Medical Sciences Commons^™

Offloading And Adherence Through Technological Advancements: Modern Approaches For Better Foot Care In Diabetes, Sicco A Bus, Neil D Reeves, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

Objective: This manuscript aims to provide a review and synthesis of contemporary advancements in footwear, sensor technology for remote monitoring, and digital health, with a focus on improving offloading and measuring and enhancing adherence to offloading in diabetic foot care.

Methods: A narrative literature review was conducted by sourcing peer-reviewed articles, clinical studies, and technological innovations. This paper includes a review of various strategies, from specifically designed footwear, smart insoles and boots to using digital health interventions, which aim to offload plantar pressure and help prevent and manage wounds more effectively by improving the adherence to such offloading.

Results: In-house …

Determinants Of Referral Network Size For Screening Colonoscopies In The Veterans Health Administration After The Implementation Of The Mission Act, Chase S Eck, Vivian Ho, Cheng Jiang, Laura A Petersen

Center for Medical Ethics and Health Policy Staff Publications

Objective: To measure key characteristics of the Veterans Health Administration's (VHA) Community Care (CC) referral network for screening colonoscopy and identify market and institutional factors associated with network size.

Data sources: VHA electronic health records, CC claim data, and National Plan and Provider Enumeration System.

Study design: In this retrospective cross-sectional study, we measure the size of the VHA's CC referral networks over time and by VHA parent facility (n = 137). We used a multivariable linear regression to identify factors associated with network size at the market-year level. Network size was measured as the number of physicians who performed …

Gene-Specific Acmg/Amp Classification Criteria For Germline Apc Variants: Recommendations From The Clingen Insight Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel\, Isabel Spier, Xiaoyu Yin, Marcy Richardson, Marta Pineda, Andreas Laner, Deborah Ritter, Julie Boyle, Pilar Mur, Thomas V O Hansen, Xuemei Shi, Khalid Mahmood, John-Paul Plazzer, Elisabet Ognedal, Margareta Nordling, Susan M Farrington, Gou Yamamoto, Stéphanie Baert-Desurmont, Alexandra Martins, Ester Borras, Carli Tops, Erica Webb, Victoria Beshay, Maurizio Genuardi, Tina Pesaran, Gabriel Capellá, Sean V Tavtigian, Andrew Latchford, Ian M Frayling, Sharon E Plon, Marc Greenblatt, Finlay A Macrae, Stefan Aretz, Insight-Clingen Hereditary Colon Cancer/Polyposis Variant Curation Expert Panel

Center for Medical Ethics and Health Policy Staff Publications

Purpose: The Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) was established by the International Society for Gastrointestinal Hereditary Tumours and the Clinical Genome Resource, who set out to develop recommendations for the interpretation of germline APC variants underlying Familial Adenomatous Polyposis, the most frequent hereditary polyposis syndrome.

Methods: Through a rigorous process of database analysis, literature review, and expert elicitation, the APC VCEP derived gene-specific modifications to the ACMG/AMP (American College of Medical Genetics and Genomics and Association for Molecular Pathology) variant classification guidelines and validated such criteria through the pilot classification of 58 variants.

Results: The APC-specific criteria …

Risk Factors For Childhood Brain Tumours: A Systematic Review And Meta-Analysis Of Observational Studies From 1976 To 2022, Felix M Onyije, Roya Dolatkhah, Ann Olsson, Liacine Bouaoun, Isabelle Deltour, Friederike Erdmann, Audrey Bonaventure, Michael E Scheurer, Jacqueline Clavel, Joachim Schüz

Center for Medical Ethics and Health Policy Staff Publications

BACKGROUND: Childhood brain tumours (CBTs) are the leading cause of cancer death in children under the age of 20 years globally. Though the aetiology of CBT remains poorly understood, it is thought to be multifactorial. We aimed to synthesize potential risk factors for CBT to inform primary prevention.

METHODS: We conducted a systematic review and meta-analysis of epidemiological studies indexed in the PubMed, Web of Science, and Embase databases from the start of those resources through 27 July 2023. We included data from case-control or cohort studies that reported effect estimates for each risk factor around the time of conception, …

Utility Of A Low-Cost 3-D Printed Microscope For Evaluating Esophageal Biopsies, Daniel G Rosen, Evandro Sobroza De Mello, Sadhna Dhingra, Sanford M Dawsey, Joe Knapper, Richard Bowman, Sharmila Anandasabapathy

Center for Medical Ethics and Health Policy Staff Publications

In this manuscript we assessed the utility of a low-cost 3D printed microscope to evaluate esophageal biopsies. We conducted a comparative analysis between the traditional microscope and our 3-D printed microscope, utilizing a set of esophageal biopsy samples obtained from patients undergoing screening endoscopy. Two pathologists independently examined 30 esophageal biopsies by light microscopy and digital images obtained using a low-cost 3D printed microscope (Observer 1 and 2). The glass slide consensus diagnosis was compared to the findings of 2 additional pathologist who independently just reviewed the digital images (Observer 3 and 4). The intra-observer agreement was substantial to almost …

Veterans Health Administration Enrollees’ Choice Of Care Setting Relates To The Expansion Of Care Options: Evidence From Screening Colonoscopies Before And After The Mission Act, Chase S Eck, Cheng Jiang, Laura A Petersen

Center for Medical Ethics and Health Policy Staff Publications

Objective: To estimate whether those enrolled in the Veterans Health Administration (VHA) were less likely to use VHA-delivered colorectal cancer screening colonoscopies after the MISSION Act.

Data sources and study setting: Secondary data were collected on VHA-enrolled Veterans from FY2017-FY2021.

Study design: This retrospective cross-sectional study measured the volume and share of screening colonoscopies that were VHA-delivered over time and by drive time eligibility-defined as living more than 60 min away from the nearest VHA specialty-care clinic. We used a multivariable logistic regression to adjust for patient and facility factors.

Data extraction: Data were extracted for VHA enrollees (n = …

The Human Vaginal Microbiota: From Clinical Medicine To Models To Mechanisms, Samantha Ottinger, Clare M Robertson, Holly Branthoover, Kathryn A Patras

Faculty, Staff and Students Publications

The composition of the vaginal microbiota is linked to numerous reproductive health problems, including increased susceptibility to infection, pregnancy complications, and impaired vaginal tissue repair; however, the mechanisms contributing to these adverse outcomes are not yet fully defined. In this review, we highlight recent clinical advancements associating vaginal microbiome composition and function with health outcomes. Subsequently, we provide a summary of emerging models employed to identify microbe-microbe interactions contributing to vaginal health, including metagenomic sequencing, multi-omics approaches, and advances in vaginal microbiota cultivation. Last, we review new in vitro, ex vivo, and in vivo models, such as organoids and humanized …

Circadian Dysfunction Induces Nafld-Related Human Liver Cancer In A Mouse Model, Jennifer Padilla, Noha M Osman, Beatrice Bissig-Choisat, Sandra L Grimm, Xuan Qin, Angela M Major, Li Yang, Dolores Lopez-Terrada, Cristian Coarfa, Feng Li, Karl-Dimiter Bissig, David D Moore, Loning Fu

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Chronic circadian dysfunction increases the risk of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC), but the underlying mechanisms and direct relevance to human HCC have not been established. In this study, we aimed to determine whether chronic circadian dysregulation can drive NAFLD-related carcinogenesis from human hepatocytes and human HCC progression.

METHODS: Chronic jet lag of mice with humanized livers induces spontaneous NAFLD-related HCCs from human hepatocytes. The clinical relevance of this model was analysed by biomarker, pathological/histological, genetic, RNA sequencing, metabolomic, and integrated bioinformatic analyses.

RESULTS: Circadian dysfunction induces glucose intolerance, NAFLD-associated human HCCs, and human …

Genome-Wide P63-Target Gene Analyses Reveal Tap63/Nrf2-Dependent Oxidative Stress Responses, Marco Napoli, Avani A Deshpande, Deepavali Chakravarti, Kimal Rajapakshe, Preethi H Gunaratne, Cristian Coarfa, Elsa R Flores

Faculty, Staff and Students Publications

The p53 family member TP63 encodes two sets of N-terminal isoforms, TAp63 and ΔNp63 isoforms. They each regulate diverse biological functions in epidermal morphogenesis and in cancer. In the skin, where their activities have been extensively characterized, TAp63 prevents premature aging by regulating the quiescence and genomic stability of stem cells required for wound healing and hair regeneration, while ΔNp63 controls maintenance and terminal differentiation of epidermal basal cells. This functional diversity is surprising given that these isoforms share a high degree of similarity, including an identical sequence for a DNA-binding domain. To understand the mechanisms of the transcriptional programs …

Respiratory Viral Detection In The Plasma And Cerebrospinal Fluid (Csf) Of Young Febrile Infants, Erin G Nicholson, Vasanthi Avadhanula, Leila C Sahni, Laura Ferlic-Stark, Lauren Maurer, Julie A Boom, Pedro A Piedra

Faculty, Staff and Students Publications

BACKGROUND: Respiratory viral infections are common in febrile infants ≤90 days. However, the detection of viruses other than enterovirus in the blood and cerebrospinal fluid (CSF) of young infants is not well defined. We sought to quantify the occurrence of respiratory viruses in the blood and CSF of febrile infants ≤90 days.

METHODS: We conducted a nested cohort study examining plasma and CSF samples from febrile infants 15-90 days via rtPCR. The samples were tested for respiratory viruses (respiratory syncytial virus, influenza, enterovirus, parechovirus, adenovirus, bocavirus). Clinical and laboratory data were also collected to determine the presence of serious bacterial …

Intradialytic Hypotension And Mortality In Adolescents And Young Adults With Kidney Failure Receiving Maintenance Hemodialysis, Xixi Zhao, Tara I Chang, Wolfgang C Winkelmayer, Jin Long, Sai Liu, Olivera Marsenic

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Intradialytic hypotension (IDH) is associated with mortality in adults with kidney failure requiring hemodialysis (HD); however, large-scale pediatric studies are lacking. Moreover, there is no evidence-based consensus definition of IDH in pediatric literature. We aimed to examine the association of commonly used definitions of IDH with mortality in adolescents and young adults.

STUDY DESIGN: This was a retrospective observational cohort study.

SETTING & PARTICIPANTS: In total, 1,199 adolescents and young adults (N = 320, aged 10-18 years and N = 879, aged 19-21 years) who initiated HD in a large dialysis organization were included.

EXPOSURES: This study …

Long-Term Non-Progression And Risk Factors For Disease Progression Among Children Living With Hiv In Botswana And Uganda: A Retrospective Cohort Study, Samuel Kyobe, Grace Kisitu, Savannah Mwesigwa, John Farirai, Eric Katagirya, Gaone Retshabile, Lesedi Williams, Angela Mirembe, Lesego Ketumile, Misaki Wayengera, John Mukisa, Gaseene Sebetso, Thabo Diphoko, Marion Amujal, Edgar Kigozi, Fred Katabazi, Ronald Oceng, Busisiwe Mlotshwa, Koketso Morapedi, Betty Nsangi, Edward Wampande, Masego Tsimako, Chester Brown, Ishmael Kasvosve, Moses Joloba, Gabriel Anabwani, Sununguko Mpoloka, Graeme Mardon, Adeodata Kekitiinwa, Neil A Hanchard, Jacqueline Kyosiimire-Lugemwa, Mogomotsi Matshaba, Dithan Kiragga

Faculty, Staff and Students Publications

OBJECTIVES: We utilize a large retrospective study cohort derived from electronic medical records to estimate the prevalence of long-term non-progression (LTNP) and determine the factors associated with progression among children infected with HIV in Botswana and Uganda.

METHODS: Electronic medical records from large tertiary HIV clinical centers in Botswana and Uganda were queried to identify LTNP children 0-18 years enrolled between June 2003 and May 2014 and extract demographic and nutritional parameters. Multivariate subdistribution hazard analyses were used to examine demographic factors and nutritional status in progression in the pre-antiretroviral therapy era.

RESULTS: Between the two countries, 14,246 antiretroviral therapy-naïve …

Should Secondary Pharmacogenomic Variants Be Actively Screened And Reported When Diagnostic Genome-Wide Sequencing Is Performed In A Child?, Jan M Friedman, Yvonne Bombard, Bruce Carleton, Amalia M Issa, Bartha Knoppers, Sharon E Plon, Vasiliki Rahimzadeh, Mary V Relling, Marc S Williams, Clara Van Karnebeek, Danya Vears, Martina C Cornel

Center for Medical Ethics and Health Policy Staff Publications

This white paper was prepared by the Global Alliance for Genomics and Health Regulatory and Ethics Work Stream's Pediatric Task Team to review and provide perspective with respect to ethical, legal, and social issues regarding the return of secondary pharmacogenomic variants in children who have a serious disease or developmental disorder and are undergoing exome or genome sequencing to identify a genetic cause of their condition. We discuss actively searching for and reporting pharmacogenetic/genomic variants in pediatric patients, different methods of returning secondary pharmacogenomic findings to the patient/parents and/or treating clinicians, maintaining these data in the patient's health record over …

A Public Health Perspective On Mitigating The Global Burden Of Chronic Liver Disease, Maya Balakrishnan, Jürgen Rehm

Faculty, Staff and Students Publications

Chronic liver disease is a significant global health problem. Epidemiological trends do not show improvement in chronic liver disease incidence but rather a shift in etiologies, with steatotic liver disease (SLD) from metabolic dysfunction and alcohol becoming increasingly important causes. Consequently, there is a pressing need to develop a comprehensive public health approach for SLD. To that end, we propose a public health framework for preventing and controlling SLD. The framework is anchored on evidence linking physical inactivity, unhealthy dietary patterns, alcohol use, and obesity with both incidence and progression of SLD. Guided by the framework, we review examples of …

Unanswered Questions Following Reports Of Secondary Malignancies After Car-T Cell Therapy, Bruce L Levine, Marcelo C Pasquini, John E Connolly, David L Porter, Michael P Gustafson, Jaap J Boelens, Edwin M Horwitz, Stephan A Grupp, Marcela V Maus, Frederick L Locke, Fabio Ciceri, Annalisa Ruggeri, John Snowden, Helen E Heslop, Crystal L Mackall, Carl H June, Anna M Sureda, Miguel-Angel Perales

Faculty, Staff and Students Publications

Reports of T cell malignancies after CAR-T cell therapy should be investigated, but existing data from follow-up studies suggest a low risk compared with other cancer treatments.

Circulating Tumor Dna And Radiological Tumor Volume Identify Patients At Risk For Relapse With Resected, Early-Stage Non-Small-Cell Lung Cancer, H T Tran, S Heeke, S Sujit, N Vokes, J Zhang, M Aminu, V K Lam, A Vaporciyan, S G Swisher, M C B Godoy, T Cascone, B Sepesi, D L Gibbons, J Wu, J V Heymach

Faculty, Staff and Student Publications

Background: Predicting relapse and overall survival (OS) in early-stage non-small-cell lung cancer (NSCLC) patients remains challenging. Therefore, we hypothesized that detection of circulating tumor DNA (ctDNA) can identify patients with increased risk of relapse and that integrating radiological tumor volume measurement along with ctDNA detectability improves prediction of outcome.

Patients and methods: We analyzed 366 serial plasma samples from 85 patients who underwent surgical resections and assessed ctDNA using a next-generation sequencing liquid biopsy assay, and measured tumor volume using a computed tomography-based three-dimensional annotation.

Results: Our results showed that patients with detectable ctDNA at baseline or after treatment and …

Dermatology Healthcare Utilization In Solid-Organ Transplant Recipients: A Retrospective Cohort Study, Carly F Stender, Lucy J Navsaria, Jiangong Niu, Nasim Khalfe, Candice L Hinkston, Sharon H Giordano, Mackenzie R Wehner

Faculty, Staff and Student Publications

No abstract provided.

Ex Vivo Expanded Cord Blood Natural Killer Cells Combined With Rituximab And High-Dose Chemotherapy And Autologous Stem Cell Transplantation For B Cell Non-Hodgkin Lymphoma, Yago Nieto, Pinaki Banerjee, Indresh Kaur, Kun Hee Kim, Dexing Fang, Peter F Thall, Lori Griffin, Melissa Barnett, Rafet Basar, Chitra Hosing, Jeremy Ramdial, Samer Srour, May Daher, David Marin, Xianli Jiang, Ken Chen, Richard Champlin, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

Relapse is the major cause of failure of high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) for B cell non-Hodgkin lymphomas (B-NHL). Improvement strategies include use in combination with effective immunotherapies. We hypothesized that the combination of rituximab/HDC/ASCT with expanded cord blood (CB)-derived natural killer (NK) cells is safe and active in B-NHL. Patients with B-NHL age 15 to 70 years and appropriate ASCT candidates were eligible for the study. The CB units were selected without considering HLA match with the recipient. The CB NK cells were expanded from day -19 to day -5. Treatment included rituximab on days …

Phase 1/2 Trial Of Avelumab Combined With Utomilumab (4–1bb Agonist), Pf-04518600 (Ox40 Agonist), Or Radiotherapy In Patients With Advanced Gynecologic Malignancies, Anne Knisely, Jibran Ahmed, Bettzy Stephen, Sarina A Piha-Paul, Daniel Karp, Abdulrazzak Zarifa, Siqing Fu, David Sanghyun Hong, Jordi Rodon Ahnert, Timothy A Yap, Apostolia M Tsimberidou, Anas Alshawa, Ecaterina E Dumbrava, Yali Yang, Juhee Song, Funda Meric-Bernstam, Amir A Jazaeri, Aung Naing

Faculty, Staff and Student Publications

Background: Immune checkpoint blockade has shown mixed results in advanced/recurrent gynecologic malignancies. Efficacy may be improved through costimulation with OX40 and 4-1BB agonists. The authors sought to evaluate the safety and efficacy of avelumab combined with utomilumab (a 4-1BB agonist), PF-04518600 (an OX40 agonist), and radiotherapy in patients with recurrent gynecologic malignancies.

Methods: The primary end point in this six-arm, phase 1/2 trial was safety of the combination regimens. Secondary end points included the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors and immune-related Response Evaluation Criteria in Solid Tumors, the disease control rate (DCR), the …

Deep Learning-Based H-Score Quantification Of Immunohistochemistry-Stained Images, Zhuoyu Wen, Danni Luo, Shidan Wang, Ruichen Rong, Bret M Evers, Liwei Jia, Yisheng Fang, Elena V Daoud, Shengjie Yang, Zifan Gu, Emily N Arner, Cheryl M Lewis, Luisa M Solis Soto, Junya Fujimoto, Carmen Behrens, Ignacio I Wistuba, Donghan M Yang, Rolf A Brekken, Kathryn A O'Donnell, Yang Xie, Guanghua Xiao

Faculty, Staff and Student Publications

Immunohistochemistry (IHC) is a well-established and commonly used staining method for clinical diagnosis and biomedical research. In most IHC images, the target protein is conjugated with a specific antibody and stained using diaminobenzidine (DAB), resulting in a brown coloration, whereas hematoxylin serves as a blue counterstain for cell nuclei. The protein expression level is quantified through the H-score, calculated from DAB staining intensity within the target cell region. Traditionally, this process requires evaluation by 2 expert pathologists, which is both time consuming and subjective. To enhance the efficiency and accuracy of this process, we have developed an automatic algorithm for …

Nci10066: A Phase 1/2 Study Of Olaparib In Combination With Ramucirumab In Previously Treated Metastatic Gastric And Gastroesophageal Junction Adenocarcinoma, Michael Cecchini, James M Cleary, Yu Shyr, Joseph Chao, Nataliya Uboha, May Cho, Anthony Shields, Shubham Pant, Laura Goff, Kristen Spencer, Edward Kim, Stacey Stein, Jeremy S Kortmansky, Sandra Canosa, Jeffrey Sklar, Elizabeth M Swisher, Marc Radke, Percy Ivy, Scott Boerner, Diane E Durecki, Chih-Yuan Hsu, Patricia Lorusso, Jill Lacy

Faculty, Staff and Student Publications

Background: Our preclinical work revealed tumour hypoxia induces homologous recombination deficiency (HRD), increasing sensitivity to Poly (ADP-ribose) polymerase inhibitors. We aimed to induce tumour hypoxia with ramucirumab thereby sensitising tumours to olaparib.

Patients and methods: This multi-institution single-arm Phase 1/2 trial enrolled patients with metastatic gastroesophageal adenocarcinoma refractory to ≥1 systemic treatment. In dose escalation, olaparib was evaluated at escalating dose levels with ramucirumab 8 mg/kg day 1 in 14-day cycles. The primary endpoint of Phase 1 was the recommended Phase 2 dose (RP2D), and in Phase 2 the primary endpoint was the overall response rate (ORR).

Results: Fifty-one patients …

Circulating Immune Signatures Across Clinical Stages Of Chronic Pancreatitis: A Pilot Study, Rasmus Hagn-Meincke, Phil A Hart, Dana K Andersen, Santhi S Vege, Evan L Fogel, Jose Serrano, Melena D Bellin, Mark D Topazian, Darwin L Conwell, Liang Li, Stephen K Van Den Eeden, Asbjørn M Drewes, Stephen J Pandol, Chris E Forsmark, William E Fisher, Dhiraj Yadav, Søren S Olesen, Walter G Park, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Objective: This pilot study seeks to identify serum immune signatures across clinical stages of patients with chronic pancreatitis (CP).

Methods: We performed a cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies-study. CP subjects were categorised into three clinical stages based on the presence/absence of metabolic complications: (1) CP with no diabetes and exocrine pancreatic dysfunction (EPD), (2) CP with either diabetes or EPD, and (3) CP with diabetes and EPD. Blinded samples were analysed using an 80-plex Luminex assay of cytokines/chemokines/adhesion molecules. Group and pairwise comparisons were performed to …

Genetic Intratumor Heterogeneity Remodels The Immune Microenvironment And Induces Immune Evasion In Brain Metastasis Of Lung Cancer, Xin Wang, Hua Bai, Jiyang Zhang, Zhijie Wang, Jianchun Duan, Hongqing Cai, Zheng Cao, Qingtang Lin, Xiaosheng Ding, Yiting Sun, Wei Zhang, Xiaoya Xu, Hao Chen, Dadong Zhang, Xiaoli Feng, Jinghai Wan, Jianjun Zhang, Jie He, Jie Wang

Faculty, Staff and Student Publications

Introduction: Brain metastasis, with the highest incidence in patients with lung cancer, significantly worsens prognosis and poses challenges to clinical management. To date, how brain metastasis evades immune elimination remains unknown.

Methods: Whole-exome sequencing and RNA sequencing were performed on 30 matched brain metastasis, primary lung adenocarcinoma, and normal tissues. Data from The Cancer Genome Atlas primary lung adenocarcinoma cohort, including multiplex immunofluorescence, were used to support the findings of bioinformatics analysis.

Results: Our study highlights the key role of intratumor heterogeneity of genomic alterations in the metastasis process, mainly caused by homologous recombination deficiency or other somatic copy number …

Development Of Resistance To Type Ii Jak2 Inhibitors In Mpn Depends On Axl Kinase And Is Targetable, Tamara Codilupi, Jakub Szybinski, Stefanie Arunasalam, Sarah Jungius, Andrew C Dunbar, Simona Stivala, Sime Brkic, Camille Albrecht, Lenka Vokalova, Julie L Yang, Katarzyna Buczak, Nilabh Ghosh, Jakob R Passweg, Alicia Rovo, Anne Angelillo-Scherrer, Dmitry Pankov, Stefan Dirnhofer, Ross L Levine, Richard Koche, Sara C Meyer

Faculty, Staff and Student Publications

PURPOSE: Myeloproliferative neoplasms (MPN) dysregulate JAK2 signaling. Because clinical JAK2 inhibitors have limited disease-modifying effects, type II JAK2 inhibitors such as CHZ868 stabilizing inactive JAK2 and reducing MPN clones, gain interest. We studied whether MPN cells escape from type ll inhibition.

EXPERIMENTAL DESIGN: MPN cells were continuously exposed to CHZ868. We used phosphoproteomic analyses and ATAC/RNA sequencing to characterize acquired resistance to type II JAK2 inhibition, and targeted candidate mediators in MPN cells and mice.

RESULTS: MPN cells showed increased IC50 and reduced apoptosis upon CHZ868 reflecting acquired resistance to JAK2 inhibition. Among >2,500 differential phospho-sites, MAPK pathway activation was …

Racial Discrimination And Interpersonal Violence In Asian American Adolescents During The Covid-19 Pandemic, Yu Lu, Elizabeth Baumler, Leila Wood, Vi D Le, Shannon P Guillot-Wright, Jeff R Temple

Faculty, Staff and Student Publications

PURPOSE: Racial discrimination targeting Asians in the United States has increased sharply since the COVID-19 pandemic. Despite a well-established link with mental/physical health outcomes, little is known about how racial discrimination relates to interpersonal violence, particularly in adolescents. To address this gap in knowledge, we examined cross-sectional and longitudinal (1-year follow-up) associations between racial discrimination and interpersonal violence perpetration and victimization in Asian American adolescents in a large US city.

METHODS: Data from Waves 3 (2020) and 4 (2021) of a randomized clinical trial of a school-based violence prevention program were examined. We limited our sample to participants who identified …

Aleukemic Chronic Myeloid Leukemia Without Neutrophilia And Thrombocytosis: A Report From The Bcr::Abl1 Pathology Group, Daniel Rivera, Wei Cui, Juehua Gao, Deniz Peker, Qian-Yun Zhang, Rajan Dewar, Lianqun Qiu, Sergej Konoplev, Zhihong Hu, Koji Sasaki, Aileen Y Hu, Shuyu E, Meng Liu, Hong Fang, Wei Wang, Guilin Tang, Jane F Apperley, Andreas Hochhaus, Jorge E Cortes, Joseph D Khoury, L Jeffrey Medeiros, Elias Jabbour, Shimin Hu

Faculty, Staff and Student Publications

Chronic myeloid leukemia (CML) is characterized by leukocytosis with left-shifted neutrophilia, basophilia, eosinophilia, and variable thrombocytosis. However, extremely rare cases of patients with CML without significant leukocytosis and thrombocytosis (aleukemic phase [ALP] CML, or CML-ALP) have been reported. Due to its rarity and limited awareness, there remains a significant knowledge gap concerning the pathologic diagnosis, disease progression, and optimal patient management and outcomes. In this multi-institutional study, we investigated 31 patients with CML-ALP. Over half (54.8%) of patients had a history of or concurrent hematopoietic or nonhematopoietic malignancies. At time of diagnosis of CML-ALP, approximately 26.7% of patients exhibited neutrophilia, …

Genomic Staging Of Multifocal Lung Squamous Cell Carcinomas Is Independent Of The Comprehensive Morphologic Assessment, Sanja Dacic, Xuanye Cao, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridion, Sabina Berezowska, Yuchen Han, Jin-Haeng Chung, Mary Beth Beasley, Lin Dongmei, David Hwang, Mari Mino-Kenudson, Yuko Minami, Mauro Papotti, Natasha Rekhtman, Anja C Roden, Erik Thunnissen, Ming-Sound Tsao, Yasushi Yatabe, Akihiko Yoshida, Linghua Wang, Douglas J Hartman, Jacob A Jerome, Humam Kadara, Teh-Ying Chou, Ignacio I Wistuba

Faculty, Staff and Student Publications

Introduction: Morphologic and molecular data for staging of multifocal lung squamous cell carcinomas (LSCCs) are limited. In this study, whole exome sequencing (WES) was used as the gold standard to determine whether multifocal LSCC represented separate primary lung cancers (SPLCs) or intrapulmonary metastases (IPMs). Genomic profiles were compared with the comprehensive morphologic assessment.

Methods: WES was performed on 20 tumor pairs of multifocal LSCC and matched normal lymph nodes using the Illumina NovaSeq6000 S4-Xp (Illumina, San Diego, CA). WES clonal and subclonal analysis data were compared with histologic assessment by 16 thoracic pathologists. In addition, the immune gene profiling of …

Inspiring New Science To Guide Healthcare In Turner Syndrome: Rationale, Design, And Methods For The Insights Registry, Roopa Kanakatti Shankar, Alexandra Carl, Jennifer R Law, Vaneeta Bamba, Wendy J Brickman, Siddharth K Prakash, Tazim Dowlut Mcelroy, Susan Howell, Iris Gutmark Little, Karen O Klein, Catherina T Pinnaro, Kelly Ranallo, Marybel Good, Shanlee M Davis

Faculty, Staff and Student Publications

Inspiring New Science to Guide Healthcare in Turner Syndrome (InsighTS) Registry is a national, multicenter registry for individuals with Turner syndrome (TS) designed to collect and store validated longitudinal clinical data from a diverse cohort of patients with TS. Herein, we describe the rationale, design, and approach used to develop the InsighTS registry, as well as the demographics of the initial participants to illustrate the registry's diversity and future utility. Multiple stakeholder groups have been involved from project conceptualization through dissemination, ensuring the registry serves the priorities of the TS community. Key features of InsighTS include recruitment strategies to facilitate …

Pluripotency Of A Founding Field: Rebranding Developmental Biology, Crystal D Rogers, Chris Amemiya, Swathi Arur, Leslie Babonis, Michael Barresi, Madelaine Bartlett, Richard Behringer, Blair Benham-Pyle, Dominique Bergmann, Ben Blackman, C Titus Brown, Bill Browne, Jasmin Camacho, Chiswili Yves Chabu, Ida Chow, Ondine Cleaver, Jonah Cool, Megan Y Dennis, Alexandra Jazz Dickinson, Stefano Di Talia, Margaret Frank, Stewart Gillmor, Eric S Haag, Iswar Hariharan, Richard Harland, Aman Husbands, Loydie Jerome-Majewska, Kristen Koenig, Carole Labonne, Michael Layden, Chris Lowe, Madhav Mani, Megan Martik, Katelyn Mckown, Cecilia Moens, Christian Mosimann, Joyce Onyenedum, Robert Reed, Ajna Rivera, Dan Rokhsar, Loic Royer, Flora Rutaganira, Rachel Shahan, Neelima Sinha, Billie Swalla, Jaimie M Van Norman, Daniel E Wagner, Athula Wikramanayake, Sophia Zebell, Siobhán M Brady

Faculty, Staff and Student Publications

The field of developmental biology has declined in prominence in recent decades, with off-shoots from the field becoming more fashionable and highly funded. This has created inequity in discovery and opportunity, partly due to the perception that the field is antiquated or not cutting edge. A 'think tank' of scientists from multiple developmental biology-related disciplines came together to define specific challenges in the field that may have inhibited innovation, and to provide tangible solutions to some of the issues facing developmental biology. The community suggestions include a call to the community to help 'rebrand' the field, alongside proposals for additional …

A Surgical Desirability Of Outcome Ranking (Door) Reveals Complex Relationships Between Race/Ethnicity, Insurance Type, And Neighborhood Deprivation, Michael A Jacobs, Susanne Schmidt, Daniel E Hall, Karyn B Stitzenberg, Lillian S Kao, Bradley B Brimhall, Chen-Pin Wang, Laura S Manuel, Hoah-Der Su, Jonathan C Silverstein, Paula K Shireman

Faculty, Staff and Student Publications

Objective: Develop an ordinal Desirability of Outcome Ranking (DOOR) for surgical outcomes to examine complex associations of Social Determinants of Health.

Background: Studies focused on single or binary composite outcomes may not detect health disparities.

Methods: Three health care system cohort study using NSQIP (2013-2019) linked with EHR and risk-adjusted for frailty, preoperative acute serious conditions (PASC), case status and operative stress assessing associations of multilevel Social Determinants of Health of race/ethnicity, insurance type (Private 13,957; Medicare 15,198; Medicaid 2835; Uninsured 2963) and Area Deprivation Index (ADI) on DOOR and the binary Textbook Outcomes (TO).

Results: Patients living in highly …