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Articles 781 - 810 of 5215

Full-Text Articles in Diseases

An Interdisciplinary Consensus Approach To Pulmonary Hypertension In Developmental Lung Disease, Nidhy P Varghese, Eric D Austin, Csaba Galambos, Mary P Mullen, Delphine Yung, R Paul Guillerman, Sara O Vargas, Catherine M Avitabile, Corey A Chartan, Nahir Cortes-Santiago, Michaela Ibach, Emma O Jackson, Jill Ann Jarrell, Roberta L Keller, Usha S Krishnan, Kalyani R Patel, Jennifer Pogoriler, Elise C Whalen, Kathryn A Wikenheiser-Brokamp, Natalie M Villafranco, Rachel K Hopper, J Usha Raj, Steven H Abman, Pediatric Pulmonary Hypertension Network (Pphnet) Sep 2024

An Interdisciplinary Consensus Approach To Pulmonary Hypertension In Developmental Lung Disease, Nidhy P Varghese, Eric D Austin, Csaba Galambos, Mary P Mullen, Delphine Yung, R Paul Guillerman, Sara O Vargas, Catherine M Avitabile, Corey A Chartan, Nahir Cortes-Santiago, Michaela Ibach, Emma O Jackson, Jill Ann Jarrell, Roberta L Keller, Usha S Krishnan, Kalyani R Patel, Jennifer Pogoriler, Elise C Whalen, Kathryn A Wikenheiser-Brokamp, Natalie M Villafranco, Rachel K Hopper, J Usha Raj, Steven H Abman, Pediatric Pulmonary Hypertension Network (Pphnet)

Faculty, Staff and Students Publications

It is increasingly recognised that diverse genetic respiratory disorders present as severe pulmonary hypertension (PH) in the neonate and young infant, but many controversies and uncertainties persist regarding optimal strategies for diagnosis and management to maximise long-term outcomes. To better define the nature of PH in the setting of developmental lung disease (DEVLD), in addition to the common diagnoses of bronchopulmonary dysplasia and congenital diaphragmatic hernia, we established a multidisciplinary group of expert clinicians from stakeholder paediatric specialties to highlight current challenges and recommendations for clinical approaches, as well as counselling and support of families. In this review, we characterise …


Fluid Overload In Pediatric Acute Respiratory Distress Syndrome After Allogeneic Hematopoietic Cell Transplantation, Colin J Sallee, Julie C Fitzgerald, Lincoln S Smith, Joseph R Angelo, Megan C Daniel, Shira J Gertz, Deyin D Hsing, Kris M Mahadeo, Jennifer A Mcarthur, Courtney M Rowan, Pediatric Acute Lung Injury Sepsis Investigators (Palisi) Network Sep 2024

Fluid Overload In Pediatric Acute Respiratory Distress Syndrome After Allogeneic Hematopoietic Cell Transplantation, Colin J Sallee, Julie C Fitzgerald, Lincoln S Smith, Joseph R Angelo, Megan C Daniel, Shira J Gertz, Deyin D Hsing, Kris M Mahadeo, Jennifer A Mcarthur, Courtney M Rowan, Pediatric Acute Lung Injury Sepsis Investigators (Palisi) Network

Faculty, Staff and Students Publications

The aim of the study is to examine the relationship between fluid overload (FO) and severity of respiratory dysfunction in children posthematopoietic cell transplantation (HCT) with pediatric acute respiratory distress syndrome (PARDS). This investigation was a secondary analysis of a multicenter retrospective cohort of children (1month to 21 years) postallogeneic HCT with PARDS receiving invasive mechanical ventilation (IMV) from 2009 to 2014. Daily FO % (FO%) and daily oxygenation index (OI) were calculated for each patient up to the first week of IMV (day 0 = intubation). Linear mixed-effect regression was employed to examine whether FO% and OI were associated …


Quality Analysis Of Online Resources For Patients Undergoing Coronary Artery Bypass Grafting, Natalia Roa-Vidal, John A Treffalls, Zachary Brennan, Omar M Sharaf, Brittany Rhoades, Lauren K Barron Sep 2024

Quality Analysis Of Online Resources For Patients Undergoing Coronary Artery Bypass Grafting, Natalia Roa-Vidal, John A Treffalls, Zachary Brennan, Omar M Sharaf, Brittany Rhoades, Lauren K Barron

Faculty, Staff and Students Publications

BACKGROUND: Online resources are becoming the primary educational resource for patients. Quality and reliability of websites about coronary artery bypass graft (CABG) procedures are unknown.

METHODS: We queried 4 search engines (Google, Bing, Yahoo!, and Dogpile) for the terms coronary artery bypass, coronary artery bypass graft, coronary artery bypass graft surgery, and CABG. The top 30 websites from each were aggregated. After exclusions, 85 websites were graded with the DISCERN instrument, patient-focused criteria, and readability calculators by a 2-reviewer system.

RESULTS:Accessibility was low; 34.1% of websites disclosed authorship, and 23.5% were available in Spanish. Median total …


Tuberculosis Prevention: Current Strategies And Future Directions, Anca Vasiliu, Leonardo Martinez, Rishi K Gupta, Yohhei Hamada, Tara Ness, Alexander Kay, Maryline Bonnet, Martina Sester, Stefan H E Kaufmann, Christoph Lange, Anna M Mandalakas Sep 2024

Tuberculosis Prevention: Current Strategies And Future Directions, Anca Vasiliu, Leonardo Martinez, Rishi K Gupta, Yohhei Hamada, Tara Ness, Alexander Kay, Maryline Bonnet, Martina Sester, Stefan H E Kaufmann, Christoph Lange, Anna M Mandalakas

Faculty, Staff and Students Publications

BACKGROUND: An estimated one fourth of the world's population is infected with Mycobacterium tuberculosis, and 5-10% of those infected develop tuberculosis in their lifetime. Preventing tuberculosis is one of the most underutilized but essential components of curtailing the tuberculosis epidemic. Moreover, current evidence illustrates that tuberculosis manifestations occur along a dynamic spectrum from infection to disease rather than a binary state as historically conceptualized. Elucidating determinants of transition between these states is crucial to decreasing the tuberculosis burden and reaching the END-TB Strategy goals as defined by the WHO. Vaccination, detection of infection, and provision of preventive treatment are key …


Characteristics Of Patients With Spontaneous Coronary Artery Dissection Presenting With Sudden Cardiac Arrest In The United States And The Potential Role Of Implantable Cardioverter Defibrillator Therapy, Chayakrit Krittanawong, Yusuf Kamran Qadeer, Song Peng Ang, Zhen Wang, Mahboob Alam, Samin Sharma, Hani Jneid Sep 2024

Characteristics Of Patients With Spontaneous Coronary Artery Dissection Presenting With Sudden Cardiac Arrest In The United States And The Potential Role Of Implantable Cardioverter Defibrillator Therapy, Chayakrit Krittanawong, Yusuf Kamran Qadeer, Song Peng Ang, Zhen Wang, Mahboob Alam, Samin Sharma, Hani Jneid

Faculty, Staff and Students Publications

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a disease entity that often occurs in young, healthy women and can cause life-threatening ventricular arrhythmias and sudden cardiac arrest. However, the characteristics and outcomes of SCAD with cardiac arrest are not well characterized.

METHODS: This study investigated the baseline characteristics of SCAD patients with cardiac arrest using the National Inpatient Sample (NIS) database between 2016 and 2020. In addition, we also sought to determine the potential impact that implantable cardioverter defibrillator (ICD) therapy had on morbidity and mortality in SCAD patients presenting with cardiac arrest.

RESULTS: Our findings showed that the SCAD …


Cmtm4 Inhibits Gastric Tumorigenesis And Metastasis, Xiurui Han, Weiwei Fu, Qinghua Sun, Jing Ning, Jing Zhang, Silvio Matsas, Fabrício Freire De Melo, Hejun Zhang, Xinyu Hao, Qiao Meng, Yueqing Gong, Huiling Zheng, Jing Zhang, Shigang Ding Aug 2024

Cmtm4 Inhibits Gastric Tumorigenesis And Metastasis, Xiurui Han, Weiwei Fu, Qinghua Sun, Jing Ning, Jing Zhang, Silvio Matsas, Fabrício Freire De Melo, Hejun Zhang, Xinyu Hao, Qiao Meng, Yueqing Gong, Huiling Zheng, Jing Zhang, Shigang Ding

Faculty, Staff and Student Publications

BACKGROUND: CKLF-like MARVEL transmembrane domain-containing 4 (CMTM4) is involved in immune regulation and tumor progression; however, its role in gastric cancer (GC) remains unclear. This study explored the role and mechanism of CMTM4 in GC.

METHODS: Immunohistochemistry was used to analyze CMTM4 expression in human gastric biopsied cells from patients with GC (N=23) or chronic superficial gastritis (N=23). To investigate the function of CMTM4 in GC cells, the gene

RESULTS: CMTM4 expression was more downregulated in the human GC tissues than the gastritis tissues. CMTM4 overexpression significantly inhibited the proliferation, migration, and invasion of the GC cells, whereas CMTM4 knockdown …


Management Targeted Genetic Evaluation Of An Idiopathic Neuropathy Cohort Through Attrv Amyloidosis Screening, Kristy A. Fisher, Santiago Diaz, Jeffrey Gelblum, Charles Brock, Niraja Suresh, Meghan Towne Aug 2024

Management Targeted Genetic Evaluation Of An Idiopathic Neuropathy Cohort Through Attrv Amyloidosis Screening, Kristy A. Fisher, Santiago Diaz, Jeffrey Gelblum, Charles Brock, Niraja Suresh, Meghan Towne

HCA Healthcare Journal of Medicine

Background

While the reported prevalence of polyneuropathies is 1%-3%, the incidence of hereditary transthyretin amyloidosis in the United States is estimated to be 1 in 100 000 individuals. Polyneuropathies are known to be difficult to treat and lead to significant morbidity. The aim of pain management is symptomatic treatment, with varying approaches to progression prevention being based on the causative pathophysiology.

We assessed the prevalence of hereditary amyloid transthyretin variant (ATTRv) amyloidosis, a progressive autosomal dominant multisystem disease caused by the abnormal formation and extracellular deposition of transthyretin protein fibrils in various tissues, in an idiopathic polyneuropathy population by using …


Inhibition Of Ulk1/2 And Kras G12c Controls Tumor Growth In Preclinical Models Of Lung Cancer, Phaedra C Ghazi, Kayla T O'Toole, Sanjana Srinivas Boggaram, Michael T Scherzer, Mark R Silvis, Yun Zhang, Madhumita Bogdan, Bryan D Smith, Guillermina Lozano, Daniel L Flynn, Eric L Snyder, Conan G Kinsey, Martin Mcmahon Aug 2024

Inhibition Of Ulk1/2 And Kras G12c Controls Tumor Growth In Preclinical Models Of Lung Cancer, Phaedra C Ghazi, Kayla T O'Toole, Sanjana Srinivas Boggaram, Michael T Scherzer, Mark R Silvis, Yun Zhang, Madhumita Bogdan, Bryan D Smith, Guillermina Lozano, Daniel L Flynn, Eric L Snyder, Conan G Kinsey, Martin Mcmahon

Faculty, Staff and Student Publications

Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRASG12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC). However, not all KRASG12C-driven NSCLCs respond to these inhibitors, and the emergence of drug resistance in those patients who do respond can be rapid and pleiotropic. Hence, based on a backbone of covalent inhibition of KRASG12C, efforts are underway to develop effective combination therapies. Here, we report that the inhibition of KRASG12C signaling increases autophagy in KRASG12C-expressing lung cancer …


Successful Management Of Pre-Existing Psoriatic Arthritis Through Targeting The Il-23/Il-17 Axis In Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy: A Case Series, Yuanteng Jeff Li, Pavlos Msaouel, Matthew Campbell, Patrick Hwu, Adi Diab, Sang T Kim Aug 2024

Successful Management Of Pre-Existing Psoriatic Arthritis Through Targeting The Il-23/Il-17 Axis In Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy: A Case Series, Yuanteng Jeff Li, Pavlos Msaouel, Matthew Campbell, Patrick Hwu, Adi Diab, Sang T Kim

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with cancer. However, these therapies are associated with adverse events including de novo immune-related adverse events or flare of pre-exiting autoimmune disorders. Up to 80% of patients with cancer and pre-existing psoriasis (PsO) or psoriatic arthritis (PsA) experience PsO/PsA flare after initiating ICIs. Targeting the interleukin (IL)-17/IL-23 axis is a mainstream of the PsO/PsA treatment. However, whether this treatment can effectively control PsO/PsA with ICI exposure while preserving anti-tumour efficacy remains unknown.

CASE REPORTS: We report three patients with PsA and cancer, who received ICIs for their cancer treatment. …


Combination Therapy Of Ido1 Inhibition And Anti-Pd1 Mediates Anti-Tumor Immunity By Promoting Memory Immunity Development And Cytotoxicity Of Γδ T And Nk Cells Via Il-2 Signaling And By Overcoming Pro-Tumor Effects Of Tgf-Β Signaling, Hyuk Jee Aug 2024

Combination Therapy Of Ido1 Inhibition And Anti-Pd1 Mediates Anti-Tumor Immunity By Promoting Memory Immunity Development And Cytotoxicity Of Γδ T And Nk Cells Via Il-2 Signaling And By Overcoming Pro-Tumor Effects Of Tgf-Β Signaling, Hyuk Jee

Dartmouth College Master’s Theses

Cutaneous melanoma is the most aggressive form of skin cancer even though it takes only about 1% of all skin cancers. Even among all cutaneous melanomas, NRAS-mutant melanoma is more aggressive than any other, and about 10-25% of all cutaneous melanoma cases have mutations in NRAS. NRAS is a member of the RAS family of proto-oncogenic GTPase proteins, and it plays a key role in signal transduction pathways responsible for cellular survival, proliferation, and metabolism. Immunotherapy is the first line of defense against NRAS-mutant melanoma because, despite tremendous efforts made for decades, it has not been successful to develop small …


Elevated Level Of Extracellular Vimentin Is Associated With An Increased Fibrin Formation Potential In Sepsis: Ex Vivo Swine Study, Marina Martinez-Vargas, Arun Saini, Subhashree Pradhan, Luis Gardea, Barbara Stoll, Inka C Didelija, K Vinod Vijayan, Trung C Nguyen, Miguel A Cruz Aug 2024

Elevated Level Of Extracellular Vimentin Is Associated With An Increased Fibrin Formation Potential In Sepsis: Ex Vivo Swine Study, Marina Martinez-Vargas, Arun Saini, Subhashree Pradhan, Luis Gardea, Barbara Stoll, Inka C Didelija, K Vinod Vijayan, Trung C Nguyen, Miguel A Cruz

Faculty, Staff and Students Publications

BACKGROUND: Sepsis can lead to coagulopathy and microvascular thrombosis. Prior studies, including ours, reported an increased level of extracellular vimentin in blood derived from septic patients. Moreover, we identified the contribution of extracellular vimentin to fibrin formation and to the fibrin clot structure ex vivo in plasma from septic patients. Here, we tested the status of plasma vimentin and its impact on fibrin clots using our recently described swine model of methicillin-resistant Staphylococcus aureus (MRSA) sepsis-induced coagulopathy.

RESULTS: We employed ELISA, size-exclusion chromatography, vimentin antibodies, confocal microscopy, and turbidity assays on piglet plasma obtained at pre- and post-MRSA inoculation. Plasma …


Facilitators And Barriers To Initiating And Completing Tuberculosis Preventive Treatment Among Children And Adolescents Living With Hiv In Uganda: A Qualitative Study Of Adolescents, Caretakers And Health Workers, Pauline Mary Amuge, Denis Ndekezi, Moses Mugerwa, Dickson Bbuye, Diana Antonia Rutebarika, Lubega Kizza, Christine Namugwanya, Angella Baita, Peter James Elyanu, Patricia Nahirya Ntege, Dithan Kiragga, Carol Birungi, Adeodata Rukyalekere Kekitiinwa, Agnes Kiragga, Moorine Peninah Sekadde, Nicole-Austin Salazar, Anna Maria Mandalakas, Philippa Musoke Aug 2024

Facilitators And Barriers To Initiating And Completing Tuberculosis Preventive Treatment Among Children And Adolescents Living With Hiv In Uganda: A Qualitative Study Of Adolescents, Caretakers And Health Workers, Pauline Mary Amuge, Denis Ndekezi, Moses Mugerwa, Dickson Bbuye, Diana Antonia Rutebarika, Lubega Kizza, Christine Namugwanya, Angella Baita, Peter James Elyanu, Patricia Nahirya Ntege, Dithan Kiragga, Carol Birungi, Adeodata Rukyalekere Kekitiinwa, Agnes Kiragga, Moorine Peninah Sekadde, Nicole-Austin Salazar, Anna Maria Mandalakas, Philippa Musoke

Faculty, Staff and Students Publications

INTRODUCTION: People living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV). We explored the facilitators and barriers to TPT initiation and completion among CALHIV among adolescents aged 10-19years and caretakers of children below 18years.

METHODS: We conducted a qualitative study …


Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska Aug 2024

Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer …


Mechanisms And Metabolic Consequences Of Adipocyte Progenitor Replicative Senescence, Tonghui Lin, Aftab Mohammad, Mikhail G Kolonin, Kristin L Eckel-Mahan Aug 2024

Mechanisms And Metabolic Consequences Of Adipocyte Progenitor Replicative Senescence, Tonghui Lin, Aftab Mohammad, Mikhail G Kolonin, Kristin L Eckel-Mahan

Faculty, Staff and Student Publications

In recent decades, obesity has become a worldwide epidemic. As a result, the importance of adipose tissue (AT) as a metabolically active storage depot for lipids and a key mediator of body-wide metabolism and energy balance has been increasingly recognized. Emerging from the studies of AT in metabolic disease is a recognition of the importance of the adipocyte progenitor cell (APC) population of AT being the gatekeeper of adipocyte function. APCs have the capability to self-renew and undergo adipogenesis to propagate new adipocytes capable of lipid storage, which is important for maintaining a healthy fat pad, devoid of dysfunctional lipid …


Adenovirus Vaccine Targeting Kinases Induces Potent Antitumor Immunity In Solid Tumors, Fei Zhu, Zheng Lu, Wenjing Tang, Guangya Zhao, Yingxiang Shao, Bowen Lu, Jiage Ding, Yanyan Zheng, Lin Fang, Huizhong Li, Gang Wang, Renjin Chen, Junnian Zheng, Dafei Chai Aug 2024

Adenovirus Vaccine Targeting Kinases Induces Potent Antitumor Immunity In Solid Tumors, Fei Zhu, Zheng Lu, Wenjing Tang, Guangya Zhao, Yingxiang Shao, Bowen Lu, Jiage Ding, Yanyan Zheng, Lin Fang, Huizhong Li, Gang Wang, Renjin Chen, Junnian Zheng, Dafei Chai

Faculty, Staff and Students Publications

BACKGROUND: Targeting kinases presents a potential strategy for treating solid tumors; however, the therapeutic potential of vaccines targeting kinases remains uncertain.

METHODS: Adenovirus (Ad) vaccines encoding Aurora kinase A (AURKA) or cyclin-dependent kinase 7 (CDK7) were developed, and their therapeutic potentials were investigated by various methods including western blot, flow cytometry, cytotoxic T lymphocyte assay, and enzyme-linked immunospot (ELISpot), in mouse and humanized solid tumor models.

RESULTS: Co-immunization with Ad-AURKA/CDK7 effectively prevented subcutaneous tumor growth in the Renca, RM-1, MC38, and Hepa1-6 tumor models. In therapeutic tumor models, Ad-AURKA/CDK7 treatment impeded tumor growth and increased immune cell infiltration. Administration of …


Synergistic Effects Of Novel Penicillin-Binding Protein 1a Amino Acid Substitutions Contribute To High-Level Amoxicillin Resistance Of, Alain Cimuanga-Mukanya, Evariste Tshibangu-Kabamba, Patrick De Jesus Ngoma Kisoko, Kartika Afrida Fauzia, Fabien Mbaya Tshibangu, Antoine Tshimpi Wola, Pascal Tshiamala Kashala, Dieudonné Mumba Ngoyi, Steve Ahuka-Mundeke, Gunturu Revathi, Ghislain Disashi-Tumba, Yasutoshi Kido, Takashi Matsumoto, Junko Akada, Yoshio Yamaoka Aug 2024

Synergistic Effects Of Novel Penicillin-Binding Protein 1a Amino Acid Substitutions Contribute To High-Level Amoxicillin Resistance Of, Alain Cimuanga-Mukanya, Evariste Tshibangu-Kabamba, Patrick De Jesus Ngoma Kisoko, Kartika Afrida Fauzia, Fabien Mbaya Tshibangu, Antoine Tshimpi Wola, Pascal Tshiamala Kashala, Dieudonné Mumba Ngoyi, Steve Ahuka-Mundeke, Gunturu Revathi, Ghislain Disashi-Tumba, Yasutoshi Kido, Takashi Matsumoto, Junko Akada, Yoshio Yamaoka

Faculty, Staff and Students Publications

The growing resistance to amoxicillin (AMX)—one of the main antibiotics used in Helicobacter pylori eradication therapy—is an increasing health concern. Several mutations of penicillin-binding protein 1A (PBP1A) are suspected of causing AMX resistance; however, only a limited set of these mutations have been experimentally explored. This study aimed to investigate four PBP1A mutations (i.e., T558S, N562H, T593A, and G595S) carried by strain KIN76, a high-level AMX-resistant clinical H. pylori isolate with an AMX minimal inhibition concentration (MIC) of 2 µg/mL. We transformed a recipient strain 26695 with the DNA containing one to four mutation allele combinations of the pbp1 gene …


Whole Genome And Reverse Protein Phase Array Landscapes Of Patient Derived Osteosarcoma Xenograft Models, Chia-Chin Wu, Licai Huang, Zhongting Zhang, Zhenlin Ju, Xingzhi Song, E Anders Kolb, Wendong Zhang, Jonathan Gill, Min Ha, Malcolm A Smith, Peter Houghton, Christopher L Morton, Raushan Kurmasheva, John Maris, Yael Mosse, Yiling Lu, Richard Gorlick, P Andrew Futreal, Hannah C Beird Aug 2024

Whole Genome And Reverse Protein Phase Array Landscapes Of Patient Derived Osteosarcoma Xenograft Models, Chia-Chin Wu, Licai Huang, Zhongting Zhang, Zhenlin Ju, Xingzhi Song, E Anders Kolb, Wendong Zhang, Jonathan Gill, Min Ha, Malcolm A Smith, Peter Houghton, Christopher L Morton, Raushan Kurmasheva, John Maris, Yael Mosse, Yiling Lu, Richard Gorlick, P Andrew Futreal, Hannah C Beird

Faculty, Staff and Student Publications

Osteosarcoma is the most common primary bone malignancy in children and young adults, and it has few treatment options. As a result, there has been little improvement in survival outcomes in the past few decades. The need for models to test novel therapies is especially great in this disease since it is both rare and does not respond to most therapies. To address this, an NCI-funded consortium has characterized and utilized a panel of patient-derived xenograft models of osteosarcoma for drug testing. The exomes, transcriptomes, and copy number landscapes of these models have been presented previously. This study now adds …


Asthma And Hyperglycemia: Exploring The Interconnected Pathways, Dharani K Narendra, Sandhya Khurana Aug 2024

Asthma And Hyperglycemia: Exploring The Interconnected Pathways, Dharani K Narendra, Sandhya Khurana

Faculty, Staff and Students Publications

The interplay between asthma and glucose metabolism disorders, such as hyperglycemia, has gained increasing attention due to the potential exacerbation of asthma symptoms and severity. This review explores the complex relationship between hyperglycemia and asthma, emphasizing the pathophysiological links, the impact of glucose metabolism disorders on asthma, and the effects of asthma medications on glucose levels. Hyperglycemia, often induced by asthma treatments like corticosteroids, has been associated with an increased risk of asthma exacerbations. This review delves into the pathophysiology underlying this association, highlighting the role of insulin resistance, metabolic syndrome, and obesity in both the development and management of …


Mitral Annular Disjunction And Its Progression During Childhood In Marfan Syndrome, Tam T Doan, Alejandra Iturralde Chavez, Santiago O Valdes, Justin D Weigand, James C Wilkinson, Anitha Parthiban, Sara B Stephens, Ricardo H Pignatelli, Shaine A Morris Aug 2024

Mitral Annular Disjunction And Its Progression During Childhood In Marfan Syndrome, Tam T Doan, Alejandra Iturralde Chavez, Santiago O Valdes, Justin D Weigand, James C Wilkinson, Anitha Parthiban, Sara B Stephens, Ricardo H Pignatelli, Shaine A Morris

Faculty, Staff and Students Publications

AIMS: Data on mitral annular disjunction (MAD) in children with Marfan syndrome (MFS) are sparse. To investigate the diagnostic yield of MAD by echocardiography and cardiac magnetic resonance imaging (CMR), its prevalence and progression during childhood.

METHODS AND RESULTS: We included patientsMFS, defined by 2010 Ghent criteria and a pathogenic FBN1 variant or ectopia lentis. Two readers measured systolic separation between the mitral valve (MV) posterior hinge point and left ventricular (LV) myocardium on initial and subsequent imaging. MAD was defined as MV-LV separation ≥2 mm, MV prolapse (MVP) as atrial displacement ≥2 mm. Kappa coefficients evaluated echocardiogram-CMR agreement. Bland-Altman …


Inflammation, Physical Activity, And Disease-Free Survival In Stage Iii Colon Cancer: Calgb/Swog 80702 (Alliance), Justin C. Brown, Chao Ma, Qian Shi, Felix Couture, Philip Kuebler, Pankaj Kumar, Benjamin Tan, Smitha Krishnamurthi, Victor Chang, Richard M. Goldberg, Eileen M. O'Reilly, Anthony F. Shields, Jeffrey A. Meyerhardt Aug 2024

Inflammation, Physical Activity, And Disease-Free Survival In Stage Iii Colon Cancer: Calgb/Swog 80702 (Alliance), Justin C. Brown, Chao Ma, Qian Shi, Felix Couture, Philip Kuebler, Pankaj Kumar, Benjamin Tan, Smitha Krishnamurthi, Victor Chang, Richard M. Goldberg, Eileen M. O'Reilly, Anthony F. Shields, Jeffrey A. Meyerhardt

School of Medicine Faculty Publications

Background: Both inflammation and insufficient physical inactivity contribute to individual-level risk of disease recurrence and death in stage III colon cancer. The extent to which increased inflammatory risk can be offset by sufficient physical activity remains unknown. Methods: This cohort study was nested within the CALGB/SWOG 80702 (Alliance) randomized trial. Inflammatory burden was quantified by high-sensitivity C-reactive protein, interleukin-6, and soluble tumor necrosis factor-α receptor 2 after recovery from tumor resection. Physical activity was measured during and after postoperative chemotherapy. The primary endpoint was disease-free survival. Results: The 3-year disease-free survival rate was 88.4% among patients with low inflammation and …


Experiences Of Parent Coaches In An Intervention For Parents Of Young Children Newly Diagnosed With Type 1 Diabetes, Carrie Tully, Manuela Sinisterra, Wendy Levy, Christine H Wang, John Barber, Hailey Inverso, Marisa E Hilliard, Maureen Monaghan, Randi Streisand Aug 2024

Experiences Of Parent Coaches In An Intervention For Parents Of Young Children Newly Diagnosed With Type 1 Diabetes, Carrie Tully, Manuela Sinisterra, Wendy Levy, Christine H Wang, John Barber, Hailey Inverso, Marisa E Hilliard, Maureen Monaghan, Randi Streisand

Faculty, Staff and Students Publications

Objectives: This paper explores parent coaching experiences supporting parents of young children newly diagnosed with type 1 diabetes in a clinical trial.

Methods: In a trial for 157 parents, those in the intervention arm (n = 116) were paired with a parent coach (n = 37; Mage = 37.9 years, SD = 3.9; 94.6% mothers, 81.1% White non-Hispanic). Parent coaches provided diabetes-specific social support. Parent coaches completed monthly surveys and satisfaction/feasibility surveys, with a subset (n = 7) undergoing qualitative interviews at the end of this study.

Results: There were 2262 contacts between participants and their parent coaches, averaging …


Lung Cell Transplantation For Pulmonary Fibrosis, Irit Milman Krentsis, Yangxi Zheng, Chava Rosen, Sarah Y Shin, Christa Blagdon, Einav Shoshan, Yuan Qi, Jing Wang, Sandeep K Yadav, Esther Bachar Lustig, Elias Shetzen, Burton F Dickey, Harry Karmouty-Quintana, Yair Reisner Aug 2024

Lung Cell Transplantation For Pulmonary Fibrosis, Irit Milman Krentsis, Yangxi Zheng, Chava Rosen, Sarah Y Shin, Christa Blagdon, Einav Shoshan, Yuan Qi, Jing Wang, Sandeep K Yadav, Esther Bachar Lustig, Elias Shetzen, Burton F Dickey, Harry Karmouty-Quintana, Yair Reisner

Faculty, Staff and Student Publications

Idiopathic pulmonary fibrosis is a major cause of death with few treatment options. Here, we demonstrate the therapeutic efficacy for lung fibrosis of adult lung cell transplantation using a single-cell suspension of the entire lung in two distinct mouse systems: bleomycin treatment and mice lacking telomeric repeat-binding factor 1 expression in alveolar type 2 (AT2) cells (SPC-Cre TRF1fl/fl), spontaneously developing fibrosis. In both models, the progression of fibrosis was associated with reduced levels of host lung progenitors, enabling engraftment of donor progenitors without any additional conditioning, in contrast to our previous studies. Two months after transplantation, engrafted progenitors …


Perceptions Of Hiv-Related Comorbidities And Usability Of A Virtual Environment For Cardiovascular Disease Prevention Education In Sexual Minority Men With Hiv: Formative Phases Of A Pilot Randomized Controlled Trial, S Raquel Ramos, Harmony Reynolds, Constance Johnson, Gail Melkus, Trace Kershaw, Julian F Thayer, Allison Vorderstrasse Aug 2024

Perceptions Of Hiv-Related Comorbidities And Usability Of A Virtual Environment For Cardiovascular Disease Prevention Education In Sexual Minority Men With Hiv: Formative Phases Of A Pilot Randomized Controlled Trial, S Raquel Ramos, Harmony Reynolds, Constance Johnson, Gail Melkus, Trace Kershaw, Julian F Thayer, Allison Vorderstrasse

Faculty, Staff and Student Publications

Background: Sexual minority men with HIV are at an increased risk of cardiovascular disease (CVD) and have been underrepresented in behavioral research and clinical trials.

Objective: This study aims to explore perceptions of HIV-related comorbidities and assess the interest in and usability of a virtual environment for CVD prevention education in Black and Latinx sexual minority men with HIV.

Methods: This is a 3-phase pilot behavioral randomized controlled trial. We report on formative phases 1 and 2 that informed virtual environment content and features using qualitative interviews, usability testing, and beta testing with a total of 25 individuals. In phase …


Clinical Features And Disease Progression In Older Individuals With Rett Syndrome, Jeffrey L Neul, Timothy A Benke, Eric D Marsh, Bernhard Suter, Cary Fu, Robin C Ryther, Steven A Skinner, David N Lieberman, Timothy Feyma, Arthur Beisang, Peter Heydemann, Sarika U Peters, Amitha Ananth, Alan K Percy Aug 2024

Clinical Features And Disease Progression In Older Individuals With Rett Syndrome, Jeffrey L Neul, Timothy A Benke, Eric D Marsh, Bernhard Suter, Cary Fu, Robin C Ryther, Steven A Skinner, David N Lieberman, Timothy Feyma, Arthur Beisang, Peter Heydemann, Sarika U Peters, Amitha Ananth, Alan K Percy

Faculty, Staff and Students Publications

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in MECP2 associated with milder severity, and that clinical features would not be static in older individuals. To address these hypotheses, we compared the distribution of MECP2 variants and clinical severity between younger individuals with Classic RTT (under 30 years old) and older individuals (over 30 years old). Contrary to expectation, enrichment of a severe MECP2 variant (R106W) was observed in the older cohort. Overall severity was not different …


Safety Of Treating Acute Pulmonary Embolism At Home: An Individual Patient Data Meta-Analysis, Dieuwke Luijten, Delphine Douillet, Kim Luijken, Cecile Tromeur, Andrea Penaloza, Olivier Hugli, Drahomir Aujesky, Stefano Barco, Joseph R Bledsoe, Kyle E Chang, Francis Couturaud, Paul L Den Exter, Carme Font, Menno V Huisman, David Jimenez, Christopher Kabrhel, Jeffrey A Kline, Stavros Konstantinides, Thijs Van Mens, Remedios Otero, W Frank Peacock, Olivier Sanchez, William B Stubblefield, Luca Valerio, David R Vinson, Philip Wells, Maarten Van Smeden, Pierre-Marie Roy, Frederikus A Klok Aug 2024

Safety Of Treating Acute Pulmonary Embolism At Home: An Individual Patient Data Meta-Analysis, Dieuwke Luijten, Delphine Douillet, Kim Luijken, Cecile Tromeur, Andrea Penaloza, Olivier Hugli, Drahomir Aujesky, Stefano Barco, Joseph R Bledsoe, Kyle E Chang, Francis Couturaud, Paul L Den Exter, Carme Font, Menno V Huisman, David Jimenez, Christopher Kabrhel, Jeffrey A Kline, Stavros Konstantinides, Thijs Van Mens, Remedios Otero, W Frank Peacock, Olivier Sanchez, William B Stubblefield, Luca Valerio, David R Vinson, Philip Wells, Maarten Van Smeden, Pierre-Marie Roy, Frederikus A Klok

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis.

METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events …


Right Ventricle-Pulmonary Artery Conduit Replacement Resolves Anomalous Single Coronary Stenosis In Repaired Tetralogy Of Fallot, Karl Kristian Lundin, Edward Hickey, Prakash Masand, Vivian Dimas, Katherine Bohard Salciccioli Aug 2024

Right Ventricle-Pulmonary Artery Conduit Replacement Resolves Anomalous Single Coronary Stenosis In Repaired Tetralogy Of Fallot, Karl Kristian Lundin, Edward Hickey, Prakash Masand, Vivian Dimas, Katherine Bohard Salciccioli

Faculty, Staff and Students Publications

A 41-year-old man with repaired tetralogy of Fallot and a single coronary artery (CA) arising anteriorly presented with dyspnea in the setting of moderate right ventricle-pulmonary artery conduit (RV-PAC) stenosis and moderate-to-severe extrinsic left main CA compression between the aorta and RV-PAC. His CA stenosis resolved after successful RV-PAC replacement.


Junctophilin-2 Regulates Mitochondrial Metabolism, Sasha Z Prisco, Lynn M Hartweck, Felipe Kazmirczak, Jenna B Mendelson, Stephanie L Deng, Madelyn Blake, Satadru K Lahiri, Xander H T Wehrens, Kurt W Prins Aug 2024

Junctophilin-2 Regulates Mitochondrial Metabolism, Sasha Z Prisco, Lynn M Hartweck, Felipe Kazmirczak, Jenna B Mendelson, Stephanie L Deng, Madelyn Blake, Satadru K Lahiri, Xander H T Wehrens, Kurt W Prins

Faculty, Staff and Students Publications

No abstract provided.


Pre-Existing Immunocompromising Conditions And Outcomes Of Acute Covid-19 Patients Admitted For Pediatric Intensive Care, Courtney M Rowan, Brenna Labere, Cameron C Young, Laura D Zambrano, Margaret M Newhams, Suden Kucukak, Elizabeth R Mcnamara, Elizabeth H Mack, Julie C Fitzgerald, Katherine Irby, Aline B Maddux, Jennifer E Schuster, Michele Kong, Heda Dapul, Stephanie P Schwartz, Melania M Bembea, Laura L Loftis, Amanda R Kolmar, Christopher J Babbitt, Ryan A Nofziger, Mark W Hall, Shira J Gertz, Natalie Z Cvijanovich, Matt S Zinter, Natasha B Halasa, Tamara T Bradford, Gwenn E Mclaughlin, Aalok R Singh, Charlotte V Hobbs, Kari Wellnitz, Mary A Staat, Bria M Coates, Hillary R Crandall, Mia Maamari, Kevin M Havlin, Adam J Schwarz, Christopher L Carroll, Emily R Levy, Kristin L Moffitt, Angela P Campbell, Adrienne G Randolph, Janet Chou Aug 2024

Pre-Existing Immunocompromising Conditions And Outcomes Of Acute Covid-19 Patients Admitted For Pediatric Intensive Care, Courtney M Rowan, Brenna Labere, Cameron C Young, Laura D Zambrano, Margaret M Newhams, Suden Kucukak, Elizabeth R Mcnamara, Elizabeth H Mack, Julie C Fitzgerald, Katherine Irby, Aline B Maddux, Jennifer E Schuster, Michele Kong, Heda Dapul, Stephanie P Schwartz, Melania M Bembea, Laura L Loftis, Amanda R Kolmar, Christopher J Babbitt, Ryan A Nofziger, Mark W Hall, Shira J Gertz, Natalie Z Cvijanovich, Matt S Zinter, Natasha B Halasa, Tamara T Bradford, Gwenn E Mclaughlin, Aalok R Singh, Charlotte V Hobbs, Kari Wellnitz, Mary A Staat, Bria M Coates, Hillary R Crandall, Mia Maamari, Kevin M Havlin, Adam J Schwarz, Christopher L Carroll, Emily R Levy, Kristin L Moffitt, Angela P Campbell, Adrienne G Randolph, Janet Chou

Faculty, Staff and Students Publications

BACKGROUND: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care.

METHODS: Fifty-five hospitals in 30 US states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients(PICU) or high-acuity unit for acute COVID-19 were included.

RESULTS: Of 1274 patients, 105 (8.2%) had an ICC, including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid-organ transplantation, 16 (15.2%) solid tumors, and 13 (12.4%) autoimmune disorders. Patients with ICCs were …


Preventive Effects Of Quercetin On The Leaky Gut By Suppression Of Il-1beta-Induced Transcription Factors Involved In An Inflammatory Pathway In Colonic Epithelial Cells, Wannaporn Chayalak, Sumpun Thammacharoen, Chatsri Deachapunya, Sutthasinee Poonyachoti Aug 2024

Preventive Effects Of Quercetin On The Leaky Gut By Suppression Of Il-1beta-Induced Transcription Factors Involved In An Inflammatory Pathway In Colonic Epithelial Cells, Wannaporn Chayalak, Sumpun Thammacharoen, Chatsri Deachapunya, Sutthasinee Poonyachoti

The Thai Journal of Veterinary Medicine

Flavonol quercetin (Q), found in vegetables and fruits, demonstrates the most potent anti-inflammatory effect. The preventive effect and cellular mechanisms of Q (Q1, Q10, and Q100 µM) on IL-1β induced leaky gut via the signaling molecules of inflammatory pathway, NF-κB p65-iκB/or p38/ERK1/2/MLCK/phospho(p)-MLC were investigated in Caco-2 cells. The cytotoxic effect of Q was initially determined by MTT assay. Transepithelial electrical resistance (TER) and apical-to-basolateral fluorescein isothiocyanate-labeled dextran (FD-4) flux were used to determine paracellular permeability. The protein expression of signaling molecules was examined by Western blot analysis, and their target MLCK mRNA expression was determined using real-time PCR. All Q …


Infant And Adult Human Intestinal Enteroids Are Morphologically And Functionally Distinct, Grace O Adeniyi-Ipadeola, Julia D Hankins, Amal Kambal, Xi-Lei Zeng, Ketki Patil, Victoria Poplaski, Carolyn Bomidi, Hoa Nguyen-Phuc, Sandra L Grimm, Cristian Coarfa, Fabio Stossi, Sue E Crawford, Sarah E Blutt, Allison L Speer, Mary K Estes, Sasirekha Ramani Aug 2024

Infant And Adult Human Intestinal Enteroids Are Morphologically And Functionally Distinct, Grace O Adeniyi-Ipadeola, Julia D Hankins, Amal Kambal, Xi-Lei Zeng, Ketki Patil, Victoria Poplaski, Carolyn Bomidi, Hoa Nguyen-Phuc, Sandra L Grimm, Cristian Coarfa, Fabio Stossi, Sue E Crawford, Sarah E Blutt, Allison L Speer, Mary K Estes, Sasirekha Ramani

Faculty, Staff and Students Publications

UNLABELLED: Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in biomedical research, few studies have used HIEs from infants. Considering the dramatic developmental changes that occur during infancy, it is important to establish models that represent infant intestinal characteristics and physiological responses. We established jejunal HIEs from infant surgical samples and performed comparisons to jejunal HIEs from adults using RNA sequencing (RNA-Seq) and morphologic analyses. We then validated differences in key pathways through functional studies and determined whether these cultures recapitulate known features of the infant …