Digital Commons Network^™

Utilization Of Evidence-Based Secondary Preventive Therapies Post-Acute Coronary Syndrome: A Heart Registry Cohort Study In Kenya, Anthony Ochola, Jasmit Shah, Jeilan Mohamed, Harun Otieno, Anders Barasa, Felix Barasa, Constantine Akwanalo, Benard Gitura, Mzee Ngunga

Internal Medicine, East Africa

Introduction: cardiovascular disease is a growing concern in Africa, with coronary artery disease emerging as a leading cause of mortality. Despite strong evidence and international guidelines recommending secondary prevention therapy post-acute coronary syndrome (ACS)-including antiplatelet agents, statins, beta blockers, and angiotensin-converting enzyme (ACE) inhibitors-suboptimal use remains a concern, especially in low- and middle-income countries. This study aimed to quantify the use of guideline-recommended secondary prevention medications after ACS in Kenya using the data from the Kenya Heart Registry study.

Methods: a cohort study was conducted using data from the Kenya Heart Registry across three hospitals in Kenya from …

International Normative Charts For Twin Weight, Length, And Head Circumference At Birth, By Gestational Age And Sex: The Twin Neonatal Cross-Sectional Study Of The Intergrowth-21st Project, Francesca Giuliani, Sonia Deantoni, Enrico Bertino, Yasmin A. Jaffer, Manorama Purwar, Fernando C. Barros, Leila Cheikh Ismail, Wu Qingqing, Ilaria Stura, Maria Carvalho

Obstetrics and Gynaecology, East Africa

Assessing the size of twins at birth using charts developed for singletons may over diagnose small for gestational age in this sub-population. The study aimed to produce international, twin-specific, newborn size normative charts by gestational age and sex. This longitudinal observational study in eight geographically diverse settings prospectively collected data between May 2009 and August 2013 from healthy pregnant women and their newborn twins. The participants were enrolled as part of the INTERGROWTH-21st study, and recruited based on World Health Organization recommendations for evaluation of anthropometric measures. All the women met, in addition to the underlying population characteristics of low …

Normative Growth Trajectories Of Fetal Brain Regions Validated By Satisfactory Maturation Of Neurodevelopmental Domains At 2 Years Of Age, Madeleine Wyburd, Stephen Kennedy, Michelle Fernandes, Nicola Dinsdale, Linde Hesse, Robert Gunier, Leila Ismail, Eric Ohuma, Michael Gravett, Maria Carvalho

Obstetrics and Gynaecology, East Africa

We previously constructed a qualitative, 3D ultrasound derived atlas of the normative spatiotemporal dynamics of fetal brain maturation. Here, using the same healthy multi-national cohort, we applied deep learning methods to 4205 fetal brain scans from 18–27 weeks’ gestation, to produce an extensive, quantitative description of the growth of 16 fetal brain structures associated with satisfactory domain-specific neurodevelopmental scores at 2 years of age. The methodology, which is publicly available, takes less than 10 seconds per scan. We define 28 region-specific, functionally relevant, normative growth trajectories, a ratio between the relative volumes of the insular (rILV) and parietal (rPLV) lobes …

The Use Of A Standardized Checklist For Image Acquisition: An Obstetric Ultrasound Quality Improvement Study, Ingrid Gichere, Nidhi Leekha, Sikolia Wanyonyi

Obstetrics and Gynaecology, East Africa

Introduction A complete anatomical survey during the mid-trimester ultrasound is critical for detecting fetal anomalies. In sub-Saharan Africa, detection rates remain low, contributing to a significant disease burden. This study evaluated whether implementing a standardized electronic checklist, based on existing guidelines, would improve image acquisition.

Methods We carried out a pre- and post-intervention quasi-experimental quality improvement study. An electronic checklist replaced the previous ultrasound report template. A baseline review involved 385 mid-trimester scans conducted between November 2022 and December 2023. Following checklist implementation and targeted sonographer training, 238 scans were reassessed from July to December 2024. The image acquisition rate …

Can Tanzanian Neurosurgeons Access Tanzanian Neurosurgical Literature? A Systematic Review And Survey Of Neurosurgical Publications, Romani R. Sabas, Julie Woodfield, Chibuikem Anthony Ikwuegbuenyi, Magalie Cadieux, Consolata Shayo, Zarina Shabhay, Happiness Rabiel, Beverly Cheserem, Joel Bwemelo, Drew N. Wright

General Surgery, East Africa

Background and Objectives: Free and open access to research data and findings promotes equity in access to healthcare knowledge and equity in patient care and treatment. To benefit the health care of the population studied, research findings must be accessible to clinicians, academics, and policymakers serving those populations. The aim of this study was to assess the extent of published Tanzanian neurosurgical data and its accessibility to those practicing within the country.

Methods: A systematic review of all published neurosurgical studies from Tanzania was conducted. Authorship, funding, and open-access status were recorded. Tanzanian neurosurgeons were surveyed by telephone or in …

Mapping Social Determinants Of Health Data In Sub-Saharan Africa: A Scoping Review Protocol, Felix Anyiam, Jessica Gjonaj, Ngeresa Osango, Richard Mugo, Peace Aber, Jasmit Shah, Judith Mangeni, Rajesh Vedanthan, Joseph Hogan, Ann Mwangi

Internal Medicine, East Africa

Introduction Research has increasingly underscored the impact of factors such as socioeconomic status, education, healthcare access, housing and environmental conditions in shaping population health outcomes. These factors, collectively called social determinants of health (SDOH), provide crucial context for understanding drivers of health outcomes. In sub-Saharan Africa (SSA), the study of SDOH is critical due to the region’s unique sociocultural and economic conditions. Understanding how SDOH interacts with health systems and capturing SDOH in data is crucial for informing modelling efforts and policies improving population health more effectively. This scoping review aims to map the types of data used to capture …

Evaluation Of The Intempo Path Set For Cyberknife Prostate And Lung Sbrt: A Single-Institution Experience, Yingcui Jia, Lei Fu, Shari Rudoler, Eric Gressen, Yevgeniy Vinogradskiy, Qianyi Xu

Department of Radiation Oncology Faculty Papers

PURPOSE: The InTempo adaptive imaging system is an important component of the Accuray CyberKnife System, designed to enhance the system's ability to track and correct tumor motion during treatment. However, a limitation of this feature is the reduction of available nodes for treatment planning. The impact of a reduced number of nodes on the quality of InTempo-based treatment plans has not previously been evaluated. This retrospective study aims to compare the dosimetry of CyberKnife plans with and without The InTempo path set for both prostate and lung stereotactic body radiotherapy (SBRT).

METHODS: This study included twelve consecutive prostate SBRT patients …

High-Flow Oxygen Therapy In Ild Exacerbations: An Imperfect Therapy, Kathleen Spritzer, Jesse Roman, Ross Summer, Gautam George

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

No abstract provided.

Intraoperative Care And Complications Of Symptomatic Adolescent And Young Adult Patients Undergoing Laparoscopy To Diagnose And/Or To Treat Endometrioses: A Multi-Institutional Review., Jacquelyn R. Evans, Katherine Bergus, Lindsey Asti, Lesley L. Breech, Ruiqi Cen, Yuan Yuan Gong, S Paige Hertweck, Holly R. Hoefgen, Anne H. Horne, Ashli A. Lawson, Seema Menon, Kathleen E. O'Brien, Shashwati Pradhan, Brenna Rachwal, Yolanda R. Smith, Priya Suvarna, Sarah Van Son, Geri Hewitt

Manuscripts, Articles, Book Chapters and Other Papers

STUDY OBJECTIVE: This multi-institutional, retrospective study explores the risks of laparoscopy for diagnosis and treatment of endometriosis to facilitate shared medical decision-making in patients age < 22 years old with chronic pain considering surgery.

METHODS: A retrospective review of patients less than 22 years old who had surgically proven endometriosis at eight pediatric hospitals was completed. Patient demographics, operative interventions, concurrent procedures, and complications were evaluated.

RESULTS: There were 284 patients with pathologically confirmed endometriosis with a median age of 16.86 years (15.51, 18.06). During the index procedure, diagnostic biopsy alone was performed (35.92%), followed by ablation (29.93%), excision (20.07%), excision and ablation (12.68%), and cryoablation (1.41%). Most common …

The Influence Of Preoperative Bowel Preparation On Surgical Site Infection In Pediatric Colorectal Surgery., Katlyn G. Mckay, Naomi-Liza Denning, Rebecca M. Rentea, Eunice Y. Huang

Manuscripts, Articles, Book Chapters and Other Papers

Surgical site infection (SSI) is one of the most common nosocomial infections that occur in pediatric patients in the United States, with colorectal procedures consistently demonstrating the highest rates of SSI. Strategies to reduce SSI in colorectal surgery include standardized perioperative colorectal care bundles, which commonly incorporate preoperative bowel preparation. Robust adult literature exists supporting the use of mechanical bowel preparation in combination with oral antibiotics to mitigate SSI; however, pediatric evidence remains less definitive. Current pediatric literature shows heterogeneity of bowel preparation use amongst surgeons, with existing literature consisting primarily of small retrospective studies. A well-designed pediatric randomized controlled …

Longitudinal Peripheral Blood Transcriptomics Reveal Novel Signatures During Cardiac Allograft Rejection., Rachad Ghazal, Min Wang, Akshatha N. Srinivas, Jenny J. Cao, Hridyanshu Vyas, Duan Liu, Asha Nair, Byron H. Smith, Li Wang, Daniel S. Yip, Parag C. Patel, David E. Steidley, Brian W. Hardaway, Alfredo L. Clavell, Sudhir S. Kushwaha, Walter D. Park, Mark D. Stegall, Howard Eisen, Naveen L. Pereira

Division of Cardiology Faculty Papers

Background: Acute cellularrejection (ACR) remains a major cause of morbidity afterhearttransplantation despite advances in immunosuppression. Whole genometranscriptomicprofiling offers a systems-based, unbiased approach to elucidate the molecular mechanisms underlying ACR. However, noninvasive,longitudinal biomarker assessments capable of capturing the temporal dynamics ofrejection biology remain scarce.

Methods: RNA sequencing ofperipheralblood fromheart transplant recipients before, during, and after ACR was compared with nonrejection controls. Pathway analysis was conducted using differentially expressed genes (DEGs), and a machine learning approach was applied to assessgene-based prediction of ACR.

Results: A total of 235 rejection-specific significant DEGs and 863 postrejection DEGs (false discovery rate < 0.05) were identified. During ACR, DEGs were enriched for T-cell activation/differentiation, apoptosis, and B-cell receptor signaling pathways. By combining the 2 sets of DEGs, a panel of 71 common genes was identified that reflected the significant, longitudinal transcriptomic dynamics of ACR. In an elastic net machine learning-based classifier, DYNLL1 and SERF2 were …

Rare Heterozygous Missense Variants In Vsx2 Are Associated With Retinal Detachment, Daniel C Brock, Justin S Dhindsa, Yifan Chen, Vida Ravanmehr, Jonathan Mitchell, Fengyuan Hu, Xiaoyin Li, Likhita Nandigam, Quanli Wang, Kevin Wu, Jessica C Butts, Hardeep S Dhindsa, Benjamin J Frankfort, Nicholas M Tran, Slavé Petrovski, Ryan S Dhindsa

Duncan NRI Faculty and Staff Publications

Retinal detachment (RD) is a sight-threatening emergency requiring urgent intervention to prevent permanent vision loss. While both environmental and genetic risk factors contribute to RD, its complete genetic architecture remains unknown. Here, we performed the largest whole genome sequencing-based case-control study in RD to date, including data from 7,276 RD cases and 236,741 controls in the UK Biobank. Through variant- and gene-level association analyses, we identified VSX2 as a genetic determinant of RD risk while confirming established associations including FAT3, RDH5, and COL2A1. Gene-level collapsing analysis revealed that rare heterozygous missense variants in VSX2 confer a 2.8-fold …

Real-World Prevalence Of Pd-L1 Positivity In Early-Stage/Metastatic Triple-Negative Breast Cancer: Primary Results And Pathology Insights From The Global Retrospective Observational Vanessa Study, Corrado D'Arrigo, Sitki Tuzlali, Romualdo Barroso-Sousa, Nagi El Saghir, Rebecca Dent, Nataša Medić-Milijić, Gyungyub Gong, Shahin Sayed, Tu Anh, Alisan Zirtiloglu

Pathology, East Africa

Aim To understand whether the worldwide implementation of PD-L1 testing in triple-negative breast cancer (TNBC) can be achieved in routine clinical practice.

Methods and results The multicentre retrospective observational VANESSA study consecutively and uniformly enrolled patients treated with systemic therapy for early or metastatic (e/m)TNBC diagnosed between 2014 and 2017. PD-L1 status was retrospectively assessed locally and centrally using the VENTANA PD-L1 (SP142) Assay (PD-L1 expression on tumour-infiltrating immune cells covering ≥1% of the tumour area). The primary objective was to determine the prevalence of PD-L1 positivity assessed locally on primary and/or metastatic tumour tissue. Concordance between local and central …

Investigation Of Teratogenic Concerns In The Coronavirus Disease Of 2019 Era, Kate Richardson, Emily C Daykin, Kathleen Shields, S Shahrukh Hashmi, Lorrie Harris-Sagaribay, Molly Daniels, Myla Ashfaq

Faculty, Staff and Student Publications

Background: MotherToBaby (MTB) is a teratogen information service that provides information about exposures during pregnancy and breastfeeding to the public and healthcare providers. During the Coronavirus Disease of 2019 (COVID-19) pandemic, MTB received an influx of queries regarding the teratogenicity of the virus and the vaccine. The purpose of this study was to assess the frequency and type of exposures asked about prior to the onset of the COVID-19 pandemic through March 2022 and to evaluate the demographics of individuals who made inquiries.

Methods: Data from MTB contacts (2018-2022) were accessed through a data-sharing agreement. The data were cleaned and …

Development And Implementation Of An Mri-Only Simulation, Planning, And Treatment Workflow For Prostate Radiotherapy Using Synthetic Ct On Mr-Linac, Reza Reiazi, Yao Ding, Sarath Vijayan, Jinzhong Yang, Ergys Subashi, Yao Zhao, Belinda M Lee, Hunter L Emory, Vi T Dinh, Greg L Swiedom, Jie Deng, Mu-Han Lin, Peter Balter, Rajat J Kudchadker, Elaine E Cha, Seungtaek Choi, Yusung Kim, Eun Young Han, Surendra Prajapati

Faculty, Staff and Student Publications

Purpose: We evaluated the feasibility of a magnetic resonance (MR)-only simulation, planning, and treatment (MROSPT) workflow for prostate cancer patients using synthetic computed tomography (sCT) generated from magnetic resonance imaging (MRI) data. By validating sCT-based dose calculations, we aimed to streamline radiotherapy workflows, eliminate the need for CT simulation, and enable reliable clinical implementation of MR-based radiotherapy for MR-linac (MRL).

Methods: We developed a comprehensive workflow encompassing the entire process from initial consultation to treatment delivery. After developing the workflow, a retrospective dosimetric validation study was performed on nine men with prostate cancer. They underwent CT and MRI simulations, and …

Utilization Of Intensive Care Interventions In Critically Ill Patients With Candidemia Versus Bacteremia: A Multicenter Retrospective Cohort Study, Mary North Jones, Masayuki Nigo, Stefano Casarin, James Kurian, Aarjav Sanghvi, Enshuo Hsu, Stephen L Jones, Ashton Connor, David B Corry, Cesar A Arias, Max W Adelman

Faculty, Staff and Students Publications

Objectives: Candida species are one of the most common causes of ICU-onset bloodstream infection (BSI). Yet, there is no robust guidance on when to initiate empiric antifungals for ICU patients suspected of BSI. We compared patients with ICU-onset candidemia vs. ICU-onset bacteremia to determine which patients may benefit from empiric antifungals.

Design: We compared characteristics between patients with bacteremia vs. candidemia at time of culture. We determined risk factors for death and constructed a multivariable regression to determine if candidemia is an independent risk factor for death.

Setting/patients: We included ICU patients from a hospital system in Houston, Texas (n …

Phase 1b Pilot Study Of Itacitinib With Alemtuzumab In Patients With T-Cell Prolymphocytic Leukemia, Tapan M Kadia, Akhil Jain, Caitlin R Rausch, Alex Bataller, Farhad Ravandi, Elias Jabbour, Wei Qiao, Gautam Borthakur, Nicholas Short, Guillermo Montalban-Bravo, Andres E Quesada, Jan Burger, Alessandra Ferrajoli, William Wierda, Chitra Hosing, Hagop Kantarjian

Faculty, Staff and Student Publications

T-cell prolymphocytic leukemia (T-PLL) is a mature T-cell neoplasm with an aggressive clinical course. Overall prognosis is poor, and treatment relies on alemtuzumab because of inadequate response to conventional chemotherapy. Three-quarters of cases harbor activating mutations in the JAK-STAT pathway (JAK1, JAK3, STAT5B, IL2RG). We report safety and efficacy from a phase 1B study evaluating the combination of the JAK1 inhibitor itacitinib with alemtuzumab. Patients (N = 15) were aged >18 years, with treatment-naïve (n = 8) or relapsed/refractory (n = 7) T-PLL with adequate organ function, European Cooperative Oncology Group Performance Status ≤2, and …

First Report Of Response To Tarlatamab In A Patient With Histologic-Transformed Sclc From Alk-Rearranged Nsclc: Case Report, Kaiwen Wang, Ceylan Altintas Taslic, Patricia De Groot, Mitchell A Parma, Alvaro Guimaraes Paula, Melody Caranto, Komal Shah, Mukulika Bose, Cole Ruoff, Loukia G Karacosta, Lauren A Byers, Carl M Gay, Jianjun Zhang, John V Heymach, Bingnan Zhang

Faculty, Staff and Student Publications

Small cell transformation has been described as a resistance mechanism to targeted therapy treated in patients with EGFR-mutated NSCLC and less often reported with those with other actionable oncogenic alterations, including ALK-rearranged NSCLC. Given lack of standard-of-care treatments for patients with actionable oncogenic alteration NSCLC transformed to SCLC, this remains a challenge and unmet need for treating these patients.

Here, we present a case of a patient with ALK-rearranged NSCLC with transformation to SCLC, who has progressed on several lines of therapies and successfully treated with tarlatamab to elicit and maintain clinical benefit, including intracranial response.

Fireproof: Intricacies Of Microglial Biology, Wei Cao

Faculty, Staff and Student Publications

No abstract provided.

Outcomes Of Therapy-Related Non-Core Binding Factor Acute Myeloid Leukemia With Venetoclax-Based Therapies, Jayastu Senapati, Jennifer Croden, Guillermo Garcia-Manero, Koichi Takahashi, Naval G Daver, Tapan M Kadia, Gautam Borthakur, Nicholas James Short, Elias Jabbour, Fadi Haddad, Jennifer Marvin-Peek, Hussein A Abbas, Prithviraj Bose, Guilin Tang, Sanam Loghavi, Elizabeth J Shpall, Jeremy Ramdial, Uday R Popat, Richard E Champlin, Farhad Ravandi, Hagop M Kantarjian, Courtney D Dinardo

Faculty, Staff and Student Publications

Prognosis in therapy‐related acute myeloid leukemia (T‐AML) remains poor, but understanding outcomes with venetoclax (VEN)‐based therapy is relevant. We retrospectively analyzed 317 adult patients with newly diagnosed T‐AML focusing on lower intensity therapy (LIT) VEN‐containing regimens. Patients with an antecedent myeloid disorder before AML diagnosis were excluded. The median age was 69 years (range 21–92); 50% evaluated patients had a complex karyotype, and 40% evaluated patients had a TP53 mutation. Composite complete response rates were higher with LIT + VEN compared to LIT (58% vs. 40%, P = 0.003) but were similar in intensive chemotherapy (IC) + VEN versus IC …

Circulating Fatty Acid Binding Protein 4 (Fabp-4) Concentrations And Mortality In Individuals With Colorectal Cancer In The European Prospective Investigation Into Cancer And Nutrition Study, Thu Thi Pham, Katharina Nimptsch, Krasimira Aleksandrova, Mazda Jenab, Veronika Fedirko, Anja Olsen, Anne Tjønneland, Claire Cadeau, Gianluca Severi, Matthias B Schulze, Renée Turzanski Fortner, Verena Katzke, Claudia Agnoli, Carlotta Sacerdote, Rosario Tumino, Simona Signoriello, Camino Trobajo-Sanmartín, Jesús-Humberto Gómez, María-Dolores Chirlaque, Maria-Jose Sánchez, Marta Crous-Bou, Anne May, Alicia Heath, Dagfinn Aune, Elisabete Weiderpass, Tobias Pischon

Faculty, Staff and Student Publications

Human fatty acid binding protein‐4 (FABP‐4), a protein elevated in obesity that promotes colon cancer cell invasiveness and metastasis, may be associated with higher mortality in individuals with colorectal cancer (CRC) and may serve as a mediator of the obesity–mortality association in these individuals. We used a causal diagram to inform covariate selection and applied Cox proportional hazards models to estimate hazard ratios (HRs) for CRC‐specific, non‐CRC‐specific, and all‐cause mortality by FABP‐4 levels measured in baseline blood samples from 1371 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. Competing risk analyses were adapted for CRC …

Hypoglossal Neuropathy In The Pathogenesis Of Fibrosis-Related Late-Radiation Associated Dysphagia: A Correlative Analysis Utilizing Electromyography To Explore The Frequency Of Clinical And Subclinical Neuropathy In A Pilot Dysphagia Trial, Holly Mcmillan, Christine Okoro, Sheila Buoy, Karin Woodman, Nicolaas Anderson, Clifton Fuller, Stephen Y Lai, Katherine Hutcheson

Faculty, Staff and Student Publications

Background: Late radiation-associated dysphagia (late-RAD) commonly presents in patients with signs of hypoglossal neuropathy, with hallmark clinical features including lingual atrophy, deviation, and fasciculation. Gold-standard electromyography (EMG) has not been used to explore the frequency of hypoglossal neuropathy in patients with late-RAD.

Methods: Exploratory post hoc secondary analysis of MANTLE trial (NCT03612531) was completed. The presence of cranial nerve XII (CN XII) neuropathy was classified by (1) features of clinical assessment as well as (2) intramuscular genioglossus EMG pre-MANTLE intervention in disease-free HNC survivors ≥ 2 years post-radiotherapy (RT) with grade ≥ 2 fibrosis and dysphagia.

Results: All …

Impact Of Treatment Interruption On Outcomes In Head And Neck Cancer: Nrg/Rtog Secondary Analysis, Laila A Gharzai, Emily Morris, Matthew J Schipper, Kelley M Kidwell, Phuc Felix Nguyen-Tân, David I Rosenthal, Maura L Gillison, Richard C Jordan, Adam S Garden, Shlomo A Koyfman, Jimmy J Caudell, Dukagjin M Blakaj, Neal E Dunlap, Greg A Krempl, John M Longo, Christopher U Jones, Michael F Gensheimer, Thomas J Galloway, Lyudmila Demora, Quynh-Thu Le, Jennifer L Shah, Krithika Suresh, Michelle Mierzwa

Faculty, Staff and Student Publications

Importance: Historical evidence demonstrated that delays or interruptions in radiotherapy (RT) are associated with poorer oncologic outcomes in head and neck squamous cell carcinoma (HNSCC). Substantial concerns arose during the COVID-19 pandemic, when treatment schedules were frequently disrupted.

Objective: To determine the association of RT interruptions with locoregional failure (LRF) and overall survival (OS).

Design, setting, and participants: This retrospective review and secondary analysis of 3 randomized clinical trials (NRG/RTOG 0129, 0522, and 1016) included patients enrolled in the trials who were treated with RT. Patients with HNSCC were grouped as (1) p16-positive oropharynx (p16+ OPSCC) and (2) p16-negative oropharynx …

Identification Of Raptor And Gli1 As Usp37 Substrates Highlight Its Context-Specific Function In Medulloblastoma Cells, Ashutosh Singh, Donghang Cheng, Amanda R Haltom, Yanwen Yang, Tara Dobson, Rashieda Hatcher, Veena Rajaram, Vidya Gopalakrishnan

Faculty, Staff and Student Publications

The USP37 gene encodes a deubiquitylase (DUB), which catalyzes the proteolytic removal of ubiquitin moieties from proteins to modulate their stability, cellular localization or activity. Its expression is downregulated in a subgroup of medulloblastomas driven by constitutive activation of sonic hedgehog (SHH) signaling. Patients with SHH-driven medulloblastomas with elevated expression of the RE1 silencing transcription factor (REST) and reduced expression of USP37 have poor outcomes. In previous studies, we showed sustained proliferation of SHH-medulloblastoma cells due to blockade of terminal cell cycle exit and neuronal differentiation stemming from a failure in USP37-dependent stabilization of its target, the cyclin-dependent kinase inhibitor …

Introducing A New Frontier In The Journal Of Pediatric Rehabilitation Medicine: An Interdisciplinary Approach Throughout The Lifespan: The Pediatric Brain Injury Section, Michael Green, Glendaliz Bosques, Kimberly Davis, Brenda Eagan-Johnson, Carty Husted

Faculty, Staff and Student Publications

No abstract provided.

Circulating Metabolites, Genetics And Lifestyle Factors In Relation To Future Risk Of Type 2 Diabetes, Jun Li, Jie Hu, Huan Yun, Zhendong Mei, Xingyan Wang, Kai Luo, Marta Guasch-Ferré, Xikun Han, Buu Truong, Jordi Merino, Chengyong Jia, Miguel Ruiz-Canela, Casey M Rebholz, Eun Hye Moon, Taryn Alkis, Guning Liu, Jie Yao, Xiyuan Zhang, Bianca C Porneala, Jordi Salas-Salvadó, Thomas J Wang, Josée Dupuis, Elizabeth Selvin, Xiuqing Guo, Shilpa N Bhupathiraju, Jennifer A Brody, Yongmei Liu, Alexis C Wood, Kari E North, Su Yon Jung, Ching-Ti Liu, Nona Sotoodehnia, Simin Liu, Lesley F Tinker, A Heather Eliassen, Joann E Manson, Jose C Florez, Robert E Gerszten, Clary B Clish, Liming Liang, Rozenn N Lemaitre, Katherine L Tucker, Stephen S Rich, Jerome I Rotter, Miguel Angel Martínez-González, Kathryn M Rexrode, James B Meigs, Eric Boerwinkle, Robert C Kaplan, Frank B Hu, Bing Yu, Qibin Qi

Faculty, Staff and Student Publications

The human metabolome reflects complex metabolic states affected by genetic and environmental factors. However, metabolites associated with type 2 diabetes (T2D) risk and their determinants remain insufficiently characterized. Here we integrated blood metabolomic, genomic and lifestyle data from up to 23,634 initially T2D-free participants from ten cohorts. Of 469 metabolites examined, 235 were associated with incident T2D during up to 26 years of follow-up, including 67 associations not previously reported across bile acid, lipid, carnitine, urea cycle and arginine/proline, glycine and histidine pathways. Further genetic analyses linked these metabolites to signaling pathways and clinical traits central to T2D pathophysiology, including …

Acta2 Pathogenic Variants Activating Heat Shock Factor 1 And Increasing Cholesterol Biosynthesis In Smooth Muscle Cells Predispose To Early Onset Atherosclerosis, Maura L Boerio, Abhijnan Chattopadhyay, Xue-Yan Duan, Aamuktha Karla, Ernesto Calderon Martinez, Amelie Pinard, Andrew K Morse, Darshan Reddy, Sree Dharma, Walter Velasco-Torrez, Julien Marcadier, Siddharth K Prakash, Sherene Shalhub, Julie De Backer, Richmond Jeremy, Shaine A Morris, Anji T Yetman, Alan C Braverman, Dianna M Milewicz

Faculty, Staff and Student Publications

Background: ACTA2 pathogenic variants predispose to thoracic aortic disease, and a subset of variants lead to early onset atherosclerotic cardiovascular disease (ASCVD). The molecular pathway linking misfolded SMA (α-smooth muscle actin) monomers to augmented atherosclerosis-associated smooth muscle cell phenotypic modulation can be modeled in vitro by stably expressing the ACTA2 p.R149C variant in Acta2-/- smooth muscle cells.

Methods: The Montalcino Aortic Consortium patient registry was used to identify cases with ACTA2 pathogenic/likely pathogenic missense variants. These patients were surveyed, and medical records were reviewed, to identify cases with early onset ASCVD. The variants for these cases, as well as …

Composite Mantle Cell Lymphoma And Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Diagnostic And Therapeutic Challenge, Matthew T Ye, Yaling Yang, M James You

Faculty, Staff and Student Publications

No abstract provided.

Quantitative Analysis Of Robustness-Based Versus Let-Based Optimization In Intensity-Modulated Proton Therapy For Pediatric Brain Tumors, Fariha Kabir Torsha, Gino Lim, Hadis Moazami Goudarzi, Radhe Mohan, David Grosshans, Wenhua Cao

Faculty, Staff and Student Publications

Purpose: To perform a quantitative analysis of the trade-off between robustness-based and linear energy transfer (LET)-based optimization of intensity-modulated proton therapy for anatomically challenging pediatric brain tumor cases.

Methods: Three pediatric brain tumor patients were included in this study. Three plans were generated for each case based on: (1) nominal optimization, without considering uncertainties and LET; (2) robust optimization, including proton range and patient setup uncertainties; and (3) LET optimization, considering increasing LET in the target and reducing LET in normal tissues. All plans were optimized with individually fine-tuned objective weighing to obtain highest achievable target coverage and meet dose …

The American College Of Radiology Diagnostic Fluoroscopy Dose Index Registry Pilot: Dosimetric Performance And Benchmarking Challenges, Steve D Mann, Donald L Miller, Grant Fong, Allen R Goode, Emily L Marshall, Thomas Nishino, Pavlina Boxx, Liqiang Ren, Celalettin Topbas, Alan H Schoenfeld, Vivek Singh, Jie Zhang

Faculty, Staff and Student Publications

Background: The ACR Diagnostic Fluoroscopy Dose Index Registry (DIR-Fluoro) is expanding to include diagnostic fluoroscopy. Variations in dose reference points and overhead radiography events may introduce unique challenges for benchmarking.

Purpose: To survey the technological status and dosimetric performance of fluoroscopes participating in the DIR-Fluoro pilot project, focusing on longitudinal stability and variability of fluoroscopic dose reporting accuracy across multiple institutions and vendors.

Methods: Sixty-six fluoroscopic systems from nine institutions (24 facilities) were surveyed for facility type, fluoroscope type, image receptor type, age, dose reporting capabilities, and other key features. Of these, 56 were evaluable. Semi-annual measurements assessed reference air …