Digital Commons Network^™

Measles Is Just A Harbinger, Catherine Troisi

Faculty, Staff and Student Publications

No abstract provided.

Immunotherapy Targeting A Leader Sequence Cathepsin G-Derived Peptide, Chunhua Shi, Ze Tian, Jun Yan, Mao Zhang, Pariya Sukhumalchandra, Edward Chang, Guojun Yang, Junping You, Meng Cui, Qing Shi, Celine Kerros, Anne Philips, Na Qiao, Hiroki Torikai, Sathvik Patchametla, Anna Sergeeva, Lisa St John, Helen He, Dmitri Wiederschain, Benjamin H Lee, Geraldine L C Paulus, Dongxing Zha, Jeffrey Molldrem, Gheath Alatrash

Faculty, Staff and Student Publications

Myeloid azurophil granules provide a rich source of intracellular leukemia antigens. Cathepsin G (CG) is a serine protease that has higher expression in acute myeloid leukemia (AML) blasts in comparison to normal myeloid progenitors. Based on the unique biology of HLA-A*0201 (HLA-A2), in which presentation of leader sequence (LS)-derived peptides is favored, we focused on the LS-CG-derived peptide CG1 (FLLPTGAEA). We previously detected CG1/HLA-A2 complexes on the surface of primary HLA-A2+ AML blasts and cell lines, and immunity targeting CG1/HLA-A2 in leukemia patients. T cell receptor (TCR)-mimic (m) antibodies are immunotherapeutic antibodies that target peptide-HLA (pHLA) complexes. Here we report …

Staged Screening Identifies People With Biomarkers Related To Neuronal Alpha-Synuclein Disease, Ethan G Brown, Lana M Chahine, Andrew Siderowf, Caroline Gochanour, Ryan Kurth, Micah J Marshall, Chelsea Caspell-Garcia, Michael C Brumm, Craig E Stanley, Monica Korell, Bridget Mcmahon, Maggie Kuhl, Kimberly Fabrizio, Laura Heathers, Luis Concha-Marambio, Claudio Soto, Sohini Chowdhury, Christopher S Coffey, Tatiana M Foroud, Tanya Simuni, Kenneth Marek, Caroline M Tanner

Faculty, Staff and Student Publications

Objective: Remote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha-synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single-photon emission computed tomography imaging (DAT-SPECT) and alpha-synuclein aggregation.

Methods: The Parkinson's Progression Markers Initiative (PPMI) recruited participants for the prodromal cohort who were 60-years and older without a Parkinson's disease diagnosis. Participants were invited to complete a University of Pennsylvania Smell Identification Test (UPSIT) independently through an online portal. Hyposmic participants were invited to complete DAT-SPECT, which determined eligibility for enrollment in …

Nicotinic Acetylcholine Receptor Expression In Merkel Cell Carcinoma Is Associated With Clinical And Histopathologic Parameters, Christopher R Cunningham, Yiannis P Dimopoulos, Ian M García-Quiñones, Denái R Milton, Manuel Delgado-Vélez, Woo Cheal Cho, Victor G Prieto, José A Lasalde-Dominicci, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.

Methods: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the …

Nicotinic Acetylcholine Receptor Expression In Merkel Cell Carcinoma Is Associated With Clinical And Histopathologic Parameters, Christopher R Cunningham, Yiannis P Dimopoulos, Ian M García-Quiñones, Denái R Milton, Manuel Delgado-Vélez, Woo Cheal Cho, Victor G Prieto, José A Lasalde-Dominicci, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.

Methods: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the …

Uric Acid Stroke Cerebroprotection Transcended Sex, Age, And Comorbidities In A Multicenter Preclinical Trial, Rakesh B Patel, Mariia Kumskova, Hanish Kodali, Ivan Budnik, Vitalii Kuznetsov, Aditi Jain, Abhishek Jha, Daniel Thedens, Nirav Dhanesha, Brijesh Sutariya, Karisma A Nagarkatti, Jessica Lamb, Pradip Kamat, Yanrong Shi, Brooklyn Avery, Takahiko Imai, Xuyan Jin, Anjali Chauhan, Ligia S B Boisserand, Mohammad B Khan, Krishnan Dhandapani, Basavaraju G Sanganahalli, Lauren H Sansing, David C Hess, Raymond C Koehler, Louise D Mccullough, Jaroslaw Aronowski, Cenk Ayata, Márcio A Diniz, Patrick D Lyden, Anna M Planas, Angel Chamorro, Anil K Chauhan, Enrique C Leira, Span Investigators

Faculty, Staff and Student Publications

Background: Past failures in translating stroke cerebroprotection provoked calls for a more rigorous methodological approach, leading to the stroke preclinical assessment network SPAN (Stroke Preclinical Assessment Network), where uric acid (UA) treatment exceeded a prespecified efficacy boundary for the primary functional outcome. Still, successful translation to humans requires confirmation of the effect of UA across key biological variables relevant to patients with stroke.

Methods: We measured the effects of intravenous UA treatment (16 mg/kg) versus intravenous saline in groups of animals enrolled in the SPAN network with diverse comorbidities, sex, and age. The masked study drug or placebo was administered …

Opportunities In Stroke Care At Safety Net Hospitals: A Socioecological Perspective, Anjail Sharrief, Joshua Wollen, Maha Almohamad, M Carter Denny, Erica Jones, Aardhra M Venkatachalam, Digvijaya Navalkele, Shivika Chandra, Mariam Ahmed, Robert Pratt, Bradley D Shy, John Mcmenamy, Chigozirim Izeogu, Lesli E Skolarus, Nneka L Ifejika, Nicole R Gonzales

Faculty, Staff and Student Publications

Safety net hospitals (SNHs) provide care to patients regardless of their insurance status or ability to pay, serving populations at the highest risk for poor stroke outcomes. These include historically marginalized racial and ethnic groups, and individuals disproportionately affected by adverse social drivers of health, including lower socioeconomic status, housing instability, and limited access to preventive care. Improving stroke care at SNHs presents a critical opportunity to strengthen care delivery for individuals with the greatest need. However, such efforts require a clear understanding of the barriers across all levels of the healthcare system. In this Perspective, the authors adopt a …

Lysyl Hydroxylase 2 Glucosylates Collagen Vi To Drive Lung Cancer Progression, Shike Wang, Houfu Guo, Reo Fukushima, Masahiko Terajima, Min Liu, Guan-Yu Xiao, Lenka Koudelková, Chao Wu, Xin Liu, Jiang Yu, Emma Burris, Jun Xu, Alvise Schiavinato, William K Russell, Mitsuo Yamauchi, Xiaochao Tan, Jonathan M Kurie

Faculty, Staff and Student Publications

Lysyl hydroxylase 2 (LH2) is highly expressed in multiple tumor types and accelerates disease progression by hydroxylating lysine residues on fibrillar collagen telopeptides to generate stable collagen cross links in tumor stroma. Here, we show that a galactosylhydroxylysyl glucosyltransferase (GGT) domain on LH2-modified type-VI collagen (Col6) to promote lung adenocarcinoma (LUAD) growth and metastasis. In tumors generated by LUAD cells lacking LH2 GGT domain activity, stroma was less stiff, and stable types of collagen cross links were reduced. Mass spectrometric analysis of total and glycosylated peptides in parental and GGT-inactive tumor samples identified Col6 chain α3 (Col6a3), a component of …

Acute Pain Trajectories In Elderly Patients With Fragility Hip Fractures, Paul Potnuru, Christina Goehl, Katherine S Becker, Alejandro Juul, Madison Aycock, Johanna Blair De Haan, Sudipta Sen, Michelle Ge, Stephen J Warner, Nadia Hernandez

Faculty, Staff and Student Publications

Background: Pain management for hospitalized elderly patients with fragility hip fractures (FHF) remains challenging. This study aims to distinguish acute pain trajectories in FHF patients that can inform personalized analgesia management.

Methods: We conducted a prospective observational study of patients aged 65 and older with FHF at a Level I trauma center. The primary outcome was daily average pain assessed for five days post-injury using the Brief Pain Inventory (BPI). We used group-based trajectory modeling (GBTM) to distinguish acute pain trajectories. Then, factors and secondary outcomes (opioid use and hospital length of stay [LOS]) associated with more severe pain trajectories …

Role Of Peripheral Amyloid-Β Aggregates In Alzheimer's Disease: Mechanistic, Diagnostic, And Therapeutic Implications, Nazaret Gamez, Rodrigo Morales

Faculty, Staff and Student Publications

No abstract provided.

Unleashing The Power Of Multiomics: Unraveling The Molecular Landscape Of Peripheral Neuropathy, Julie Choi, Zitian Tang, Wendy Dong, Jenna Ulibarri, Elvisa Mehinovic, Simone Thomas, Ahmet Höke, Sheng Chih Jin

Faculty, Staff and Student Publications

Peripheral neuropathies (PNs) affect over 20 million individuals in the United States, manifesting as a wide range of sensory, motor, and autonomic nerve symptoms. While various conditions such as diabetes, metabolic disorders, trauma, autoimmune disease, and chemotherapy-induced neurotoxicity have been linked to PN, approximately one-third of PN cases remain idiopathic, underscoring a critical gap in our understanding of these disorders. Over the years, considerable efforts have focused on unraveling the complex molecular pathways underlying PN to advance diagnosis and treatment. Traditional methods such as linkage analysis, fluorescence in situ hybridization, polymerase chain reaction, and Sanger sequencing identified initial genetic variants …

The Placenta Regulates Intrauterine Fetal Growth Via Exosomal Pparγ, Xiaofang Luo, Biao Huang, Ping Xu, Hao Wang, Baozhen Zhang, Li Lin, Jiujiang Liao, Mingyu Hu, Xiyao Liu, Jiayu Huang, Yong Fu, Mark D Kilby, Rodney E Kellems, Xiujun Fan, Yang Xia, Philip N Baker, Hongbo Qi, Chao Tong

Faculty, Staff and Student Publications

Abnormal adipogenesis is a major contributor to fetal growth restriction (FGR) and its associated complications. However, the underlying etiology remains unclear. Here, it is reported that the placentas of women with pregnancies complicated with FGR exhibit peroxisome proliferator-activated receptor γ (PPARγ) inactivation. In mice, trophoblast-specific ablation of murine PPARγ reproduces the phenotype of human fetuses with FGR and defective adipogenesis. Coculture of trophoblasts with preadipocytes significantly improves preadipocyte commitment and differentiation and increases the transcription of a series of adipogenic genes via intercellular transfer of exosomal PPARγ proteins. Moreover, nanoparticle-mediated placenta-specific delivery of rosiglitazone (RGZ) significantly rescues adipogenesis defects in …

Calcium-Sensing Receptor As A Novel Target For The Treatment Of Idiopathic Pulmonary Fibrosis, Kasope Wolffs, Renjiao Li, Bethan Mansfield, Daniel A Pass, Richard T Bruce, Ping Huang, Rachel Paes De Araújo, Bahareh Sadat Haddadi, Luis A J Mur, Jordanna Dally, Ryan Moseley, Rupert Ecker, Harry Karmouty-Quintana, Keir E Lewis, A John Simpson, Jeremy P T Ward, Christopher J Corrigan, Renata Z Jurkowska, Benjamin D Hope-Gill, Daniela Riccardi, Polina L Yarova

Faculty, Staff and Student Publications

Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and no curative therapies. Fibroblast activation by transforming growth factor β1 (TGFβ1) and disrupted metabolic pathways, including the arginine-polyamine pathway, play crucial roles in IPF development. Polyamines are agonists of the calcium/cation-sensing receptor (CaSR), activation of which is detrimental for asthma and pulmonary hypertension, but its role in IPF is unknown. To address this question, we evaluated polyamine abundance using metabolomic analysis of IPF patient saliva. Furthermore, we examined CaSR functional expression in human lung fibroblasts (HLFs), assessed the anti-fibrotic effects of a CaSR antagonist, NPS2143, in TGFβ1-activated normal …

The Impact Of Atlas Parcellation On Functional Connectivity Analysis Across Six Psychiatric Disorders, Xiaoya Wu, Chuang Liang, Juan Bustillo, Peter Kochunov, Xuyun Wen, Jing Sui, Rongtao Jiang, Xiao Yang, Zening Fu, Daoqiang Zhang, Vince D Calhoun, Shile Qi

Faculty, Staff and Student Publications

Neuropsychiatric disorders are associated with altered functional connectivity (FC); however, the reported regional patterns of functional alterations suffered from low replicability and high variability. This is partly because of differences in the atlas and delineation techniques used to measure FC-related deficits within/across disorders. We systematically investigated the impact of the brain parcellation approach on the FC-based brain network analysis. We focused on identifying the replicable FCs using three structural brain atlases, including Automated Anatomical Labeling (AAL), Brainnetome atlas (BNA) and HCP_MMP_1.0, and four functional brain parcellation approaches: Yeo-Networks (Yeo), Gordon parcel (Gordon) and two Schaefer parcelletions, among correlation, group difference, …

The Interaction Between Antithrombin And Endothelial Heparan Sulfate Mitigates Pulmonary Thromboinflammation After Trauma And Hemorrhagic Shock, Maria Del Pilar Huby Vidaurre, Ava K Mokhtari, Baron K Osborn, Bryan A Cotton, Yao-Wei Wang, Yongmei Xu, Katelyn Arnold, Jian Liu, Jillian R Richter, Jessica C Cardenas

Faculty, Staff and Student Publications

Introduction:

Trauma and hemorrhagic shock (T/HS) are associated with multiple organ injury. Antithrombin (AT) has anti-inflammatory and organ protective activity through its interaction with endothelial heparan sulfate containing a 3-O-sulfate modification. Our objective was to examine the effects of T/HS on 3-O-sulfated (3-OS) heparan sulfate expression and determine whether AT-heparan sulfate interactions are necessary for its anti-inflammatory properties.

Methods:

Male Sprague Dawley rats underwent laparotomy, gut distension and fixed-pressure hemorrhagic shock (HS) and resuscitation. Liquid chromatography-coupled mass spectrometry analyses were performed to measure pulmonary and plasma heparan sulfate di/tetrasaccharides. Pulmonary mRNA levels were assessed by nCounter …

Vitamin D-Related Genetic Variants And Prostate Cancer Risk In Black Men, Tracy M Layne, Joseph H Rothstein, Xiaoyu Song, Shaneda Warren Andersen, Emma K T Benn, Weiva Sieh, Robert J Klein

Faculty, Staff and Student Publications

Background: The relationship between vitamin D and prostate cancer has primarily been characterized among White men. Black men, however, have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine critical genes in the vitamin D pathway and prostate cancer risk in Black men.

Methods: We assessed a total of 73 candidate variants in genes (namely GC, CYP27A1, CYP27B1, CYP24A1, VDR, and RXRA) including functional variants previously associated with prostate cancer and circulating 25(OHD) in White men. Associations with prostate cancer risk were examined using genome-wide …

The Effect Of Alzheimer's Disease Genetic Factors On Limbic White Matter Microstructure, Anna Lorenz, Aditi Sathe, Dimitrios Zaras, Yisu Yang, Alaina Durant, Michael E Kim, Chenyu Gao, Nancy R Newlin, Karthik Ramadass, Praitayini Kanakaraj, Nazirah Mohd Khairi, Zhiyuan Li, Tianyuan Yao, Yuankai Huo, Logan Dumitrescu, Niranjana Shashikumar, Kimberly R Pechman, Trevor Bryan Jackson, Abigail W Workmeister, Shannon L Risacher, Lori L Beason-Held, Yang An, Konstantinos Arfanakis, Guray Erus, Christos Davatzikos, Mohamad Habes, Di Wang, Duygu Tosun, Arthur W Toga, Paul M Thompson, Elizabeth C Mormino, Panpan Zhang, Kurt Schilling, Marilyn Albert, Walter Kukull, Sarah A Biber, Bennett A Landman, Sterling C Johnson, Barbara Bendlin, Julie Schneider, Lisa L Barnes, David A Bennett, Angela L Jefferson, Susan M Resnick, Andrew J Saykin, Timothy J Hohman, Derek B Archer

Faculty, Staff and Student Publications

Introduction: White matter (WM) microstructure is essential for brain function but deteriorates with age and in neurodegenerative conditions such as Alzheimer's disease (AD). Diffusion MRI, enhanced by advanced bi-tensor models accounting for free water (FW), enables in vivo quantification of WM microstructural differences.

Methods: To evaluate how AD genetic risk factors affect limbic WM microstructure - crucial for memory and early impacted in disease - we conducted linear regression analyses in a cohort of 2,614 non-Hispanic White aging adults (aged 50.12 to 100.85 years). The study evaluated 36 AD risk variants across 26 genes, the association between AD polygenic scores …

Il13rα2-Targeting Antibodies For Immuno-Pet In Solid Malignancies, Leah Gajecki, Irina V Lebedeva, Yu-Rou Liao, Daisy Ambriz, Lukas M Carter, Melina Kumpf, Samantha Lovibond, Justin S Hachey, Maya S Graham, Michael Postow, Jason S Lewis, David P Andrew, Manuel Baca, Heiko Schöder, Steven M Larson, Darren R Veach, Simone Krebs

Faculty, Staff and Student Publications

Interleukin-13 receptor α-2 (IL13Rα2) is a cell surface receptor frequently expressed in solid malignancies, such as glioblastoma and melanoma, with limited expression in healthy tissue, rendering it an ideal target for noninvasive and specific tumor delineation. In this study, we report the development of 5 novel IL13Rα2-targeted human monoclonal antibodies (mAbs) KLG-1-5; in subsequent in vitro and in vivo studies after radiolabeling with 89Zr, we evaluate their performance to identify a lead candidate.

Methods: Five novel human anti-IL13Rα2 mAbs KLG-1-5 were developed and in vitro binding properties and target specificity assessed. In vivo 89Zr-immuno-PET using KLG-1-5 was conducted in a …

Prediction Of Grade 4 Radiation-Induced Lymphopenia During Chemoradiation Therapy For Lung Cancer Patients: Insights From Two Past Trials, Serena Monti, Giuseppe Palma, Ting Xu, Radhe Mohan, Zhongxing Liao, Laura Cella

Faculty, Staff and Student Publications

Background and purpose: Radiation-induced lymphopenia (RIL) is a significant side effect associated with radiation therapy (RT) with important prognostic implications. We developed and tested a normal tissue complication probability (NTCP) model for Grade 4 (G4) RIL in patients with locally advanced Non-Small-Cell Lung Cancer (NSCLC) who underwent concurrent chemotherapy and RT, analyzing data from patients enrolled in two clinical trials.

Materials and methods: We retrospectively analyzed the data from NCT00915005 (MDA-cohort) and NCT00533949 (RTOG0617-cohort) trials. After finding the candidate predictors of G4-RIL, defined as absolute lymphocyte count (ALC) at nadir < 0.2*109 cells/l during RT, we trained an NTCP model on the MDA-cohort and tested it on the RTOG-cohort, based on common available variables in the two cohorts. Model performance was assessed in terms of discrimination and calibration.

Results: In the MDA-cohort, 55 out of 161 (34%) patients …

Efficacy And Safety Of Denileukin Diftitox-Cxdl, An Improved Purity Formulation Of Denileukin Diftitox, In Patients With Relapsed Or Refractory Cutaneous T-Cell Lymphoma, Francine M Foss, Youn H Kim, H Miles Prince, Oleg E Akilov, Christiane Querfeld, Lucia Seminario-Vidal, David C Fisher, Timothy M Kuzel, Costas K Yannakou, Larisa J Geskin, Tatyana Feldman, Lubomir Sokol, Pamela Blair Allen, Nam Hoang Dang, Fernando Cabanillas, Henry K Wong, Chean Eng Ooi, Dongyuan Xing, Nicholas Sauter, Preeti Singh, Myron Czuczman, Madeleine Duvic

Faculty, Staff and Student Publications

Purpose: Denileukin diftitox (DD)-cxdl is a fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2. This phase III, multicenter, open-label, single-arm registrational trial evaluated the efficacy and safety of DD-cxdl in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL).

Patients and methods: In the main study, which followed a dose-finding lead-in, DD-cxdl was administered intravenously daily (5 days; 9 µg/kg/d once daily) every 21 days for up to eight cycles. Patients in the primary efficacy analysis set (PEAS) were required to have stage IA-IIIB CTCL (mycosis fungoides and/or Sézary syndrome) and at least ≥one previous systemic therapy. …

Evaluation Of A Comprehensive Set Of Normal Tissue Complication Probability Models For Patients With Head And Neck Cancer In An International Cohort, Suzanne P M De Vette, Maria I Van Rijn-Dekker, Lisa Van Den Bosch, Kylie Keijzer, Hendrike Neh, Hung Chu, Yan Li, Mark L Frederiks, Hans Paul Van Der Laan, Jolien Heukelom, Peter Van Luijk, Arjen Van Der Schaaf, Roel J H M Steenbakkers, Nanna M Sijtsema, Katherine A Hutcheson, Clifton D Fuller, Johannes A Langendijk, Amy C Moreno, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Background/purpose: Normal tissue complication probability (NTCP) models can be used to guide radiation therapy (RT) decisions by estimating side-effect risks pretreatment to minimize (late) side-effects. Recently, a comprehensive individual toxicity risk (CITOR) profile of NTCP models addressing common side-effects in head and neck cancer (HNC) patients was developed. This study investigates the generalizability of these models in an international setting, with different treatment approaches and side-effect assessments, promoting their integration into more widespread clinical practice.

Materials/methods: From a prospective registry study, 407 HNC patients were included who were treated with definitive RT with or without systemic therapy between 2015 and …

Cytokine Storms In Covid-19, Hemophagocytic Lymphohistiocytosis, And Car-T Therapy, James P Long, Rishab Prakash, Paul Edelkamp, Mark Knafl, Anath C Lionel, Ranjit Nair, Sairah Ahmed, Paolo Strati, Luis E Malpica Castillo, Ajlan Al-Zaki, Kelly Chien, Dai Chihara, Jason Westin, Fareed Khawaja, Loretta J Nastoupil, Victor Mulanovich, Andrew Futreal, Scott E Woodman, Naval G Daver, Christopher R Flowers, Sattva Neelapu, Joanna-Grace Manzano, Swaminathan P Iyer

Faculty, Staff and Student Publications

Importance: Cytokine storm (CS) is a hyperinflammatory syndrome causing multiorgan dysfunction and high mortality, especially in patients with malignant hematologic neoplasms. Triggers include malignant neoplasm-associated hemophagocytic lymphohistiocytosis (MN-HLH), cytokine release syndrome from chimeric antigen receptor T-cell therapy (CAR-T CRS), and COVID-19, but the underlying mechanisms of inflammation and their impact on outcomes are poorly understood.

Objective: To delineate the inflammatory patterns characterizing different CS etiologies and their association with clinical outcomes.

Design, setting, and participants: This retrospective cohort study was conducted at the MD Anderson Cancer Center in Houston, Texas, between March 1, 2020, and November 20, 2022, using the …

Circulating Short-Chain And Branched Short-Chain Fatty Acids And The Risk Of Incident Type 2 Diabetes: Findings From The 4c Study, Shuangyuan Wang, Hong Lin, Xiaojing Jia, Yiting Lin, Chunyan Hu, Mian Li, Yu Xu, Min Xu, Jie Zheng, Xinjie Zhao, Yanli Li, Lulu Chen, Tianshu Zeng, Ruying Hu, Zhen Ye, Lixin Shi, Qing Su, Yuhong Chen, Xuefeng Yu, Li Yan, Tiange Wang, Zhiyun Zhao, Guijun Qin, Qin Wan, Gang Chen, Meng Dai, Di Zhang, Bihan Qiu, Xiaoyan Zhu, Ruixin Liu, Xiao Wang, Xulei Tang, Zhengnan Gao, Feixia Shen, Xuejiang Gu, Zuojie Luo, Yingfen Qin, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Guixia Wang, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Jiajun Zhao, Yiming Mu, Guowang Xu, Shenghan Lai, Donghui Li, Guang Ning, Weiqing Wang, Yufang Bi, Jieli Lu

Faculty, Staff and Student Publications

Previous studies suggested that fecal short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs and BCFAs with incident diabetes risk in both men and women remains unidentified in prospective cohort studies. In this study, we examined a panel of nine serum SCFAs and BCFAs in 3414 subjects with incident diabetes, and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort study. In fully adjusted conditional logistic regression models, total SCFAs, total BCFAs, and isovaleric acid were significantly associated with incident type 2 diabetes mellitus (T2DM) …

A Plain Language Summary Of The Ascertain Trial: Oral Decitabine And Cedazuridine Versus Intravenous Decitabine For Mds Or Cmml, Guillermo Garcia-Manero, James Mccloskey, Elizabeth A Griffiths, Karen W L Yee, Amer M Zeidan, Aref Al-Kali, H Joachim Deeg, Mitchell Sabloff, Mary-Margaret Keating, Nancy Zhu, Nashat Y Gabrail, Salman Fazal, Joseph Maly, Olatoyosi Odenike, Amy E Dezern, Casey L O'Connell, Gail J Roboz, Lambert Busque, Rena Buckstein, Harshad Amin, Brian Leber, Aditi Shastri, Aram Oganesian, Harold N Keer, Mohammad Azab, Michael R Savona

Faculty, Staff and Student Publications

What is this summary about?This summary describes results from a phase 3 clinical trial called ASCERTAIN.Researchers compared two treatments in people with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML), either of which can develop into acute myeloid leukemia (AML). One group was treated with oral decitabine and cedazuridine (oral DEC-C) and the other with intravenous decitabine.Treatment was given in a series of cycles. In the first cycle, people were randomly assigned to receive oral DEC-C or intravenous decitabine and then switched to the other treatment in the second cycle. After the first two cycles, everyone …

Age-Associated Proteins Explain The Role Of Medial Temporal Lobe Networks In Alzheimer’S Disease, Adam Turnbull, Yejin Kim, Kai Zhang, Xiaoqian Jiang, Zihuai He, Victor W Henderson, F Vankee Lin

Faculty, Staff and Student Publications

The structural connectivity (SC) of the medial temporal lobe and its associated cortical anterior temporal and posterior medial networks (MTL-AT-PM) is linked to pathologies and memory decline in Alzheimer's disease (AD). However, neuroimaging analyses cannot tell us how SC changes occur in AD at the molecular level and do not provide a means of intervening to slow/prevent pathology-related changes in MTL-AT-PM SC. The current study aimed to understand how and where AD-related changes occur within MTL-AT-PM using proteomics. We used a 4-step approach in 101 older adults from a local sample, aiming to understand how proteins and SC in combination …

Insulin-Like Growth Factor 2 As A Driving Force For Exponential Expansion And Differentiation Of The Neonatal Thymus, Seung Woo Kang, Bryan R Helm, Yu Wang, Shiyun Xiao, Wen Zhang, Anusha Vasudev, Ken S Lau, Qi Liu, Ellen R Richie, Laura P Hale, Nancy R Manley

Faculty, Staff and Student Publications

Like all organs, the thymus grows in size and function rapidly during development, but this growth comes to a halt after birth. However, the molecular mechanisms behind such a transition in the thymus remain obscure. Using single-cell RNA sequencing (scRNA-seq) of the murine thymic stroma, we identified that major transcriptomic changes occur in the endothelium and mesenchyme across the transition to homeostasis. Differentially expressed gene and intercellular network analyses of temporally resolved scRNA-seq data revealed fibroblast-derived insulin-like growth factor 2 (IGF2) as a candidate driving neonatal thymic expansion. We demonstrated that IGF2 activity promotes a cortical thymic epithelial cell-specific proliferation …

Cost-Effectiveness Of Personalized Policies For Implementing Organ-At-Risk Sparing Adaptive Radiation Therapy In Head And Neck Cancer, Seyedmohammadhossein Hosseinian, Daniel Suarez-Aguirre, Cem Dede, Raul Garcia, Lucas Mccullum, Mehdi Hemmati, Aysenur Karagoz, Abdallah S R Mohamed, Stephen Y Lai, Katherine A Hutcheson, Amy C Moreno, Kristy K Brock, Fatemeh Nosrat, Clifton D Fuller, Andrew J Schaefer

Faculty, Staff and Student Publications

Background and purpose: The principle of adaptive radiation therapy (ART) is to adjust radiation plans in response to anatomical changes during treatment. The purpose of this study was to develop a decision-making model for implementation of personalized ART that balances the costs and clinical benefits of radiation plan adaptations in head and neck cancer (HNC).

Materials and methods: Using retrospective imaging data from 52 HNC patients, a Markov decision process (MDP) model was developed to determine optimal timing for plan adaptations based on the difference in normal tissue complication probability (ΔNTCP) between planned and delivered doses to organs-at-risk. To capture …

American College Of Radiology Manual On Mr Safety: 2024 Update And Revisions, Ivan Pedrosa, David A Altman, Jonathan R Dillman, Michael N Hoff, Alexander M Mckinney, Scott B Reeder, Jeffrey M Rogg, R Jason Stafford, James A Webb, Dina L Hernandez, Robert E Watson

Faculty, Staff and Student Publications

Since the introduction of the American College of Radiology (ACR) MRI safety guidelines in 2002, the indications for use of MRI in clinical care and research have continued to expand. Similarly, MRI technologies have evolved, with multiple field strengths now available for human imaging. While several publications have updated the ACR recommendations since the first guidelines, a single source in a structured format was lacking. Accordingly, the ACR Committee on MR Safety recently updated the online ACR Manual on MR Safety that compiles ACR recommendations for safe use of MRI equipment in humans into a single document. This review describes …

Characterization Of A Time-Resolved, Real-Time Scintillation Dosimetry System For Ultra-High Dose-Rate Radiation Therapy Applications, Alexander Baikalov, Daline Tho, Kevin Liu, Stefan Bartzsch, Sam Beddar, Emil Schüler

Faculty, Staff and Student Publications

Purpose: Scintillation dosimetry has promising qualities for ultra-high-dose-rate (UHDR) radiation therapy (RT), but no system has shown compatibility with mean dose rates (DR¯) above 100 Gy/s and doses per pulse (Dp) exceeding 1.5 Gy typical of UHDR (FLASH)-RT. The aim of this study was to characterize a novel scintillation dosimetry system with the potential of accommodating UHDRs.

Methods and materials: We undertook a thorough dosimetric characterization of the system on an UHDR electron beamline. The system's response as a function of dose, DR¯, Dp, and the pulse dose-rate (DRp) was investigated, as was the system's dose sensitivity (signal per unit …

Defining A 'Cells To Society' Research Framework For Appendiceal Tumours, Andreana N Holowatyj, Michael J Overman, Konstantinos I Votanopoulos, Andrew M Lowy, Patrick Wagner, Mary K Washington, Cathy Eng, Wai Chin Foo, Richard M Goldberg, Mojgan Hosseini, Kamran Idrees, Douglas B Johnson, Ardaman Shergill, Erin Ward, Nicholas C Zachos, Deborah Shelton

Faculty, Staff and Student Publications

Tumours of the appendix — a vestigial digestive organ attached to the colon — are rare. Although we estimate that around 3,000 new appendiceal cancer cases are diagnosed annually in the USA, the challenges of accurately diagnosing and identifying this tumour type suggest that this number may underestimate true population incidence. In the current absence of disease-specific screening and diagnostic imaging modalities, or well-established risk factors, the incidental discovery of appendix tumours is often prompted by acute presentations mimicking appendicitis or when the tumour has already spread into the abdominal cavity — wherein the potential misclassification of appendiceal tumours as …