Medical Specialties Commons^™

Modified Messengers: Flatworm Stem Cells And Regeneration Are Guarded By Rna Methylation, Blair W Benham-Pyle

Faculty, Staff and Students Publications

The contribution of RNA modifications to whole-body regeneration remains unclear. In this issue, Dagan et al (2022) show that m6a mRNA pathway components are critically required for stem cell differentiation, survival, and tissue renewal in the planarian Schmidtea mediterranea.

Identification Of Novel Susceptibility Methylation Loci For Pancreatic Cancer In A Two-Phase Epigenome-Wide Association Study, Ziqiao Wang, Yue Lu, Myriam Fornage, Li Jiao, Jianjun Shen, Donghui Li, Peng Wei

Faculty, Staff and Student Publications

The role of DNA methylation and its interplay with gene expression in the susceptibility to pancreatic cancer (PanC) remains largely unexplored. To fill in this gap, we conducted an integrative two-phase epigenome-wide association study (EWAS) of PanC using genomic DNA from 44 cases and 556 controls (20 local controls and 536 public controls in the Framingham Heart Study) in phase 1 and 23 cases and 22 controls in phase 2. We validated the findings using pre-diagnostic blood samples from 13 cases and 26 controls in the Women's Health Initiative (WHI) Study. We further examined gene expression in peripheral leukocytes of …

Oxytocin Signaling Is Necessary For Synaptic Maturation Of Adult-Born Neurons, Brandon T Pekarek, Mikhail Kochukov, Brittney Lozzi, Timothy Wu, Patrick J Hunt, Burak Tepe, Elizabeth Hanson Moss, Evelyne K Tantry, Jessica L Swanson, Sean W Dooling, Mayuri Patel, Benjamin D W Belfort, Juan M Romero, Suyang Bao, Matthew C Hill, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

Neural circuit plasticity and sensory response dynamics depend on forming new synaptic connections. Despite recent advances toward understanding the consequences of circuit plasticity, the mechanisms driving circuit plasticity are unknown. Adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and circuit integration. We and others have shown that efficient adult-born neuron circuit integration hinges on presynaptic activity in the form of diverse signaling peptides. Here, we demonstrate a novel oxytocin-dependent mechanism of adult-born neuron synaptic maturation and circuit integration. We reveal spatial …

Clinical And Molecular Features Of Pediatric Cancer Patients With Lynch Syndrome, Sarah Scollon, Mohammad K Eldomery, Jacquelyn Reuther, Frank Y Lin, Samara L Potter, Lauren Desrosiers, Kenneth L Mcclain, Valeria Smith, Jack Meng-Fen Su, Rajkumar Venkatramani, Jianhong Hu, Viktoriya Korchina, Neda Zarrin-Khameh, Richard A Gibbs, Donna M Muzny, Christine Eng, Angshumoy Roy, D Williams Parsons, Sharon E Plon

Faculty, Staff and Students Publications

BACKGROUND: The association of childhood cancer with Lynch syndrome is not established compared with the significant pediatric cancer risk in recessive constitutional mismatch repair deficiency syndrome (CMMRD).

PROCEDURE: We describe the clinical features, germline analysis, and tumor genomic profiling of patients with Lynch syndrome among patients enrolled in pediatric cancer genomic studies.

RESULTS: There were six of 773 (0.8%) pediatric patients with solid tumors identified with Lynch syndrome, defined as a germline heterozygous pathogenic variant in one of the mismatch repair (MMR) genes (three with MSH6, two with MLH1, and one with MSH2). Tumor analysis demonstrated evidence for somatic second …

An Automated Treatment Planning Framework For Spinal Radiation Therapy And Vertebral-Level Second Check, Tucker J Netherton, Callistus Nguyen, Carlos E Cardenas, Caroline Chung, Ann H Klopp, Lauren E Colbert, Dong Joo Rhee, Christine B Peterson, Rebecca Howell, Peter Balter, Laurence E Court

Faculty, Staff and Student Publications

Purpose: Complicating factors such as time pressures, anatomic variants in the spine, and similarities in adjacent vertebrae are associated with incorrect level treatments of the spine. The purpose of this work was to mitigate such challenges by fully automating the treatment planning process for diagnostic and simulation computed tomography (CT) scans.

Methods and materials: Vertebral bodies are labeled on CT scans of any length using 2 intendent deep-learning models-mirroring 2 different experts labeling the spine. Then, a U-Net++ architecture was trained, validated, and tested to contour each vertebra (n = 220 CT scans). Features from the CT and auto-contours were …

A Multi-Omics Framework Reveals Strawberry Flavor Genes And Their Regulatory Elements, Zhen Fan, Denise M Tieman, Steven J Knapp, Philipp Zerbe, Randi Famula, Christopher R Barbey, Kevin M Folta, Rodrigo R Amadeu, Manbo Lee, Youngjae Oh, Seonghee Lee, Vance M Whitaker

Faculty, Staff and Student Publications

Flavor is essential to consumer preference of foods and is an increasing focus of plant breeding programs. In fruit crops, identifying genes underlying volatile organic compounds has great promise to accelerate flavor improvement, but polyploidy and heterozygosity in many species have slowed progress. Here we use octoploid cultivated strawberry to demonstrate how genomic heterozygosity, transcriptomic intricacy and fruit metabolomic diversity can be treated as strengths and leveraged to uncover fruit flavor genes and their regulatory elements. Multi-omics datasets were generated including an expression quantitative trait loci map with 196 diverse breeding lines, haplotype-phased genomes of a highly-flavored breeding selection, a …

Potential Focal Adhesion Kinase Inhibitors In Management Of Cancer: Therapeutic Opportunities From Herbal Medicine, Feiyu Chen, Zhangfeng Zhong, Cheng Zhang, Yuanjun Lu, Yau-Tuen Chan, Ning Wang, Di Zhao, Yibin Feng

Faculty, Staff and Student Publications

Focal adhesion kinase (FAK) is a multifunctional protein involved in cellular communication, integrating and transducing extracellular signals from cell-surface membrane receptors. It plays a central role intracellularly and extracellularly within the tumor microenvironment. Perturbations in FAK signaling promote tumor occurrence and development, and studies have revealed its biological behavior in tumor cell proliferation, migration, and adhesion. Herein we provide an overview of the complex biology of the FAK family members and their context-dependent nature. Next, with a focus on cancer, we highlight the activities of FAK signaling in different types of cancer and how knowledge of them is being used …

Diffuse Large B-Cell Lymphoma With Phenotype Switch, Anaplastic Features And Aberrant T-Cell Marker Expression During Disease Evolution, Xiaoqiong Wang, Pei Lin, Jie Xu, Shaoying Li

Faculty, Staff and Student Publications

No abstract provided.

Lenalidomide-Based Maintenance After Autologous Hematopoietic Stem Cell Transplantation For Patients With High-Risk Multiple Myeloma, Oren Pasvolsky, Denái R Milton, Mikael Rauf, Mark R Tanner, Qaiser Bashir, Samer Srour, Guilin Tang, Neeraj Saini, Jeremy Ramdial, Adeel Masood, Yago Nieto, Hans C Lee, Krina K Patel, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Maintenance therapy with single-agent lenalidomide (Len) after autologous hematopoietic stem cell transplantation (autoHCT) for multiple myeloma (MM) is associated with improved progression-free survival (PFS). However, MM patients with high-risk chromosomal abnormalities (HRMMs) may need a more intense regimen. We hypothesized that adding another antimyeloma drug to Len maintenance would lead to improved outcomes. We conducted this retrospective single-center chart review analysis of adult HRMM patients who underwent autoHCT between 2008 and 2018, followed by Len-based maintenance therapy. High-risk cytogenetics were defined as del(17p), t(4;14), t(14;16), 1q21 gain or amplification by fluorescence in situ hybridization. We divided patients into those who …

Contemporary Outcomes In Idh-Mutated Acute Myeloid Leukemia: The Impact Of Co-Occurring Npm1 Mutations And Venetoclax-Based Treatment, Curtis A Lachowiez, Patrick K Reville, Hagop Kantarjian, Elias Jabbour, Gautam Borthakur, Naval Daver, Ghayas Issa, Ken Furudate, Tomoyuki Tanaka, Sherry Pierce, Guilin Tang, Keyur P Patel, Jeffrey Medeiros, Hussein A Abbas, Fadi Haddad, Daniel Hammond, Nicholas J Short, Abhishek Maiti, Musa Yilmaz, Koji Sasaki, Koichi Takahashi, Naveen Pemmaraju, Marina Konopleva, Guillermo Garcia-Manero, Farhad Ravandi, Tapan M Kadia, Sanam Loghavi, Courtney D Dinardo

Faculty, Staff and Student Publications

Isocitrate dehydrogenase 1 or 2 (IDH1 or IDH2) mutations occur frequently in newly diagnosed (ND) acute myeloid leukemia (AML) often with co-occurring NPM1 mutations, which may influence treatment outcomes. Detailed analysis of IDH-mutated AML treated with venetoclax and influence of co-occurring NPM1 mutations remains unclear. This retrospective single-center cohort study evaluated clinical and molecular demographics,response and survival, and impact of co-occurring NPM1 mutations in patients with IDH1 or IDH2-mutated AML. 556 patients with IDH1, IDH2, and/or NPM1 mutated AML were included. Patients with IDH1mut AML (N = 119) were more likely to have older age, sAML, ELN-adverse risk disease, and …

Clinical Outcomes And Impact Of Therapeutic Intervention In Patients With Acute Myeloid Leukemia Who Experience Measurable Residual Disease (Mrd) Recurrence Following Mrd-Negative Remission, Nicholas J Short, Walid Macaron, Tapan Kadia, Courtney Dinardo, Ghayas C Issa, Naval Daver, Sa Wang, Jeff Jorgensen, Daniel Nguyen, Aram Bidikian, Keyur P Patel, Sanam Loghavi, Marina Konopleva, Musa Yilmaz, Elias Jabbour, Abhishek Maiti, Hussein A Abbas, Elizabeth Shpall, Uday Popat, Gheath Al-Atrash, Sherry Pierce, Hagop M Kantarjian, Farhad Ravandi

Faculty, Staff and Student Publications

Recurrence of MRD in AML is associated with imminent relapse unless intervened upon. Change in chemotherapy regimen and/or immediate transplant improve outcomes.

International Delphi Consensus Guidelines For Follow-Up After Prophylactic Total Gastrectomy: The Life After Prophylactic Total Gastrectomy (Lap-Tg) Study, Geoffrey Roberts, Patrick R Benusiglio, Tanya Bisseling, Daniel Coit, Jeremy L Davis, Sam Grimes, Theresa A Guise, Richard Hardwick, Kirsty Harris, Paul Furman Mansfield, Jeremy Rossaak, Karen Chelcun Schreiber, Peter P Stanich, Vivian E Strong, Pardeep Kaurah

Faculty, Staff and Student Publications

Background: Prophylactic total gastrectomy (PTG) remains the only means of preventing gastric cancer for people with genetic mutations predisposing to Hereditary Diffuse Gastric Cancer (HDGC), mainly in the CDH1 gene. The small but growing cohort of people undergoing PTG at a young age are expected to have a life-expectancy close to the general population, however, knowledge of the long-term effects of, and monitoring requirements after, PTG is limited. This study aims to define the standard of care for follow-up after PTG.

Methods: Through a combination of literature review and two-round Delphi consensus of major HDGC/PTG units and physicians, and patient …

Low-Dose Dasatinib 50 Mg/Day Versus Standard-Dose Dasatinib 100 Mg/Day As Frontline Therapy In Chronic Myeloid Leukemia In Chronic Phase: A Propensity Score Analysis, Elias Jabbour, Koji Sasaki, Fadi G Haddad, Ghayas C Issa, Jeffrey Skinner, Sara Dellasala, Musa Yilmaz, Alessandra Ferrajoli, Prithviraj Bose, Philip Thompson, Yesid Alvarado, Nitin Jain, Guillermo Garcia-Manero, Koichi Takahashi, Gautam Borthakur, Naveen Pemmaraju, Sherry Pierce, Hagop Kantarjian

Faculty, Staff and Student Publications

Low-dose dasatinib is safe and effective in patients with chronic myeloid leukemia in chronic phase (CML-CP). No randomized trials have compared the outcome with standard-dose dasatinib. This study aims to compare the outcome of patients with CML-CP treated with frontline dasatinib 50 versus 100 mg/day. We analyzed 233 patients with newly diagnosed CML-CP treated with low-dose dasatinib (N = 83) or standard-dose dasatinib (N = 150). Propensity score analysis with 1:1 matching was performed and identified 77 patients in each cohort without significant baseline differences. Response rates were reported as the cumulative incidences of complete cytogenetic response, major molecular response …

Acute Depletion Of Human Core Nucleoporin Reveals Direct Roles In Transcription Control But Dispensability For 3d Genome Organization, Xiaoyu Zhu, Chuangye Qi, Ruoyu Wang, Joo-Hyung Lee, Jiaofang Shao, Lanxin Bei, Feng Xiong, Phuoc T Nguyen, Guojie Li, Joanna Krakowiak, Su-Pin Koh, Lukas M Simon, Leng Han, Travis I Moore, Wenbo Li

Faculty, Staff and Student Publications

The nuclear pore complex (NPC) comprises more than 30 nucleoporins (NUPs) and is a hallmark of eukaryotes. NUPs have been suggested to be important in regulating gene transcription and 3D genome organization. However, evidence in support of their direct roles remains limited. Here, by Cut&Run, we find that core NUPs display broad but also cell-type-specific association with active promoters and enhancers in human cells. Auxin-mediated rapid depletion of two NUPs demonstrates that NUP93, but not NUP35, directly and specifically controls gene transcription. NUP93 directly activates genes with high levels of RNA polymerase II loading and transcriptional elongation by facilitating full …

Quantitative Mri Of Chronic Pancreatitis: Results From A Multi-Institutional Prospective Study, Magnetic Resonance Imaging As A Non-Invasive Method For Assessment Of Pancreatic Fibrosis (Minimap), Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Paul R Territo, Xuandong Zhao, Scott A Persohn, Anil K Dasyam, Zarine K Shah, Sudhakar K Venkatesh, Naoki Takahashi, Ashley Wachsman, Liang Li, Yan Li, Stephen J Pandol, Walter G Park, Santhi S Vege, Phil A Hart, Mark Topazian, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Purpose: To determine if quantitative MRI techniques can be helpful to evaluate chronic pancreatitis (CP) in a setting of multi-institutional study.

Methods: This study included a subgroup of participants (n = 101) enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study (NCT03099850) from February 2019 to May 2021. MRI was performed on 1.5 T using Siemens and GE scanners at seven clinical centers across the USA. Quantitative MRI parameters of the pancreas included T1 relaxation time, extracellular volume (ECV) fraction, apparent diffusion coefficient (ADC), and fat signal fraction. We report the diagnostic …

Longitudinal Associations Of Risk Factors And Hepatocellular Carcinoma In Patients With Cured Hepatitis C Virus Infection, Jennifer R Kramer, Yumei Cao, Liang Li, Donna Smith, Jagpreet Chhatwal, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Student Publications

Introduction: There are limited data on the effect and evolution of risk factors for hepatocellular carcinoma (HCC) in patients with virologically cured hepatitis C virus (HCV) infection.

Methods: We conducted a retrospective cohort study of patients with HCV who achieved sustained virological response with direct-acting antivirals from 130 Veterans Administration hospitals during 2014-2018, followed through 2021. Cox proportional hazards models were constructed at 3 landmark times (baseline and 12 and 24 months after sustained virological response) to examine associations between demographic, clinical, and behavioral factors and HCC risk, stratified by cirrhosis status.

Results: Among 92,567 patients (32% cirrhosis), 3,247 cases …

Treatment-Related Pulmonary Adverse Events Induced By Chemoradiation And Durvalumab Affect Survival In Locally Advanced Non-Small Cell Lung Cancer, Ting Xu, Lirong Wu, Saumil Gandhi, Wang Jing, Quyhn-Nhu Nguyen, Aileen Chen, Joe Y Chang, Roza Nurieva, Ajay Sheshadri, Mehmet Altan, Percy P Lee, Steven H Lin, Zhongxing Liao

Faculty, Staff and Student Publications

Purpose: We compared treatment-related pulmonary adverse events (TRPAE), progression-free survival (PFS), and overall survival (OS) among locally advanced non-small cell lung cancer (NSCLC) patients who received concurrent chemoradiotherapy (CRT) versus CRT followed by immune check point inhibitor (ICI) immunotherapy (CRTI).

Materials and methods: TRPAE was defined as any pulmonary events as defined in CTCAE v.5 occurring within 12 months after completion of radiotherapy. Outcomes were compared between CRT and CTRI by Cox proportional hazard regression and Kaplan-Meier analyses. We also assessed if TRPAE-induced discontinuation of ICI affected survival.

Results: We analyzed 326 patients treated between July 2010 and November 2019; …

Handwashing Results In Incomplete Nicotine Removal From Fingers Of Individuals Who Smoke: A Randomized Controlled Experiment, Thomas F Northrup, Angela L Stotts, Robert Suchting, Amir M Khan, Michelle R Klawans, Charles Green, Eunha Hoh, Melbourne F Hovell, Georg E Matt, Penelope J E Quintana

Faculty, Staff and Student Publications

Objective: Tobacco residue, also known as third-hand smoke (THS), contains toxicants and lingers in dust and on surfaces and clothes. THS also remains on hands of individuals who smoke, with potential transfer to infants during visitation while infants are hospitalized in neonatal intensive care units (NICUs), raising concerns (e.g., hindered respiratory development) for vulnerable infants. Previously unexplored, this study tested handwashing (HW) and sanitization efficacy for finger-nicotine removal in a sample of adults who smoked and were visiting infants in an NICU.

Study design: A cross-sectional sample was recruited to complete an interview, carbon monoxide breath samples, and three nicotine …

Is Loss Of P53 A Driver Of Ductal Carcinoma In Situ Progression?, Rhiannon L Morrissey, Alastair M Thompson, Guillermina Lozano

Faculty, Staff and Student Publications

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive carcinoma. Multiple studies have shown that DCIS lesions typically possess a driver mutation associated with cancer development. Mutation in the TP53 tumour suppressor gene is present in 15-30% of pure DCIS lesions and in ~30% of invasive breast cancers. Mutations in TP53 are significantly associated with high-grade DCIS, the most likely form of DCIS to progress to invasive carcinoma. In this review, we summarise published evidence on the prevalence of mutant TP53 in DCIS (including all DCIS subtypes), discuss the availability of mouse models for the study of DCIS …

Validation Of Cancer-Type-Dependent Benefit From Immune Checkpoint Blockade In Tmb-H Tumors Identified By The Foundationone Cdx Assay, D J Mcgrail, P G Pilié, N U Rashid, L Voorwerk, M Slagter, M Kok, E Jonasch, M Khasraw, A B Heimberger, N T Ueno, R Ferrarotto, J T Chang, S-Y Lin

Faculty, Staff and Student Publications

No abstract provided.

A Semi-Mechanistic Dose-Finding Design In Oncology Using Pharmacokinetic/Pharmacodynamic Modeling, Xiao Su, Yisheng Li, Peter Müller, Chia-Wei Hsu, Haitao Pan, Kim-Anh Do

Faculty, Staff and Student Publications

While a number of phase I dose-finding designs in oncology exist, the commonly used ones are either algorithmic or empirical model-based. We propose a new framework for modeling the dose-response relationship, by systematically incorporating the pharmacokinetic (PK) data collected in the trial and the hypothesized mechanisms of the drug effects, via dynamic PK/PD modeling, as well as modeling of the relationship between a latent cumulative pharmacologic effect and a binary toxicity outcome. This modeling framework naturally incorporates the information on the impact of dose, schedule and method of administration (e.g., drug formulation and route of administration) on toxicity. The resulting …

Flow Cytometry Immunophenotypic Features Of Pure Erythroid Leukemia And The Distinction From Reactive Erythroid Precursors, Hong Fang, Sa A Wang, M James You, Shimin Hu, Roberto N Miranda, Zhenya Tang, Pei Lin, Jeffrey L Jorgensen, Jie Xu, Beenu Thakral, Ellen J Schlette, Siba El Hussein, Carlos Bueso-Ramos, L Jeffrey Medeiros, Wei Wang

Faculty, Staff and Student Publications

BACKGROUND: The immunophenotype of pure erythroid leukemia (PEL) as determined by flow cytometry immunophenotypic analysis is not well characterized. The immunophenotypic difference between PEL and reactive conditions is under-explored.

METHODS: We assessed and compared the immunophenotype of 24 PEL cases and 28 reactive cases containing early erythroid precursors by flow cytometry.

RESULTS: The neoplastic erythroid cells in all PEL cases were positive for CD36 and CD71. CD45 was also positive in all cases, but the expression level was often dimmer than granulocytes. CD117 expression ranged from partial to uniform, and CD235a was often only positive in the CD117-dim to negative …

Contemporary Primary Treatment Of Women With Stage Ii-Iv Low-Grade Serous Ovarian/Peritoneal Cancer (Lgsoc): Determinants Of Relapse And Disease-Free Survival, David M Gershenson, Lauren P Cobb, Shannon N Westin, Yingao Zhang, Amir Jazaeri, Anais Malpica, Charlotte C Sun

Faculty, Staff and Student Publications

Objective: The purpose of the present study is to describe a cohort who received contemporary primary treatment for stage II-IV low-grade serous ovarian/peritoneal cancer (LGSOC), including patient characteristics and determinants of relapse and disease-free survival.

Methods: The study included 99 patients: 1) with pathologically confirmed stage II-IV LGSOC of the ovary or peritoneum, 2) who underwent primary treatment consisting of cytoreductive surgery and either a) platinum/taxane chemotherapy followed by aromatase inhibitor maintenance therapy or b) aromatase inhibitor monotherapy, and 3) for whom there was availability of clinical data. Descriptive statistics were used to characterize clinicodemographic features. Subgroups were compared for …

Impact Of Conditioning Chemotherapy On Lymphocyte Kinetics And Outcomes In Lbcl Patients Treated With Car T-Cell Therapy, Paolo Strati, Andrew P Jallouk, Ryan Sun, Jaihee Choi, Kaberi Das, Hua-Jay Cherng, Sairah Ahmed, Hun J Lee, Swaminathan P Iyer, Ranjit Nair, Loretta J Nastoupil, Raphael E Steiner, Chad D Huff, Yao Yu, Haleigh Mistry, Brittany Pulsifer, Mansoor Noorani, Neeraj Saini, Elizabeth J Shpall, Partow Kebriaei, Christopher R Flowers, Jason R Westin, Michelle A T Hildebrandt, Sattva S Neelapu

Faculty, Staff and Student Publications

Conditioning chemotherapy (CCT) has been shown to be essential for optimal efficacy of chimeric antigen receptor (CAR) T-cell therapy. Here, we determined whether the change in absolute lymphocyte count, referred to as delta lymphocyte index (DLIx), may serve as a surrogate marker for pharmacodynamic effects of CCT and whether it associated with germline genetic variants in patients with large B-cell lymphoma (LBCL). One-hundred and seventy-one patients were included, of which 86 (50%) received bridging therapy post-leukapheresis. Median DLIx was 0.5 × 109/L (range, 0.01-2.75 × 109/L) and was significantly higher in patients who achieved complete response (p = 0.04). On …

Clinical Exome Sequencing Uncovers A High Frequency Of Mendelian Disorders In Infants With Stroke: A Retrospective Analysis, Runjun D Kumar, Linyan Meng, Pengfei Liu, Christina Y Miyake, Kim C Worley, Weimin Bi, Seema R Lalani

Faculty, Staff and Students Publications

Background:

Stroke causes significant disability and is a common cause of death worldwide. Previous studies have estimated that 1-5% of stroke is attributable to monogenic etiologies. We set out to assess the utility of clinical exome sequencing (ES) in the evaluation of stroke.

Methods:

We retrospectively analyzed 124 individuals who received ES at the Baylor Genetics reference lab between 2012 and 2021 who had stroke as a major part of their reported phenotype.

Results:

Ages ranged from 10 days to 69 years. 8.9% of the cohort received a diagnosis, including 25% of infants less than 1 year old; an additional …

Magnetic Resonance-Guided Radiation Therapy For Head And Neck Cancers, Danny Lavigne, Sweet Ping Ng, Brian O'Sullivan, Phuc Felix Nguyen-Tan, Edith Filion, Laurent Létourneau-Guillon, Clifton D Fuller, Houda Bahig

Faculty, Staff and Student Publications

Despite the significant evolution of radiation therapy (RT) techniques in recent years, many patients with head and neck cancer still experience significant toxicities during and after treatments. The increased soft tissue contrast and functional sequences of magnetic resonance imaging (MRI) are particularly attractive in head and neck cancer and have led to the increasing development of magnetic resonance-guided RT (MRgRT). This approach refers to the inclusion of the additional information acquired from a diagnostic or planning MRI in radiation treatment planning, and now extends to online high-quality daily imaging generated by the recently developed MR-Linac. MRgRT holds numerous potentials, including …

Proteo-Genomic Characterization Of Virus-Associated Liver Cancers Reveals Potential Subtypes And Therapeutic Targets, Masashi Fujita, Mei-Ju May Chen, Doris Rieko Siwak, Shota Sasagawa, Ayako Oosawa-Tatsuguchi, Koji Arihiro, Atsushi Ono, Ryoichi Miura, Kazuhiro Maejima, Hiroshi Aikata, Masaki Ueno, Shinya Hayami, Hiroki Yamaue, Kazuaki Chayama, Ju-Seog Lee, Yiling Lu, Gordon B Mills, Han Liang, Satoshi S Nishizuka, Hidewaki Nakagawa

Faculty, Staff and Student Publications

Primary liver cancer is a heterogeneous disease in terms of its etiology, histology, and therapeutic response. Concurrent proteomic and genomic characterization of a large set of clinical liver cancer samples can help elucidate the molecular basis of heterogeneity and thus serve as a valuable resource for personalized liver cancer treatment. In this study, we perform proteomic profiling of ~300 proteins on 259 primary liver cancer tissues with reverse-phase protein arrays, mutational analysis using whole genome sequencing and transcriptional analysis with RNA-Seq. Patients are of Japanese ethnic background and mainly HBV or HCV positive, providing insight into this important liver cancer …

Distinct Organization Of Two Cortico-Cortical Feedback Pathways, Shan Shen, Xiaolong Jiang, Federico Scala, Jiakun Fu, Paul Fahey, Dmitry Kobak, Zhenghuan Tan, Na Zhou, Jacob Reimer, Fabian Sinz, Andreas S Tolias

Duncan NRI Faculty and Staff Publications

Neocortical feedback is critical for attention, prediction, and learning. To mechanically understand its function requires deciphering its cell-type wiring. Recent studies revealed that feedback between primary motor to primary somatosensory areas in mice is disinhibitory, targeting vasoactive intestinal peptide-expressing interneurons, in addition to pyramidal cells. It is unknown whether this circuit motif represents a general cortico-cortical feedback organizing principle. Here we show that in contrast to this wiring rule, feedback between higher-order lateromedial visual area to primary visual cortex preferentially activates somatostatin-expressing interneurons. Functionally, both feedback circuits temporally sharpen feed-forward excitation eliciting a transient increase–followed by a prolonged decrease–in pyramidal …

Cluster Analysis Of Short Sensory Profile Data Reveals Sensory-Based Subgroups In Autism Spectrum Disorder, Ariel M Lyons-Warren, Michael F Wangler, Ying-Wooi Wan

Duncan NRI Faculty and Staff Publications

Autism spectrum disorder is a common, heterogeneous neurodevelopmental disorder lacking targeted treatments. Additional features include restricted, repetitive patterns of behaviors and differences in sensory processing. We hypothesized that detailed sensory features including modality specific hyper- and hypo-sensitivity could be used to identify clinically recognizable subgroups with unique underlying gene variants. Participants included 378 individuals with a clinical diagnosis of autism spectrum disorder who contributed Short Sensory Profile data assessing the frequency of sensory behaviors and whole genome sequencing results to the Autism Speaks’ MSSNG database. Sensory phenotypes in this cohort were not randomly distributed with 10 patterns describing 43% (162/378) …

Systematic Analysis Of Mobile Genetic Elements Mediating Β-Lactamase Gene Amplification In Noncarbapenemase-Producing Carbapenem-Resistant Enterobacterales Bloodstream Infections, W C Shropshire, A Konovalova, P Mcdaneld, M Gohel, B Strope, P Sahasrabhojane, C N Tran, D Greenberg, J Kim, X Zhan, S Aitken, M Bhatti, T C Savidge, T J Treangen, B M Hanson, C A Arias, S A Shelburne

Faculty, Staff and Student Publications

Noncarbapenemase-producing carbapenem-resistant Enterobacterales (non-CP-CRE) are increasingly recognized as important contributors to prevalent carbapenem-resistant Enterobacterales (CRE) infections. However, there is limited understanding of mechanisms underlying non-CP-CRE causing invasive disease. Long- and short-read whole-genome sequencing was used to elucidate carbapenem nonsusceptibility determinants in Enterobacterales bloodstream isolates at MD Anderson Cancer Center in Houston, Texas. We investigated carbapenem nonsusceptible Enterobacterales (CNSE) mechanisms (i.e., isolates with carbapenem intermediate resistance phenotypes or greater) through a combination of phylogenetic analysis, antimicrobial resistance gene detection/copy number quantification, porin assessment, and mobile genetic element (MGE) characterization. Most CNSE isolates sequenced were non-CP-CRE (41/79; 51.9%), whereas 25.3% (20/79) were …