Digital Commons Network^™

Draft Genome Sequences For A Staphylococcus Aureus And A Staphylococcus Haemolyticus Isolate From Nasal Swab Samples From Healthy Females, Sandra Jablonska, Hannah Brown, Helen Appleberry, Catherine Putonti, Alex Kula

Biology: Faculty Publications and Other Works

Staphylococcus aureus and Staphylococcus haemolyticus are common members of the human microbiota, but they are also opportunistic pathogens. To identify antibiotic resistance in healthy individuals, we present the genome sequences of S. aureus 139 N-1 and S. haemolyticus 173 N-3, both isolated from nasal swab samples from asymptomatic female participants.

Insights Into Personalized Care Strategies For Wilms Tumor: A Narrative Literature Review, Salma Karam, Ahmad Gebreil, Ahmed Alksas, Hossam Magdy Balaha, Ashraf Khalil, Mohammed Ghazal, Sohail Contractor, Ayman El-Baz

All Works

Wilms tumor (WT), or nephroblastoma, is the predominant renal malignancy in the pediatric population. This narrative review explores the evolution of personalized care strategies for WT, synthesizing critical developments in molecular diagnostics and treatment approaches to enhance patient-specific outcomes. We surveyed recent literature from the last five years, focusing on high-impact research across major databases such as PubMed, Scopus, and Web of Science. Diagnostic advancements, including liquid biopsies and diffusion-weighted MRI, have improved early detection precision. The prognostic significance of genetic markers, particularly WT1 mutations and miRNA profiles, is discussed. Novel predictive tools integrating genetic and clinical data to anticipate …

Archeota Spring/ Summer 2024, Emily Mizokami, Ali Phelps, Celina Lozano, Araceli Argueta, Chelsey Abbott, Danielle Bonsignore, Sarah Lewis

Archeota

Archeota is a platform for SJSU iSchool students to contribute to the archival conversation. It is written BY students, FOR students. It provides substantive content on archival concerns and issues and promotes professional development in the field of archival studies. Archeota upholds the core values of the archival profession.

Contents:

Reslience and Pride at the LLACE by Emily Mizokami

Black Americana at the Museum of Ventura County by Ali Phelps

Interview with Archivist Maria Carillo Colato by Celina Lozano

Gabriel Vidal's Central American Music Archive by Araceli Argueta

Preserving Peanuts by Danielle Bonsignore

Interference Archives by Chelsey Abbott

Preservation Workshop …

Radiation Dose Attenuation Using Radpad In Cath Lab For Primary And Secondary Operators – Radar-Cath Study, Sandeepan Saha, Aditya Kapoor, Kamlesh Raut, Arpita Katheria, Harshit Khare, Ankit Sahu, Roopali Khanna, Sudeep Kumar, Naveen Garg, Satyendra Tewari

Faculty, Staff and Student Publications

BACKGROUND: Radiation injury is an important concern for interventional cardiologists and needs to be addressed. RADPAD is a radiation protection drape that has been shown to reduce the radiation exposure of the primary operator (PO). While Indian data on radiation exposure of the PO in the cath lab are scarce, the exposure of the secondary operator (SO) is even less well studied.

AIMS: The aim of this study was to evaluate the efficacy of RADPAD drapes in reducing radiation doses in the cath lab for the primary as well as the secondary operator.

METHODS: A total of 160 patients (40 …

Eus-Guided Hydrogel Injection To Separate Pancreatic Head Carcinoma From Duodenum For Enhanced Radiotherapy: Multi-Site Feasibility Study, Manoop S Bhutani, Amol K Narang, Kai Ding, Brenna Casey, Kumar Krishnan, Eugene J Koay, Theodore S Hong, Joseph M Herman, Kristen H Griffin, Eun Ji Shin

Faculty, Staff and Student Publications

Background and study aims The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum.

Patients and methods In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas. Procedure characteristics were recorded, including hydrogel volume and space created. Patients were monitored for adverse events (AEs) and radiotherapy toxicity.

Results …

Sequencing Of Kaposi’S Sarcoma Herpesvirus (Kshv) Genomes From Persons Of Diverse Ethnicities And Provenances With Kshv-Associated Diseases Demonstrate Multiple Infections, Novel Polymorphisms, And Low Intra-Host Variance, Vickie A Marshall, Elena M Cornejo Castro, Charles A Goodman, Nazzarena Labo, Isabella Liu, Nicholas C Fisher, Kyle N Moore, Ananthakrishnan Nair, Taina Immonen, Brandon F Keele, Mark N Polizzotto, Thomas S Uldrick, Yunxiang Mu, Tanuja Saswat, Laurie T Krug, Kevin M Mcbride, Kathryn Lurain, Ramya Ramaswami, Robert Yarchoan, Denise Whitby

Faculty, Staff and Student Publications

Recently published near full-length KSHV genomes from a Cameroon Kaposi sarcoma case-control study showed strong evidence of viral recombination and mixed infections, but no sequence variations associated with disease. Using the same methodology, an additional 102 KSHV genomes from 76 individuals with KSHV-associated diseases have been sequenced. Diagnoses comprise all KSHV-associated diseases (KAD): Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated large cell lymphoma (KSHV-LCL), a type of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). Participants originated from 22 different countries, providing the opportunity to obtain new near full-length sequences of a wide diversity of KSHV genomes. …

Ccr2+ Monocytes Promote White Matter Injury And Cognitive Dysfunction After Myocardial Infarction, Edward B Thorp, Mallory Filipp, Maria Dima, Chunfeng Tan, Matthew Feinstein, Brian Popko, Matthew Deberge

Faculty, Staff and Student Publications

Survivors of myocardial infarction are at increased risk for vascular dementia. Neuroinflammation has been implicated in the pathogenesis of vascular dementia, yet little is known about the cellular and molecular mediators of neuroinflammation after myocardial infarction. Using a mouse model of myocardial infarction coupled with flow cytometric analyses and immunohistochemistry, we discovered increased monocyte abundance in the brain after myocardial infarction, which was associated with increases in brain-resident perivascular macrophages and microglia. Myeloid cell recruitment and activation was also observed in post-mortem brains of humans that died after myocardial infarction. Spatial and single cell transcriptomic profiling of brain-resident myeloid cells …

The Time-Dependent Association Between Irritable Bowel Syndrome And All-Cause And Cause-Specific Mortality: A Prospective Cohort Study Within The Uk Biobank, Fangyu Li, Yukiko Yano, Lola Étiévant, Carrie R Daniel, Shreela V Sharma, Eric L Brown, Ruosha Li, Erikka Loftfield, Qing Lan, Rashmi Sinha, Baharak Moshiree, Maki Inoue-Choi, Emily Vogtmann

Faculty, Staff and Student Publications

Introduction: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, but few studies have evaluated mortality risks among individuals with IBS. We explored the association between IBS and all-cause and cause-specific mortality in the UK Biobank.

Methods: We included 502,369 participants from the UK Biobank with mortality data through 2022. IBS was defined using baseline self-report and linkage to primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality using multivariable Cox proportional hazards regression models within partitioned follow-up time categories (0-5, >5-10, and >10 …

Reproducibility Of Quantitative Myocardial Perfusion And Coronary Flow Capacity By Positron Emission Tomography: 3d Digital Silicon Photomultiplier Solid State Vs Legacy 2d Analogue Systems For Clinical Practice And Trials, Amanda Roby, Lindsey Harmon, Kelly Sander, Linh Bui, Danai Kitkungvan, Monica Patel, Jagat Narula, Nils P Johnson, K Lance Gould

Faculty, Staff and Student Publications

Aims: Quantitative rest-stress myocardial perfusion in millilitres per minute per gram among multiple 2D and 3D positron emission tomography-computed tomography (PET-CT) scanners is essential for personalized cardiac management and clinical trials. Accordingly, this study reports the accuracy and precision of quantitative rest-stress millilitres per minute per gram and coronary flow capacity among 2D and two different digital 3D silicon photomultiplier (SiPM) PET-CT scanners for quantifying the severity of coronary pathophysiology for clinical trials or guiding interventions vs. medical treatment.

Methods and results: One hundred seventy-one participants underwent 748 paired serial rest or stress PET perfusion imaging in the same person …

Use Of Ipsc-Derived Smooth Muscle Cells To Model Physiology And Pathology, Callie S Kwartler, Jose Emiliano Esparza Pinelo

Faculty, Staff and Student Publications

The implementation of human induced pluripotent stem cell (hiPSC) models has introduced an additional tool for identifying molecular mechanisms of disease that complement animal models. Patient-derived or CRISPR/Cas9-edited induced pluripotent stem cells differentiated into smooth muscle cells (SMCs) have been leveraged to discover novel mechanisms, screen potential therapeutic strategies, and model in vivo development. The field has evolved over almost 15 years of research using hiPSC-SMCs and has made significant strides toward overcoming initial challenges such as the lineage specificity of SMC phenotypes. However, challenges both specific (eg, the lack of specific markers to thoroughly validate hiPSC-SMCs) and general (eg, …

Expanded-Access Use Of Elamipretide In A Patient With Membrane Protein-Associated Neurodegeneration, Jorge Patino, Anna Haertling Clearman, Lindsey Miller, Mary Kay Koenig

Faculty, Staff and Student Publications

This case report presents a progressively declining 17-year-old patient with membrane protein-associated neurodegeneration who demonstrated symptomatic improvements in her dysarthria, dysphagia, and gait, and objective improvements in her 6-minute walk test and 5 times sit-to-stand test during elamipretide treatment.

Behavioral Therapies Targeting Reward Mechanisms In Substance Use Disorders, Margaret C Wardle, Heather E Webber, Jin H Yoon, Angela M Heads, Angela L Stotts, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

Behavioral therapies are considered best practices in the treatment of substance use disorders (SUD) and used as first-line approaches for SUDs without FDA-approved pharmacotherapies. Decades of research on the neuroscience of drug reward and addiction have informed the development of current leading behavioral therapies that, while differing in focus and technique, have in common the overarching goal of shifting reward responding away from drug and toward natural non-drug rewards. This review begins by describing key neurobiological processes of reward in addiction, followed by a description of how various behavioral therapies address specific reward processes. Based on this review, a conceptual …

Mitochondrial Health, Physical Functioning, And Daily Affect: Bioenergetic Mechanisms Of Dementia Caregiver Well-Being, E Lydia Wu-Chung, Luis D Medina, Jensine Paoletti-Hatcher, Vincent Lai, Jennifer M Stinson, Itee Mahant, Paul E Schulz, Cobi J Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Objective: Chronic stress adversely affects mental and physical well-being. However, health outcomes vary among people experiencing the same stressor. Individual differences in physical and emotional well-being may depend on mitochondrial biology, as energy production is crucial for stress regulation. This study investigated whether mitochondrial respiratory capacity corresponds to individual differences in dementia spousal caregivers' mental and physical health.

Methods: Spousal caregivers of individuals with Alzheimer's disease and related dementias ( N = 102, mean age = 71, 78% female, 83% White) provided peripheral blood samples and completed self-report questionnaires on quality of life, caregiver burden, and a 7-day affect scale. …

A Bayesian Latent-Subgroup Platform Design For Dose Optimization, Rongji Mu, Xiaojiang Zhan, Rui Sammi Tang, Ying Yuan

Faculty, Staff and Student Publications

The US Food and Drug Administration launched Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development, calling for the paradigm shift from finding the maximum tolerated dose to the identification of optimal biological dose (OBD). Motivated by a real-world drug development program, we propose a master-protocol-based platform trial design to simultaneously identify OBDs of a new drug, combined with standards of care or other novel agents, in multiple indications. We propose a Bayesian latent subgroup model to accommodate the treatment heterogeneity across indications, and employ Bayesian hierarchical models to borrow information within subgroups. At …

Response-Adapted Ultra-Low-Dose 4 Gy Radiation As Definitive Therapy Of Gastric Malt Lymphoma: A Single-Centre, Pilot Trial, Jillian R Gunther, Jie Xu, Manoop S Bhutani, Paolo Strati, Penny Q Fang, Susan Y Wu, Bouthaina S Dabaja, Wenli Dong, Priya R Bhosale, Christopher R Flowers, Ranjit Nair, Luis Malpica Castillo, Luis Fayad, Swaminathan P Iyer, Simrit Parmer, Michael Wang, Hun Ju Lee, Felipe Samaniego, Jason Westin, Sairah Ahmed, Chijioke C Nze, Preetesh Jain, Sattva S Neelapu, Maria A Rodriguez, Dai Chihara, Loretta J Nastoupil, Chelsea C Pinnix

Faculty, Staff and Student Publications

Background: Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach.

Methods: We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total …

Identification Of A Clinically Efficacious Car T Cell Subset In Diffuse Large B Cell Lymphoma By Dynamic Multidimensional Single-Cell Profiling, Ali Rezvan, Gabrielle Romain, Mohsen Fathi, Darren Heeke, Melisa Martinez-Paniagua, Xingyue An, Irfan N Bandey, Melisa J Montalvo, Jay R T Adolacion, Arash Saeedi, Fatemeh Sadeghi, Kristen Fousek, Nahum Puebla-Osorio, Laurence J N Cooper, Chantale Bernatchez, Harjeet Singh, Nabil Ahmed, Mike Mattie, Adrian Bot, Sattva Neelapu, Navin Varadarajan

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) T cells used for the treatment of B cell malignancies can identify T cell subsets with superior clinical activity. Here, using infusion products of individuals with large B cell lymphoma, we integrated functional profiling using timelapse imaging microscopy in nanowell grids with subcellular profiling and single-cell RNA sequencing to identify a signature of multifunctional CD8+ T cells (CD8-fit T cells). CD8-fit T cells are capable of migration and serial killing and harbor balanced mitochondrial and lysosomal volumes. Using independent datasets, we validate that CD8-fit T cells (1) are present premanufacture and are associated with clinical responses …

Molecular Characterization Of Metastatic Oncocytoma With Exceptional Response To Treatment: A Case Report, Bradley R Webster, Christopher J Ricketts, Cathy D Vocke, Dionna Gamble, Daniel R Crooks, Ye Yang, Lindsay Friedman, Antoun Toubaji, Pavlos Msaouel, Jonathan M Hernandez, W Marston Linehan, Mark W Ball

Faculty, Staff and Student Publications

Comprehensive molecular characterization and effective therapy in a rare case of metastatic renal oncocytoma.

Impact Of Apolipoprotein E Genotype On Neurocognitive Function In Patients With Brain Metastases: An Analysis Of Nrg Oncology's Rtog 0614, Jeffrey S Wefel, Snehal Deshmukh, Paul D Brown, David R Grosshans, Erik P Sulman, Jane H Cerhan, Minesh P Mehta, Deepak Khuntia, Wenyin Shi, Mark V Mishra, John H Suh, Nadia N Laack, Yuhchyau Chen, Amarinthia Amy Curtis, Joanna M Laba, Ahmed Elsayed, Anu Thakrar, Stephanie L Pugh, Deborah W Bruner

Faculty, Staff and Student Publications

Purpose: Whole-brain radiation therapy (WBRT) is a common treatment for brain metastases and is frequently associated with decline in neurocognitive functioning (NCF). The e4 allele of the apolipoprotein E (APOE) gene is associated with increased risk of Alzheimer disease and NCF decline associated with a variety of neurologic diseases and insults. APOE carrier status has not been evaluated as a risk factor for onset time or extent of NCF impairment in patients with brain metastases treated with WBRT.

Methods and materials: NRG/Radiation Therapy Oncology Group 0614 treated adult patients with brain metastases with 37.5 Gy of WBRT (+/- memantine), performed …

Technical Note: Radiological Clinical Equivalence For Phantom Materials In Carbon Ion Therapy, Paige A Taylor, Alfredo Mirandola, Mario Ciocca, Shannon Hartzell, Alessandro Vai, Paola Alvarez, Rebecca M Howell, Eugene J Koay, Christopher R Peeler, Christine B Peterson, Stephen F Kry

Faculty, Staff and Student Publications

Purpose: As carbon ion radiotherapy increases in use, there are limited phantom materials for heterogeneous or anthropomorphic phantom measurements. This work characterized the radiological clinical equivalence of several phantom materials in a therapeutic carbon ion beam.

Methods: Eight materials were tested for radiological material-equivalence in a carbon ion beam. The materials were computed tomography (CT)-scanned to obtain Hounsfield unit (HU) values, then irradiated in a monoenergetic carbon ion beam to determine relative linear stopping power (RLSP). The corresponding HU and RLSP for each phantom material were compared to clinical carbon ion calibration curves. For absorbed dose comparison, ion chamber measurements …

Cholesterol-Dependent Lxr Transcription Factor Activity Represses Pronociceptive Effects Of Estrogen In Sensory Neurons And Pain Induced By Myelin Basic Protein Fragments, Swathi K Hullugundi, Jennifer Dolkas, Andrei V Chernov, Tony L Yaksh, Kelly A Eddinger, Mila Angert, Glaucilene Ferreira Catroli, Alex Y Strongin, Patrick M Dougherty, Yan Li, Oswal Quehenberger, Aaron Armando, Veronica I Shubayev

Faculty, Staff and Student Publications

Background: A bioactive myelin basic protein (MBP) fragment, comprising MBP84-104, is released in sciatic nerve after chronic constriction injury (CCI). Intraneural injection (IN) of MBP84-104 in an intact sciatic nerve is sufficient to induce persistent neuropathic pain-like behavior via robust transcriptional remodeling at the injection site and ipsilateral dorsal root ganglia (DRG) and spinal cord. The sex (female)-specific pronociceptive activity of MBP84-104 associates with sex-specific changes in cholesterol metabolism and activation of estrogen receptor (ESR)1 signaling.

Methods: In male and female normal and post-CCI rat sciatic nerves, we assessed: (i) cholesterol precursor and metabolite levels by lipidomics; (ii) MBP84-104 interactors …

Cancer Incidence After Diagnosis Of Abdominal Aortic Aneurysm-Brief Report, Lingfeng Luo, Allen M Haas, Caitlin F Bell, Richard A Baylis, Shaunak S Adkar, Changhao Fu, Ivan Angelov, Sharon H Giordano, Derek Klarin, Nicholas J Leeper, Kevin T Nead

Faculty, Staff and Student Publications

Background: Epidemiological and mechanistic data support a potential causal link between cardiovascular disease (CVD) and cancer. Abdominal aortic aneurysms (AAAs) represent a common form of CVD with at least partially distinct genetic and biologic pathogenesis from other forms of CVD. The risk of cancer and how this risk differs compared with other forms of CVD, is unknown among AAA patients. We conducted a retrospective cohort study using the IBM MarketScan Research Database to test whether individuals with AAA have a higher cancer risk independent of traditional shared risk factors.

Methods: All individuals ≥18 years of age with ≥36 months of …

Pten Deficiency Induces An Extrahepatic Cholangitis-Cholangiocarcinoma Continuum Via Aurora Kinase A In Mice, Yan Yang, Jiale Wang, Jianhua Wan, Qianqian Cheng, Zenong Cheng, Xueli Zhou, Oliver Wang, Kelvin Shi, Lingxiang Wang, Bin Wang, Xiaohui Zhu, Jiaxiang Chen, Dongfeng Feng, Yang Liu, Yasmin Jahan-Mihan, Ashley N Haddock, Brandy H Edenfield, Guang Peng, Jessica D Hohenstein, Chantal E Mccabe, Daniel R O'Brien, Chen Wang, Sumera I Ilyas, Liuyan Jiang, Michael S Torbenson, Huamin Wang, Raouf E Nakhleh, Xuemei Shi, Ying Wang, Yan Bi, Gregory J Gores, Tushar Patel, Baoan Ji

Faculty, Staff and Student Publications

Background & aims: The PTEN-AKT pathway is frequently altered in extrahepatic cholangiocarcinoma (eCCA). We aimed to evaluate the role of PTEN in the pathogenesis of eCCA and identify novel therapeutic targets for this disease.

Methods: The Pten gene was genetically deleted using the Cre-loxp system in biliary epithelial cells. The pathologies were evaluated both macroscopically and histologically. The characteristics were further analyzed by immunohistochemistry, reverse-transcription PCR, cell culture, and RNA sequencing. Some features were compared to those in human eCCA samples. Further mechanistic studies utilized the conditional knockout of Trp53 and Aurora kinase A (Aurka) genes. We also tested the …

Navigating The Critical Translational Questions For Implementing Flash In The Clinic, Billy W Loo, Ioannis I Verginadis, Brita Singers Sørensen, Anthony E Mascia, John P Perentesis, Albert C Koong, Emil Schüler, Erinn B Rankin, Peter G Maxim, Charles L Limoli, Marie-Catherine Vozenin

Faculty, Staff and Student Publications

The "FLASH effect" is an increased therapeutic index, that is, reduced normal tissue toxicity for a given degree of anti-cancer efficacy, produced by ultra-rapid irradiation delivered on time scales orders of magnitude shorter than currently conventional in the clinic for the same doses. This phenomenon has been observed in numerous preclinical in vivo tumor and normal tissue models. While the underlying biological mechanism(s) remain to be elucidated, a path to clinical implementation of FLASH can be paved by addressing several critical translational questions. Technological questions pertinent to each beam type (eg, electron, proton, photon) also dictate the logical progression of …

The Dynamic Trpv2 Ion Channel Proximity Proteome Reveals Functional Links Of Calcium Flux With Cellular Adhesion Factors Ncam And L1cam In Neurite Outgrowth, Pamela N Gallo, Elaine Mihelc, Robyn Eisert, Gary A Bradshaw, Florian Dimek, Andreas Leffler, Marian Kalocsay, Vera Moiseenkova-Bell

Faculty, Staff and Student Publications

TRPV2 voltage-insensitive, calcium-permeable ion channels play important roles in cancer progression, immune response, and neuronal development. Despite TRPV2's physiological impact, underlying endogenous proteins mediating TRPV2 responses and affected signaling pathways remain elusive. Using quantitative peroxidase-catalyzed (APEX2) proximity proteomics we uncover dynamic changes in the TRPV2-proximal proteome and identify calcium signaling and cell adhesion factors recruited to the molecular channel neighborhood in response to activation. Quantitative TRPV2 proximity proteomics further revealed activation-induced enrichment of protein clusters with biological functions in neural and cellular projection. We demonstrate a functional connection between TRPV2 and the neural immunoglobulin cell adhesion molecules NCAM and L1CAM. …

Intratumoral Injection Of Immunotherapeutics: State Of The Art And Future Directions, Rahul A Sheth, Eric Wehrenberg-Klee, Sapna P Patel, Kristy K Brock, Nicos Fotiadis, Thierry De Baère

Faculty, Staff and Student Publications

Systemic immunotherapies have led to tremendous progress across the cancer landscape. However, several challenges exist, potentially limiting their efficacy in the treatment of solid tumors. Direct intratumoral injection can increase the therapeutic index of immunotherapies while overcoming many of the barriers associated with systemic administration, including limited bioavailability to tumors and potential systemic safety concerns. However, challenges remain, including the lack of standardized approaches for administration, issues relating to effective drug delivery, logistical hurdles, and safety concerns specific to this mode of administration. This article reviews the biologic rationale for the localized injection of immunotherapeutic agents into tumors. It also …

Plasmacytoid Dendritic Cells Control Homeostasis Of Megakaryopoiesis, Florian Gaertner, Hellen Ishikawa-Ankerhold, Susanne Stutte, Wenwen Fu, Jutta Weitz, Anne Dueck, Bhavishya Nelakuditi, Valeria Fumagalli, Dominic Van Den Heuvel, Larissa Belz, Gulnoza Sobirova, Zhe Zhang, Anna Titova, Alejandro Martinez Navarro, Kami Pekayvaz, Michael Lorenz, Louisa Von Baumgarten, Jan Kranich, Tobias Straub, Bastian Popper, Vanessa Zheden, Walter Anton Kaufmann, Chenglong Guo, Guido Piontek, Saskia Von Stillfried, Peter Boor, Marco Colonna, Sebastian Clauß, Christian Schulz, Thomas Brocker, Barbara Walzog, Christoph Scheiermann, William C Aird, Claus Nerlov, Konstantin Stark, Tobias Petzold, Stefan Engelhardt, Michael Sixt, Robert Hauschild, Martina Rudelius, Robert A J Oostendorp, Matteo Iannacone, Matthias Heinig, Steffen Massberg

Faculty, Staff and Student Publications

Platelet homeostasis is essential for vascular integrity and immune defence1,2. Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis) remains unclear3,4. Here we use intravital imaging to track the cellular dynamics of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs) as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver IFNα to the MK niche triggering local on-demand proliferation and maturation of MK progenitors. This pDC-dependent feedback loop is crucial for MK …

Reliable Detection Of Generalized Convulsive Seizures Using An Off-The-Shelf Digital Watch: A Multisite Phase 2 Study, Yash Shashank Vakilna, Xiaojin Li, Jaison S Hampson, Yan Huang, John C Mosher, Yuri Dabaghian, Xi Luo, Blanca Talavera, Sandipan Pati, Masel Todd, Ryan Hays, Charles Akos Szabo, Guo-Qiang Zhang, Samden D Lhatoo

Faculty, Staff and Student Publications

Objective: The aim of this study was to develop a machine learning algorithm using an off-the-shelf digital watch, the Samsung watch (SM-R800), and evaluate its effectiveness for the detection of generalized convulsive seizures (GCS) in persons with epilepsy.

Methods: This multisite epilepsy monitoring unit (EMU) phase 2 study included 36 adult patients. Each patient wore a Samsung watch that contained accelerometer, gyroscope, and photoplethysmographic sensors. Sixty-eight time and frequency domain features were extracted from the sensor data and were used to train a random forest algorithm. A testing framework was developed that would better reflect the EMU setting, consisting of …

A Modular Trial Of Androgen Signaling Inhibitor Combinations Testing A Risk-Adapted Strategy In Patients With Metastatic Castration-Resistant Prostate Cancer, Ana M Aparicio, Rebecca S S Tidwell, Shalini S Yadav, Jiun-Sheng Chen, Miao Zhang, Jingjing Liu, Shuai Guo, Patrick G Pilié, Yao Yu, Xingzhi Song, Haswanth Vundavilli, Sonali Jindal, Keyi Zhu, Paul V Viscuse, Justin M Lebenthal, Andrew W Hahn, Rama Soundararajan, Paul G Corn, Amado Zurita-Saavedra, Sumit K Subudhi, Jianhua Zhang, Wenyi Wang, Chad Huff, Patricia Troncoso, James P Allison, Padmanee Sharma, Christopher J Logothetis

Faculty, Staff and Student Publications

Purpose: To determine the efficacy and safety of risk-adapted combinations of androgen signaling inhibitors and inform disease classifiers for metastatic castration-resistant prostate cancers.

Patients and methods: In a modular, randomized phase II trial, 192 men were treated with 8 weeks of abiraterone acetate, prednisone, and apalutamide (AAPA; module 1) and then allocated to modules 2 or 3 based on satisfactory (≥50% PSA decline from baseline and < 5 circulating tumor cell/7.5 mL) versus unsatisfactory status. Men in the former were randomly assigned to continue AAPA alone (module 2A) or with ipilimumab (module 2B). Men in the latter group had carboplatin + cabazitaxel added to AAPA (module 3). Optional baseline biopsies were subjected to correlative studies.

Results: Median overall survival (from allocation) was 46.4 [95% confidence interval (CI), 39.2-68.2], 41.4 (95% CI, 33.3-49.9), and 18.7 (95% CI, 14.3-26.3) months in modules 2A (n = 64), 2B (n = 64), and …

Student Perceptions Of Integrated Stem Education In A High School Geometry Class, Alyssa Noland

Dissertations

Integrated Science Technology Engineering Mathematics (STEM) education provides students with opportunities to solve integrated real-world problems. Integrated STEM instruction aims to develop 21^st-century skills in students and promote interest in STEM subjects through authentic real-world tasks. Student perceptions can help educators and administrators to understand the benefits and constraints of integrated STEM instruction. This qualitative case study was designed to understand student perceptions of integrated STEM instruction and student perceptions of the value or applications of mathematics. The situated STEM learning and social constructivism theoretical frameworks guided the design of the lessons and methods of the study. High …

Dynamic Metabolic Flux Analysis Amidst Data Variability: Sphingolipid Biosynthesis Case Study In Arabidopsis Thaliana Cell Cultures, Abraham Boluwatife Osinuga

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Sphingolipids are pivotal for plant development and stress responses. Growing interest has been directed towards fully comprehending the regulatory mechanisms of the sphingolipid pathway. In this study, we explore its de novo biosynthesis and homeostasis in Arabidopsis thaliana cell cultures, shedding light on fundamental metabolic mechanisms. Employing ¹⁵N isotope labeling and quantitative dynamic modeling approach, we obtained data with notable variations and developed a regularized and constraint-based Dynamic Metabolic Flux Analysis (r-DMFA) framework to predict metabolic shifts due to enzymatic changes. Our analysis revealed key enzymes such as sphingoid-base hydroxylase (SBH) and long-chain-base kinase …