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Third Year Medical Student Knowledge Gaps After A Virtual Surgical Rotation, Alexander S Kim, Elizabeth C Wick, Julie Ann Sosa, Jessica Gosnell, Matthew Y C Lin, Sanziana A Roman Jul 2022

Third Year Medical Student Knowledge Gaps After A Virtual Surgical Rotation, Alexander S Kim, Elizabeth C Wick, Julie Ann Sosa, Jessica Gosnell, Matthew Y C Lin, Sanziana A Roman

Faculty, Staff and Student Publications

INTRODUCTION: This study describes perceived knowledge gaps of third-year medical students after participating in a virtual surgical didactic rotation (EMLR) and shortened in-person surgery rotation during the COVID-19 Pandemic.

METHODS: Open-ended and Likert questions were administered at the end of the virtual rotation and inperson-surgical rotation to medical students. Three blinded coders identified themes by semantic analysis.

RESULTS: 82 students (51% of all MS3s) participated in the EMLR. Semantic analysis revealed gaps in perioperative management (Post-EMLR:18.4%, Post-Inpatient:26.5%), anatomy (Post-EMLR:8.2%, PostInpatient:26.5%). and surgical skills (Post-EMLR: 43.0%, Post-Inpatient: 44.1%). Students also described gaps related to OR etiquette (Post-EMLR: 12.2%, Post-Inpatient: 8.8%) and …


Comparison Of Different Metrics Of Cerebral Autoregulation In Association With Major Morbidity And Mortality After Cardiac Surgery, Brian Bush, Marek Czosnyka, Peter Smielewski, Charles H Brown Jul 2022

Comparison Of Different Metrics Of Cerebral Autoregulation In Association With Major Morbidity And Mortality After Cardiac Surgery, Brian Bush, Marek Czosnyka, Peter Smielewski, Charles H Brown

Faculty, Staff and Student Publications

BACKGROUND: Cardiac surgery studies have established the clinical relevance of personalised arterial blood pressure management based on cerebral autoregulation. However, variabilities exist in autoregulation evaluation. We compared the association of several cerebral autoregulation metrics, calculated using different methods, with outcomes after cardiac surgery.

METHODS: Autoregulation was measured during cardiac surgery in 240 patients. Mean flow index and cerebral oximetry index were calculated as Pearson's correlations between mean arterial pressure (MAP) and transcranial Doppler blood flow velocity or near-infrared spectroscopy signals. The lower limit of autoregulation and optimal mean arterial pressure were identified using mean flow index and cerebral oximetry index. …


Hypertension In Pregnancy And Adverse Outcomes Among Low-Risk Nulliparous People Expectantly Managed At Or After 39 Weeks: A Secondary Analysis Of A Randomized Controlled Trial, Alan T N Tita, Dwight J Rouse, George R Saade, John M Thorp, Maged M Costantine, Edward K Chien, Brian M Casey, Sindhu K Srinivas, Geeta K Swamy, Hyagriv N Simhan, Eunice Kennedy Shriver National Institute Of Child Health And Human Development (Nichd) Maternal-Fetal Medicine Units (Mfmu) Network Jul 2022

Hypertension In Pregnancy And Adverse Outcomes Among Low-Risk Nulliparous People Expectantly Managed At Or After 39 Weeks: A Secondary Analysis Of A Randomized Controlled Trial, Alan T N Tita, Dwight J Rouse, George R Saade, John M Thorp, Maged M Costantine, Edward K Chien, Brian M Casey, Sindhu K Srinivas, Geeta K Swamy, Hyagriv N Simhan, Eunice Kennedy Shriver National Institute Of Child Health And Human Development (Nichd) Maternal-Fetal Medicine Units (Mfmu) Network

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate whether hypertensive disorders of pregnancy (HDP) among low-risk nulliparous women expectantly managed at or after 39 weeks of gestation are associated with adverse outcomes.

DESIGN: Secondary analysis of a randomised trial.

SETTING: Multicentre, USA.

POPULATION: Individuals in the expectantly managed group who delivered on or after 39 weeks.

METHODS: Multivariable analysis to estimate adjusted relative risks (aRR) for binomial outcomes, adjusted odds ratios (aOR) for multinomial outcomes and 95% CI.

MAIN OUTCOME MEASURES: Composite adverse maternal outcome including placental abruption, pulmonary oedema, postpartum haemorrhage, postpartum infection, venous thromboembolism or intensive care unit admission. Secondary outcomes included a …


Medical Training In Home Care Medicine: The Time Is Now Jul 2022

Medical Training In Home Care Medicine: The Time Is Now

Faculty, Staff and Student Publications

No abstract provided.


Targeting Syndecan-1: New Opportunities In Cancer Therapy, Zecheng Yang, Shuaitong Chen, Haoqiang Ying, Wantong Yao Jul 2022

Targeting Syndecan-1: New Opportunities In Cancer Therapy, Zecheng Yang, Shuaitong Chen, Haoqiang Ying, Wantong Yao

Faculty, Staff and Student Publications

Syndecan-1 (SDC1, CD138) is one of the heparan sulfate proteoglycans and is essential for maintaining normal cell morphology, interacting with the extracellular and intracellular protein repertoire, as well as mediating signaling transduction upon environmental stimuli. The critical role of SDC1 in promoting tumorigenesis and metastasis has been increasingly recognized in various cancer types, implying a promising potential of utilizing SDC1 as a novel target for cancer therapy. This review summarizes the current knowledge on SDC1 structure and functions, including its role in tumor biology. We also discuss the highlights and limitations of current SDC1-targeted therapies as well as the obstacles …


Estimated Size Of The Clinical Medical Imaging Physics Workforce In The United States, David E Hintenlang Jul 2022

Estimated Size Of The Clinical Medical Imaging Physics Workforce In The United States, David E Hintenlang

Faculty, Staff and Student Publications

There is no current authoritative accounting of the number of clinical imaging physicists practicing in the United States. Information about the workforce is needed to inform future efforts to secure training pathways and opportunities. In this study, the AAPM Diagnostic Demand and Supply Projection Working Group collected lists of medical physicists from several state registration and licensure programs and the Conference of Radiation Control Program Directors (CRCPD) registry. By cross-referencing individuals among these lists, we were able to estimate the current imaging physics workforce in the United States by extrapolating based on population. The imaging physics workforce in the United …


Impact Of Risk-Based Sexually Transmitted Infection Screening In The Emergency Department, Donna B Jeffe Jul 2022

Impact Of Risk-Based Sexually Transmitted Infection Screening In The Emergency Department, Donna B Jeffe

Faculty, Staff and Student Publications

OBJECTIVES: Sexually transmitted infections (STIs), including chlamydia, gonorrhea, and human immunodeficiency virus (HIV) pose a significant health burden in adolescents. Many adolescents receiving care in the emergency department (ED) are in need of testing, regardless of their chief complaint. Our objective was to determine whether an electronic, risk-based STI screening program in our ED was associated with an increase in STI testing among at-risk adolescents.

METHODS: We conducted a retrospective cohort analysis of patient outcomes in our pediatric ED after integrating an Audio-enhanced Computer-Assisted Self-Interview (ACASI) as standard of care. It obtained a focused sexual history and generated STI testing …


Respiratory Effects Of Thyrotropin-Releasing Hormone And Its Analogue Taltirelin On Opioid-Induced Respiratory Depression, Martijn Boon, Albert Dahan Jul 2022

Respiratory Effects Of Thyrotropin-Releasing Hormone And Its Analogue Taltirelin On Opioid-Induced Respiratory Depression, Martijn Boon, Albert Dahan

Faculty, Staff and Student Publications

No abstract provided.


Heart Transplant Recipient 1-Year Outcomes During The Covid-19 Pandemic, Matthew Rafiei, Alfredo Trento, Joanna Chikwe, Fardad Esmailian, Jon A Kobashigawa Jul 2022

Heart Transplant Recipient 1-Year Outcomes During The Covid-19 Pandemic, Matthew Rafiei, Alfredo Trento, Joanna Chikwe, Fardad Esmailian, Jon A Kobashigawa

Faculty, Staff and Student Publications

The COVID-19 pandemic initially brought forth considerable challenges to the field of heart transplantation. To prevent the spread of the virus and protect immunocompromised recipients, our center made the following modifications to post-transplant outpatient management: eliminating early coronary angiograms, video visits for postoperative months 7, 9, and 11, and home blood draws for immunosuppression adjustments. To assess if these changes have impacted patient outcomes, the current study examines 1-year outcomes for patients transplanted during the pandemic. Between March and September 2020, we assessed 50 heart transplant patients transplanted during the pandemic. These patients were compared to patients who were transplanted …


Urgent Cytoreduction For Newly Diagnosed Acute Myeloid Leukemia Patients Allows Acquisition Of Pretreatment Genomic Data And Enrollment On Investigational Clinical Trials, Kunhwa Kim, Marina Konopleva, Courtney D Dinardo, Gautam Borthakur, Sanam Loghavi, Naval Daver, Elias Jabbour, Caitlin R Rausch, Musa Yilmaz, Koji Sasaki, Nicholas J Short, Nitin Jain, Mark Brandt, Sherry Pierce, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Tapan M Kadia Jul 2022

Urgent Cytoreduction For Newly Diagnosed Acute Myeloid Leukemia Patients Allows Acquisition Of Pretreatment Genomic Data And Enrollment On Investigational Clinical Trials, Kunhwa Kim, Marina Konopleva, Courtney D Dinardo, Gautam Borthakur, Sanam Loghavi, Naval Daver, Elias Jabbour, Caitlin R Rausch, Musa Yilmaz, Koji Sasaki, Nicholas J Short, Nitin Jain, Mark Brandt, Sherry Pierce, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

Newly diagnosed acute myeloid leukemia is often deemed a medical emergency, requiring urgent treatment. This is in contradiction with the need for accurate cytogenetic and molecular data, which is not immediately available, to select optimal therapy. We hypothesized that cytoreduction with hydroxyurea or cytarabine would enable urgent disease control and provide a bridge to clinical trial enrollment. We analyzed three prospective frontline clinical trials that allowed the use of cytoreduction before treatment initiation. Among 274 patients with a median age of 62 (range, 18-89), there was no significant difference in short- and long-term outcome and safety among patients who did …


Obscurin Regulates Ankyrin Macromolecular Complex Formation Jul 2022

Obscurin Regulates Ankyrin Macromolecular Complex Formation

Faculty, Staff and Student Publications

Obscurin is a large scaffolding protein in striated muscle that maintains sarcolemmal integrity and aligns the sarcoplasmic reticulum with the underlying contractile machinery. Ankyrins are a family of adaptor proteins with some isoforms that interact with obscurin. Previous studies have examined obscurin interacting with individual ankyrins. In this study, we demonstrate that two different ankyrins interact with obscurin's carboxyl terminus via independent ankyrin-binding domains (ABDs). Using in-vitro binding assays, co-precipitation assays, and FLIM-FRET analysis, we show that obscurin interacts with small ankyrin 1.5 (sAnk1.5) and the muscle-specific ankyrin-G isoform (AnkG107). While there is no direct interaction between sAnk1.5 and AnkG107, …


Elimination Of Pseudo-Hfos In Ieeg Using Sparse Representation And Random Forest Classifier, Candan Gurses Jul 2022

Elimination Of Pseudo-Hfos In Ieeg Using Sparse Representation And Random Forest Classifier, Candan Gurses

Faculty, Staff and Student Publications

High-Frequency Oscillation (HFO) is a promising biomarker of the epileptogenic zone. However, sharp artifacts might easily pass the conventional HFO detectors as real HFOs and reduce the seizure onset zone (SOZ) localization. We hypothesize that, unlike pseudo-HFOs, which originates from artifacts with sharp changes or arbitrary waveform characteristic, real HFOs could be represented by a limited number of oscillatory waveforms. Accordingly, to distinguish true ones from pseudo-HFOs, we established a new classification method based on sparse representation of candidate events that passed an initial detector with high sensitivity but low specificity. Specifically, using the Orthogonal Matching Pursuit (OMP) and a …


A Win Consortium Phase I Study Exploring Avelumab, Palbociclib, And Axitinib In Advanced Non-Small Cell Lung Cancer, Benjamin Solomon, Ana Callejo, Jair Bar, Guy Berchem, Lyudmila Bazhenova, Fanny Wunder, Nicolas Girard, J Jack Lee, Raed Sulaiman, Bruce Prouse, Catherine Bresson, Hila Ventura, Shai Magidi, Eitan Rubin, Brandon Young, Amir Onn, Brian Leyland-Jones, Richard L Schilsky, Vladimir Lazar, Enriqueta Felip, Razelle Kurzrock Jul 2022

A Win Consortium Phase I Study Exploring Avelumab, Palbociclib, And Axitinib In Advanced Non-Small Cell Lung Cancer, Benjamin Solomon, Ana Callejo, Jair Bar, Guy Berchem, Lyudmila Bazhenova, Fanny Wunder, Nicolas Girard, J Jack Lee, Raed Sulaiman, Bruce Prouse, Catherine Bresson, Hila Ventura, Shai Magidi, Eitan Rubin, Brandon Young, Amir Onn, Brian Leyland-Jones, Richard L Schilsky, Vladimir Lazar, Enriqueta Felip, Razelle Kurzrock

Faculty, Staff and Student Publications

Background: The Worldwide Innovative Network (WIN) Consortium has developed the Simplified Interventional Mapping System (SIMS) to better define the cancer molecular milieu based on genomics/transcriptomics from tumor and analogous normal tissue biopsies. SPRING is the first trial to assess a SIMS-based tri-therapy regimen in advanced non-small cell lung cancer (NSCLC).

Methods: Patients with advanced NSCLC (no EGFR, ALK, or ROS1 alterations; PD-L1 unrestricted; ≤2 prior therapy lines) received avelumab, axitinib, and palbociclib (3 + 3 dose escalation design).

Results: Fifteen patients were treated (five centers, four countries): six at each of dose levels 1 (DL1) and DL2; three at DL3. …


Hap40 Is A Conserved Central Regulator Of Huntingtin And A Potential Modulator Of Huntington’S Disease Pathogenesis, Shiyu Xu, Gang Li, Xin Ye, Dongsheng Chen, Zhihua Chen, Moretti Daniele, Alessandra Ceccacci, Licia Tomei, Lili Ye, Yue Yu, Amanda Solbach, Stephen M Farmer, Erin Furr Stimming, George Mcallister, Deanna M Marchionini, Sheng Zhang Jul 2022

Hap40 Is A Conserved Central Regulator Of Huntingtin And A Potential Modulator Of Huntington’S Disease Pathogenesis, Shiyu Xu, Gang Li, Xin Ye, Dongsheng Chen, Zhihua Chen, Moretti Daniele, Alessandra Ceccacci, Licia Tomei, Lili Ye, Yue Yu, Amanda Solbach, Stephen M Farmer, Erin Furr Stimming, George Mcallister, Deanna M Marchionini, Sheng Zhang

Faculty, Staff and Student Publications

Perturbation of huntingtin (HTT)'s physiological function is one postulated pathogenic factor in Huntington's disease (HD). However, little is known how HTT is regulated in vivo. In a proteomic study, we isolated a novel ~40kDa protein as a strong binding partner of Drosophila HTT and demonstrated it was the functional ortholog of HAP40, an HTT associated protein shown recently to modulate HTT's conformation but with unclear physiological and pathologic roles. We showed that in both flies and human cells, HAP40 maintained conserved physical and functional interactions with HTT. Additionally, loss of HAP40 resulted in similar phenotypes as HTT knockout. More strikingly, …


Treatment-Free Remission In Patients With Chronic Myeloid Leukemia Following The Discontinuation Of Tyrosine Kinase Inhibitors, Fadi G Haddad, Koji Sasaki, Ghayas C Issa, Guillermo Garcia-Manero, Farhad Ravandi, Jorge Cortes, Naveen Pemmaraju, Yesid Alvarado, Musa Yilmaz, Gautam Borthakur, Courtney Dinardo, Nitin Jain, Naval Daver, Nicholas J Short, Elias Jabbour, Hagop Kantarjian Jul 2022

Treatment-Free Remission In Patients With Chronic Myeloid Leukemia Following The Discontinuation Of Tyrosine Kinase Inhibitors, Fadi G Haddad, Koji Sasaki, Ghayas C Issa, Guillermo Garcia-Manero, Farhad Ravandi, Jorge Cortes, Naveen Pemmaraju, Yesid Alvarado, Musa Yilmaz, Gautam Borthakur, Courtney Dinardo, Nitin Jain, Naval Daver, Nicholas J Short, Elias Jabbour, Hagop Kantarjian

Faculty, Staff and Student Publications

Tyrosine kinase inhibitors (TKIs) discontinuation in patients with Philadelphia-chromosome-positive chronic myeloid leukemia (Ph-positive CML) is increasingly considered. We aim to evaluate the outcome of patients with CML who discontinued TKIs, and determine the factors associated with differences in the success rates of treatment-free remission (TFR). Patients with Ph-positive CML treated between October 1999 and February 2017 who discontinued therapy were analyzed. A major molecular response (MMR) was defined as BCR-ABL1/ABL1 ratio on the International Scale ≤0.1%. TFR failure was defined as the loss of MMR on any single test. We analyzed TFR rates according to duration and depth of response, …


A Spef1-Interacting Microtubule Quartet Protein In Trypanosoma Brucei Promotes Flagellar Inheritance By Regulating Basal Body Segregation Jul 2022

A Spef1-Interacting Microtubule Quartet Protein In Trypanosoma Brucei Promotes Flagellar Inheritance By Regulating Basal Body Segregation

Faculty, Staff and Student Publications

The human parasite Trypanosoma brucei contains a motile flagellum that determines the plane of cell division, controls cell morphology, and mediates cell-cell communication. During the cell cycle, inheritance of the newly formed flagellum requires its correct positioning toward the posterior of the cell, which depends on the faithful segregation of multiple flagellum-associated cytoskeletal structures including the basal body, the flagellar pocket collar, the flagellum attachment zone, and the hook complex. A specialized group of four microtubules termed the microtubule quartet (MtQ) originates from the basal body and runs through the flagellar pocket collar and the hook complex to extend, along …


A Randomized, Double-Blind Trial Of Triheptanoin For Drug-Resistant Epilepsy In Glucose Transporter 1 Deficiency Syndrome, Ingrid E Scheffer, Adrian Lacy, Ronald Davis, Angela Garcia-Cazorla, Russell P Saneto, Melanie Brandabur, Susan Blair, Tony Koutsoukos, Darryl De Vivo Jul 2022

A Randomized, Double-Blind Trial Of Triheptanoin For Drug-Resistant Epilepsy In Glucose Transporter 1 Deficiency Syndrome, Ingrid E Scheffer, Adrian Lacy, Ronald Davis, Angela Garcia-Cazorla, Russell P Saneto, Melanie Brandabur, Susan Blair, Tony Koutsoukos, Darryl De Vivo

Faculty, Staff and Student Publications

Objective: This study was undertaken to evaluate efficacy and long-term safety of triheptanoin in patients >1 year old, not on a ketogenic diet, with drug-resistant seizures associated with glucose transporter 1 deficiency syndrome (Glut1DS).

Methods: UX007G-CL201 was a randomized, double-blind, placebo-controlled trial. Following a 6-week baseline period, eligible patients were randomized 3:1 to triheptanoin or placebo. Dosing was titrated to 35% of total daily calories over 2 weeks. After an 8-week placebo-controlled period, all patients received open-label triheptanoin through Week 52.

Results: The study included 36 patients (15 children, 13 adolescents, eight adults). A median 12.6% reduction in overall seizure …


Limbic And Paralimbic Respiratory Modulation: From Inhibition To Enhancement, Jaison S Hampson, Nuria Lacuey Jul 2022

Limbic And Paralimbic Respiratory Modulation: From Inhibition To Enhancement, Jaison S Hampson, Nuria Lacuey

Faculty, Staff and Student Publications

Objective: Increased understanding of the role of cortical structures in respiratory control may help the understanding of seizure-induced respiratory dysfunction that leads to sudden unexpected death in epilepsy (SUDEP). The aim of this study was to characterize respiratory responses to electrical stimulation (ES), including inhibition and enhancement of respiration.

Methods: We prospectively recruited 19 consecutive patients with intractable epilepsy undergoing stereotactic electroencephalography (EEG) evaluation from June 2015 to June 2018. Inclusion criteria were patients ≥18 years in whom ES was indicated for clinical mapping of ictal onset or eloquent cortex as part of the presurgical evaluation. ES was carried out …


A Pilot Study To Determine The Incidence, Type, And Severity Of Non-Routine Events In Neonates Undergoing Gastrostomy Tube Placement, Sarah Moroz, Amanda Lorinc, Jamie Robinson, Marlee Crankshaw, Timothy Newman, Matthew B Weinger, Martin L Blakely Jul 2022

A Pilot Study To Determine The Incidence, Type, And Severity Of Non-Routine Events In Neonates Undergoing Gastrostomy Tube Placement, Sarah Moroz, Amanda Lorinc, Jamie Robinson, Marlee Crankshaw, Timothy Newman, Matthew B Weinger, Martin L Blakely

Faculty, Staff and Student Publications

BACKGROUND: Non-routine events (NRE) are defined as any suboptimal occurrences in a process being measured in the opinion of the reporter and comes from the field of human factors engineering. These typically occur well up-stream of an adverse event and NRE measurement has not been applied to the complex context of neonatal surgery. We sought to apply this novel safety event measurement methodology to neonates in the NICU undergoing gastrostomy tube placement.

METHODS: A prospective pilot study was conducted between November 2016 and August 2020 in the Level IV NICU and the pediatric operating rooms of an urban academic children's …


A Missing Piece Of The Puzzle: Patient And Provider Perspectives On Pain Management Needs And Opioid Prescribing In Inflammatory Bowel Disease Care, Jonah J Stulberg Jul 2022

A Missing Piece Of The Puzzle: Patient And Provider Perspectives On Pain Management Needs And Opioid Prescribing In Inflammatory Bowel Disease Care, Jonah J Stulberg

Faculty, Staff and Student Publications

BACKGROUND: Recent data have shown high rates of opioid misuse among inflammatory bowel disease (IBD) patients. We conducted a qualitative study to explore IBD patient and provider perceptions and experiences with pain management and opioid prescribing.

METHODS: We conducted a focus group with IBD patients and semistructured interviews with IBD-focused physicians and nurses. We used an inductive approach for analysis and the constant comparison method to develop and refine codes and identify prominent themes. We analyzed interview and focus group data concurrently to triangulate themes.

RESULTS: Nine patients and 10 providers participated. We grouped themes into 3 categories: (1) current …


Michigan Plan For Appropriate Tailored Healthcare In Pregnancy Prenatal Care Recommendations: A Practical Guide For Maternity Care Clinicians, Christopher M Zahn Jul 2022

Michigan Plan For Appropriate Tailored Healthcare In Pregnancy Prenatal Care Recommendations: A Practical Guide For Maternity Care Clinicians, Christopher M Zahn

Faculty, Staff and Student Publications

Prenatal care is an important preventive service designed to improve the health of pregnant patients and their infants. Prenatal care delivery recommendations have remained unchanged since 1930, when the 12-14 in-person visit schedule was first established to detect preeclampsia. In 2020, the American College of Obstetricians and Gynecologists, in collaboration with the University of Michigan, convened a panel of maternity care experts to determine new prenatal care delivery recommendations. The panel recognized the need to include emerging evidence and experience, including significant changes in prenatal care delivery during the COVID-19 pandemic, pre-existing knowledge of the importance of individualized care plans, …


Reshaping The Tumor Microenvironment With Oncolytic Viruses, Positive Regulation Of The Immune Synapse, And Blockade Of The Immunosuppressive Oncometabolic Circuitry, Yisel Rivera-Molina, Hong Jiang, Xuejun Fan, Joy Gumin, Frederick F Lang, Christopher Alvarez-Breckenridge, Filipa Godoy-Vitorino, Lisha Zhu, W Jim Zheng, Lijie Zhai, Erik Ladomersky, Kristen L Lauing, Marta M Alonso, Derek A Wainwright, Candelaria Gomez-Manzano, Juan Fueyo Jul 2022

Reshaping The Tumor Microenvironment With Oncolytic Viruses, Positive Regulation Of The Immune Synapse, And Blockade Of The Immunosuppressive Oncometabolic Circuitry, Yisel Rivera-Molina, Hong Jiang, Xuejun Fan, Joy Gumin, Frederick F Lang, Christopher Alvarez-Breckenridge, Filipa Godoy-Vitorino, Lisha Zhu, W Jim Zheng, Lijie Zhai, Erik Ladomersky, Kristen L Lauing, Marta M Alonso, Derek A Wainwright, Candelaria Gomez-Manzano, Juan Fueyo

Faculty, Staff and Student Publications

Background: Oncolytic viruses are considered part of immunotherapy and have shown promise in preclinical experiments and clinical trials. Results from these studies have suggested that tumor microenvironment remodeling is required to achieve an effective response in solid tumors. Here, we assess the extent to which targeting specific mechanisms underlying the immunosuppressive tumor microenvironment optimizes viroimmunotherapy.

Methods: We used RNA-seq analyses to analyze the transcriptome, and validated the results using Q-PCR, flow cytometry, and immunofluorescence. Viral activity was analyzed by replication assays and viral titration. Kyn and Trp metabolite levels were quantified using liquid chromatography-mass spectrometry. Aryl hydrocarbon receptor (AhR) activation …


Genotype-To-Phenotype Associations In The Aggressive Variant Prostate Cancer Molecular Profile (Avpc-M) Components, Rama Soundararajan, Paul Viscuse, Patrick Pilie, Jingjing Liu, Souzana Logotheti, Daniele Lorenzini, Wei Lu, Luisa Maren Solis Soto, Ignacio I Wistuba, Mingchu Xu, Xingzhi Song, Peter D A Shepherd, Nora M Navone, Rebecca S S Tidwell, Guillermina Lozano, Christopher Logothetis, Jianhua Zhang, James P Long, Marcos R Estecio, Vasiliki Tzelepi, Ana M Aparicio Jun 2022

Genotype-To-Phenotype Associations In The Aggressive Variant Prostate Cancer Molecular Profile (Avpc-M) Components, Rama Soundararajan, Paul Viscuse, Patrick Pilie, Jingjing Liu, Souzana Logotheti, Daniele Lorenzini, Wei Lu, Luisa Maren Solis Soto, Ignacio I Wistuba, Mingchu Xu, Xingzhi Song, Peter D A Shepherd, Nora M Navone, Rebecca S S Tidwell, Guillermina Lozano, Christopher Logothetis, Jianhua Zhang, James P Long, Marcos R Estecio, Vasiliki Tzelepi, Ana M Aparicio

Faculty, Staff and Student Publications

The aggressive variant prostate cancer molecular profile (AVPC-m), composed of combined defects in TP53, RB1 and PTEN, characterizes a subset of prostate cancers linked to androgen indifference and platinum sensitivity. To contribute to the optimization of the AVPC-m assessment for inclusion in prospective clinical trials, we investigated the status of the AVPC-m components in 28 patient tumor-derived xenografts (PDXs) developed at MDACC. We subjected single formalin-fixed, paraffin-embedded (FFPE) blocks from each PDX to immunohistochemistry (IHC), targeted next-generation genomic sequencing (NGS) and Clariom-S Affymetrix human microarray expression profiling. Standard validated IHC assays and a 10% labeling index cutoff resulted in high …


Validation Of A High Flow Rate Puff Topography System Designed For Measurement Of Sub-Ohm, Third Generation Electronic Nicotine Delivery Systems, Jooyeon Hwang Jun 2022

Validation Of A High Flow Rate Puff Topography System Designed For Measurement Of Sub-Ohm, Third Generation Electronic Nicotine Delivery Systems, Jooyeon Hwang

Faculty, Staff and Student Publications

There are few known puff topography devices designed solely for gathering electronic cigarette puff topography information, and none made for high-powered sub-ohm devices. Ten replicate Bernoulli flow cells were designed and 3D printed. The relationship between square root of pressure difference and flow rate was determined across 0−70 L/min. One representative flow cell was used to estimate puff volume and flow rate under six simulated puffing regimes (0.710 L, 2.000 L and 3.000 L, at low and high flow rates) to determine the system’s accuracy and utility of using dual pressure sensors for flow measurement. The relationship between flow rate …


Reflections On Beam Configuration Optimization For Intensity-Modulated Proton Therapy, Wenhua Cao, Humberto Rocha, Radhe Mohan, Gino Lim, Hadis M Goudarzi, Joana M Dias Jun 2022

Reflections On Beam Configuration Optimization For Intensity-Modulated Proton Therapy, Wenhua Cao, Humberto Rocha, Radhe Mohan, Gino Lim, Hadis M Goudarzi, Joana M Dias

Faculty, Staff and Student Publications

Presumably, intensity-modulated proton radiotherapy (IMPT) is the most powerful form of proton radiotherapy. In the current state of the art, IMPT beam configurations (i.e. the number of beams and their directions) are, in general, chosen subjectively based on prior experience and practicality. Beam configuration optimization (BCO) for IMPT could, in theory, significantly enhance IMPT's therapeutic potential. However, BCO is complex and highly computer resource-intensive. Some algorithms for BCO have been developed for intensity-modulated photon therapy (IMRT). They are rarely used clinically mainly because the large number of beams typically employed in IMRT renders BCO essentially unnecessary. Moreover, in the newer …


Transmission, Strain Diversity, And Zoonotic Potential Of Chronic Wasting Disease Jun 2022

Transmission, Strain Diversity, And Zoonotic Potential Of Chronic Wasting Disease

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting several species of captive and free-ranging cervids. In the past few decades, CWD has been spreading uncontrollably, mostly in North America, resulting in a high increase of CWD incidence but also a substantially higher number of geographical regions affected. The massive increase in CWD poses risks at several levels, including contamination of the environment, transmission to animals cohabiting with cervids, and more importantly, a putative transmission to humans. In this review, I will describe the mechanisms and routes responsible for the efficient transmission of CWD, the strain diversity of natural CWD, …


The Three Two-Pore Channel Subtypes From Rabbit Exhibit Distinct Sensitivity To Phosphoinositides, Voltage, And Extracytosolic Ph, Xinghua Feng, Jian Xiong, Weijie Cai, Jin-Bin Tian, Michael X Zhu Jun 2022

The Three Two-Pore Channel Subtypes From Rabbit Exhibit Distinct Sensitivity To Phosphoinositides, Voltage, And Extracytosolic Ph, Xinghua Feng, Jian Xiong, Weijie Cai, Jin-Bin Tian, Michael X Zhu

Faculty, Staff and Student Publications

Two pore channels (TPCs) are implicated in vesicle trafficking, virus infection, and autophagy regulation. As Na+- or Ca2+-permeable channels, TPCs have been reported to be activated by NAADP, PI(3,5)P2, and/or high voltage. However, a comparative study on the function and regulation of the three mammalian TPC subtypes is currently lacking. Here, we used the electrophysiological recording of enlarged endolysosome vacuoles, inside-out and outside-out membrane patches to examine the three TPCs of rabbit (Oryctolagus cuniculus, or Oc) heterologously expressed in HEK293 cells. While PI(3,5)P2 evoked Na+ currents with a potency order of OcTPC1 > OcTPC3 > OcTPC2, only OcTPC2 displayed a strict dependence …


Phosphatidylserine And Phosphatidylethanolamine Asymmetry Have A Negligible Effect On The Global Structure, Dynamics, And Interactions Of The Kras Lipid Anchor Jun 2022

Phosphatidylserine And Phosphatidylethanolamine Asymmetry Have A Negligible Effect On The Global Structure, Dynamics, And Interactions Of The Kras Lipid Anchor

Faculty, Staff and Student Publications

The intrinsically disordered C-terminus of the prominent oncogenic protein KRAS-4B (KRAS) selectively interacts and clusters with phosphatidylserine (PS) lipids in the plasma membrane (PM). This 11-residue segment, called tK, contains a polybasic domain (PBD) of six contiguous lysine residues and a farnesylated cysteine. Previous molecular dynamics (MD) simulation studies of tK in phosphatidylcholine (PC)/PS bilayers have suggested that backbone conformational dynamics modulate tK-PS interactions. These simulations have been conducted in symmetric membranes whereas the PM is compositionally asymmetric, with the inner leaflet, where KRAS is localized, being enriched with PS and phosphatidylethanolamine (PE) lipids. To examine if bilayer asymmetry affects …


Promoting Cancer Health Equity: A Qualitative Study Of Mentee And Mentor Perspectives Of A Training Program For Underrepresented Scholars In Cancer Health Disparities, Anastasia Rogova, Isabel Martinez Leal, Maggie Britton, Shine Chang, Kamisha H Escoto, Crystal Roberson, Lorraine R Reitzel Jun 2022

Promoting Cancer Health Equity: A Qualitative Study Of Mentee And Mentor Perspectives Of A Training Program For Underrepresented Scholars In Cancer Health Disparities, Anastasia Rogova, Isabel Martinez Leal, Maggie Britton, Shine Chang, Kamisha H Escoto, Crystal Roberson, Lorraine R Reitzel

Faculty, Staff and Student Publications

Racial and ethnic minorities, and women, experience stark disparities in cancer risk behaviors and mortality rates, yet often remain underrepresented in scientific research positions. We conducted an exploratory, qualitative study to examine the value of mentored research experience as part of an NCI-funded research training program designed to increase the representation of minority and women scientists in cancer disparities research. Using individual interviews, we explored 16 mentees' and 7 mentors' program experiences and perspectives to identify the most effective strategies to build strong mentoring relationships that could ultimately contribute to increased representation in health disparities research. Two expert analysts employed …


Inflammatory Breast Cancer: The Cytokinome Of Post-Mastectomy Wound Fluid Augments Proliferation, Invasion, And Stem Cell Markers, Alshaimaa Tarek, Shrouk Khalaf El-Sayed, Wendy A Woodward, Mohamed El-Shinawi, Jon Mark Hirshon Jun 2022

Inflammatory Breast Cancer: The Cytokinome Of Post-Mastectomy Wound Fluid Augments Proliferation, Invasion, And Stem Cell Markers, Alshaimaa Tarek, Shrouk Khalaf El-Sayed, Wendy A Woodward, Mohamed El-Shinawi, Jon Mark Hirshon

Faculty, Staff and Student Publications

Inflammatory breast cancer (IBC) is an aggressive phenotype with a high recurrence and low survival rate. Approximately 90% of local breast cancer recurrences occur adjacent to the same quadrant as the initial cancer, implying that tumor recurrence may be caused by residual cancer cells and/or quiescent cancer stem cells (CSCs) in the tumor. We hypothesized that wound fluid (WF) collected after modified radical mastectomy (MRM) may activate cancer cells and CSCs, promoting epithelial mesenchymal transition (EMT) and invasion. Therefore, we characterized the cytokinome of WF drained from post-MRM cavities of non-IBC and IBC patients. The WF of IBC patients showed …