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Articles 13411 - 13440 of 18697

Full-Text Articles in Medical Specialties

The Impact Of Covid-19 On Pediatric Cardiac Arrest Outcomes: A Systematic Review And Meta-Analysis, Alla Navolokina, Jacek Smereka, Bernd W Böttiger, Michal Pruc, Raúl Juárez-Vela, Mansur Rahnama-Hezavah, Zubaid Rafique, Frank W Peacock, Kamil Safiejko, Lukasz Szarpak Jan 2023

The Impact Of Covid-19 On Pediatric Cardiac Arrest Outcomes: A Systematic Review And Meta-Analysis, Alla Navolokina, Jacek Smereka, Bernd W Böttiger, Michal Pruc, Raúl Juárez-Vela, Mansur Rahnama-Hezavah, Zubaid Rafique, Frank W Peacock, Kamil Safiejko, Lukasz Szarpak

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic, required the donning of personal protective equipment during clinical contact, and continues to be a significant worldwide public health concern. Pediatric cardiac arrest is a rare but critical condition with a high mortality rate, the outcomes of which may be negatively affected by donning personal protective equipment. The aim of this study is to perform a systematic review and meta-analysis of the impact of the COVID-19 pandemic on pediatric cardiac arrest outcomes. We conducted a systematic review with meta-analysis in the following databases: PubMed, EMBASE, Scopus, Web of Science, …


Multicenter International Study Of The Consensus Immunoscore For The Prediction Of Relapse And Survival In Early-Stage Colon Cancer, Bernhard Mlecnik, Alessandro Lugli, Gabriela Bindea, Florence Marliot, Carlo Bifulco, Jiun-Kae Jack Lee, Inti Zlobec, Tilman T Rau, Martin D Berger, Iris D Nagtegaal, Elisa Vink-Börger, Arndt Hartmann, Carol I Geppert, Julie Kolwelter, Susanne Merkel, Robert Grützmann, Marc Van Den Eynde, Anne Jouret-Mourin, Alex Kartheuser, Daniel Léonard, Christophe Remue, Julia Wang, Prashant Bavi, Michael H A Roehrl, Pamela S Ohashi, Linh T Nguyen, Seongjun Han, Heather L Macgregor, Sara Hafezi-Bakhtiari, Bradly G Wouters, Giuseppe V Masucci, Emilia K Andersson, Eva Zavadova, Michal Vocka, Jan Spacek, Lubos Petruzelka, Bohuslav Konopasek, Pavel Dundr, Helena Skalova, Kristyna Nemejcova, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Gennaro Ciliberto, Michele Maio, Luigi Laghi, Fabio Grizzi, Tessa Fredriksen, Bénédicte Buttard, Lucie Lafontaine, Pauline Maby, Amine Majdi, Assia Hijazi, Carine El Sissy, Amos Kirilovsky, Anne Berger, Christine Lagorce, Christopher Paustian, Carmen Ballesteros-Merino, Jeroen Dijkstra, Carlijn Van De Water, Shannon Van Lent-Van Vliet, Nikki Knijn, Ana-Maria Mușină, Dragos-Viorel Scripcariu, Boryana Popivanova, Mingli Xu, Tomonobu Fujita, Shoichi Hazama, Nobuaki Suzuki, Hiroaki Nagano, Kiyotaka Okuno, Toshihiko Torigoe, Noriyuki Sato, Tomohisa Furuhata, Ichiro Takemasa, Prabhu Patel, Hemangini H Vora, Birva Shah, Jayendrakumar B Patel, Kruti N Rajvik, Shashank J Pandya, Shilin N Shukla, Yili Wang, Guanjun Zhang, Yutaka Kawakami, Francesco M Marincola, Paolo A Ascierto, Bernard A Fox, Franck Pagès, Jérôme Galon Jan 2023

Multicenter International Study Of The Consensus Immunoscore For The Prediction Of Relapse And Survival In Early-Stage Colon Cancer, Bernhard Mlecnik, Alessandro Lugli, Gabriela Bindea, Florence Marliot, Carlo Bifulco, Jiun-Kae Jack Lee, Inti Zlobec, Tilman T Rau, Martin D Berger, Iris D Nagtegaal, Elisa Vink-Börger, Arndt Hartmann, Carol I Geppert, Julie Kolwelter, Susanne Merkel, Robert Grützmann, Marc Van Den Eynde, Anne Jouret-Mourin, Alex Kartheuser, Daniel Léonard, Christophe Remue, Julia Wang, Prashant Bavi, Michael H A Roehrl, Pamela S Ohashi, Linh T Nguyen, Seongjun Han, Heather L Macgregor, Sara Hafezi-Bakhtiari, Bradly G Wouters, Giuseppe V Masucci, Emilia K Andersson, Eva Zavadova, Michal Vocka, Jan Spacek, Lubos Petruzelka, Bohuslav Konopasek, Pavel Dundr, Helena Skalova, Kristyna Nemejcova, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Gennaro Ciliberto, Michele Maio, Luigi Laghi, Fabio Grizzi, Tessa Fredriksen, Bénédicte Buttard, Lucie Lafontaine, Pauline Maby, Amine Majdi, Assia Hijazi, Carine El Sissy, Amos Kirilovsky, Anne Berger, Christine Lagorce, Christopher Paustian, Carmen Ballesteros-Merino, Jeroen Dijkstra, Carlijn Van De Water, Shannon Van Lent-Van Vliet, Nikki Knijn, Ana-Maria Mușină, Dragos-Viorel Scripcariu, Boryana Popivanova, Mingli Xu, Tomonobu Fujita, Shoichi Hazama, Nobuaki Suzuki, Hiroaki Nagano, Kiyotaka Okuno, Toshihiko Torigoe, Noriyuki Sato, Tomohisa Furuhata, Ichiro Takemasa, Prabhu Patel, Hemangini H Vora, Birva Shah, Jayendrakumar B Patel, Kruti N Rajvik, Shashank J Pandya, Shilin N Shukla, Yili Wang, Guanjun Zhang, Yutaka Kawakami, Francesco M Marincola, Paolo A Ascierto, Bernard A Fox, Franck Pagès, Jérôme Galon

Faculty, Staff and Student Publications

Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival …


The Legacy Of The Covid-19 Pandemic For Childhood Vaccination In The Usa, Douglas J Opel, Noel T Brewer, Alison M Buttenheim, Timothy Callaghan, Richard M Carpiano, Chelsea Clinton, Jad A Elharake, Lisa C Flowers, Alison P Galvani, Peter J Hotez, Jason L Schwartz, Regina M Benjamin, Arthur Caplan, Renee Diresta, Rekha Lakshmanan, Yvonne A Maldonado, Michelle M Mello, Wendy E Parmet, Daniel A Salmon, Joshua M Sharfstein, Saad B Omer Jan 2023

The Legacy Of The Covid-19 Pandemic For Childhood Vaccination In The Usa, Douglas J Opel, Noel T Brewer, Alison M Buttenheim, Timothy Callaghan, Richard M Carpiano, Chelsea Clinton, Jad A Elharake, Lisa C Flowers, Alison P Galvani, Peter J Hotez, Jason L Schwartz, Regina M Benjamin, Arthur Caplan, Renee Diresta, Rekha Lakshmanan, Yvonne A Maldonado, Michelle M Mello, Wendy E Parmet, Daniel A Salmon, Joshua M Sharfstein, Saad B Omer

Faculty, Staff and Students Publications

No abstract provided.


Echinococcus Multilocularis Calreticulin Interferes With C1q-Mediated Complement Activation, Siqi Xian, Lujuan Chen, Yan Yan, Jianfang Chen, Guixia Yu, Yuxiao Shao, Bin Zhan, Yanhai Wang, Limei Zhao Jan 2023

Echinococcus Multilocularis Calreticulin Interferes With C1q-Mediated Complement Activation, Siqi Xian, Lujuan Chen, Yan Yan, Jianfang Chen, Guixia Yu, Yuxiao Shao, Bin Zhan, Yanhai Wang, Limei Zhao

Faculty, Staff and Students Publications

As a zoonotic disease caused by Echinococcus multilocularis larvae, alveolar echinococcosis (AE) is one of the most severe forms of parasitic infection. Over a long evolutional process E. multilocularis has developed complex strategies to escape host immune attack and survive within a host. However, the mechanisms underlying immune evasion remain unclear. Here we investigated the binding activity of E. multilocularis calreticulin (EmCRT), a highly conserved Ca2+-binding protein, to human complement C1q and its ability to inhibit classical complement activation. ELISA, Far Western blotting and immunoprecipitation results demonstrated that both recombinant and natural EmCRTs bound to human C1q, …


Benchmarking Outcomes For Molecularly Characterized Synchronous Oligo Metastatic Non-Small-Cell Lung Cancer Reveals Egfr Mutations To Be Associated With Longer Overall Survival, Brian De, Ahsan S Farooqi, Kyle G Mitchell, Ethan B Ludmir, Jeff Lewis, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, J Jack Lee, Stephen G Swisher, Don L Gibbons, Jianjun Zhang, Xiuning Le, Yasir Y Elamin, Daniel R Gomez, Matthew S Ning, Steven H Lin, Zhongxing Liao, Joe Y Chang, Ara A Vaporciyan, John V Heymach, Mara B Antonoff, Saumil J Gandhi Jan 2023

Benchmarking Outcomes For Molecularly Characterized Synchronous Oligo Metastatic Non-Small-Cell Lung Cancer Reveals Egfr Mutations To Be Associated With Longer Overall Survival, Brian De, Ahsan S Farooqi, Kyle G Mitchell, Ethan B Ludmir, Jeff Lewis, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, J Jack Lee, Stephen G Swisher, Don L Gibbons, Jianjun Zhang, Xiuning Le, Yasir Y Elamin, Daniel R Gomez, Matthew S Ning, Steven H Lin, Zhongxing Liao, Joe Y Chang, Ara A Vaporciyan, John V Heymach, Mara B Antonoff, Saumil J Gandhi

Faculty, Staff and Student Publications

PURPOSE: Local consolidative therapy (LCT) for patients with synchronous oligometastatic non-small-cell lung cancer is an evolving treatment strategy, but outcomes following LCT stratified by genetic mutations have not been reported. We sought to identify genomic associations with overall survival (OS) and progression-free survival (PFS) for these patients.

METHODS: We identified all patients presenting between 2000 and 2017 with stage IV non-small-cell lung cancer and ≤ 3 synchronous metastatic sites. Patients were grouped according to mutational statuses. Primary outcomes included OS and PFS following initial diagnosis.

RESULTS: Of 194 included patients, 121 received comprehensive LCT to all sites of disease with …


Predicting The Risk Of A Clinical Event Using Longitudinal Data: The Generalized Landmark Analysis, Yi Yao, Liang Li, Brad Astor, Wei Yang, Tom Greene Jan 2023

Predicting The Risk Of A Clinical Event Using Longitudinal Data: The Generalized Landmark Analysis, Yi Yao, Liang Li, Brad Astor, Wei Yang, Tom Greene

Faculty, Staff and Student Publications

Background: In the development of prediction models for a clinical event, it is common to use the static prediction modeling (SPM), a regression model that relates baseline predictors to the time to event. In many situations, the data used in training and validation are from longitudinal studies, where predictor variables are time-varying and measured at clinical visits. But these data are not used in SPM. The landmark analysis (LA), previously proposed for dynamic prediction with longitudinal data, has interpretational difficulty when the baseline is not a risk-changing clinical milestone, as is often the case in observational studies of chronic disease …


Civicdb 2022: Evolution Of An Open-Access Cancer Variant Interpretation Knowledgebase, Kilannin Krysiak, Arpad M Danos, Jason Saliba, Joshua F Mcmichael, Adam C Coffman, Susanna Kiwala, Erica K Barnell, Lana Sheta, Cameron J Grisdale, Lynzey Kujan, Shahil Pema, Jake Lever, Sarah Ridd, Nicholas C Spies, Veronica Andric, Andreea Chiorean, Damian T Rieke, Kaitlin A Clark, Caralyn Reisle, Ajay C Venigalla, Mark Evans, Payal Jani, Hideaki Takahashi, Avila Suda, Peter Horak, Deborah I Ritter, Xin Zhou, Benjamin J Ainscough, Sean Delong, Chimene Kesserwan, Mario Lamping, Haolin Shen, Alex R Marr, My H Hoang, Kartik Singhal, Mariam Khanfar, Brian V Li, Wan-Hsin Lin, Panieh Terraf, Laura B Corson, Yasser Salama, Katie M Campbell, Kirsten M Farncombe, Jianling Ji, Xiaonan Zhao, Xinjie Xu, Rashmi Kanagal-Shamanna, Ian King, Kelsy C Cotto, Zachary L Skidmore, Jason R Walker, Jinghui Zhang, Aleksandar Milosavljevic, Ronak Y Patel, Rachel H Giles, Raymond H Kim, Lynn M Schriml, Elaine R Mardis, Steven J M Jones, Gordana Raca, Shruti Rao, Subha Madhavan, Alex H Wagner, Malachi Griffith, Obi L Griffith Jan 2023

Civicdb 2022: Evolution Of An Open-Access Cancer Variant Interpretation Knowledgebase, Kilannin Krysiak, Arpad M Danos, Jason Saliba, Joshua F Mcmichael, Adam C Coffman, Susanna Kiwala, Erica K Barnell, Lana Sheta, Cameron J Grisdale, Lynzey Kujan, Shahil Pema, Jake Lever, Sarah Ridd, Nicholas C Spies, Veronica Andric, Andreea Chiorean, Damian T Rieke, Kaitlin A Clark, Caralyn Reisle, Ajay C Venigalla, Mark Evans, Payal Jani, Hideaki Takahashi, Avila Suda, Peter Horak, Deborah I Ritter, Xin Zhou, Benjamin J Ainscough, Sean Delong, Chimene Kesserwan, Mario Lamping, Haolin Shen, Alex R Marr, My H Hoang, Kartik Singhal, Mariam Khanfar, Brian V Li, Wan-Hsin Lin, Panieh Terraf, Laura B Corson, Yasser Salama, Katie M Campbell, Kirsten M Farncombe, Jianling Ji, Xiaonan Zhao, Xinjie Xu, Rashmi Kanagal-Shamanna, Ian King, Kelsy C Cotto, Zachary L Skidmore, Jason R Walker, Jinghui Zhang, Aleksandar Milosavljevic, Ronak Y Patel, Rachel H Giles, Raymond H Kim, Lynn M Schriml, Elaine R Mardis, Steven J M Jones, Gordana Raca, Shruti Rao, Subha Madhavan, Alex H Wagner, Malachi Griffith, Obi L Griffith

Faculty, Staff and Students Publications

CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC's functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination …


Excretory/Secretory Proteome Of Females And Males Of The Hookworm Ancylostoma Ceylanicum, Samuel C Uzoechi, Bruce A Rosa, Kumar Sachin Singh, Young-Jun Choi, Bethany K Bracken, Paul J Brindley, R Reid Townsend, Robert Sprung, Bin Zhan, Maria-Elena Bottazzi, John M Hawdon, Yide Wong, Alex Loukas, Sergej Djuranovic, Makedonka Mitreva Jan 2023

Excretory/Secretory Proteome Of Females And Males Of The Hookworm Ancylostoma Ceylanicum, Samuel C Uzoechi, Bruce A Rosa, Kumar Sachin Singh, Young-Jun Choi, Bethany K Bracken, Paul J Brindley, R Reid Townsend, Robert Sprung, Bin Zhan, Maria-Elena Bottazzi, John M Hawdon, Yide Wong, Alex Loukas, Sergej Djuranovic, Makedonka Mitreva

Faculty, Staff and Students Publications

The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated by hookworm’s excretory/secretory products (ESPs), which have a wide spectrum of biological functions. We used ultra-high performance mass spectrometry to comprehensively profile and compare female and male ESPs from the zoonotic human hookworm Ancylostoma ceylanicum, which is a natural parasite of dogs, cats, and humans. We improved the genome annotation, decreasing the number of protein-coding genes by 49% while improving completeness from 92 to 96%. Compared to the previous genome annotation, we detected 11% and 10% more spectra in …


Establishing 3d Endometrial Organoids From The Mouse Uterus, Suni Tang, Sydney E Parks, Zian Liao, Dominique I Cope, Sarah E Blutt, Diana Monsivais Jan 2023

Establishing 3d Endometrial Organoids From The Mouse Uterus, Suni Tang, Sydney E Parks, Zian Liao, Dominique I Cope, Sarah E Blutt, Diana Monsivais

Faculty, Staff and Students Publications

Endometrial tissue lines the inner cavity of the uterus and is under the cyclical control of estrogen and progesterone. It is a tissue that is composed of luminal and glandular epithelium, a stromal compartment, a vascular network, and a complex immune cell population. Mouse models have been a powerful tool to study the endometrium, revealing critical mechanisms that control implantation, placentation, and cancer. The recent development of 3D endometrial organoid cultures presents a state-of-the-art model to dissect the signaling pathways that underlie endometrial biology. Establishing endometrial organoids from genetically engineered mouse models, analyzing their transcriptomes, and visualizing their morphology at …


Family Income And Cardiovascular Disease Risk In American Adults, Abdul Mannan Khan Minhas, Vardhmaan Jain, Monica Li, Robert W Ariss, Marat Fudim, Erin D Michos, Salim S Virani, Laurence Sperling, Anurag Mehta Jan 2023

Family Income And Cardiovascular Disease Risk In American Adults, Abdul Mannan Khan Minhas, Vardhmaan Jain, Monica Li, Robert W Ariss, Marat Fudim, Erin D Michos, Salim S Virani, Laurence Sperling, Anurag Mehta

Faculty, Staff and Students Publications

Socioeconomic status is an overlooked risk factor for cardiovascular disease (CVD). Low family income is a measure of socioeconomic status and may portend greater CVD risk. Therefore, we assessed the association of family income with cardiovascular risk factor and disease burden in American adults. This retrospective analysis included data from participants aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) cycles between 2005 and 2018. Family income to poverty ratio (PIR) was calculated by dividing family (or individual) income by poverty guidelines specific to the survey year and used as a measure of socioeconomic status. The …


Qualitative Study Of Pathways To Care Among Adults With Diabetes In Rural Guatemala, Anita Nandkumar Chary, Meghna Nandi, David Flood, Scott Tschida, Katharine Wilcox, Sophie Kurschner, Pablo Garcia, Peter Rohloff Jan 2023

Qualitative Study Of Pathways To Care Among Adults With Diabetes In Rural Guatemala, Anita Nandkumar Chary, Meghna Nandi, David Flood, Scott Tschida, Katharine Wilcox, Sophie Kurschner, Pablo Garcia, Peter Rohloff

Faculty, Staff and Students Publications

OBJECTIVE: The burden of diabetes mellitus is increasing in low-income and middle-income countries (LMICs). Few studies have explored pathways to care among individuals with diabetes in LMICs. This study evaluates care trajectories among adults with diabetes in rural Guatemala.

DESIGN: A qualitative investigation was conducted as part of a population-based study assessing incidence and risk factors for chronic kidney disease in two rural sites in Guatemala. A random sample of 807 individuals had haemoglobin A1c (HbA1c) screening for diabetes in both sites. Based on results from the first 6 months of the population study, semistructured interviews were performed with 29 …


Human Generation Times Across The Past 250,000 Years, Richard J Wang, Samer I Al-Saffar, Jeffrey Rogers, Matthew W Hahn Jan 2023

Human Generation Times Across The Past 250,000 Years, Richard J Wang, Samer I Al-Saffar, Jeffrey Rogers, Matthew W Hahn

Faculty, Staff and Students Publications

The generation times of our recent ancestors can tell us about both the biology and social organization of prehistoric humans, placing human evolution on an absolute time scale. We present a method for predicting historical male and female generation times based on changes in the mutation spectrum. Our analyses of whole-genome data reveal an average generation time of 26.9 years across the past 250,000 years, with fathers consistently older (30.7 years) than mothers (23.2 years). Shifts in sex-averaged generation times have been driven primarily by changes to the age of paternity, although we report a substantial increase in female generation …


Optimal Timing Of Antiretroviral Therapy Initiation In Children And Adolescents With Human Immunodeficiency Virus-Associated Pulmonary Tuberculosis, Alexander Kay, Jose Mendez-Reyes, Tara Devezin, Meenakshi Bakaya, Teresa Steffy, Sandile Dlamini, Amos Msekandiana, Tara Ness, Jason Bacha, Pauline Amuge, Mogomotsi Matshaba, Moses Chodota, Phoebe Nyasulu, Lineo Thahane, Lumumbwa Mwita, Adeodata Kekitiinwa, Andrew Dinardo, Bhekumusa Lukhele, H Lester Kirchner, Anna Mandalakas Jan 2023

Optimal Timing Of Antiretroviral Therapy Initiation In Children And Adolescents With Human Immunodeficiency Virus-Associated Pulmonary Tuberculosis, Alexander Kay, Jose Mendez-Reyes, Tara Devezin, Meenakshi Bakaya, Teresa Steffy, Sandile Dlamini, Amos Msekandiana, Tara Ness, Jason Bacha, Pauline Amuge, Mogomotsi Matshaba, Moses Chodota, Phoebe Nyasulu, Lineo Thahane, Lumumbwa Mwita, Adeodata Kekitiinwa, Andrew Dinardo, Bhekumusa Lukhele, H Lester Kirchner, Anna Mandalakas

Faculty, Staff and Students Publications

BACKGROUND: There is insufficient evidence in children and adolescents with human immunodeficiency virus (CAHIV) to guide the timing of antiretroviral treatment (ART) initiation after starting treatment for pulmonary tuberculosis (pTB). To address this knowledge gap, we evaluated the risk of mortality associated with timing of ART initiation in ART-naive CAHIV treated for pTB.

METHODS: Data were extracted from electronic medical records of ART-naive patients, aged 0-19 years, who were treated for HIV-associated pTB at Baylor Centers of Excellence in Botswana, Eswatini, Malawi, Lesotho, Tanzania, or Uganda between 2013 and 2020. Data were analyzed against a primary outcome of all-cause mortality …


Pickles V3: The Updated Database Of Pooled In Vitro Crispr Knockout Library Essentiality Screens, Lance C Novak, Juihsuan Chou, Medina Colic, Christopher A Bristow, Traver Hart Jan 2023

Pickles V3: The Updated Database Of Pooled In Vitro Crispr Knockout Library Essentiality Screens, Lance C Novak, Juihsuan Chou, Medina Colic, Christopher A Bristow, Traver Hart

Faculty, Staff and Student Publications

PICKLES (https://pickles.hart-lab.org) is an updated web interface to a freely available database of genome-scale CRISPR knockout fitness screens in human cell lines. Using a completely rewritten interface, researchers can explore gene knockout fitness phenotypes across cell lines and tissue types and compare fitness profiles with fitness, expression, or mutation profiles of other genes. The database has been updated to include data from three CRISPR libraries (Avana, Score, and TKOv3), and includes information from 1162 whole-genome screens probing the knockout fitness phenotype of 18 959 genes. Source code for the interface and the integrated database are available for download.


Bcl2l11 Induction Mediates Sensitivity To Src And Mek1/2 Inhibition In Thyroid Cancer, Madison M Rose, Veronica L Espinoza, Katelyn J Hoff, Laura A Pike, Vibha Sharma, Marie-Claude Hofmann, Aik Choon Tan, Nikita Pozdeyev, Rebecca E Schweppe Jan 2023

Bcl2l11 Induction Mediates Sensitivity To Src And Mek1/2 Inhibition In Thyroid Cancer, Madison M Rose, Veronica L Espinoza, Katelyn J Hoff, Laura A Pike, Vibha Sharma, Marie-Claude Hofmann, Aik Choon Tan, Nikita Pozdeyev, Rebecca E Schweppe

Faculty, Staff and Student Publications

Patients with advanced thyroid cancer, including advanced papillary thyroid cancer and anaplastic thyroid cancer (ATC), have low survival rates because of the lack of efficient therapies available that can combat their aggressiveness. A total of 90% of thyroid cancers have identifiable driver mutations, which often are components of the MAPK pathway, including BRAF, RAS, and RET-fusions. In addition, Src is a non-receptor tyrosine kinase that is overexpressed and activated in thyroid cancer, which we and others have shown is a clinically relevant target. We have previously demonstrated that combined inhibition of Src with dasatinib and the MAPK …


Immune Environment And Antigen Specificity Of The T Cell Receptor Repertoire Of Malignant Ascites In Ovarian Cancer, Kyoko Yoshida-Court, Tatiana V Karpinets, Aparna Mitra, Travis N Solley, Stephanie Dorta-Estremera, Travis T Sims, Andrea Y Delgado Medrano, Molly B El Alam, Mustapha Ahmed-Kaddar, Erica J Lynn, K Jagannadha Sastry, Jianhua Zhang, Andrew Futreal, Alpa Nick, Karen Lu, Lauren E Colbert, Ann H Klopp Jan 2023

Immune Environment And Antigen Specificity Of The T Cell Receptor Repertoire Of Malignant Ascites In Ovarian Cancer, Kyoko Yoshida-Court, Tatiana V Karpinets, Aparna Mitra, Travis N Solley, Stephanie Dorta-Estremera, Travis T Sims, Andrea Y Delgado Medrano, Molly B El Alam, Mustapha Ahmed-Kaddar, Erica J Lynn, K Jagannadha Sastry, Jianhua Zhang, Andrew Futreal, Alpa Nick, Karen Lu, Lauren E Colbert, Ann H Klopp

Faculty, Staff and Student Publications

We evaluated the association of disease outcome with T cell immune-related characteristics and T cell receptor (TCR) repertoire in malignant ascites from patients with high-grade epithelial ovarian cancer. Ascitic fluid samples were collected from 47 high-grade epithelial ovarian cancer patients and analyzed using flow cytometry and TCR sequencing to characterize the complementarity determining region 3 TCR β-chain. TCR functions were analyzed using the McPAS-TCR and VDJ databases. TCR clustering was implemented using Grouping of Lymphocyte Interactions by Paratope Hotspots software. Patients with poor prognosis had ascites characterized by an increased ratio of CD8+ T cells to regulatory T cells, which …


Antagonistic Effect Of Cyclin-Dependent Kinases And A Calcium-Dependent Phosphatase On Polyglutamine-Expanded Androgen Receptor Toxic Gain Of Function, Diana Piol, Laura Tosatto, Emanuela Zuccaro, Eric N Anderson, Antonella Falconieri, Maria J Polanco, Caterina Marchioretti, Federica Lia, Joseph White, Elisa Bregolin, Giovanni Minervini, Sara Parodi, Xavier Salvatella, Giorgio Arrigoni, Andrea Ballabio, Albert R La Spada, Silvio C E Tosatto, Fabio Sambataro, Diego L Medina, Udai B Pandey, Manuela Basso, Maria Pennuto Jan 2023

Antagonistic Effect Of Cyclin-Dependent Kinases And A Calcium-Dependent Phosphatase On Polyglutamine-Expanded Androgen Receptor Toxic Gain Of Function, Diana Piol, Laura Tosatto, Emanuela Zuccaro, Eric N Anderson, Antonella Falconieri, Maria J Polanco, Caterina Marchioretti, Federica Lia, Joseph White, Elisa Bregolin, Giovanni Minervini, Sara Parodi, Xavier Salvatella, Giorgio Arrigoni, Andrea Ballabio, Albert R La Spada, Silvio C E Tosatto, Fabio Sambataro, Diego L Medina, Udai B Pandey, Manuela Basso, Maria Pennuto

Duncan NRI Faculty and Staff Publications

Spinal and bulbar muscular atrophy is caused by polyglutamine (polyQ) expansions in androgen receptor (AR), generating gain-of-function toxicity that may involve phosphorylation. Using cellular and animal models, we investigated what kinases and phosphatases target polyQ-expanded AR, whether polyQ expansions modify AR phosphorylation, and how this contributes to neurodegeneration. Mass spectrometry showed that polyQ expansions preserve native phosphorylation and increase phosphorylation at conserved sites controlling AR stability and transactivation. In small-molecule screening, we identified that CDC25/CDK2 signaling could enhance AR phosphorylation, and the calcium-sensitive phosphatase calcineurin had opposite effects. Pharmacologic and genetic manipulation of these kinases and phosphatases modified polyQ-expanded AR …


Rbp Image Database: A Resource For The Systematic Characterization Of The Subcellular Distribution Properties Of Human Rna Binding Proteins, Louis Philip Benoit Bouvrette, Xiaofeng Wang, Jonathan Boulais, Jian Kong, Easin Uddin Syed, Steven M Blue, Lijun Zhan, Sara Olson, Rebecca Stanton, Xintao Wei, Brian Yee, Eric L Van Nostrand, Xiang-Dong Fu, Christopher B Burge, Brenton R Graveley, Gene W Yeo, Eric Lécuyer Jan 2023

Rbp Image Database: A Resource For The Systematic Characterization Of The Subcellular Distribution Properties Of Human Rna Binding Proteins, Louis Philip Benoit Bouvrette, Xiaofeng Wang, Jonathan Boulais, Jian Kong, Easin Uddin Syed, Steven M Blue, Lijun Zhan, Sara Olson, Rebecca Stanton, Xintao Wei, Brian Yee, Eric L Van Nostrand, Xiang-Dong Fu, Christopher B Burge, Brenton R Graveley, Gene W Yeo, Eric Lécuyer

Faculty, Staff and Students Publications

RNA binding proteins (RBPs) are central regulators of gene expression implicated in all facets of RNA metabolism. As such, they play key roles in cellular physiology and disease etiology. Since different steps of post-transcriptional gene expression tend to occur in specific regions of the cell, including nuclear or cytoplasmic locations, defining the subcellular distribution properties of RBPs is an important step in assessing their potential functions. Here, we present the RBP Image Database, a resource that details the subcellular localization features of 301 RBPs in the human HepG2 and HeLa cell lines, based on the results of systematic immuno-fluorescence studies …


Regrowing The Heart, One Tree At A Time, Jeffrey D Steimle, James F Martin Jan 2023

Regrowing The Heart, One Tree At A Time, Jeffrey D Steimle, James F Martin

Faculty, Staff and Students Publications

While many animals can completely repair injured tissues, the mammalian heart possesses limited regenerative capabilities. Yan and Cigliola et al. show that AAV-mediated, zebrafish-derived tissue regeneration enhancer elements (TREEs) can direct pro-regenerative gene expression in injured cardiac tissue of mice and pigs that turn off following repair.


Agreement Between Patient’S Description Of Abdominal Symptoms Of Possible Upper Gastrointestinal Cancer And General Practitioner Consultation Notes: A Qualitative Analysis Of Video-Recorded Uk Primary Care Consultation Data, Victoria Hardy, Juliet Usher-Smith, Stephanie Archer, Rebecca Barnes, John Lancaster, Margaret Johnson, Matthew Thompson, Jon Emery, Hardeep Singh, Fiona M Walter Jan 2023

Agreement Between Patient’S Description Of Abdominal Symptoms Of Possible Upper Gastrointestinal Cancer And General Practitioner Consultation Notes: A Qualitative Analysis Of Video-Recorded Uk Primary Care Consultation Data, Victoria Hardy, Juliet Usher-Smith, Stephanie Archer, Rebecca Barnes, John Lancaster, Margaret Johnson, Matthew Thompson, Jon Emery, Hardeep Singh, Fiona M Walter

Faculty, Staff and Students Publications

Introduction: Abdominal symptoms are common in primary care but infrequently might be due to an upper gastrointestinal (UGI) cancer. Patients' descriptions may differ from medical terminology used by general practitioners (GPs). This may affect how information about abdominal symptoms possibly due to an UGI cancer are documented, creating potential missed opportunities for timely investigation.

Objectives: To explore how abdominal symptoms are communicated during primary care consultations, and identify characteristics of patients' descriptions that underpin variation in the accuracy and completeness with which they are documented in medical records.

Methods and analysis: Primary care consultation video recordings, transcripts and medical records …


Rare Eif4a2 Variants Are Associated With A Neurodevelopmental Disorder Characterized By Intellectual Disability, Hypotonia, And Epilepsy, Maimuna S Paul, Anna R Duncan, Casie A Genetti, Hongling Pan, Adam Jackson, Patricia E Grant, Jiahai Shi, Michele Pinelli, Nicola Brunetti-Pierri, Alexandra Garza-Flores, Dave Shahani, Russell P Saneto, Giuseppe Zampino, Chiara Leoni, Emanuele Agolini, Antonio Novelli, Ulrike Blümlein, Tobias B Haack, Wolfram Heinritz, Eva Matzker, Bader Alhaddad, Rami Abou Jamra, Tobias Bartolomaeus, Saber Alhamdan, Raphael Carapito, Bertrand Isidor, Seiamak Bahram, Alyssa Ritter, Kosuke Izumi, Ben Pode Shakked, Ortal Barel, Bruria Ben Zeev, Amber Begtrup, Deanna Alexis Carere, Sureni V Mullegama, Timothy Blake Palculict, Daniel G Calame, Katharina Schwan, Alicia R P Aycinena, Rasa Traberg, Genomics England Research Consortium, Sofia Douzgou, Harrison Pirt, Naila Ismayilova, Siddharth Banka, Hsiao-Tuan Chao, Pankaj B Agrawal Jan 2023

Rare Eif4a2 Variants Are Associated With A Neurodevelopmental Disorder Characterized By Intellectual Disability, Hypotonia, And Epilepsy, Maimuna S Paul, Anna R Duncan, Casie A Genetti, Hongling Pan, Adam Jackson, Patricia E Grant, Jiahai Shi, Michele Pinelli, Nicola Brunetti-Pierri, Alexandra Garza-Flores, Dave Shahani, Russell P Saneto, Giuseppe Zampino, Chiara Leoni, Emanuele Agolini, Antonio Novelli, Ulrike Blümlein, Tobias B Haack, Wolfram Heinritz, Eva Matzker, Bader Alhaddad, Rami Abou Jamra, Tobias Bartolomaeus, Saber Alhamdan, Raphael Carapito, Bertrand Isidor, Seiamak Bahram, Alyssa Ritter, Kosuke Izumi, Ben Pode Shakked, Ortal Barel, Bruria Ben Zeev, Amber Begtrup, Deanna Alexis Carere, Sureni V Mullegama, Timothy Blake Palculict, Daniel G Calame, Katharina Schwan, Alicia R P Aycinena, Rasa Traberg, Genomics England Research Consortium, Sofia Douzgou, Harrison Pirt, Naila Ismayilova, Siddharth Banka, Hsiao-Tuan Chao, Pankaj B Agrawal

Faculty, Staff and Students Publications

Eukaryotic initiation factor-4A2 (EIF4A2) is an ATP-dependent RNA helicase and a member of the DEAD-box protein family that recognizes the 5' cap structure of mRNAs, allows mRNA to bind to the ribosome, and plays an important role in microRNA-regulated gene repression. Here, we report on 15 individuals from 14 families presenting with global developmental delay, intellectual disability, hypotonia, epilepsy, and structural brain anomalies, all of whom have extremely rare de novo mono-allelic or inherited bi-allelic variants in EIF4A2. Neurodegeneration was predominantly reported in individuals with bi-allelic variants. Molecular modeling predicts these variants would perturb structural interactions in key protein domains. …


Comparison Between The Casia Ss-1000 And Pentacam In Measuring Corneal Curvatures And Corneal Thickness Maps, Robert M Feldman, Gene Kim, Alice Z Chuang, Atsushi Shiraishi, Keiichiro Okamoto, Makoto Tsukamoto Jan 2023

Comparison Between The Casia Ss-1000 And Pentacam In Measuring Corneal Curvatures And Corneal Thickness Maps, Robert M Feldman, Gene Kim, Alice Z Chuang, Atsushi Shiraishi, Keiichiro Okamoto, Makoto Tsukamoto

Faculty, Staff and Student Publications

PURPOSE: To compare the intra-device repeatability and inter-device reproducibility between two anterior segment imaging instruments, the CASIA SS-1000 (Tomey Corp., Nagoya, Japan) and Pentacam (OCULUS, Arlington, WA) in measuring anterior segment parameters.

METHODS: Single-center, prospective clinical trial. Participants ≥20 years of age were included. One eye was randomly selected, each imaged by three CASIA SS-1000 devices and three Pentacam devices by three different examiners. Each photographer operated a pair of devices, one CASIA SS-1000 and one Pentacam. The image order for each participant was determined by a random permutation table. Three images were taken from each device. A total of …


Characteristics And Weight Loss Practices From A Cohort Of 20,000 Patients Using Direct-To-Consumer Telehealth: Observational Cross-Sectional Study, Deborah Bade Horn, Elizabeth Pash, Megan S Zhou, Lauren Broffman, Damian Bialonczyk, Tzvi Doron, Elaine Chiquette Jan 2023

Characteristics And Weight Loss Practices From A Cohort Of 20,000 Patients Using Direct-To-Consumer Telehealth: Observational Cross-Sectional Study, Deborah Bade Horn, Elizabeth Pash, Megan S Zhou, Lauren Broffman, Damian Bialonczyk, Tzvi Doron, Elaine Chiquette

Faculty, Staff and Student Publications

BACKGROUND: Despite the increasing prevalence of obesity, the use of pharmacotherapy treatment remains low. Telehealth platforms have the potential to facilitate access to pharmacotherapy interventions, but little is known about telehealth patients.

OBJECTIVE: This study describes a large patient population taking Plenity, an oral superabsorbent hydrogel (OSH) used in the treatment of excess weight or obesity (BMI 25-40 kg/m

METHODS: This was a cross-sectional assessment of a random sample of 20,000 telehealth patients who completed a structured, web-based visit and received at least one prescription of OSH. Patients were eligible to receive care via telehealth if they were adults, were …


Chronic Conditions, Late Mortality, And Health Status After Childhood Aml: A Childhood Cancer Survivor Study Report, Lucie M Turcotte, Jillian A Whitton, Wendy M Leisenring, Rebecca M Howell, Joseph P Neglia, Rachel Phelan, Kevin C Oeffinger, Kirsten K Ness, William G Woods, E Anders Kolb, Leslie L Robison, Gregory T Armstrong, Eric J Chow Jan 2023

Chronic Conditions, Late Mortality, And Health Status After Childhood Aml: A Childhood Cancer Survivor Study Report, Lucie M Turcotte, Jillian A Whitton, Wendy M Leisenring, Rebecca M Howell, Joseph P Neglia, Rachel Phelan, Kevin C Oeffinger, Kirsten K Ness, William G Woods, E Anders Kolb, Leslie L Robison, Gregory T Armstrong, Eric J Chow

Faculty, Staff and Student Publications

Five-year survival following childhood acute myeloid leukemia (AML) has increased following improvements in treatment and supportive care. Long-term health outcomes are unknown. To address this, cumulative incidence of late mortality and grades 3 to 5 chronic health condition (CHC) were estimated among 5-year AML survivors diagnosed between 1970 and 1999. Survivors were compared by treatment group (hematopoietic cell transplantation [HCT], chemotherapy with cranial radiation [chemo + CRT], chemotherapy only [chemo-only]), and diagnosis decade. Self-reported health status was compared across treatments, diagnosis decade, and with siblings. Among 856 survivors (median diagnosis age, 7.1 years; median age at last follow-up, 29.4 years), …


Feasibility, Acceptability, And Efficacy Of Home-Based Transcranial Direct Current Stimulation On Pain In Older Adults With Alzheimer’S Disease And Related Dementias: A Randomized Sham-Controlled Pilot Clinical Trial, Geraldine Martorella, Hongyu Miao, Duo Wang, Lindsey Park, Kenneth Mathis, Juyoung Park, Julia Sheffler, Lisa Granville, Antonio L Teixeira, Paul E Schulz, Hyochol Ahn Jan 2023

Feasibility, Acceptability, And Efficacy Of Home-Based Transcranial Direct Current Stimulation On Pain In Older Adults With Alzheimer’S Disease And Related Dementias: A Randomized Sham-Controlled Pilot Clinical Trial, Geraldine Martorella, Hongyu Miao, Duo Wang, Lindsey Park, Kenneth Mathis, Juyoung Park, Julia Sheffler, Lisa Granville, Antonio L Teixeira, Paul E Schulz, Hyochol Ahn

Faculty, Staff and Student Publications

Although transcranial direct current stimulation (tDCS) is emerging as a convenient pain relief modality for several chronic pain conditions, its feasibility, acceptability, and preliminary efficacy on pain in patients with Alzheimer’s disease and related dementias (ADRD) have not been investigated. The purpose of this pilot study was to assess the feasibility, acceptability, and preliminary efficacy of 5, 20-min home-based tDCS sessions on chronic pain in older adults with ADRD. We randomly assigned 40 participants to active (n = 20) or sham (n = 20) tDCS. Clinical pain intensity was assessed using a numeric rating scale (NRS) with patients …


Utility Of Computed Tomography In Diagnosis Of A Patent Ductus Arteriosus In Pulmonary Artery Endarteritis, Anneliese J Grewing, Betul Yilmaz Furtun, Melissa K Webb Jan 2023

Utility Of Computed Tomography In Diagnosis Of A Patent Ductus Arteriosus In Pulmonary Artery Endarteritis, Anneliese J Grewing, Betul Yilmaz Furtun, Melissa K Webb

Faculty, Staff and Students Publications

A 15-year-old patient with infective endarteritis had a pulmonary artery vegetation but no ductus arteriosus on echocardiogram. Computed tomography scan revealed a closed ductus that became patent after antibiotics and anticoagulation. Infective endarteritis should be considered in patients with a pulmonary artery vegetation even if no ductus is seen on echocardiogram. (Level of Difficulty: Intermediate.)


Global Gene Expression Analysis Reveals Complex Cuticle Organization Of The Tribolium Compound Eye, Qing Chen, Arun Kirshna Sasikala-Appukuttan, Zahabiya Husain, Anura Shrivastava, Marla Spain, Edward D Sendler, Bryce Daines, Stefan Fischer, Rui Chen, Tiffany A Cook, Markus Friedrich Jan 2023

Global Gene Expression Analysis Reveals Complex Cuticle Organization Of The Tribolium Compound Eye, Qing Chen, Arun Kirshna Sasikala-Appukuttan, Zahabiya Husain, Anura Shrivastava, Marla Spain, Edward D Sendler, Bryce Daines, Stefan Fischer, Rui Chen, Tiffany A Cook, Markus Friedrich

Faculty, Staff and Students Publications

The red flour beetle Tribolium castaneum is a resource-rich model for genomic and developmental studies. To extend previous studies on Tribolium eye development, we produced transcriptomes for normal-eyed and eye-depleted heads of pupae and adults to identify differentially transcript-enriched (DE) genes in the visual system. Unexpectedly, cuticle-related genes were the largest functional class in the pupal compound eye DE gene population, indicating differential enrichment in three distinct cuticle components: clear lens facet cuticle, highly melanized cuticle of the ocular diaphragm, which surrounds the Tribolium compound eye for internal fortification, and newly identified facet margins of the tanned cuticle, possibly enhancing …


A Low-Fat/Sucrose Diet Rich In Complex Carbohydrates Reverses High-Fat/Sucrose Diet-Induced Corneal Dysregulation, Prince K Akowuah, Carolina Lema, Rolando E Rumbaut, Alan R Burns Jan 2023

A Low-Fat/Sucrose Diet Rich In Complex Carbohydrates Reverses High-Fat/Sucrose Diet-Induced Corneal Dysregulation, Prince K Akowuah, Carolina Lema, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

High-fat/sucrose diet feeding in mice causes loss of corneal nerve function and impairs corneal wound healing. While changing to a diet with a low fat/sugar composition and enrichments in complex carbohydrates mitigates the reduction in nerve function, it remains to be determined if it has an effect on corneal wound healing. In this study, 6-week-old C57BL/6 male mice were fed either a normal diet or a high-fat/sucrose diet for 20 weeks. A third group (diet reversal) was placed on a high-fat/sucrose diet for 10 weeks followed by a normal diet for an additional 10 weeks. A central corneal epithelial abrasion …


Notch Blockade Specifically In Bone Marrow-Derived Fsp-1-Positive Cells Ameliorates Renal Fibrosis, Yongdong Wu, Ming Liang, Fengzhang Huang, Owen H Cheng, Xiaoguang Xiao, Tae Hoon Lee, Luan Truong, Jizhong Cheng Jan 2023

Notch Blockade Specifically In Bone Marrow-Derived Fsp-1-Positive Cells Ameliorates Renal Fibrosis, Yongdong Wu, Ming Liang, Fengzhang Huang, Owen H Cheng, Xiaoguang Xiao, Tae Hoon Lee, Luan Truong, Jizhong Cheng

Faculty, Staff and Students Publications

Background: The infiltration of inflammatory cells during a kidney injury stimulates myofibroblast activation leading to kidney fibrosis. Fibroblast-specific protein 1 (FSP-1) positive cells have been reported as either myofibroblasts or monocytes during tissue fibrosis. The functions of FSP-1+ cells that are associated with the development of renal fibrosis and the signaling pathways that regulate FSP-1+ cell activation have not been well defined. Methods: In mice with unilateral ureteral obstruction (UUO), we characterized FSP-1+ cells and determined the role of the Notch signaling pathway in the activation of bone marrow-derived FSP-1+ cells during kidney fibrosis. Results: In kidneys from mice with …


Single-Cell Multi-Omics Integration For Unpaired Data By A Siamese Network With Graph-Based Contrastive Loss, Chaozhong Liu, Linhua Wang, Zhandong Liu Jan 2023

Single-Cell Multi-Omics Integration For Unpaired Data By A Siamese Network With Graph-Based Contrastive Loss, Chaozhong Liu, Linhua Wang, Zhandong Liu

Faculty, Staff and Students Publications

BACKGROUND: Single-cell omics technology is rapidly developing to measure the epigenome, genome, and transcriptome across a range of cell types. However, it is still challenging to integrate omics data from different modalities. Here, we propose a variation of the Siamese neural network framework called MinNet, which is trained to integrate multi-omics data on the single-cell resolution by using graph-based contrastive loss.

RESULTS: By training the model and testing it on several benchmark datasets, we showed its accuracy and generalizability in integrating scRNA-seq with scATAC-seq, and scRNA-seq with epitope data. Further evaluation demonstrated our model's unique ability to remove the batch …