Digital Commons Network^™

Worth A Pound Of Cure? Emerging Strategies And Challenges In Cancer Immunoprevention, Saurav D Haldar, Eduardo Vilar, Anirban Maitra, Neeha Zaidi

Faculty, Staff and Student Publications

Cancer immunoprevention applies immunologic approaches such as vaccines to prevent, rather than to treat or cure, cancer. Despite limited success in the treatment of advanced disease, the development of cancer vaccines to intercept premalignant states is a promising area of current research. These efforts are supported by the rationale that vaccination in the premalignant setting is less susceptible to mechanisms of immune evasion compared with established cancer. Prophylactic vaccines have already been developed for a minority of cancers mediated by oncogenic viruses (e.g., hepatitis B and human papillomavirus). Extending the use of preventive vaccines to non-virally driven malignancies remains an …

Cell-Based Noninvasive Prenatal Testing (Cbnipt)-A Review On The Current Developments And Future Prospects, Mohamad Ali Maktabi, Liesbeth Vossaert, Ignatia B Van Den Veyver

Center for Medical Ethics and Health Policy Staff Publications

Considering the diagnostic limitations of cfDNA-based noninvasive prenatal testing (NIPT), scientists have long been interested in isolating and analyzing rare intact fetal and trophoblast cells from maternal blood or endocervical samples to diagnose fetal genetic conditions. These cells may be scarce and difficult to isolate, but they are a direct source of pure fetal genetic material. In this review, we summarize the history of cell-based NIPT, present an updated review on its current developments, evaluate its genetic diagnostic potential, and discuss its future prospects for clinical use.

Childhood Exposure To Parental Threatening Behaviors And Anxiety In Emerging Adulthood: Indirect Effects Of Perceived Stress, Erika S Trent, Andres G Viana, Elizabeth M Raines, Haley E Conroy Busch, Karina Silva, Eric A Storch, Michael J Zvolensky

Center for Medical Ethics and Health Policy Staff Publications

Background: Although childhood exposure to parental threatening behaviors is associated with elevated anxiety in emerging adulthood, the underlying mechanisms remain unexplored. Perceived stress-a subjective experience comprised of feelings of helplessness (being unable to cope or exert control) and poor self-efficacy (confidence in one's ability to manage stressors)-is one candidate mechanism. The present investigation examined the underlying role of perceived stress in the association between childhood exposure to parental threatening behaviors and anxiety symptom severity in a sample of emerging adults.

Methods: Participants (N = 855; Mage = 18.75 years, SD = 1.05, range 18-24; 70.8% female) were recruited from a …

Integrating Social Determinants Of Health Into Ethical Digital Simulations, Kristin Kostick-Quenet, Vasiliki Rahimzadeh, Sharmila Anandasabapathy, Meghan Hurley, Anika Sonig, Amy Mcguire

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Epigenome-Wide Association Study Using Peripheral Blood Leukocytes Identifies Genomic Regions Associated With Periodontal Disease And Edentulism In The Atherosclerosis Risk In Communities Study, Naisi Zhao, Flavia Teles, Jiayun Lu, Devin C Koestler, James Beck, Eric Boerwinkle, Jan Bressler, Karl T Kelsey, Elizabeth A Platz, Dominique S Michaud

Faculty, Staff and Student Publications

AIM: To investigate individual susceptibility to periodontitis by conducting an epigenome-wide association study using peripheral blood.

MATERIALS AND METHODS: We included 1077 African American and 457 European American participants of the Atherosclerosis Risk in Communities (ARIC) study who had completed a dental examination or reported being edentulous at Visit 4 and had available data on DNA methylation from Visit 2 or 3. DNA methylation levels were compared by periodontal disease severity and edentulism through discovery analyses and subsequent testing of individual CpGs.

RESULTS: Our discovery analysis replicated findings from a previous study reporting a region in gene ZFP57 (6p22.1) that …

Clinical Impact Of Patient-Prosthesis Mismatch After Aortic Valve Replacement With A Mechanical Or Biological Prosthesis, Milos Matkovic, Nemanja Aleksic, Ilija Bilbija, Ana Antic, Jelena Milin Lazovic, Marko Cubrilo, Aleksandar Milojevic, Igor Zivkovic, Svetozar Putnik

The Texas Heart Institute Journal

BACKGROUND: Patient-prosthesis mismatch (PPM) may impair functional capacity and survival after aortic valve replacement. This study aimed to investigate the impact of PPM on long-term survival and quality of life after mechanical and biological aortic valve replacement.

METHODS: This study included 595 consecutive patients who had undergone isolated aortic valve replacement. Patients were divided into 2 groups according to prosthesis type. The baseline and operative characteristics, survival rates, complications, and quality of life of the groups with and without PPM were compared for up to 6 years. The PPM calculation was performed using the effective orifice area value provided by …

Intravenous Aviptadil And Remdesivir For Treatment Of Covid-19-Associated Hypoxaemic Respiratory Failure In The Usa (Tesico): A Randomised, Placebo-Controlled Trial, Samuel M Brown, Christina E Barkauskas, Birgit Grund, Shweta Sharma, Andrew N Phillips, Lindsay Leither, Ithan D Peltan, Michael Lanspa, Daniel L Gilstrap, Ahmad Mourad, Kathleen Lane, Jeremy R Beitler, Alexis L Serra, Ivan Garcia, Eyad Almasri, Mohamed Fayed, Kinsley Hubel, Estelle S Harris, Elizabeth A Middleton, Macy A G Barrios, Kusum S Mathews, Neha N Goel, Samuel Acquah, Jarrod Mosier, Cameron Hypes, Elizabeth Salvagio Campbell, Akram Khan, Catherine L Hough, Jennifer G Wilson, Joseph E Levitt, Abhijit Duggal, Siddharth Dugar, Andrew J Goodwin, Charles Terry, Peter Chen, Sam Torbati, Nithya Iyer, Uriel S Sandkovsky, Nicholas J Johnson, Bryce R H Robinson, Michael A Matthay, Neil R Aggarwal, Ivor S Douglas, Jonathan D Casey, Manuel Hache-Marliere, J Georges Youssef, William Nkemdirim, Brad Leshnower, Omar Awan, Sonal Pannu, Darragh Shane O'Mahony, Prasad Manian, J W Awori Hayanga, Glenn W Wortmann, Bruno M Tomazini, Robert F Miller, Jens-Ulrik Jensen, Daniel D Murray, Nina A Bickell, Jigna Zatakia, Sarah Burris, Elizabeth S Higgs, Ven Natarajan, Robin L Dewar, Adam Schechner, Nayon Kang, Alejandro Arenas-Pinto, Fleur Hudson, Adit A Ginde, Wesley H Self, Angela J Rogers, Cathryn F Oldmixon, Haley Morin, Adriana Sanchez, Amy C Weintrob, Alexandre Biasi Cavalcanti, Anne Davis-Karim, Nicole Engen, Eileen Denning, B Taylor Thompson, Annetine C Gelijns, Virginia Kan, Victoria J Davey, Jens D Lundgren, Abdel G Babiker, James D Neaton, H Clifford Lane

Faculty, Staff and Student Publications

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.

METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly …

Greater Male Variability In Daily Energy Expenditure Develops Through Puberty, Lewis G Halsey, Vincent Careau, Philip N Ainslie, Heliodoro Alemán-Mateo, Lene F Andersen, Liam J Anderson, Leonore Arab, Issad Baddou, Linda Bandini, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Soren Brage, Maciej S Buchowski, Nancy Butte, Stephan G Camps, Regian Casper, Graeme L Close, Lisa H Colbert, Jamie A Cooper, Richard Cooper, Prasangi Dabare, Sai Krupa Das, Peter S W Davies, Sanjoy Deb, Christine Delisle Nyström, William Dietz, Lara R Dugas, Simon Eaton, Ulf Ekelund, Asmaa El Hamdouchi, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Annelies H Goris, Michael Gurven, Hinke Haisma, Catherine Hambly, Daniel Hoffman, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Wantanee Kriengsinyos, Rebecca Kuriyan, Robert F Kushner, Estelle V Lambert, Pulani Lanerolle, Christel L Larsson, Nader Lessan, Marie Löf, Corby Martin, Eric Matsiko, Gerwin A Meijer, James C Morehen, James P Morton, Aviva Must, Marian Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietilainen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto Rabinovich, Susan B Racette, David A Raichen, Eric Ravussin, Leanne Redman, John J Reilly, Rebecca Reynolds, Susan Roberts, Jennifer C Rood, Dulani Samaranayake, Luís B Sardinha, Albertine J Scuitt, Analiza M Silva, Srishti Sinha, Anders M Sjödin, Eric Stice, Albert Stunkard, Samuel S Urlacher, Mauro Eduardo Valencia, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jeanine A Verbunt, Jonathan C K Wells, George Wilson, Brian Wood, Tsukasa Yoshida, Xueying Zhang, Alexia Murphy-Alford, Cornelia Loechl, Amy Luke, Herman Pontzer, Jennifer Rood, Hiroyuki Sagayama, Klaas R Westerterp, William W Wong, Yosuke Yamada, John R Speakman

Faculty, Staff and Student Publications

There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at …

A Novel Grk3-Hdac2 Regulatory Pathway Is A Key Direct Link Between Neuroendocrine Differentiation And Angiogenesis In Prostate Cancer Progression, Samira Naderinezhad, Guoliang Zhang, Zheng Wang, Dayong Zheng, Mohit Hulsurkar, Michael Bakhoum, Ning Su, Han Yang, Tao Shen, Wenliang Li

Faculty, Staff and Students Publications

The mechanisms underlying the progression of prostate cancer (PCa) to neuroendocrine prostate cancer (NEPC), an aggressive PCa variant, are largely unclear. Two prominent NEPC phenotypes are elevated NE marker expression and heightened angiogenesis. Identifying the still elusive direct molecular links connecting angiogenesis and neuroendocrine differentiation (NED) is crucial for our understanding and targeting of NEPC. Here we found that histone deacetylase 2 (HDAC2), whose role in NEPC has not been reported, is one of the most upregulated epigenetic regulators in NEPC. HDAC2 promotes both NED and angiogenesis. G protein-coupled receptor kinase 3 (GRK3), also upregulated in NEPC, is a critical …

A Defect In Mitochondrial Fatty Acid Synthesis Impairs Iron Metabolism And Causes Elevated Ceramide Levels, Debdeep Dutta, Oguz Kanca, Seul Kee Byeon, Paul C Marcogliese, Zhongyuan Zuo, Rishi V Shridharan, Jun Hyoung Park, Undiagnosed Diseases Networ, Guang Lin, Ming Ge, Gali Heimer, Jennefer N Kohler, Matthew T Wheeler, Benny A Kaipparettu, Akhilesh Pandey, Hugo J Bellen

Faculty, Staff and Students Publications

In most eukaryotic cells, fatty acid synthesis (FAS) occurs in the cytoplasm and in mitochondria. However, the relative contribution of mitochondrial FAS (mtFAS) to the cellular lipidome is not well defined. Here we show that loss of function of Drosophila mitochondrial enoyl coenzyme A reductase (Mecr), which is the enzyme required for the last step of mtFAS, causes lethality, while neuronal loss of Mecr leads to progressive neurodegeneration. We observe a defect in Fe-S cluster biogenesis and increased iron levels in flies lacking mecr, leading to elevated ceramide levels. Reducing the levels of either iron or ceramide suppresses the neurodegenerative …

Phenoscore Quantifies Phenotypic Variation For Rare Genetic Diseases By Combining Facial Analysis With Other Clinical Features Using A Machine-Learning Framework, Alexander J M Dingemans, Max Hinne, Kim M G Truijen, Lia Goltstein, Jeroen Van Reeuwijk, Nicole De Leeuw, Janneke Schuurs-Hoeijmakers, Rolph Pfundt, Illja J Diets, Joery Den Hoed, Elke De Boer, Jet Coenen-Van Der Spek, Sandra Jansen, Bregje W Van Bon, Noraly Jonis, Charlotte W Ockeloen, Anneke T Vulto-Van Silfhout, Tjitske Kleefstra, David A Koolen, Philippe M Campeau, Elizabeth E Palmer, Hilde Van Esch, Gholson J Lyon, Fowzan S Alkuraya, Anita Rauch, Ronit Marom, Diana Baralle, Pleuntje J Van Der Sluijs, Gijs W E Santen, R Frank Kooy, Marcel A J Van Gerven, Lisenka E L M Vissers, Bert B A De Vries

Faculty, Staff and Students Publications

Several molecular and phenotypic algorithms exist that establish genotype-phenotype correlations, including facial recognition tools. However, no unified framework that investigates both facial data and other phenotypic data directly from individuals exists. We developed PhenoScore: an open-source, artificial intelligence-based phenomics framework, combining facial recognition technology with Human Phenotype Ontology data analysis to quantify phenotypic similarity. Here we show PhenoScore's ability to recognize distinct phenotypic entities by establishing recognizable phenotypes for 37 of 40 investigated syndromes against clinical features observed in individuals with other neurodevelopmental disorders and show it is an improvement on existing approaches. PhenoScore provides predictions for individuals with variants …

Factors Influencing Prescribing The First Add-On Disease-Modifying Antirheumatic Drugs In Patients Initiating Methotrexate For Rheumatoid Arthritis, Yinan Huang, Satabdi Chatterjee, Sandeep K Agarwal, Hua Chen, Michael L Johnson, Rajender R Aparasu

Faculty, Staff and Students Publications

BACKGROUND: Advances in Disease-Modifying Antirheumatic Drugs (DMARDs) have expanded the treatment landscape for Rheumatoid Arthritis (RA). Guidelines recommend adding either conventional synthetic (cs), biologic (b), or targeted synthetic (ts) DMARDs to methotrexate (MTX) for managing RA. Limited evidence exists regarding the factors that contribute to adding a DMARD agent to the MTX regimen. This study examined the factors associated with adding the first DMARD in RA patients initiating MTX.

METHODS: This retrospective cohort study utilized the MarketScan data (2012-2014) involving adults (aged ≥18) with RA initiating an MTX (index date) between Jul 1, 2012 and Dec 30, 2013, and with …

Loss Of Growth Differentiation Factor 15 Exacerbates Lung Injury In Neonatal Mice, Faeq Al-Mudares, Manuel Cantu Gutierrez, Abiud Cantu, Weiwu Jiang, Lihua Wang, Xiaoyu Dong, Bhagavatula Moorthy, Eniko Sajti, Krithika Lingappan

Faculty, Staff and Students Publications

Growth differentiation factor 15 (GDF15) is a divergent member of the transforming growth factor-β (TGF-β) superfamily, and its expression increases under various stress conditions, including inflammation, hyperoxia, and senescence. GDF15 expression is increased in neonatal murine bronchopulmonary dysplasia (BPD) models, and GDF15 loss exacerbates oxidative stress and decreases cellular viability in vitro. Our overall hypothesis is that the loss of GDF15 will exacerbate hyperoxic lung injury in the neonatal lung in vivo. We exposed neonatal

Age Differences In Core Symptoms And Symptom Relationships In Patients With Irritable Bowel Syndrome: A Network Analysis, Pei-Lin Yang, Kendra J Kamp, Robert L Burr, Hsin-Yi Jean Tang, Adrian Dobra, Robert J Shulman, Margaret M Heitkemper

Faculty, Staff and Students Publications

INTRODUCTION: Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, characterized by symptoms of abdominal pain and changes in bowel habits. It often co-occurs with extraintestinal somatic and psychological symptoms. However, the nature of the interrelationships among these symptoms is unclear. Although previous studies have noted age differences in IBS prevalence and specific symptom severity, it remains unknown whether specific symptoms and symptom relationships may differ by age.

METHODS: Symptom data were collected in 355 adults with IBS (mean age 41.4 years, 86.2% female). Network analysis was used to examine the interrelationships among 28 symptoms and to identify …

Transfusion Reactions Associated With Covid-19 Convalescent Plasma In Outpatient Clinical Trials, Moises A Huaman, Jay S Raval, James H Paxton, Giselle S Mosnaim, Bela Patel, Shweta Anjan, Barry R Meisenberg, Adam C Levine, Christi E Marshall, Anusha Yarava, Aarthi G Shenoy, Sonya L Heath, Judith S Currier, Yuriko Fukuta, Janis E Blair, Emily S Spivak, Joann R Petrini, Patrick B Broderick, William Rausch, Marieelena Cordisco, Jean Hammel, Benjamin Greenblatt, Valerie C Cluzet, Daniel Cruser, Kevin Oei, Matthew Abinante, Laura L Hammitt, Catherine G Sutcliffe, Donald N Forthal, Martin S Zand, Edward R Cachay, Seble G Kassaye, Malathi Ram, Ying Wang, Piyali Das, Karen Lane, Nichol A Mcbee, Amy L Gawad, Nicky Karlen, Daniel E Ford, Oliver Laeyendecker, Andrew Pekosz, Sabra L Klein, Stephan Ehrhardt, Bryan Lau, Sheriza N Baksh, David M Shade, Arturo Casadevall, Daniel F Hanley, Jiangda Ou, Thomas J Gniadek, Alyssa Ziman, Shmuel Shoham, Kelly A Gebo, Evan M Bloch, Aaron A R Tobian, David J Sullivan, Jonathan M Gerber

Faculty, Staff and Students Publications

BACKGROUND: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials.

STUDY DESIGN AND METHODS: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.S. that evaluated the efficacy of CCP versus control plasma in various ambulatory settings. Multivariable logistic regression was used to assess whether CCP was associated with transfusion reactions, after adjusting for potential confounders.

RESULTS: The combined study reported 79/1351 (5.9%) adverse events during the transfusion visit, with the majority 62/1351 …

Myths And Methodologies: Cardiopulmonary Exercise Testing For Surgical Risk Stratification In Patients With An Abdominal Aortic Aneurysm; Balancing Risk Over Benefit, Damian M Bailey, Richard G Davies, George A Rose, Michael H Lewis, Ahmed Abd Aldayem, Chistopher P Twine, Wael Awad, Matti Jubouri, Idhrees Mohammed, Carlos A Mestres, Edward P Chen, Joseph S Coselli, Ian M Williams, Mohamad Bashir, International Academic Surgical Consortium (Thalamus)

Faculty, Staff and Students Publications

The extent to which patients with an abdominal aortic aneurysm (AAA) should exercise remains unclear, given theoretical concerns over the perceived risk of blood pressure-induced rupture, which is often catastrophic. This is especially pertinent during cardiopulmonary exercise testing, when patients are required to perform incremental exercise to symptom-limited exhaustion for the determination of cardiorespiratory fitness. This multimodal metric is being used increasingly as a complementary diagnostic tool to inform risk stratification and subsequent management of patients undergoing AAA surgery. In this review, we bring together a multidisciplinary group of physiologists, exercise scientists, anaesthetists, radiologists and surgeons to challenge the enduring …

Revisiting The Use Of Antibiotics To Prevent Copd Exacerbation: Is Doxycycline The Answer?, Muhammad Adrish, Nicola A Hanania

Faculty, Staff and Students Publications

No abstract provided.

Il17a Blockade With Ixekizumab Suppresses Muvb Signaling In Clinical Psoriasis, Scott A Ochsner, Mesias Pedroza, Rudolf T Pillich, Venkatesh Krishnan, Bruce W Konicek, Ernst R Dow, So Young Park, Sandeep K Agarwal, Neil J Mckenna

Faculty, Staff and Students Publications

Unbiased informatics approaches have the potential to generate insights into uncharacterized signaling pathways in human disease. In this study, we generated longitudinal transcriptomic profiles of plaque psoriasis lesions from patients enrolled in a clinical trial of the anti-IL17A antibody ixekizumab (IXE). This dataset was then computed against a curated matrix of over 700 million data points derived from published psoriasis and signaling node perturbation transcriptomic and chromatin immunoprecipitation-sequencing datasets. We observed substantive enrichment within both psoriasis-induced and IXE-repressed gene sets of transcriptional targets of members of the MuvB complex, a master regulator of the mitotic cell cycle. These gene sets …

Characterizing Control Of Memory Cd8 T Cell Differentiation By Btb-Zf Transcription Factor Zbtb20, Nicholas K Preiss, Yasmin Kamal, Owen M Wilkins, Chenyang Li, Fred W Kolling, Heidi W Trask, Young-Kwang Usherwood, Chao Cheng, Hildreth R Frost, Edward J Usherwood

Faculty, Staff and Students Publications

Members of the BTB-ZF transcription factor family regulate the immune system. Our laboratory identified that family member Zbtb20 contributes to the differentiation, recall responses, and metabolism of CD8 T cells. Here, we report a characterization of the transcriptional and epigenetic signatures controlled by Zbtb20 at single-cell resolution during the effector and memory phases of the CD8 T cell response. Without Zbtb20, transcriptional programs associated with memory CD8 T cell formation were up-regulated throughout the CD8 T response. A signature of open chromatin was associated with genes controlling T cell activation, consistent with the known impact on differentiation. In addition, memory …

The Transcription Factor Chrebp Links Mitochondrial Lipidomes To Mitochondrial Morphology And Progression Of Diabetic Kidney Disease, Li Li, Jianyin Long, Koki Mise, Naravat Poungavrin, Philip L Lorenzi, Iqbal Mahmud, Lin Tan, Pradip K Saha, Yashpal S Kanwar, Benny H Chang, Farhad R Danesh

Faculty, Staff and Students Publications

A substantial body of evidence has established the contributions of both mitochondrial dynamics and lipid metabolism to the pathogenesis of diabetic kidney disease (DKD). However, the precise interplay between these two key metabolic regulators of DKD is not fully understood. Here, we uncover a link between mitochondrial dynamics and lipid metabolism by investigating the role of carbohydrate-response element-binding protein (ChREBP), a glucose-responsive transcription factor and a master regulator of lipogenesis, in kidney podocytes. We find that inducible podocyte-specific knockdown of ChREBP in diabetic db/db mice improves key biochemical and histological features of DKD in addition to significantly reducing mitochondrial fragmentation. …

Children’S Oncology Group’S 2023 Blueprint For Research: Non-Hodgkin Lymphoma, Nader Kim El-Mallawany, Sarah Alexander, Mark Fluchel, Robert J Hayashi, Eric J Lowe, Lisa Giulino-Roth, Birte Wistinghausen, Michelle Hermiston, Carl E Allen

Faculty, Staff and Students Publications

Pediatric non-Hodgkin lymphoma (NHL) includes over 30 histologies (many with subtypes), with approximately 800 cases per year in the United States. Improvements in survival in NHL over the past 5 decades align with the overall success of the cooperative trial model with dramatic improvements in outcomes. As an example, survival for advanced Burkitt lymphoma is now >95%. Major remaining challenges include survival for relapsed and refractory disease and long-term morbidity in NHL survivors. Langerhans cell histiocytosis (LCH) was added to the NHL Committee portfolio in recognition of LCH as a neoplastic disorder and the tremendous unmet need for improved outcomes. …

Fetal Echocardiographic Z Score Pilot Project: Study Design And Impact Of Gestational Age And Variable Type On Reproducibility Of Measurements Within And Across Investigators, Anita J Moon-Grady, Hyejung Lee, Leo Lopez, Oluwatosin Fatusin, Lindsay R Freud, Whitnee Hogan, Anita Krishnan, Carol Mcfarland, L Luann Minich, Shaine A Morris, Nelangi Pinto, Angela P Presson, Theresa A Tacy, Mary T Donofrio

Faculty, Staff and Students Publications

Background: Fetal echocardiography is widely available, but normative data are not robust. In this pilot study, the authors evaluated (1) the feasibility of prespecified measurements in a normal fetal echocardiogram to inform study design and (2) measurement variability to assign thresholds of clinical significance and guide analyses in larger fetal echocardiographic Z score initiatives.

Methods: Images from predefined gestational age groups (16-20, >20-24, >24-28, and >28-32 weeks) were retrospectively analyzed. Fetal echocardiography expert raters attended online group training and then independently analyzed 73 fetal studies (18 per age group) in a fully crossed design of 53 variables; each observer repeated …

Understanding Ip3r Channels: From Structural Underpinnings To Ligand-Dependent Conformational Landscape, Mariah R Baker, Guizhen Fan, Vikas Arige, David I Yule, Irina I Serysheva

Faculty, Staff and Student Publications

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are ubiquitously expressed large-conductance Ca2+-permeable channels predominantly localized to the endoplasmic reticulum (ER) membranes of virtually all eukaryotic cell types. IP3Rs work as Ca2+ signaling hubs through which diverse extracellular stimuli and intracellular inputs are processed and then integrated to result in delivery of Ca2+ from the ER lumen to generate cytosolic Ca2+ signals with precise temporal and spatial properties. IP3R-mediated Ca2+ signals control a vast repertoire of cellular functions ranging from gene transcription and secretion to the more enigmatic brain activities such as learning and memory. IP3Rs open and release Ca2+ when they bind both …

Host-Derived Reactive Oxygen Species Trigger Activation Of The Candida Albicans Transcription Regulator Rtg1/3, Mazen Oneissi, Melissa R Cruz, Bernardo Ramírez-Zavala, Elena Lindemann-Perez, Joachim Morschhäuser, Danielle A Garsin, J Christian Perez

Faculty, Staff and Student Publications

The signals that denote mammalian host environments and dictate the activation of signaling pathways in human-associated microorganisms are often unknown. The transcription regulator Rtg1/3 in the human fungal pathogen Candida albicans is a crucial determinant of host colonization and pathogenicity. Rtg1/3's activity is controlled, in part, by shuttling the regulator between the cytoplasm and nucleus of the fungus. The host signal(s) that Rtg1/3 respond(s) to, however, have remained unclear. Here we report that neutrophil-derived reactive oxygen species (ROS) direct the subcellular localization of this C. albicans transcription regulator. Upon engulfment of Candida cells by human or mouse neutrophils, the regulator …

Life’S Essential 8: Optimizing Health In Older Adults, Manish Kumar, Ariela Orkaby, Caitlan Tighe, Dennis T Villareal, Hayley Billingsley, Michael G Nanna, Min Ji Kwak, Namit Rohant, Shreya Patel, Parag Goyal, Scott Hummel, Christina Al-Malouf, Amie Kolimas, Ashok Krishnaswami, Mike W Rich, James Kirkpatrick, Abdulla A Damluji, George A Kuchel, Daniel E Forman, Karen P Alexander

Faculty, Staff and Student Publications

The population worldwide is getting older as a result of advances in public health, medicine, and technology. Older individuals are living longer with a higher prevalence of subclinical and clinical cardiovascular disease (CVD). In 2010, the American Heart Association introduced a list of key prevention targets, known as "Life's Simple 7" to increase CVD-free survival, longevity, and quality of life. In 2022, sleep health was added to expand the recommendations to "Life's Essential 8" (eat better, be more active, stop smoking, get adequate sleep, manage weight, manage cholesterol, manage blood pressure, and manage diabetes). These prevention targets are intended to …

Dynamics Of Inflammatory Responses After Sars-Cov-2 Infection By Vaccination Status In The Usa: A Prospective Cohort Study, Xianming Zhu, Kelly A Gebo, Alison G Abraham, Feben Habtehyimer, Eshan U Patel, Oliver Laeyendecker, Thomas J Gniadek, Reinaldo E Fernandez, Owen R Baker, Malathi Ram, Edward R Cachay, Judith S Currier, Yuriko Fukuta, Jonathan M Gerber, Sonya L Heath, Barry Meisenberg, Moises A Huaman, Adam C Levine, Aarthi Shenoy, Shweta Anjan, Janis E Blair, Daniel Cruser, Donald N Forthal, Laura L Hammitt, Seble Kassaye, Giselle S Mosnaim, Bela Patel, James H Paxton, Jay S Raval, Catherine G Sutcliffe, Matthew Abinante, Patrick Broderick, Valerie Cluzet, Marie Elena Cordisco, Benjamin Greenblatt, Joann Petrini, William Rausch, David Shade, Karen Lane, Amy L Gawad, Sabra L Klein, Andrew Pekosz, Shmuel Shoham, Arturo Casadevall, Evan M Bloch, Daniel Hanley, David J Sullivan, Aaron A R Tobian

Faculty, Staff and Student Publications

BACKGROUND: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection.

METHODS: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples …

New Records Of Ornithodoros Turicata (Ixodida: Argasidae) In Rural And Urban Sites In The Mexican States Of Aguascalientes And Zacatecas Indicate The Potential For Tick-Borne Relapsing Fever, Edwin Vázquez-Guerrero, José Luis González-Quiroz, María Lilia Domínguez-López, Alexander R Kneubehl, Aparna Krishnavajhala, Michael W Curtis, Alejandro Ponce-Mendoza, Paulina Estrada-De Los Santos, Job E Lopez, J Antonio Ibarra

Faculty, Staff and Students Publications

Soft ticks from the Ornithodoros genus are vectors of relapsing fever (RF) spirochetes around the world. In Mexico, they were originally described in the 19th century. However, few recent surveillance studies have been conducted in Mexico, and regions where RF spirochetes circulate remain vague. Here, the presence of soft ticks in populated areas was assessed in two sites from the Mexican states of Aguascalientes and Zacatecas. Argasidae ticks were collected, identified by morphology and mitochondrial 16S rDNA gene sequencing, and tested for RF borreliae. The specimens in both sites were identified as Ornithodoros turicata but no RF spirochetes were detected. …

Public Reporting For Coronary Artery Bypass Graft Surgery: The Quest For The Optimal Scorecard, Hiba Ghandour, Aaron J Weiss, Mario Gaudino, Michael Halkos, Danny Chu, Bradley S Taylor, John Puskas, Deepak L Bhatt, Marco Zenati, John Stulak, Todd Rosengart, Husam H Balkhy, Eugene H Blackstone, Lars G Svensson, Faisal G Bakaeen, Ozgun Erten, Tara Karamlou, Edward G Soltesz, A Marc Gillinov, Anthony Warmuth, Eric E Roselli, Nicholas G Smedira

Faculty, Staff and Students Publications

Objective: A number of publicly available rating algorithms are used to assess hospital performance in coronary artery bypass grafting (CABG). However, concerns remain that these algorithms fail to correlate with each other and inadequately capture the case complexity of individual center practices.

Methods: Composite star ratings for isolated CABG from the Society of Thoracic Surgeons public reporting database were extracted for 2018-2019. U.S. News & World Report Best Hospitals was used to extract CABG ratings as well as overall cardiology and heart surgery ranking, and the Centers for Medicare & Medicaid Services Hospital Compare was used to extract CABG volume …

Rna Interference Targeting Angptl3 For Triglyceride And Cholesterol Lowering: Phase 1 Basket Trial Cohorts, Gerald F Watts, Christian Schwabe, Russell Scott, Patrick A Gladding, David Sullivan, John Baker, Peter Clifton, James Hamilton, Bruce Given, Stacey Melquist, Rong Zhou, Ting Chang, Javier San Martin, Daniel Gaudet, Ira J Goldberg, Joshua W Knowles, Robert A Hegele, Christie M Ballantyne

Faculty, Staff and Students Publications

Elevated triglycerides and non-high-density lipoprotein cholesterol (HDL-C) are risk factors for atherosclerotic cardiovascular disease (ASCVD). ARO-ANG3 is an RNA interference therapy that targets angiopoietin-like protein 3 (ANGPTL3), a regulator of lipoprotein metabolism. This first-in-human, phase 1, randomized, placebo-controlled, open-label trial investigated single and repeat ARO-ANG3 doses in four cohorts of fifty-two healthy participants and one cohort of nine participants with hepatic steatosis, part of a basket trial. Safety (primary objective) and pharmacokinetics (in healthy participants) and pharmacodynamics (secondary objectives) of ARO-ANG3 were evaluated. ARO-ANG3 was generally well tolerated, with similar frequencies of treatment-emergent adverse events in active and placebo groups. …

Oral Delivery Of Rnai For Cancer Therapy, Humayra Afrin, Renu Geetha Bai, Raj Kumar, Sheikh Shafin Ahmad, Sandeep K Agarwal, Md Nurunnabi

Faculty, Staff and Students Publications

Cancer is a major health concern worldwide and is still in a continuous surge of seeking for effective treatments. Since the discovery of RNAi and their mechanism of action, it has shown promises in targeted therapy for various diseases including cancer. The ability of RNAi to selectively silence the carcinogenic gene makes them ideal as cancer therapeutics. Oral delivery is the ideal route of administration of drug administration because of its patients' compliance and convenience. However, orally administered RNAi, for instance, siRNA, must cross various extracellular and intracellular biological barriers before it reaches the site of action. It is very …