods: This single-institution, patient-clustered, tumor-based retrospective study included patients undergoing microwave and radiofrequency ablation between 2016 and 2021. Patients without intraprocedural and initial follow-up contrast-enhanced CT, residual tumors, or with follow-up less than 1 year without LTP were excluded. Minimal ablative margin was quantified by a biomechanical deformable image registration method with segmentations of CLMs on intraprocedural preablation …

Dose-Dense Mini-Hyper-Cvd, Inotuzumab Ozogamicin And Blinatumomab Achieves Rapid Mrd-Negativity In Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia, Nicholas J Short, Elias Jabbour, Trevor Jamison, Shilpa Paul, Branko Cuglievan, David Mccall, Amber Gibson, Nitin Jain, Fadi G Haddad, Lewis F Nasr, Kayleigh R Marx, Caitlin Rausch, J Michael Savoy, Rebecca Garris, Farhad Ravandi, Hagop Kantarjian

Faculty, Staff and Student Publications

Background: The combination of low-intensity chemotherapy and inotuzumab ozogamicin (INO), with sequential blinatumomab, is highly effective in older adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) and in relapsed or refractory B-cell ALL. Earlier, "dose-dense" administration of blinatumomab could lead to earlier and deeper measurable residual disease (MRD) responses and better outcomes.

Patients and methods: We performed a retrospective analysis of the safety and efficacy of a dose-dense regimen of mini-hyper-CVD (mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with mini-methotrexate and cytarabine), INO, and blinatumomab in patients with B-cell ALL.

Results: Twenty-one patients were treated (frontline, n = 9; MRD …

Chromatin Remodeling In Patient-Derived Colorectal Cancer Models, Kun Xiang, Ergang Wang, John Mantyh, Gabrielle Rupprecht, Marcos Negrete, Golshid Sanati, Carolyn Hsu, Peggy Randon, Anders Dohlman, Kai Kretzschmar, Shree Bose, Nicholas Giroux, Shengli Ding, Lihua Wang, Jorge Prado Balcazar, Qiang Huang, Pasupathi Sundaramoorthy, Rui Xi, Shannon Jones Mccall, Zhaohui Wang, Chongming Jiang, Yubin Kang, Scott Kopetz, Gregory E Crawford, Steven M Lipkin, Xiao-Fan Wang, Hans Clevers, David Hsu, Xiling Shen

Faculty, Staff and Student Publications

Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the transcriptomic and chromatin accessibility landscapes of matched colorectal cancer (CRC) PDO, PDX, PDO-derived PDX (PDOX), and original patient tumors (PT) are compared. Two major remodeling axes are discovered. The first axis delineates PDMC from PT, and the second axis distinguishes PDX and PDO. PDOX are more similar to PDX than PDO, indicating the growth environment is a driving force for chromatin adaptation. Transcription factors …

Disease Progression, Survival, And Molecular Disparities In Black And White Patients With Endometrioid Endometrial Carcinoma In Real-World Registries And Gog/Nrg Oncology Randomized Phase Iii Clinical Trials, Zachary A Kopelman, Chunqiao Tian, Jordyn Tumas, Neil T Phippen, Christopher M Tarney, Erica R Hope, Stuart S Winkler, Suzanne Jokajtys, Calen W Kucera, John K Chan, Michael T Richardson, Daniel S Kapp, Chad A Hamilton, Charles A Leath, Nathaniel L Jones, Rodney P Rocconi, John H Farley, Angeles Alvarez Secord, Casey M Cosgrove, Matthew A Powell, Ann Klopp, Joan L Walker, Gini F Fleming, Nicholas W Bateman, Thomas P Conrads, G Larry Maxwell, Kathleen M Darcy

Faculty, Staff and Student Publications

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC).

METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death.

RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) …

Normal Risk Ovarian Screening Study: 21-Year Update, Chae Young Han, Karen H Lu, Gwen Corrigan, Alexandra Perez, Sharlene D Kohring, Joseph Celestino, Deepak Bedi, Enrique Bedia, Therese Bevers, David Boruta, Matthew Carlson, Laura Holman, Leroy Leeds, Cara Mathews, Georgia Mccann, Richard G Moore, Matthew Schlumbrecht, Brian Slomovitz, Dan Tobias, Yvette Williams-Brown, Michael W Bevers, Jinsong Liu, Terrie G Gornet, Beverly C Handy, Zhen Lu, Jacob S Bedia, Steven J Skates, Robert C Bast

Faculty, Staff and Student Publications

Purpose: The Normal Risk Ovarian Screening Study (NROSS) tested a two-stage screening strategy in postmenopausal women at conventional hereditary risk where significantly rising cancer antigen (CA)-125 prompted transvaginal sonography (TVS) and abnormal TVS prompted surgery to detect ovarian cancer.

Methods: A total of 7,856 healthy postmenopausal women were screened annually for a total of 50,596 woman-years in a single-arm study (ClinicalTrials.gov identifier: NCT00539162). Serum CA125 was analyzed with the Risk of Ovarian Cancer Algorithm (ROCA) each year. If risk was unchanged and < 1:2,000, women returned in a year. If risk increased above 1:500, TVS was undertaken immediately, and if risk was intermediate, CA125 was repeated in 3 months with a further increase in risk above 1:500 prompting referral for TVS. An average of 2% of participants were referred to TVS annually.

Results: Thirty-four patients were referred for operations detecting 15 ovarian cancers and two borderline tumors with 12 …

Histologic And Genomic Analysis Of Conjunctival Scc In African And American Cohorts Reveal Uv Light And Hpv Signatures And High Tumor Mutation Burden, Frederico O Gleber-Netto, Priyadharsini Nagarajan, Oded Sagiv, Curtis R Pickering, Neil Gross, Jing Ning, Melisachew M Yeshi, Yonas Mitku, Michael T Tetzlaff, Bita Esmaeli

Faculty, Staff and Student Publications

Purpose: Conjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with the rest of the world. This study aims to compare the genomic, immunophenotypic, and histologic features between patients from the United States and Ethiopia, to identify etiopathogenic mechanisms and unveil potential treatment strategies.

Methods: We compared histologic features and mutational profiles using whole exome sequencing, high-risk human papillomavirus (HPV) status, PD-L1 expression, and tumor-infiltrating lymphocytes in conjSCC tumors of patients from Ethiopia (ETH; n = 25) and the United States (from MD Anderson [the MDA cohort]; n = 29). Genomic alterations were compared …

Seamark: Phase Ii Study Of First-Line Encorafenib And Cetuximab Plus Pembrolizumab For Msi-H/Dmmr Brafv600e-Mutant Mcrc, Elena Elez, Scott Kopetz, Josep Tabernero, Tanios Bekaii-Saab, Julien Taieb, Takayuki Yoshino, Gulam Manji, Kathrine Fernandez, Antonello Abbattista, Xiaosong Zhang, Van K Morris

Faculty, Staff and Student Publications

Patients with both BRAF V600E mutations and microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) have poor prognosis. Currently, there are no specifically targeted first-line treatment options indicated for patients with mCRC whose tumors harbor both molecular aberrations. Pembrolizumab is a checkpoint inhibitor approved for the treatment of MSI-H/dMMR mCRC, and the BRAF inhibitor encorafenib, in combination with cetuximab, is approved for previously treated BRAF V600E-mutant mCRC. Combination of pembrolizumab with encorafenib and cetuximab may synergistically enhance antitumor activity in patients with BRAF V600E-mutant, MSI-H/dMMR mCRC. SEAMARK is a randomized phase II study comparing the efficacy of the combination …

Dietary Magnesium Replacement For Prevention Of Hypomagnesemia In Patients With Ovarian Cancer Receiving Carboplatin-Based Chemotherapy, Wenli Liu, Larissa Meyer, Meroë Morse, Yisheng Li, Juhee Song, Rosalinda Engle, Gabriel Lopez, Santhosshi Narayanan, Pamela T Soliman, Lois Ramondetta, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

Purpose: Hypomagnesemia is a common side effect of platinum-based chemotherapy and predicts poor overall survival in some cancers. Standard magnesium replacement strategies are often inadequate for maintaining magnesium levels. We hypothesized that a daily dietary magnesium replacement approach through magnesium-rich foods would help maintain adequate magnesium levels during platinum-based treatment.

Materials and methods: We conducted a prospective feasibility study of magnesium-rich diets in patients 18 years and older with previously untreated ovarian cancer scheduled to receive carboplatin-containing chemotherapy of at least six consecutive cycles. Education about magnesium-rich diets was provided at enrollment and then weekly during chemotherapy. Feasibility was defined …

A Randomized, Non-Comparative Phase 2 Study Of Neoadjuvant Immune-Checkpoint Blockade In Retroperitoneal Dedifferentiated Liposarcoma And Extremity/Truncal Undifferentiated Pleomorphic Sarcoma, Christina L Roland, Elise F Nassif Haddad, Emily Z Keung, Wei-Lien Wang, Alexander J Lazar, Heather Lin, Manoj Chelvanambi, Edwin R Parra, Khalida Wani, B Ashleigh Guadagnolo, Andrew J Bishop, Elizabeth M Burton, Kelly K Hunt, Keila E Torres, Barry W Feig, Christopher P Scally, Valerae O Lewis, Justin E Bird, Ravin Ratan, Dejka Araujo, M Alexandra Zarzour, Shreyaskumar Patel, Robert Benjamin, Anthony P Conley, J Andrew Livingston, Vinod Ravi, Hussein A Tawbi, Patrick P Lin, Bryan S Moon, Robert L Satcher, Bilal Mujtaba, Russell G Witt, Raymond S Traweek, Brandon Cope, Rossana Lazcano, Chia-Chin Wu, Xiao Zhou, Mohammad M Mohammad, Randy A Chu, Jianhua Zhang, Ashish Damania, Pranoti Sahasrabhojane, Taylor Tate, Kate Callahan, Sa Nguyen, Davis Ingram, Rohini Morey, Shadarra Crosby, Grace Mathew, Sheila Duncan, Cibelle F Lima, Jean-Yves Blay, Wolf Herman Fridman, Kenna Shaw, Ignacio Wistuba, Andrew Futreal, Nadim Ajami, Jennifer A Wargo, Neeta Somaiah

Faculty, Staff and Student Publications

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells …

Tp53 Mutation Is Frequent In Mantle Cell Lymphoma With Ezh2 Expression And Have Dismal Outcome When Both Are Present, Do Hwan Kim, Saima Siddiqui, Preetesh Jain, Michael Wang, Beenu Thakral, Shaoying Li, Roberto Miranda, Francisco Vega, L Jeffrey Medeiros, Chi Young Ok

Faculty, Staff and Student Publications

Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(-) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and …

Tp53 Mutation Is Frequent In Mantle Cell Lymphoma With Ezh2 Expression And Have Dismal Outcome When Both Are Present, Do Hwan Kim, Saima Siddiqui, Preetesh Jain, Michael Wang, Beenu Thakral, Shaoying Li, Roberto Miranda, Francisco Vega, L Jeffrey Medeiros, Chi Young Ok

Faculty, Staff and Student Publications

Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(-) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and …

Thematic Analysis Of Alzheimer's Medication Management Discussion In A Non-Moderated Online Forum, Jia Liu, Kylie Meyer, Ashlie Glassner, Mitzi Gonzales, Rebecca J Bartlett Ellis, Hyejin Park, Lixin Song, Neela Patel, Jing Wang

Faculty, Staff and Student Publications

Background: Managing medications for Alzheimer's disease and related dementias is challenging for caregivers. Information about caregivers' strategies to manage these challenges is needed to inform intervention development.

Objective: This study aimed to understand caregivers' medication management experiences by analyzing online community discussions.

Methods: Posts were extracted from the ALZConnected® Forum using keywords "medication" and "drug" via web scraping. The researchers applied thematic analysis.

Results: Four major themes emerged: (1) role transition of medication management responsibilities, (2) caregivers' uncertainty about medication purpose and values, (3) conflicts between the care recipients and caregivers, and (4) difficulty accessing and affording medications.

Conclusions: The …

The Value Of Global Collaborations, Chris Trauernicht, Laurence Court

Faculty, Staff and Student Publications

No abstract provided.

Investigation Of Potential Gut Health Biomarkers In Broiler Chicks Challenged By Campylobacter Jejuni And Submitted To A Continuous Water Disinfection Program, Tilemachos Mantzios, Despoina E. Kiousi, Georgia D. Brellou, Georgios A. Papadopoulos, Vangelis Economou, Marili Vasilogianni, Elisavet Kanari, Evanthia Petridou, Ilias Giannenas, Guillermo Tellez-Isaias, Aglaia Pappa, Alex Galanis, Vasilios Tsiouris

Poultry Science Faculty Publications and Presentations

The exploration of novel biomarkers to assess poultry health is of paramount importance, not only to enhance our understanding of the pathogenicity of zoonotic agents but also to evaluate the efficacy of novel treatments as alternatives to antibiotics. The present study aimed to investigate potential gut health biomarkers in broiler chicks challenged by Campylobacter jejuni and subjected to a continuous water disinfection program. A total of 144 one-day-old hatched broiler chicks were randomly allocated to four treatment groups with four replicates each, according to the following experimental design: Group A received untreated drinking water; Group B received drinking water treated …

Lac-Phe Mediates The Effects Of Metformin On Food Intake And Body Weight, Shuke Xiao, Veronica L Li, Xuchao Lyu, Xudong Chen, Wei Wei, Fahim Abbasi, Joshua W Knowles, Alan Sheng-Hwa Tung, Shuliang Deng, Gaurav Tiwari, Xu Shi, Shuning Zheng, Laurie Farrell, Zsu-Zsu Chen, Kent D Taylor, Xiuqing Guo, Mark O Goodarzi, Alexis C Wood, Yii-Der Ida Chen, Leslie A Lange, Stephen S Rich, Jerome I Rotter, Clary B Clish, Usman A Tahir, Robert E Gerszten, Mark D Benson, Jonathan Z Long

Children’s Nutrition Research Center Staff Publications

Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. There is ongoing debate about the mechanisms that mediate metformin’s effects on energy balance. Here, we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite N-lactoyl-phenylalanine (Lac-Phe) in cells, in mice and two independent human cohorts. Metformin drives Lac-Phe biosynthesis through the inhibition of complex I, increased glycolytic flux and intracellular lactate mass action. Intestinal epithelial CNDP2+ cells, not macrophages, are the principal in vivo source of basal and metformin-inducible Lac-Phe. Genetic ablation of Lac-Phe biosynthesis in male mice renders animals resistant to the …

Cranio-Cervical Abnormalities In Moderate-To-Severe Osteogenesis Imperfecta – Genotypic And Phenotypic Determinants, Juliana Marulanda, Jean-Marc Retrouvey, Brendan Lee, V Reid Sutton, Frank Rauch, Michelle Briner

Faculty, Staff and Students Publications

INTRODUCTION: Cranio-cervical anomalies are significant complications of osteogenesis imperfecta (OI), a rare bone fragility disorder that is usually caused by mutations in collagen type I encoding genes.

OBJECTIVE: To assess cranio-cervical anomalies and associated clinical findings in patients with moderate-to-severe OI using 3D cone beam computed tomography (CBCT) scans.

METHODS: Cross-sectional analysis of CBCT scans in 52 individuals with OI (age 10-37 years; 32 females) and 40 healthy controls (age 10-32 years; 26 females). Individuals with a diagnosis of OI type III (severe, n = 11), type IV (moderate, n = 33) and non-collagen OI (n = 8) were recruited …

An Oocyte-Specific Cas9-Expressing Mouse For Germline Crispr/Cas9-Mediated Genome Editing, Denise G Lanza, Jianqiang Mao, Isabel Lorenzo, Lan Liao, John R Seavitt, M Cecilia Ljungberg, Elizabeth M Simpson, Francesco J Demayo, Jason D Heaney

Faculty, Staff and Students Publications

Cas9 transgenes can be employed for genome editing in mouse zygotes. However, using transgenic instead of exogenous Cas9 to produce gene-edited animals creates unique issues including ill-defined transgene integration sites, the potential for prolonged Cas9 expression in transgenic embryos, and increased genotyping burden. To overcome these issues, we generated mice harboring an oocyte-specific, Gdf9 promoter driven, Cas9 transgene (Gdf9-Cas9) targeted as a single copy into the Hprt1 locus. The X-linked Hprt1 locus was selected because it is a defined integration site that does not influence transgene expression, and breeding of transgenic males generates obligate transgenic females to serve as embryo …

Effectiveness Of Cord Blood As A Strategy To Rule Out Conjugated Hyperbilirubinemia, Miray Kurtca, Sanjiv Harpavat, Sridevi Devaraj

Faculty, Staff and Students Publications

Early detection of biliary atresia is crucial for timely intervention and improved outcomes in infants with elevated conjugated bilirubin levels. This study aims to investigate the viability of cord blood gas analysis as a novel method for assessing conjugated bilirubin levels. Infants with high heel stick levels also showed elevated cord blood bilirubin levels, indicating that cord blood testing could replace the need for repeat heel stick tests, especially benefiting low birth weight infants. Ongoing research, including larger cohorts and alternative bilirubin measurement methods, will further validate this innovative screening approach. Infants with biliary atresia have high conjugated bilirubin levels …

A Mutation In Tbxt Causes Congenital Vertebral Malformations In Humans And Mice, Shuxia Chen, Yunping Lei, Yajun Yang, Chennan Liu, Lele Kuang, Li Jin, Richard H Finnell, Xueyan Yang, Hongyan Wang

Faculty, Staff and Students Publications

T-box transcription factor T (TBXT; T) is required for mesodermal formation and axial skeletal development. Although it has been extensively studied in various model organisms, human congenital vertebral malformations (CVMs) involving T are not well established. Here, we report a family with 15 CVM patients distributed across 4 generations. All affected individuals carry a heterozygous mutation, T c.596A>G (p.Q199R), which is not found in unaffected family members, indicating co-segregation of the genotype and phenotype. In vitro assays show that T p.Q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity, but reduces its transcriptional activity compared to the wild-type. …

Cyclophilin A Supports Translation Of Intrinsically Disordered Proteins And Affects Haematopoietic Stem Cell Ageing, Laure Maneix, Polina Iakova, Charles G Lee, Shannon E Moree, Xuan Lu, Gandhar K Datar, Cedric T Hill, Eric Spooner, Jordon C K King, David B Sykes, Borja Saez, Bruno Di Stefano, Xi Chen, Daniela S Krause, Ergun Sahin, Francis T F Tsai, Margaret A Goodell, Bradford C Berk, David T Scadden, André Catic

Faculty, Staff and Students Publications

Loss of protein function is a driving force of ageing. We have identified peptidyl-prolyl isomerase A (PPIA or cyclophilin A) as a dominant chaperone in haematopoietic stem and progenitor cells. Depletion of PPIA accelerates stem cell ageing. We found that proteins with intrinsically disordered regions (IDRs) are frequent PPIA substrates. IDRs facilitate interactions with other proteins or nucleic acids and can trigger liquid-liquid phase separation. Over 20% of PPIA substrates are involved in the formation of supramolecular membrane-less organelles. PPIA affects regulators of stress granules (PABPC1), P-bodies (DDX6) and nucleoli (NPM1) to promote phase separation and increase cellular stress resistance. …

Tgf-Β1 And Tgf-Βr1 Variants Are Associated With Clinical Outcomes In Smoking-Related Head And Neck Cancer Patients Treated With Chemoradiation Through Modulating Microrna-Mediated Regulation, Zihao Niu, Peng Sun, Mark E Zafereo, Hongliang Liu, Peng Wei, Jia Wu, Neil D Gross, Sanjay Shete, Qingyi Wei, Guibin Zheng, Andy G Sikora, George A Calin, Guojun Li

Faculty, Staff and Student Publications

TGF-β1 and TGF-βR1 play important roles in immune and inflammatory responses. Genetic variants of TGF-β1 rs1800470 and TGF-βR1 rs334348 have emerged as potentially prognostic biomarkers for HPV-related head and neck cancer, while their prognostic effect on survival of smoking-related head and neck cancer remains unknown. This study included 1403 patients with smoking-related head and neck cancer, and all these patients were genotyped for TGF-β1 rs1800470 and TGF-βR1 rs334348. Both univariate and multivariate analyses were performed to evaluate associations between the two functional genetic variants in microRNA binding sites of TGF-β1 and TGF-βR1 and survivals. Patients with TGF-β1 rs1800470 CT or …

Myeloid-Derived Suppressor Cell Mitochondrial Fitness Governs Chemotherapeutic Efficacy In Hematologic Malignancies, Saeed Daneshmandi, Jee Eun Choi, Qi Yan, Cameron R. Macdonald, Manu Pandey, Mounika Goruganthu, Nathan Roberts, Prashant K. Singh, Richard M. Higashi, Andrew N. Lane, Teresa W-M Fan, Jianmin Wang, Philip L. Mccarthy, Elizabeth A. Repasky, Hemn Mohammadpour

Markey Cancer Center Faculty Publications

Myeloid derived suppressor cells (MDSCs) are key regulators of immune responses and correlate with poor outcomes in hematologic malignancies. Here, we identify that MDSC mitochondrial fitness controls the efficacy of doxorubicin chemotherapy in a preclinical lymphoma model. Mechanistically, we show that triggering STAT3 signaling via β2-adrenergic receptor (β2-AR) activation leads to improved MDSC function through metabolic reprogram- ing, marked by sustained mitochondrial respiration and higher ATP generation which reduces AMPK signaling, altering energy metabolism. Furthermore, induced STAT3 signaling in MDSCs enhances glutamine consumption via the TCA cycle. Metabolized glutamine generates itaconate which downregulates mitochondrial reactive oxygen species via regulation of …

Randomized Controlled Trial Of The Cmr Immersive Virtual Reality (Ivr) Headset Training Compared To E-Learning For Operating Room Configuration Of The Cmr Versius Robot, Catherine L Eley, Varun Palaniappan, Abbie Carter, Opeyemi Sogaolu, James Horwood, Michael Davies, Jared Torkington, James Ansell

Faculty, Staff and Student Publications

Robotic surgery offers potential advantages over laparoscopic procedures, but the training for configuring robotic systems in the operating room remains underexplored. This study seeks to validate immersive virtual reality (IVR) headset training for setting up the CMR Versius in the operating room. This single-blinded randomized control trial randomised medical students with no prior robotic experience using an online randomiser. The intervention group received IVR headset training, and the control group, e-learning modules. Assessors were blinded to participant group. Primary endpoint was overall score (OS): Likert-scale 1-5: 1 reflecting independent performance, with increasing verbal prompts to a maximum score of 5, …

Activation Of Endogenous Retroviruses And Induction Of Viral Mimicry By Mek1/2 Inhibition In Pancreatic Cancer, Alice Cortesi, Francesco Gandolfi, Fabiana Arco, Pierluigi Di Chiaro, Emanuele Valli, Sara Polletti, Roberta Noberini, Francesco Gualdrini, Sergio Attanasio, Francesca Citron, I-Lin Ho, Rutvi Shah, Er-Yen Yen, Mara Cetty Spinella, Simona Ronzoni, Simona Rodighiero, Nico Mitro, Tiziana Bonaldi, Serena Ghisletti, Silvia Monticelli, Andrea Viale, Giuseppe Riccardo Diaferia, Gioacchino Natoli

Faculty, Staff and Student Publications

While pancreatic ductal adenocarcinomas (PDACs) are addicted to KRAS-activating mutations, inhibitors of downstream KRAS effectors, such as the MEK1/2 kinase inhibitor trametinib, are devoid of therapeutic effects. However, the extensive rewiring of regulatory circuits driven by the attenuation of the KRAS pathway may induce vulnerabilities of therapeutic relevance. An in-depth molecular analysis of the transcriptional and epigenomic alterations occurring in PDAC cells in the initial hours after MEK1/2 inhibition by trametinib unveiled the induction of endogenous retroviruses (ERVs) escaping epigenetic silencing, leading to the production of double-stranded RNAs and the increased expression of interferon (IFN) genes. We tracked ERV activation …

Visual Analysis Of Bone Malignancies Immunotherapy: A Bibliometric Analysis From 2010 To 2023, Kaiyu Shen, Liu Yang, Shuaiyi Ke, Wencang Gao

Faculty, Staff and Student Publications

Background: Bone malignancies (BM), including osteosarcoma, Ewing's sarcoma, chondrosarcoma, and chordoma, are characterized by high rates of recurrence and mortality, despite the availability of diverse treatment approaches. Immunotherapy has gained increasing importance in cancer treatment. However, there is a lack of comprehensive studies that utilize bibliometric analysis to explore immunotherapy for BM.

Methods: A literature search of English studies on BM and immunotherapy from 2010 to 2023 was conducted in the Web of Science Core Collection database. Bibliometric analysis tools such as VOSviewer, CiteSpace, and R Studio were utilized to examine global trends and research hotspots in this field.

Results: …

Pre-Covid-19 Hospital Quality And Hospital Response To Covid-19: Examining Associations Between Risk-Adjusted Mortality For Patients Hospitalised With Covid-19 And Pre-Covid-19 Hospital Quality, Doris Peter, Shu-Xia Li, Yongfei Wang, Jing Zhang, Jacqueline Grady, Kerry Mcdowell, Erica Norton, Zhenqiu Lin, Susannah Bernheim, Arjun K Venkatesh, Lee A Fleisher, Michelle Schreiber, Lisa G Suter, Elizabeth W Triche

Faculty, Staff and Student Publications

OBJECTIVES: The extent to which care quality influenced outcomes for patients hospitalised with COVID-19 is unknown. Our objective was to determine if prepandemic hospital quality is associated with mortality among Medicare patients hospitalised with COVID-19.

DESIGN: This is a retrospective observational study. We calculated hospital-level risk-standardised in-hospital and 30-day mortality rates (risk-standardised mortality rates, RSMRs) for patients hospitalised with COVID-19, and correlation coefficients between RSMRs and pre-COVID-19 hospital quality, overall and stratified by hospital characteristics.

SETTING: Short-term acute care hospitals and critical access hospitals in the USA.

PARTICIPANTS: Hospitalised Medicare beneficiaries (Fee-For-Service and Medicare Advantage) age 65 and older hospitalised …

Ndrgs In Breast Cancer: A Review And In Silico Analysis, Emilly S Villodre, Anh P N Nguyen, Bisrat G Debeb

Faculty, Staff and Student Publications

Simple Summary

Breast cancer is the most common cancer in women and one of the deadliest. While survival rates for patients with breast cancer have seen notable improvements in recent decades, current treatment strategies still face significant limitations, especially for patients with aggressive, therapy-resistant, and metastatic breast cancers. For this reason, it is important to identify new targets in order to develop more effective therapeutic strategies. The N-myc downstream regulated gene family (NDRGs), comprising NDRG1, NDRG2, NDRG3, and NDRG4, has been previously described as tumor suppressors. However, recent findings challenge this perception, particularly for NDRG1, …

Regional Analysis To Delineate Intrasample Heterogeneity With Regionalst, Yue Lyu, Chong Wu, Wei Sun, Ziyi Li

Faculty, Staff and Student Publications

MOTIVATION: Spatial transcriptomics has greatly contributed to our understanding of spatial and intra-sample heterogeneity, which could be crucial for deciphering the molecular basis of human diseases. Intra-tumor heterogeneity, e.g. may be associated with cancer treatment responses. However, the lack of computational tools for exploiting cross-regional information and the limited spatial resolution of current technologies present major obstacles to elucidating tissue heterogeneity.

RESULTS: To address these challenges, we introduce RegionalST, an efficient computational method that enables users to quantify cell type mixture and interactions, identify sub-regions of interest, and perform cross-region cell type-specific differential analysis for the first time. Our simulations …

Dissection, Histological Processing, And Gene Expression Analysis Of Murine Supraclavicular Brown Adipose Tissue, Mark G Waterstraat, Ziyi Wang, Mari Kogiso, Rommel Caballero-Juarez, Miao-Hsueh Chen

Children’s Nutrition Research Center Staff Publications

Brown adipose tissue (BAT)-mediated thermogenesis plays an important role in the regulation of metabolism, and its morphology and function can be greatly impacted by environmental stimuli in mice and humans. Currently, murine interscapular BAT (iBAT), which is located between two scapulae in the upper dorsal flank of mice, is the main BAT depot used by research laboratories to study BAT function. Recently, a few previously unknown BAT depots were identified in mice, including one analogous to human supraclavicular brown adipose tissue. Unlike iBAT, murine supraclavicular brown adipose tissue (scBAT) is situated in the intermediate layer of the neck and thus …

Admix-Kit: An Integrated Toolkit And Pipeline For Genetic Analyses Of Admixed Populations, Kangcheng Hou, Stephanie Gogarten, Joohyun Kim, Xing Hua, Julie-Alexia Dias, Quan Sun, Ying Wang, Taotao Tan, Elizabeth G Atkinson, Alicia Martin, Jonathan Shortt, Jibril Hirbo, Yun Li, Bogdan Pasaniuc, Haoyu Zhang

Faculty, Staff and Students Publications

SUMMARY: Admixed populations, with their unique and diverse genetic backgrounds, are often underrepresented in genetic studies. This oversight not only limits our understanding but also exacerbates existing health disparities. One major barrier has been the lack of efficient tools tailored for the special challenges of genetic studies of admixed populations. Here, we present admix-kit, an integrated toolkit and pipeline for genetic analyses of admixed populations. Admix-kit implements a suite of methods to facilitate genotype and phenotype simulation, association testing, genetic architecture inference, and polygenic scoring in admixed populations.

AVAILABILITY AND IMPLEMENTATION: Admix-kit package is open-source and available at https://github.com/KangchengHou/admix-kit. …