Digital Commons Network^™

The Bile Acid Induced Hepatokine Orosomucoid Suppresses Adipocyte Differentiation, Aaron R Cox, Sean M Hartig, David D Moore, Kang Ho Kim

Faculty, Staff and Students Publications

Bile acids have recently emerged as key metabolic hormones with beneficial impacts in multiple metabolic diseases. We previously discovered that hepatic bile acid overload distally modulates glucose and fatty acid metabolism in adipose tissues to exert anti-obesity effects. However, the detailed mechanisms that explain the salutary effects of serum bile acid elevation remain unclear. Here, proteomic profiling identified a new hepatokine, Orosomucoid (ORM) that governs liver-adipose tissue crosstalk. Hepatic ORMs were highly induced by both genetic and dietary bile acid overload. To address the direct metabolic effects of ORM, purified ORM proteins were administered during adipogenic differentiation of 3T3-L1 cells …

Lifestyle Risk Factors, Quality Of Life, And Intervention Preferences Of Barrett's Esophagus Patients: A Prospective Cohort Study, Mohamed Othman, Hoda J Badr

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Lifestyle counseling to achieve a healthy weight, quit smoking, and reduce alcohol is a cornerstone in the management of Barrett's Esophagus (BE). However, little is known about whether patients make these recommended lifestyle changes or the impact of non-adherence on their quality of life (QOL). This study characterized the lifestyle risk factors, QOL, and intervention preferences of BE patients as a first step toward developing lifestyle change interventions for this population.

METHODS: Patients with a confirmed BE diagnosis (N = 106) completed surveys at a surveillance endoscopy visit (baseline) and at 3- and 6-month follow-ups. Patients reported …

Adipocyte-Specific Ablation Of Pu1 Promotes Energy Expenditure And Ameliorates Metabolic Syndrome In Aging Mice, Aditya More, Scott A Ochsner, Eduardo Lopez, David Saul, Weijun Pang, Yuxiang Sun, Neil J Mckenna, Qiang Tong

Faculty, Staff and Students Publications

Objective: Although PU.1/Spi1 is known as a master regulator for macrophage development and function, we have reported previously that it is also expressed in adipocytes and is transcriptionally induced in obesity. Here, we investigated the role of adipocyte PU.1 in the development of the age-associated metabolic syndrome.

Methods: We generated mice with adipocyte-specific PU.1 knockout, assessed metabolic changes in young and older adult PU.1^fl/fl (control) and AdipoqCre PU.1^fl/fl (aPU.1KO) mice, including body weight, body composition, energy expenditure, and glucose homeostasis. We also performed transcriptional analyses using RNA-Sequencing of adipocytes from these mice.

Results: aPU.1KO mice have elevated energy …

Creating A 'Community Of Inquiry': A Framework For Optimizing The Virtual Education Experience

Faculty, Staff and Students Publications

This article was migrated. The article was marked as recommended.

Background: Medical educators must learn to implement technologic advances to create meaningful learning experiences, implementing media tools that are effective in meeting evolving academic needs and fostering interpersonal engagement. The increasing time constraints in a department of more than 1,600 faculty interspersed throughout a large metropolitan complex served as the catalyst for utilizing technology to create a framework for providing virtual faculty development.

Objective: To use a Community of Inquiry (CoI) as a framework to guide the development of an interactive, virtual writing retreat.

Methods: We used the three elements …

Enhancing Glucose Metabolism Via Gluconeogenesis Is Therapeutic In A Zebrafish Model Of Dravet Syndrome, Matthew T Dinday, Scott C Baraban, Manisha Patel

Faculty, Staff and Students Publications

Energy-producing pathways are novel therapeutic targets for the treatment of neurodevelopmental disorders. Here, we focussed on correcting metabolic defects in a catastrophic paediatric epilepsy, Dravet syndrome which is caused by mutations in sodium channel NaV1.1 gene, SCN1A. We utilized a translatable zebrafish model of Dravet syndrome (scn1lab) which exhibits key characteristics of patients with Dravet syndrome and shows metabolic deficits accompanied by down-regulation of gluconeogenesis genes, pck1 and pck2. Using a metabolism-based small library screen, we identified compounds that increased gluconeogenesis via up-regulation of pck1 gene expression in scn1lab larvae. Treatment with PK11195, a pck1 activator …

Pharmacologically Induced Ex Copula Ejaculation In Horses And Donkeys

Faculty, Staff and Students Publications

Pharmacologically induced ex copula ejaculation is a method used for collection of semen when the traditional methods of semen collection are not feasible. Common indications for this method include health issues that either preclude the physical act of mating or result in impaired erection and ejaculation. The method also offers an alternative when there is a lack of equipment and facilities required for semen collection using the conventional artificial vagina method. A variety of pharmacological protocols for ex copula ejaculation in stallions have been evaluated in both research and clinical settings with no serious side-effects reported. In general, these protocols …

Buprenorphine For Chronic Pain: A Safer Alternative To Traditional Opioids, Vwaire Orhurhu, Bilal Dar, Bennett Kramer, Anvinh Nguyen, John Pruit, Charles Halsted, Alan D Kaye, Jamal Hasoon

Faculty, Staff and Students Publications

With the ongoing public health crisis with prescription opioids, there is a need for safer alternatives for medication management in chronic pain patients. Buprenorphine is a partial mu-opioid agonist which is commonly utilized to treat patients with opioid-use disorders. The purpose of this review is to discuss the potential use of this medication for the treatment of chronic pain instead of resorting to more traditional Schedule II opioids. Buprenorphine offers a safer alternative for patients who require opioids to manage chronic pain, given the unique pharmacological properties that allow it to provide adequate analgesia with less abuse potential.

A New Aortic Arch Dissection Classification: The Fuwai Classification, Wei Pan, Qian Chang, Xiangyang Qian, Xiaogang Sun, Bo Wei, Liang Zhang, Shen Liu, Wenxiang Jiang, Cuntao Yu

Faculty, Staff and Students Publications

Aims: We describe a new aortic arch dissection (AcD) classification, which we have called the Fuwai classification. We then compare the clinical characteristics and long-term prognoses of different classifications.

Methods: All AcD patients who underwent surgical procedures at Fuwai Hospital from 2010 to 2015 were included in the study. AcD procedures are divided into three types: Fuwai type Cp, Ct, and Cd. Type Cp is defined as the innominate artery or combined with the left carotid artery involved. Type Cd is defined as the left subclavian artery or combined with the left carotid artery involved. All other AcD surgeries are …

Rapid Induction Of The Unfolded Protein Response And Apoptosis By Estrogen Mimic Ttc-352 For The Treatment Of Endocrine-Resistant Breast Cancer, Sean W Fanning, Jay S Hanspal, Ping Fan, Charles E Foulds, Yue Chen, Anna Malovannaya, Antrix Jain, Rui Xiong, Geoffrey L Greene, Debra A Tonetti, Gregory R J Thatcher, V Craig Jordan

Faculty, Staff and Students Publications

Patients with long-term estrogen-deprived breast cancer (BC), after resistance to tamoxifen or aromatase inhibitors develops, can experience tumor regression when treated with estrogens. Estrogen’s anti-tumor effect is attributed to apoptosis via the estrogen receptor (ER). Estrogen treatment can have unpleasant gynecological and non-gynecological adverse events thus the development of safer estrogenic agents remains a clinical priority. Here, we study synthetic selective estrogen mimics (SEMs) BMI-135 and TTC-352, and the naturally-occurring estrogen estetrol (E4), which are proposed as safer estrogenic agents compared to 17β-estradiol (E2), for the treatment of endocrine-resistant BC. TTC-352 and E4 are being evaluated in BC clinical trials. …

Open Problems In Extracellular Rna Data Analysis: Insights From An Ercc Online Workshop, Matthew Roth, Pieter Mestdagh, Klaas E A Max, Joel Rozowsky, Karolina Elżbieta Kaczor-Urbanowicz, Justin Chang, Leonora Balaj, Bojan Losic, Eric L Van Nostrand, Emily Laplante, Bogdan Mateescu, Brian S White, Rongshan Yu, Aleksander Milosavljevic, Gustavo Stolovitzky, Ryan M Spengler

Faculty, Staff and Students Publications

We now know RNA can survive the harsh environment of biofluids when encapsulated in vesicles or by associating with lipoproteins or RNA binding proteins. These extracellular RNA (exRNA) play a role in intercellular signaling, serve as biomarkers of disease, and form the basis of new strategies for disease treatment. The Extracellular RNA Communication Consortium (ERCC) hosted a two-day online workshop (April 19–20, 2021) on the unique challenges of exRNA data analysis. The goal was to foster an open dialog about best practices and discuss open problems in the field, focusing initially on small exRNA sequencing data. Video recordings of workshop …

A Novel Statistical Method For Interpreting The Pathogenicity Of Rare Variants, Alejandro Sarrion-Perdigones, Yezabel Gonzalez, Koen J T Venken, Rui Chen

Faculty, Staff and Students Publications

PURPOSE: To achieve the ultimate goal of personalized treatment of patients, accurate molecular diagnosis and precise interpretation of the impact of genetic variants on gene function is essential. With sequencing cost becoming increasingly affordable, the accurate distinguishing of benign from pathogenic variants becomes the major bottleneck. Although large normal population sequence databases have become a key resource in filtering benign variants, they are not effective at filtering extremely rare variants.

METHODS: To address this challenge, we developed a novel statistical test by combining sequencing data from a patient cohort with a normal control population database. By comparing the expected and …

The Association Of Pre-Kidney Transplant Dialysis Modality With De Novo Posttransplant Heart Failure, Carl Walther, Maria E Montez-Rath, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

BACKGROUND: Heart failure (HF) after kidney transplantation is a significant but understudied problem. Pretransplant dialysis modality could influence incident HF risk through differing cardiac stressors. However, whether pretransplant dialysis modality is associated with the development of posttransplant HF is unknown.

METHODS: We used the US Renal Data System to assemble a cohort of 27,701 patients who underwent their first kidney transplant in the USA between the years 2005 and 2012 and who had Medicare fee-for-service coverage for >6 months preceding their transplant date. Patients with any HF diagnosis prior to transplant were excluded. Detailed baseline patient characteristics and comorbidities were …

An International Study Of Interobserver Variability Of “String Sign” Of Pancreatic Cysts Among Experienced Endosonographers, Leonard B Bacharier, Sandy Durrani, Daniel J Jackson, Fernando D Martinez, Anne M Fitzpatrick, Amparito Cunningham, Susan Kunselman, Lisa M Wheatley, Cindy Bauer, Carla M Davis, Bob Geng, Kirsten M Kloepfer, Craig Lapin, Andrew H Liu, Jacqueline A Pongracic, Stephen J Teach, James Chmiel, Jonathan M Gaffin, Matthew Greenhawt, Meera R Gupta, Peggy S Lai, Robert F Lemanske, Wayne J Morgan, William J Sheehan, Jeffrey Stokes, Peter S Thorne, Hans C Oettgen, Elliot Israel

Faculty, Staff and Students Publications

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In …

Case Report: Dupilumab Successfully Controls Severe Eczema In A Child With Elevated Ige Levels And Recurrent Skin Infections, Carla M Davis, Joud Hajjar

Faculty, Staff and Students Publications

The efficacy of dupilumab in pediatric patients with severe eczema presenting in the setting of elevated immunoglobulin E (IgE) levels and recurrent bacterial skin infections is not well-understood. Here we present the case of a child with elevated IgE levels in whom dupilumab treatment led to remarkable control of his eczema and recurrent skin infections. We also review the use of dupilumab in other patients with molecularly proven cases of hyper IgE (HIGE) syndrome. Our case supports the notion that dupilumab may have a seminal application in treating severe eczema that occurs in the setting of elevated IgE levels and …

Meta-Analysis Comparing Outcomes Of Catheter Ablation For Ventricular Arrhythmia In Ischemic Versus Nonischemic Cardiomyopathy, Anindya Mukherjee, Sudhanva V Char, Bhavna Jain, T Jared Bunch, Michael Gold, Adedayo A Adeboye, Mohammad Saeed

Faculty, Staff and Students Publications

BACKGROUND: Catheter ablation is an effective treatment for ventricular arrhythmia (VA) in ischemic cardiomyopathy (ICM). However, results in non-ICM (NICM) patients are not satisfactory, and studies comparing differences between NICM and ICM are limited. We conducted a meta-analysis of procedural characteristics and long-term outcomes of catheter ablation for VA, comparing results between ICM and NICM.

METHODS: Studies in the PubMed, EMBASE, and Cochrane databases were systematically reviewed. Four studies reporting comparison of catheter ablation of VA between ICM and NICM were examined. The Newcastle-Ottawa Scale was used to appraise study quality. A random-effects model with inverse variance method was used …

Conduction Disorders In The Setting Of Acute Stemi, Jani Rankinen, Antoni Bayés De Luna

Faculty, Staff and Students Publications

ST-elevation myocardial (STEMI) is frequently associated with conduction disorders. Regional myocardial ischemia or injury may affect the cardiac conduction system at various locations, and neural reflexes or changes in the balance of the autonomous nervous system may be involved. Sinoatrial and atrioventricular blocks are more frequent in inferior than anterior STEMI, while new left anterior fascicular block and right bundle branch block indicate proximal occlusion of the left anterior descending coronary artery. New left bundle branch block is associated with multi-vessel disease. Most conduction disorders associated with STEMI are reversible with reperfusion therapy, but they may still impair prognosis because …

Trace Element Concentrations In Blood And Scute Tissues From Wild And Captive Hawaiian Green Sea Turtles (Chelonia Mydas), T Todd Jones, Jeff Pawloski, Marc R Rice, Amanda D French, Jing Liu, George P Cobb, David M Klein

Faculty, Staff and Students Publications

Sea turtles are exposed to trace elements through water, sediment, and food. Exposure to these elements has been shown to decrease immune function, impair growth, and decrease reproductive output in wildlife. This study compares trace element concentrations in green turtles in captivity at Sea Life Park Hawaii (n = 6) to wild green turtles in Kapoho Bay, HI (n = 5 to 7). Blood and scute samples were collected and analyzed for eleven elements via inductively coupled plasma-mass spectrometry (ICP-MS). Selenium was significantly greater (p < 0.05) in the blood of captive turtles compared to wild turtles, while V, Ni, and Pb were significantly greater in the blood of wild turtles. In scute, V, Cu, Se, and Cr were significantly greater in captive turtles, while As was significantly greater in wild turtles. Pelleted food fed to the captive turtles and representative samples of the wild turtle diet were analyzed via ICP-MS to calculate trophic transfer factors and daily intake values. Wild turtles had greater estimated daily intake than captive turtles for all elements except Cu and Se. Because captive turtles are fed a diet very different from their wild counterparts, captive turtles do not represent control or reference samples for chemical exposure studies in wild turtles. No toxic thresholds are known for sea turtles, but rehabilitation and managed care facilities should monitor sea turtle elemental concentrations to ensure the animals’ health.

Examining Social Vulnerability And The Association With Covid-19 Incidence In Harris County, Texas, Alison Rector, Dania Mofleh, Eric Boerwinkle

Faculty, Staff and Student Publications

Studies have investigated the association between social vulnerability and SARS-CoV-2 incidence. However, few studies have examined small geographic units such as census tracts, examined geographic regions with large numbers of Hispanic and Black populations, controlled for testing rates, and incorporated stay-at-home measures into their analyses. Understanding the relationship between social vulnerability and SARS-CoV-2 incidence is critical to understanding the interplay between social determinants and implementing risk mitigation guidelines to curtail the spread of infectious diseases. The objective of this study was to examine the relationship between CDC's Social Vulnerability Index (SVI) and SARS-CoV-2 incidence while controlling for testing rates and …

Exploring The Hazards Of Scaling Up Clinical Data Analyses: A Drug Side Effect Discovery Case Report

Faculty, Staff and Student Publications

We assessed the scalability of pharmacological signal detection use case from a single-site CDW to a large aggregated clinical data warehouse (single-site database with 754,214 distinct patient IDs vs. multisite database with 49.8M). We aimed to explore whether a larger clinical dataset would provide clearer signals for secondary analyses such as detecting the known relationship between prednisone and weight. We found significant weight gain rate using the single-site data but not from using aggregated data (0.0104 kg/day, p

Determining Risk Factors That Affect Progression In Patients With Nonproliferative Diabetic Retinopathy, Wenyaw Chan

Faculty, Staff and Student Publications

PURPOSE: to determine risk factors that affect nonproliferative diabetic retinopathy (NPDR) progression and establish a predictive model to estimate the probability of and time to progression in NPDR.

RESULTS: Two hundred thirty patients were included. Initially, 65 eyes (28.3%) had no retinopathy; 73 (31.7%) mild NPDR; 60 (26.1%) moderate NPDR; and 32 (13.9%) severe NPDR. Patients were followed for a mean of 5.8 years (±2.0 years; range 2.1-9.4 years). 164 (71.3%) eyes progressed during the follow-up. Time-independent risk factors affecting progression rate were age (hazard ratio (HR) = 0.99,

CONCLUSION: HbA1c level is a significant modifiable risk factor in controlling …

Determination Of Optimal Deployment Strategy For Reboa In Patients With Non-Compressible Hemorrhage Below The Diaphragm, Charles J Fox, Thomas Scalea, Eileen M Bulger, Kenji Inaba, Bryan C Morse, Laura J Moore

Faculty, Staff and Student Publications

BACKGROUND: Non-compressible truncal hemorrhage (NCTH) is the leading cause of preventable death after trauma. Resuscitative endovascular balloon occlusion of the aorta (REBOA) achieves temporary hemorrhage control, supporting cardiac and cerebral perfusion prior to definitive hemostasis. Aortic zone selection algorithms vary among institutions. We evaluated the efficacy of an algorithm for REBOA use.

METHODS: A multicenter prospective, observational study conducted at six level 1 trauma centers over 12 months. Inclusion criteria were age >15 years with evidence of infradiaphragmatic NCTH needing emergent hemorrhage control within 60 min of ED arrival. An algorithm characterized by the results of focused assessment with sonography …

Developing And Evaluating A Quality Improvement Intervention To Facilitate Patient Navigation In The Accountable Health Communities Model, Vanessa R Schick

Faculty, Staff and Student Publications

Introduction: The Accountable Health Communities (AHC) Model was designed to address the health-related social needs of Centers for Medicare & Medicaid Services beneficiaries. Bridge organizations across the AHC Model have identified lack of technical assistance and peer planning as potential barriers to Model success, particularly around patient navigation. The technical assistance and peer planning literature lacks an organizing, conceptual framework, but implementation science frameworks could serve as useful guides. The Strengthening Peer AHC Navigation (SPAN) research protocol seeks to fill this gap and will apply three implementation science frameworks, Consolidated Framework for Implementation Research, Intervention Mapping, and the Expert Recommendations …

Applying Machine Learning Approaches To Suicide Prediction Using Healthcare Data: Overview And Future Directions, Celine Larkin, Joshua Semeter, Gregory Simon, Rachel E Davis-Martin

Faculty, Staff and Student Publications

Objective: Early identification of individuals who are at risk for suicide is crucial in supporting suicide prevention. Machine learning is emerging as a promising approach to support this objective. Machine learning is broadly defined as a set of mathematical models and computational algorithms designed to automatically learn complex patterns between predictors and outcomes from example data, without being explicitly programmed to do so. The model's performance continuously improves over time by learning from newly available data.

Method: This concept paper explores how machine learning approaches applied to healthcare data obtained from electronic health records, including billing and claims data, can …

Structural Racism And Immigrant Health: Exploring The Association Between Wage Theft, Mental Health, And Injury Among Latino Day Laborers, Casey P Durand

Faculty, Staff and Student Publications

BACKGROUND: Although wage theft has been discussed primarily as a labor and human rights issue, it can be conceptualized as an issue of structural racism with important consequences for immigrant health.

OBJECTIVES: The objectives of this study were to: 1) identify sociodemographic, employment, and stress-related characteristics that increase Latino day laborers' odds of experiencing wage theft; 2) assess the association between wage theft and serious work-related injury; 3) assess the association between wage theft and three indicators of mental health-depression, social isolation, and alcohol use-as a function of wage theft; and 4) assess serious work-related injury as a function of …

Gender Differences In Fear And Risk Perception During The Covid-19 Pandemic

Faculty, Staff and Student Publications

The COVID-19 pandemic has led many people to suffer from emotional distress. Previous studies suggest that women process and express affective experiences, such as fear, with a greater intensity compared to men. We administered an online survey to a sample of participants in the United States that measures fear of COVID-19, perceptions about health and financial risks, and preventative measures taken. Despite the empirical fact that men are more likely to experience adverse health consequences from COVID-19, women report greater fear and more negative expectations about health-related consequences of COVID-19 than men. However, women are more optimistic than men regarding …

Patterns And Risk Factors Of Opioid-Suspected Ems Overdose In Houston Metropolitan Area, 2015-2019: A Bayesian Spatiotemporal Analysis, David Persse

Faculty, Staff and Student Publications

BACKGROUND: Opioid-related overdose deaths are the top accidental cause of death in the United States, and development of regional strategies to address this epidemic should begin with a better understanding of where and when overdoses are occurring.

METHODS AND FINDINGS: In this study, we relied on emergency medical services data to investigate the geographical and temporal patterns in opioid-suspected overdose incidents in one of the largest and most ethnically diverse metropolitan areas (Houston Texas). Using a cross sectional design and Bayesian spatiotemporal models, we identified zip code areas with excessive opioid-suspected incidents, and assessed how the incidence risks were associated …

The Impact Of The Th17:Treg Axis On The Iga-Biome Across The Glycemic Spectrum, David Aguilar, Eric L Brown

Faculty, Staff and Student Publications

Secretory IgA (SIgA) is released into mucosal surfaces where its function extends beyond that of host defense to include the shaping of resident microbial communities by mediating exclusion/inclusion of respective microbes and regulating bacterial gene expression. In this capacity, SIgA acts as the fulcrum on which host immunity and the health of the microbiota are balanced. We recently completed an analysis of the gut and salivary IgA-Biomes (16S rDNA sequencing of SIgA-coated/uncoated bacteria) in Mexican-American adults that identified IgA-Biome differences across the glycemic spectrum. As Th17:Treg ratio imbalances are associated with gut microbiome dysbiosis and chronic inflammatory conditions such as …

N95 Respirator Reuse, Decontamination Methods, And Microbial Burden: A Randomized Controlled Trial, Michael C Lorenz, Hannah B Wilson, Jumah Ahmad, Ronda Alexander, William Bryan, Luke Burke, Martin J Citardi, Jose Elias, Tang Ho, Jack Jacob, Garren Low, Pedro Miramón, Aniruddha U Patki, William C Yao, Amber U Luong

Faculty, Staff and Student Publications

PURPOSE: to evaluate the effectiveness and ease of N95 respirator decontamination methods in a clinic setting and to identify the extent of microbial colonization on respirators associated with reuse.

METHODS: In a prospective fashion, N95 respirators (n = 15) were randomized to a decontamination process (time, dry heat, or ultraviolet C light [UVC]) in outpatient clinics. Each respirator was re-used up to 5 separate clinic sessions. Swabs on each respirator for SARS-CoV-2, bacteria, and fungi were obtained before clinic, after clinic and post-treatment. Mask integrity was checked after each treatment (n = 68). Statistical analyses were performed to determine factors …

The Association Between Short-Term Emotion Dynamics And Cigarette Dependence: A Comprehensive Examination Of Dynamic Measures, Hsien-Chang Lin, Megan E Piper

Faculty, Staff and Student Publications

BACKGROUND: The association between short-term emotion dynamics and long-term psychopathology has been well established in the psychology literature. Yet, dynamic measures for inertia and instability of negative and positive affect have not been studied in terms of their association with cigarette dependence. This study builds an important bridge between the psychology and substance use literatures by introducing these novel measures and conducting a comprehensive examination of such association with intervention implications.

METHODS: This study conducted secondary analysis on the data from a community sample of 136 dual users (e-cigarette + cigarette) and 101 exclusive smokers who completed both the two-week …

Utilization Of Target Lesion Heterogeneity For Treatment Efficacy Assessment In Late Stage Lung Cancer, Amer A Beg, Jhanelle E Gray, Eric B Haura, Trevor A Rose, Ben Creelan

Faculty, Staff and Student Publications

RATIONALE: Recent studies have discovered several unique tumor response subgroups outside of response classification by Response Evaluation Criteria for Solid Tumors (RECIST), such as mixed response and oligometastasis. These subtypes have a distinctive property, lesion heterogeneity defined as diversity of tumor growth profiles in RECIST target lesions. Furthermore, many cancer clinical trials have been activated to evaluate various treatment options for heterogeneity-related subgroups (e.g., 29 trials so far listed in clinicaltrials.gov for cancer patients with oligometastasis). Some of the trials have shown survival benefit by tailored treatment strategies. This evidence presents the unmet need to incorporate lesion heterogeneity to improve …