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Articles 3661 - 3690 of 9452
Full-Text Articles in Medical Specialties
Integration Of Ζ-Deficient Cars Into The Cd3Ζ Gene Conveys Potent Cytotoxicity In T And Nk Cells, Jonas Kath, Clemens Franke, Vanessa Drosdek, Weijie Du, Viktor Glaser, Carla Fuster-Garcia, Maik Stein, Tatiana Zittel, Sarah Schulenberg, Caroline E Porter, Lena Andersch, Annette Künkele, Joshua Alcaniz, Jens Hoffmann, Hinrich Abken, Mohamed Abou-El-Enein, Axel Pruß, Masataka Suzuki, Toni Cathomen, Renata Stripecke, Hans-Dieter Volk, Petra Reinke, Michael Schmueck-Henneresse, Dimitrios L Wagner
Integration Of Ζ-Deficient Cars Into The Cd3Ζ Gene Conveys Potent Cytotoxicity In T And Nk Cells, Jonas Kath, Clemens Franke, Vanessa Drosdek, Weijie Du, Viktor Glaser, Carla Fuster-Garcia, Maik Stein, Tatiana Zittel, Sarah Schulenberg, Caroline E Porter, Lena Andersch, Annette Künkele, Joshua Alcaniz, Jens Hoffmann, Hinrich Abken, Mohamed Abou-El-Enein, Axel Pruß, Masataka Suzuki, Toni Cathomen, Renata Stripecke, Hans-Dieter Volk, Petra Reinke, Michael Schmueck-Henneresse, Dimitrios L Wagner
Faculty, Staff and Students Publications
Chimeric antigen receptor (CAR)-redirected immune cells hold significant therapeutic potential for oncology, autoimmune diseases, transplant medicine, and infections. All approved CAR-T therapies rely on personalized manufacturing using undirected viral gene transfer, which results in nonphysiological regulation of CAR-signaling and limits their accessibility due to logistical challenges, high costs and biosafety requirements. Random gene transfer modalities pose a risk of malignant transformation by insertional mutagenesis. Here, we propose a novel approach utilizing CRISPR-Cas gene editing to redirect T cells and natural killer (NK) cells with CARs. By transferring shorter, truncated CAR-transgenes lacking a main activation domain into the human CD3ζ (CD247) …
Troponin: Think Before Testing, Shakirat Ganiyu, Fatimah Bello, Danielle Stone, Gregory Ruhnke, James Stone
Troponin: Think Before Testing, Shakirat Ganiyu, Fatimah Bello, Danielle Stone, Gregory Ruhnke, James Stone
School of Medicine Publications
This is a high-value care-based quality improvement project that was carried out to decrease inappropriate troponin testing in the emergency department (ED) of a tertiary health institution in the United States with the goal of promoting evidence-based practices, minimizing waste, and enhancing the quality of care.
Stepping Into The Light: Defining Culprit Lesion In Non-St Elevation Myocardial Infarction, Aditya Doni Pradana M.D., M.Sc, Arditya Damarkusuma M.D., M.Med (Clin Epi), Fiha, Hariadi Hariawan M.D., Fiha, Finasim, Dr., Fica, Fascc, Fapsic, Fscai
Stepping Into The Light: Defining Culprit Lesion In Non-St Elevation Myocardial Infarction, Aditya Doni Pradana M.D., M.Sc, Arditya Damarkusuma M.D., M.Med (Clin Epi), Fiha, Hariadi Hariawan M.D., Fiha, Finasim, Dr., Fica, Fascc, Fapsic, Fscai
Journal of the Saudi Heart Association
Identifying the infarct-related artery (IRA) in a non-ST-segment-elevation acute myocardial infarction (NSTEMI) can be very challenging, particularly in a hospital that cannot perform intracoronary imaging due to certain limitations. This is because, by angiography, most patients present with multivessel coronary artery disease (CAD), diffuse disease, or non-significant CAD. We present a case of a 60-year-old female patient presented with substernal chest pain and palpitations of 6 hours duration. The first hospital contacts 12-lead electrocardiogram (ECG) showed ventricular tachycardia (VT) with unstable hemodynamics, after stabilization patient was transported to the catheterization laboratory for immediate percutaneous coronary intervention (PCI). With a clue …
Incidence, Risk Factors And Outcomes Of Acute Kidney Injury In Neonates Undergoing Open-Heart Surgeries: Single Center Experience, Faisal A. Alghamdi, Mohammed A. Bin Mahfooz, Hatim F. Almutairi, Nasser S. Alshaiban, Khaled E. Alotibi, Omar M. Kabbani, Mohamed S. Kabbani
Incidence, Risk Factors And Outcomes Of Acute Kidney Injury In Neonates Undergoing Open-Heart Surgeries: Single Center Experience, Faisal A. Alghamdi, Mohammed A. Bin Mahfooz, Hatim F. Almutairi, Nasser S. Alshaiban, Khaled E. Alotibi, Omar M. Kabbani, Mohamed S. Kabbani
Journal of the Saudi Heart Association
Background: Incidence and outcomes of acute kidney injury (AKI) among neonates who underwent open-heart surgery are not well highlighted in the literature. We aim to assess the incidence, risk factors, and outcome of AKI among neonates undergoing open-heart surgery. Methods: This is a retrospective cohort study between 2016 and 2021 for all neonates requiring open heart surgery. The cases were divided into 2 groups: the AKI (index) group and the non-AKI (control) group. The two groups were statistically compared for risk factors, needs for dialysis, and outcomes. Results: 100 patients fulfilled the inclusion criteria. Among them, 74 (74%) developed AKI, …
What Are The Lessons Learned From A Survivorship Trial During The Pandemic?, Alanna J. Horowitz, Sharneet J. Sandhu, Sherry J. Guo, Gabriel Barreto-D'Silva, Leonardo Barreto-D'Silva, Krishna Gunturu
What Are The Lessons Learned From A Survivorship Trial During The Pandemic?, Alanna J. Horowitz, Sharneet J. Sandhu, Sherry J. Guo, Gabriel Barreto-D'Silva, Leonardo Barreto-D'Silva, Krishna Gunturu
The Lahey Journal
Purpose: The American Cancer Society (ACS) has acknowledged the importance of maintaining a healthy diet and engaging in regular physical activity for cancer survivors. While studies have found that adherence to these guidelines improves long-term quality of life, several studies showed that up to 70% of cancer survivors do not meet the standards. The purpose of this pilot study is to determine the effectiveness of a multi-disciplinary survivorship clinic (MDSC) in helping patients adhere to the ACS survivorship guidelines and its impacts on quality of life (QOL).
Methods: Primary objective of the study is to encourage cancer patients to adhere …
Effects Of A 10-Week Footstrike Transition Programme On Tibial Stress Fracture Probability; A Randomized Controlled Intervention Using Finite Element And Probabilistic Modelling, Jonathan Sinclair, Paul J. Taylor
Effects Of A 10-Week Footstrike Transition Programme On Tibial Stress Fracture Probability; A Randomized Controlled Intervention Using Finite Element And Probabilistic Modelling, Jonathan Sinclair, Paul J. Taylor
Baltic Journal of Health and Physical Activity
Introduction: The aim of this study was to undertake a randomized control trial examining the effects of a 10-week footstrike transition program on tibial stress fracture risk compared to control. Material and methods: Twenty habitual rearfoot strike runners were randomly assigned to either footstrike or control groups. The footstrike group undertook a graduated 10-week program which allowed them to convert their habitual rearfoot strike pattern, whereas the control group maintained their normal training regime without any alterations to their strike pattern. Running biomechanics were collected using an eight-camera motion capture system, and ground reaction forces using a force plate. Tibial …
Editorial For "Parallel Cnn-Deep Learning Clinical-Imaging Signature For Assessing Pathologic Grade And Prognosis Of Soft Tissue Sarcoma Patients", Pegah Khosravi
Publications and Research
No abstract provided.
Metformin In Systemic Lupus Erythematosus: Investigating Cardiovascular Impact And Nephroprotective Effects In Lupus Nephritis, Yurilu A. Gonzalez Moret, Kevin Bryan Lo, Irene J. Tan
Metformin In Systemic Lupus Erythematosus: Investigating Cardiovascular Impact And Nephroprotective Effects In Lupus Nephritis, Yurilu A. Gonzalez Moret, Kevin Bryan Lo, Irene J. Tan
Einstein Health Papers
OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by widespread organ inflammation. Metformin, commonly used for diabetes mellitus type 2, has been explored for its anti-inflammatory potential in SLE. This study investigates the association of metformin use on renal and cardiovascular outcomes in patients with SLE.
METHODS: This is a retrospective study. We used the multicenter research network (TriNetX) database from 88 health care organizations globally. Patients with SLE aged 18 and above, admitted between January 1, 2014, and April 21, 2024, were included. Propensity score matching compared patients with SLE on metformin with those not on metformin, considering demographics, laboratory …
Neuroecological Links Of The Exposome And One Health, Agustin Ibanez, Lucia Melloni, Paweł Świeboda, William Hynes, Burcin Ikiz, Rym Ayadi, Massamba Thioye, Consuelo Walss-Bass, Bahar Güntekin, Jyoti Mishra, Mohamed Salama, Sarah Dunlop, Claudia Duran-Aniotz, Harris A Eyre
Neuroecological Links Of The Exposome And One Health, Agustin Ibanez, Lucia Melloni, Paweł Świeboda, William Hynes, Burcin Ikiz, Rym Ayadi, Massamba Thioye, Consuelo Walss-Bass, Bahar Güntekin, Jyoti Mishra, Mohamed Salama, Sarah Dunlop, Claudia Duran-Aniotz, Harris A Eyre
Faculty, Staff and Student Publications
This NeuroView assesses the interplay among exposome, One Health, and brain capital in health and disease. Physical and social exposomes affect brain health, and green brain skills are required for environmental health strategies. Ibanez et al. address current gaps and strategies needed in research, policy, and technology, offering a road map for stakeholders.
Challenges And Opportunities In Cancer Immunotherapy: A Society For Immunotherapy Of Cancer (Sitc) Strategic Vision, Leisha A Emens, Pedro J Romero, Ana Carrizosa Anderson, Tullia C Bruno, Christian M Capitini, Deborah Collyar, James L Gulley, Patrick Hwu, Avery D Posey, Ann W Silk, Jennifer A Wargo
Challenges And Opportunities In Cancer Immunotherapy: A Society For Immunotherapy Of Cancer (Sitc) Strategic Vision, Leisha A Emens, Pedro J Romero, Ana Carrizosa Anderson, Tullia C Bruno, Christian M Capitini, Deborah Collyar, James L Gulley, Patrick Hwu, Avery D Posey, Ann W Silk, Jennifer A Wargo
Faculty, Staff and Student Publications
Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and spatial transcriptomics have provided deep insights into the immunobiology of the tumor …
Mediterranean Diet Information On Tiktok And Implications For Digital Health Promotion Research: Social Media Content Analysis, Margaret Raber, Haley Allen, Sophia Huang, Maria Vazquez, Echo Warner, Debbe Thompson
Mediterranean Diet Information On Tiktok And Implications For Digital Health Promotion Research: Social Media Content Analysis, Margaret Raber, Haley Allen, Sophia Huang, Maria Vazquez, Echo Warner, Debbe Thompson
Children’s Nutrition Research Center Staff Publications
Background: The Mediterranean diet has been linked to reduced risk for several cardiometabolic diseases. The lack of a clear definition of the Mediterranean diet in the scientific literature and the documented proliferation of nutrition misinformation on the internet suggest the potential for confusion among consumers seeking web-based Mediterranean diet information.
Objective: We conducted a social media content analysis of information about the Mediterranean diet on the influential social media platform, TikTok, to examine public discourse about the diet and identify potential areas of misinformation. We then analyzed these findings in the context of health promotion to identify potential challenges and …
Keep Fingers On The Cpg Islands, Xing Zhang, Robert M Blumenthal, Xiaodong Cheng
Keep Fingers On The Cpg Islands, Xing Zhang, Robert M Blumenthal, Xiaodong Cheng
Faculty, Staff and Student Publications
The post-genomic era has ushered in the extensive application of epigenetic editing tools, allowing for precise alterations of gene expression. The use of reprogrammable editors that carry transcriptional corepressors has significant potential for long-term epigenetic silencing for the treatment of human diseases. The ideal scenario involves precise targeting of a specific genomic location by a DNA-binding domain, ensuring there are no off-target effects and that the process yields no genetic remnants aside from specific epigenetic modifications (i.e., DNA methylation). A notable example is a recent study on the mouse
Microglial P2y6 Calcium Signaling Promotes Phagocytosis And Shapes Neuroimmune Responses In Epileptogenesis, Anthony D Umpierre, Bohan Li, Katayoun Ayasoufi, Whitney L Simon, Shunyi Zhao, Manling Xie, Grace Thyen, Benjamin Hur, Jiaying Zheng, Yue Liang, Dale B Bosco, Mark A Maynes, Zhaofa Wu, Xinzhu Yu, Jaeyun Sung, Aaron J Johnson, Yulong Li, Long-Jun Wu
Microglial P2y6 Calcium Signaling Promotes Phagocytosis And Shapes Neuroimmune Responses In Epileptogenesis, Anthony D Umpierre, Bohan Li, Katayoun Ayasoufi, Whitney L Simon, Shunyi Zhao, Manling Xie, Grace Thyen, Benjamin Hur, Jiaying Zheng, Yue Liang, Dale B Bosco, Mark A Maynes, Zhaofa Wu, Xinzhu Yu, Jaeyun Sung, Aaron J Johnson, Yulong Li, Long-Jun Wu
Faculty, Staff and Student Publications
Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo uridine diphosphate (UDP) fluorescent sensor, GRABUDP1.0, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions. UDP can signal through the microglial-enriched P2Y6 receptor to increase calcium activity during epileptogenesis. P2Y6 calcium activity is associated with lysosome biogenesis and enhanced production of NF-κB-related cytokines. In the hippocampus, knockout of the P2Y6 receptor prevents microglia from fully engulfing neurons. Attenuating microglial calcium signaling through calcium …
To Revise Or Not Revise? Isolated Margin Positivity In Localized Pancreatic Ductal Adenocarcinoma, Victoria S. Wu, Henry J. Stitzel, John B. Ammori, Jeffrey Hardacre, Lee M. Ocuin
To Revise Or Not Revise? Isolated Margin Positivity In Localized Pancreatic Ductal Adenocarcinoma, Victoria S. Wu, Henry J. Stitzel, John B. Ammori, Jeffrey Hardacre, Lee M. Ocuin
Faculty Scholarship
Background: The study determined the proportion of patients with pancreatic adenocarcinoma (PDAC) who had margin-positive disease and no other adverse pathologic findings (APF) using institutional and administrative datasets. Methods: Patients with clinical stage I or II PDAC in the National Cancer Database (NCDB 2010–2020) and those who underwent pancreatectomy at the authors’ institution (2010–2021) were identified. Isolated margin positivity (IMP) was defined as a positive surgical margin with no APF (negative nodes, no lymphovascular/perineural invasion). Results: The study included 225 patients from the authors’ institution and 23,598 patients from the NCDB. The margin-positive rates were 21.8% and 20.3%, and the …
A Single Cell Rna Sequence Atlas Of The Early Drosophila Larval Eye, Komal Kumar Bollepogu Raja, Kelvin Yeung, Yumei Li, Rui Chen, Graeme Mardon
A Single Cell Rna Sequence Atlas Of The Early Drosophila Larval Eye, Komal Kumar Bollepogu Raja, Kelvin Yeung, Yumei Li, Rui Chen, Graeme Mardon
Faculty, Staff and Students Publications
The Drosophila eye has been an important model to understand principles of differentiation, proliferation, apoptosis and tissue morphogenesis. However, a single cell RNA sequence resource that captures gene expression dynamics from the initiation of differentiation to the specification of different cell types in the larval eye disc is lacking. Here, we report transcriptomic data from 13,000 cells that cover six developmental stages of the larval eye. Our data show cell clusters that correspond to all major cell types present in the eye disc ranging from the initiation of the morphogenetic furrow to the differentiation of each photoreceptor cell type as …
Leveraging Integrated Rna Sequencing To Decipher Adrenomedullin's Protective Mechanisms In Experimental Bronchopulmonary Dysplasia, Subarna Palit, Amrit Kumar Shrestha, Shyam Thapa, Sandra L Grimm, Cristian Coarfa, Fabian Theis, Lukas M Simon, Binoy Shivanna
Leveraging Integrated Rna Sequencing To Decipher Adrenomedullin's Protective Mechanisms In Experimental Bronchopulmonary Dysplasia, Subarna Palit, Amrit Kumar Shrestha, Shyam Thapa, Sandra L Grimm, Cristian Coarfa, Fabian Theis, Lukas M Simon, Binoy Shivanna
Faculty, Staff and Students Publications
Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly affecting premature infants, with limited therapeutic options and increased long-term consequences. Adrenomedullin (Adm), a proangiogenic peptide hormone, has been found to protect rodents against experimental BPD. This study aims to elucidate the molecular and cellular mechanisms through which Adm influences BPD pathogenesis using a lipopolysaccharide (LPS)-induced model of experimental BPD in mice. Bulk RNA sequencing of Adm-sufficient (wild-type or Adm+/+) and Adm-haplodeficient (Adm+/−) mice lungs, integrated with single-cell RNA sequencing data, revealed distinct gene expression patterns and cell type alterations associated with Adm deficiency …
The Glucosylamine Oxidation Pathway Of Vitamin C Recycling, James M. Hempe, Daniel S. Hsia, Arthur Hagar, Larry Byers
The Glucosylamine Oxidation Pathway Of Vitamin C Recycling, James M. Hempe, Daniel S. Hsia, Arthur Hagar, Larry Byers
School of Medicine Faculty Publications
The proposed glucosylamine oxidation pathway (GOP) is a two-step, intraerythrocyte, thermodynamically favorable nonenzymatic reaction that first binds glucose to the N-terminal valine of beta globin (βVal1) to form a closed-chain glucosylamine that can spontaneously reduce oxidized vitamin C to its antioxidant form. This review summarizes analytical, biochemical and clinical research supporting the existence of the GOP and the surprising hypothesis that βVal1 glucosylamine is a reducing agent that works cooperatively with reduced glutathione to dynamically regulate vitamin C recycling during naturally occurring periods of transiently or chronically elevated blood glucose and oxidant production. Rationale for the existence of the GOP …
Case Report: Dementia Sensitivity To Altitude Changes And Effective Treatment With Hyperbaric Air And Glutathione Precursors, Edward F. Fogarty, Paul G. Harch
Case Report: Dementia Sensitivity To Altitude Changes And Effective Treatment With Hyperbaric Air And Glutathione Precursors, Edward F. Fogarty, Paul G. Harch
School of Medicine Faculty Publications
A 78-year-old man with dementia experienced waxing and waning of symptoms with changes in altitude as he traveled from his home in the Rocky Mountains to lower elevations and back. To replicate the improvement in his symptoms with travel to lower elevations (higher pressure), the patient was treated with a near-identical repressurization in a hyperbaric chamber using compressed air. With four 1-h treatments at 1.3 Atmospheres Absolute (ATA) and concurrent administration of low-dose oral glutathione amino acid precursors, he recovered speech and showed improvement in activities of daily living. Regional broadcast media had documented his novel recovery. Nosocomial COVID-19 and …
Identifying Overdose Risk Factors For People Hospitalized With Injection Drug Use-Associated Infections In Maine, Melanie Mait, Kim Murray, Tania D. Strout, Kinna Thakarar
Identifying Overdose Risk Factors For People Hospitalized With Injection Drug Use-Associated Infections In Maine, Melanie Mait, Kim Murray, Tania D. Strout, Kinna Thakarar
Journal of Maine Medical Center
Introduction: The overdose crisis continues to be a significant problem, particularly in rural states such as Maine. The objectives of this study were to: 1) describe demographic and health characteristics and 2) identify overdose risk factors among people in Maine hospitalized with injection drug use (IDU)-associated infections.
Methods: We performed descriptive analysis of demographics, health characteristics, and injection practices, stratified by lifetime history of overdose. We conducted an exploratory logistic regression analysis, controlling for gender, homelessness, having experienced an emergency department (ED) visit in the past 3-months, and endorsement of injecting alone in the past 30 days to examine …
Let’S Go! 2022-2023 Educational Programs: Developing A Standardized Obesity Medicine Curriculum Through A Realist Evaluation, Isaac Stickney, Peter Amann, Victoria Rogers, Austin Steward, Kayla Bronzo, Alec Luro, Robert Bing-You
Let’S Go! 2022-2023 Educational Programs: Developing A Standardized Obesity Medicine Curriculum Through A Realist Evaluation, Isaac Stickney, Peter Amann, Victoria Rogers, Austin Steward, Kayla Bronzo, Alec Luro, Robert Bing-You
Journal of Maine Medical Center
Problem: Obesity is linked to more than 200 chronic conditions, lower quality of life, and worse outcomes for patients. Let’s Go! is a community engagement initiative that works with communities to create environments that support healthy behaviors that impact obesity. Let’s Go! provides educational programming for all medical learners and providers throughout Maine and Carroll County, New Hampshire. The goal of Let’s Go! is to address the health outcomes of obesity and the stigma associated with it, including its impact on patients’ mental health and clinicians’ unconscious biases.
Approach: We used a realist evaluation, a framework in which the social …
Does The Use Of Double Hormone Replacement Therapy For Trauma Patient Organ Donors Improve Organ Recovery For Transplant, Eden M. Gallegos, Tanner Reed, Paige Deville, Blake Platt, Claudia Leonardi, Lillian Bellfi, Jessica Dufrene, Saad Chaudhary, John Hunt, Lance Stuke, Patrick Greiffenstein, Jonathan Schoen, Alan Marr, Anil Paramesh, Alison A. Smith
Does The Use Of Double Hormone Replacement Therapy For Trauma Patient Organ Donors Improve Organ Recovery For Transplant, Eden M. Gallegos, Tanner Reed, Paige Deville, Blake Platt, Claudia Leonardi, Lillian Bellfi, Jessica Dufrene, Saad Chaudhary, John Hunt, Lance Stuke, Patrick Greiffenstein, Jonathan Schoen, Alan Marr, Anil Paramesh, Alison A. Smith
School of Graduate Studies Faculty Publications
BACKGROUND With an ongoing demand for transplantable organs, optimization of donor management protocols, specifically in trauma populations, is important for obtaining a high yield of viable organs per patient. Endocrine management of brain-dead potential organ donors (BPODs) is controversial, leading to heterogeneous clinical management approaches. Previous studies have shown that when levothyroxine was combined with other treatments, including steroids, vasopressin, and insulin, BPODs had better organ recovery and survival outcomes were increased for transplant recipients. AIM To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients. METHODS A retrospective review …
The Cdk9 Inhibitor Enitociclib Overcomes Resistance To Btk Inhibition And Car-T Therapy In Mantle Cell Lymphoma, Vivian Jiang, William Lee, Tianci Zhang, Alexa Jordan, Fangfang Yan, Qingsong Cai, Joseph Mcintosh, Jovanny Vargas, Yang Liu, Michael Wang
The Cdk9 Inhibitor Enitociclib Overcomes Resistance To Btk Inhibition And Car-T Therapy In Mantle Cell Lymphoma, Vivian Jiang, William Lee, Tianci Zhang, Alexa Jordan, Fangfang Yan, Qingsong Cai, Joseph Mcintosh, Jovanny Vargas, Yang Liu, Michael Wang
Faculty, Staff and Student Publications
Inhibitors of Bruton's tyrosine kinase (BTKi) and chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 are paradigm-shifting advances in treating patients with aggressive mantle cell lymphoma (MCL). However, clinical relapses following BTKi and CD19-directed CAR-T treatments are a fast-growing medical challenge. Development of novel therapies to overcome BTKi resistance (BTKi-R) and BTKi-CAR-T dual resistance (Dual-R) are urgently needed. Our single-cell RNA sequencing data revealed major transcriptomic reprogramming, with great enrichment of MYC-targets evolving as resistance to these therapies developed. Interestingly, cyclin-dependent kinase 9 (CDK9), a critical component of the positive transcription elongation factor-b complex, was among the top upregulated genes …
Fate-Mapping And Functional Dissection Reveal Perilous Influence Of Type I Interferon Signaling In Mouse Brain Aging, Ethan R Roy, Sanming Li, Sepideh Saroukhani, Yanyu Wang, Wei Cao
Fate-Mapping And Functional Dissection Reveal Perilous Influence Of Type I Interferon Signaling In Mouse Brain Aging, Ethan R Roy, Sanming Li, Sepideh Saroukhani, Yanyu Wang, Wei Cao
Faculty, Staff and Student Publications
Background: Aging significantly elevates the risk of developing neurodegenerative diseases. Neuroinflammation is a universal hallmark of neurodegeneration as well as normal brain aging. Which branches of age-related neuroinflammation, and how they precondition the brain toward pathological progression, remain ill-understood. The presence of elevated type I interferon (IFN-I) has been documented in the aged brain, but its role in promoting degenerative processes, such as the loss of neurons in vulnerable regions, has not been studied in depth.
Methods: To comprehend the scope of IFN-I activity in the aging brain, we surveyed IFN-I-responsive reporter mice at multiple ages. We also examined 5- …
Neurogranin Modulates The Rate Of Association Between Calmodulin And Target Peptides, John A Putkey, Laurel Hoffman, Vladimir Berka, Xu Wang
Neurogranin Modulates The Rate Of Association Between Calmodulin And Target Peptides, John A Putkey, Laurel Hoffman, Vladimir Berka, Xu Wang
Faculty, Staff and Student Publications
The best-known mode of action of calmodulin (CaM) is binding of Ca2+ to its N- and C-domains, followed by binding to target proteins. An underappreciated facet of this process is that CaM is typically bound to proteins at basal levels of free Ca2+, including the small, intrinsically disordered, neuronal IQ-motif proteins called PEP-19 and neurogranin (Ng). PEP-19 and Ng would not be effective competitive inhibitors of high-affinity Ca2+-dependent CaM targets at equilibrium because they bind to CaM with relatively low affinity, but they could influence the time course of CaM signaling by affecting the rate of association of CaM with …
Targeting Il-11r/Ezh2 Signaling Axis As A Therapeutic Strategy For Osteosarcoma Lung Metastases, Eswaran Devarajan, R Eric Davis, Hannah C Beird, Wei-Lien Wang, V Behrana Jensen, Arumugam Jayakumar, Cheuk Hong Leung, Heather Y Lin, Chia-Chin Wu, Stephanie A Ihezie, Jen-Wei Tsai, P Andrew Futreal, Valerae O Lewis
Targeting Il-11r/Ezh2 Signaling Axis As A Therapeutic Strategy For Osteosarcoma Lung Metastases, Eswaran Devarajan, R Eric Davis, Hannah C Beird, Wei-Lien Wang, V Behrana Jensen, Arumugam Jayakumar, Cheuk Hong Leung, Heather Y Lin, Chia-Chin Wu, Stephanie A Ihezie, Jen-Wei Tsai, P Andrew Futreal, Valerae O Lewis
Faculty, Staff and Student Publications
Lung metastases are the primary cause of death for osteosarcoma (OS) patients. We recently validated interleukin-11 receptor α (IL-11Rα) as a molecular target for the inhibition of OS lung metastases. Since there is no clinically approved antibody against this receptor, we sought to identify downstream targets that mediate the effects of IL-11Rα signaling. We used shRNA to deplete IL-11Rα from OS cells; as a complementary approach, we added IL-11 exogenously to OS cells. The resulting changes in gene expression identified EZH2 as a downstream candidate. This was confirmed by knockdown of IL-11Rα in OS cells, which led to increased expression …
Repeat Controlled Human Plasmodium Falciparum Infections Delay Bloodstream Patency And Reduce Symptoms, Patricia Ferrer, Andrea A Berry, Allison N Bucsan, Surendra K Prajapati, Karthik Krishnan, Michelle C Barbeau, David M Rickert, Sandra Mendoza Guerrero, Miho Usui, Yonas Abebe, Asha Patil, Sumana Chakravarty, Peter F Billingsley, Faith Pa'ahana-Brown, Kathy Strauss, Biraj Shrestha, Effie Nomicos, Gregory A Deye, B Kim Lee Sim, Stephen L Hoffman, Kim C Williamson, Kirsten E Lyke
Repeat Controlled Human Plasmodium Falciparum Infections Delay Bloodstream Patency And Reduce Symptoms, Patricia Ferrer, Andrea A Berry, Allison N Bucsan, Surendra K Prajapati, Karthik Krishnan, Michelle C Barbeau, David M Rickert, Sandra Mendoza Guerrero, Miho Usui, Yonas Abebe, Asha Patil, Sumana Chakravarty, Peter F Billingsley, Faith Pa'ahana-Brown, Kathy Strauss, Biraj Shrestha, Effie Nomicos, Gregory A Deye, B Kim Lee Sim, Stephen L Hoffman, Kim C Williamson, Kirsten E Lyke
Faculty, Staff and Student Publications
Resistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the host response against controlled repeat exposures to P. falciparum (Pf) NF54 strain-infected mosquitoes, we systematically monitored malaria-naïve participants through an initial exposure to uninfected mosquitoes and 4 subsequent homologous exposures to Pf-infected mosquitoes over 21 months (n = 8 males) (ClinicalTrials.gov# NCT03014258). The primary outcome was to determine whether protective immunity against parasite infection develops following repeat CHMI and the secondary outcomes were to track the clinical signs and symptoms of malaria and anti-Pf antibody …
Phase 2 Study Of Neoadjuvant Enzalutamide And Paclitaxel For Luminal Androgen Receptor-Enriched Tnbc: Trial Results And Insights Into “Arness”, Bora Lim, Sahil Seth, Clinton Yam, Lei Huo, Takeo Fujii, Jangsoon Lee, Roland Bassett, Sara Nasser, Lisa Ravenberg, Jason White, Alyson Clayborn, Gil Guerra, Jennifer K Litton, Senthil Damodaran, Rachel Layman, Vicente Valero, Debasish Tripathy, Michael Lewis, Lacey E Dobrolecki, Jonathan Lei, Rosalind Candelaria, Banu Arun, Gaiane Rauch, Li Zhao, Jianhua Zhang, Qingqing Ding, W Fraser Symmans, Jeffrey T Chang, Alastair M Thompson, Stacy L Moulder, Naoto T Ueno
Phase 2 Study Of Neoadjuvant Enzalutamide And Paclitaxel For Luminal Androgen Receptor-Enriched Tnbc: Trial Results And Insights Into “Arness”, Bora Lim, Sahil Seth, Clinton Yam, Lei Huo, Takeo Fujii, Jangsoon Lee, Roland Bassett, Sara Nasser, Lisa Ravenberg, Jason White, Alyson Clayborn, Gil Guerra, Jennifer K Litton, Senthil Damodaran, Rachel Layman, Vicente Valero, Debasish Tripathy, Michael Lewis, Lacey E Dobrolecki, Jonathan Lei, Rosalind Candelaria, Banu Arun, Gaiane Rauch, Li Zhao, Jianhua Zhang, Qingqing Ding, W Fraser Symmans, Jeffrey T Chang, Alastair M Thompson, Stacy L Moulder, Naoto T Ueno
Faculty, Staff and Student Publications
Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m2 weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a …
Real World Predictors Of Response And 24-Month Survival In High-Grade Tp53-Mutated Myeloid Neoplasms, Amandeep Kaur, Alexandra E Rojek, Emily Symes, Mariam T Nawas, Anand A Patel, Jay L Patel, Payal Sojitra, Barina Aqil, Madina Sukhanova, Megan E Mcnerney, Leo P Wu, Aibek Akmatbekov, Jeremy Segal, Melissa Y Tjota, Sandeep Gurbuxani, Jason X Cheng, Su-Yeon Yeon, Harini V Ravisankar, Carrie Fitzpatrick, Angela Lager, Michael W Drazer, Caner Saygin, Pankhuri Wanjari, Panagiotis Katsonis, Olivier Lichtarge, Jane E Churpek, Sharmila B Ghosh, Ami B Patel, Madhu P Menon, Daniel A Arber, Peng Wang, Girish Venkataraman
Real World Predictors Of Response And 24-Month Survival In High-Grade Tp53-Mutated Myeloid Neoplasms, Amandeep Kaur, Alexandra E Rojek, Emily Symes, Mariam T Nawas, Anand A Patel, Jay L Patel, Payal Sojitra, Barina Aqil, Madina Sukhanova, Megan E Mcnerney, Leo P Wu, Aibek Akmatbekov, Jeremy Segal, Melissa Y Tjota, Sandeep Gurbuxani, Jason X Cheng, Su-Yeon Yeon, Harini V Ravisankar, Carrie Fitzpatrick, Angela Lager, Michael W Drazer, Caner Saygin, Pankhuri Wanjari, Panagiotis Katsonis, Olivier Lichtarge, Jane E Churpek, Sharmila B Ghosh, Ami B Patel, Madhu P Menon, Daniel A Arber, Peng Wang, Girish Venkataraman
Faculty, Staff and Students Publications
Current therapies for high-grade TP53-mutated myeloid neoplasms (≥10% blasts) do not offer a meaningful survival benefit except allogeneic stem cell transplantation in the minority who achieve a complete response to first line therapy (CR1). To identify reliable pre-therapy predictors of complete response to first-line therapy (CR1) and outcomes, we assembled a cohort of 242 individuals with TP53-mutated myeloid neoplasms and ≥10% blasts with well-annotated clinical, molecular and pathology data. Key outcomes examined were CR1 & 24-month survival (OS24). In this elderly cohort (median age 68.2 years) with 74.0% receiving frontline non-intensive regimens (hypomethylating agents +/- venetoclax), the overall cohort CR1 …
Legend Of Merlin And The Quest For Cardiac Lineage Commitment, Rich Gang Li, James F Martin
Legend Of Merlin And The Quest For Cardiac Lineage Commitment, Rich Gang Li, James F Martin
Faculty, Staff and Students Publications
No abstract provided.
Author Correction: Il-12 Reprograms Car-Expressing Natural Killer T Cells To Long-Lived Th1-Polarized Cells With Potent Antitumor Activity, Elisa Landoni, Mark G Woodcock, Gabriel Barragan, Gabriele Casirati, Vincenzo Cinella, Simone Stucchi, Leah M Flick, Tracy A Withers, Hanna Hudson, Giulia Casorati, Paolo Dellabona, Pietro Genovese, Barbara Savoldo, Leonid S Metelitsa, Gianpietro Dotti
Author Correction: Il-12 Reprograms Car-Expressing Natural Killer T Cells To Long-Lived Th1-Polarized Cells With Potent Antitumor Activity, Elisa Landoni, Mark G Woodcock, Gabriel Barragan, Gabriele Casirati, Vincenzo Cinella, Simone Stucchi, Leah M Flick, Tracy A Withers, Hanna Hudson, Giulia Casorati, Paolo Dellabona, Pietro Genovese, Barbara Savoldo, Leonid S Metelitsa, Gianpietro Dotti
Faculty, Staff and Students Publications
No abstract provided.