Medicine and Health Sciences Commons^™

Rational Design Of A Self-Assembling High Performance Organic Nanofluorophore For Intraoperative Nir-Ii Image-Guided Tumor Resection Of Oral Cancer, Xianwei Sun, Praveen Kumar Chintakunta, Andrew A Badachhape, Rohan Bhavane, Huan-Jui Lee, David S Yang, Zbigniew Starosolski, Ketan B Ghaghada, Peter G Vekilov, Ananth V Annapragada, Eric A Tanifum

Faculty, Staff and Students Publications

The first line of treatment for most solid tumors is surgical resection of the primary tumor with adequate negative margins. Incomplete tumor resections with positive margins account for over 75% of local recurrences and the development of distant metastases. In cases of oral cavity squamous cell carcinoma (OSCC), the rate of successful tumor removal with adequate margins is just 50–75%. Advanced real‐time imaging methods that improve the detection of tumor margins can help improve success rates,overall safety, and reduce the cost. Fluorescence imaging in the second near‐infrared (NIR‐II) window has the potential to revolutionize the field due to its high …

Efficacy And Safety Of Azithromycin Versus Placebo To Treat Lower Respiratory Tract Infections Associated With Low Procalcitonin: A Randomised, Placebo-Controlled, Double-Blind, Non-Inferiority Trial, Ephraim L Tsalik, Nadine G Rouphael, Ruxana T Sadikot, Maria C Rodriguez-Barradas, Micah T Mcclain, Dana M Wilkins, Christopher W Woods, Geeta K Swamy, Emmanuel B Walter, Hana M El Sahly, Wendy A Keitel, Mark J Mulligan, Bonifride Tuyishimire, Elisavet Serti, Toshimitsu Hamasaki, Scott R Evans, Varduhi Ghazaryan, Marina S Lee, Ebbing Lautenbach, Antibacterial Resistance Leadership Group, Trap-Lrti Study Group

Faculty, Staff and Student Publications

BACKGROUND: Lower respiratory tract infections are frequently treated with antibiotics, despite a viral cause in many cases. It remains unknown whether low procalcitonin concentrations can identify patients with lower respiratory tract infection who are unlikely to benefit from antibiotics. We aimed to compare the efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections in patients with low procalcitonin.

METHODS: We conducted a randomised, placebo-controlled, double-blind, non-inferiority trial at five health centres in the USA. Adults aged 18 years or older with clinically suspected non-pneumonia lower respiratory tract infection and symptom duration from 24 h to 28 …

Total Daily Energy Expenditure Has Declined Over The Past Three Decades Due To Declining Basal Expenditure, Not Reduced Activity Expenditure, John R Speakman, Jasper M A De Jong, Srishti Sinha, Klaas R Westerterp, Yosuke Yamada, Hiroyuki Sagayama, Philip N Ainslie, Liam J Anderson, Lenore Arab, Kweku Bedu-Addo, Stephane Blanc, Alberto G Bonomi, Pascal Bovet, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Lara R Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Santu Ghosh, Annelies H Goris, Michael Gurven, Lewis G Halsey, Catherine Hambly, Hinke H Haisma, Daniel Hoffman, Sumei Hu, Annemiek M Joosen, Jennifer L Kaplan, Peter Katzmarzyk, William E Kraus, Robert F Kushner, William R Leonard, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, Erwin P Meijer, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, Susan B Roberts, Michael C Rudolph, Luis B Sardinha, Albertine J Schuit, Analiza M Silva, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Brian M Wood, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia U Loechl, Anura Kurpad, Amy H Luke, Herman Pontzer, Matthew S Rodeheffer, Jennifer Rood, Dale A Schoeller, William W Wong

Faculty, Staff and Student Publications

Obesity is caused by prolonged positive energy balance1,2. Whether reduced energy expenditure stemming from reduced activity levels contributes, is debated3,4. Here we used the IAEA DLW database on energy expenditure of adults in the USA and Europe (n = 4799) to explore patterns in total (TEE: n=4799), basal (BEE: n = 1432) and physical activity energy expenditure (AEE: n = 1432) over time. In both sexes total energy expenditure (TEE) adjusted for body composition and age declined with time, while adjusted AEE increased over time. In males adjusted BEE decreased significantly, but …

Familial Hypercholesterolemia In The Electronic Medical Records And Genomics Network: Prevalence, Penetrance, Cardiovascular Risk, And Outcomes After Return Of Results, Ozan Dikilitas, Alborz Sherafati, Seyedmohammad Saadatagah, Benjamin A Satterfield, David C Kochan, Katherine C Anderson, Wendy K Chung, Scott J Hebbring, Zachary M Salvati, Richard R Sharp, Amy C Sturm, Richard A Gibbs, Robb Rowley, Eric Venner, Jodell E Linder, Laney K Jones, Emma F Perez, Josh F Peterson, Gail P Jarvik, Heidi L Rehm, Hana Zouk, Dan M Roden, Marc S Williams, Teri A Manolio, Iftikhar J Kullo

Faculty, Staff and Students Publications

BACKGROUND: The implications of secondary findings detected in large-scale sequencing projects remain uncertain. We assessed prevalence and penetrance of pathogenic familial hypercholesterolemia (FH) variants, their association with coronary heart disease (CHD), and 1-year outcomes following return of results in phase III of the electronic medical records and genomics network.

METHODS: Adult participants (n=18 544) at 7 sites were enrolled in a prospective cohort study to assess the clinical impact of returning results from targeted sequencing of 68 actionable genes, including

RESULTS: The prevalence of FH-associated pathogenic variants was 1 in 188 (69 of 13,019 unselected participants). Penetrance was 87.5%. The …

Neurochemical Effects Of Sepsis On The Brain, Tatiana Barichello, Vijayasree V Giridharan, Carlos Henrique R Catalão, Cristiane Ritter, Felipe Dal-Pizzol

Faculty, Staff and Student Publications

Sepsis is a life-threatening organ dysfunction triggered by a dysregulated host immune response to eliminate an infection. After the host immune response is activated, a complex, dynamic, and time-dependent process is triggered. This process promotes the production of inflammatory mediators, including acute-phase proteins, complement system proteins, cytokines, chemokines, and antimicrobial peptides, which are required to initiate an inflammatory environment for eliminating the invading pathogen. The physiological response of this sepsis-induced systemic inflammation can affect blood-brain barrier (BBB) function; subsequently, endothelial cells produce inflammatory mediators, including cytokines, chemokines, and matrix metalloproteinases (MMPs) that degrade tight junction (TJ) proteins and decrease BBB …

Genetic Correlations Between Alzheimer’S Disease And Gut Microbiome Genera, Davis Cammann, Yimei Lu, Melika J Cummings, Mark L Zhang, Joan Manuel Cue, Jenifer Do, Jeffrey Ebersole, Xiangning Chen, Edwin C Oh, Jeffrey L Cummings, Jingchun Chen

Faculty, Staff and Student Publications

A growing body of evidence suggests that dysbiosis of the human gut microbiota is associated with neurodegenerative diseases like Alzheimer's disease (AD) via neuroinflammatory processes across the microbiota-gut-brain axis. The gut microbiota affects brain health through the secretion of toxins and short-chain fatty acids, which modulates gut permeability and numerous immune functions. Observational studies indicate that AD patients have reduced microbiome diversity, which could contribute to the pathogenesis of the disease. Uncovering the genetic basis of microbial abundance and its effect on AD could suggest lifestyle changes that may reduce an individual's risk for the disease. Using the largest genome-wide …

Genome-Wide Crispr Screens Reveal Zatt As A Synthetic Lethal Target Of Top2-Poison Etoposide That Can Act In A Tdp2-Independent Pathway, Jeong-Min Park, Huimin Zhang, Litong Nie, Chao Wang, Min Huang, Xu Feng, Mengfan Tang, Zhen Chen, Yun Xiong, Namsoo Lee, Siting Li, Ling Yin, Traver Hart, Junjie Chen

Faculty, Staff and Student Publications

Etoposide (ETO) is an anticancer drug that targets topoisomerase II (TOP2). It stabilizes a normally transient TOP2-DNA covalent complex (TOP2cc), thus leading to DNA double-strand breaks (DSBs). Tyrosyl-DNA phosphodiesterases two (TDP2) is directly involved in the repair of TOP2cc by removing phosphotyrosyl peptides from 5'-termini of DSBs. Recent studies suggest that additional factors are required for TOP2cc repair, which include the proteasome and the zinc finger protein associated with TDP2 and TOP2, named ZATT. ZATT may alter the conformation of TOP2cc in a way that renders the accessibility of TDP2 for TOP2cc removal. In this study, our genome-wide clustered regularly …

Targeting The Molecular And Immunologic Features Of Leiomyosarcoma, Brandon M Cope, Raymond S Traweek, Rossana Lazcano, Emily Z Keung, Alexander J Lazar, Christina L Roland, Elise F Nassif

Faculty, Staff and Student Publications

Leiomyosarcoma (LMS) is a rare, aggressive mesenchymal tumor with smooth muscle differentiation. LMS is one of the most common histologic subtypes of soft tissue sarcoma; it most frequently occurs in the extremities, retroperitoneum, or uterus. LMS often demonstrates aggressive tumor biology, with a higher risk of developing distant metastatic disease than most sarcoma histologic types. The prognosis is poor, particularly in patients with uterine disease, and there is a need for the development of more effective therapies. Genetically, LMS is karyotypically complex and characterized by a low tumor mutational burden, with frequent alterations in TP53, RB1, PTEN, …

Covariate-Specific Evaluation Of Continuous Biomarker, Ziyi Li, Yijian Huang, Dattatraya Patil, Mark Rubin, Martin G Sanda

Faculty, Staff and Student Publications

Diagnostic tests usually need to operate at a high sensitivity or specificity level in practice. Accordingly, specificity at the controlled sensitivity, or vice versa, is a clinically sensible performance metric for evaluating continuous biomarkers. Meanwhile, the performance of a biomarker may vary across sub-populations as defined by covariates, and covariate-specific evaluation can be informative. In this article, we develop a novel modeling and estimation method for covariate-specific specificity at a controlled sensitivity level. Unlike existing methods which typically adopt elaborate models of covariate effects over the entire biomarker distribution, our approach models covariate effects locally at a specific sensitivity level …

The En-Tex Resource Of Multi-Tissue Personal Epigenomes & Variant-Impact Models, Joel Rozowsky, Jiahao Gao, Beatrice Borsari, Yucheng T Yang, Timur Galeev, Gamze Gürsoy, Charles B Epstein, Kun Xiong, Jinrui Xu, Tianxiao Li, Jason Liu, Keyang Yu, Ana Berthel, Zhanlin Chen, Fabio Navarro, Maxwell S Sun, James Wright, Justin Chang, Christopher J F Cameron, Noam Shoresh, Elizabeth Gaskell, Jorg Drenkow, Jessika Adrian, Sergey Aganezov, François Aguet, Gabriela Balderrama-Gutierrez, Samridhi Banskota, Guillermo Barreto Corona, Sora Chee, Surya B Chhetri, Gabriel Conte Cortez Martins, Cassidy Danyko, Carrie A Davis, Daniel Farid, Nina P Farrell, Idan Gabdank, Yoel Gofin, David U Gorkin, Mengting Gu, Vivian Hecht, Benjamin C Hitz, Robbyn Issner, Yunzhe Jiang, Melanie Kirsche, Xiangmeng Kong, Bonita R Lam, Shantao Li, Bian Li, Xiqi Li, Khine Zin Lin, Ruibang Luo, Mark Mackiewicz, Ran Meng, Jill E Moore, Jonathan Mudge, Nicholas Nelson, Chad Nusbaum, Ioann Popov, Henry E Pratt, Yunjiang Qiu, Srividya Ramakrishnan, Joe Raymond, Leonidas Salichos, Alexandra Scavelli, Jacob M Schreiber, Fritz J Sedlazeck, Lei Hoon See, Rachel M Sherman, Xu Shi, Minyi Shi, Cricket Alicia Sloan, J Seth Strattan, Zhen Tan, Forrest Y Tanaka, Anna Vlasova, Jun Wang, Jonathan Werner, Brian Williams, Min Xu, Chengfei Yan, Lu Yu, Christopher Zaleski, Jing Zhang, Kristin Ardlie, J Michael Cherry, Eric M Mendenhall, William S Noble, Zhiping Weng, Morgan E Levine, Alexander Dobin, Barbara Wold, Ali Mortazavi, Bing Ren, Jesse Gillis, Richard M Myers, Michael P Snyder, Jyoti Choudhary, Aleksandar Milosavljevic, Michael C Schatz, Bradley E Bernstein, Roderic Guigó, Thomas R Gingeras, Mark Gerstein

Faculty, Staff and Students Publications

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of 1,635 open-access datasets from four donors (∼30 tissues × ∼15 assays). The datasets are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating a catalog of >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes and are less conserved than corresponding, non-allele-specific ones. Surprisingly, a deep-learning transformer model can predict the allele-specific activity based only on local nucleotide-sequence context, highlighting the importance of transcription-factor-binding …

Inferring Gene Regulatory Networks From Rna-Seq Data Using Kernel Classification, Amira Al-Aamri, Andrzej S Kudlicki, Maher Maalouf, Kamal Taha, Dirar Homouz

Faculty, Staff and Student Publications

Gene expression profiling is one of the most recognized techniques for inferring gene regulators and their potential targets in gene regulatory networks (GRN). The purpose of this study is to build a regulatory network for the budding yeast Saccharomyces cerevisiae genome by incorporating the use of RNA-seq and microarray data represented by a wide range of experimental conditions. We introduce a pipeline for data analysis, data preparation, and training models. Several kernel classification models; including one-class, two-class, and rare event classification methods, are used to categorize genes. We test the impact of the normalization techniques on the overall performance of …

Hpv-Related Anal Cancer Is Associated With Changes In The Anorectal Microbiome During Cancer Development, Jacob H Elnaggar, Victoria O Huynh, Daniel Lin, R Tyler Hillman, Chike O Abana, Molly B El Alam, Katarina C Tomasic, Tatiana V Karpinets, Ramez Kouzy, Jae L Phan, Jennifer Wargo, Emma B Holliday, Prajnan Das, Melissa P Mezzari, Nadim J Ajami, Erica J Lynn, Bruce D Minsky, Van K Morris, Andrea Milbourne, Craig A Messick, Ann H Klopp, P Andrew Futreal, Cullen M Taniguchi, Kathleen M Schmeler, Lauren E Colbert

Faculty, Staff and Student Publications

BACKGROUND: Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease.

METHODS: Patients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade …

Correction: Single-Cell Multi-Omics Integration For Unpaired Data By A Siamese Network With Graph-Based Contrastive Loss, Chaozhong Liu, Linhua Wang, Zhandong Liu

Faculty, Staff and Students Publications

No abstract provided.

Rare Variant Enrichment Analysis Supports Greb1l As A Contributory Driver Gene In The Etiology Of Mayer-Rokitansky-Küster-Hauser Syndrome, Angad Jolly, Haowei Du, Christelle Borel, Na Chen, Sen Zhao, Christopher M Grochowski, Ruizhi Duan, Jawid M Fatih, Moez Dawood, Sejal Salvi, Shalini N Jhangiani, Donna M Muzny, André Koch, Konstantinos Rouskas, Stavros Glentis, Efthymios Deligeoroglou, Flora Bacopoulou, Carol A Wise, Jennifer E Dietrich, Ignatia B Van Den Veyver, Antigone S Dimas, Sara Brucker, V Reid Sutton, Richard A Gibbs, Stylianos E Antonarakis, Nan Wu, Zeynep H Coban-Akdemir, Lan Zhu, Jennifer E Posey, James R Lupski

Faculty, Staff and Student Publications

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, only WNT4 (MIM: 603490) variants have been definitively associated with a subtype of MRKH with hyperandrogenism (MIM: 158330). DNA from 148 clinically diagnosed MRKH probands across 144 unrelated families and available family members from North America, Europe, and South America were exome sequenced (ES) and by family-based genomics analyzed for rare likely deleterious variants. A replication cohort consisting of 442 Han Chinese individuals with MRKH was …

Hsc-Independent Definitive Hematopoiesis Persists Into Adult Life, Michihiro Kobayashi, Haichao Wei, Takashi Yamanashi, Nathalia Azevedo Portilho, Samuel Cornelius, Noemi Valiente, Chika Nishida, Haizi Cheng, Augusto Latorre, W Jim Zheng, Joonsoo Kang, Jun Seita, David J Shih, Jia Qian Wu, Momoko Yoshimoto

Faculty, Staff and Student Publications

It is widely believed that hematopoiesis after birth is established by hematopoietic stem cells (HSCs) in the bone marrow and that HSC-independent hematopoiesis is limited only to primitive erythro-myeloid cells and tissue-resident innate immune cells arising in the embryo. Here, surprisingly, we find that significant percentages of lymphocytes are not derived from HSCs, even in 1-year-old mice. Instead, multiple waves of hematopoiesis occur from embryonic day 7.5 (E7.5) to E11.5 endothelial cells, which simultaneously produce HSCs and lymphoid progenitors that constitute many layers of adaptive T and B lymphocytes in adult mice. Additionally, HSC lineage tracing reveals that the contribution …

Clinical Outcomes Associated With Npm1 Mutations In Patients With Relapsed Or Refractory Aml, Ghayas C Issa, Aram Bidikian, Sangeetha Venugopal, Marina Konopleva, Courtney D Dinardo, Tapan M Kadia, Gautam Borthakur, Elias Jabbour, Naveen Pemmaraju, Musa Yilmaz, Nicholas J Short, Abhishek Maiti, Koji Sasaki, Lucia Masarova, Sherry Pierce, Koichi Takahashi, Guilin Tang, Sanam Loghavi, Keyur Patel, Michael Andreeff, Kapil Bhalla, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Naval Daver

Faculty, Staff and Student Publications

Mutations in Nucleophosmin 1 (NPM1) are associated with a favorable prognosis in newly diagnosed acute myeloid leukemia (AML), however, their prognostic impact in relapsed/refractory (R/R) settings are unknown. In a retrospective analysis, we identified 206 patients (12%) with mutated NPM1 (NPM1c) and compared their outcomes to 1516 patients (88%) with NPM1 wild-type (NPM1wt). NPM1c was associated with higher rates of complete remission or complete remission with incomplete count recovery compared with NPM1wt following each line of salvage therapy (first salvage, 56% vs 37%; P < .0001; second salvage, 33% vs 22%; P = .02; third salvage, 24% vs 14%; P = .02). However, NPM1 mutations had no impact on relapse-free survival (RFS) and overall survival (OS) with each salvage therapy with a median OS following salvage 1, 2 or 3 therapies in NPM1c vs NPM1wt of 7.8 vs 6.0; 5.3 vs 4.1; and 3.5 vs 3.6 months, respectively. Notably, the addition of venetoclax to salvage regimens in patients with NPM1c improved RFS and OS (median RFS, 15.8 vs 4.6 months; P = .05; median OS, 14.7 vs 5.9 months; P = .02). In conclusion, NPM1 mutational status has a minimal impact on prognosis in relapsed or refractory AML; therefore, novel treatment strategies are required to improve outcomes in this entity.

Venetoclax For Acute Myeloid Leukemia In Pediatric Patients: A Texas Medical Center Experience, Adriana Trabal, Amber Gibson, Jiasen He, David Mccall, Michael Roth, Cesar Nuñez, Miriam Garcia, Meredith Buzbee, Laurie Toepfer, Aram Bidikian, Naval Daver, Tapan Kadia, Nicholas J Short, Ghayas C Issa, Farhad Ravandi, Courtney D Dinardo, Guillermo Montalban Bravo, Sofia Garces, Andrea Marcogliese, Hana Paek, Zoann Dreyer, Julienne Brackett, Michele Redell, Joanna Yi, Guillermo Garcia-Manero, Marina Konopleva, Alexandra Stevens, Branko Cuglievan

Faculty, Staff and Student Publications

The BCL-2 inhibitor venetoclax improves survival for adult patients with acute myeloid leukemia (AML) in combination with lower-intensity therapies, but its benefit in pediatric patients with AML remains unclear. We retrospectively reviewed two Texas Medical Center institutions' experience with venetoclax in 43 pediatric patients with AML; median age 17 years (range, 0.6-21). This population was highly refractory; 44% of patients (n = 19) had ≥3 prior lines of therapy, 37% (n = 16) had received a prior bone marrow transplant, and 81% (n = 35) had unfavorable genetics KMT2A (n = 17), WT1 (n = 13), FLT3-ITD (n = 10), …

Convergent Deployment Of Ancestral Functions During The Evolution Of Mammalian Flight Membranes, Charles Y Feigin, Jorge A Moreno, Raul Ramos, Sarah A Mereby, Ares Alivisatos, Wei Wang, Renée Van Amerongen, Jasmin Camacho, John J Rasweiler, Richard R Behringer, Bruce Ostrow, Maksim V Plikus, Ricardo Mallarino

Faculty, Staff and Student Publications

Lateral flight membranes, or patagia, have evolved repeatedly in diverse mammalian lineages. While little is known about patagium development, its recurrent evolution may suggest a shared molecular basis. By combining transcriptomics, developmental experiments, and mouse transgenics, we demonstrate that lateral Wnt5a expression in the marsupial sugar glider (Petaurus breviceps) promotes the differentiation of its patagium primordium. We further show that this function of Wnt5a reprises ancestral roles in skin morphogenesis predating mammalian flight and has been convergently used during patagium evolution in eutherian bats. Moreover, we find that many genes involved in limb development have been redeployed during …

Cervicovaginal Microbiota Profiles In Precancerous Lesions And Cervical Cancer Among Ethiopian Women, Brhanu Teka, Kyoko Yoshida-Court, Ededia Firdawoke, Zewditu Chanyalew, Muluken Gizaw, Adamu Addissie, Adane Mihret, Lauren E Colbert, Tatiana Cisneros Napravnik, Molly B El Alam, Erica J Lynn, Melissa Mezzari, Jhingran Anuja, Eva Johanna Kantelhardt, Andreas M Kaufmann, Ann H Klopp, Tamrat Abebe

Faculty, Staff and Student Publications

Although high-risk human papillomavirus infection is a well-established risk factor for cervical cancer, other co-factors within the local microenvironment may play an important role in the development of cervical cancer. The current study aimed to characterize the cervicovaginal microbiota in women with premalignant dysplasia or invasive cervical cancer compared with that of healthy women. The study comprised 120 Ethiopian women (60 cervical cancer patients who had not received any treatment, 25 patients with premalignant dysplasia, and 35 healthy women). Cervicovaginal specimens were collected using either an Isohelix DNA buccal swab or an Evalyn brush, and ribosomal RNA sequencing was used …

Health-Related Quality Of Life In Adolescents And Young Adults With Cancer Who Received Radiation Therapy: A Scoping Review, Kelsey L Corrigan, Bryce B Reeve, John M Salsman, Elizabeth J Siembida, Lauren M Andring, Yimin Geng, Ramez Kouzy, J Andrew Livingston, Susan K Peterson, Andrew J Bishop, Grace L Smith, Jillian R Gunther, Susan K Parsons, Michael Roth

Faculty, Staff and Student Publications

Purpose: Radiation therapy (RT) is a critical component of treatment for adolescents and young adults (AYAs, age 15-39 years old) diagnosed with cancer. Limited prior studies have focused on AYAs receiving RT despite the potentially burdensome effects of RT. We reviewed the literature to assess health-related quality of life (HRQOL) in AYAs with cancer who received RT.

Methods: The MEDLINE, EMBASE, and Web of Science databases were searched in January 2022 to identify studies that analyzed HRQOL measured by patient-reported outcomes in AYAs who received RT. After title (n = 286) and abstract (n = 58) screening and full-text review …

Aberrant Function Of Pathogenic Stat3 Mutant Proteins Is Linked To Altered Stability Of Monomers And Homodimers, Moses M Kasembeli, Efiyenia Kaparos, Uddalak Bharadwaj, Ahmad Allaw, Alain Khouri, Bianca Acot, David J Tweardy

Faculty, Staff and Student Publications

STAT3 mutations, predominantly in the DNA-binding domain (DBD) and Src-homology 2 domain (SH2D), cause rare cases of immunodeficiency, malignancy, and autoimmunity. The exact mechanisms by which these mutations abrogate or enhance STAT3 function are not completely understood. Here, we examined how loss-of-function (LOF) and gain-of-function (GOF) STAT3 mutations within the DBD and SH2D affect monomer and homodimer protein stability as well as their effect on key STAT3 activation events, including recruitment to phosphotyrosine (pY) sites within peptide hormone receptors, tyrosine phosphorylation at Y705, dimerization, nuclear translocation, and DNA binding. The DBD LOF mutants showed reduced DNA binding when homodimerized, whereas …

A Phase 2 Study Of Interleukin-22 And Systemic Corticosteroids As Initial Treatment For Acute Gvhd Of The Lower Gi Tract, Doris M Ponce, Amin M Alousi, Ryotaro Nakamura, John Slingerland, Marco Calafiore, Karamjeet S Sandhu, Juliet N Barker, Sean Devlin, Jinru Shia, Sergio Giralt, Miguel-Angel Perales, Gillian Moore, Samira Fatmi, Cristina Soto, Antonio Gomes, Paul Giardina, Leeann Marcello, Xiaoqiang Yan, Tom Tang, Kevin Dreyer, Jianmin Chen, William L Daley, Jonathan U Peled, Marcel R M Van Den Brink, Alan M Hanash

Faculty, Staff and Student Publications

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality following allogeneic hematopoietic transplantation. In experimental models, interleukin-22 promotes epithelial regeneration and induces innate antimicrobial molecules. We conducted a multicenter single-arm phase 2 study evaluating the safety and efficacy of a novel recombinant human interleukin-22 dimer, F-652, used in combination with systemic corticosteroids for treatment of newly diagnosed lower gastrointestinal acute GVHD. The most common adverse events were cytopenias and electrolyte abnormalities, and there were no dose-limiting toxicities. Out of 27 patients, 19 (70%; 80% confidence interval, 56%-79%) achieved a day-28 treatment response, meeting the prespecified primary endpoint. Responders …

Large Scale Crowdsourced Radiotherapy Segmentations Across A Variety Of Cancer Anatomic Sites, Kareem A Wahid, Diana Lin, Onur Sahin, Michael Cislo, Benjamin E Nelms, Renjie He, Mohammed A Naser, Simon Duke, Michael V Sherer, John P Christodouleas, Abdallah S R Mohamed, James D Murphy, Clifton D Fuller, Erin F Gillespie

Faculty, Staff and Student Publications

Clinician generated segmentation of tumor and healthy tissue regions of interest (ROIs) on medical images is crucial for radiotherapy. However, interobserver segmentation variability has long been considered a significant detriment to the implementation of high-quality and consistent radiotherapy dose delivery. This has prompted the increasing development of automated segmentation approaches. However, extant segmentation datasets typically only provide segmentations generated by a limited number of annotators with varying, and often unspecified, levels of expertise. In this data descriptor, numerous clinician annotators manually generated segmentations for ROIs on computed tomography images across a variety of cancer sites (breast, sarcoma, head and neck, …

Stellettin B Renders Glioblastoma Vulnerable To Poly (Adp-Ribose) Polymerase Inhibitors Via Suppressing Homology-Directed Repair, Xin Peng, Yingying Wang, Shaolu Zhang, Zhennan Tao, Yuxiang Dai, Francois X Claret, Moshe Elkabets, Hou-Wen Lin, Zhe-Sheng Chen, Dexin Kong

Faculty, Staff and Student Publications

No abstract provided.

Potential Mitigation Of Environmental Impacts Of Intensive Plum Production In Southeast China With Maintenance Of High Yields: Evaluation Using Life Cycle Assessment, Xiaojun Yan, Delian Ye, Yafu Tang, Muhammad Atif Muneer, Peter Christie, Congyue Tou, Weidong Xu, Bingrong Shen, Jinxian Xu, Jiangzhou Zhang

Faculty, Staff and Student Publications

INTRODUCTION: Intensive plum production usually involves high yields but also high environmental costs due to excessive fertilizer inputs. Quantitative analysis of the environmental effects of plum production is thereby required in the development of optimum strategies to promote sustainable fruit production.

METHODS: We collected survey questionnaires from 254 plum production farms in Zhao'an county, Fujian province, southeast China to assess the environmental impacts by life cycle assessment (LCA) methodology. The farms were categorized into four groups based on yield and environmental impacts, i.e., LL (low yield and low environmental impact), LH (low yield but high environmental impact), HL (high yield …

Acupuncture Treatment For Post-Stroke Depression: Intestinal Microbiota And Its Role, Hailun Jiang, Shizhe Deng, Jieying Zhang, Junjie Chen, Boxuan Li, Weiming Zhu, Menglong Zhang, Chao Zhang, Zhihong Meng

Faculty, Staff and Student Publications

Stroke-induced depression is a common complication and an important risk factor for disability. Besides psychiatric symptoms, depressed patients may also exhibit a variety of gastrointestinal symptoms, and even take gastrointestinal symptoms as the primary reason for medical treatment. It is well documented that stress may disrupt the balance of the gut microbiome in patients suffering from post-stroke depression (PSD), and that disruption of the gut microbiome is closely related to the severity of the condition in depressed patients. Therefore, maintaining the balance of intestinal microbiota can be the focus of research on the mechanism of acupuncture in the treatment of …

Conjugation's Toolkit: The Roles Of Nonstructural Proteins In Bacterial Sex, Matthew B Cooke, Christophe Herman

Faculty, Staff and Students Publications

Bacterial conjugation, a form of horizontal gene transfer, relies on a type 4 secretion system (T4SS) and a set of nonstructural genes that are closely linked. These nonstructural genes aid in the mobile lifestyle of conjugative elements but are not part of the T4SS apparatus for conjugative transfer, such as the membrane pore and relaxosome, or the plasmid maintenance and replication machineries. While these nonstructural genes are not essential for conjugation, they assist in core conjugative functions and mitigate the cellular burden on the host. This review compiles and categorizes known functions of nonstructural genes by the stage of conjugation …

Pd-L1 + Macrophages Are Associated With Favorable Features In Primary Mediastinal (Thymic) Large B-Cell Lymphoma, Raphael E Steiner, Edwin R Parra, Francisco Vega, Lei Feng, Jason R Westin, Sattva S Neelapu, Paolo Strati, Michael R Green, Christopher R Flowers, Luisa M Solis, Ignacio I Wistuba, Sairah Ahmed, Ranjit Nair, Fredrick B Hagemeister, Mansoor Noorani, Mario L Marques-Piubelli

Faculty, Staff and Student Publications

Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is a rare, aggressive subtype of non-Hodgkin lymphoma and has a complex inflammatory microenvironment. Although most patients can be cured with standard-of-care immunochemotherapy, patients who have disease relapse have an unfavorable prognosis. Pre-treatment prognostic biomarkers in PMBCL are needed. In this retrospective study, we analyzed the clinical features and outcomes of PMBCL patients and their association with immune cell subpopulations identified by multiplex immunofluorescence at initial diagnosis. Two different antibody panels were used to assess macrophages in tissue biopsy specimens collected before the initiation of induction therapy. Twelve PMBCL patients, including five patients …

Dna Damage Response-Related Proteins Are Prognostic For Outcome In Both Adult And Pediatric Acute Myelogenous Leukemia Patients: Samples From Adults And From Children Enrolled In A Children's Oncology Group Study, Stefan E Hubner, Eduardo S De Camargo Magalhães, Fieke W Hoff, Brandon D Brown, Yihua Qiu, Terzah M Horton, Steven M Kornblau

Faculty, Staff and Student Publications

The survival of malignant leukemic cells is dependent on DNA damage repair (DDR) signaling. Reverse Phase Protein Array (RPPA) data sets were assembled using diagnostic samples from 810 adult and 500 pediatric acute myelogenous leukemia (AML) patients and were probed with 412 and 296 strictly validated antibodies, respectively, including those detecting the expression of proteins directly involved in DDR. Unbiased hierarchical clustering identified strong recurrent DDR protein expression patterns in both adult and pediatric AML. Globally, DDR expression was associated with gene mutational statuses and was prognostic for outcomes including overall survival (OS), relapse rate, and remission duration (RD). In …

Multicenter Phase Ii Trial Of The Wee1 Inhibitor Adavosertib In Refractory Solid Tumors Harboring, Siqing Fu, Shuyang Yao, Yuan Yuan, Rebecca A Previs, Anthony D Elias, Richard D Carvajal, Thomas J George, Ying Yuan, Lihou Yu, Shannon N Westin, Yan Xing, Ecaterina E Dumbrava, Daniel D Karp, Sarina A Piha-Paul, Apostolia M Tsimberidou, Jordi Rodon Ahnert, Naoko Takebe, Karen Lu, Khandan Keyomarsi, Funda Meric-Bernstam

Faculty, Staff and Student Publications

PURPOSE: Preclinical cancer models harboring

PATIENTS AND METHODS: Patients aged ≥ 18 years with measurable disease and refractory solid tumors harboring

RESULTS: Thirty patients were enrolled. The median follow-up duration was 9.9 months. Eight patients had partial responses (PRs), and three had stable disease (SD) ≥ 6 months, with an ORR of 27% (95% CI, 12 to 46), a SD ≥ 6 months/PR rate of 37% (95% CI, 20 to 56), a median progression-free survival duration of 4.1 months (95% CI, 1.8 to 6.4), and a median overall survival duration of 9.9 months (95% CI, 4.8 to 15). Fourteen patients …