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Smurf1 Attenuates Endoplasmic Reticulum Stress By Promoting The Degradation Of Keap1 To Activate Nrf2 Antioxidant Pathway, Kyrillos Eskander Mar 2023

Smurf1 Attenuates Endoplasmic Reticulum Stress By Promoting The Degradation Of Keap1 To Activate Nrf2 Antioxidant Pathway, Kyrillos Eskander

Faculty, Staff and Student Publications

Cerebral small-vessels are generally located in the brain at branch points from major cerebral blood vessels and perfuse subcortical structures such as the white matter tracts, basal ganglia, thalamus, and pons. Cerebral small-vessel disease (CSVD) can lead to several different clinical manifestations including ischemic lacunar stroke, intracerebral hemorrhage, and vascular dementia. Risk factors for CSVD overlap with conventional vascular risk factors including hypertension, diabetes mellitus, and hypercholesterolemia, as well as genetic causes. As in cardiovascular disease, treatment of CSVD involves both primary and secondary prevention. Aspirin has not been established as a primary prevention strategy for CSVD among the general …


A Bidirectional Single-Cell Migration And Retrieval Chip For Quantitative Study Of Dendritic Cell Migration, Ning Shao, Yufu Zhou, Jun Yao, Pengchao Zhang, Yanni Song, Xin Han, Xuewu Liu Mar 2023

A Bidirectional Single-Cell Migration And Retrieval Chip For Quantitative Study Of Dendritic Cell Migration, Ning Shao, Yufu Zhou, Jun Yao, Pengchao Zhang, Yanni Song, Xin Han, Xuewu Liu

Faculty, Staff and Student Publications

Dendritic cell (DC) migration is a fundamental step during execution of its adaptive immunity functions. Studying DC migration characteristics is critical for development of DC-dependent allergy treatments, vaccines, and cancer immunotherapies. Here, a microfluidics-based single-cell migration platform is described that enables high-throughput and precise bidirectional cell migration assays. It also allows selective retrieval of cell subpopulations that have different migratory potentials. Using this microfluidic platform, DC migration is investigated in response to different chemoattractants and inhibitors, quantitatively describe DC migration patterns and retrieve DC subpopulations of different migratory potentials for differential gene expression analysis. This platform opens an avenue for …


Aapm Medical Physics Practice Guideline 13a: Hdr Brachytherapy, Part A, Susan L Richardson, Ivan M Buzurovic, Gil'ad N Cohen, Wesley S Culberson, Claire Dempsey, Christopher S Melhus, Daniel J Scanderbeg, Samantha J Simiele Mar 2023

Aapm Medical Physics Practice Guideline 13a: Hdr Brachytherapy, Part A, Susan L Richardson, Ivan M Buzurovic, Gil'ad N Cohen, Wesley S Culberson, Claire Dempsey, Christopher S Melhus, Daniel J Scanderbeg, Samantha J Simiele

Faculty, Staff and Student Publications

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines (MPPGs) will be reviewed for the purpose of revision or renewal, as appropriate, on their …


A Phase I, Open-Label, Dose Confirmation, Escalation, And Expansion Trial Of Bi 1810631 As Monotherapy In Patients With Advanced Or Metastatic Solid Tumors With Her2 Aberrations, John Heymach, Frans Opdam, Minal Barve, Neil Gibson, Behbood Sadrolhefazi, Noboru Yamamoto Mar 2023

A Phase I, Open-Label, Dose Confirmation, Escalation, And Expansion Trial Of Bi 1810631 As Monotherapy In Patients With Advanced Or Metastatic Solid Tumors With Her2 Aberrations, John Heymach, Frans Opdam, Minal Barve, Neil Gibson, Behbood Sadrolhefazi, Noboru Yamamoto

Faculty, Staff and Student Publications

Background: BI 1810631 is a human HER2-selective tyrosine kinase inhibitor that covalently binds to both wild-type and mutated HER2 receptors, including exon 20 insertion mutations, whilst sparing EGFR signaling. This phase Ia/Ib, open-label, non-randomized study will determine the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of BI 1810631 in patients with HER2 aberration-positive solid tumors (NCT04886804).

Patients and methods: In phase Ia, patients with histologically/cytologically confirmed HER2 aberration-positive advanced/metastatic solid tumors will receive BI 1810631 orally twice daily (BID) or once daily (QD) at escalating doses. Starting dose level is 15 mg BID; QD …


Naltrexone-Bupropion Combinations Do Not Affect Cocaine Self-Administration In Humans, Sean D Regnier, William W Stoops, Joshua A Lile, Joseph L Alcorn, B Levi Bolin, Lon R Hays, Craig R Rush Mar 2023

Naltrexone-Bupropion Combinations Do Not Affect Cocaine Self-Administration In Humans, Sean D Regnier, William W Stoops, Joshua A Lile, Joseph L Alcorn, B Levi Bolin, Lon R Hays, Craig R Rush

Faculty, Staff and Student Publications

The FDA has not yet approved a pharmacotherapy for cocaine use disorder despite nearly four decades of research. This study determined the initial efficacy, safety, and tolerability of naltrexone-bupropion combinations as a putative pharmacotherapy for cocaine use disorder. Thirty-one (31) non-treatment seeking participants with cocaine use disorder completed a mixed-design human laboratory study. Participants were randomly assigned to the naltrexone conditions (i.e., 0, 50 mg/day; between-subject factor) and maintained on escalating doses of bupropion (i.e., 0, 100, 200, 400 mg/day; within-subject factor) for at least four days prior to the conduct of experimental sessions. Cocaine self-administration (IN, 0, 40, 80 …


Risk Factors For Bronchiolitis Obliterans Syndrome After Initial Detection Of Pulmonary Impairment After Hematopoietic Cell Transplantation, Mansour Alkhunaizi, Badar Patel, Luis Bueno, Neel Bhan, Tahreem Ahmed, Rima Saliba, Burton F Dickey, Lara Bashoura, David E Ost, Liang Li, Shikun Wang, Elizabeth Shpall, Richard E Champlin, Rohtesh Mehta, Uday R Popat, Chitra Hosing, Amin M Alousi, Ajay Sheshadri Mar 2023

Risk Factors For Bronchiolitis Obliterans Syndrome After Initial Detection Of Pulmonary Impairment After Hematopoietic Cell Transplantation, Mansour Alkhunaizi, Badar Patel, Luis Bueno, Neel Bhan, Tahreem Ahmed, Rima Saliba, Burton F Dickey, Lara Bashoura, David E Ost, Liang Li, Shikun Wang, Elizabeth Shpall, Richard E Champlin, Rohtesh Mehta, Uday R Popat, Chitra Hosing, Amin M Alousi, Ajay Sheshadri

Faculty, Staff and Student Publications

Pulmonary chronic graft-versus-host-disease (cGVHD), or bronchiolitis obliterans syndrome (BOS), is a highly morbid complication of hematopoietic cell transplantation (HCT). The clinical significance of a single instance of pulmonary decline not meeting the criteria for BOS is unclear. We conducted a retrospective analysis in a cohort of patients who had an initial post-HCT decline in the absolute value of forced expiratory volume in 1 second (FEV1) of ≥10% or mid-expiratory flow rate of ≥25% but not meeting the criteria for BOS (pre-BOS). We examined the impact of clinical variables in patients with pre-BOS on the risk for subsequent BOS. Pre-BOS developed …


Vidutolimod In Combination With Atezolizumab With And Without Radiation Therapy In Patients With Programmed Cell Death Protein 1 Or Programmed Death-Ligand 1 Blockade-Resistant Advanced Nsclc, Marcelo V Negrao, Vassiliki A Papadimitrakopoulou, Andrew C Price, Alda L Tam, Muhammad Furqan, Erminia Massarelli, John V Heymach, Anne S Tsao, Gary V Walker, Lalit Vora, David Mauro, Heather Kelley, James E Wooldridge, Arthur M Krieg, Jiaxin Niu Mar 2023

Vidutolimod In Combination With Atezolizumab With And Without Radiation Therapy In Patients With Programmed Cell Death Protein 1 Or Programmed Death-Ligand 1 Blockade-Resistant Advanced Nsclc, Marcelo V Negrao, Vassiliki A Papadimitrakopoulou, Andrew C Price, Alda L Tam, Muhammad Furqan, Erminia Massarelli, John V Heymach, Anne S Tsao, Gary V Walker, Lalit Vora, David Mauro, Heather Kelley, James E Wooldridge, Arthur M Krieg, Jiaxin Niu

Faculty, Staff and Student Publications

INTRODUCTION: Vidutolimod, a CpG-A TLR9 agonist, was investigated in a phase 1b study (CMP-001-003; ClinicalTrials.gov, NCT03438318) in combination with atezolizumab with and without radiation therapy (RT) in patients with advanced NSCLC.

METHODS: Patients with progressive disease after anti-programmed cell death protein 1 or programmed death-ligand 1 therapy received either vidutolimod and atezolizumab (part A) or vidutolimod, atezolizumab, and RT (part B). The primary objective was to evaluate the safety of vidutolimod and atezolizumab with and without RT. Key secondary end point was best objective response rate per Response Evaluation Criteria in Solid Tumors, version 1.1.

RESULTS: Between March 28, 2018, …


Clinical Characteristics And Cause Of Death Among Hospitalized Decedents With Cancer And Covid-19, Dereddi Raja Reddy, John A Cuenca, Joshua Botdorf, Mayoora Muthu, Ankit Hanmandlu, John Crommett, Nisha Rathi, Bilja Sajith, Mark Knafl, Hussein A Abbas, Scott E Woodman, Joseph L Nates Mar 2023

Clinical Characteristics And Cause Of Death Among Hospitalized Decedents With Cancer And Covid-19, Dereddi Raja Reddy, John A Cuenca, Joshua Botdorf, Mayoora Muthu, Ankit Hanmandlu, John Crommett, Nisha Rathi, Bilja Sajith, Mark Knafl, Hussein A Abbas, Scott E Woodman, Joseph L Nates

Faculty, Staff and Student Publications

There is scant information on the clinical progression, end-of-life decisions, and cause of death of patients with cancer diagnosed with COVID-19. Therefore, we conducted a case series of patients admitted to a comprehensive cancer center who did not survive their hospitalization. To determine the cause of death, 3 board-certified intensivists reviewed the electronic medical records. Concordance regarding cause of death was calculated. Discrepancies were resolved through a joint case-by-case review and discussion among the 3 reviewers. During the study period, 551 patients with cancer and COVID-19 were admitted to a dedicated specialty unit; among them, 61 (11.6%) were nonsurvivors. Among …


Immunocompromised Host Pneumonia: Definitions And Diagnostic Criteria: An Official American Thoracic Society Workshop Report, Guang-Shing Cheng, Kristina Crothers, Stefano Aliberti, Anne Bergeron, Michael Boeckh, Catia Cilloniz, Nathan Dean, Charles S Dela Cruz, Robert P Dickson, Alexander L Greninger, Chadi A Hage, Tobias M Hohl, Steven M Holland, Barbara E Jones, Joseph Keane, Mark Metersky, Rachel Miller, Anne Puel, Julio Ramirez, Marcos I Restrepo, Ajay Sheshadri, Bashar Staitieh, Jeffrey Tarrand, Kevin L Winthrop, Richard G Wunderink, Scott E Evans Mar 2023

Immunocompromised Host Pneumonia: Definitions And Diagnostic Criteria: An Official American Thoracic Society Workshop Report, Guang-Shing Cheng, Kristina Crothers, Stefano Aliberti, Anne Bergeron, Michael Boeckh, Catia Cilloniz, Nathan Dean, Charles S Dela Cruz, Robert P Dickson, Alexander L Greninger, Chadi A Hage, Tobias M Hohl, Steven M Holland, Barbara E Jones, Joseph Keane, Mark Metersky, Rachel Miller, Anne Puel, Julio Ramirez, Marcos I Restrepo, Ajay Sheshadri, Bashar Staitieh, Jeffrey Tarrand, Kevin L Winthrop, Richard G Wunderink, Scott E Evans

Faculty, Staff and Student Publications

Pneumonia imposes a significant clinical burden on people with immunocompromising conditions. Millions of individuals live with compromised immunity because of cytotoxic cancer treatments, biological therapies, organ transplants, inherited and acquired immunodeficiencies, and other immune disorders. Despite broad awareness among clinicians that these patients are at increased risk for developing infectious pneumonia, immunocompromised people are often excluded from pneumonia clinical guidelines and treatment trials. The absence of a widely accepted definition for immunocompromised host pneumonia is a significant knowledge gap that hampers consistent clinical care and research for infectious pneumonia in these vulnerable populations. To address this gap, the American Thoracic …


Causes Of Clonal Hematopoiesis: A Review, Lijin Joo, Catherine C Bradley, Steven H Lin, Paul A Scheet, Kevin T Nead Mar 2023

Causes Of Clonal Hematopoiesis: A Review, Lijin Joo, Catherine C Bradley, Steven H Lin, Paul A Scheet, Kevin T Nead

Faculty, Staff and Student Publications

PURPOSE OF REVIEW: Clonal hematopoiesis (CH) is an age-dependent process detectable using advanced sequencing technologies and is associated with multiple adverse health outcomes including cardiovascular disease and cancer. The purpose of this review is to summarize known causes of CH mutations and to identify key areas and considerations for future research on CH.

RECENT FINDINGS: Studies have identified multiple potential causes of CH mutations including smoking, cancer therapies, cardiometabolic disease, inflammation, and germline risk factors. Additionally, large-scale studies have facilitated the identification of gene-specific effects of CH mutation risk factors that may have unique downstream health implications. For example, cancer …


Health Disparities Experienced By Hispanic Americans With Multiple Myeloma: A Systematic Review Mar 2023

Health Disparities Experienced By Hispanic Americans With Multiple Myeloma: A Systematic Review

Faculty, Staff and Student Publications

Health disparities in multiple myeloma (MM) disproportionately affect minorities. Characterization of health disparities encountered by Hispanic Americans with MM is necessary to identify gaps and inform future strategies to eliminate them. We performed a systematic review of publications that described health disparities relevant to Hispanic Americans with MM through December 2021. We included all original studies which compared incidence, treatment, and/or outcomes of Hispanic Americans with other ethnic groups. Eight hundred and sixty-eight articles were identified of which 22 original study articles were included in our systematic review. The number of publications varied over time with the highest number of …


Prevalence Of Long-Term Physical Sequelae Among Patients Treated With Multi-Drug And Extensively Drug-Resistant Tuberculosis: A Systematic Review And Meta-Analysis, Ty Akalu, Aca Clements, Hf Wolde, Ka Alene Mar 2023

Prevalence Of Long-Term Physical Sequelae Among Patients Treated With Multi-Drug And Extensively Drug-Resistant Tuberculosis: A Systematic Review And Meta-Analysis, Ty Akalu, Aca Clements, Hf Wolde, Ka Alene

Peninsula Medical School

Background Physical sequelae related to multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are emerging and under-recognised global challenges. This systematic review and meta-analysis aimed to quantify the prevalence and the types of long-term physical sequelae associated with patients treated for MDR- and XDR-TB. Methods We systematically searched CINAHL (EBSCO), MEDLINE (via Ovid), Embase, Scopus, and Web of Science from inception through to July 1, 2022, and the last search was updated to January 23, 2023. We included studies reporting physical sequelae associated with all forms of drug-resistant TB, including rifampicin-resistant TB (RR-TB), MDR-TB, Pre-XDR-TB, and XDR-TB. The primary …


Measuring Dna Modifications With The Comet Assay: A Compendium Of Protocols, Awadhesh N. Jha Mar 2023

Measuring Dna Modifications With The Comet Assay: A Compendium Of Protocols, Awadhesh N. Jha

School of Biological and Marine Sciences

The comet assay is a versatile method to detect nuclear DNA damage in individual eukaryotic cells, from yeast to human. The types of damage detected encompass DNA strand breaks and alkali-labile sites (e.g., apurinic/apyrimidinic sites), alkylated and oxidized nucleobases, DNA–DNA crosslinks, UV-induced cyclobutane pyrimidine dimers and some chemically induced DNA adducts. Depending on the specimen type, there are important modifications to the comet assay protocol to avoid the formation of additional DNA damage during the processing of samples and to ensure sufficient sensitivity to detect differences in damage levels between sample groups. Various applications of the comet assay have been …


Crk2 Controls Cytoskeleton Morphogenesis In Trypanosoma Brucei By Phosphorylating Β-Tubulin To Regulate Microtubule Dynamics Mar 2023

Crk2 Controls Cytoskeleton Morphogenesis In Trypanosoma Brucei By Phosphorylating Β-Tubulin To Regulate Microtubule Dynamics

Faculty, Staff and Student Publications

Microtubules constitute a vital part of the cytoskeleton in eukaryotes by mediating cell morphogenesis, cell motility, cell division, and intracellular transport. The cytoskeleton of the parasite Trypanosoma brucei contains an array of subpellicular microtubules with their plus-ends positioned toward the posterior cell tip, where extensive microtubule growth and cytoskeleton remodeling take place during early cell cycle stages. However, the control mechanism underlying microtubule dynamics at the posterior cell tip remains elusive. Here, we report that the S-phase cyclin-dependent kinase-cyclin complex CRK2-CYC13 in T. brucei regulates microtubule dynamics by phosphorylating β-tubulin on multiple evolutionarily conserved serine and threonine residues to inhibit …


Novel Therapeutic Medications For Venous Thromboembolism Prevention In Trauma Patients: Findings From The Consensus Conference To Implement Optimal Venous Thromboembolism Prophylaxis In Trauma, Amanda L Teichman Mar 2023

Novel Therapeutic Medications For Venous Thromboembolism Prevention In Trauma Patients: Findings From The Consensus Conference To Implement Optimal Venous Thromboembolism Prophylaxis In Trauma, Amanda L Teichman

Faculty, Staff and Student Publications

Trauma patients are at high risk for venous thromboembolism (VTE). Despite evidence-based guidelines and concerted efforts in trauma centers to implement optimal chemoprophylaxis strategies, VTE remains a frequent diagnosis in trauma patients. Current chemoprophylaxis strategies largely focus on the subcutaneous injection of low-molecular-weight heparin, which is administered twice daily. Novel approaches to pharmacologic VTE prophylaxis have the potential to reduce VTE rates by improving patient compliance through oral administration or through their ability to target alternative pathways that mediate thrombosis. While novel pharmacologic VTE prophylaxis strategies have been studied in nontrauma patients, there is a paucity of literature in trauma …


Effect Of Sirolimus On Insulin Dynamics In Horses, Kate L Kemp Mar 2023

Effect Of Sirolimus On Insulin Dynamics In Horses, Kate L Kemp

Faculty, Staff and Student Publications

BACKGROUND: Sirolimus, a mechanistic target of rapamycin inhibitor, suppresses insulin production in other species and has therapeutic potential for hyperinsulinemia in horses.

HYPOTHESIS/OBJECTIVE: Determine the pharmacokinetics (PKs) of sirolimus and evaluate its effect on insulin dynamics in healthy and insulin dysregulation (ID) horses.

ANIMALS: Eight Standardbred geldings.

METHODS: A PK study was performed followed by a placebo-controlled, randomized, crossover study. Blood sirolimus concentrations were measured by liquid chromatography-mass-spectrometry. PK indices were estimated by fitting a 2-compartment model using nonlinear least squares regression. An oral glucose test (OGT) was conducted before and 4, 24, 72, and 144 hours after administration of …


Approaches For Optimizing Venous Thromboembolism Prevention In Injured Patients: Findings From The Consensus Conference To Implement Optimal Venous Thromboembolism Prophylaxis In Trauma, Allison E Berndtson, Todd Costantini, Elliott R Haut Mar 2023

Approaches For Optimizing Venous Thromboembolism Prevention In Injured Patients: Findings From The Consensus Conference To Implement Optimal Venous Thromboembolism Prophylaxis In Trauma, Allison E Berndtson, Todd Costantini, Elliott R Haut

Faculty, Staff and Student Publications

Venous thromboembolism (VTE) is a major issue in trauma patients. Without prophylaxis, the rate of deep venous thrombosis approaches 60% and even with chemoprophylaxis may be nearly 30%. Advances in VTE reduction are imperative to reduce the burden of this issue in the trauma population. Novel approaches in VTE prevention may include new medications, dosing regimens, and extending prophylaxis to the postdischarge phase of care. Standard dosing regimens of low-molecular-weight heparin are insufficient in trauma, shifting our focus toward alternative dosing strategies to improve prophylaxis. Mixed data suggest that anti-Xa-guided dosage, weight-based dosing, and thromboelastography are among these potential strategies. …


Ninety-Day Mortality Following Transoral Robotic Surgery Or Radiation At Commission On Cancer-Accredited Facilities, Jeffrey M Switchenko, Ashley J Schlafstein, Conor E Steuer, Jill S Remick, Soumon Rudra, Mark W Mcdonald, Nabil F Saba, William A Stokes, Mihir R Patel, James E Bates Mar 2023

Ninety-Day Mortality Following Transoral Robotic Surgery Or Radiation At Commission On Cancer-Accredited Facilities, Jeffrey M Switchenko, Ashley J Schlafstein, Conor E Steuer, Jill S Remick, Soumon Rudra, Mark W Mcdonald, Nabil F Saba, William A Stokes, Mihir R Patel, James E Bates

Faculty, Staff and Student Publications

BACKGROUND: Postoperative mortality for oropharynx squamous cell carcinoma (OPSCC) with transoral robotic surgery (TORS) varies from 0.2% to 6.5% on trials; the real-world rate is unknown.

METHODS: NCDB study from 2010 to 2017 for patients with cT1-2N0-2M0 OPSCC with Charleson-Deyo score 0-1. Ninety-day mortality assessed from start and end of treatment at Commission on Cancer-accredited facilities.

RESULTS: 3639 patients were treated with TORS and 1937 with radiotherapy. TORS cohort had more women and higher income, was younger, more often treated at academic centers, and more likely to have private insurance (all p < 0.05). Ninety-day mortality was 1.3% with TORS and 0.7% or 1.4% from start or end of radiotherapy, respectively. From end of therapy, there was no significant difference on MVA between treatment modality.

CONCLUSIONS: There is minimal difference between 90-day mortality …


Impact Of Time To Treatment On Endovascular Thrombectomy Outcomes In The Early Versus Late Treatment Time Windows, David Z Rose, Nils Mueller-Kronast, Nicole B Sur, Chuanhui Dong, Gillian Gordon Perue, Marissa Lepain, Sebastian Koch, Nastajjia Krementz, Erika Marulanda-Londoño, Ricardo Hanel, Brijesh Mehta, Dileep R Yavagal, Tatjana Rundek, Ralph L Sacco, Jose G Romano Mar 2023

Impact Of Time To Treatment On Endovascular Thrombectomy Outcomes In The Early Versus Late Treatment Time Windows, David Z Rose, Nils Mueller-Kronast, Nicole B Sur, Chuanhui Dong, Gillian Gordon Perue, Marissa Lepain, Sebastian Koch, Nastajjia Krementz, Erika Marulanda-Londoño, Ricardo Hanel, Brijesh Mehta, Dileep R Yavagal, Tatjana Rundek, Ralph L Sacco, Jose G Romano

Faculty, Staff and Student Publications

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows.

METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and …


Singlet Oxygen Quenching By Resveratrol Derivatives, Jin Hyeok Yoon Mar 2023

Singlet Oxygen Quenching By Resveratrol Derivatives, Jin Hyeok Yoon

Faculty, Staff and Student Publications

We investigated the singlet oxygen quenching ability of several derivatives of trans-resveratrol which have been reported to have significant antioxidant ability, including photoprotective activity. We measured the total rate constants of singlet oxygen removal (kT) by the methylated resveratrol derivative 1,3-dimethoxy-5-[(E)-2-(4-methoxyphenyl)ethenyl]benzene, and the partially methylated resveratrol derivatives 4-((E)-2-(3,5-dimethoxyphenyl)ethenyl)phenol (pterostilbene), 5-[(E)-2-(4-methoxyphenyl)ethenyl]benzene-1,3-diol and (2R,3R)-3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)-2,3-dihydrochromen-4-one (dihydromyricetin). A protic solvent system results in higher kT values, except for the completely methylated derivative. We also investigated the ability of trans-resveratrol to directly act as a photosensitizer (rather than via secondary photoproducts resulting from other primary photochemical …


Tubers Affecting The Fusiform Face Area Are Associated With Autism Diagnosis, Arina Ovchinnikova, Hope Northrup, Joyce Y Wu, Simon K Warfield, Jurriaan M Peters, Michael D Fox, Acern Study Group Mar 2023

Tubers Affecting The Fusiform Face Area Are Associated With Autism Diagnosis, Arina Ovchinnikova, Hope Northrup, Joyce Y Wu, Simon K Warfield, Jurriaan M Peters, Michael D Fox, Acern Study Group

Faculty, Staff and Student Publications

OBJECTIVE: Tuberous sclerosis complex (TSC) is associated with focal brain "tubers" and a high incidence of autism spectrum disorder (ASD). The location of brain tubers associated with autism may provide insight into the neuroanatomical substrate of ASD symptoms.

METHODS: We delineated tuber locations for 115 TSC participants with ASD (n = 31) and without ASD (n = 84) from the Tuberous Sclerosis Complex Autism Center of Excellence Research Network. We tested for associations between ASD diagnosis and tuber burden within the whole brain, specific lobes, and at 8 regions of interest derived from the ASD neuroimaging literature, including the anterior …


Epstein-Barr Virus-Associated Lymphoepithelial Carcinoma Arising In The Parotid Gland: A Case Report And Literature Review, Tomomi Yamaguchi-Ishochi Mar 2023

Epstein-Barr Virus-Associated Lymphoepithelial Carcinoma Arising In The Parotid Gland: A Case Report And Literature Review, Tomomi Yamaguchi-Ishochi

Faculty, Staff and Student Publications

A 60-year-old woman presented with a 3-year history of a slow-growing, painless mass in their left parotid gland. Ultrasonography revealed a well-circumscribed, lobulated, hypoechoic mass measuring 19x12x10 mm in the left parotid gland. Computed tomography revealed a well-circumscribed, solid mass with homogeneous enhancement. Fluorodeoxyglucose-positron emission tomography revealed uptake by the tumor but no uptake in other organs, including the nasopharynx. The patient underwent superficial parotidectomy with adequate safety margins and selective neck dissection followed by radiotherapy. No facial paralysis or recurrence of the tumor had been observed as of 20 months post-operation. Histologically, the tumor was composed of sheets of …


A National, Electronic Health Record-Based Study Of Perinatal Hemorrhagic And Ischemic Stroke, Alicia Zha Mar 2023

A National, Electronic Health Record-Based Study Of Perinatal Hemorrhagic And Ischemic Stroke, Alicia Zha

Faculty, Staff and Student Publications

BACKGROUND: Perinatal stroke occurs in approximately 1 in 1100 live births. Large electronic health record (EHR) data can provide information on exposures associated with perinatal stroke in a larger number of patients than is achievable through traditional clinical studies. The objective of this study is to assess prevalence and odds ratios of known and theorized comorbidities with perinatal ischemic and hemorrhagic stroke.

METHODS: The data for patients aged 0-28 days with a diagnosis of either ischemic or hemorrhagic stroke were extracted from the Cerner Health Facts Electronic Medical Record (EMR) database. Incidence of birth demographics and perinatal complications were recorded. …


Temporal Stability Of The Hemodynamic Response Function Across The Majority Of Human Cerebral Cortex, Madhukar H Trivedi Mar 2023

Temporal Stability Of The Hemodynamic Response Function Across The Majority Of Human Cerebral Cortex, Madhukar H Trivedi

Faculty, Staff and Student Publications

BACKGROUND: Artificial intelligence is currently being used to facilitate early disease detection, better understand disease progression, optimize medication/treatment dosages, and uncover promising novel treatments and potential outcomes.

METHODS: Utilizing the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) dataset, we built a machine learning model to predict depression remission rates using same clinical data as features for each of the first three antidepressant treatment steps in STAR*D. We only used early treatment data (baseline and first follow up) in each STAR*D step to temporally analyze predictive features of remission at the end of the step.

RESULTS: Our model showed significant prediction …


Gender-Associated Cardiometabolic Risk Profiles And Health Behaviors In Patients With Type 2 Diabetes: A Cross-Sectional Analysis Of The Joint Asia Diabetes Evaluation (Jade) Program, Vanessa Lau, K H Yoon, Alexander T B Tan, Yook-Chin Chia, Aravind Sosale, Banshi D Saboo, Jothydev Kesavadev, Su-Yen Goh, Thy Khue Nguyen, Yotsapon Thewjitcharoen, Raymond Suwita, Ronald C W Ma, Elaine Y K Chow, Andrea O Y Luk, Juliana C N Chan Mar 2023

Gender-Associated Cardiometabolic Risk Profiles And Health Behaviors In Patients With Type 2 Diabetes: A Cross-Sectional Analysis Of The Joint Asia Diabetes Evaluation (Jade) Program, Vanessa Lau, K H Yoon, Alexander T B Tan, Yook-Chin Chia, Aravind Sosale, Banshi D Saboo, Jothydev Kesavadev, Su-Yen Goh, Thy Khue Nguyen, Yotsapon Thewjitcharoen, Raymond Suwita, Ronald C W Ma, Elaine Y K Chow, Andrea O Y Luk, Juliana C N Chan

Faculty, Staff and Student Publications

Background

In Asia, diabetes-associated death due to cardiorenal diseases were 2–3 times higher in women than men which might be due to gender disparity in quality of care and health habits.

Methods

Adults with type 2 diabetes (T2D) from 11 Asian countries/areas were assessed using the same protocol (2007–2015). We compared treatment target attainment (HbA1c < 7%, blood pressure [BP] < 130/80 mmHg, risk-based LDL-cholesterol, lack of central obesity [waist circumference <90 cm in men or <80 cm in women), use of cardiorenal-protective drugs (renin-angiotensin system [RAS] inhibitors, statins), and self-reported health habits including self-monitoring blood glucose (SMBG) by gender. Analyses were stratified by countries/areas, age of natural menopause (<50 vs. ≥50 years), and comorbidities (atherosclerotic cardiovascular disease [ASCVD], heart failure, kidney impairment [eGFR < 60 mL/min/1.73 m2]).

Findings

Among 106,376 patients (53.2% men; median (interquartile range) diabetes duration: 6.0 (2.0–12.0) years; mean ± SD HbA1c 8.0 ± 1.9%; 27% insulin-treated), women were older and …


Building The Foundation For A Community-Generated National Research Blueprint For Inherited Bleeding Disorders: Research Priorities To Transform The Care Of People With Hemophilia, Amy L Dunn, James Jorgenson, Scott D Martin, Suzanne Martin, Shannon L Meeks, Alfredo A Narvaez, Doris V Quon, Mark T Reding, Ulrike M Reiss, Brittany Savage, Kim Schafer, Bruno Steiner, Courtney Thornburg, Lena M Volland, Annette Von Drygalski Mar 2023

Building The Foundation For A Community-Generated National Research Blueprint For Inherited Bleeding Disorders: Research Priorities To Transform The Care Of People With Hemophilia, Amy L Dunn, James Jorgenson, Scott D Martin, Suzanne Martin, Shannon L Meeks, Alfredo A Narvaez, Doris V Quon, Mark T Reding, Ulrike M Reiss, Brittany Savage, Kim Schafer, Bruno Steiner, Courtney Thornburg, Lena M Volland, Annette Von Drygalski

Faculty, Staff and Student Publications

BACKGROUND: Decades of research have transformed hemophilia from severely limiting children's lives to a manageable disorder compatible with a full, active life, for many in high-income countries. The direction of future research will determine whether exciting developments truly advance health equity for all people with hemophilia (PWH). National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive inclusive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them.

RESEARCH DESIGN AND METHODS: Working group (WG) 1 of the NHF State of the Science Research Summit distilled the community-identified priorities for …


Patterns Of Co-Occurring Birth Defects In Children With Anotia And Microtia, Daryl A Scott, Christian P Schaaf, Joseph W Ray, Han Chen, A J Agopian, Philip J Lupo Mar 2023

Patterns Of Co-Occurring Birth Defects In Children With Anotia And Microtia, Daryl A Scott, Christian P Schaaf, Joseph W Ray, Han Chen, A J Agopian, Philip J Lupo

Faculty, Staff and Student Publications

Many infants with anotia or microtia (A/M) have co-occurring birth defects, although few receive syndromic diagnoses in the perinatal period. Evaluation of co-occurring birth defects in children with A/M could identify patterns indicative of undiagnosed/unrecognized syndromes. We obtained information on co-occurring birth defects among infants with A/M for delivery years 1999-2014 from the Texas Birth Defects Registry. We calculated observed-to-expected ratios (OER) to identify birth defect combinations that occurred more often than expected by chance. We excluded children diagnosed with genetic or chromosomal syndromes from analyses. Birth defects and syndromes/associations diagnosed ≤1 year of age were considered. We identified 1310 …


Pyroptosis In Neutrophils: Multimodal Integration Of Inflammasome And Regulated Cell Death Signaling Pathways Mar 2023

Pyroptosis In Neutrophils: Multimodal Integration Of Inflammasome And Regulated Cell Death Signaling Pathways

Faculty, Staff and Student Publications

Pyroptosis is a proinflammatory mode of lytic cell death mediated by accumulation of plasma membrane (PM) macropores composed of gasdermin-family (GSDM) proteins. It facilitates two major functions in innate immunity: (i) elimination of intracellular replicative niches for pathogenic bacteria; and (ii) non-classical secretion of IL-1 family cytokines that amplify host-beneficial inflammatory responses to microbial infection or tissue damage. Physiological roles for gasdermin D (GSDMD) in pyroptosis and IL-1β release during inflammasome signaling have been extensively characterized in macrophages. This involves cleavage of GSDMD by caspase-1 to generate GSDMD macropores that mediate IL-1β efflux and progression to pyroptotic lysis. Neutrophils, which …


Volume Of Subcortical Brain Regions In Social Anxiety Disorder: Mega-Analytic Results From 37 Samples In The Enigma-Anxiety Working Group, Laura S Van Velzen, Ramiro Salas, Andrea P Jackowski, Pedro M Pan, Giovanni A Salum, James R Blair, Karina S Blair, Joy Hirsch, Spiro P Pantazatos, Franklin R Schneier, Ardesheer Talati, Karin Roelofs, Inge Volman, Laura Blanco-Hinojo, Narcís Cardoner, Jesus Pujol, Katja Beesdo-Baum, Christopher R K Ching, Sophia I Thomopoulos, Andreas Jansen, Tilo Kircher, Axel Krug, Igor Nenadić, Frederike Stein, Udo Dannlowski, Dominik Grotegerd, Hannah Lemke, Susanne Meinert, Alexandra Winter, Michael Erb, Benjamin Kreifelts, Qiyong Gong, Su Lui, Fei Zhu, Benson Mwangi, Jair C Soares, Mon-Ju Wu, Ali Bayram, Mesut Canli, Raşit Tükel, P Michiel Westenberg, Alexandre Heeren, Henk R Cremers, David Hofmann, Thomas Straube, Alexander G G Doruyter, Christine Lochner, Jutta Peterburs, Marie-José Van Tol, Raquel E Gur, Antonia N Kaczkurkin, Bart Larsen, Theodore D Satterthwaite, Courtney A Filippi, Andrea L Gold, Anita Harrewijn, André Zugman, Robin Bülow, Hans J Grabe, Henry Völzke, Katharina Wittfeld, Joscha Böhnlein, Katharina Dohm, Harald Kugel, Elisabeth Schrammen, Peter Zwanzger, Elisabeth J Leehr, Lisa Sindermann, Tali M Ball, Gregory A Fonzo, Martin P Paulus, Alan Simmons, Murray B Stein, Heide Klumpp, K Luan Phan, Tomas Furmark, Kristoffer N T Månsson, Amirhossein Manzouri, Suzanne N Avery, Jennifer Urbano Blackford, Jacqueline A Clauss, Brandee Feola, Jennifer C Harper, Chad M Sylvester, Ulrike Lueken, Dick J Veltman, Anderson M Winkler, Neda Jahanshad, Daniel S Pine, Paul M Thompson, Dan J Stein, Nic J A Van Der Wee Mar 2023

Volume Of Subcortical Brain Regions In Social Anxiety Disorder: Mega-Analytic Results From 37 Samples In The Enigma-Anxiety Working Group, Laura S Van Velzen, Ramiro Salas, Andrea P Jackowski, Pedro M Pan, Giovanni A Salum, James R Blair, Karina S Blair, Joy Hirsch, Spiro P Pantazatos, Franklin R Schneier, Ardesheer Talati, Karin Roelofs, Inge Volman, Laura Blanco-Hinojo, Narcís Cardoner, Jesus Pujol, Katja Beesdo-Baum, Christopher R K Ching, Sophia I Thomopoulos, Andreas Jansen, Tilo Kircher, Axel Krug, Igor Nenadić, Frederike Stein, Udo Dannlowski, Dominik Grotegerd, Hannah Lemke, Susanne Meinert, Alexandra Winter, Michael Erb, Benjamin Kreifelts, Qiyong Gong, Su Lui, Fei Zhu, Benson Mwangi, Jair C Soares, Mon-Ju Wu, Ali Bayram, Mesut Canli, Raşit Tükel, P Michiel Westenberg, Alexandre Heeren, Henk R Cremers, David Hofmann, Thomas Straube, Alexander G G Doruyter, Christine Lochner, Jutta Peterburs, Marie-José Van Tol, Raquel E Gur, Antonia N Kaczkurkin, Bart Larsen, Theodore D Satterthwaite, Courtney A Filippi, Andrea L Gold, Anita Harrewijn, André Zugman, Robin Bülow, Hans J Grabe, Henry Völzke, Katharina Wittfeld, Joscha Böhnlein, Katharina Dohm, Harald Kugel, Elisabeth Schrammen, Peter Zwanzger, Elisabeth J Leehr, Lisa Sindermann, Tali M Ball, Gregory A Fonzo, Martin P Paulus, Alan Simmons, Murray B Stein, Heide Klumpp, K Luan Phan, Tomas Furmark, Kristoffer N T Månsson, Amirhossein Manzouri, Suzanne N Avery, Jennifer Urbano Blackford, Jacqueline A Clauss, Brandee Feola, Jennifer C Harper, Chad M Sylvester, Ulrike Lueken, Dick J Veltman, Anderson M Winkler, Neda Jahanshad, Daniel S Pine, Paul M Thompson, Dan J Stein, Nic J A Van Der Wee

Faculty, Staff and Student Publications

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven …


2023-03-01 Miss Seattle Contestant Lauren Sturgill Highlights Inner Beauty, Madden Armstrong Mar 2023

2023-03-01 Miss Seattle Contestant Lauren Sturgill Highlights Inner Beauty, Madden Armstrong

The Spectator Online

No abstract provided.