Medical Sciences Commons^™

Multiagent Chemotherapy And Stereotactic Body Radiation Therapy In Patients With Unresectable Pancreatic Adenocarcinoma: A Prospective Nonrandomized Controlled Trial, Colin S Hill, Lauren Rosati, Hao Wang, Hua-Ling Tsai, Jin He, Amy Hacker-Prietz, Daniel A Laheru, Lei Zheng, Shuchi Sehgal, Vincent Bernard, Dung T Le, Timothy M Pawlik, Matthew J Weiss, Amol K Narang, Joseph M Herman

Faculty, Staff and Student Publications

PURPOSE: In a prospective multicenter study, gemcitabine monotherapy followed by stereotactic body radiation therapy (SBRT) was well tolerated with outcomes comparable to chemoradiation for locally advanced pancreatic cancer (LAPC). Recent trials have reported improved survival with multiagent chemotherapy (MA-CTX) alone. This prospective trial explored whether SBRT could be safely delivered after MA-CTX. Herein, we report the long-term outcomes of adding SBRT after MA-CTX in LAPC patients and evaluate whether genetic profiles of specimens obtained before SBRT influence outcomes.

METHODS AND MATERIALS: This prospective nonrandomized controlled phase 2 trial enrolled 44 LAPC and 4 locally recurrent patients after multidisciplinary evaluation between …

Impact Of Psychosocial, Behavioral And Lifestyle Factors On Subjective Cognitive Complaints And Perceived Quality Of Life In A Large Cohort Of Italian Breast Cancer Patients, Thomas West, Corrado Cavallero, Rita Ceccherini, Silva Foladore, Daniele Generali, Francesco Versace, Bruna Scaggiante

Faculty, Staff and Student Publications

The impact of psychosocial and behavioral factors on Cancer Related Cognitive Impairment manifestations is still under debate. Study's purpose is to determine the prevalence rate of cancer related cognitive impairment in a cohort of Italian breast cancer patients and to evaluate the implication of specific behavioral factors. For these purposes, a total of 233 women (106 breast cancer patients and 127 age-matched controls without oncological diagnosis) completed a questionnaire investigating cognitive functionality (FACT-Cog v3.0), sociodemographic characteristics, clinical information, psychosocial and behavioral factors (cognitive reserve, sleep quality, dietary habits, physical activity). The results indicated a higher prevalence rate of subjective cognitive …

Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Robert Dubin, Ken Chen, Amanda P Beck, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann

Faculty, Staff and Student Publications

Background and aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota.

Methods: We generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are …

Serglycin Is Involved In Tgf-Β Induced Epithelial-Mesenchymal Transition And Is Highly Expressed By Immune Cells In Breast Cancer Tissue, Marta Tellez-Gabriel, Xavier Tekpli, Trine M Reine, Beate Hegge, Stephanie R Nielsen, Meng Chen, Line Moi, Lisa Svartdal Normann, Lill-Tove R Busund, George A Calin, Gunhild M Mælandsmo, Maria Perander, Achilleas D Theocharis, Svein O Kolset, Erik Knutsen

Faculty, Staff and Student Publications

Serglycin is a proteoglycan highly expressed by immune cells, in which its functions are linked to storage, secretion, transport, and protection of chemokines, proteases, histamine, growth factors, and other bioactive molecules. In recent years, it has been demonstrated that serglycin is also expressed by several other cell types, such as endothelial cells, muscle cells, and multiple types of cancer cells. Here, we show that serglycin expression is upregulated in transforming growth factor beta (TGF-β) induced epithelial-mesenchymal transition (EMT). Functional studies provide evidence that serglycin plays an important role in the regulation of the transition between the epithelial and mesenchymal phenotypes, …

Research Career Intentions Among Non-Native English-Speaking Graduate And Postdoctoral Trainees In Stem-Results From Cross-Sectional And Longitudinal Studies, Hwa Young Lee, Shine Chang, Cheryl B Anderson, Erin K Dahlstrom, Carrie Cameron

Faculty, Staff and Student Publications

International graduate trainees, many of whom are non-native English-speaking (L2) trainees, comprise more than half of graduate-level trainees in STEM, but little is known regarding factors that influence their career intentions, especially those that foster their growth as scientists to achieve their full potential in research. Thus, the purpose of our studies was to examine the relationship between L2 status and contextual factors that help shape the learning experiences and plans for research-focused careers. Study 1 collected cross-sectional survey data from doctoral and postdoctoral trainees (N=510) from research institutes in the Texas Medical Center in Houston. We examined which factors …

B Cells Are Required To Generate Optimal Anti-Melanoma Immunity In Response To Checkpoint Blockade, Shubhra Singh, Jason Roszik, Neeraj Saini, Vipul Kumar Singh, Karishma Bavisi, Zhiqiang Wang, Long T Vien, Zixi Yang, Suprateek Kundu, Richard E Davis, Laura Bover, Adi Diab, Sattva S Neelapu, Willem W Overwijk, Kunal Rai, Manisha Singh

Faculty, Staff and Student Publications

Immunotherapies such as checkpoint blockade therapies are known to enhance anti-melanoma CD8+ T cell immunity, but only a fraction of patients treated with these therapies achieve durable immune response and disease control. It may be that CD8+ T cells need help from other immune cells to generate effective and long-lasting anti-tumor immunity or that CD8+ T cells alone are insufficient for complete tumor regression and cure. Melanoma contains significant numbers of B cells; however, the role of B cells in anti-melanoma immunity is controversial. In this study, B16 melanoma mouse models were used to determine the role of B cells …

Automated Segmentation Of Colorectal Liver Metastasis And Liver Ablation On Contrast-Enhanced Ct Images, Brian M Anderson, Bastien Rigaud, Yuan-Mao Lin, A Kyle Jones, Hynseon Christine Kang, Bruno C Odisio, Kristy K Brock

Faculty, Staff and Student Publications

Objectives: Colorectal cancer (CRC), the third most common cancer in the USA, is a leading cause of cancer-related death worldwide. Up to 60% of patients develop liver metastasis (CRLM). Treatments like radiation and ablation therapies require disease segmentation for planning and therapy delivery. For ablation, ablation-zone segmentation is required to evaluate disease coverage. We hypothesize that fully convolutional (FC) neural networks, trained using novel methods, will provide rapid and accurate identification and segmentation of CRLM and ablation zones.

Methods: Four FC model styles were investigated: Standard 3D-UNet, Residual 3D-UNet, Dense 3D-UNet, and Hybrid-WNet. Models were trained on 92 patients from …

Cgas-Sting Pathway Targeted Therapies And Their Applications In The Treatment Of High-Grade Glioma, Shashwat Tripathi, Hinda Najem, Akanksha Sanjay Mahajan, Peng Zhang, Justin T Low, Alexander H Stegh, Michael A Curran, David M Ashley, Charles David James, Amy B Heimberger

Faculty, Staff and Student Publications

Median survival of patients with glioblastoma (GBM) treated with standard of care which consists of maximal safe resection of the contrast-enhancing portion of the tumor followed by radiation therapy with concomitant adjuvant temozolomide (TMZ) remains 15 months. The tumor microenvironment (TME) is known to contain immune suppressive myeloid cells with minimal effector T cell infiltration. Stimulator of interferon genes (STING) is an important activator of immune response and results in production of Type 1 interferon and antigen presentation by myeloid cells. This review will discuss important developments in STING agonists, potential biomarkers for STING response, and new combinatorial therapeutic approaches …

Recent Advances On Dna Base Flipping: A General Mechanism For Writing, Reading, And Erasing Dna Modifications, Ren Ren, John R Horton, Samuel Hong, Xiaodong Cheng

Faculty, Staff and Student Publications

The modification of DNA bases is a classic hallmark of epigenetics. Four forms of modified cytosine-5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine-have been discovered in eukaryotic DNA. In addition to cytosine carbon-5 modifications, cytosine and adenine methylated in the exocyclic amine-N4-methylcytosine and N6-methyladenine-are other modified DNA bases discovered even earlier. Each modified base can be considered a distinct epigenetic signal with broader biological implications beyond simple chemical changes. Since 1994, several crystal structures of proteins and enzymes involved in writing, reading, and erasing modified bases have become available. Here, we present a structural synopsis of writers, readers, and erasers of the modified …

Use Of The Fully Spectroscopic Pixelated Cadmium Telluride Detector For Benchtop X-Ray Fluorescence Computed Tomography, Sandun Jayarathna, Hem Moktan, Sang Hyun Cho

Faculty, Staff and Student Publications

In this work, we integrated a commercially-available fully-spectroscopic pixelated cadmium telluride (CdTe) detector system as a two-dimensional (2D) array detector into our existing benchtop cone-beam x-ray fluorescence computed tomography (XFCT) system. After integrating this detector, known as High-Energy X-ray Imaging Technology (HEXITEC), we performed quantitative imaging of gold nanoparticle (GNP) distribution in a small animal-sized phantom using our benchtop XFCT system. Owing to the upgraded detector component within our benchtop XFCT system, we were able to conduct this phantom imaging in an unprecedented manner by volumetric XFCT scans followed by XFCT image reconstruction in 3D. The current results showed that …

Inhibition Of The Cd47-Sirpα Axis For Cancer Therapy: A Systematic Review And Meta-Analysis Of Emerging Clinical Data, Ji Son, Rodney Cheng-En Hsieh, Heather Y Lin, Kate J Krause, Ying Yuan, Amadeo B Biter, James Welsh, Michael A Curran, David S Hong

Faculty, Staff and Student Publications

CD47-SIRPα interaction acts as a "don't eat me" signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). …

Cell-Directed Aptamer Therapeutic Targeting For Cancers Including Those Within The Central Nervous System, Jun Wei, Renduo Song, Aria Sabbagh, Anantha Marisetty, Neal Shukla, Dexing Fang, Hinda Najem, Martina Ott, James Long, Lijie Zhai, Maciej S Lesniak, Charles David James, Leonidas Platanias, Michael Curran, Amy B Heimberger

Faculty, Staff and Student Publications

Osteopontin (OPN) is produced by tumor cells as well as by myeloid cells and is enriched in the tumor microenvironment (TME) of many cancers. Given the roles of OPN in tumor progression and immune suppression, we hypothesized that targeting OPN with aptamers that have high affinity and specificity could be a promising therapeutic strategy. Bi-specific aptamers targeting ligands for cellular internalization were conjugated to siRNAs to suppress OPN were created, and therapeutic leads were selected based on target engagement and

Evaluation Of Deep Learning-Based Multiparametric Mri Oropharyngeal Primary Tumor Auto-Segmentation And Investigation Of Input Channel Effects: Results From A Prospective Imaging Registry, Kareem A Wahid, Sara Ahmed, Renjie He, Lisanne V Van Dijk, Jonas Teuwen, Brigid A Mcdonald, Vivian Salama, Abdallah S R Mohamed, Travis Salzillo, Cem Dede, Nicolette Taku, Stephen Y Lai, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

Background/purpose: Oropharyngeal cancer (OPC) primary gross tumor volume (GTVp) segmentation is crucial for radiotherapy. Multiparametric MRI (mpMRI) is increasingly used for OPC adaptive radiotherapy but relies on manual segmentation. Therefore, we constructed mpMRI deep learning (DL) OPC GTVp auto-segmentation models and determined the impact of input channels on segmentation performance.

Materials/methods: GTVp ground truth segmentations were manually generated for 30 OPC patients from a clinical trial. We evaluated five mpMRI input channels (T2, T1, ADC, Ktrans, Ve). 3D Residual U-net models were developed and assessed using leave-one-out cross-validation. A baseline T2 model was compared to mpMRI models (T2 + T1, …

Recurrent Hgnet-Mn1 Altered (Astroblastoma Mn1-Altered) Of The Foramen Magnum: Case Report And Molecular Classification, Sricharan Gopakumar, Malcolm F Mcdonald, Himanshu Sharma, Claudio E Tatsui, Gregory N Fuller, Ganesh Rao

Faculty, Staff and Student Publications

Background: Astroblastoma is a rare primary brain tumor of unclear origin, often occurring in young patients less than 30-years-old. It typically arises supratentorially and is diagnosed based on histological features including vascular hyalinization and perivascular pseudorosettes. Recent molecular characterization of primary CNS high-grade neuroepithelial tumors with meningioma I alteration (HGNET-MN1) found that HGNET-MN1 and tumors with morphological signatures of astroblastoma clustered together. Further analysis revealed such astroblastomas have MN1 alteration and the 2021 WHO classification of tumors of the CNS now recognizes astroblastoma MN1-altered as a new entity.

Case description: Here, we present the case of …

Proton Image-Guided Radiation Assignment For Therapeutic Escalation Via Selection Of Locally Advanced Head And Neck Cancer Patients [Pirates]: A Phase I Safety And Feasibility Trial Of Mri-Guided Adaptive Particle Radiotherapy, Lisanne V Van Dijk, Steven J Frank, Ying Yuan, Brandon Gunn, Amy C Moreno, Abdallah S R Mohamed, Kathryn E Preston, Yun Qing, Michael T Spiotto, William H Morrison, Anna Lee, Jack Phan, Adam S Garden, David I Rosenthal, Johannes A Langendijk, Clifton D Fuller

Faculty, Staff and Student Publications

Introduction: Radiation dose-escalation for head and neck cancer (HNC) patients aiming to improve cure rates is challenging due to the increased risk of unacceptable treatment-induced toxicities. With "Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients" (PIRATES), we present a novel treatment approach that is designed to facilitate dose-escalation while minimizing the risk of dose-limiting toxicities for locally advanced HPV-negative HNC patients. The aim of this Phase I trial is to assess the safety & feasibility of PIRATES approach.

Methods: The PIRATES protocol employs a multi-faceted dose-escalation approach to minimize the risk …

Progression Free Survival Prediction For Head And Neck Cancer Using Deep Learning Based On Clinical And Pet/Ct Imaging Data, Mohamed A Naser, Kareem A Wahid, Abdallah S R Mohamed, Moamen Abobakr Abdelaal, Renjie He, Cem Dede, Lisanne V Van Dijk, Clifton D Fuller

Faculty, Staff and Student Publications

Determining progression-free survival (PFS) for head and neck squamous cell carcinoma (HNSCC) patients is a challenging but pertinent task that could help stratify patients for improved overall outcomes. PET/CT images provide a rich source of anatomical and metabolic data for potential clinical biomarkers that would inform treatment decisions and could help improve PFS. In this study, we participate in the 2021 HECKTOR Challenge to predict PFS in a large dataset of HNSCC PET/CT images using deep learning approaches. We develop a series of deep learning models based on the DenseNet architecture using a negative log-likelihood loss function that utilizes PET/CT …

Combining Tumor Segmentation Masks With Pet/Ct Images And Clinical Data In A Deep Learning Framework For Improved Prognostic Prediction In Head And Neck Squamous Cell Carcinoma, Kareem A Wahid, Renjie He, Cem Dede, Abdallah S R Mohamed, Moamen Abobakr Abdelaal, Lisanne V Van Dijk, Clifton D Fuller, Mohamed A Naser

Faculty, Staff and Student Publications

PET/CT images provide a rich data source for clinical prediction models in head and neck squamous cell carcinoma (HNSCC). Deep learning models often use images in an end-to-end fashion with clinical data or no additional input for predictions. However, in the context of HNSCC, the tumor region of interest may be an informative prior in the generation of improved prediction performance. In this study, we utilize a deep learning framework based on a DenseNet architecture to combine PET images, CT images, primary tumor segmentation masks, and clinical data as separate channels to predict progression-free survival (PFS) in days for HNSCC …

Establishment And Validation Of Pre-Therapy Cervical Vertebrae Muscle Quantification As A Prognostic Marker Of Sarcopenia In Patients With Head And Neck Cancer, Brennan Olson, Jared Edwards, Catherine Degnin, Nicole Santucci, Michelle Buncke, Jeffrey Hu, Yiyi Chen, Clifton D Fuller, Mathew Geltzeiler, Aaron J Grossberg, Daniel Clayburgh

Faculty, Staff and Student Publications

Background: Sarcopenia is prognostic for survival in patients with head and neck cancer (HNC). However, identification of this high-risk feature remains challenging without computed tomography (CT) imaging of the abdomen or thorax. Herein, we establish sarcopenia thresholds at the C3 level and determine if C3 sarcopenia is associated with survival in patients with HNC.

Methods: This retrospective cohort study was conducted in consecutive patients with a squamous cell carcinoma of the head and neck with cross-sectional abdominal or neck imaging within 60 days prior to treatment. Measurement of cross-sectional muscle area at L3 and C3 levels was performed from CT …

Anatomy And Function Of Ventral Tegmental Area Glutamate Neurons, Jing Cai, Qingchun Tong

Faculty, Staff and Student Publications

The ventral tegmental area (VTA) is well known for regulating reward consumption, learning, memory, and addiction behaviors through mediating dopamine (DA) release in downstream regions. Other than DA neurons, the VTA is known to be heterogeneous and contains other types of neurons, including glutamate neurons. In contrast to the well-studied and established functions of DA neurons, the role of VTA glutamate neurons is understudied, presumably due to their relatively small quantity and a lack of effective means to study them. Yet, emerging studies have begun to reveal the importance of glutamate release from VTA neurons in regulating diverse behavioral repertoire …

Targeting Mcl-1 Dysregulates Cell Metabolism And Leukemia-Stroma Interactions And Resensitizes Acute Myeloid Leukemia To Bcl-2 Inhibition, Bing Z Carter, Po Yee Mak, Wenjing Tao, Marc Warmoes, Philip L Lorenzi, Duncan Mak, Vivian Ruvolo, Lin Tan, Justin Cidado, Lisa Drew, Michael Andreeff

Faculty, Staff and Student Publications

MCL-1 and BCL-2 are both frequently overexpressed in acute myeloid leukemia and critical for the survival of acute myeloid leukemia cells and acute myeloid leukemia stem cells. MCL-1 is a key factor in venetoclax resistance. Using genetic and pharmacological approaches, we discovered that MCL-1 regulates leukemia cell bioenergetics and carbohydrate metabolisms, including the TCA cycle, glycolysis and pentose phosphate pathway and modulates cell adhesion proteins and leukemia-stromal interactions. Inhibition of MCL-1 sensitizes to BCL-2 inhibition in acute myeloid leukemia cells and acute myeloid leukemia stem/progenitor cells, including those with intrinsic and acquired resistance to venetoclax through cooperative release of pro-apoptotic …

Increasing Referral Of At-Risk Women For Genetic Counseling And Brca Testing Using A Screening Tool In A Community Breast Imaging Center, Banu K Arun, Susan K Peterson, Lilian E Sweeney, Rachel D Bluebond, Rebecca S S Tidwell, Sukh Makhnoon, Anne C Kushwaha

Faculty, Staff and Student Publications

BACKGROUND: Genetic evaluation and testing for hereditary breast and ovarian cancer (HBOC) remain suboptimal. The authors evaluated the feasibility of using a screening tool at a breast imaging center to increase HBOC assessment referrals.

METHODS: A brief questionnaire based on the National Comprehensive Cancer Network HBOC genetic counseling referral guidelines was developed and added to the standard intake forms of patients undergoing mammography at a community breast imaging center from 2012 through 2015. Patients who met the criteria in the guidelines were referred for genetic counseling.

RESULTS: A total of 34,851 patients were screened during the study period, and 1246 …

Glioma And The Gut-Brain Axis: Opportunities And Future Perspectives, Antonio Dono, Jack Nickles, Ana G Rodriguez-Armendariz, Braden C Mcfarland, Nadim J Ajami, Leomar Y Ballester, Jennifer A Wargo, Yoshua Esquenazi

Faculty, Staff and Student Publications

The gut-brain axis has presented a valuable new dynamic in the treatment of cancer and central nervous system (CNS) diseases. However, little is known about the potential role of this axis in neuro-oncology. The goal of this review is to highlight potential implications of the gut-brain axis in neuro-oncology, in particular gliomas, and future areas of research. The gut-brain axis is a well-established biochemical signaling axis that has been associated with various CNS diseases. In neuro-oncology, recent studies have described gut microbiome differences in tumor-bearing mice and glioma patients compared to controls. These differences in the composition of the microbiome …

Residual Cancer Burden After Neoadjuvant Chemotherapy And Long-Term Survival Outcomes In Breast Cancer: A Multicentre Pooled Analysis Of 5161 Patients, Christina Yau, Marie Osdoit, Marieke Van Der Noordaa, Sonal Shad, Jane Wei, Diane De Croze, Anne-Sophie Hamy, Marick Laé, Fabien Reyal, Gabe S Sonke, Tessa G Steenbruggen, Maartje Van Seijen, Jelle Wesseling, Miguel Martín, Maria Del Monte-Millán, Sara López-Tarruella, Judy C Boughey, Matthew P Goetz, Tanya Hoskin, Rebekah Gould, Vicente Valero, Stephen B Edge, Jean E Abraham, John M S Bartlett, Carlos Caldas, Janet Dunn, Helena Earl, Larry Hayward, Louise Hiller, Elena Provenzano, Stephen-John Sammut, Jeremy S Thomas, David Cameron, Ashley Graham, Peter Hall, Lorna Mackintosh, Fang Fan, Andrew K Godwin, Kelsey Schwensen, Priyanka Sharma, Angela M Demichele, Kimberly Cole, Lajos Pusztai, Mi-Ok Kim, Laura J Van 'T Veer, Laura J Esserman, W Fraser Symmans

Faculty, Staff and Student Publications

Background: Previous studies have independently validated the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. We used results from several independent cohorts in a pooled patient-level analysis to evaluate the relationship of RCB with long-term prognosis across different phenotypic subtypes of breast cancer, to assess generalisability in a broad range of practice settings.

Methods: In this pooled analysis, 12 institutes and trials in Europe and the USA were identified by personal communications with site investigators. We obtained participant-level RCB results, and data on clinical and pathological stage, tumour subtype and grade, and treatment and follow-up in November, 2019, …

Dose Accumulation For Mr-Guided Adaptive Radiotherapy: From Practical Considerations To State-Of-The-Art Clinical Implementation, Brigid A Mcdonald, Cornel Zachiu, John Christodouleas, Mohamed A Naser, Mark Ruschin, Jan-Jakob Sonke, Daniela Thorwarth, Daniel Létourneau, Neelam Tyagi, Tony Tadic, Jinzhong Yang, X Allen Li, Uffe Bernchou, Daniel E Hyer, Jeffrey E Snyder, Edyta Bubula-Rehm, Clifton D Fuller, Kristy K Brock

Faculty, Staff and Student Publications

MRI-linear accelerator (MR-linac) devices have been introduced into clinical practice in recent years and have enabled MR-guided adaptive radiation therapy (MRgART). However, by accounting for anatomical changes throughout radiation therapy (RT) and delivering different treatment plans at each fraction, adaptive radiation therapy (ART) highlights several challenges in terms of calculating the total delivered dose. Dose accumulation strategies-which typically involve deformable image registration between planning images, deformable dose mapping, and voxel-wise dose summation-can be employed for ART to estimate the delivered dose. In MRgART, plan adaptation on MRI instead of CT necessitates additional considerations in the dose accumulation process because MRI …

Contemporary Evidence On Colorectal Liver Metastases Ablation: Toward A Paradigm Shift In Locoregional Treatment, Yuan-Mao Lin, Reto Bale, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Image-guided percutaneous ablation techniques represent an attractive local therapy for the treatment of colorectal liver metastases (CLM) given its low risk of severe complications, which allows for early initiation of adjuvant therapies and spare functional liver parenchyma, allowing repeated treatments at the time of recurrence. However, ablation does not consistently achieve similar oncological outcomes to surgery, with the latter being currently considered the first-line local treatment modality in international guidelines. Recent application of computer-assisted ablation planning, guidance, and intra-procedural response assessment has improved percutaneous ablation outcomes. In addition, the evolving understanding of tumor molecular profiling has brought to light several …

Metabolic Imaging Using Hyperpolarization For Assessment Of Premalignancy, Shivanand Pudakalakatti, Priyank Raj, Travis C Salzillo, José S Enriquez, Dontrey Bourgeois, Prasanta Dutta, Mark Titus, Shayan Shams, Priya Bhosale, Michael Kim, Florencia Mcallister, Pratip K Bhattacharya

Faculty, Staff and Student Publications

There is an unmet need for noninvasive surrogate markers that can help identify premalignant lesions across different tumor types. Here we describe the methodology and technical details of protocols employed for in vivo

Associations Of High-Sensitivity Troponin And Natriuretic Peptide Levels With Outcomes After Intensive Blood Pressure Lowering: Findings From The Sprint Randomized Clinical Trial, Jarett D Berry, Vijay Nambi, Walter T Ambrosius, Haiying Chen, Anthony A Killeen, Addison Taylor, Robert D Toto, Elsayed Z Soliman, John W Mcevoy, Ambarish Pandey, Parag H Joshi, Stefan Blankenberg, Dalane W Kitzman, Christie M Ballantyne, James A De Lemos

Faculty, Staff and Students Publications

IMPORTANCE: Elevated high-sensitivity cardiac troponin T (hscTnT) and N-terminal pro-B-type natriuretic peptide (NTproBNP) levels are associated with risk of heart failure (HF) and mortality among individuals in the general population. However, it is unknown if this risk is modifiable.

OBJECTIVE: To test the hypothesis that elevated hscTnT and NTproBNP levels would identify individuals with the greatest risk for mortality and HF and the largest benefit associated with intensive systolic blood pressure (SBP) lowering.

DESIGN, SETTING, AND PARTICIPANTS: This is a nonprespecified post hoc analysis of the multicenter, prospective, randomized clinical Systolic Blood Pressure Intervention Trial (SPRINT), conducted from October 20, …

Modeling Recurrence In Idiopathic Subglottic Stenosis With Mobile Peak Expiratory Flow, Kyle Kimura, Liping Du, Lynn D Berry, Li-Ching Huang, Sheau-Chiann Chen, David O Francis, Alexander Gelbard

Faculty, Staff and Student Publications

OBJECTIVES/HYPOTHESIS: We sought to establish normative peak expiratory flow (PEF) data for patients with idiopathic subglottic stenosis (iSGS), evaluate whether immediate changes in PEF after a procedure predict long-term treatment response, and test if a decline in longitudinal PEF is associated with disease recurrence.

STUDY DESIGN: International, prospective, 3-year multicenter cohort study of 810 patients with untreated, newly diagnosed, or previously treated iSGS.

METHODS: iSGS patients consented and enrolled in the North American Airway Collaborative (NoAAC) iSGS

RESULTS: Within the NoAAC iSGS1000 cohort, 810 patients participated in a 3-year, prospective study comparing surgical treatment efficacy and 385 had appropriate PEF …

Nrf1 Association With Auts2-Polycomb Mediates Specific Gene Activation In The Brain, Sanxiong Liu, Kimberly A Aldinger, Chi Vicky Cheng, Takae Kiyama, Mitali Dave, Hanna K Mcnamara, Wukui Zhao, James M Stafford, Nicolas Descostes, Pedro Lee, Stefano G Caraffi, Ivan Ivanovski, Edoardo Errichiello, Christiane Zweier, Orsetta Zuffardi, Michael Schneider, Antigone S Papavasiliou, M Scott Perry, Jennifer Humberson, Megan T Cho, Astrid Weber, Andrew Swale, Tudor C Badea, Chai-An Mao, Livia Garavelli, William B Dobyns, Danny Reinberg

Faculty, Staff and Student Publications

The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.5, are known to comprise novel components, AUTS2, P300, and CK2, that convert this repressive function to that of transcription activation. Here, we report that individuals harboring mutations in the HX repeat domain of AUTS2 exhibit defects in AUTS2 and P300 interaction as well as a developmental disorder reflective of Rubinstein-Taybi syndrome, which is mainly associated with a heterozygous pathogenic variant in CREBBP/EP300. Moreover, the absence of AUTS2 or mutation in its …

Perspectives From The Society For Pediatric Research: Advice On Sustaining Science And Mentoring During Covid-19, Catherine S Forster, Suong T Nguyen, Weston T Powell, Daniel J Moore, Jacqueline Ho, Melvin B Heyman, Tara L Wenger, Fernando Gonzalez, Margaret Hostetter, Andrew Nowalk, Caroline E Rassbach, Debra Boyer, Pnina Weiss, Rebecca L Blankenburg, Jordan S Orange, Kate G Ackerman, Audrea M Burns, National Pediatric Physician-Scientist Collaborative Workgroup

Faculty, Staff and Students Publications

The COVID-19 pandemic will leave an indelible mark on the careers of current medical trainees. Given the disruptions to medical education, economic impact on institutions, and the uncertainties around future job prospects, trainees are facing unprecedented challenges. This situation is especially concerning for futures of pediatric physician-scientist trainees, where concerns regarding maintaining the pipeline were well documented prior to the emergence of COVID-19. In this Perspectives article, we leverage the unique expertise of our workgroup to address concerns of physician-scientist trainees and to provide suggestions on how to navigate career trajectories in the post-COVID-19 era. We identified and addressed four …