Digital Commons Network^™

Hands-On Training About Data Clustering With Orange Data Mining Toolbox, Janez Demšar, Blaž Zupan

Faculty, Staff and Students Publications

Data clustering is a core data science approach widely used and referenced in the scientific literature. Its algorithms are often intuitive and can lead to exciting, insightful results that are easy to interpret. For these reasons, data clustering techniques could be the first method encountered in data science training. This paper proposes a hands-on approach to data clustering training suitable for introductory courses. The education approach features problem-based training that starts with the data and gradually introduces various data processing and analysis methods, illustrating them through visual representations of data and models. The proposed training is suitable for a general …

Machine Learning-Based Prediction Model For Icu Mortality After Continuous Renal Replacement Therapy Initiation In Children, Sameer Thadani, Tzu-Chun Wu, Danny T Y Wu, Aadil Kakajiwala, Danielle E Soranno, Gerard Cortina, Rachana Srivastava, Katja M Gist, Shina Menon, Worldwide Exploration Of Renal Replacement Outcomes Collaborative In Kidney Diseases (We-Rock) Collaborators

Faculty, Staff and Students Publications

BACKGROUND: Continuous renal replacement therapy (CRRT) is the favored renal replacement therapy in critically ill patients. Predicting clinical outcomes for CRRT patients is difficult due to population heterogeneity, varying clinical practices, and limited sample sizes.

OBJECTIVE: We aimed to predict survival to ICUs and hospital discharge in children and young adults receiving CRRT using machine learning (ML) techniques.

DERIVATION COHORT: Patients less than 25 years of age receiving CRRT for acute kidney injury and/or volume overload from 2015 to 2021 (80%).

VALIDATION COHORT: Internal validation occurred in a testing group of patients from the dataset (20%).

PREDICTION MODEL: Retrospective international …

Chronic Β3-Ar Stimulation Activates Distinct Thermogenic Mechanisms In Brown And White Adipose Tissue And Improves Systemic Metabolism In Aged Mice, Duraipandy Natarajan, Bhuvana Plakkot, Kritika Tiwari, Shoba Ekambaram, Weidong Wang, Michael Rudolph, Mahmoud A Mohammad, Shaji K Chacko, Madhan Subramanian, Stefano Tarantini, Andriy Yabluchanskiy, Zoltan Ungvari, Anna Csiszar, Priya Balasubramanian

Faculty, Staff and Students Publications

Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle-aged and older populations, which bear the highest obesity prevalence in the United States (approximately 40%), remains uncertain due to age-related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3-adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18-month-old) C57BL/6JN mice. Sustained β3-AR treatment resulted in reduced fat mass, increased energy expenditure, increased fatty acid oxidation and mitochondrial activity in adipose depots, improved glucose homeostasis, and a …

Randomized, Observer-Blind, Controlled Phase 1 Study Of The Safety And Immunogenicity Of The Na-Gst-1/Alhydrogel Hookworm Vaccine With Or Without A Cpg Odn Adjuvant In Hookworm-Naïve Adults, David J Diemert, Maria Zumer, Mark Bova, Christina Gibbs-Tewary, Elissa M Malkin, Doreen Campbell, Lara Hoeweler, Guangzhao Li, Maria Elena Bottazzi, Peter J Hotez, Jeffrey M Bethony

Faculty, Staff and Students Publications

BACKGROUND: Recombinant Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) formulated on Alhydrogel (Na-GST-1/Alhydrogel) is being developed to prevent anemia and other complications of N. americanus infection. Antibodies induced by vaccination with recombinant Na-GST-1 are hypothesized to interfere with the blood digestion pathway of adult hookworms in the host. Phase 1 trials have demonstrated the safety of Na-GST-1 formulated on Alhydrogel, but further optimization of the vaccine adjuvant formulation may improve humoral immune responses, thereby increasing the likelihood of vaccine efficacy.

METHODS: A randomized, observer-blind, dose escalation Phase 1 trial was conducted in 24 healthy, hookworm-naïve adults. In each cohort of 12 participants, 4 …

Immunopeptidomic Mhc-I Profiling And Immunogenicity Testing Identifies Tcj2 As A New Chagas Disease Mrna Vaccine Candidate, Leroy Versteeg, Rakesh Adhikari, Gonteria Robinson, Jungsoon Lee, Junfei Wei, Nelufa Islam, Brian Keegan, William K Russell, Cristina Poveda, Maria Jose Villar, Kathryn Jones, Maria Elena Bottazzi, Peter Hotez, Edwin Tijhaar, Jeroen Pollet

Faculty, Staff and Students Publications

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease. Globally 6 to 7 million people are infected by this parasite of which 20-30% will progress to develop Chronic Chagasic Cardiomyopathy (CCC). Despite its high disease burden, no clinically approved vaccine exists for the prevention or treatment of CCC. Developing vaccines that can stimulate T. cruzi-specific CD8+ cytotoxic T cells and eliminate infected cells requires targeting parasitic antigens presented on major histocompatibility complex-I (MHC-I) molecules. We utilized mass spectrometry-based immunopeptidomics to investigate which parasitic peptides are displayed on MHC-I of T. cruzi infected cells. Through duplicate experiments, we identified an …

Comparison Of Predicted And Actual Dermatitis Generated From Computed Tomography Images And Dose Distribution Maps, Yasuhide Miyabe, Saori Oshiro, Hiroto Seki, Yusuke Muroi, Eriko Kawashima, Megumi Hosoda, Kento Ohashi, Hiromu Yamanaka, Mingliang Shao, Hiromi Sugawara, Jyunetsu Mizoe, Ritsuko Komaki

Faculty, Staff and Students Publications

Anticipating the onset, location and severity of radiation dermatitis before radiotherapy can aid in dermatological care. This study developed a method for creation of a prediction diagram for dermatitis and conducted a comparative verification between the prediction diagram and actual patient condition. The prediction diagram involved converting skin doses into 2 Gy fractionated equivalent doses using α/β of 10.0, defining regions of interest (ROIs) from 20-50 Gy at 10 Gy intervals. Overlaps between these ROIs at each dose level and the skin (external) was sequentially color-coded as blue, yellow, red, and purple. The study included four patients: two underwent head …

Template-Assisted Covalent Modification Underlies Activity Of Covalent Molecular Glues, Yen-Der Li, Michelle W Ma, Muhammad Murtaza Hassan, Moritz Hunkeler, Mingxing Teng, Kedar Puvar, Justine C Rutter, Ryan J Lumpkin, Brittany Sandoval, Cyrus Y Jin, Anna M Schmoker, Scott B Ficarro, Hakyung Cheong, Rebecca J Metivier, Michelle Y Wang, Shawn Xu, Woong Sub Byun, Brian J Groendyke, Inchul You, Logan H Sigua, Isidoro Tavares, Charles Zou, Jonathan M Tsai, Paul M C Park, Hojong Yoon, Felix C Majewski, Haniya T Sperling, Jarrod A Marto, Jun Qi, Radosław P Nowak, Katherine A Donovan, Mikołaj Słabicki, Nathanael S Gray, Eric S Fischer, Benjamin L Ebert

Faculty, Staff and Students Publications

Molecular glues are proximity-inducing small molecules that have emerged as an attractive therapeutic approach. However, developing molecular glues remains challenging, requiring innovative mechanistic strategies to stabilize neoprotein interfaces and expedite discovery. Here we unveil a trans-labeling covalent molecular glue mechanism, termed ‘template-assisted covalent modification’. We identified a new series of BRD4 molecular glue degraders that recruit CUL4DCAF16 ligase to the second bromodomain of BRD4 (BRD4BD2). Through comprehensive biochemical, structural and mutagenesis analyses, we elucidated how pre-existing structural complementarity between DCAF16 and BRD4BD2 serves as a template to optimally orient the degrader for covalent modification of DCAF16Cys58. This process stabilizes …

Aging-Associated Mechanisms Of Atrial Fibrillation Progression And Their Therapeutic Potential, Shuai Zhao, Aaron M Johnston, Chi Him Kendrick Yiu, Lucia M Moreira, Svetlana Reilly, Xander H T Wehrens

Faculty, Staff and Students Publications

Atrial fibrillation (AF) is the most common sustained arrhythmia, with a particularly high prevalence in the elderly. As the global aging population rapidly expands, it is increasingly important to examine how alterations to the aging heart contribute to an increased AF susceptibility. This work critically reviews the key molecular mechanisms that may underpin the complex association between aging and AF. Moreover, we identify emerging novel opportunities for therapeutic intervention that may be able to prevent and/or improve the current treatment paradigms for age-related AF. This review contributes to a holistic understanding of the intricate relationship between aging and AF.

Testosterone Acts Through The Membrane Protein Gprc6a To Cause Cardiac Edema In Zebrafish Embryos, Vahid Zadmajid, Shayan Shahriar, Daniel A Gorelick

Faculty, Staff and Students Publications

Androgens are classically thought to act through intracellular androgen receptors (AR/NR3C4), but they can also trigger non-genomic effects via membrane proteins. Although several membrane androgen receptors have been characterized in vitro, their functions in vivo remain unclear. Using a chemical-genetic screen in zebrafish, we found that GPRC6A, a G-protein-coupled receptor, mediates non-genomic androgen actions during embryonic development. Exposure to androgens (androstanedione, DHT and testosterone) caused cardiac edema or tail curvature in wild-type embryos, as well as in ar mutants, suggesting AR-independent pathways. We then mutated putative membrane androgen receptors [gprc6a, hcar1-4 and zip9 (slc39a9)] and found that only gprc6a mutants …

Epinephrine Versus Dopamine In Children, What Is The Current Evidence And What Do We Need? A Systematic Review And Meta-Analysis, Rohit S Loomba, Riddhi D Patel, Enrique G Villarreal, Juan S Farias, Saul Flores

Faculty, Staff and Students Publications

Introduction: Pediatric patients often receive vasoactive agents following cardiothoracic surgery or when in shock. The use of vasoactive agents varies between different settings and has largely changed because of anecdotal observations or small observational studies. Although vasoactive agents are frequently used, there are limited studies in pediatric populations comparing them to one another. The purpose of this systematic review is to quantify the comparative effects of epinephrine and dopamine while identifying gaps in knowledge.

Methods: A systematic review of published manuscripts was completed to identify full-text manuscripts in English using PubMed, Embase, and Cochrane databases. Studies were included if they …

Lack Of Association Of First And Second-Line Medication Dosing And Progression To Refractory Status Epilepticus In Children, Cristina Barcia Aguilar, Marta Amengual-Gual, J Nicholas Brenton, Kevin E Chapman, Justice Clark, William D Gaillard, Joshua L Goldstein, Howard P Goodkin, Robert Kahoud, Yi-Chen Lai, Mohamad A Mikati, Lindsey A Morgan, Eric T Payne, Craig A Press, Latania Reece, Tristan T Sands, Kumar Sannagowdara, Theodore Sheehan, Renée A Shellhaas, Robert C Tasker, Mark S Wainwright, Bo Zhang, Tobias Loddenkemper

Faculty, Staff and Students Publications

Purpose: Evaluate the relationship between first and second-line medication dosing and progression to refractory status epilepticus (RSE) in children.

Methods: This is a retrospective analysis of prospectively collected data from September 2014 to February 2020 of children with status epilepticus (SE) who received at least two antiseizure medications (ASMs). We evaluated the risk of developing RSE after receiving a low total benzodiazepine dose (lower than 100 % of the minimum recommended dose for each benzodiazepine dose administered within 10 min) and a low first non-benzodiazepine ASM dose (lower than 100 % of the minimum recommended dose of non-benzodiazepine ASM given …

Are Prediction Models Moving Closer To Clinical Application In The Diagnosis Of Type Of Diabetes In Youth?, Fida Bacha

Faculty, Staff and Students Publications

No abstract provided.

Proteomic Analysis Uncovers Multiprotein Signatures Associated With Early Diabetic Kidney Disease In Youth With Type 2 Diabetes Mellitus, Laura Pyle, Ye Ji Choi, Phoom Narongkiatikhun, Kumar Sharma, Sushrut Waikar, Anita Layton, Kalie L Tommerdahl, Ian De Boer, Timothy Vigers, Robert G Nelson, Jane Lynch, Frank Brosius, Pierre J Saulnier, Jesse A Goodrich, Jeanie B Tryggestad, Elvira Isganaitis, Fida Bacha, Kristen J Nadeau, Daniel Van Raalte, Matthias Kretzler, Hiddo Heerspink, Petter Bjornstad

Faculty, Staff and Students Publications

Background: The onset of diabetic kidney disease (DKD) in youth with type 2 diabetes (T2D) mellitus often occurs early, leading to complications in young adulthood. Risk biomarkers associated with the early onset of DKD are urgently needed in youth with T2D.

Methods: We conducted an in-depth analysis of 6596 proteins (SomaScan 7K) in 374 baseline plasma samples from the Treatment Options for Type 2 Diabetes in Adolescents and Youth study to identify multiprotein signatures associated with the onset of albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g), a rapid decline in eGFR (annual eGFR decline >3 ml/min per 1.73 m2 and/or ≥3.3% …

Shared Genetic Architecture Of Non-Viral Cirrhosis With Several Pleiotropic Traits: A Nested Case-Control Study In The Uk Biobank, Jinyoung Byun, Hyun-Seok Kim, Younghun Han, Aaron P Thrift, Sabrina M Lin, Xiangjun Xiao, Hyeyeun Lim, Goo Jun, Stacia M Desantis, Hashem B El-Serag, Fasiha Kanwal, Christopher I Amos

Faculty, Staff and Students Publications

Background & aims: Cirrhosis is a leading cause of liver-related mortality and a multifactorial disease. To date, the complex genetic architecture of non-viral cirrhosis has not been fully explored. Cross-trait genetic correlations can elucidate the common genetic etiology of genetically correlated phenotypes. This study aims to identify polygenic and pleiotropic traits associated with cirrhosis using the linkage disequilibrium score regression analysis.

Methods: We conducted genome-wide association analysis of 9,622,842 imputed SNPs on 3,368 non-viral cirrhosis cases and 258,258 controls, and cross-trait analysis between non-viral cirrhosis and various polygenic and pleiotropic traits using the UK Biobank cohort study. We further performed …

Health Implications Of Racial Differences In Serum Growth Differentiation Factor Levels Among Men With Obesity, Siresha Bathina, Virginia Fuenmayor Lopez, Mia Prado, Elliot Ballato, Georgia Colleluori, Maryam Tetlay, Dennis Tan Villareal, Sanjay Mediwala, Rui Chen, Clifford Qualls, Reina Armamento-Villareal

Faculty, Staff and Students Publications

Growth differentiation factor (GDF15) has been considered a biomarker and recently a hormonal driver for diseases in different populations. However, the role of GDF15 as a biomarker of health outcomes in obese men from different racial/ethnic background has not been evaluated. The objective of this study was to investigate the racial/ethnic differences on the relationship between GDF15 and markers of glucometabolic status, hormonal profile, body composition and bone mineral density (BMD) in obese men. One hundred ninety-three obese men from diverse racial/ethnic backgrounds were enrolled. BMD and body composition were measured by dual energy X-ray absorptiometry. Serum GDF15, osteocalcin, C-terminal …

A Reproducible Pipeline For Parcellation Of The Anterior Limb Of The Internal Capsule, Karianne Sretavan, Henry Braun, Zoe Liu, Daniel Bullock, Tara Palnitkar, Remi Patriat, Jayashree Chandrasekaran, Samuel Brenny, Matthew D Johnson, Alik S Widge, Noam Harel, Sarah R Heilbronner

Faculty, Staff and Students Publications

Background: The anterior limb of the internal capsule (ALIC) is a white matter structure that connects the prefrontal cortex (PFC) to the brainstem, thalamus, and subthalamic nucleus. It is a target for deep brain stimulation for obsessive-compulsive disorder. There is strong interest in improving deep brain stimulation targeting by using diffusion tractography to reconstruct and target specific ALIC fiber pathways, but this methodology is susceptible to errors and lacks validation. To address these limitations, we developed a novel diffusion tractography pipeline that generates reliable and biologically validated ALIC white matter reconstructions.

Methods: Following algorithm development and refinement, we analyzed 43 …

A New Ex Vivo Model System To Analyze Factors Affecting The Integrity Of Fetal Membranes In Fetoscopic Surgery, Serjosha Robmann, Raoul Hopf, Costanza Giampietro, Lukas Moser, Alexandra Dolder, Magdalena Sanz Cortes, Martin Ehrbar, Nicole Ochsenbein, Jan Deprest, Edoardo Mazza

Faculty, Staff and Students Publications

We developed an ex vivo model system to analyze the influence of relevant environmental and mechanical factors potentially affecting the integrity of fetal membranes during fetoscopic surgery. The set-up exposes amniochorion membranes to insufflation at predefined levels of gas pressure, flow, humidity, and temperature. Change in fetal membranes stiffness is quantified during the phase mimicking surgery through measurement of membranes' strain in response to cyclic overpressure. The trocar induced perforation creates a mechanical weakness whose stability is assessed by increasing the insufflation pressure until membrane rupture. Damage of the epithelial cells lining the amnion is assessed through live-dead staining. Initial …

The Long Road Of Drug Development For Endometriosis – Pains, Gains, And Hopes, Zian Liao, Diana Monsivais, Martin M Matzuk

Faculty, Staff and Students Publications

Endometriosis, defined by the growth of endometrial tissues outside of the uterine cavity, is a global health burden for ∼200 million women. Patients with endometriosis usually present with chronic pain and are often diagnosed with infertility. The pathogenesis of endometriosis is still an open question; however, tissue stemness and immunological and genetic factors have been extensively discussed in the establishment of endometriotic lesions. Current treatments for endometriosis can be categorized into pharmacological management of hormone levels and surgical removal of the lesions. Both approaches have limited efficacy, with recurrences often encountered; thus, there is no complete cure for the disease …

Exploring Fibroblast Interactions On Nanocrystalline Surfaces In Physiological Environments Through A Phenomenological Lens, R D K Misra, Aladin M Boriek

Faculty, Staff and Students Publications

The cytological behaviour and functional dynamics (adhesion, spreading, synthesis of proteins) of fibroblasts when interacting with biomedical surfaces are intricately influenced by the inherent nature of surface (nanocrystalline or microcrystalline), where the nanocrystalline (NC) surface is preferred in relation to the microcrystalline (MC) surface. This preference is a direct consequence of the distinct differences in physical and chemical characteristics between NC and MC surfaces, which include crystal boundary bio-physical attributes, electron work function, surface energy, and charge carrier density. The observed variances in cytological behaviour at the interfaces of NC and MC bio-surfaces can be attributed to these fundamental differences, …

Chemogenetic Neuronal Silencing Decouples C-Jun Activation From Cell Death In The Temporal Cortex, Caleb A Wood, Preethi Somasundaram, Jacob M Dundee, Melissa A Rudy, Trent A Watkins, Joanna L Jankowsky

Faculty, Staff and Students Publications

Initial symptoms of neurodegenerative diseases are often defined by the loss of the most vulnerable neural populations specific to each disorder. In the early stages of Alzheimer's disease, vulnerable circuits in the temporal lobe exhibit diminished activity prior to overt degeneration. It remains unclear whether these functional changes contribute to regional vulnerability or are simply a consequence of pathology. We previously found that entorhinal neurons in the temporal cortex undergo cell death following transient suppression of electrical activity, suggesting a causal role for activity disruption in neurodegeneration. Here we demonstrate that electrical arrest of this circuit stimulates the injury-response transcription …

Bst2 Facilitates Activation Of Hematopoietic Stem Cells Through Erk Signaling, Marcus A Florez, Apoorva Thatavarty, Duy T Le, Holly A Hill, Youngjae Jeong, Brian M Ho, Pawel Kus, Trisha K Wathan, Bailee N Kain, Shixia Huang, Dongsu Park, Katherine Y King

Faculty, Staff and Students Publications

The proinflammatory cytokine interferon-gamma (IFNγ) is upregulated in a variety of infections and contributes to bone marrow failure through hematopoietic stem cell (HSC) activation and subsequent exhaustion. The cell surface protein, bone marrow stromal antigen 2 (BST2), is a key mediator of this process, as it is induced upon interferon stimulation and required for interferon-dependent HSC activation. To identify the mechanism by which BST2 promotes interferon-dependent HSC activation, we evaluated its role in niche localization, immune cell function, lipid raft formation, and intracellular signaling. Our studies indicated that knock out (KO) of BST2 in a murine model does not disrupt …

Persistent Growth-Promoting Effects Of Vosoritide In Children With Achondroplasia Are Accompanied By Improvements In Physical And Social Aspects Of Health-Related Quality Of Life, Ravi Savarirayan, Melita Irving, William R Wilcox, Carlos A Bacino, Julie E Hoover-Fong, Paul Harmatz, Lynda E Polgreen, Klaus Mohnike, Carlos E Prada, Takuo Kubota, Paul Arundel, Antonio Leiva-Gea, Richard Rowell, Andrea Low, Ian Sabir, Alice Huntsman-Labed, Jonathan Day

Faculty, Staff and Students Publications

Purpose: Evaluate the impact of vosoritide on health-related quality of life in children with achondroplasia.

Methods: Participants received vosoritide (15 μg/kg/day) in an extension trial (NCT03424018) after having participated in a placebo-controlled trial (NCT03197766).

Results: The population comprised 119 participants (mean [SD] age 9.7 [2.6] years). Mean treatment duration was 4 (0.78) years. At year 3, the largest mean (SD) changes were observed in the Quality of Life of Short Stature Youth physical score (5.99 [19.41], caregiver reported; 6.32 [20.15], self-reported) and social score (2.85 [8.29] and 6.76 [22.64], respectively). Changes were greatest in participants with …

Families’ Experiences Accessing Care After Genomic Sequencing In The Pediatric Cancer Context: “It’S Just Been A Big Juggle”, Blake Vuocolo, Amanda M Gutierrez, Jill O Robinson, Alva M Recinos, Lauren R Desrosiers, Mary A Majumder, Juan Carlos Bernini, Jonathan Gill, Timothy Griffin, Gail E Tomlinson, Kelly Vallance, Amy L Mcguire, D Williams Parsons, Sharon E Plon, Sarah Scollon

Faculty, Staff and Students Publications

Access to genomic sequencing (GS) and resulting recommendations have not been well described in pediatric oncology. GS results may provide a cancer predisposition syndrome (CPS) diagnosis that warrants screening and specialist visits beyond cancer treatment, including testing or surveillance for family members. The Texas KidsCanSeq (KCS) Study evaluated implementation of GS in a diverse pediatric oncology population. We conducted semi-structured interviews (n = 20) to explore experiences of KCS patients' families around learning about a CPS diagnosis and following up on recommended care. We used qualitative content analysis to develop themes and subthemes across families' descriptions of their experiences accessing …

10 Practical Priorities To Prevent And Manage Serious Allergic Reactions: Ga2len Anacare And Efa Anaphylaxis Manifesto, Antonella Muraro, Debra De Silva, Marcia Podesta, Aikaterini Anagnostou, Victoria Cardona, Susanne Halken, Pete Smith, Luciana Kase Tanno, Paul Turner, Margitta Worm, Montserrat Alvaro-Lozano, Stefania Arasi, Anna Asarnoj, Simona Barni, Kirsten Beyer, Lucy A Bilaver, Andrew Bird, Roberta Bonaguro, Helen A Brough, R Sharon Chinthrajah, Emma E Cook, Céline Demoulin, Antoine Deschildre, Timothy E Dribin, Motohiro Ebisawa, Montserrat Fernandez-Rivas, Alessandro Fiocchi, David M Fleischer, Eleanor Garrow, Jennifer Gerdts, Mattia Giovannini, Kirsi M Järvinen, Mary Kelly, Edward F Knol, Gideon Lack, Francesca Lazzarotto, Thuy-My Le, Stephanie Leonard, Jay Lieberman, Michael Makris, Lianne Mandelbaum, Mary Jane Marchisotto, Gustavo Andres Marino, Francesca Mori, Caroline Nilsson, Anna Nowak-Wegrzyn, Mikaela Odemyr, H N G Oude Elberink, Kati Palosuo, Nandinee Patel, Jennifer Pier, Sung Poblete, Rima Rachid, Pablo Rodríguez Del Río, Maria Said, Hugh A Sampson, Angel Sánchez Sanz, Sabine Schnadt, Fallon Schultz, Alice Toniolo, Julia E M Upton, Carina Venter, Brian P Vickery, Berber Vlieg-Boerstra, Julie Wang, Graham Roberts, Torsten Zuberbier, Ga2len Anacare Centres And Efa

Faculty, Staff and Students Publications

This Anaphylaxis Manifesto calls on communities to prioritise 10 practical actions to improve the lives of people at risk of serious allergic reactions. The Global Allergy and Asthma European Network and the European Federation of Allergy and Airways Diseases Patients' Associations (EFA) compiled patient-centric priorities. We used qualitative consensus methods, research evidence and feedback from over 200 patient groups, stakeholder organisations and healthcare professionals. We encourage healthcare, education and food organisations to collaborate with people at risk of serious allergic reactions to tackle safety, anxiety and financial burdens for individuals and societies. Key priorities for prevention include awareness-raising campaigns for …

Genome-Derived Ampullary Adenocarcinoma Classifier And Postresection Prognostication, Brett L Ecker, Kenneth Seier, Austin M Eckhoff, Gabriella N Tortorello, Peter J Allen, Vinod P Balachandran, Nicola Blackburn, Michael I D'Angelica, Ronald P Dematteo, Daniel G Blazer, Jeffrey A Drebin, William E Fisher, Danielle Fortuna, Anthony J Gill, Marie-Claude Gingras, T Peter Kingham, Major K Lee, Michael E Lidsky, Daniel P Nussbaum, Michael J Overman, Jaswinder S Samra, Ronglai Shen, Carlie S Sigel, Kevin C Soares, Charles M Vollmer, Alice C Wei, Sabino Zani, Robert E Roses, Mithat Gonen, William R Jarnagin

Faculty, Staff and Students Publications

Importance: Ampullary adenocarcinoma (AA) is characterized by clinical and genomic heterogeneity. A previously developed genomic classifier defined biologically distinct phenotypes with greater accuracy than standard histologic classification. External validation is needed before routine clinical use.

Objective: To test external validity of the prognostic value of the hidden genome classifier of AA.

Design, setting, and participants: This retrospective cohort study took place at 6 international academic institutions. Consecutive patients (n = 192) who underwent curative-intent resection of histologically confirmed AA were included. The data were analyzed from January 2005 through July 2020.

Exposures: The multilevel meta-feature regression model previously trained on …

Association Of Left Atrial Function With Frailty: The Atherosclerosis Risk In Communities (Aric) Study, Daokun Sun, Romil R Parikh, Wendy Wang, Anne Eaton, Pamela L Lutsey, B Gwen Windham, Riccardo M Inciardi, Scott D Solomon, Christie M Ballantyne, Amil M Shah, Lin Yee Chen

Faculty, Staff and Students Publications

Background: Frailty is common in people with cardiovascular disease. Worse left atrial (LA) function is an independent risk factor for cardiovascular disease. However, whether worse LA function is associated with frailty is unclear.

Methods: We included 3292 older adults from the Atherosclerosis Risk in Communities study who were non-frail at baseline (visit 5, 2011-2013) and had LA function (reservoir, conduit, and contractile strain) measured from two-dimensional speckle-tracking echocardiography. LA stiffness index was calculated as a ratio of E/e' to LA reservoir strain. Frailty was defined using the validated Fried frailty phenotype. Incident frailty was assessed between 2016 and 2019 during …

Experiences In Providing A Community Educational Resource For The All Of Us Researcher Workbench, Deborah I Ritter, Jinyoung Byun, Jun Wang, Stephen Richards, Pamela N Luna, Laterrica Williams, Julie R Coleman, Jasmine N Baker, Shamika Ketkar, Ashley M Butler, Latanya Hammonds-Odie, Elizabeth G Atkinson, Kim C Worley, Debra D Murray, Brendan Lee, Steven E Scherer

Faculty, Staff and Students Publications

OBJECTIVE: Educational offerings to fill the bioinformatics knowledge gap are a key component to enhancing access and use of health data from the All of Us Research Program. We developed a Train the Trainer-based, innovative training series including project-based learning, modular on-demand demonstrations, and unstructured tutorial time as a model for educational engagement in the All of Us community.

MATERIALS AND METHODS: We highlight our training modules and content, with training survey data informing cycles of development in the creation of a 6-module training series with modular demonstrations.

RESULTS: We have conducted 2 public iterations of the Train the Trainer …

Hemodynamic And Clinical Outcomes With Balloon-Expandable Valves Versus Self-Expanding Valves In Patients With Small Aortic Annulus Undergoing Transcatheter Aortic Valve Replacement: A Meta-Analysis Of Randomized Controlled Trials And Propensity Score Matched Studies, Mushood Ahmed, Areeba Ahsan, Shehroze Tabassum, Irra Tariq, Eeshal Zulfiqar, Mahnoor Farooq Raja, Asma Mahmood, Raheel Ahmed, Farhan Shahid, Syed Khurram M Gardezi, Mahboob Alam, Rodrigo Bagur, Mamas A Mamas

Faculty, Staff and Students Publications

Transcatheter aortic valve replacement (TAVR) is considered more effective than surgical aortic valve implantation for patients with a small aortic annulus (SAA), however, the comparative efficacy of different transcatheter heart valves (THVs) remains uncertain. A literature search was performed across databases from their inception until June 2024 to identify eligible randomized controlled trials (RCTs) and propensity-score matched (PSM) studies. Clinical outcomes were evaluated using a random-effects model to pool risk ratios (RRs) with 95 % confidence intervals (CIs). The analysis included 10 studies with 2,960 patients. BEVs were associated with a significantly smaller indexed effective orifice area (MD: -0.18, 95 …

Development And Evaluation Of A Training Curriculum To Engage Researchers On Accessing And Analyzing The All Of Us Data, Julie R Coleman, Jasmine N Baker, Shamika Ketkar, Ashley M Butler, Laterrica Williams, Latanya Hammonds-Odie, Elizabeth G Atkinson, Debra D Murray, Brendan Lee, Kim C Worley

Faculty, Staff and Students Publications

OBJECTIVE: The All of Us Evenings with Genetics (EwG) Research Program at Baylor College of Medicine (BCM), funded to engage research scholars to work with the All of Us data, developed a training curriculum for the Researcher Workbench, the platform to access and analyze All of Us data. All of Us EwG developed the curriculum so that it could teach scholars regardless of their skills and background in programming languages and cloud computing. All of Us EwG delivered this curriculum at the first annual All of Us EwG Faculty Summit in May 2022. The curriculum was evaluated both during and …

Steering Research On Mrna Splicing In Cancer Towards Clinical Translation, Olga Anczukow, Frédéric H-T Allain, Brittany L Angarola, Douglas L Black, Angela N Brooks, Chonghui Cheng, Ana Conesa, Edie I Crosse, Eduardo Eyras, Ernesto Guccione, Sydney X Lu, Karla M Neugebauer, Priyanka Sehgal, Xiao Song, Zuzana Tothova, Juan Valcárcel, Kevin M Weeks, Gene W Yeo, Andrei Thomas-Tikhonenko

Faculty, Staff and Students Publications

Splicing factors are affected by recurrent somatic mutations and copy number variations in several types of haematologic and solid malignancies, which is often seen as prima facie evidence that splicing aberrations can drive cancer initiation and progression. However, numerous spliceosome components also 'moonlight' in DNA repair and other cellular processes, making their precise role in cancer difficult to pinpoint. Still, few would deny that dysregulated mRNA splicing is a pervasive feature of most cancers. Correctly interpreting these molecular fingerprints can reveal novel tumour vulnerabilities and untapped therapeutic opportunities. Yet multiple technological challenges, lingering misconceptions, and outstanding questions hinder clinical translation. …