Medicine and Health Sciences Commons^™

Lineage Plasticity And Stemness Phenotypes In Prostate Cancer: Harnessing The Power Of Integrated "Omics" Approaches To Explore Measurable Metrics, Souzana Logotheti, Eugenia Papadaki, Vasiliki Zolota, Christopher Logothetis, Aristidis G Vrahatis, Rama Soundararajan, Vasiliki Tzelepi

Faculty, Staff and Student Publications

Prostate cancer (PCa), the most frequent and second most lethal cancer type in men in developed countries, is a highly heterogeneous disease. PCa heterogeneity, therapy resistance, stemness, and lethal progression have been attributed to lineage plasticity, which refers to the ability of neoplastic cells to undergo phenotypic changes under microenvironmental pressures by switching between developmental cell states. What remains to be elucidated is how to identify measurements of lineage plasticity, how to implement them to inform preclinical and clinical research, and, further, how to classify patients and inform therapeutic strategies in the clinic. Recent research has highlighted the crucial role …

Quantitative Longitudinal Mapping Of Radiation-Treated Prostate Cancer Using Mr Fingerprinting With Radial Acquisition And Subspace Reconstruction, Victoria Y Yu, Ricardo Otazo, Can Wu, Ergys Subashi, Manuel Baumann, Peter Koken, Mariya Doneva, Peter Mazurkewitz, Daniel Shasha, Michael Zelefsky, Laura Cervino, Ouri Cohen

Faculty, Staff and Student Publications

MR fingerprinting (MRF) enables fast multiparametric quantitative imaging with a single acquisition and has been shown to improve diagnosis of prostate cancer. However, most prostate MRF studies were performed with spiral acquisitions that are sensitive to B0 inhomogeneities and consequent blurring. In this work, a radial MRF acquisition with a novel subspace reconstruction technique was developed to enable fast T1/T2 mapping in the prostate in under 4 min. The subspace reconstruction exploits the extensive temporal correlations in the MRF dictionary to pre-compute a low dimensional space for the solution and thus reduce the number of radial spokes to accelerate the …

Evaluating The Knowledge, Attitudes, And Practices Of Healthcare Workers Regarding High-Risk Nosocomial Infections: A Global Cross-Sectional Study, Elham M Khatrawi, Priyadarshi Prajjwal, Muhammad Farhan, Pugazhendi Inban, Shraddha Gurha, Saud M S Al-Ezzi, Mohammed D M Marsool, Prerna Ahuja, Mohammed A Mateen, Felix O Aina, Omniat A Hussin

Faculty, Staff and Student Publications

BACKGROUND: Healthcare workers (HCWs) play a vital role in delivering care and are frequently exposed to the risk of acquiring infections within the hospital setting. Around 15% of hospitalized patients suffer from these infections globally. However, the role and awareness of HCWs in the transmission of hospital-acquired infections (HAIs) or nosocomial infections is still unclear. This study aimed to evaluate the knowledge, attitude, and practices (KAP) toward high-risk microbial infections among HCWs on a global scale to identify measures to address this problem.

METHOD: A cross-sectional descriptive study was conducted between 2022 and 2023, with HCWs selected as the study …

Fibronectin Contributes To A Braf Inhibitor-Driven Invasive Phenotype In Thyroid Cancer Through Egr1, Which Can Be Blocked By Inhibition Of Erk1/2, Hannah M Hicks, Nikita Pozdeyev, Sharon B Sams, Umarani Pugazhenthi, Elise S Bales, Marie-Claude Hofmann, Logan R Mckenna, Rebecca E Schweppe

Faculty, Staff and Student Publications

Mutations in BRAF are common in advanced papillary and anaplastic thyroid cancer (PTC and ATC). However, patients with BRAF-mutant PTC currently lack therapies targeting this pathway. Despite the approved combination of BRAF and MEK1/2 inhibition for patients with BRAF-mutant ATC, these patients often progress. Thus, we screened a panel of BRAF-mutant thyroid cancer cell lines to identify new therapeutic strategies. We showed that thyroid cancer cells resistant to BRAF inhibition (BRAFi) exhibit an increase in invasion and a proinvasive secretome in response to BRAFi. Using reverse-phase protein array (RPPA), we identified a nearly 2-fold increase in expression of the extracellular …

Subsequent Female Breast Cancer Risk Associated With Anthracycline Chemotherapy For Childhood Cancer, Yuehan Wang, Cécile M Ronckers, Flora E Van Leeuwen, Chaya S Moskowitz, Wendy Leisenring, Gregory T Armstrong, Florent De Vathaire, Melissa M Hudson, Claudia E Kuehni, Michael A Arnold, Charlotte Demoor-Goldschmidt, Daniel M Green, Tara O Henderson, Rebecca M Howell, Matthew J Ehrhardt, Joseph P Neglia, Kevin C Oeffinger, Helena J H Van Der Pal, Leslie L Robison, Michael Schaapveld, Lucie M Turcotte, Nicolas Waespe, Leontien C M Kremer, Jop C Teepen

Faculty, Staff and Student Publications

Anthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from six well-established studies, of whom 782 (4.4%) developed a SBC, and analyzed dose-dependent effects of individual anthracycline agents on developing SBC and interactions with chest radiotherapy. A dose-dependent increased SBC risk was seen for doxorubicin (hazard ratio (HR) per 100 mg m

Clinical Relevance Of Myc/Bcl2 Expression And Cell Of Origin In Patients With Diffuse Large B-Cell Lymphoma Treated With Autologous Transplant, Taha Al-Juhaishi, Yingjun Wang, Denái R Milton, Zijun Y Xu-Monette, Elias Jabbour, May Daher, Jin S Im, Qaiser Bashir, Swaminathan P Iyer, David Marin, Amanda L Olson, Uday Popat, Muzaffar Qazilbash, Gabriela Rondon, Alison M Gulbis, Richard E Champlin, Ken H Young, Issa F Khouri

Faculty, Staff and Student Publications

Dual expression of MYC and BCL2 proteins (double-expressor lymphoma [DEL]) as well as cell of origin (COO) are important prognostic factors in patients with diffuse large B-cell lymphoma (DLBCL) after conventional chemotherapy. We studied the prognostic impact of DEL and COO in patients with relapsed DLBCL treated with autologous stem cell transplant (ASCT). Three-hundred and three patients with stored tissue samples were identified. Classification was successful in 267 patients: 161 (60%) were DEL/non-double hit (DHL), 98 (37%) were non-DEL/non-DHL, and 8 (3%) were DEL/DHL. Compared to non-DEL/non-DHL, DEL/DHL had worse overall survival while DEL/non-DHL did not significantly differ in overall …

Gut Oncomicrobiome Signatures (Goms) As Next-Generation Biomarkers For Cancer Immunotherapy, Andrew Maltez Thomas, Marine Fidelle, Bertrand Routy, Guido Kroemer, Jennifer A Wargo, Nicola Segata, Laurence Zitvogel

Faculty, Staff and Student Publications

Oncogenesis is associated with intestinal dysbiosis, and stool shotgun metagenomic sequencing in individuals with this condition might constitute a non-invasive approach for the early diagnosis of several cancer types. The prognostic relevance of antibiotic intake and gut microbiota composition urged investigators to develop tools for the detection of intestinal dysbiosis to enable patient stratification and microbiota-centred clinical interventions. Moreover, since the advent of immune-checkpoint inhibitors (ICIs) in oncology, the identification of biomarkers for predicting their efficacy before starting treatment has been an unmet medical need. Many previous studies addressing this question, including a meta-analysis described herein, have led to the …

Efficacy Of Immune Checkpoint Inhibitors For The Treatment Of Advanced Melanoma In Patients With Concomitant Chronic Lymphocytic Leukemia, S H Cass, J W D Tobin, Y D Seo, G Gener-Ricos, E Z Keung, E M Burton, M A Davies, J L Mcquade, A J Lazar, R Mason, M Millward, S Sandhu, C Khoo, L Warburton, V Guerra, A Haydon, H Dearden, A M Menzies, M S Carlino, J L Smith, P Mollee, M Burgess, S Mapp, C Keane, V Atkinson, S A Parikh, S N Markovic, W Ding, T G Call, P J Hampel, G V Long, J A Wargo, A Ferrajoli

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses.

PATIENTS AND METHODS: In this international multicenter study, a retrospective review of clinical databases identified patients …

Cell Entry And Release Of Quasi-Enveloped Human Hepatitis Viruses, Anshuman Das, Efraín E Rivera-Serrano, Xin Yin, Christopher M Walker, Zongdi Feng, Stanley M Lemon

Faculty, Staff and Student Publications

Infectious hepatitis type A and type E are caused by phylogenetically distinct single-stranded, positive-sense RNA viruses that were once considered to be non-enveloped. However, studies show that both are released nonlytically from hepatocytes as 'quasi-enveloped' virions cloaked in host membranes. These virion types predominate in the blood of infected individuals and mediate virus spread within the liver. They lack virally encoded proteins on their surface and are resistant to neutralizing anti-capsid antibodies induced by infection, yet they efficiently enter cells and initiate new rounds of virus replication. In this Review, we discuss the mechanisms by which specific peptide sequences in …

Time For Bugs: The Immune Microenvironment And Microbes In Precancer, Mikayla Borthwick Bowen, Beth A Helmink, Jennifer A Wargo, Melinda S Yates

Faculty, Staff and Student Publications

Major advances in our understanding of the tumor immune microenvironment (TIME) in established cancer have been made, including the influence of host-intrinsic (host genomics) and -extrinsic factors (such as diet and the microbiome) on treatment response. Nonetheless, the immune and microbiome milieu across the spectrum of precancerous tissue and early neoplasia is a growing area of interest. There are emerging data describing the contribution of the immune microenvironment and microbiota on benign and premalignant tissues, with opportunities to target these factors in cancer prevention and interception. Throughout this review, we provide rationale for not only the critical need to further …

A Transformer-Based Hierarchical Registration Framework For Multimodality Deformable Image Registration, Yao Zhao, Xinru Chen, Brigid Mcdonald, Cenji Yu, Abdalah S R Mohamed, Clifton D Fuller, Laurence E Court, Tinsu Pan, He Wang, Xin Wang, Jack Phan, Jinzhong Yang

Faculty, Staff and Student Publications

Deformable image registration (DIR) between daily and reference images is fundamentally important for adaptive radiotherapy. In the last decade, deep learning-based image registration methods have been developed with faster computation time and improved robustness compared to traditional methods. However, the registration performance is often degraded in extra-cranial sites with large volume containing multiple anatomic regions, such as Computed Tomography (CT)/Magnetic Resonance (MR) images used in head and neck (HN) radiotherapy. In this study, we developed a hierarchical deformable image registration (DIR) framework, Patch-based Registration Network (Patch-RegNet), to improve the accuracy and speed of CT-MR and MR-MR registration for head-and-neck MR-Linac …

Bayesian Hierarchical Quantile Regression With Application To Characterizing The Immune Architecture Of Lung Cancer, Priyam Das, Christine B Peterson, Yang Ni, Alexandre Reuben, Jiexin Zhang, Jianjun Zhang, Kim-Anh Do, Veerabhadran Baladandayuthapani

Faculty, Staff and Student Publications

The successful development and implementation of precision immuno-oncology therapies requires a deeper understanding of the immune architecture at a patient level. T-cell receptor (TCR) repertoire sequencing is a relatively new technology that enables monitoring of T-cells, a subset of immune cells that play a central role in modulating immune response. These immunologic relationships are complex and are governed by various distributional aspects of an individual patient's tumor profile. We propose Bayesian QUANTIle regression for hierarchical COvariates (QUANTICO) that allows simultaneous modeling of hierarchical relationships between multilevel covariates, conducts explicit variable selection, estimates quantile and patient-specific coefficient effects, to induce individualized …

Spatially-Aware Clustering Improves Ajcc-8 Risk Stratification Performance In Oropharyngeal Carcinomas, Guadalupe Canahuate, Andrew Wentzel, Abdallah S R Mohamed, Lisanne V Van Dijk, David M Vock, Baher Elgohari, Hesham Elhalawani, Clifton D Fuller, G Elisabeta Marai

Faculty, Staff and Student Publications

OBJECTIVE: Evaluate the effectiveness of machine learning tools that incorporate spatial information such as disease location and lymph node metastatic patterns-of-spread, for prediction of survival and toxicity in HPV+ oropharyngeal cancer (OPC).

MATERIALS & METHODS: 675 HPV+ OPC patients that were treated at MD Anderson Cancer Center between 2005 and 2013 with curative intent IMRT were retrospectively collected under IRB approval. Risk stratifications incorporating patient radiometric data and lymph node metastasis patterns via an anatomically-adjacent representation with hierarchical clustering were identified. These clusterings were combined into a 3-level patient stratification and included along with other known clinical features in a …

Interleukin-10 In Cancer Immunotherapy: From Bench To Bedside, Mohamad Adham Salkeni, Aung Naing

Faculty, Staff and Student Publications

Interleukin (IL)-10 was one of the first cytokines to be recognized. However, its functionality in promoting antitumor immunity was described more recently. Context- and concentration-dependent biological effects are the hallmarks of the pleiotropic role of IL-10. Despite reducing tumor-promoting inflammation, IL-10 may have a role in rejuvenating exhausted tumor-resident T cells. Contrary to the assumption that IL-10 produces an immunosuppressive tumor microenvironment (TME), it promotes activation of tumor-resident CD8+ T cells, which aids tumor rejection. Emerging data from published early-Phase trials have shown mixed results in different tumor types. In this review, we summarize the biological effects of IL-10 and …

Disparities In Cancer Mortality Patterns: A Comprehensive Examination Of Us Rural And Urban Adults, 1999–2020, Itunu O Sokale, Syed Ahsan Raza, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Cancer mortality rates overall in the U.S. have decreased significantly; however, the rate of decline has not been uniform across sociodemographic groups. We aimed to compare trends in cancer mortality rates from 1999 to 2020 between rural and urban individuals and to examine whether any rural-urban differences are uniform across racial and ethnic groups.

METHODS: We used U.S.-wide data from the National Center for Health Statistics, for all cancer deaths among individuals aged 25 years or older. We estimated average annual percentage change (AAPC) in age-standardized cancer mortality rates in the U.S. by cancer type, rural-urban status, sex, and …

Early Initiation Of B-Vitamin Supplementation May Reduce Symptoms And Explain Intrafamilial Variability: Insights From Two Sibling Pairs From The Tango2 Natural History Study, Christina Y Miyake, Saad A Ehsan, Lilei Zhang, Samuel J Mackenzie, Mahshid S Azamian, Daryl A Scott, Andres Hernandez-Garcia, Seema R Lalani

Faculty, Staff and Students Publications

TANGO2-deficiency disorder (TDD) is an autosomal recessive condition arising from pathogenic biallelic variants in the TANGO2 gene. TDD is characterized by symptoms typically beginning in late infancy including delayed developmental milestones, cognitive impairment, dysarthria, expressive language deficits, and gait abnormalities. There is wide phenotypic variability where some are severely affected while others have mild symptoms. This variability has been documented even among sibling pairs who share the same genotype, but reasons for this variability have not been well understood. Emerging data suggest a potential link between B-complex or multivitamin supplementation and decreased metabolic crises in TDD. In this report, we …

Kidney Health And Function With Left Ventricular Assist Devices, Leonardo Pozo Garcia, Carl P Walther

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Mechanical circulatory support (MCS) is a group of evolving therapies used for indications ranging from temporary support during a cardiac procedure to permanent treatment of advanced heart failure. MCS is primarily used to support left ventricle function, in which case the devices are termed left ventricular assist devices (LVADs). Kidney dysfunction is common in patients requiring these devices, yet the impact of MCS itself on kidney health in many settings remains uncertain.

RECENT FINDINGS: Kidney dysfunction can manifest in many different forms in patients requiring MCS. It can be because of preexisting systemic disorders, acute illness, procedural …

From Pre-Copd To Copd: A Simple, Low Cost And Easy To Implement (Slim) Risk Calculator, Miguel J Divo, Congjian Liu, Francesca Polverino, Peter J Castaldi, Bartolome R Celli, Yohannes Tesfaigzi

Faculty, Staff and Students Publications

BACKGROUND: The lifetime risk of developing clinical COPD among smokers ranges from 13% to 22%. Identifying at-risk individuals who will develop overt disease in a reasonable timeframe may allow for early intervention. We hypothesised that readily available clinical and physiological variables could help identify ever-smokers at higher risk of developing chronic airflow limitation (CAL).

METHODS: Among 2273 Lovelace Smokers' Cohort (LSC) participants, we included 677 (mean age 54 years) with normal spirometry at baseline and a minimum of three spirometries, each 1 year apart. Repeated spirometric measurements were used to determine incident CAL. Using logistic regression, demographics, anthropometrics, smoking history, …

Maternal Metabolism Influences Neural Tube Closure, Rachel A Keuls, Richard H Finnell, Ronald J Parchem

Faculty, Staff and Students Publications

Changes in maternal nutrient availability due to diet or disease significantly increase the risk of neural tube defects (NTDs). Because the incidence of metabolic disease continues to rise, it is urgent that we better understand how altered maternal nutrient levels can influence embryonic neural tube development. Furthermore, primary neurulation occurs before placental function during a period of histiotrophic nutrient exchange. In this review we detail how maternal metabolites are transported by the yolk sac to the developing embryo. We discuss recent advances in understanding how altered maternal levels of essential nutrients disrupt development of the neuroepithelium, and identify points of …

Sports Drinks Effect On Salivary Volume And Ph In Children After Exercise: A Randomized Clinical Study, Matina V. Angelopoulou, Alicia Malak-Santaga, Andreas Agouropoulos, Cesar D. Gonzalez

School of Dentistry Faculty Research and Publications

BACKGROUND: The aim of this study was to examine the sports’ related oral health behavior and the effect of sports drinks on the salivary volume and acidity of 6 to 14 years old children.

METHODS: Sixty-eight children with a median age of 8 years old from Waterford Tennis Association camp participated in the study. Each child was randomly assigned to either the control group that consumed water or the experimental group that consumed a sports drink. Salivary volume and acidity were measured for all groups before exercise, right after exercise and after consuming the rehydrating agent. Salivary volume was measured …

Treatment Preference And Quality Of Life Impact: Ravulizumab Vs Eculizumab For Atypical Hemolytic Uremic Syndrome, Teri J Mauch, Michael R Chladek, Spero Cataland, Shruti Chaturvedi, Bradley P Dixon, Katherine Garlo, Christoph Gasteyger, Anuja Java, Jorge Leguizamo, Lucy Lloyd-Price, Tan P Pham, Tara Symonds, Ioannis Tomazos, Yan Wang

2020-Current year OA Pubs

No abstract provided.

Neutralization, Effector Function And Immune Imprinting Of Omicron Variants, Amin Addetia, James Brett Case, Suzanne M Scheaffer, Bradley Whitener, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain

Postacute Sequelae Of Covid-19 At 2 Years, Benjamin Bowe, Yan Xie, Ziyad Al-Aly

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to postacute sequelae in multiple organ systems, but evidence is mostly limited to the first year postinfection. We built a cohort of 138,818 individuals with SARS-CoV-2 infection and 5,985,227 noninfected control group from the US Department of Veterans Affairs and followed them for 2 years to estimate the risks of death and 80 prespecified postacute sequelae of COVID-19 (PASC) according to care setting during the acute phase of infection. The increased risk of death was not significant beyond 6 months after infection among nonhospitalized but remained significantly elevated through the …

Unexpected Drug-Induced Liver Injury Associated With Menofit: A Synbiotic Menopause Supplement, Apaar Dadlani, Azubuogu Anudu, E Celia Marginean

Faculty, Staff and Students Publications

MenoFit is a widely available over-the-counter synbiotic supplement, which is marketed for use in relieving menopausal symptoms. So far, there is no published data on liver injury because of its use. We present the first reported case of MenoFit-induced liver injury in a patient who presented with 1 week of jaundice and abnormal liver biochemical tests in the absence of other risk factors and negative comprehensive workup for known etiologies of liver disease.

Exome Sequencing Implicates Dgkz , Esrra , And Gxylt1 For Modulating Granuloma Formation In Crohn Disease, R Alan Harris, Allyson H Bush, Todd N Eagar, Justin Qian, Michael P Greenwood, Antone R Opekun, Robert Baldassano, Stephen L Guthery, Joshua D Noe, Anthony Otley, Joel R Rosh, Subra Kugathasan, Richard Kellermayer

Faculty, Staff and Students Publications

Non-caseating granulomas may indicate a more aggressive phenotype of Crohn disease (CD). Genetic associations of granulomatous CD (GCD) may help elucidate disease pathogenesis. Whole-exome sequencing was performed on peripheral blood-derived DNA from 17 pediatric patients with GCD and 19 with non-GCD (NGCD), and from an independent validation cohort of 44 GCD and 19 NGCD cases. PLINK (a tool set for whole-genome association and population-based linkage analyses) analysis was used to identify single nucleotide polymorphisms (SNPs) differentiating between groups, and subgroup allele frequencies were also compared to a public genomic database (gnomAD). The Combined Annotation Dependent Depletion scoring tool was used …

Differences In Hyperandrogenism Related To Early Detection Of Non-Classical Congenital Adrenal Hyperplasia On Second Newborn Screen, Bonnie Mccann-Crosby, Mark C Liang, Mitchell E Geffner, Christina M Koppin, Nicole R Fraga, V Reid Sutton, Lefkothea P Karaviti, Gagandeep Bhullar, Mimi S Kim

Faculty, Staff and Students Publications

Screening for congenital adrenal hyperplasia (CAH) remains heterogenous across geographies—we sought to determine the proportion of non-classical CAH (NCAH) detection by one vs. two newborn screens (NBS) in two U.S. regions. Data were collected at tertiary centers in Houston (HOU) and Los Angeles (LA) on 35 patients with NCAH, comparing patients identified via the NBS vs. during childhood, 17-hydroxyprogesterone (17-OHP) levels, genotype, and phenotype. The NBS filter-paper 17-OHP levels and daily cutoffs were recorded on initial and second screens. In all, 53% of patients with NCAH in the HOU cohort were identified as infants via the second NBS. Patients identified …

Equine Bronchial Epithelial Cells Are Susceptible To Cell Entry With A Sars-Cov-2 Pseudovirus But Reveal Low Replication Efficiency, Rebecca M Legere, Angelica R Allegro, Yvonne Affram, Bibiana Petri Da Silveira, Jennifer L Fridley, Kelsey M Wells, Numan Oezguen, Robert C Burghardt, Gus A Wright, Jeroen Pollet, Angela I Bordin, Paul De Figueiredo, Julian L Leibowitz, Noah D Cohen

Faculty, Staff and Students Publications

Objective: To examine the susceptibility of cultured primary equine bronchial epithelial cells (EBECs) to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus relative to human bronchial epithelial cells (HBECs).

Sample: Primary EBEC cultures established from healthy adult horses and commercially sourced human bronchial epithelial cells (HBECs) were used as a positive control.

Methods: Angiotensin-converting enzyme 2 (ACE2) expression by EBECs was demonstrated using immunofluorescence, western immunoblot, and flow cytometry. EBECs were transduced with a lentivirus pseudotyped with the SARS-CoV-2 spike protein that binds to ACE2 and expresses the enhanced green fluorescent protein (eGFP) as a reporter. Cells were transduced …

The Novel Salt-M Score Predicts 1-Year Post-Transplant Mortality In Patients With Severe Acute-On-Chronic Liver Failure, Ruben Hernaez, Constantine J Karvellas, Yan Liu, Sophie-Caroline Sacleux, Saro Khemichian, Lance L Stein, Kirti Shetty, Christina C Lindenmeyer, Justin R Boike, Douglas A Simonetto, Robert S Rahimi, Prasun K Jalal, Manhal Izzy, Michael S Kriss, Gene Y Im, Ming V Lin, Janice H Jou, Brett E Fortune, George Cholankeril, Alexander Kuo, Nadim Mahmud, Fasiha Kanwal, Faouzi Saliba, Vinay Sundaram, Thierry Artzner, Rajiv Jalan, Multi-Organ Dysfunction And Evaluation For Liver Transplantation (Model) Consortium

Faculty, Staff and Students Publications

Background & aims: Twenty-eight-day mortality ranges from 30-90% in patients with acute-on-chronic liver failure grades 2/3 (severe ACLF). Though liver transplantation (LT) has demonstrated a survival benefit, the scarcity of donor organs and uncertainty regarding post-LT mortality among patients with severe ACLF may cause hesitancy. We developed and externally validated a model to predict 1-year post-LT mortality in severe ACLF, called the Sundaram ACLF-LT-Mortality (SALT-M) score, and estimated the median length of stay (LoS) after LT (ACLF-LT-LoS).

Methods: In 15 LT centers in the US, we retrospectively identified a cohort of patients with severe ACLF transplanted between 2014-2019, followed up …

Children’S Oncology Group’S 2023 Blueprint For Research: Epidemiology, Philip J Lupo, Erin L Marcotte, Michael E Scheurer, Jenny N Poynter, Logan G Spector

Faculty, Staff and Students Publications

The Children's Oncology Group (COG) Epidemiology Committee has a primary focus on better understanding the etiologies of childhood cancers. Over the past 10 years, the committee has leveraged the Childhood Cancer Research Network, and now more recently Project:EveryChild (PEC), to conduct epidemiologic assessments of various childhood cancers, including osteosarcoma, neuroblastoma, germ cell tumors, Ewing sarcoma, rhabdomyosarcoma, and Langerhans cell histiocytosis. More recent studies have utilized questionnaire data collected as part of PEC to focus on specific characteristics and/or features, including the presence of congenital disorders and the availability of stored cord blood. Members of the COG Epidemiology Committee have also …

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 …