Medical Specialties Commons^™

Multidisciplinary Amputation Prevention At The Debakey Va Hospital: Our First Decade, Neal R Barshes, Aimee D Garcia, Cezarina Mindru, Maria Rodriguez-Barradas, Panos Kougias, David M Green, Samir S Awad

Faculty, Staff and Students Publications

BACKGROUND: In 2011, the Veterans Health Administration (VHA) undertook multidisciplinary efforts to improve care for patients with nonhealing foot ulcers and reduce leg amputation rates. This article examines the impact of interdisciplinary care for amputation prevention in the VHA.

METHODS: The VHA patient population was characterized using internal registries. Texas hospital admission data were used to identify sex and zip-code matched cohorts. VHA provided data on national and local frequencies of various amputations and the number of patients with diabetes.

RESULTS: Compared to matched nonveteran patients, veterans treated at VHA hospitals were older and more often self-identified as Black. They …

Analysis Of The Correlation Between In-Hospital Adverse Events And Transcatheter Aortic Valve Replacement Outcomes, Stanislava Matejin, Pavel Poredos, Anja Boc, Vinko Boc, Wahaj Aman, Igor D. Gregoric, Biswajit Kar

Journal of Shock and Hemodynamics

Transcatheter aortic valve replacement (TAVR) has been recommended as the standard treatment for elderly patients with severe aortic stenosis (AS) and those at increased risk for conventional surgical procedures. Recently, TAVR has been recognized as the treatment of choice for intermediate-risk patients or even low-risk populations with AS. Our study aimed to identify factors influencing adverse events after TAVR procedures. This single-center, retrospective cohort study involved patients with severe AS treated with TAVR from 2016 to 2019. The patient’s electronic medical record was reviewed, and those with valve-in-valve replacements and missing demographical data were excluded. We analyzed risk factors related …

Optimal Infused Cd34+ Cell Dose In Multiple Myeloma Patients Undergoing Upfront Autologous Hematopoietic Stem Cell Transplantation, Oren Pasvolsky, Curtis Marcoux, Denái R Milton, Babar Pal, Mark R Tanner, Qaiser Bashir, Samer Srour, Jaehyun Lee, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Yosra Aljawai, Partow Kebriaei, Melody R Becnel, Hans C Lee, Krina K Patel, Sheeba K Thomas, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Autologous transplantation remains the standard of care for eligible multiple myeloma (MM) patients, yet optimal CD34+ cell dose remains unclear. We conducted a retrospective study on MM patients undergoing upfront transplant between 2005 and 2021 and divided them into low (≤2.5 × 106 cells/kg) and high (>2.5 × 106 cells/kg) CD34+ dose groups. We included 2479 patients, 95 in the low CD34+ group and 2384 in the high CD34+ group. Patients in the low CD34+ group were older (63.2 vs 61.1 years, p = 0.013), more often had R-ISS III (19% vs 9%, p = 0.014), received plerixafor (60% …

Takotsubo Syndrome: An International Expert Consensus Report On Practical Challenges And Specific Conditions (Part-2: Specific Entities, Risk Stratification And Challenges After Recovery), Kenan Yalta, John E Madias, Nicholas G Kounis, Shams Y-Hassan, Marija Polovina, Servet Altay, Alexandre Mebazaa, Mehmet Birhan Yilmaz, Yuri Lopatin, Mamas A Mamas, Robert J Gil, Ritu Thamman, Abdallah Almaghraby, Biykem Bozkurt, Gani Bajraktari, Thomas Fink, Vassil Traykov, Stephane Manzo-Silberman, Ulvi Mirzoyev, Sekib Sokolovic, Zviad V Kipiani, Cecilia Linde, Petar M Seferovic

Faculty, Staff and Students Publications

Takotsubo syndrome (TTS) still remains as an enigmatic phenomenon. In particular, long-term challenges (including clinical recurrence and persistent symptoms) and specific entities in the setting of TTS have been the evolving areas of interest. On the other hand, a significant gap still exists regarding the proper risk-stratification of this phenomenon in the short and long terms. The present paper, the second part (part-2) of the consensus report, aims to discuss less well-known aspects of TTS including specific entities, challenges after recovery and risk-stratification.

Ten-Year Outcomes After Bariatric Surgery In Adolescents, Justin R Ryder, Todd M Jenkins, Changchun Xie, Anita P Courcoulas, Carroll M Harmon, Michael A Helmrath, Stephanie Sisley, Marc P Michalsky, Mary Brandt, Thomas H Inge

Faculty, Staff and Students Publications

No abstract provided.

Opioid Use In Thoracic Surgery: A Retrospective Study On Postoperative Complications, Jerry Xiao, Duc T Nguyen, Zoe K Lichtenberg, Elsie Rizk, Leonora M Meisenbach, Ray Chihara, Edward A Graviss, Min P Kim

Faculty, Staff and Students Publications

Background: Opioids are important medications that are used to control postoperative pain. The enhanced recovery after surgery (ERAS) program has reduced opioid use after surgery. In a surgical practice with a robust ERAS program, we wanted to determine if there was a relationship between in-hospital opioid use and postoperative complications.

Methods: We performed a retrospective nested case-control study of patients who underwent thoracic surgical intervention at the Houston Methodist Hospital (HMH) between 11/2020 and 11/2021 from the thoracic surgery database with hospital morphine milligram equivalent (MME) information, comparing patients who did and did not experience postoperative complications. We determined the …

Takotsubo Syndrome: An International Expert Consensus Report On Practical Challenges And Specific Conditions (Part-1: Diagnostic And Therapeutic Challenges), Kenan Yalta, John E Madias, Nicholas G Kounis, Shams Y-Hassan, Marija Polovina, Servet Altay, Alexandre Mebazaa, Mehmet Birhan Yilmaz, Yuri Lopatin, Mamas A Mamas, Robert J Gil, Ritu Thamman, Abdallah Almaghraby, Biykem Bozkurt, Gani Bajraktari, Thomas Fink, Vassil Traykov, Stephane Manzo-Silberman, Ulvi Mirzoyev, Sekib Sokolovic, Zviad V Kipiani, Cecilia Linde, Petar M Seferovic

Faculty, Staff and Students Publications

In the recent years, there has been a burgeoning interest in Takotsubo syndrome (TTS), which is renowned as a specific form of reversible myocardial dysfunction. Despite the extensive literature available on TTS, clinicians still face several practical challenges associated with the diagnosis and management of this phenomenon. This potentially results in the underdiagnosis and improper management of TTS in clinical practice. The present paper, the first part (part-1) of the consensus report, aims to cover diagnostic and therapeutic challenges associated with TTS along with certain recommendations to combat these challenges.

Tumor-Associated Tractography Derived From High-Angular-Resolution Q-Space Mri May Predict Patterns Of Cellular Invasion In Glioblastoma, Owen P Leary, John P Zepecki, Mattia Pizzagalli, Steven A Toms, David D Liu, Yusuke Suita, Yao Ding, Jihong Wang, Renjie He, Caroline Chung, Clifton D Fuller, Jerrold L Boxerman, Nikos Tapinos, Richard J Gilbert

Faculty, Staff and Student Publications

BACKGROUND: The invasion of glioblastoma cells beyond the visible tumor margin depicted by conventional neuroimaging is believed to mediate recurrence and predict poor survival. Radiomic biomarkers that are associated with the direction and extent of tumor infiltration are, however, non-existent.

METHODS: Patients from a single center with newly diagnosed glioblastoma (

RESULTS: In the principal enrollment cohort of patients with glioblastoma, all cases displayed tractography patterns with tumor-intersecting tract bundles extending into brain parenchyma, a phenotype which was reproduced in PDX mice as well as in a larger comparison cohort of glioblastoma patients (

CONCLUSIONS: QSI discriminates tumor-specific patterns of …

Volumetric Ct Assessment Of In Situ Induced Hepatic Lesions In A Transgenic Swine Model, Derek Smetanick, Danielle Stolley, David Fuentes, Natalie W Fowlkes, Faith Shakoor, Maria Sophia Stenkamp, Samantha Hicks, Steve Parrish, Erik Cressman

Faculty, Staff and Student Publications

The growth rate of in situ-induced hepatic lesions in an Oncopig large animal model is quantitatively assessed. Oncopigs (n = 9) received baseline triple-phase CT scans prior to lesion induction. Lesions were subsequently induced by delivering the Ad-Cre vector to four locations in the liver. Triple-phase CT scans were obtained weekly to track the growth of the lesions. Animals were sacrificed at 14, 21, or 28 days (n = 3 in each group). The overall success rate of lesion generation was ~78%. Histopathology sections consistently revealed lesions that were highly inflammatory and consisted of a large leukocyte population without clear …

Type I Met Inhibitors Cooperate With Pd-1 Blockade To Promote Rejection Of Hepatocellular Carcinoma, Ricardo Deazevedo, Madeline Steiner, Broderick X Turner, Arthur Liu, Sherwin Newton, Joanna Schmidt, Rachel Fleming, Angelica Tolentino, Ahmed O Kaseb, Michael A Curran

Faculty, Staff and Student Publications

Blockade of the immune checkpoints programmed death-1 (PD-1) and cytotoxic lymphocyte antigen 4 has improved outcomes for patients with hepatocellular carcinoma (HCC), yet most still fail to achieve objective clinical benefit. MET plays key roles in both HCC tumorigenesis and immunosuppressive conditioning; however, inhibition of MET causes upregulation of PD-ligand 1 (PD-L1) suggesting the use of these inhibitors in the context of PD-1 blockade. We sought to investigate across the Hepa1-6, HCA-1 and diethylnitrosamine (DEN) models of HCC whether the combination of more specific type I versus more pleiotropic type II MET inhibitors would confer superior outcomes in combination with …

Enhancing Surgical Guidance: Deep Learning-Based Liver Vessel Segmentation In Real-Time Ultrasound Video Frames, Muhammad Awais, Mais Al Taie, Caleb S O'Connor, Austin H Castelo, Belkacem Acidi, Hop S Tran Cao, Kristy K Brock

Faculty, Staff and Student Publications

Background/objectives: In the field of surgical medicine, the planning and execution of liver resection procedures present formidable challenges, primarily attributable to the intricate and highly individualized nature of liver vascular anatomy. In the current surgical milieu, intraoperative ultrasonography (IOUS) has become indispensable; however, traditional 2D ultrasound imaging's interpretability is hindered by noise and speckle artifacts. Accurate identification of critical structures for preservation during hepatectomy requires advanced surgical skills.

Methods: An AI-based model that can help detect and recognize vessels including the inferior vena cava (IVC); the right (RHV), middle (MHV), and left (LVH) hepatic veins; the portal vein (PV) and …

Tumour-Intrinsic Pdl1 Signals Regulate The Chk2 Dna Damage Response In Cancer Cells And Mediate Resistance To Chk1 Inhibitors, Clare E Murray, Anand V R Kornepati, Carlos Ontiveros, Yiji Liao, Bárbara De La Peña Avalos, Cody M Rogers, Zexuan Liu, Yilun Deng, Haiyan Bai, Suresh Kari, Alvaro S Padron, Jacob T Boyd, Ryan Reyes, Curtis A Clark, Robert S Svatek, Rong Li, Yanfen Hu, Meiling Wang, José R Conejo-Garcia, Lauren A Byers, Kavya Ramkumar, Anil K Sood, Jung-Min Lee, Christin E Burd, Ratna K Vadlamudi, Harshita B Gupta, Weixing Zhao, Eloïse Dray, Patrick Sung, Tyler J Curiel

Faculty, Staff and Student Publications

Background: Aside from the canonical role of PDL1 as a tumour surface-expressed immune checkpoint molecule, tumour-intrinsic PDL1 signals regulate non-canonical immunopathological pathways mediating treatment resistance whose significance, mechanisms, and therapeutic targeting remain incompletely understood. Recent reports implicate tumour-intrinsic PDL1 signals in the DNA damage response (DDR), including promoting homologous recombination DNA damage repair and mRNA stability of DDR proteins, but many mechanistic details remain undefined.

Methods: We genetically depleted PDL1 from transplantable mouse and human cancer cell lines to understand consequences of tumour-intrinsic PDL1 signals in the DNA damage response. We complemented this work with studies of primary human tumours …

Targeting A Chemo-Induced Adaptive Signaling Circuit Confers Therapeutic Vulnerabilities In Pancreatic Cancer, Yohei Saito, Yi Xiao, Jun Yao, Yunhai Li, Wendao Liu, Arseniy E Yuzhalin, Yueh-Ming Shyu, Hongzhong Li, Xiangliang Yuan, Ping Li, Qingling Zhang, Ziyi Li, Yongkun Wei, Xuedong Yin, Jun Zhao, Seyed M Kariminia, Yao-Chung Wu, Jinyang Wang, Jun Yang, Weiya Xia, Yutong Sun, Eek-Hoon Jho, Paul J Chiao, Rosa F Hwang, Haoqiang Ying, Huamin Wang, Zhongming Zhao, Anirban Maitra, Mien-Chie Hung, Ronald A Depinho, Dihua Yu

Faculty, Staff and Student Publications

Advanced pancreatic ductal adenocarcinomas (PDACs) respond poorly to all therapies, including the first-line treatment, chemotherapy, the latest immunotherapies, and KRAS-targeting therapies. Despite an enormous effort to improve therapeutic efficacy in late-stage PDAC patients, effective treatment modalities remain an unmet medical challenge. To change the status quo, we explored the key signaling networks underlying the universally poor response of PDAC to therapy. Here, we report a previously unknown chemo-induced symbiotic signaling circuit that adaptively confers chemoresistance in patients and mice with advanced PDAC. By integrating single-cell transcriptomic data from PDAC mouse models and clinical pathological information from PDAC patients, we identified …

A Stronger Impact On Career Development For Early- And Mid-Career Faculty, Daniel A Gorelick, Jason Gertz, Kaitlin J Basham, Lindsey S Treviño

Faculty, Staff and Students Publications

Nuclear receptors are important in normal physiology and disease. Physicians and scientists who study nuclear receptors organize and attend conferences and symposia devoted to foundational and translational nuclear receptor research, but the field lacks a platform for early-stage investigators and aspiring leaders. In 2019, Zeynep Madak-Erdogan, Rebecca Riggins, and Matthew Sikora founded Nuclear Receptor (NR) Interdisciplinary Meeting for Progress And Collaboration Together (IMPACT, https://nrimpact.com), a collaborative group designed for early- and mid-career faculty who study nuclear receptors in any context or organism [1]. NR IMPACT addresses challenges for early- and mid-career faculty. Here, we review the progress of NR IMPACT …

Dna-Binding Proteins From Mbd Through Zf To Ben: Recognition Of Cytosine Methylation Status By One Arginine With Two Conformations, Xing Zhang, Robert M Blumenthal, Xiaodong Cheng

Faculty, Staff and Student Publications

Maintenance methylation, of palindromic CpG dinucleotides at DNA replication forks, is crucial for the faithful mitotic inheritance of genomic 5-methylcytosine (5mC) methylation patterns. MBD proteins use two arginine residues to recognize symmetrically-positioned methyl groups in fully-methylated 5mCpG/5mCpG and 5mCpA/TpG dinucleotides. In contrast, C2H2 zinc finger (ZF) proteins recognize CpG and CpA, whether methylated or not, within longer specific sequences in a site- and strand-specific manner. Unmethylated CpG sites, often within CpG island (CGI) promoters, need protection by protein factors to maintain their hypomethylated status. Members of the BEN domain proteins bind CGCG or CACG elements within CGIs to regulate gene …

Developmental-Status-Aware Transcriptional Decomposition Establishes A Cell State Panorama Of Human Cancers, Yikai Luo, Han Liang

Faculty, Staff and Student Publications

Background: Cancer cells evolve under unique functional adaptations that unlock transcriptional programs embedded in adult stem and progenitor-like cells for progression, metastasis, and therapeutic resistance. However, it remains challenging to quantify the stemness-aware cell state of a tumor based on its gene expression profile.

Methods: We develop a developmental-status-aware transcriptional decomposition strategy using single-cell RNA-sequencing-derived tissue-specific fetal and adult cell signatures as anchors. We apply our method to various biological contexts, including developing human organs, adult human tissues, experimentally induced differentiation cultures, and bulk human tumors, to benchmark its performance and to reveal novel biology of entangled developmental signaling in …

Prenatal Opioid And Alcohol Exposures: Association With Altered Placental Serotonin Transporter Structure And/Or Expression, Nune Darbinian, Nana Merabova, Gabriel Tatevosian, Sandra Adele, Armine Darbinyan, Mary F Morrison, C Lindsay Devane, Sammanda Ramamoorthy, Laura Goetzl, Michael E Selzer

Faculty, Staff and Student Publications

Fetal exposures to many drugs of abuse, e.g., opioids and alcohol (EtOH), are associated with adverse neurodevelopmental problems in early childhood, including abnormalities in activity of the serotonin (5HT) transporter (SERT), which transports 5HT across the placenta. Little is known about the effects of these drugs on SERT expression. Pregnant women who used EtOH or opioids were compared to gestational age-matched controls using a structured questionnaire to determine prenatal substance exposure. Following elective pregnancy termination, placental membranous vesicles and exosomes were prepared from first and second trimester human placentas. Changes in EtOH- or opioid-exposed placental SERT expression and modifications were …

Effective Deep Brain Stimulation For Obsessive-Compulsive Disorder After Failed Anterior Capsulotomy: Illustrative Cases, Anthony K Allam, Nisha Giridharan, Mohammed Hasen, Garrett P Banks, Gabriel Reyes, Huy Dang, Katherine E Kabotyanski, Alyssa G Hertz, Sarah R Heilbronner, Nicole Provenza, Eric A Storch, Wayne K Goodman, Sameer A Sheth

Faculty, Staff and Students Publications

BACKGROUND: Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by recurrent, unwanted thoughts (obsessions) and repetitive behaviors (compulsions) performed to relieve distress related to the obsessions. For patients with severe illness refractory to first-line pharmacotherapy and psychotherapy, neurosurgical treatments such as deep brain stimulation (DBS) and stereotactic lesioning are an option. The choice between DBS and lesioning is often driven by patient preference, but these options are not mutually exclusive. Here, the authors highlight the success of one surgical therapy (DBS) after the failure of another (lesioning).

OBSERVATIONS: Two patients with severe, treatment-refractory OCD underwent DBS lead implantation targeting the …

The Contribution Of Neutrophil Extracellular Traps To Coagulopathy In Patients With Covid-19-Related Thrombosis, Carolyn Enochs, Gabriela Delevati Colpo, Lucy Couture, Lynae Baskin, Ana E Cahuiche, Eunyoung Angela Lee, Shahid Nimjee, Louise D Mccullough

Faculty, Staff and Student Publications

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is associated with hypercoagulability and increased incidence of thrombotic events. In this study, we investigated the levels of neutrophil extracellular trap biomarkers and von Willebrand factor to assess if these could predict the occurrence of a thrombotic event in COVID-19 patients. We enrolled 202 patients hospitalized with symptomatic COVID-19 infection. Of those, 104 patients did not experience any type of thrombotic events before or during their hospitalization. These patients were compared to the other cohort of 98, who experienced thrombotic events before or during their hospitalization. In total, …

Ten Challenges And Opportunities In Computational Immuno-Oncology, Riyue Bao, Alan Hutson, Anant Madabhushi, Vanessa D Jonsson, Spencer R Rosario, Jill S Barnholtz-Sloan, Elana J Fertig, Himangi Marathe, Lyndsay Harris, Jennifer Altreuter, Qingrong Chen, James Dignam, Andrew J Gentles, Edgar Gonzalez-Kozlova, Sacha Gnjatic, Erika Kim, Mark Long, Martin Morgan, Eytan Ruppin, David Van Valen, Hong Zhang, Natalie Vokes, Daoud Meerzaman, Song Liu, Eliezer M Van Allen, Yi Xing

Faculty, Staff and Student Publications

Immuno-oncology has transformed the treatment of cancer, with several immunotherapies becoming the standard treatment across histologies. Despite these advancements, the majority of patients do not experience durable clinical benefits, highlighting the imperative for ongoing advancement in immuno-oncology. Computational immuno-oncology emerges as a forefront discipline that draws on biomedical data science and intersects with oncology, immunology, and clinical research, with the overarching goal to accelerate the development of effective and safe immuno-oncology treatments from the laboratory to the clinic. In this review, we outline 10 critical challenges and opportunities in computational immuno-oncology, emphasizing the importance of robust computational strategies and interdisciplinary …

Iron Deficiency And Internalizing Symptoms Among Adolescents In The National Health And Nutrition Examination Survey, Dimitri Fiani, Solangia Engler, Yang Ni, Sherecce Fields, Chadi Calarge

Faculty, Staff and Students Publications

Background: Iron Deficiency (ID) affects two billion people worldwide, predominantly adolescent girls, and may be associated with increased psychopathology. The associations between ID and symptoms of depression and anxiety in adolescents were examined using data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey of a nationally representative sample of non-institutionalized Americans.

Methods: The current analysis included survey cycles where both iron-related markers and mental health-related outcomes were collected in adolescents 12 to 17 years old. Acute and serious medical conditions, acute inflammation, and abnormal birth weight led to exclusion. Linear multivariable regression analyses examined the association …

Multiomic And Clinical Analysis Of Multiply Recurrent Meningiomas Reveals Risk Factors, Underlying Biology, And Insights Into Evolution, Sangami Pugazenthi, Bhuvic Patel, Collin W English, William A Leidig, Kyle P Mcgeehan, Colin R Mccornack, Shinghei Mok, Markus Anzaldua-Campos, Shervin Hosseingholi Nouri, Kaleigh Roberts, Ajay Chatrath, A Khan, Ron Gadot, Hiroko Yano, Tiemo J Klisch, Akdes S Harmanci, Akash J Patel, Albert H Kim

Faculty, Staff and Students Publications

An important subset of meningiomas behaves aggressively and is characterized by multiple recurrences. We identify clinical, genetic, and epigenetic predictors of multiply recurrent meningiomas (MRMs) and evaluate the evolution of these meningiomas in patient-matched samples. On multivariable binomial logistic regression, MRMs were significantly associated with male sex (P = 0.012), subtotal resection (P = 0.001), higher number of meningiomas on presentation (P = 0.017), and histopathological sheeting (P = 0.002). Multiomic analysis of primary meningiomas revealed that MRMs have greater copy number losses (P = 0.0313) and increased DNA methylation (P = 0.0155). In …

A Call To Action: The Shea Research Agenda To Combat Healthcare-Associated Infections, Jennie H Kwon, Sonali D Advani, Westyn Branch-Elliman, Barbara I Braun, Vincent Chi-Chung Cheng, Kathleen Chiotos, Peggy Douglas, Shruti K Gohil, Sara C Keller, Eili Y Klein, Sarah L Krein, Eric T Lofgren, Katreena Merrill, Rebekah W Moehring, Elizabeth Monsees, Luci Perri, Felicia Scaggs Huang, Mark A Shelly, Felicia Skelton, Emily S Spivak, Pranavi V Sreeramoju, Katie J Suda, Joseph Y Ting, Gregory David Weston, Mohamed H Yassin, Matthew J Ziegler, Lona Mody

Faculty, Staff and Students Publications

No abstract provided.

Interpreting The Biological Effects Of Protons As A Function Of Physical Quantity: Linear Energy Transfer Or Microdosimetric Lineal Energy Spectrum?, Fada Guan, Lawrence Bronk, Matthew Kerr, Yuting Li, Leslie A Braby, Mary Sobieski, Xiaochun Wang, Xiaodong Zhang, Clifford Stephan, David R Grosshans, Radhe Mohan

Faculty, Staff and Student Publications

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The …

Interpreting The Biological Effects Of Protons As A Function Of Physical Quantity: Linear Energy Transfer Or Microdosimetric Lineal Energy Spectrum?, Fada Guan, Lawrence Bronk, Matthew Kerr, Yuting Li, Leslie A Braby, Mary Sobieski, Xiaochun Wang, Xiaodong Zhang, Clifford Stephan, David R Grosshans, Radhe Mohan

Faculty, Staff and Student Publications

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The …

Pclaf-Dream Drives Alveolar Cell Plasticity For Lung Regeneration, Bongjun Kim, Yuanjian Huang, Kyung-Pil Ko, Shengzhe Zhang, Gengyi Zou, Jie Zhang, Moon Jong Kim, Danielle Little, Lisandra Vila Ellis, Margherita Paschini, Sohee Jun, Kwon-Sik Park, Jichao Chen, Carla Kim, Jae-Il Park

Faculty, Staff and Student Publications

Cell plasticity, changes in cell fate, is crucial for tissue regeneration. In the lung, failure of regeneration leads to diseases, including fibrosis. However, the mechanisms governing alveolar cell plasticity during lung repair remain elusive. We previously showed that PCLAF remodels the DREAM complex, shifting the balance from cell quiescence towards cell proliferation. Here, we find that PCLAF expression is specific to proliferating lung progenitor cells, along with the DREAM target genes transactivated by lung injury. Genetic ablation of Pclaf impairs AT1 cell repopulation from AT2 cells, leading to lung fibrosis. Mechanistically, the PCLAF-DREAM complex transactivates CLIC4, triggering TGF-β signaling activation, …

Salvage Reirradiation With Proton Beam Therapy For Locoregionally Recurrent Non-Small Cell Lung Cancer, Matthew S Ning, Abigael Odwuor, Joe Y Chang, Saumil Gandhi, Zhongxing Liao, Steven H Lin, Aileen Chen, James W Welsh, Quynh-Nhu Nguyen, Michael S O'Reilly, Stephen G Chun, Julianna Bronk, David Qian, Percy Lee

Faculty, Staff and Student Publications

Background/objectives: This retrospective study evaluates outcomes of 66 patients who underwent reirradiation (re-RT) with proton beam therapy (PBT) for recurrent non-small cell lung cancer.

Methods: Toxicity was scored via the CTCAE v5.0, and outcomes estimated using the Kaplan-Meier method, with associations evaluated via Cox proportional hazards and logistic regression analyses.

Results: Patients were treated to a median re-RT prescription of 66 Gy/33 fxs (BED10 = 79 Gy; IQR: 71-84 Gy) at an interval of 1.4 years from prior RT. Half (50%) received concurrent chemotherapy. At 14 months follow-up, the median OS and PFS were 5 months (95%CI: 13-17) and 12.5 …

Aromatase, Testosterone, Tmprss2: Determinants Of Covid-19 Severity, Eric C Mohan, Jude P J Savarraj, Gabriela D Colpo, Diego Morales, Carson E Finger, Alexis Mcalister, Hilda Ahnstedt, Huimahn Choi, Louise D Mccullough, Bharti Manwani

Faculty, Staff and Student Publications

Background: Male sex has been identified as a risk factor for worse COVID-19 outcomes. This sex difference has been mostly attributed to the complex role of sex hormones. Cell surface entry of SARS-CoV-2 is mediated by the transmembrane protease serine 2 (TMPRSS2) which is under transcriptional regulation by androgens. P450 aromatase enzyme converts androgens to estrogens. This study measured concentrations of aromatase enzyme, testosterone, estradiol, and TMPRSS-2 in plasma of hospitalized COVID-19 patients to elucidate the dynamics of sex-linked disparity in COVID-19 and correlate them with disease severity and mortality.

Methods: In this prospective cohort study, a total of 265 …

Interpreting The Biological Effects Of Protons As A Function Of Physical Quantity: Linear Energy Transfer Or Microdosimetric Lineal Energy Spectrum?, Fada Guan, Lawrence Bronk, Matthew Kerr, Yuting Li, Leslie A Braby, Mary Sobieski, Xiaochun Wang, Xiaodong Zhang, Clifford Stephan, David R Grosshans, Radhe Mohan

Faculty, Staff and Student Publications

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The …

Childhood Neglect Is Associated With Alterations In Neural Prediction Error Signaling And The Response To Novelty, Joseph Aloi, Kathleen I Crum, Karina S Blair, Ru Zhang, Johannah Bashford-Largo, Sahil Bajaj, Soonjo Hwang, Bruno B Averbeck, Nim Tottenham, Matthew Dobbertin, R James R Blair

Faculty, Staff and Student Publications

Background: One in eight children experience early life stress (ELS), which increases risk for psychopathology. ELS, particularly neglect, has been associated with reduced responsivity to reward. However, little work has investigated the computational specifics of this disrupted reward response - particularly with respect to the neural response to Reward Prediction Errors (RPE) - a critical signal for successful instrumental learning - and the extent to which they are augmented to novel stimuli. The goal of the current study was to investigate the associations of abuse and neglect, and neural representation of RPE to novel and non-novel stimuli.

Methods: One hundred …