Digital Commons Network^™

Mird Pamphlet No 28, Part 2: Comparative Evaluation Of Mirdcalc Dosimetry Software Across A Compendium Of Diagnostic Radiopharmaceuticals, Lukas M Carter, Juan C Ocampo Ramos, Edmond A Olguin, Justin L Brown, Daniel Lafontaine, Derek W Jokisch, Wesley E Bolch, Adam L Kesner

Faculty, Staff and Student Publications

Radiopharmaceutical dosimetry is usually estimated via organ-level MIRD schema-style formalisms, which form the computational basis for commonly used clinical and research dosimetry software. Recently, MIRDcalc internal dosimetry software was developed to provide a freely available organ-level dosimetry solution that incorporates up-to-date models of human anatomy, addresses uncertainty in radiopharmaceutical biokinetics and patient organ masses, and offers a 1-screen user interface as well as quality assurance tools. The present work describes the validation of MIRDcalc and, secondarily, provides a compendium of radiopharmaceutical dose coefficients obtained with MIRDcalc. Biokinetic data for about 70 currently and historically used radiopharmaceuticals were obtained from the …

Predicting Severity Of Radiation Induced Lymphopenia In Individual Proton Therapy Patients For Varying Dose Rate And Fractionation Using Dynamic 4-Dimensional Blood Flow Simulations, Lucas Mccullum, Jungwook Shin, Stella Xing, Chris Beekman, Jan Schuemann, Theodore Hong, Dan Duda, Radhe Mohan, Steven H Lin, Camilo M Correa-Alfonso, Sean Domal, Julia Withrow, Wesley Bolch, Harald Paganetti, Clemens Grassberger

Faculty, Staff and Student Publications

PURPOSE: Radiation-induced lymphopenia has gained attention recently as the result of its correlation with survival in a range of indications, particularly when combining radiation therapy (RT) with immunotherapy. The purpose of this study is to use a dynamic blood circulation model combined with observed lymphocyte depletion in patients to derive the in vivo radiosensitivity of circulating lymphocytes and study the effect of RT delivery parameters.

METHODS AND MATERIALS: We assembled a cohort of 17 patients with hepatocellular carcinoma treated with proton RT alone in 15 fractions (fx) using conventional dose rates (beam-on time [BOT], 120 seconds) for whom weekly absolute …

Mechanical And Contact Characteristics Of Foam Materials Within Wound Dressings: Theoretical And Practical Considerations In Treatment, Amit Gefen, Paulo Alves, Dimitri Beeckman, José Luis Lázaro-Martínez, Hadar Lev-Tov, Bijan Najafi, Terry Swanson, Kevin Woo

Center on Aging Staff Publications

In the treatment of acute and chronic wounds, the clinical performance of a given foam‐based dressing, and, ultimately, the wound healing and cost of care outcomes are strongly influenced by the mechanical performance of the foam material/s within that dressing. Most aspects of the mechanical performance of foam materials, for example, their stiffness, frictional properties, conformability, swelling characteristics and durability, and the overall mechanical protection provided by a foam‐based dressing to a wound strongly depend on the microstructure of the foam components, particularly on their microtopography, density and porosity. This article, therefore, provides, for the first time, a comprehensive, self‐inclusive …

Multiscale Analysis Of Pangenomes Enables Improved Representation Of Genomic Diversity For Repetitive And Clinically Relevant Genes, Chen-Shan Chin, Sairam Behera, Asif Khalak, Fritz J Sedlazeck, Peter H Sudmant, Justin Wagner, Justin M Zook

Faculty, Staff and Students Publications

Advancements in sequencing technologies and assembly methods enable the regular production of high-quality genome assemblies characterizing complex regions. However, challenges remain in efficiently interpreting variation at various scales, from smaller tandem repeats to megabase rearrangements, across many human genomes. We present a PanGenome Research Tool Kit (PGR-TK) enabling analyses of complex pangenome structural and haplotype variation at multiple scales. We apply the graph decomposition methods in PGR-TK to the class II major histocompatibility complex demonstrating the importance of the human pangenome for analyzing complicated regions. Moreover, we investigate the Y-chromosome genes, DAZ1/DAZ2/DAZ3/DAZ4, of which structural variants have been linked to …

Spatial Mapping Of The Dna Adducts In Cancer, Kimiko L Krieger, Elise K Mann, Kevin J Lee, Elyse Bolterstein, Deborah Jebakumar, Michael M Ittmann, Valeria L Dal Zotto, Mohamed Shaban, Arun Sreekumar, Natalie R Gassman

Faculty, Staff and Students Publications

DNA adducts and strand breaks are induced by various exogenous and endogenous agents. Accumulation of DNA damage is implicated in many disease processes, including cancer, aging, and neurodegeneration. The continuous acquisition of DNA damage from exogenous and endogenous stressors coupled with defects in DNA repair pathways contribute to the accumulation of DNA damage within the genome and genomic instability. While mutational burden offers some insight into the level of DNA damage a cell may have experienced and subsequently repaired, it does not quantify DNA adducts and strand breaks. Mutational burden also infers the identity of the DNA damage. With advances …

Clinical Outcomes Associated With Overestimation Of Oxygen Saturation By Pulse Oximetry In Patients Hospitalized With Covid-19, Ashraf Fawzy, Tianshi David Wu, Kunbo Wang, Kenneth E Sands, Arielle M Fisher, Shanna A Arnold Egloff, Jeffrey D Dellavolpe, Theodore J Iwashyna, Yanxun Xu, Brian T Garibaldi

Faculty, Staff and Students Publications

IMPORTANCE: Many pulse oximeters have been shown to overestimate oxygen saturation in persons of color, and this phenomenon has potential clinical implications. The relationship between overestimation of oxygen saturation with timing of COVID-19 medication delivery and clinical outcomes remains unknown.

OBJECTIVE: To investigate the association between overestimation of oxygen saturation by pulse oximetry and delay in administration of COVID-19 therapy, hospital length of stay, risk of hospital readmission, and in-hospital mortality.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients hospitalized for COVID-19 at 186 acute care facilities in the US with at least 1 functional arterial oxygen saturation (SaO2) …

Loss Of Cytochrome P450 (Cyp)1b1 Mitigates Hyperoxia Response In Adult Mouse Lung By Reprogramming Metabolism And Translation, Sandra L Grimm, Rachel E Stading, Matthew J Robertson, Tanmay Gandhi, Chenlian Fu, Weiwu Jiang, Guobin Xia, Krithika Lingappan, Cristian Coarfa, Bhagavatula Moorthy

Faculty, Staff and Students Publications

Oxygen supplementation is life saving for premature infants and for COVID-19 patients but can induce long-term pulmonary injury by triggering inflammation, with xenobiotic-metabolizing CYP enzymes playing a critical role. Murine studies showed that CYP1B1 enhances, while CYP1A1 and CYP1A2 protect from, hyperoxic lung injury. In this study we tested the hypothesis that Cyp1b1-null mice would revert hyperoxia-induced transcriptomic changes observed in WT mice at the transcript and pathway level. Wild type (WT) C57BL/6J and Cyp1b1-null mice aged 8-10 weeks were maintained in room air (21% O

Knowledge Acquisition Efficacy Of A Remote Flipped Classroom On Learning About Removable Partial Dentures, Yuka Inamochi, Eiko Yoshida Kohno, Junichiro Wada, Natsuko Murakami, Atsushi Takaichi, Yuki Arai, Takeshi Ueno, Kenji Fueki, Noriyuki Wakabayashi

Faculty, Staff and Student Publications

Purpose: Coronavirus disease 2019 has forced the use of remote education worldwide. In 2020, the authors conducted a fully digitized, remote flipped (RF) classroom focusing on removable partial dentures. This study aimed to evaluate the learning outcomes of the RF classroom and compare these with those of the on-site classroom.

Methods: The fourth-year dental students in 2017-2019 attended on-site flipped classroom (OF; n=70) or on-site lecture classroom (OL; n=67), and those in 2020 (n=58) attended the RF classroom. Lecture videos and text were provided online in the OF and RF groups, while only the text was given to the OL …

Non-Invasive Arterial Blood Pressure Measurement And Spo2 Estimation Using Ppg Signal: A Deep Learning Framework, Yan Chu, Kaichen Tang, Yu-Chun Hsu, Tongtong Huang, Dulin Wang, Wentao Li, Sean I Savitz, Xiaoqian Jiang, Shayan Shams

Faculty, Staff and Student Publications

BACKGROUND: Monitoring blood pressure and peripheral capillary oxygen saturation plays a crucial role in healthcare management for patients with chronic diseases, especially hypertension and vascular disease. However, current blood pressure measurement methods have intrinsic limitations; for instance, arterial blood pressure is measured by inserting a catheter in the artery causing discomfort and infection.

METHOD: Photoplethysmogram (PPG) signals can be collected via non-invasive devices, and therefore have stimulated researchers' interest in exploring blood pressure estimation using machine learning and PPG signals as a non-invasive alternative. In this paper, we propose a Transformer-based deep learning architecture that utilizes PPG signals to conduct …

Loss Of Function Mutation In Ank Causes Aberrant Mineralization And Acquisition Of Osteoblast-Like-Phenotype By The Cells Of The Intervertebral Disc, Takashi Ohnishi, Victoria Tran, Kimheak Sao, Pranay Ramteke, William Querido, Ruteja A. Barve, Koen Van De Wetering, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Pathological mineralization of intervertebral disc is debilitating and painful and linked to disc degeneration in a subset of human patients. An adenosine triphosphate efflux transporter, progressive ankylosis (ANK) is a regulator of extracellular inorganic pyrophosphate levels and plays an important role in tissue mineralization. However, the function of ANK in intervertebral disc has not been fully explored. Herein we analyzed the spinal phenotype of Ank mutant mice (ank/ank) with attenuated ANK function. Micro-computed tomography and histological analysis showed that loss of ANK function results in the aberrant annulus fibrosus mineralization and peripheral disc fusions with cranial to caudal progression in …

Loss Of Function Mutation In Ank Causes Aberrant Mineralization And Acquisition Of Osteoblast-Like-Phenotype By The Cells Of The Intervertebral Disc, Takashi Ohnishi, Victoria Tran, Kimheak Sao, Pranay Ramteke, William Querido, Ruteja A Barve, Koen Van De Wetering, Makarand V Risbud

2020-Current year OA Pubs

Pathological mineralization of intervertebral disc is debilitating and painful and linked to disc degeneration in a subset of human patients. An adenosine triphosphate efflux transporter, progressive ankylosis (ANK) is a regulator of extracellular inorganic pyrophosphate levels and plays an important role in tissue mineralization. However, the function of ANK in intervertebral disc has not been fully explored. Herein we analyzed the spinal phenotype of Ank mutant mice (ank/ank) with attenuated ANK function. Micro-computed tomography and histological analysis showed that loss of ANK function results in the aberrant annulus fibrosus mineralization and peripheral disc fusions with cranial to caudal progression in …

Accumulation Of Chronic Disease Among Survivors Of Childhood Cancer Predicts Early Mortality, Adam J Esbenshade, Lu Lu, Debra L Friedman, Kevin C Oeffinger, Gregory T Armstrong, Kevin R Krull, Joseph P Neglia, Wendy M Leisenring, Rebecca Howell, Robyn Partin, Amy Sketch, Leslie L Robison, Kirsten K Ness

Faculty, Staff and Student Publications

Purpose: Cancer survivors develop cancer and treatment-related morbidities at younger than normal ages and are at risk for early mortality, suggestive of an aging phenotype. The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) is specifically designed to describe the accumulation of comorbidities over time with estimates of severity such as total score (TS) which is a sum of possible conditions weighted by severity. These severity scores can then be used to predict future mortality.

Methods: CIRS-G scores were calculated in cancer survivors and their siblings from Childhood Cancer Survivor Study cohort members from two time points 19 years apart and …

Differentials And Predictors Of Food Insecurity Among Federally Qualified Health Center Target Populations In Philadelphia: A Cross-Sectional Study, Galicano Kai Inguito, Brandon Joa, James Gardner, Eric N Fung, Laura Layer, Karen Fritz

Department of Medicine Faculty Papers

BACKGROUND: Over the past decade, the prevalence of food insecurity declined in the United States but curiously climbed in Philadelphia, Pennsylvania, a sizable metropolitan area where many households experience food insecurity and are dependent on programs like SNAP. Therefore, we aimed to determine the burden of food insecurity among populations near Philadelphia Federally Qualified Health Center (FQHC) clinic sites.

METHODS: This cross-sectional study was conducted in North Philadelphia, a populous and impoverished section of Philadelphia with many zip codes reporting 30-45% or more of the population below the federal poverty line. Students and clinicians affiliated with a local FQHC conducted …

Gbmdeconvoluter Accurately Infers Proportions Of Neoplastic And Immune Cell Populations From Bulk Glioblastoma Transcriptomics Data., Shoaib Ajaib, Disha Lodha, Steven Pollock, Gemma Hemmings, Martina A Finetti, Arief Gusnanto, Aruna Chakrabarty, Azzam Ismail, Erica Wilson, Frederick S Varn, Bethany Hunter, Andrew Filby, Asa A Brockman, David Mcdonald, Roel G W Verhaak, Rebecca A Ihrie, Lucy F Stead

Faculty Research 2023

BACKGROUND: Characterizing and quantifying cell types within glioblastoma (GBM) tumors at scale will facilitate a better understanding of the association between the cellular landscape and tumor phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumor microenvironment from bulk RNA sequencing data.

METHODS: We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T-cells, NK-cells, microglia, tumor associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal progenitor-like and mesenchymal GBM cancer cells …

A Bayesian Network Approach To Social And Nonsocial Cognition In Schizophrenia: Are Some Domains More Fundamental Than Others?, Samuel J Abplanalp, Junghee Lee, William P Horan, Robert S Kern, David L Penn, Michael F Green

Faculty, Staff and Student Publications

OBJECTIVES: Social and nonsocial cognition are defined as distinct yet related constructs. However, the relative independence of individual variables-and whether specific tasks directly depend on performance in other tasks-is still unclear. The current study aimed to answer this question by using a Bayesian network approach to explore directional dependencies among social and nonsocial cognitive domains.

STUDY DESIGN: The study sample comprised 173 participants with schizophrenia (71.7% male; 28.3% female). Participants completed 5 social cognitive tasks and the MATRICS Consensus Cognitive Battery. We estimated Bayesian networks using directed acyclic graph structures to examine directional dependencies among the variables.

STUDY RESULTS: After …

Multi-Task Learning With Dynamic Re-Weighting To Achieve Fairness In Healthcare Predictive Modeling, Can Li, Sirui Ding, Na Zou, Xia Hu, Xiaoqian Jiang, Kai Zhang

Faculty, Staff and Student Publications

The emphasis on fairness in predictive healthcare modeling has increased in popularity as an approach for overcoming biases in automated decision-making systems. The aim is to guarantee that sensitive characteristics like gender, race, and ethnicity do not influence prediction outputs. Numerous algorithmic strategies have been proposed to reduce bias in prediction results, mitigate prejudice toward minority groups and promote prediction fairness. The goal of these strategies is to ensure that model prediction performance does not exhibit significant disparity among sensitive groups. In this study, we propose a novel fairness-achieving scheme based on multitask learning, which fundamentally differs from conventional fairness-achieving …

Minimal Positional Substring Cover Is A Haplotype Threading Alternative To Li And Stephens Model, Ahsan Sanaullah, Degui Zhi, Shaojie Zhang

Faculty, Staff and Student Publications

The Li and Stephens (LS) hidden Markov model (HMM) models the process of reconstructing a haplotype as a mosaic copy of haplotypes in a reference panel. For small panels, the probabilistic parameterization of LS enables modeling the uncertainties of such mosaics. However, LS becomes inefficient when sample size is large, because of its linear time complexity. Recently the PBWT, an efficient data structure capturing the local haplotype matching among haplotypes, was proposed to offer a fast method for giving some optimal solution (Viterbi) to the LS HMM. Previously, we introduced the minimal positional substring cover (MPSC) problem as an alternative …

Distinct Serum Immune Profiles Define The Spectrum Of Acute And Chronic Pancreatitis From The Multicenter Prospective Evaluation Of Chronic Pancreatitis For Epidemiologic And Translational Studies (Proceed) Study, Bomi Lee, Elaina K Jones, Murli Manohar, Liang Li, Dhiraj Yadav, Darwin L Conwell, Phil A Hart, Santhi Swaroop Vege, Evan L Fogel, Jose Serrano, Dana Andersen, Melena D Bellin, Mark D Topazian, Stephen K Van Den Eeden, Stephen J Pandol, Chris E Forsmark, William E Fisher, Walter G Park, Sohail Z Husain, Aida Habtezion, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and progressing in some cases to recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Currently, there are no approved therapies or early diagnostic or prognostic biomarkers for pancreatitis. The current study examined whether patient serum immune profiling could identify noninvasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis.

METHODS: Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study of the Chronic …

Machine Learning For Ecg Diagnosis And Risk Stratification Of Occlusion Myocardial Infarction, Salah S Al-Zaiti, Christian Martin-Gill, Jessica K Zègre-Hemsey, Zeineb Bouzid, Ziad Faramand, Mohammad O Alrawashdeh, Richard E Gregg, Stephanie Helman, Nathan T Riek, Karina Kraevsky-Phillips, Gilles Clermont, Murat Akcakaya, Susan M Sereika, Peter Van Dam, Stephen W Smith, Yochai Birnbaum, Samir Saba, Ervin Sejdic, Clifton W Callaway

Faculty, Staff and Students Publications

Patients with occlusion myocardial infarction (OMI) and no ST-elevation on presenting electrocardiogram (ECG) are increasing in numbers. These patients have a poor prognosis and would benefit from immediate reperfusion therapy, but, currently, there are no accurate tools to identify them during initial triage. Here we report, to our knowledge, the first observational cohort study to develop machine learning models for the ECG diagnosis of OMI. Using 7,313 consecutive patients from multiple clinical sites, we derived and externally validated an intelligent model that outperformed practicing clinicians and other widely used commercial interpretation systems, substantially boosting both precision and sensitivity. Our derived …

Creativity In Energy Balance, Obesity And Feeding Behavior Research, Some Thoughts, Stephen J French, David B Allison

Children’s Nutrition Research Center Staff Publications

This review provides an overview of examples of especially creative work related to the fields of ingestive behavior, energetics (defined as the study of the acquisition, storage, and use of metabolizable energy by biological organisms and the causes and consequences of such acquisition, storage, and use), and nutrition, focusing on both individual works and discoveries, as well as bodies of works and in some cases the working styles of particular scientists. The paper then discusses some principles extracted from our observations as well as from the literature on creativity pointing out some factors that seem to make for more creative …

Parametric Delineation Uncertainties Contouring (Pduc) Modeling On Ct Scans Of Prostate Cancer Patients, Vi Ly, Lizhong Liu, Carlos Cardenas, Sean Maroongroge, Brian De, Daniel El Basha, Laurence Court, Xi Luo

Faculty, Staff and Student Publications

PURPOSE: Variability in contouring contributes to large variations in radiation therapy planning and treatment outcomes. The development and testing of tools to automatically detect contouring errors require a source of contours that includes well-understood and realistic errors. The purpose of this work was to develop a simulation algorithm that intentionally injects errors of varying magnitudes into clinically accepted contours and produces realistic contours with different levels of variability.

METHODS: We used a dataset of CT scans from 14 prostate cancer patients with clinician-drawn contours of the regions of interest (ROI) of the prostate, bladder, and rectum. Using our newly developed …

Monte Carlo-Derived 99m Tc Uptake Quantification With Commercial Planar Mbi: Tumor And Breast Activity Concentrations, Benjamin P Lopez, S Cheenu Kappadath

Faculty, Staff and Student Publications

BACKGROUND: Current molecular breast imaging (MBI) images are limited to qualitative evaluation, not absolute measurement, of

PURPOSE: This work assesses the accuracy of previously-published and newly-proposed tumor and normal breast tissue

METHODS: Quantification techniques were tested in over 4000 simulated acquisitions of spherical and ellipsoid tumors with clinically relevant uptake conditions using a validated Monte Carlo application of the GE Discovery NM750b system. The evaluated techniques consisted of four tumor total activity methodologies (two single-detector-based and two geometric-mean-based), two tumor MBI volume methodologies (diameter-based and ROI-based), and two normal tissue activity concentration methodologies (single-detector-based and geometric-mean-based). The most accurate of …

Non-Negative Matrix Factorization Improves The Efficiency Of Recording Frequency-Following Responses In Normal-Hearing Adults And Neonates., Fuh-Cherng Jeng, Tzu-Hao Lin, Breanna N Hart, Karen Montgomery-Reagan, Kalyn Mcdonald

Ambulatory and Primary Care Articles

OBJECTIVE: One challenge in extracting the scalp-recorded frequency-following response (FFR) is related to its inherently small amplitude, which means that the response cannot be identified with confidence when only a relatively small number of recording sweeps are included in the averaging procedure.

DESIGN: This study examined how the non-negative matrix factorisation (NMF) algorithm with a source separation constraint could be applied to improve the efficiency of FFR recordings. Conventional FFRs elicited by an English vowel/i/with a rising frequency contour were collected.

RESULTS: The improvements of FFR recordings, defined as the correlation coefficient and root-mean-square differences across a sweep series of …

Remote Neuronal Activity Drives Glioma Progression Through Sema4f, Emmet Huang-Hobbs, Yi-Ting Cheng, Yeunjung Ko, Estefania Luna-Figueroa, Brittney Lozzi, Kathryn R Taylor, Malcolm Mcdonald, Peihao He, Hsiao-Chi Chen, Yuhui Yang, Ehson Maleki, Zhung-Fu Lee, Sanjana Murali, Michael R Williamson, Dongjoo Choi, Rachel Curry, James Bayley, Junsung Woo, Ali Jalali, Michelle Monje, Jeffrey L Noebels, Akdes Serin Harmanci, Ganesh Rao, Benjamin Deneen

Faculty, Staff and Students Publications

The tumor microenvironment (TME) plays an essential role in malignancy and neurons have emerged as a key component of the TME that promotes tumorigenesis across a host of cancers1,2. Recent studies on glioblastoma (GBM) highlight bi-directional signaling between tumors and neurons that propagates a vicious cycle of proliferation, synaptic integration, and brain hyperactivity3-8; however, the identity of neuronal subtypes and tumor subpopulations driving this phenomenon are incompletely understood. Here we show that callosal projection neurons located in the hemisphere contralateral to primary GBM tumors promote progression and widespread infiltration. Using this platform …

Mathematical Analysis Of Hemoglobin Target In Univentricular Parallel Circulation, Mubbasheer Ahmed, Sebastian I Acosta, George M Hoffman, James S Tweddell, Nancy S Ghanayem

Faculty, Staff and Students Publications

Objective: The hemoglobin threshold for a decision to transfuse red blood cells in univentricular patients with parallel circulation is unclear. A pediatric expertise initiative put forth a "weak recommendation" for avoiding reflexive transfusion beyond a hemoglobin of 9 g/dL. We have created a mathematical model to assess the impact of hemoglobin thresholds in patients with parallel circulation.

Methods: A univentricular circulation was mathematically modeled. We examined the impact on oxygen extraction ratios and systemic and venous oxygen saturations by varying hemoglobin levels, pulmonary to systemic blood flow ratios, and total cardiac output.

Results: Applying a total cardiac index of 6 …

Privacy Preserving Identification Of Population Stratification For Collaborative Genomic Research, Leonard Dervishi, Wenbiao Li, Anisa Halimi, Xiaoqian Jiang, Jaideep Vaidya, Erman Ayday

Faculty, Staff and Student Publications

The rapid improvements in genomic sequencing technology have led to the proliferation of locally collected genomic datasets. Given the sensitivity of genomic data, it is crucial to conduct collaborative studies while preserving the privacy of the individuals. However, before starting any collaborative research effort, the quality of the data needs to be assessed. One of the essential steps of the quality control process is population stratification: identifying the presence of genetic difference in individuals due to subpopulations. One of the common methods used to group genomes of individuals based on ancestry is principal component analysis (PCA). In this article, we …

A Novel Peptide 'T14' Reflects Age And Photo-Aging In Human Skin, Sheila Rocha, Sara Garcia Ratés, Tumisang Moswete, Kristopher Kalleberg, Anna Villa, Jason P Harcup, Susan A Greenfield

Faculty, Staff and Student Publications

T14 is a 14mer peptide derived from the C-terminus of acetylcholinesterase (AChE). Once cleaved, it is independently bioactive of the parent molecule and enhances calcium influx in different cell types, in a range of scenarios: it binds to an allosteric site selectively on the alpha-7 receptor, where it modulates calcium influx and is thus a potential trophic agent, as already reported in a range of normal developmental scenarios. However, if inappropriately activated, this erstwhile beneficial effect converts to a toxic one, resulting in pathologies as disparate as Alzheimer’s and various metastatic cancers. Given that epidermal keratinocyte cells have the same …

Using Ai-Generated Suggestions From Chatgpt To Optimize Clinical Decision Support, Siru Liu, Aileen P Wright, Barron L Patterson, Jonathan P Wanderer, Robert W Turer, Scott D Nelson, Allison B Mccoy, Dean F Sittig, Adam Wright

Faculty, Staff and Student Publications

OBJECTIVE: To determine if ChatGPT can generate useful suggestions for improving clinical decision support (CDS) logic and to assess noninferiority compared to human-generated suggestions.

METHODS: We supplied summaries of CDS logic to ChatGPT, an artificial intelligence (AI) tool for question answering that uses a large language model, and asked it to generate suggestions. We asked human clinician reviewers to review the AI-generated suggestions as well as human-generated suggestions for improving the same CDS alerts, and rate the suggestions for their usefulness, acceptance, relevance, understanding, workflow, bias, inversion, and redundancy.

RESULTS: Five clinicians analyzed 36 AI-generated suggestions and 29 human-generated suggestions …

Long-Term Outcomes And Molecular Correlates Of Sotorasib Efficacy In Patients With Pretreated Kras G12c-Mutated Non–Small-Cell Lung Cancer: 2-Year Analysis Of Codebreak 100, Grace K Dy, Ramaswamy Govindan, Vamsidhar Velcheti, Gerald S Falchook, Antoine Italiano, Jürgen Wolf, Adrian G Sacher, Toshiaki Takahashi, Suresh S Ramalingam, Christophe Dooms, Dong-Wan Kim, Alfredo Addeo, Jayesh Desai, Martin Schuler, Pascale Tomasini, David S Hong, Piro Lito, Qui Tran, Simon Jones, Abraham Anderson, Antreas Hindoyan, Wendy Snyder, Ferdinandos Skoulidis, Bob T Li

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

In the longest follow-up, to our knowledge, for a KRAS^G12C inhibitor, we assessed the long-term efficacy, safety, and biomarkers of sotorasib in patients with KRAS G12C-mutated advanced non–small-cell lung cancer (NSCLC) from the CodeBreaK 100 clinical …

Long-Term Outcomes And Molecular Correlates Of Sotorasib Efficacy In Patients With Pretreated Kras G12c-Mutated Non-Small-Cell Lung Cancer: 2-Year Analysis Of Codebreak 100, Grace K Dy, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

No abstract provided.