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A Spatiotemporal Map Of Reading Aloud, Zachary J Roccaforte Jul 2022

A Spatiotemporal Map Of Reading Aloud, Zachary J Roccaforte

Faculty, Staff and Student Publications

Reading words aloud is a fundamental aspect of literacy. The rapid rate at which multiple distributed neural substrates are engaged in this process can only be probed via techniques with high spatiotemporal resolution. We probed this with direct intracranial recordings covering most of the left hemisphere in 46 humans (26 male, 20 female) as they read aloud regular, exception and pseudo-words. We used this to create a spatiotemporal map of word processing and to derive how broadband γ activity varies with multiple word attributes critical to reading speed: lexicality, word frequency, and orthographic neighborhood. We found that lexicality is encoded …


Vitamin E Enhances Cancer Immunotherapy By Reinvigorating Dendritic Cells Via Targeting Checkpoint Shp1, Xiangliang Yuan, Yimin Duan, Yi Xiao, Kai Sun, Yutao Qi, Zamal Ahmed, Jun Yao, Hongzhong Li, Lin Zhang, Arseniy E Yuzhalin, Ping Li, Chenyu Zhang, Akosua Badu-Nkansah, Yohei Saito, Xianghua Liu, Wen-Ling Kuo, Haoqiang Ying, Shao-Cong Sun, Jenny C Chang, John A Tainer, Dihua Yu Jul 2022

Vitamin E Enhances Cancer Immunotherapy By Reinvigorating Dendritic Cells Via Targeting Checkpoint Shp1, Xiangliang Yuan, Yimin Duan, Yi Xiao, Kai Sun, Yutao Qi, Zamal Ahmed, Jun Yao, Hongzhong Li, Lin Zhang, Arseniy E Yuzhalin, Ping Li, Chenyu Zhang, Akosua Badu-Nkansah, Yohei Saito, Xianghua Liu, Wen-Ling Kuo, Haoqiang Ying, Shao-Cong Sun, Jenny C Chang, John A Tainer, Dihua Yu

Faculty, Staff and Student Publications

Despite the popular use of dietary supplements during conventional cancer treatments, their impacts on the efficacies of prevalent immunotherapies, including immune-checkpoint therapy (ICT), are unknown. Surprisingly, our analyses of electronic health records revealed that ICT-treated patients with cancer who took vitamin E (VitE) had significantly improved survival. In mouse models, VitE increased ICT antitumor efficacy, which depended on dendritic cells (DC). VitE entered DCs via the SCARB1 receptor and restored tumor-associated DC functionality by directly binding to and inhibiting protein tyrosine phosphatase SHP1, a DC-intrinsic checkpoint. SHP1 inhibition, genetically or by VitE treatment, enhanced tumor antigen cross-presentation by DCs and …


Macrophage Migration Inhibitory Factor (Mif) Makes Complex Contributions To Pain-Related Hyperactivity Of Nociceptors After Spinal Cord Injury, Kerry E Chu Jul 2022

Macrophage Migration Inhibitory Factor (Mif) Makes Complex Contributions To Pain-Related Hyperactivity Of Nociceptors After Spinal Cord Injury, Kerry E Chu

Faculty, Staff and Student Publications

Neuropathic pain is a major, inadequately treated challenge for people with spinal cord injury (SCI). While SCI pain mechanisms are often assumed to be in the CNS, rodent studies have revealed mechanistic contributions from primary nociceptors. These neurons become chronically hyperexcitable after SCI, generating ongoing electrical activity that promotes ongoing pain. A major question is whether extrinsic chemical signals help to drive ongoing electrical activity after SCI. People living with SCI exhibit acute and chronic elevation of circulating levels of macrophage migration inhibitory factor (MIF), a cytokine implicated in preclinical pain models. Probable nociceptors isolated from male rats and exposed …


Advancing Academic Capacity In Physical And Rehabilitation Medicine To Strengthen Rehabilitation In Health Systems Worldwide: A Joint Effort By The European Academy Of Rehabilitation Medicine, The Association Of Academic Physiatrists, And The International Society Of Physical And Rehabilitation Medicine, Christoph Gutenbrunner, Stefano Negrini, Zaliha Omar, Linamara Rizzo Battistella, Gwen Sowa, Henk Stam, Jerome Bickenbach, European Academy Of Rehabilitation Medicine, Association Of Academic Physiatrists, International Society Of Physical And Rehabilitation Medicine Jul 2022

Advancing Academic Capacity In Physical And Rehabilitation Medicine To Strengthen Rehabilitation In Health Systems Worldwide: A Joint Effort By The European Academy Of Rehabilitation Medicine, The Association Of Academic Physiatrists, And The International Society Of Physical And Rehabilitation Medicine, Christoph Gutenbrunner, Stefano Negrini, Zaliha Omar, Linamara Rizzo Battistella, Gwen Sowa, Henk Stam, Jerome Bickenbach, European Academy Of Rehabilitation Medicine, Association Of Academic Physiatrists, International Society Of Physical And Rehabilitation Medicine

Faculty, Staff and Student Publications

No abstract provided.


Drug-Target Network Study Reveals The Core Target-Protein Interactions Of Various Covid-19 Treatments, Andi Liu, Wendao Liu, Xiaoqian Jiang, Yejin Kim, Yan Guo, Zhongming Zhao Jul 2022

Drug-Target Network Study Reveals The Core Target-Protein Interactions Of Various Covid-19 Treatments, Andi Liu, Wendao Liu, Xiaoqian Jiang, Yejin Kim, Yan Guo, Zhongming Zhao

Faculty, Staff and Student Publications

The coronavirus disease 2019 (COVID-19) pandemic has caused a dramatic loss of human life and devastated the worldwide economy. Numerous efforts have been made to mitigate COVID-19 symptoms and reduce the death rate. We conducted literature mining of more than 250 thousand published works and curated the 174 most widely used COVID-19 medications. Overlaid with the human protein-protein interaction (PPI) network, we used Steiner tree analysis to extract a core subnetwork that grew from the pharmacological targets of ten credible drugs ascertained by the CTD database. The resultant core subnetwork consisted of 34 interconnected genes, which were associated with 36 …


Novel Markers For Liquid Biopsies In Cancer Management: Circulating Platelets And Extracellular Vesicles, Sara Corvigno, Anna Maria Johnson, Kwong-Kwok Wong, Min Soon Cho, Vahid Afshar-Kharghan, Anil K Sood Jul 2022

Novel Markers For Liquid Biopsies In Cancer Management: Circulating Platelets And Extracellular Vesicles, Sara Corvigno, Anna Maria Johnson, Kwong-Kwok Wong, Min Soon Cho, Vahid Afshar-Kharghan, Anil K Sood

Faculty, Staff and Student Publications

Although radiologic imaging and histologic assessment of tumor tissues are classic approaches for diagnosis and monitoring of treatment response, they have many limitations. These include challenges in distinguishing benign from malignant masses, difficult access to the tumor, high cost of the procedures, and tumor heterogeneity. In this setting, liquid biopsy has emerged as a potential alternative for both diagnostic and monitoring purposes. The approaches to liquid biopsy include cell-free DNA/circulating tumor DNA, long and micro noncoding RNAs, proteins/peptides, carbohydrates/lectins, lipids, and metabolites. Other approaches include detection and analysis of circulating tumor cells, extracellular vesicles, and tumor-activated platelets. Ultimately, reliable use …


Arrhythmia Monitoring And Outcomes In Patients With Cardiac Sarcoidosis: Insights From The Cardiac Sarcoidosis Consortium, Kenneth A Ellenbogen, Steven J Kalbfleisch, Francis D Murgatroyd, David A Steckman, Lynda E Rosenfeld, Ann C Garlitski, Kyoko Soejima, Adarsh K Bhan, Vasanth Vedantham, Timm M Dickfeld, David B De Lurgio, Pyotr G Platonov, Matthew M Zipse, Suguru Nishiuchi, Matthew L Ortman, Calambur Narasimhan, Kris K Patton, David G Rosenthal, Siddharth S Mukerji, Jarieke C Hoogendoorn, Katja Zeppenfeld, William H Sauer, Jordana Kron Jul 2022

Arrhythmia Monitoring And Outcomes In Patients With Cardiac Sarcoidosis: Insights From The Cardiac Sarcoidosis Consortium, Kenneth A Ellenbogen, Steven J Kalbfleisch, Francis D Murgatroyd, David A Steckman, Lynda E Rosenfeld, Ann C Garlitski, Kyoko Soejima, Adarsh K Bhan, Vasanth Vedantham, Timm M Dickfeld, David B De Lurgio, Pyotr G Platonov, Matthew M Zipse, Suguru Nishiuchi, Matthew L Ortman, Calambur Narasimhan, Kris K Patton, David G Rosenthal, Siddharth S Mukerji, Jarieke C Hoogendoorn, Katja Zeppenfeld, William H Sauer, Jordana Kron

Faculty, Staff and Student Publications

No abstract provided.


Pd-1/Pd-L1 Pathway: A Therapeutic Target In Cd30+ Large Cell Lymphomas, Wei Xie, L Jeffrey Medeiros, Shaoying Li, Guilin Tang, Guang Fan Jul 2022

Pd-1/Pd-L1 Pathway: A Therapeutic Target In Cd30+ Large Cell Lymphomas, Wei Xie, L Jeffrey Medeiros, Shaoying Li, Guilin Tang, Guang Fan

Faculty, Staff and Student Publications

The programmed death-ligands, PD-L1 and PD-L2, reside on tumor cells and can bind with programmed death-1 protein (PD-1) on T-cells, resulting in tumor immune escape. PD-1 ligands are highly expressed in some CD30+ large cell lymphomas, including classic Hodgkin lymphoma (CHL), primary mediastinal large B-cell lymphoma (PMBL), Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL), and anaplastic large cell lymphoma (ALCL). The genetic alteration of the chromosome 9p24.1 locus, the location of


The Use Of Second-Generation Antipsychotics And The Changes In Physical Growth In Children And Adolescents With Perinatally Acquired Hiv, Hyun-Eui Kim Jul 2022

The Use Of Second-Generation Antipsychotics And The Changes In Physical Growth In Children And Adolescents With Perinatally Acquired Hiv, Hyun-Eui Kim

Faculty, Staff and Student Publications

The mitochondrial unfolded protein response (UPRmt) is dedicated to promoting mitochondrial proteostasis and is linked to extreme longevity. The key regulator of this process is the transcription factor ATFS-1, which, upon UPRmt activation, is excluded from the mitochondria and enters the nucleus to regulate UPRmt genes. However, the repair proteins synthesized as a direct result of UPRmt activation must be transported into damaged mitochondria that had previously excluded ATFS-1 owing to reduced import efficiency. To address this conundrum, we analyzed the role of the import machinery when the UPRmt was induced. Using in vitro and in vivo analysis of mitochondrial …


Covid-Associated Avascular Necrosis Of The Maxilla-A Rare, New Side Effect Of Covid-19 Jul 2022

Covid-Associated Avascular Necrosis Of The Maxilla-A Rare, New Side Effect Of Covid-19

Faculty, Staff and Student Publications

Purpose: The purpose of this article is to present an interesting, rare case of a patient who experienced avascular necrosis of the maxilla associated with COVID-19 infection.

Methods and results: Our team retrospectively evaluated this patient's chart after completion of surgical management. The patient is a 72-year-old male who presented to the University of Texas Health Science Center at Houston for surgical management of his infarcted maxilla, which developed as a sequela of infection with COVID-19. A literature review was completed using PubMed. Twenty-five articles are reviewed and discussed.

Conclusions: Infection with COVID-19 confers a hypercoagulable state in patients, leading …


Cas9/Nickase-Induced Allelic Conversion By Homologous Chromosome-Templated Repair In Drosophila Somatic Cells, Carissa Klanseck, Victor Lopez Del Amo, Ethan Bier, Annabel Guichard Jul 2022

Cas9/Nickase-Induced Allelic Conversion By Homologous Chromosome-Templated Repair In Drosophila Somatic Cells, Carissa Klanseck, Victor Lopez Del Amo, Ethan Bier, Annabel Guichard

Faculty, Staff and Student Publications

Repair of double-strand breaks (DSBs) in somatic cells is primarily accomplished by error-prone nonhomologous end joining and less frequently by precise homology-directed repair preferentially using the sister chromatid as a template. Here, a


Potential Impact Of Revised Nci Eligibility Criteria Guidance: Prior Malignancy Exclusion In Breast Cancer Clinical Trials, Asal Rahimi Jul 2022

Potential Impact Of Revised Nci Eligibility Criteria Guidance: Prior Malignancy Exclusion In Breast Cancer Clinical Trials, Asal Rahimi

Faculty, Staff and Student Publications

BACKGROUND: Many individuals with cancer have survived a prior cancer and for this reason may have been excluded from clinical trials. Recent NCI guidance recommends including these individuals, especially when the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low. Using breast cancer as an example, we determined the potential effect this policy change may have on clinical trial accrual.

PATIENTS AND METHODS: We reviewed protocols of NCI-sponsored breast cancer clinical trials activated in 1991 through 2016. We quantified prevalence of prior cancer-related exclusion criteria and assessed the association with trial characteristics using Fisher's …


Impact Of Explainable Artificial Intelligence Assistance On Clinical Decision-Making Of Novice Dental Clinicians Jul 2022

Impact Of Explainable Artificial Intelligence Assistance On Clinical Decision-Making Of Novice Dental Clinicians

Faculty, Staff and Student Publications

OBJECTIVE: Despite artificial intelligence (AI) being used increasingly in healthcare, implementation challenges exist leading to potential biases during the clinical decision process of the practitioner. The interaction of AI with novice clinicians was investigated through an identification task, an important component of diagnosis, in dental radiography. The study evaluated the performance, efficiency, and confidence level of dental students on radiographic identification of furcation involvement (FI), with and without AI assistance.

MATERIALS AND METHODS: Twenty-two third- and 19 fourth-year dental students (DS3 and DS4, respectively) completed remotely administered surveys to identify FI lesions on a series of dental radiographs. The control …


Muc1 And Polarity Markers Inadl And Scrib Identify Salivary Ductal Cells Jul 2022

Muc1 And Polarity Markers Inadl And Scrib Identify Salivary Ductal Cells

Faculty, Staff and Student Publications

Current treatments for xerostomia/dry mouth are palliative and largely ineffective. A permanent clinical resolution is being developed to correct hyposalivation using implanted hydrogel-encapsulated salivary human stem/progenitor cells (hS/PCs) to restore functional salivary components and increase salivary flow. Pluripotent epithelial cell populations derived from hS/PCs, representing a basal stem cell population in tissue, can differentiate along either secretory acinar or fluid-transporting ductal lineages. To develop tissue-engineered salivary gland replacement tissues, it is critical to reliably identify cells in tissue and as they enter these alternative lineages. The secreted protein α-amylase, the transcription factor MIST1, and aquaporin-5 are typical markers for acinar …


Maternal Obesity, Pregnancy Weight Gain, And Birth Weight And Risk Of Colorectal Cancer, Minjae Lee, Barbara A Cohn Jul 2022

Maternal Obesity, Pregnancy Weight Gain, And Birth Weight And Risk Of Colorectal Cancer, Minjae Lee, Barbara A Cohn

Faculty, Staff and Student Publications

Objective: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Obesity is a well-established risk factor for CRC, and fetal or developmental origins of obesity may underlie its effect on cancer in adulthood. We examined associations of maternal obesity, pregnancy weight gain, and birth weight and CRC in adult offspring.

Design: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California (N=18 751 live births among 14 507 mothers). Clinical information was abstracted from mothers' medical records 6 months prior to pregnancy through delivery. Diagnoses of …


Assessment Of Electronic Health Record For Cancer Research And Patient Care Through A Scoping Review Of Cancer Natural Language Processing, Huan He, Sijia Liu, Sungrim Moon, Michelle Mai, Irbaz B Riaz, Nan Wang, Ping Yang, Hua Xu, Jeremy L Warner, Hongfang Liu Jul 2022

Assessment Of Electronic Health Record For Cancer Research And Patient Care Through A Scoping Review Of Cancer Natural Language Processing, Huan He, Sijia Liu, Sungrim Moon, Michelle Mai, Irbaz B Riaz, Nan Wang, Ping Yang, Hua Xu, Jeremy L Warner, Hongfang Liu

Faculty, Staff and Student Publications

Purpose: The advancement of natural language processing (NLP) has promoted the use of detailed textual data in electronic health records (EHRs) to support cancer research and to facilitate patient care. In this review, we aim to assess EHR for cancer research and patient care by using the Minimal Common Oncology Data Elements (mCODE), which is a community-driven effort to define a minimal set of data elements for cancer research and practice. Specifically, we aim to assess the alignment of NLP-extracted data elements with mCODE and review existing NLP methodologies for extracting said data elements.

Methods: Published literature studies were searched …


Skin Cancer Education Interventions For Primary Care Providers: A Scoping Review, Misha V Koshelev Jul 2022

Skin Cancer Education Interventions For Primary Care Providers: A Scoping Review, Misha V Koshelev

Faculty, Staff and Student Publications

Primary care physicians (PCPs) are often the first line of defense against skin cancers. Despite this, many PCPs do not receive a comprehensive training in skin conditions. Educational interventions aimed at skin cancer screening instruction for PCPs offer an opportunity to detect skin cancer at earlier stages and subsequent improved morbidity and mortality. A scoping review was conducted to collect data about previously reported skin cancer screening interventions for PCPs. A structured literature search found 51 studies describing 37 unique educational interventions. Curriculum elements utilized by the interventions were divided into categories that would facilitate comparison including curriculum components, delivery …


Impact Of Gap Distance Between Fenestration And Aortic Wall On Target Artery Instability Following Fenestrated-Branched Endovascular Aortic Repair, Giulianna B Marcondes, Gustavo S Oderich Jul 2022

Impact Of Gap Distance Between Fenestration And Aortic Wall On Target Artery Instability Following Fenestrated-Branched Endovascular Aortic Repair, Giulianna B Marcondes, Gustavo S Oderich

Faculty, Staff and Student Publications

Objective: Target artery (TA) instability has been the most frequent indication for secondary intervention after fenestrated and branched endovascular aortic repair (FB-EVAR) of pararenal and thoracoabdominal aortic aneurysms (TAAAs). The aim of the present study was to evaluate the effect of the gap distance between the endograft reinforced fenestration and TA origin at the aortic wall (fenestration gap [FG]) on target-related outcomes after FB-EVAR.

Methods: The clinical data and imaging studies of 430 patients enrolled in a prospective, nonrandomized study to evaluate FB-EVAR using manufactured stent grafts were reviewed. Of the 430 patients, 340 (79%) had had more than one …


Effects Of Combined Gentamicin And Furosemide Treatment On Cochlear Macrophages Jul 2022

Effects Of Combined Gentamicin And Furosemide Treatment On Cochlear Macrophages

Faculty, Staff and Student Publications

Combining aminoglycosides and loop diuretics often serves as an effective ototoxic approach to deafen experimental animals. The treatment results in rapid hair cell loss with extended macrophage presence in the cochlea, creating a sterile inflammatory environment. Although the early recruitment of macrophages is typically neuroprotective, the delay in the resolution of macrophage activity can be a complication if the damaged cochlea is used as a model to study subsequent therapeutic strategies. Here, we applied a high dose combination of systemic gentamicin and furosemide in


Bloodstream Infections In Hematologic Malignancy Patients With Fever And Neutropenia: Are Empirical Antibiotic Therapies In The United States Still Effective?, Andrea J Zimmer, Erica Stohs, Jane Meza, Christopher Arnold, John W Baddley, Zeinab El Boghdadly, Eileen K Maziarz, Jose G Montoya, Steven Pergam, Kenneth V Rolston, Michael J Satlin, Gowri Satyanarayana, Shmuel Shoham, Lynne Strasfeld, Randy Taplitz, Thomas J Walsh, Jo-Anne H Young, Yuning Zhang, Alison G Freifeld Jul 2022

Bloodstream Infections In Hematologic Malignancy Patients With Fever And Neutropenia: Are Empirical Antibiotic Therapies In The United States Still Effective?, Andrea J Zimmer, Erica Stohs, Jane Meza, Christopher Arnold, John W Baddley, Zeinab El Boghdadly, Eileen K Maziarz, Jose G Montoya, Steven Pergam, Kenneth V Rolston, Michael J Satlin, Gowri Satyanarayana, Shmuel Shoham, Lynne Strasfeld, Randy Taplitz, Thomas J Walsh, Jo-Anne H Young, Yuning Zhang, Alison G Freifeld

Faculty, Staff and Student Publications

Background: Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant.

Methods: In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation.

Results: Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with …


Functional Genomic Analysis Of Epithelioid Sarcoma Reveals Distinct Proximal And Distal Subtype Biology, Samuel V Rasmussen, Jia Xiang Jin, Lissett R Bickford, Andrew D Woods, Felix Sahm, Kiyo Nagamori, Keila E Torres, Angelo Sidoni, Erin R Rudzinski, Khin Thway, Robin L Jones, Alessio Ciulli, Hollis Wright, Melvin Lathara, Ganapati Srinivasa, Kavya Kannan, Paul H Huang, Thomas G P Grünewald, Noah E Berlow, Charles Keller Jul 2022

Functional Genomic Analysis Of Epithelioid Sarcoma Reveals Distinct Proximal And Distal Subtype Biology, Samuel V Rasmussen, Jia Xiang Jin, Lissett R Bickford, Andrew D Woods, Felix Sahm, Kiyo Nagamori, Keila E Torres, Angelo Sidoni, Erin R Rudzinski, Khin Thway, Robin L Jones, Alessio Ciulli, Hollis Wright, Melvin Lathara, Ganapati Srinivasa, Kavya Kannan, Paul H Huang, Thomas G P Grünewald, Noah E Berlow, Charles Keller

Faculty, Staff and Student Publications

Background: Metastatic epithelioid sarcoma (EPS) remains a largely unmet clinical need in children, adolescents and young adults despite the advent of EZH2 inhibitor tazemetostat.

Methods: In order to realise consistently effective drug therapies, a functional genomics approach was used to identify key signalling pathway vulnerabilities in a spectrum of EPS patient samples. EPS biopsies/surgical resections and cell lines were studied by next-generation DNA exome and RNA deep sequencing, then EPS cell cultures were tested against a panel of chemical probes to discover signalling pathway targets with the most significant contributions to EPS tumour cell maintenance.

Results: Other biologically inspired functional …


Adding Customized Electron Energy Beams To Truebeam Linear Accelerators, Song Gao, Manickam Muruganandham, Weiliang Du, Jared Ohrt, Rajat J Kudchadker Jul 2022

Adding Customized Electron Energy Beams To Truebeam Linear Accelerators, Song Gao, Manickam Muruganandham, Weiliang Du, Jared Ohrt, Rajat J Kudchadker

Faculty, Staff and Student Publications

Purpose: To better meet clinical needs and facilitate optimal treatment planning, we added two new electron energy beams (7 and 11 MeV) to two Varian TrueBeam linacs.

Methods: We worked with the vendor to create two additional customized electron energies without hardware modifications. For each beam, we set the bending magnet current and then optimized other beam-specific parameters to achieve depths of 50% ionization (I50 ) of 2.9 cm for 7 MeV and 4.2 cm for the 11 MeV beam with the 15 × 15 cm2 cone at 100 cm source-to-surface distance (SSD) by using an ionization chamber profiler (ICP) …


Lfa-1 Activation Enriches Tumor-Specific T Cells In A Cold Tumor Model And Synergizes With Ctla-4 Blockade, Amber Hickman, Joost Koetsier, Trevin Kurtanich, Michael C Nielsen, Glenn Winn, Salah-Eddine Bentebibel, Simone Punt, Leila Williams, Cara Haymaker, Charles B Chesson, Faisal Fa'ak, Ana L Dominguez, Richard Jones, Isere Kuiatse, Amy R Caivano, Sayadeth Khounlo, Navin D Warier, Upendra Marathi, Robert V Market, Ronald J Biediger, John W Craft, Patrick Hwu, Michael A Davies, Darren G Woodside, Peter Vanderslice, Adi Diab, Willem W Overwijk, Yared Hailemichael Jul 2022

Lfa-1 Activation Enriches Tumor-Specific T Cells In A Cold Tumor Model And Synergizes With Ctla-4 Blockade, Amber Hickman, Joost Koetsier, Trevin Kurtanich, Michael C Nielsen, Glenn Winn, Salah-Eddine Bentebibel, Simone Punt, Leila Williams, Cara Haymaker, Charles B Chesson, Faisal Fa'ak, Ana L Dominguez, Richard Jones, Isere Kuiatse, Amy R Caivano, Sayadeth Khounlo, Navin D Warier, Upendra Marathi, Robert V Market, Ronald J Biediger, John W Craft, Patrick Hwu, Michael A Davies, Darren G Woodside, Peter Vanderslice, Adi Diab, Willem W Overwijk, Yared Hailemichael

Faculty, Staff and Student Publications

The inability of CD8+ effector T cells (Teffs) to reach tumor cells is an important aspect of tumor resistance to cancer immunotherapy. The recruitment of these cells to the tumor microenvironment (TME) is regulated by integrins, a family of adhesion molecules that are expressed on T cells. Here, we show that 7HP349, a small-molecule activator of lymphocyte function-associated antigen-1 (LFA-1) and very late activation antigen-4 (VLA-4) integrin cell-adhesion receptors, facilitated the preferential localization of tumor-specific T cells to the tumor and improved antitumor response. 7HP349 monotherapy had modest effects on anti-programmed death 1-resistant (anti-PD-1-resistant) tumors, whereas combinatorial treatment with anti-cytotoxic …


Mice Lacking Wnt9a Or Wnt4 Are Prone To Develop Spontaneous Osteoarthritis With Age And Display Alteration In Either The Trabecular Or Cortical Bone Compartment, Stefan Teufel, Lena Wolff, Ulrich König, Akio Kobayashi, Richard Behringer Jul 2022

Mice Lacking Wnt9a Or Wnt4 Are Prone To Develop Spontaneous Osteoarthritis With Age And Display Alteration In Either The Trabecular Or Cortical Bone Compartment, Stefan Teufel, Lena Wolff, Ulrich König, Akio Kobayashi, Richard Behringer

Faculty, Staff and Student Publications

Osteoarthritis (OA) is a common degenerative disease of the joint, with a complex multifactorial not yet fully understood etiology. Over the past years, the Wnt signaling pathway has been implicated in osteoarthritis. In a recent genomewide association study (GWAS), the chromosomal location on chromosome 1, linked to the Wnt3a-Wnt9a gene locus, was identified as the most significant locus associated with a thumb osteoarthritis endophenotype. Previously, it was shown that WNT9a is involved in maintaining synovial cell identity in the elbow joint during embryogenesis. Here, we report that the conditional loss of Wnt9a in the Prx1-Cre expressing limb mesenchyme or Prg4-CreER …


Prediction Of Survival With Intensive Chemotherapy In Acute Myeloid Leukemia, Koji Sasaki, Farhad Ravandi, Tapan Kadia, Courtney Dinardo, Gautam Borthakur, Nitin Jain, Elias Jabbour, Guillermo Garcia-Manero, Joseph Khoury, Sergej Konoplev, Sanam Loghavi, Keyur Patel, Guillermo Montalban-Bravo, Lucia Masarova, Marina Konopleva, Hagop Kantarjian Jul 2022

Prediction Of Survival With Intensive Chemotherapy In Acute Myeloid Leukemia, Koji Sasaki, Farhad Ravandi, Tapan Kadia, Courtney Dinardo, Gautam Borthakur, Nitin Jain, Elias Jabbour, Guillermo Garcia-Manero, Joseph Khoury, Sergej Konoplev, Sanam Loghavi, Keyur Patel, Guillermo Montalban-Bravo, Lucia Masarova, Marina Konopleva, Hagop Kantarjian

Faculty, Staff and Student Publications

Progress with intensive chemotherapy and supportive care measures has improved survival in newly diagnosed acute myeloid leukemia (AML). Predicting outcome helps in treatment decision making. We analyzed survival as the treatment endpoint in 3728 patients with newly diagnosed AML treated with intensive chemotherapy from 1980 to 2021. We divided the total study group (3:1 basis) into a training (n = 2790) and a validation group (n = 938). The associations between survival and 27 characteristics were investigated. In the training cohort, the multivariate analysis identified 12 consistent adverse prognostic variables independently associated with worse survival: older age, therapy-related myeloid neoplasm, …


Leveraging Single-Cell Sequencing To Unravel Intratumour Heterogeneity And Tumour Evolution In Human Cancers, Amy L Bowes, Maxime Tarabichi, Nischalan Pillay, Peter Van Loo Jul 2022

Leveraging Single-Cell Sequencing To Unravel Intratumour Heterogeneity And Tumour Evolution In Human Cancers, Amy L Bowes, Maxime Tarabichi, Nischalan Pillay, Peter Van Loo

Faculty, Staff and Student Publications

Intratumour heterogeneity (ITH) and tumour evolution are well-documented phenomena in human cancers. While the advent of next-generation sequencing technologies has facilitated the large-scale capture of genomic data, the field of single-cell genomics is nascent but rapidly advancing and generating many new insights into the complex molecular mechanisms of tumour biology. In this review, we provide an overview of current single-cell DNA sequencing technologies, exploring how recent methodological advancements have enumerated new insights into ITH and tumour evolution. Areas highlighted include the potential power of single-cell genome sequencing studies to explore evolutionary dynamics contributing to tumourigenesis through to progression, metastasis, and …


Shared Nearest Neighbors Approach And Interactive Browser For Network Analysis Of A Comprehensive Non-Small-Cell Lung Cancer Data Set, Stephanie T Schmidt, Neal Akhave, Ryan E Knightly, Alexandre Reuben, Natalie Vokes, Jun Li, Lauren A Byers, Beatriz Sanchez-Espiridion, Lixia Diao, Jing Wang, Lorenzo Federico, Marie-Andree Forget, Daniel J Mcgrail, Annikka Weissferdt, Shiaw-Yih Lin, Younghee Lee, Erika Suzuki, Jeffrey J Kovacs, Carmen Behrens, Ignacio I Wistuba, Andrew Futreal, Ara Vaporciyan, Boris Sepesi, John V Heymach, Chantale Bernatchez, Cara Haymaker, Tina Cascone, Jianjun Zhang, Christopher A Bristow, Timothy P Heffernan, Marcelo V Negrao, Don L Gibbons, Icon Team Jul 2022

Shared Nearest Neighbors Approach And Interactive Browser For Network Analysis Of A Comprehensive Non-Small-Cell Lung Cancer Data Set, Stephanie T Schmidt, Neal Akhave, Ryan E Knightly, Alexandre Reuben, Natalie Vokes, Jun Li, Lauren A Byers, Beatriz Sanchez-Espiridion, Lixia Diao, Jing Wang, Lorenzo Federico, Marie-Andree Forget, Daniel J Mcgrail, Annikka Weissferdt, Shiaw-Yih Lin, Younghee Lee, Erika Suzuki, Jeffrey J Kovacs, Carmen Behrens, Ignacio I Wistuba, Andrew Futreal, Ara Vaporciyan, Boris Sepesi, John V Heymach, Chantale Bernatchez, Cara Haymaker, Tina Cascone, Jianjun Zhang, Christopher A Bristow, Timothy P Heffernan, Marcelo V Negrao, Don L Gibbons, Icon Team

Faculty, Staff and Student Publications

Purpose: Advances in biological measurement technologies are enabling large-scale studies of patient cohorts across multiple omics platforms. Holistic analysis of these data can generate actionable insights for translational research and necessitate new approaches for data integration and mining.

Methods: We present a novel approach for integrating data across platforms on the basis of the shared nearest neighbors algorithm and use it to create a network of multiplatform data from the immunogenomic profiling of non-small-cell lung cancer project.

Results: Benchmarking demonstrates that the shared nearest neighbors-based network approach outperforms a traditional gene-gene network in capturing established interactions while providing new ones …


Guidelines On Models Of Diabetic Heart Disease, Kimberley M Mellor, Michinari Nakamura, Oliver J Rider, Matthieu Ruiz, Adam R Wende, John R Ussher Jul 2022

Guidelines On Models Of Diabetic Heart Disease, Kimberley M Mellor, Michinari Nakamura, Oliver J Rider, Matthieu Ruiz, Adam R Wende, John R Ussher

Faculty, Staff and Student Publications

Diabetes is a major risk factor for cardiovascular diseases, including diabetic cardiomyopathy, atherosclerosis, myocardial infarction, and heart failure. As cardiovascular disease represents the number one cause of death in people with diabetes, there has been a major emphasis on understanding the mechanisms by which diabetes promotes cardiovascular disease, and how antidiabetic therapies impact diabetic heart disease. With a wide array of models to study diabetes (both type 1 and type 2), the field has made major progress in answering these questions. However, each model has its own inherent limitations. Therefore, the purpose of this guidelines document is to provide the …


Opposing Roles Of Hdac6 In Liver Regeneration And Hepatocarcinogenesis, Trung Nghia Tran, Joo-Yong Lee Jul 2022

Opposing Roles Of Hdac6 In Liver Regeneration And Hepatocarcinogenesis, Trung Nghia Tran, Joo-Yong Lee

Faculty, Staff and Student Publications

Histone deacetylase 6 (HDAC6), a deacetylase of p53, has emerged as a privileged inhibitory target for cancer therapy because of its deacetylating activity for p53 at K120 and K373/382. However, intricate roles of HDAC6 in hepatocellular carcinogenesis have been suggested by recent evidence, namely that HDAC6 ablation suppresses innate immunity, which plays critical roles in tumor immunosurveillance and antitumor immune responses. Therefore, it is valuable to determine whether HDAC6 ablation inhibits hepatocellular carcinogenesis using in vivo animal models. Here, we firstly showed that HDAC6 ablation increased K320 acetylation of p53, known as pro-survival acetylation, in all tested animal models but …


Distress Tolerance: Prospective Associations With Cognitive-Behavioral Therapy Outcomes In Adults With Posttraumatic Stress And Substance Use Disorders, Scott D Lane Jul 2022

Distress Tolerance: Prospective Associations With Cognitive-Behavioral Therapy Outcomes In Adults With Posttraumatic Stress And Substance Use Disorders, Scott D Lane

Faculty, Staff and Student Publications

Distress tolerance (DT; perceived or actual ability to tolerate aversive physical or emotional states) is related to both posttraumatic stress disorder (PTSD) symptoms and substance use disorders (SUD). This investigation evaluates self-report and behavioral measures of DT as potential predictors of PTSD and SUD cognitive-behavioral therapy outcomes. Participants included 41 treatment-seeking adults (53.7% women; 73.2% African American; Mage= 44.90, SD = 9.68) who met at least four symptoms of DSM-5 PTSD and DSM-IV substance dependence, assessed via structured interviews. At baseline (pre-treatment), participants completed the Distress Tolerance Scale (DTS), Mirror-Tracing Persistence Task (MTPT), Breath Holding task, and Paced Auditory …