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Articles 5731 - 5760 of 11132

Full-Text Articles in Diseases

Endothelial Activation And Fibrotic Changes Are Impeded By Laminar Flow-Induced Chk1-Senp2 Activity Through Mechanisms Distinct From Endothelial-To-Mesenchymal Cell Transition, Minh T H Nguyen, Masaki Imanishi, Shengyu Li, Khanh Chau, Priyanka Banerjee, Loka Reddy Velatooru, Kyung Ae Ko, Venkata S K Samanthapudi, Young J Gi, Ling-Ling Lee, Rei J Abe, Elena Mcbeath, Anita Deswal, Steven H Lin, Nicolas L Palaskas, Robert Dantzer, Keigi Fujiwara, Mae K Borchrdt, Estefani Berrios Turcios, Elizabeth A Olmsted-Davis, Sivareddy Kotla, John P Cooke, Guangyu Wang, Jun-Ichi Abe, Nhat-Tu Le Jan 2023

Endothelial Activation And Fibrotic Changes Are Impeded By Laminar Flow-Induced Chk1-Senp2 Activity Through Mechanisms Distinct From Endothelial-To-Mesenchymal Cell Transition, Minh T H Nguyen, Masaki Imanishi, Shengyu Li, Khanh Chau, Priyanka Banerjee, Loka Reddy Velatooru, Kyung Ae Ko, Venkata S K Samanthapudi, Young J Gi, Ling-Ling Lee, Rei J Abe, Elena Mcbeath, Anita Deswal, Steven H Lin, Nicolas L Palaskas, Robert Dantzer, Keigi Fujiwara, Mae K Borchrdt, Estefani Berrios Turcios, Elizabeth A Olmsted-Davis, Sivareddy Kotla, John P Cooke, Guangyu Wang, Jun-Ichi Abe, Nhat-Tu Le

Faculty, Staff and Student Publications

BACKGROUND: The deSUMOylase sentrin-specific isopeptidase 2 (SENP2) plays a crucial role in atheroprotection. However, the phosphorylation of SENP2 at T368 under disturbed flow (D-flow) conditions hinders its nuclear function and promotes endothelial cell (EC) activation. SUMOylation has been implicated in D-flow-induced endothelial-to-mesenchymal transition (endoMT), but the precise role of SENP2 in counteracting this process remains unclear.

METHOD: We developed a phospho-specific SENP2 S344 antibody and generated knock-in (KI) mice with a phospho-site mutation of SENP2 S344A using CRISPR/Cas9 technology. We then investigated the effects of SENP2 S344 phosphorylation under two distinct flow patterns and during hypercholesteremia (HC)-mediated EC activation.

RESULT: …


The Health-Promoting Effects And The Mechanism Of Intermittent Fasting, Simin Liu, Min Zeng, Weixi Wan, Ming Huang, Xiang Li, Zixian Xie, Shang Wang, Yu Cai Jan 2023

The Health-Promoting Effects And The Mechanism Of Intermittent Fasting, Simin Liu, Min Zeng, Weixi Wan, Ming Huang, Xiang Li, Zixian Xie, Shang Wang, Yu Cai

Faculty, Staff and Student Publications

Intermittent fasting (IF) is an eating pattern in which individuals go extended periods with little or no energy intake after consuming regular food in intervening periods. IF has several health-promoting effects. It can effectively reduce weight, fasting insulin levels, and blood glucose levels. It can also increase the antitumor activity of medicines and cause improvement in the case of neurological diseases, such as memory deficit, to achieve enhanced metabolic function and prolonged longevity. Additionally, IF activates several biological pathways to induce autophagy, encourages cell renewal, prevents cancer cells from multiplying and spreading, and delays senescence. However, IF has specific adverse …


Induction Of Thrombotic Thrombocytopenic Purpura By Dengue Virus Infection In A Critical Patient: Role Of Therapeutic Plasma Exchange, Rathindra Nath Biswas, Sudipta Sekhar Das, Anupam Chakrapani, Subrata Sen Jan 2023

Induction Of Thrombotic Thrombocytopenic Purpura By Dengue Virus Infection In A Critical Patient: Role Of Therapeutic Plasma Exchange, Rathindra Nath Biswas, Sudipta Sekhar Das, Anupam Chakrapani, Subrata Sen

Faculty, Staff and Student Publications

Thrombotic thrombocytopenic purpura (TTP) secondary to dengue fever is a very unusual occurrence. Both conditions are fatal and can result in significant mortality and morbidity if left untreated. In this case, we present a young lady who suffered dengue fever followed by microangiopathic anemia, thrombocytopenic purpura, and altered sensorium. Investigations revealed microangiopathic hemolysis; there was no evidence of disseminated intravascular coagulation. As soon as, we diagnosed the patient as having TTP, we treated her with serial plasma exchange therapy, steroids, and monoclonal antibodies such as rituximab. The patient responded very well to the treatment and completely recovered from neurological symptoms …


View-Sharing For 4d Magnetic Resonance Imaging With Randomized Projection-Encoding Enables Improvements Of Respiratory Motion Imaging For Treatment Planning In Abdominothoracic Radiotherapy, Ergys Subashi, Li Feng, Yilin Liu, Scott Robertson, Paul Segars, Bastiaan Driehuys, Christopher R Kelsey, Fang-Fang Yin, Ricardo Otazo, Jing Cai Jan 2023

View-Sharing For 4d Magnetic Resonance Imaging With Randomized Projection-Encoding Enables Improvements Of Respiratory Motion Imaging For Treatment Planning In Abdominothoracic Radiotherapy, Ergys Subashi, Li Feng, Yilin Liu, Scott Robertson, Paul Segars, Bastiaan Driehuys, Christopher R Kelsey, Fang-Fang Yin, Ricardo Otazo, Jing Cai

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The accuracy and precision of radiation therapy are dependent on the characterization of organ-at-risk and target motion. This work aims to demonstrate a 4D magnetic resonance imaging (MRI) method for improving spatial and temporal resolution in respiratory motion imaging for treatment planning in abdominothoracic radiotherapy.

MATERIALS AND METHODS: The spatial and temporal resolution of phase-resolved respiratory imaging is improved by considering a novel sampling function based on quasi-random projection-encoding and peripheral k-space view-sharing. The respiratory signal is determined directly from k-space, obviating the need for an external surrogate marker. The average breathing curve is used to optimize …


Pyrolyzed Deketene Curcumin Controls Regulatory T Cell Generation And Gastric Cancer Metabolism Cooperate With 2-Deoxy-D-Glucose, Takashi Maruyama, Hirofumi Miyazaki, Yun-Ji Lim, Jian Gu, Masaki Ishikawa, Taichi Yoshida, Wanjun Chen, Yuji Owada, Hiroyuki Shibata Jan 2023

Pyrolyzed Deketene Curcumin Controls Regulatory T Cell Generation And Gastric Cancer Metabolism Cooperate With 2-Deoxy-D-Glucose, Takashi Maruyama, Hirofumi Miyazaki, Yun-Ji Lim, Jian Gu, Masaki Ishikawa, Taichi Yoshida, Wanjun Chen, Yuji Owada, Hiroyuki Shibata

Faculty, Staff and Student Publications

Pyrolyzed deketene curcumin GO-Y022 prevents carcinogenesis in a gastric cancer mouse model. However, it is still less clear if GO-Y022 affects tumor-induced immune suppression. In this study, we found that GO-Y022 inhibited Treg generation in the presence of transforming growth factor beta 1 (TGF-β). However, GO-Y022 showed less impact on Foxp3+ Tregs in the gastric tumor microenvironment. Gastric tumor cells produce a large amount of L-lactate in the presence of GO-Y022 and diminish the inhibitory role of GO-Y022 against Treg generation in response to TGF-β. Therefore, naïve CD4+ T cells co-cultured with GO-Y022 treated gastric tumor cells increased Treg generation. …


Cytosolic Dna Sensing Protein Pathway Is Activated In Human Hearts With Dilated Cardiomyopathy, Leila Rouhi, Sirisha M Cheedipudi, Benjamin Cathcart, Priyatansh Gurha, Ali J Marian Jan 2023

Cytosolic Dna Sensing Protein Pathway Is Activated In Human Hearts With Dilated Cardiomyopathy, Leila Rouhi, Sirisha M Cheedipudi, Benjamin Cathcart, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

INTRODUCTION: The genome is constantly exposed to numerous stressors, which induce DNA lesions, including double-stranded DNA breaks (DSBs). DSBs are the most dangerous, as they induce genomic instability. In response to DNA damage, the cell activates nuclear DNA damage response (DDR) and the cytosolic DNA sensing protein (CDSP) pathways, the latter upon release of the DSBs to the cytosol. The CDSP pathway activates NFκB and IRF3, which induce the expression of the pro-inflammatory genes. There is scant data on the activation of the CDSP pathway in human hearts with dilated cardiomyopathy (DCM).

AIM: We aimed to determine expression levels of …


Review Article: New Treatments For Advanced Differentiated Thyroid Cancers And Potential Mechanisms Of Drug Resistance, Sarah Hamidi, Marie-Claude Hofmann, Priyanka C Iyer, Maria E Cabanillas, Mimi I Hu, Naifa L Busaidy, Ramona Dadu Jan 2023

Review Article: New Treatments For Advanced Differentiated Thyroid Cancers And Potential Mechanisms Of Drug Resistance, Sarah Hamidi, Marie-Claude Hofmann, Priyanka C Iyer, Maria E Cabanillas, Mimi I Hu, Naifa L Busaidy, Ramona Dadu

Faculty, Staff and Student Publications

The treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has undergone major advancements in the last decade, causing a paradigm shift in the management and prognosis of these patients. Better understanding of the molecular drivers of tumorigenesis and access to next generation sequencing of tumors have led to the development and Food and Drug Administration (FDA)-approval of numerous targeted therapies for RR-DTCs, including antiangiogenic multikinase inhibitors, and more recently, fusion-specific kinase inhibitors such as RET inhibitors and NTRK inhibitors. BRAF + MEK inhibitors have also been approved for BRAF-mutated solid tumors and are routinely used in RR-DTCs in …


Children Then, Adults Now: Long-Term Outcomes-Performance At 15, 20, And 25 Years Of Cochlear Implant Use, João Elói Moura, Jorge Humberto Martins, Marisa Alves, Graça Oliveira, Daniela Ramos, Helena Alves, Ricardo Caiado, António Teixeira, Luís Filipe Silva, Jorge Migueis Jan 2023

Children Then, Adults Now: Long-Term Outcomes-Performance At 15, 20, And 25 Years Of Cochlear Implant Use, João Elói Moura, Jorge Humberto Martins, Marisa Alves, Graça Oliveira, Daniela Ramos, Helena Alves, Ricardo Caiado, António Teixeira, Luís Filipe Silva, Jorge Migueis

Faculty, Staff and Student Publications

MOTIVATION: Severe to profound sensorineural hearing loss interferes with a child's development at the cognitive, linguistic, academic, and social levels. Since the beginning of the pediatric auditory rehabilitation program through cochlear implantation in the Ear, Nose, and Throat (ENT) Service of the Coimbra Hospital and University Center (CHUC), Portugal, its mentors defended the early diagnosis of hearing loss followed by timely intervention, and this was considered the starting point to optimize (re)habilitation through this method. Three decades or so later, recently we conducted this study to evaluate the performance of patients implanted in the initial phase of the cochlear implantation …


Wnt Signaling In Liver Regeneration, Disease, And Cancer, Gengyi Zou, Jae-Il Park Jan 2023

Wnt Signaling In Liver Regeneration, Disease, And Cancer, Gengyi Zou, Jae-Il Park

Faculty, Staff and Student Publications

The liver exhibits the highest recovery rate from acute injuries. However, in chronic liver disease, the long-term loss of hepatocytes often leads to adverse consequences such as fibrosis, cirrhosis, and liver cancer. The Wnt signaling plays a pivotal role in both liver regeneration and tumorigenesis. Therefore, manipulating the Wnt signaling has become an attractive approach to treating liver disease, including cancer. Nonetheless, given the crucial roles of Wnt signaling in physiological processes, blocking Wnt signaling can also cause several adverse effects. Recent studies have identified cancer-specific regulators of Wnt signaling, which would overcome the limitation of Wnt signaling target approaches. …


Exercise And Ischemia-Activated Pathways In Limb Muscle Angiogenesis And Vascular Regeneration, Vihang A Narkar Jan 2023

Exercise And Ischemia-Activated Pathways In Limb Muscle Angiogenesis And Vascular Regeneration, Vihang A Narkar

Faculty, Staff and Student Publications

Exercise has a profound effect on cardiovascular disease, particularly through vascular remodeling and regeneration. Peripheral artery disease (PAD) is one such cardiovascular condition that benefits from regular exercise or rehabilitative physical therapy in terms of slowing the progression of disease and delaying amputations. Various rodent pre-clinical studies using models of PAD and exercise have shed light on molecular pathways of vascular regeneration. Here, I review key exercise-activated signaling pathways (nuclear receptors, kinases, and hypoxia inducible factors) in the skeletal muscle that drive paracrine regenerative angiogenesis. The rationale for highlighting the skeletal muscle is that it is the largest organ recruited …


Chronic Liver Disease-Related Mortality In Diabetes Before And During The Covid-19 In The United States, Donghee Kim, Omar Alshuwaykh, Brittany B Dennis, George Cholankeril, Joshua W Knowles, Aijaz Ahmed Jan 2023

Chronic Liver Disease-Related Mortality In Diabetes Before And During The Covid-19 In The United States, Donghee Kim, Omar Alshuwaykh, Brittany B Dennis, George Cholankeril, Joshua W Knowles, Aijaz Ahmed

Faculty, Staff and Students Publications

BACKGROUND: Global pandemic of COVID-19 represents an unprecedented challenge. COVID-19 has predominantly targeted vulnerable populations with pre-existing chronic medical diseases, such as diabetes and chronic liver disease.

AIMS: We estimated chronic liver disease-related mortality trends among individuals with diabetes before and during the COVID-19 pandemic.

METHODS: Utilizing the US national mortality database and Census, we determined the quarterly age-standardized chronic liver disease-related mortality and quarterly percentage change (QPC) among individuals with diabetes.

RESULTS: The quarterly age-standardized mortality for chronic liver disease and/or cirrhosis among individuals with diabetes remained stable before the COVID-19 pandemic and sharply increased during the COIVD-19 pandemic …


Documented Adverse Drug Reactions And Discontinuation Of Angiotensin-Converting Enzyme Inhibitors And Angiotensin Receptor Blockers In Chronic Kidney Disease, L Parker Gregg, Peter A Richardson, Michael A Herrera, Julia M Akeroyd, Shehrezade A Jafry, Glenn T Gobbel, Sheena Wydermyer, Jennifer Arney, Adriana Hung, Michael E Matheny, Salim S Virani, Sankar D Navaneethan Jan 2023

Documented Adverse Drug Reactions And Discontinuation Of Angiotensin-Converting Enzyme Inhibitors And Angiotensin Receptor Blockers In Chronic Kidney Disease, L Parker Gregg, Peter A Richardson, Michael A Herrera, Julia M Akeroyd, Shehrezade A Jafry, Glenn T Gobbel, Sheena Wydermyer, Jennifer Arney, Adriana Hung, Michael E Matheny, Salim S Virani, Sankar D Navaneethan

Faculty, Staff and Students Publications

INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are frequently discontinued in patients with chronic kidney disease (CKD). Documented adverse drug reactions (ADRs) in medical records may provide insight into the reasons for treatment discontinuation.

METHODS: In this retrospective cohort of US veterans from 2005 to 2019, we identified individuals with CKD and a current prescription for an ACEi or ARB (current user group) or a discontinued prescription within the preceding 5 years (discontinued group). Documented ADRs in structured datasets associated with an ACEi or ARB were categorized into 17 pre-specified groups. Logistic regression assessed associations of documented …


Risk Stratification For Hepatocellular Cancer Among Patients With Cirrhosis Using A Hepatic Fat Polygenic Risk Score, Aaron P Thrift, Fasiha Kanwal, Yanhong Liu, Saira Khaderi, Amit G Singal, Jorge A Marrero, Nicole Loo, Sumeet K Asrani, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Spiridon Tsavachidis, Xiangjun Gu, Christopher I Amos, Hashem B El-Serag Jan 2023

Risk Stratification For Hepatocellular Cancer Among Patients With Cirrhosis Using A Hepatic Fat Polygenic Risk Score, Aaron P Thrift, Fasiha Kanwal, Yanhong Liu, Saira Khaderi, Amit G Singal, Jorge A Marrero, Nicole Loo, Sumeet K Asrani, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Spiridon Tsavachidis, Xiangjun Gu, Christopher I Amos, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND: Polygenic risk scores (PRS) hold the promise to refine prognostication in hepatocellular cancer (HCC). The few available HCC PRS include germline risk variants identified among individuals of mostly European ancestry, but data are lacking on the transportability of these PRS in multiethnic U.S patients with cirrhosis from multiple etiologies.

METHODS: We used data from 1644 patients with cirrhosis enrolled in two prospective cohort studies in the U.S. Patients were followed until HCC diagnosis, death, liver transplantation, or last study visit through June 30, 2021. The high-risk variants in PNPLA3-MBOAT7-TM6SF2-GCKR were combined in a PRS and we evaluated its association …


A Rare Case Of Isolated Thoracic Al-Amyloidoma Causing Complete Atelectasis Of The Right Lung, Smruti Rath, Nicholas Joseph Dcunha, Neel Bhan, Bettye Cox, Muhammad Adrish Jan 2023

A Rare Case Of Isolated Thoracic Al-Amyloidoma Causing Complete Atelectasis Of The Right Lung, Smruti Rath, Nicholas Joseph Dcunha, Neel Bhan, Bettye Cox, Muhammad Adrish

Faculty, Staff and Students Publications

Tumoral amyloidosis, or amyloidoma, is a benign, but rare form of amyloidosis that has been reported with a favorable prognosis following surgical resection in some case reports. We present a case of acute on chronic respiratory failure secondary to extensive growth of a thoracic amyloidoma causing atelectasis of the right lung. Our case patient had greater morbidity due to late presentation and extensive disease at diagnosis, precluding any surgical intervention. Radiation therapy and medical management were unsuccessful in reducing disease burden. Early diagnosis and detection are pivotal to improving survival in patients with isolated thoracic amyloidoma.


Native Bk Polyomavirus Nephropathy In An Orthotopic Heart Transplant Patient, Zachary M Thompson, George Ajene, Prathit A Kulkarni, Nidhi Aggarwal, Savitri Fedson, Maulin K Shah Jan 2023

Native Bk Polyomavirus Nephropathy In An Orthotopic Heart Transplant Patient, Zachary M Thompson, George Ajene, Prathit A Kulkarni, Nidhi Aggarwal, Savitri Fedson, Maulin K Shah

Faculty, Staff and Students Publications

BK polyomavirus nephropathy (BKVN) is a common cause of nephropathy in kidney transplant patients and is typically seen within the first year after transplantation. BK polyomavirus nephropathy can occur in the native kidneys of patients with nonrenal solid-organ transplants (NRSOT). However, this is rare, especially outside the early post-transplant period, and BKVN is not usually considered in the differential diagnosis for acute kidney injury in NRSOT patients. We present a case of a 75-year-old man who had undergone orthotopic heart transplant 13 years prior with stable allograft function who developed progressive renal dysfunction in the setting of recent unilateral obstructive …


Emerging Challenges To Cellular Therapy Of Cancer, Premal D Lulla, Malcolm Brenner Jan 2023

Emerging Challenges To Cellular Therapy Of Cancer, Premal D Lulla, Malcolm Brenner

Faculty, Staff and Students Publications

Cellular immunotherapy of cancer in the form of chimeric antigen receptor-modified T-cell therapy has become a standard treatment for lymphoid and more recently plasma cell malignancies. Although their successes in these cancers represent a breakthrough for adoptive cell therapy, there are several challenges to their continued growth in the field of cancer medicine. In this review, we discuss the progress made thus far toward achieving "off-the-shelf" accessibility of cell therapies that has the potential to greatly offset the costs associated with the current practice of making patient-specific products. We also review the innovations under investigation that attempt to make cellular …


The Rsv F P27 Peptide: Current Knowledge, Important Questions, Wanderson Rezende, Hadley E Neal, Rebecca E Dutch, Pedro A Piedra Jan 2023

The Rsv F P27 Peptide: Current Knowledge, Important Questions, Wanderson Rezende, Hadley E Neal, Rebecca E Dutch, Pedro A Piedra

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) remains a leading cause of hospitalizations and death for young children and adults over 65. The worldwide impact of RSV has prioritized the search for an RSV vaccine, with most targeting the critical fusion (F) protein. However, questions remain about the mechanism of RSV entry and RSV F triggering and fusion promotion. This review highlights these questions, specifically those surrounding a cleaved 27 amino acids long peptide within F, p27.


Squamous Cell Carcinoma With Unusual Benign-Appearing Cystic Features On Histology, Usman Asad, Suzanne Alkul, Ikue Shimizu, Jennifer Ranario Jan 2023

Squamous Cell Carcinoma With Unusual Benign-Appearing Cystic Features On Histology, Usman Asad, Suzanne Alkul, Ikue Shimizu, Jennifer Ranario

Faculty, Staff and Students Publications

Squamous cell carcinoma (SCC) is a malignancy that arises from keratinocytes of the epidermis. Cystic variants of several types of cutaneous neoplasms have been rarely described in the literature. We report a case of biopsy-proven, well-differentiated invasive SCC treated with Mohs surgery. On frozen sections, the pathology slides showed benign-appearing cystic structures in the margins that persisted after it had appeared that the original malignancy had been cleared. After taking another Mohs stage due to clinical suspicion, additional SCC was found and was subsequently cleared after two more Mohs stages. To the best of our knowledge, this is the first …


Integrative Metabolomics And Transcriptomics Analysis Reveals Novel Therapeutic Vulnerabilities In Lung Cancer, Jose Thaiparambil, Jianrong Dong, Sandra L Grimm, Dimuthu Perera, Chandra Shekar R Ambati, Vasanta Putluri, Matthew J Robertson, Tajhal D Patel, Brandon Mistretta, Preethi H Gunaratne, Min P Kim, Jason T Yustein, Nagireddy Putluri, Cristian Coarfa, Randa El-Zein Jan 2023

Integrative Metabolomics And Transcriptomics Analysis Reveals Novel Therapeutic Vulnerabilities In Lung Cancer, Jose Thaiparambil, Jianrong Dong, Sandra L Grimm, Dimuthu Perera, Chandra Shekar R Ambati, Vasanta Putluri, Matthew J Robertson, Tajhal D Patel, Brandon Mistretta, Preethi H Gunaratne, Min P Kim, Jason T Yustein, Nagireddy Putluri, Cristian Coarfa, Randa El-Zein

Faculty, Staff and Students Publications

BACKGROUND: Non-small cell lung cancer (NSCLC) comprises the majority (~85%) of all lung tumors, with lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being the most frequently diagnosed histological subtypes. Multi-modal omics profiling has been carried out in NSCLC, but no studies have yet reported a unique metabolite-related gene signature and altered metabolic pathways associated with LUAD and LUSC.

METHODS: We integrated transcriptomics and metabolomics to analyze 30 human lung tumors and adjacent noncancerous tissues. Differential co-expression was used to identify modules of metabolites that were altered between normal and tumor.

RESULTS: We identified unique metabolite-related gene signatures specific for …


Heterologous Mrna-Protein Vaccination With Tc24 Induces A Robust Cellular Immune Response Against Trypanosoma Cruzi, Characterized By An Increased Level Of Polyfunctional Cd8+ T-Cells, Cristina Poveda, Ana Carolina Leão, Chiara Mancino, Francesca Taraballi, Yi-Lin Chen, Rakesh Adhikari, Maria Jose Villar, Rakhi Kundu, Duc M Nguyen, Leroy Versteeg, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Jeroen Pollet, Kathryn M Jones Jan 2023

Heterologous Mrna-Protein Vaccination With Tc24 Induces A Robust Cellular Immune Response Against Trypanosoma Cruzi, Characterized By An Increased Level Of Polyfunctional Cd8+ T-Cells, Cristina Poveda, Ana Carolina Leão, Chiara Mancino, Francesca Taraballi, Yi-Lin Chen, Rakesh Adhikari, Maria Jose Villar, Rakhi Kundu, Duc M Nguyen, Leroy Versteeg, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Jeroen Pollet, Kathryn M Jones

Faculty, Staff and Students Publications

Tc24 is a Trypanosoma cruzi-derived flagellar protein that, when formulated with a TLR-4 agonist adjuvant, induces a balanced immune response in mice, elevating IgG2a antibody titers and IFN-γ levels. Furthermore, vaccination with the recombinant Tc24 protein can reduce parasite levels and improve survival during acute infection. Although some mRNA vaccines have been proven to elicit a stronger immune response than some protein vaccines, they have not been used against T. cruzi. This work evaluates the immunogenicity of a heterologous prime/boost vaccination regimen using protein and mRNA-based Tc24 vaccines. Mice (C57BL/6) were vaccinated twice subcutaneously, three weeks apart, with …


Pre-Treatment Inflamed Tumor Immune Microenvironment Is Associated With Folfirinox Response In Pancreatic Cancer, Zachary Gao, Sung Wook Kang, Derek Erstad, Joseph Azar, George Van Buren, William Fisher, Zequn Sun, Mark P Rubinstein, Hyun-Sung Lee, E Ramsay Camp Jan 2023

Pre-Treatment Inflamed Tumor Immune Microenvironment Is Associated With Folfirinox Response In Pancreatic Cancer, Zachary Gao, Sung Wook Kang, Derek Erstad, Joseph Azar, George Van Buren, William Fisher, Zequn Sun, Mark P Rubinstein, Hyun-Sung Lee, E Ramsay Camp

Faculty, Staff and Students Publications

INTRODUCTION: Pancreatic adenocarcinoma (PDAC) is an aggressive tumor with limited response to both chemotherapy and immunotherapy. Pre-treatment tumor features within the tumor immune microenvironment (TiME) may influence treatment response. We hypothesized that the pre-treatment TiME composition differs between metastatic and primary lesions and would be associated with response to modified FOLFIRINOX (mFFX) or gemcitabine-based (Gem-based) therapy.

METHODS: Using RNAseq data from a cohort of treatment-naïve, advanced PDAC patients in the COMPASS trial, differential gene expression analysis of key immunomodulatory genes in were analyzed based on multiple parameters including tumor site, response to mFFX, and response to Gem-based treatment. The relative …


Inotropic Score And Vasoactive Inotropic Score As Predictors Of Outcomes In Congenital Diaphragmatic Hernia: A Single Center Retrospective Study, Srirupa Hari Gopal, Cynthia L Toy, Morcos Hanna, Betul Yilmaz Furtun, Joseph L Hagan, Ahmed A Nassr, Caraciolo J Fernandes, Sundeep Keswani, Sharada H Gowda Jan 2023

Inotropic Score And Vasoactive Inotropic Score As Predictors Of Outcomes In Congenital Diaphragmatic Hernia: A Single Center Retrospective Study, Srirupa Hari Gopal, Cynthia L Toy, Morcos Hanna, Betul Yilmaz Furtun, Joseph L Hagan, Ahmed A Nassr, Caraciolo J Fernandes, Sundeep Keswani, Sharada H Gowda

Faculty, Staff and Students Publications

BACKGROUND: Neonates with congenital diaphragmatic hernia (CDH) have varying degrees of pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac dysfunction. These neonates frequently require vasoactive support and are at high risk for mortality and morbidity, including prolonged ventilator support, need for extracorporeal membrane oxygenation (ECMO), prolonged length of stay, and need for tracheostomy. However, identifying which infants are at increased risk can be challenging. In this study, we sought to investigate the utility of the inotropic score (IS) and vasoactive inotropic score (VIS) as tools to predict significant clinical outcomes and overall survival in patients with CDH. Additionally, we evaluated the …


Combining Charlson Comorbidity And Vacs Indices Improves Prognostic Accuracy For All-Cause Mortality For Patients With And Without Hiv In The Veterans Health Administration, Kathleen A Mcginnis, Amy C Justice, Vincent C Marconi, Maria C Rodriguez-Barradas, Ronald G Hauser, Krisann K Oursler, Sheldon T Brown, Kendall J Bryant, Janet P Tate, Veterans Aging Cohort Study Affiliations Jan 2023

Combining Charlson Comorbidity And Vacs Indices Improves Prognostic Accuracy For All-Cause Mortality For Patients With And Without Hiv In The Veterans Health Administration, Kathleen A Mcginnis, Amy C Justice, Vincent C Marconi, Maria C Rodriguez-Barradas, Ronald G Hauser, Krisann K Oursler, Sheldon T Brown, Kendall J Bryant, Janet P Tate, Veterans Aging Cohort Study Affiliations

Faculty, Staff and Students Publications

INTRODUCTION: As people age with HIV (PWH), many comorbid diseases are more common than among age matched comparators without HIV (PWoH). While the Veterans Aging Cohort (VACS) Index 2.0 accurately predicts mortality in PWH using age and clinical biomarkers, the only included comorbidity is hepatitis C. We asked whether adding comorbid disease groupings from the Charlson Comorbidity Index (CCI) improves the accuracy of VACS Index.

METHODS: To maximize our ability to model mortality among older age groups, we began with PWoH in Veterans Health Administration (VA) from 2007-2017, divided into development and validation samples. Baseline predictors included age, and components …


A Rapid, Low-Cost, And Highly Sensitive Sars-Cov-2 Diagnostic Based On Whole-Genome Sequencing, Per A Adastra, Neva C Durand, Namita Mitra, Saul Godinez Pulido, Ragini Mahajan, Alyssa Blackburn, Zane L Colaric, Joshua W M Theisen, David Weisz, Olga Dudchenko, Andreas Gnirke, Suhas S P Rao, Parwinder Kaur, Erez Lieberman Aiden, Aviva Presser Aiden Jan 2023

A Rapid, Low-Cost, And Highly Sensitive Sars-Cov-2 Diagnostic Based On Whole-Genome Sequencing, Per A Adastra, Neva C Durand, Namita Mitra, Saul Godinez Pulido, Ragini Mahajan, Alyssa Blackburn, Zane L Colaric, Joshua W M Theisen, David Weisz, Olga Dudchenko, Andreas Gnirke, Suhas S P Rao, Parwinder Kaur, Erez Lieberman Aiden, Aviva Presser Aiden

Faculty, Staff and Students Publications

Early detection of SARS-CoV-2 infection is key to managing the current global pandemic, as evidence shows the virus is most contagious on or before symptom onset. Here, we introduce a low-cost, high-throughput method for diagnosing and studying SARS-CoV-2 infection. Dubbed Pathogen-Oriented Low-Cost Assembly & Re-Sequencing (POLAR), this method amplifies the entirety of the SARS-CoV-2 genome. This contrasts with typical RT-PCR-based diagnostic tests, which amplify only a few loci. To achieve this goal, we combine a SARS-CoV-2 enrichment method developed by the ARTIC Network (https://artic.network/) with short-read DNA sequencing and de novo genome assembly. Using this method, we can reliably ( …


Characteristics Of Type 2 Diabetes In Female And Male Youth, Beatriz Castillo Rodriguez, Marcela Astudillo, Mustafa Tosur, Ahmad Rafaey, Siripoom Mckay, Fida Bacha, Ashok Balasubramanyam, Maria J Redondo Jan 2023

Characteristics Of Type 2 Diabetes In Female And Male Youth, Beatriz Castillo Rodriguez, Marcela Astudillo, Mustafa Tosur, Ahmad Rafaey, Siripoom Mckay, Fida Bacha, Ashok Balasubramanyam, Maria J Redondo

Faculty, Staff and Students Publications

The incidence of type 2 diabetes in children is rising and carries a worse prognosis than in adults. The influence of sex on pediatric type 2 diabetes outcomes has not been well investigated. We studied 715 youth with type 2 diabetes diagnosed at a median age of 13.7 years and compared sex differences in demographic, clinical, and laboratory characteristics within the first year of diagnosis. Females diagnosed with type 2 diabetes were younger and at a higher stage of pubertal development than males, yet presented with lower A1Cs, a lower prevalence of diabetic ketoacidosis, and higher HDL cholesterol levels.


Enrollment Of Underrepresented Racial And Ethnic Groups In The Rare And Atypical Diabetes Network (Radiant), Mustafa Tosur, Laura Gandolfo, Ashok Balasubramanyam, Rochelle N Naylor, Toni I Pollin, Neda Rasouli, Sara J Cromer, John B Buse, Maria J Redondo, Radiant Study Group Jan 2023

Enrollment Of Underrepresented Racial And Ethnic Groups In The Rare And Atypical Diabetes Network (Radiant), Mustafa Tosur, Laura Gandolfo, Ashok Balasubramanyam, Rochelle N Naylor, Toni I Pollin, Neda Rasouli, Sara J Cromer, John B Buse, Maria J Redondo, Radiant Study Group

Faculty, Staff and Students Publications

INTRODUCTION: Diabetes mellitus in underrepresented racial and ethnic groups (URG) is rapidly increasing in incidence and has worse outcomes than diabetes in non-Hispanic White individuals. Rare and Atypical Diabetes Network (RADIANT) established recruitment targets based on the racial and ethnic distribution of the USA to enroll a diverse study population. We examined participation of URG across RADIANT study stages and described strategies to enhance recruitment and retention of URG.

MATERIALS AND METHODS: RADIANT is a multicenter NIH-funded study of people with uncharacterized forms of atypical diabetes. RADIANT participants consent online and progress through three sequential study stages, as eligible.

RESULTS: …


Delphi Panel Consensus Regarding Current Clinical Practice Management Options For Demodex Blepharitis, Marjan Farid, Brandon D Ayres, Eric Donnenfeld, Ian Benjamin Gaddie, Preeya K Gupta, Edward Holland, Richard Lindstrom, Stephen C Pflugfelder, Paul M Karpecki, Kelly K Nichols, Christopher E Starr, Elizabeth Yeu Jan 2023

Delphi Panel Consensus Regarding Current Clinical Practice Management Options For Demodex Blepharitis, Marjan Farid, Brandon D Ayres, Eric Donnenfeld, Ian Benjamin Gaddie, Preeya K Gupta, Edward Holland, Richard Lindstrom, Stephen C Pflugfelder, Paul M Karpecki, Kelly K Nichols, Christopher E Starr, Elizabeth Yeu

Faculty, Staff and Students Publications

PURPOSE: To obtain consensus on Demodex blepharitis (DB) treatment using a modified Delphi panel process.

METHODS: Literature search identified gaps in knowledge surrounding treatment of DB. Twelve ocular surface disease experts comprised the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH). They completed a live roundtable discussion in addition to 3 surveys consisting of scaled, open-ended, true/false, and multiple-choice questions pertaining to the treatment of DB. Consensus for scaled questions using a 1 to 9 Likert scale was predefined as median scores of 7–9 and 1–3. For other question types, consensus was achieved when 8 of 12 panelists agreed. …


Dry Eye Disease In Astronauts: A Narrative Review, Timon Ax, Bergita Ganse, Fabian N Fries, Nóra Szentmáry, Cintia S De Paiva, Francesc March De Ribot, Slade O Jensen, Berthold Seitz, Thomas J Millar Jan 2023

Dry Eye Disease In Astronauts: A Narrative Review, Timon Ax, Bergita Ganse, Fabian N Fries, Nóra Szentmáry, Cintia S De Paiva, Francesc March De Ribot, Slade O Jensen, Berthold Seitz, Thomas J Millar

Faculty, Staff and Students Publications

Long-duration spaceflight can have adverse effects on human health. One of the most common ocular conditions experienced by astronauts is dry eye disease (DED). Symptoms of DED include feelings of eye irritation, eye strain, foreign body sensation and blurred vision. Over 30% of International Space Station expedition crew members reported irritation and foreign body sensation. We reviewed the current literature on the prevalence and mechanisms of DED in astronauts and its potential implications for long-duration spaceflight, including the influence of environmental factors, such as microgravity and fluid shift on tear film physiology in space. DED has negative effects on astronaut …


Engaging Patients In Antimicrobial Stewardship: Co-Designed Educational Tool To Improve Periprocedural Care Through De-Implementation Of Guideline-Discordant Antimicrobial Use, Hawra Al Lawati, Marlena Shin, Rebecca Lamkin, Tyler Thompson, Isabella Epshtein, Hillary Mull, Dipandita Basnet Thapa, Dimitri Drekonja, Maria C Rodriguez-Barradas, Teena Huan Xu, Howard Gold, A Rani Elwy, Judy Strymish, Westyn Branch-Elliman Jan 2023

Engaging Patients In Antimicrobial Stewardship: Co-Designed Educational Tool To Improve Periprocedural Care Through De-Implementation Of Guideline-Discordant Antimicrobial Use, Hawra Al Lawati, Marlena Shin, Rebecca Lamkin, Tyler Thompson, Isabella Epshtein, Hillary Mull, Dipandita Basnet Thapa, Dimitri Drekonja, Maria C Rodriguez-Barradas, Teena Huan Xu, Howard Gold, A Rani Elwy, Judy Strymish, Westyn Branch-Elliman

Faculty, Staff and Students Publications

Effective de-implementation models often include replacement of an ineffective practice with an alternative. We co-developed patient education materials as a replacement strategy for inappropriate post-procedural antibiotics in cardiac device procedures. Lessons learned and developed materials may be used to promote infection prevention in other periprocedural settings.


Premature Senescence And Cardiovascular Disease Following Cancer Treatments: Mechanistic Insights, Ashita Jain, Diego Casanova, Alejandra Valdivia Padilla, Angelica Paniagua Bojorges, Sivareddy Kotla, Kyung Ae Ko, Venkata S K Samanthapudi, Khanh Chau, Minh T H Nguyen, Jake Wen, Selina L Hernandez Gonzalez, Shaefali P Rodgers, Elizabeth A Olmsted-Davis, Dale J Hamilton, Cielito Reyes-Gibby, Sai-Ching J Yeung, John P Cooke, Joerg Herrmann, Eduardo N Chini, Xiaolei Xu, Syed Wamique Yusuf, Momoko Yoshimoto, Philip L Lorenzi, Brain Hobbs, Sunil Krishnan, Efstratios Koutroumpakis, Nicolas L Palaskas, Guangyu Wang, Anita Deswal, Steven H Lin, Jun-Ichi Abe, Nhat-Tu Le Jan 2023

Premature Senescence And Cardiovascular Disease Following Cancer Treatments: Mechanistic Insights, Ashita Jain, Diego Casanova, Alejandra Valdivia Padilla, Angelica Paniagua Bojorges, Sivareddy Kotla, Kyung Ae Ko, Venkata S K Samanthapudi, Khanh Chau, Minh T H Nguyen, Jake Wen, Selina L Hernandez Gonzalez, Shaefali P Rodgers, Elizabeth A Olmsted-Davis, Dale J Hamilton, Cielito Reyes-Gibby, Sai-Ching J Yeung, John P Cooke, Joerg Herrmann, Eduardo N Chini, Xiaolei Xu, Syed Wamique Yusuf, Momoko Yoshimoto, Philip L Lorenzi, Brain Hobbs, Sunil Krishnan, Efstratios Koutroumpakis, Nicolas L Palaskas, Guangyu Wang, Anita Deswal, Steven H Lin, Jun-Ichi Abe, Nhat-Tu Le

Faculty, Staff and Student Publications

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality, especially among the aging population. The "response-to-injury" model proposed by Dr. Russell Ross in 1999 emphasizes inflammation as a critical factor in atherosclerosis development, with atherosclerotic plaques forming due to endothelial cell (EC) injury, followed by myeloid cell adhesion and invasion into the blood vessel walls. Recent evidence indicates that cancer and its treatments can lead to long-term complications, including CVD. Cellular senescence, a hallmark of aging, is implicated in CVD pathogenesis, particularly in cancer survivors. However, the precise mechanisms linking premature senescence to CVD in cancer survivors remain …