Medicine and Health Sciences Commons^™

Single-Nucleotide Variant Calling In Single-Cell Sequencing Data With Monopogen, Jinzhuang Dou, Li Ding, Et Al.

2020-Current year OA Pubs

Single-cell omics technologies enable molecular characterization of diverse cell types and states, but how the resulting transcriptional and epigenetic profiles depend on the cell's genetic background remains understudied. We describe Monopogen, a computational tool to detect single-nucleotide variants (SNVs) from single-cell sequencing data. Monopogen leverages linkage disequilibrium from external reference panels to identify germline SNVs and detects putative somatic SNVs using allele cosegregating patterns at the cell population level. It can identify 100 K to 3 M germline SNVs achieving a genotyping accuracy of 95%, together with hundreds of putative somatic SNVs. Monopogen-derived genotypes enable global and local ancestry inference …

Red Flag Signs And Symptoms For Patients With Early-Onset Colorectal Cancer: A Systematic Review And Meta-Analysis, Joshua Demb, Cassandra D L Fritz, Yin Cao, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Early-onset colorectal cancer (EOCRC), defined as a diagnosis at younger than age 50 years, is increasing, and so-called red flag signs and symptoms among these individuals are often missed, leading to diagnostic delays. Improved recognition of presenting signs and symptoms associated with EOCRC could facilitate more timely diagnosis and impact clinical outcomes.

OBJECTIVE: To report the frequency of presenting red flag signs and symptoms among individuals with EOCRC, to examine their association with EOCRC risk, and to measure variation in time to diagnosis from sign or symptom presentation.

DATA SOURCES: PubMed/MEDLINE, Embase, CINAHL, and Web of Science were searched …

Astrocytes As A Mechanism For Contextually-Guided Network Dynamics And Function, Lulu Gong, Fabio Pasqualetti, Thomas Papouin, Shinung Ching

2020-Current year OA Pubs

Astrocytes are a ubiquitous and enigmatic type of non-neuronal cell and are found in the brain of all vertebrates. While traditionally viewed as being supportive of neurons, it is increasingly recognized that astrocytes play a more direct and active role in brain function and neural computation. On account of their sensitivity to a host of physiological covariates and ability to modulate neuronal activity and connectivity on slower time scales, astrocytes may be particularly well poised to modulate the dynamics of neural circuits in functionally salient ways. In the current paper, we seek to capture these features via actionable abstractions within …

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum And Novel Clinical Observations In 241 Patients, Rachael C. Heath Jeffery, Jennifer A. Thompson, Johnny Lo, Enid S. Chelva, Sean Armstrong, Jose S. Pulido, Rebecca Procopio, Andrea L. Vincent, Lorenzo Bianco, Maurizio Battaglia Parodi, Lucia Ziccardi, Giulio Antonelli, Lucilla Barbano, João P. Marques, Sara Geada, Ana L. Carvalho, Wei C. Tang, Choi M. Chan, Camiel J. F. Boon, Jonathan Hensman, Ta-Ching Chen, Chien-Yu Lin, Pei-Lung Chen, Ajoy Vincent, Anupreet Tumber, Elise Heon, John R. Grigg, Robyn V. Jamieson, Elisa E. Cornish, Benjamin M. Nash, Shyamanga Borooah, Lauren N. Ayton, Alexis Ceecee Britten-Jones, Thomas L. Edwards, Jonathan B. Ruddle, Abhishek Sharma, Rowan G. Porter, Tina M. Lamey, Terri L. Mclaren, Samuel Mclenachan, Danial Roshandel, Fred K. Chen

Wills Eye Hospital Papers

PURPOSE: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene.

METHODS: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations.

RESULTS: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, …

Outcomes Of Infectious Panuveitis Associated With Simultaneous Multi-Positive Ocular Fluid Polymerase Chain Reaction, Viet Q. Chau, John W. Hinkle, Chris Y. Wu, Parastou Pakravan, Vincent Volante, Jesse D. Sengillo, Patrick C. Staropoli, Darlene Miller, Nicolas A. Yannuzzi, Thomas A. Albini

Wills Eye Hospital Papers

PURPOSE: To evaluate features of infectious panuveitis associated with multiple pathogens detected by ocular fluid sampling.

METHODS: Single-center, retrospective, consecutive case series of patients with aqueous/vitreous polymerase chain reaction testing with >1 positive result in a single sample from 2001 to 2021.

RESULTS: Of 1,588 polymerase chain reaction samples, 28 (1.76%) were positive for two pathogens. Most common pathogens were cytomegalovirus (n = 16, 57.1%) and Epstein-Barr virus (n = 13, 46.4%), followed by varicella zoster virus (n = 8, 28.6%), Toxoplasma gondii (n = 6, 21.4%), herpes simplex virus 2 (n = 6, 21.4%), herpes simplex virus 1 (n …

Travel-Time Disparities In Access To Proton Beam Therapy For Cancer Treatment, Todd Burus, Alexander Vanhelene, Michael Rooney, Krystle Lang Kuhs, W. Jay Christian, Christopher Mcnair, Sanjay Mishra, Arnold Paulino, Grace Smith, Steven Frank, Jeremy Warner

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

IMPORTANCE: Proton beam therapy is an emerging radiotherapy treatment for patients with cancer that may produce similar outcomes as traditional photon-based therapy for many cancers while delivering lower amounts of toxic radiation to surrounding tissue. Geographic proximity to a proton facility is a critical component of ensuring equitable access both for indicated diagnoses and ongoing clinical trials.

OBJECTIVE: To characterize the distribution of proton facilities in the US, quantify drive-time access for the population, and investigate the likelihood of long commutes for certain population subgroups.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study analyzed travel times to proton facilities in …

Prevalence Of Distal Symmetrical Polyneuropathy By Diabetes Prevention Program Treatment Group, Diabetes Status, Duration Of Diabetes, And Cumulative Glycemic Exposure, Christine G Lee, Adam Ciarleglio, Sharon L Edelstein, Jill P Crandall, Dana Dabelea, Ronald B Goldberg, Steven E Kahn, William C Knowler, Maxwell T Ma, Neil H White, William H Herman, Diabetes Prevention Program Research Group

Children’s Nutrition Research Center Staff Publications

Objective: To assess associations between distal symmetric polyneuropathy (DSPN) and Diabetes Prevention Program (DPP) treatment groups, diabetes status or duration, and cumulative glycemic exposure approximately 21 years after DPP randomization.

Research design and methods: In the DPP, 3,234 adults ≥25 years old at high risk for diabetes were randomized to an intensive lifestyle (ILS), metformin, or placebo intervention to prevent diabetes. After the DPP ended, 2,779 joined the Diabetes Prevention Program Outcomes Study (DPPOS). Open-label metformin was continued, placebo was discontinued, ILS was provided in the form of semiannual group-based classes, and all participants were offered quarterly lifestyle classes. Symptoms …

Patterns Of Undertreatment And Overtreatment In Adjuvant Radiotherapy For Early-Stage Endometrial Cancer Based On Molecular Classification, Otilia Ciobanu, Yixuan He, Alicia R Martin, Jill S Remick, Joseph W Shelton, Tony Y Eng, David C Qian

Faculty, Staff and Student Publications

The quality improvement study examines the use of risk-adaptive adjuvant radiotherapy in women with non–mismatch repair deficiency endometrial cancer.

Abnormality Of Early White Matter Development In Tuberous Sclerosis Complex And Autism Spectrum Disorder: Longitudinal Analysis Of Diffusion Tensor Imaging Measures, Siddharth Srivastava, Fanghan Yang, Anna K Prohl, Peter E Davis, Jamie K Capal, Rajna Filip-Dhima, E Martina Bebin, Darcy A Krueger, Hope Northrup, Joyce Y Wu, Simon K Warfield, Mustafa Sahin, Bo Zhang, Tacern Study Group

Faculty, Staff and Student Publications

Background:

Abnormalities in white matter development may influence development of autism spectrum disorder in tuberous sclerosis complex (TSC). Our goals for this study were as follows: (1) use data from a longitudinal neuroimaging study of tuberous sclerosis complex (TACERN) to develop optimized linear mixed effects models for analyzing longitudinal, repeated diffusion tensor imaging metrics (fractional anisotropy, mean diffusivity) pertaining to select white matter tracts, in relation to positive Autism Diagnostic Observation Schedule–Second Edition classification at 36 months, and (2) perform an exploratory analysis using optimized models applied to all white matter tracts from these data.

Methods:

Eligible participants (3-12 months) …

Physical Activity Policies At National And Subnational Levels: A Study In Colombia, Costa Rica, Ecuador, And Mexico, Juliana Mejía Grueso, Michael Pratt, Eugen Resendiz, Deborah Salvo, Gloria Isabel Niño Cruz, Nubia Yaneth Ruiz Gómez, Rafael Alexander Leandro Gómez, Inés Revuelta Sánchez, Gerardo Alonso Araya Vargas, Angélica María Ochoa Avilés, Raúl Francisco Pérez Tasigchana, Alejandra Jáuregui, Pedro C Hallal, Andrea Ramírez Varela

Faculty, Staff and Student Publications

Background: National physical activity (PA) policy processes are only beginning to be studied in Latin America, and little attention has focused at the subnational level. This study examined national-subnational relations in the policy process (agenda setting, policy formulation, adoption, implementation, and evaluation) in selected Latin American countries.

Methods: The Global Observatory for Physical Activity's (GoPA!) INTEGRATE-PA-Pol tool was applied in Colombia, Costa Rica, Ecuador, and Mexico. Data were collected in matched pairs of the capital plus one noncapital city among national and subnational policymakers (n = 27), previously identified by the GoPA! Country Contacts. PA policy development and implementation were …

Risk Evaluation In Occupational Safety And Health Research: Results From A Benchmarking Exercise Of Federal And Academic Irbs, Sarah A Felknor, Jessica M K Streit, Angela M Morley, John D Piacentino

Faculty, Staff and Student Publications

OBJECTIVE: Research involving working populations can pose unique ethical and risk evaluation challenges. The purpose of this benchmarking project was to assess how federal agencies and academic institutions approach the interpretation and application of key risk evaluation concepts in research involving workers in their places of employment.

METHODS: Key informant interviews were conducted to ascertain current practices related to assessing soundness of research design, determining risk reasonableness and research relatedness of risks, and evaluating the risk of noninvasive clinical tests in occupational settings.

RESULTS: There were noteworthy commonalities among the approaches described to review and address critical aspects of risk …

Risk Factors For Blunt Cerebrovascular Injury In A Cohort Of Pediatric Patients With Cervical Seat Belt Sign, Daniel A Najar, Marylou Cardenas-Turanzas, Jadeyn King, Manish N Shah, Charles S Cox, Irma T Ugalde

The Brown Foundation: Institute of Molecular Medicine

Background: Blunt cerebrovascular injury (BVCI), injury to the carotid or vertebral arteries, may result from forces involving seatbelts. Although previous studies have not found a seat belt sign to be a significant predictor for BCVI, it is still used to screen patients for BCVI.

Objective: This study aims to determine risk factors for BCVI within a cohort of patients with seat belt signs.

Methods: We conducted a retrospective cohort study using our institutional trauma registry and included patients younger than 18 years with blunt trauma who both had a computed tomography angiography (CTA) of the neck performed and had evidence …

Primary Care Patient Interests In Joining A Planned Multi-Cancer Early Detection Clinical Trial, Ronald E. Myers, Mie Hallman, Ayako Shimada, Melissa Dicarlo, Kaitlyn V. Davis, William T. Leach, Christopher V. Chambers

Department of Medical Oncology Faculty Papers

INTRODUCTION: Clinical trials are being conducted and are being planned to assess the safety and efficacy of multi-cancer early detection (MCED) tests for use in cancer screening. This study aimed to determine the feasibility of primary care patient outreach in recruiting participants to a planned MCED clinical trial, assess patient interest in trial participation, and measure decisional conflict related to participation.

METHODS: The research team used the electronic medical record of a large, urban health care system to identify primary care patients 50-80 years of age who were potentially eligible for a planned MCED trial. We mailed information about the …

Breaking Barriers: An Innovative Tool To Assess The National And City-Level Physical Activity Policy Development To Practice Disconnect, Eugen Resendiz, Andrea Ramírez-Varela, Juliana Mejía-Grueso, Jane Moon, Josef Mitáš, Ross C Brownson, Deborah Salvo, Michael Pratt

Faculty, Staff and Student Publications

Background: Population-level physical activity increases are improbable without intersectoral collaboration across government levels and sectors to develop and implement physical activity promotion policies. This study aims to provide information about the development of the Interaction between National and Local Government Levels in Development and Implementation of Physical Activity Policies Tool (INTEGRATE PA-Pol). A framework was created to examine the development and implementation of national and subnational physical activity policies and the (mis)alignment between government levels.

Methods: The work was conducted in 3 phases: (1) a scoping review was carried out to identify local government physical activity promotion policies and instruments …

Ictal Central Apnea Is Predictive Of Mesial Temporal Seizure Onset: An Intracranial Investigation, Nuria Lacuey, Blanca Talavera, Oman Magana-Tellez, Oscar Mancera-Páez, Norma Hupp, Xi Luo, Johnson P Hampson, Jaison Hampson, M R Sandhya Rani, Manuela Ochoa-Urrea, Omar A Alamoudi, Stephen Melius, Sandipan Pati, Jay Gavvala, Nitin Tandon, John C Mosher, Samden D Lhatoo

Faculty, Staff and Student Publications

Objective: Ictal central apnea (ICA) is a semiological sign of focal epilepsy, associated with temporal and frontal lobe seizures. In this study, using qualitative and quantitative approaches, we aimed to assess the localizational value of ICA. We also aimed to compare ICA clinical utility in relation to other seizure semiological features of focal epilepsy.

Methods: We analyzed seizures in patients with medically refractory focal epilepsy undergoing intracranial stereotactic electroencephalographic (SEEG) evaluations with simultaneous multimodal cardiorespiratory monitoring. A total of 179 seizures in 72 patients with reliable artifact-free respiratory signal were analyzed.

Results: ICA was seen in 55 of 179 (30.7%) …

Culturally Competent Education And Human Papillomavirus Self-Sampling Achieves Healthy People 2030 Cervical Screening Target Among Low-Income Non-Hispanic Black And Hispanic Women, Surendra S Shastri, Lorna H Mcneill, Sanjay Shete

Faculty, Staff and Student Publications

Purpose: Disparities in cervical cancer screening, incidence, and mortality exist in the United States. Cervical cancer incidence and mortality rates in Texas are 20% and 32% higher, respectively, than national averages. Within Texas, these rates are significantly higher among non-Hispanic (NH) Black and Hispanic women. Cervical cancer screening uptake is lower among NH Black and Hispanic women (72.9% and 75.9%, respectively) compared with White women (85.5%) in Texas.

Methods: During March-August 2023, we conducted a pilot study that offered culturally competent education and human papillomavirus (HPV) self-sampling kits to women in two public housing projects in Houston, TX, that have …

Fungi In Cancer, Jessica Galloway-Peña, Iliyan D Iliev, Florencia Mcallister

Faculty, Staff and Student Publications

Both the gut and the tumour microbiome are now established as crucial regulators of cancer phenotypes and have been implicated in cancer initiation, progression and therapy response. Although the role of bacteria in these processes is beginning to be unravelled, the relevance of fungi is only just emerging. In this Viewpoint, we asked experts to discuss the current knowledge on the mycobiome–cancer connection and share their opinion on how to best solve open questions.

Impact Of Revised International Staging System 2 Risk Stratification On Outcomes Of Patients With Multiple Myeloma Receiving Autologous Haematopoietic Stem Cell Transplantation, Kamal Alzahrani, Oren Pasvolsky, Zhongya Wang, Denái R Milton, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Hans C Lee, Krina K Patel, Elisabet E Manasanch, Partow Kebriaei, Sheeba K Thomas, Donna M Weber, Robert Z Orlowski, Elizabeth J Shpall, Richard Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

The second revision of the International Staging System (R2-ISS) is a simple tool to risk-stratify newly diagnosed multiple myeloma (NDMM) patients. Here, we completed a retrospective analysis to evaluate the utility of R2-ISS in NDMM patients who underwent up-front autologous haematopoietic stem cell transplantation (auto-HCT). A total of 1291 patients were included, with a median age of 62 years (range 29-83). The distribution of R2-ISS stages was: 123 (10%) stage I, 471 (36%) stage II, 566 (44%) stage III and 131 (10%) stage IV. With a median follow-up of 42.2 months (range 0.3-181.0), the median PFS was 73.0, 65.2, 44.0 …

Safety And Long-Term Survival Results Of The Addition Of Inotuzumab Ozogamicin To The Conditioning Regimen Of Allogeneic Stem Cell Transplantation: A Single-Center Phase 1,2 Trial, Issa F Khouri, Kamal Alzahrani, Hagop Kantarjian, Denái R Milton, Alison M Gulbis, Koji Sasaki, Nitin Jain, Nicholas J Short, Tapan Kadia, May Daher, Hind Rafei, Jin S Im, David Marin, Amanda L Olson, Uday Popat, Muzaffar Qazilbash, Jeremy Ramdial, Gabriela Rondon, Samer Srour, Partow Kebriaei, Elizabeth Shpall, Richard Champlin, Elias J Jabbour

Faculty, Staff and Student Publications

Here we report on the first prospective study evaluating the safety and long-term survival when an escalating dose of inotuzumab ozogamicin (INO) (0.6, 1.2, or 1.8 mg/m2 on day 13) was added to one alkylator-containing conditioning regimen in patients with relapsed CD22 (+) lymphoid malignancies who were candidates for hematopoietic stem cell transplantation (HSCT). Twenty-six patients were enrolled. Six (23%) of these patients entered the phase 1 study: four were treated at an INO dose of 0.6 mg/m2 and two at dose of 1.2 mg/m2. None of these patients experienced dose-limiting toxicities. The remaining 20 (77%) patients entered the phase …

Model Tuning Or Prompt Tuning? A Study Of Large Language Models For Clinical Concept And Relation Extraction, Cheng Peng, Xi Yang, Kaleb E Smith, Zehao Yu, Aokun Chen, Jiang Bian, Yonghui Wu

Faculty, Staff and Student Publications

Objective: To develop soft prompt-based learning architecture for large language models (LLMs), examine prompt-tuning using frozen/unfrozen LLMs, and assess their abilities in transfer learning and few-shot learning.

Methods: We developed a soft prompt-based learning architecture and compared 4 strategies including (1) fine-tuning without prompts; (2) hard-prompting with unfrozen LLMs; (3) soft-prompting with unfrozen LLMs; and (4) soft-prompting with frozen LLMs. We evaluated GatorTron, a clinical LLM with up to 8.9 billion parameters, and compared GatorTron with 4 existing transformer models for clinical concept and relation extraction on 2 benchmark datasets for adverse drug events and social determinants of health (SDoH). …

Dpar: Decoupled Graph Neural Networks With Node-Level Differential Privacy, Qiuchen Zhang, Hong Kyu Lee, Jing Ma, Jian Lou, Carl Yang, Li Xiong

Faculty, Staff and Student Publications

Graph Neural Networks (GNNs) have achieved great success in learning with graph-structured data. Privacy concerns have also been raised for the trained models which could expose the sensitive information of graphs including both node features and the structure information. In this paper, we aim to achieve node-level differential privacy (DP) for training GNNs so that a node and its edges are protected. Node DP is inherently difficult for GNNs because all direct and multi-hop neighbors participate in the calculation of gradients for each node via layer-wise message passing and there is no bound on how many direct and multi-hop neighbors …

A Radiotherapy Community Data-Driven Approach To Determine Which Complexity Metrics Best Predict The Impact Of Atypical Tps Beam Modeling On Clinical Dose Calculation Accuracy, Fre'etta Mae Dayo Brooks, Mallory Carson Glenn, Victor Hernandez, Jordi Saez, Hunter Mehrens, Julianne Marie Pollard-Larkin, Rebecca Maureen Howell, Christine Burns Peterson, Christopher Lee Nelson, Catharine Helen Clark, Stephen Frasier Kry

Faculty, Staff and Student Publications

PURPOSE: To quantify the impact of treatment planning system beam model parameters, based on the actual spread in radiotherapy community data, on clinical treatment plans and determine which complexity metrics best describe the impact beam modeling errors have on dose accuracy.

METHODS: Ten beam modeling parameters for a Varian accelerator were modified in RayStation to match radiotherapy community data at the 2.5, 25, 50, 75, and 97.5 percentile levels. These modifications were evaluated on 25 patient cases, including prostate, non-small cell lung, H&N, brain, and mesothelioma, generating 1,000 plan perturbations. Differences in the mean planned dose to clinical target volumes …

Programming A Ferroptosis-To-Apoptosis Transition Landscape Revealed Ferroptosis Biomarkers And Repressors For Cancer Therapy, Yaron Vinik, Avi Maimon, Vinay Dubey, Harsha Raj, Ifat Abramovitch, Sergey Malitsky, Maxim Itkin, Avi Ma'ayan, Frank Westermann, Eyal Gottlieb, Eytan Ruppin, Sima Lev

Faculty, Staff and Student Publications

Ferroptosis and apoptosis are key cell-death pathways implicated in several human diseases including cancer. Ferroptosis is driven by iron-dependent lipid peroxidation and currently has no characteristic biomarkers or gene signatures. Here a continuous phenotypic gradient between ferroptosis and apoptosis coupled to transcriptomic and metabolomic landscapes is established. The gradual ferroptosis-to-apoptosis transcriptomic landscape is used to generate a unique, unbiased transcriptomic predictor, the Gradient Gene Set (GGS), which classified ferroptosis and apoptosis with high accuracy. Further GGS optimization using multiple ferroptotic and apoptotic datasets revealed highly specific ferroptosis biomarkers, which are robustly validated in vitro and in vivo. A subset of …

Noninferiority Of Hypofractionated Vs Conventional Postprostatectomy Radiotherapy For Genitourinary And Gastrointestinal Symptoms: The Nrg-Gu003 Phase 3 Randomized Clinical Trial, Mark K Buyyounouski, Stephanie L Pugh, Ronald C Chen, Mark J Mann, Rajat J Kudchadker, Andre A Konski, Omar Y Mian, Jeff M Michalski, Eric Vigneault, Richard K Valicenti, Maroie Barkati, Colleen A F Lawton, Louis Potters, Drew C Monitto, Jeffrey A Kittel, Thomas M Schroeder, Raquibul Hannan, Casey E Duncan, Joseph P Rodgers, Felix Feng, Howard M Sandler

Faculty, Staff and Student Publications

Importance: No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy.

Objective: To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years.

Design, setting, and participants: In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (< 0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed.

Intervention: Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT).

Main outcomes and measures: The coprimary end points were the 2-year …

A Randomized Trial Of Two Remote Health Care Delivery Models On The Uptake Of Genetic Testing And Impact On Patient-Reported Psychological Outcomes In Families With Pancreatic Cancer: The Genetic Education, Risk Assessment, And Testing (Generate) Study, Nicolette J Rodriguez, C Sloane Furniss, Matthew B Yurgelun, Chinedu Ukaegbu, Pamela E Constantinou, Ileana Fortes, Alyson Caruso, Alison N Schwartz, Jill E Stopfer, Meghan Underhill-Blazey, Barbara Kenner, Scott H Nelson, Sydney Okumura, Alicia Y Zhou, Tara B Coffin, Hajime Uno, Miki Horiguchi, Allyson J Ocean, Florencia Mcallister, Andrew M Lowy, Alison P Klein, Lisa Madlensky, Gloria M Petersen, Judy E Garber, Scott M Lippman, Michael G Goggins, Anirban Maitra, Sapna Syngal

Faculty, Staff and Student Publications

Background & aims: Genetic testing uptake for cancer susceptibility in family members of patients with cancer is suboptimal. Among relatives of patients with pancreatic ductal adenocarcinoma (PDAC), The GENetic Education, Risk Assessment, and TEsting (GENERATE) study evaluated 2 online genetic education/testing delivery models and their impact on patient-reported psychological outcomes.

Methods: Eligible participants had ≥1 first-degree relative with PDAC, or ≥1 first-/second-degree relative with PDAC with a known pathogenic germline variant in 1 of 13 PDAC predisposition genes. Participants were randomized by family, between May 8, 2019, and June 1, 2021. Arm 1 participants underwent a remote interactive telemedicine session …

Somatic Gene Mutation Patterns And Burden Influence Outcomes With Enasidenib In Relapsed/Refractory Idh2-Mutated Aml, Alberto Risueño, Wendy L See, Iryna Bluemmert, Stéphane De Botton, Courtney D Dinardo, Amir T Fathi, Andre C Schuh, Pau Montesinos, Paresh Vyas, Thomas Prebet, Anita Gandhi, Maroof Hasan

Faculty, Staff and Student Publications

Limited treatment options are available for patients with relapsed/refractory acute myeloid leukemia (R/R AML). We recently reported results from the phase 3 IDHENTIFY trial (NCT02577406) showing improved response rates and event-free survival with enasidenib monotherapy compared with conventional care regimens (CCR) in heavily pretreated, older patients with late-stage R/R AML bearing IDH2 mutations. Here we investigated the prognostic impact of mutational burden and different co-mutation patterns at study entry within the predominant IDH2 variant subclasses, IDH2-R140 and IDH2-R172. The prognostic relevance of these variants is well documented in newly diagnosed AML, but data are lacking in R/R AML. In this …

Supporting Career Development For Early- And Mid-Career Professionals Working In The Bipolar Disorder Field: Key Initiatives To Be Implemented By The International Society For Bipolar Disorders Early- And Mid-Career Committee, Katie M Douglas, Sarah H Sperry, Olivia M Dean, Gabriel R Fries, Fabiano A Gomes, Joanna Jiménez Pavón, Emma Morton, Rachel H B Mitchell, Tamsyn E Van Rheenen, Norma Verdolini, Ni Xu, Georgina M Hosang, Rebekah S Huber

Faculty, Staff and Student Publications

No abstract provided.

Management And Outcomes Of Patients With Refractory Solitary Plasmacytoma After Treatment With Definitive Radiation Therapy, Penny Fang, Chelsea C Pinnix, Susan Y Wu, Hans C Lee, Krina K Patel, Neeraj Saini, Melody R Becnel, Gregory Kaufman, Sheeba K Thomas, Robert Z Orlowski, Behrang Amini, Pei Lin, Bouthaina S Dabaja, Jillian R Gunther

Faculty, Staff and Student Publications

Purpose: Radiation therapy (RT) is the standard treatment for solitary plasmacytoma (SP); however, the optimal management of RT-refractory SPs is unknown. We examined outcomes after early systemic therapy, surgical resection, or observation for patients with RT-refractory disease and assessed the potential impact of treatment selection on disease outcomes.

Methods and materials: We retrospectively reviewed patients with SP treated with definitive radiation and evaluated at a single institution with persistent disease on imaging or biopsy. Descriptive statistics were used to characterize patient and disease characteristics and treatment outcomes.

Results: Of 102 total SP patients, 17 (17%) were RT-refractory. The median RT …

Jak2v617f Reversible Activation Shows Its Essential Requirement In Myeloproliferative Neoplasms, Andrew J Dunbar, Robert L Bowman, Young C Park, Kavi O'Connor, Franco Izzo, Robert M Myers, Abdul Karzai, Zachary Zaroogian, Won Jun Kim, Inés Fernández-Maestre, Michael R Waarts, Abbas Nazir, Wenbin Xiao, Tamara Codilupi, Max Brodsky, Mirko Farina, Louise Cai, Sheng F Cai, Benjamin Wang, Wenbin An, Julie L Yang, Shoron Mowla, Shira E Eisman, Amritha Varshini Hanasoge Somasundara, Jacob L Glass, Tanmay Mishra, Remie Houston, Emily Guzzardi, Anthony R Martinez Benitez, Aaron D Viny, Richard P Koche, Sara C Meyer, Dan A Landau, Ross L Levine

Faculty, Staff and Student Publications

Gain-of-function mutations activating JAK/STAT signaling are seen in the majority of patients with myeloproliferative neoplasms (MPN), most commonly JAK2V617F. Although clinically approved JAK inhibitors improve symptoms and outcomes in MPNs, remissions are rare, and mutant allele burden does not substantively change with chronic therapy. We hypothesized this is due to limitations of current JAK inhibitors to potently and specifically abrogate mutant JAK2 signaling. We therefore developed a conditionally inducible mouse model allowing for sequential activation, and then inactivation, of Jak2V617F from its endogenous locus using a combined Dre-rox/Cre-lox dual-recombinase system. Jak2V617F deletion abrogates MPN features, induces depletion of mutant-specific hematopoietic …

Foundation Models, Generative Ai, And Large Language Models: Essentials For Nursing, Angela Ross, Kathleen Mcgrow, Degui Zhi, Laila Rasmy

Faculty, Staff and Student Publications

We are in a booming era of artificial intelligence, particularly with the increased availability of technologies that can help generate content, such as ChatGPT. Healthcare institutions are discussing or have started utilizing these innovative technologies within their workflow. Major electronic health record vendors have begun to leverage large language models to process and analyze vast amounts of clinical natural language text, performing a wide range of tasks in healthcare settings to help alleviate clinicians' burden. Although such technologies can be helpful in applications such as patient education, drafting responses to patient questions and emails, medical record summarization, and medical research …