Medicine and Health Sciences Commons^™

Streptavidin-Drug Conjugates Streamline Optimization Of Antibody-Based Hematopoietic Stem Cell Transplant Conditioning, Aditya R Yelamali, Ezhilarasi Chendamarai, Julie K Ritchey, Michael P Rettig, John F Dipersio, Stephen P Persaud

2020-Current year OA Pubs

Hematopoietic stem cell transplantation (HSCT) conditioning using antibody-drug conjugates (ADC) is a promising approach to preparing patients for transplant, potentially avoiding the severe toxicities of conventional chemotherapy- and irradiation-based conditioning regimens. The toxic payload determines the efficacy and potential toxicities of an ADC, but comparison of different payloads in conjugates designed for HSCT conditioning has not been reported. Such comparisons would be greatly facilitated by methods enabling efficient screening of many combinations of antibody and payload. Herein, we used Click chemistry to conjugate four different small molecule payloads to a streptavidin backbone, yielding streptavidin-drug conjugates that can be combined with …

Clinical Characteristics And Real-World Outcomes In Patients With Mucopolysaccharidosis Ii Over 18 Years: Final Report Of The Hunter Outcome Survey, Joseph Muenzer, Jaco Botha, Hernan Amartino, Roberto Giugliani, Paul Harmatz, Christoph Kampmann, Bianca Link, Shuan-Pei Lin, David Molter, Julian Raiman, Maurizio Scarpa, Anna Tylki-Szymańska, Siddharth Jain, David A H Whiteman, Barbara K Burton

2020-Current year OA Pubs

BACKGROUND: Mucopolysaccharidosis II (MPS II) is a rare, progressive, X-linked lysosomal storage disease. Enzyme replacement therapy (ERT) with intravenous (IV) idursulfase has been approved for the treatment of patients with MPS II since 2005. The Hunter Outcome Survey (HOS; NCT03292887) was established as a condition of approval to monitor the long-term safety and effectiveness of idursulfase. Here, we report the final results from HOS.

METHODS: HOS was a multicenter, long-term, observational registry that enrolled patients with a biochemically and/or genetically confirmed diagnosis of MPS II who were untreated or treated with idursulfase and/or bone marrow transplant. Patients were enrolled prospectively …

Risk Factors For Early Right Ventricular-To-Pulmonary Artery Conduit Failure In Congenital Heart Disease, Fawaz Naeem, Travus J White, J William Gaynor, Xuemei Zhang, Steve Ampah, Andrew C Glatz, Laura Mercer-Rosa, Meryl S Cohen

2020-Current year OA Pubs

OBJECTIVES: Right ventricle-to-pulmonary artery conduits are a mainstay of treatment for patients with congenital heart defects. We investigated the association of underlying genetic abnormalities with conduit failure and hypothesized that 22q11.2 deletion syndrome was associated with shorter time to failure.

METHODS: We conducted a single-center retrospective cohort study at the Children's Hospital of Philadelphia. Patients who underwent right ventricle-to-pulmonary artery conduit placement as part of a biventricular repair at 0 to 24 months of age between January 2010 and June 2020 were included. The primary exposure of interest was diagnosis of 22q11.2 deletion syndrome, and the outcome was time to …

From Sex Differences To Sex Inequalities In Life Expectancy: A Cross-Country Observational Benchmarking Analysis, Angela Y. Chang, Emily K. Johnson, Sarah Bolongaita, Kent Buse, Sarah J. Hawkes, Omar Karlsson, Felicia M. Knaul, Margaret E. Kruk, Ole F. Norheim, Osondu Ogbuoji, David Watkins, Dean T. Jamison

2020-Current year OA Pubs

BACKGROUND: The answer to whether females or males have better health, and which sex is the more disadvantaged, has depended in part on the metric and how the inequality is measured. This study introduces a new method for analyzing and interpreting sex inequalities in health outcomes-defined as the avoidable sex differences in health outcomes-that is systematic and potentially more objective. For this paper, we focus on life expectancy at different ages.

METHODS AND FINDINGS: We introduce the adjusted sex ratio as a measure of sex inequalities and determining sex disadvantage. First, we calculated the sex ratio of life expectancy at …

In Situ Structural Mechanism Of Epothilone-B-Induced Cns Axon Regeneration, Satish Bodakuntla, Kenichiro Taira, Yurika Yamada, Pelayo Alvarez-Brecht, A King Cada, Nirakar Basnet, Rui Zhang, Antonio Martinez-Sanchez, Christian Biertümpfel, Naoko Mizuno

2020-Current year OA Pubs

Axons in the adult central nervous system (CNS) do not regenerate following injury, in contrast to neurons in the peripheral nervous system and neuronal growth during embryonic development. The molecular mechanisms that prevent regeneration of neurons in the CNS remain largely unknown

A Longitudinal And Multimodal Simulation-Based Curriculum Improved Internal Medicine Residents' Confidence In Procedures, Point-Of-Care Ultrasound, And Clinical Decision-Making., Sarah Grebennikov, Aisha Imam, Megan Kang, Aimee E Willett, Brad Gable, Sanjay Patel

Medical Education Articles

Introduction Internal medicine training has historically relied on classroom-based lectures, typically delivered through morning and noon conferences, which offer broad content coverage but limited experiential learning. Simulation-based education improves resident confidence, procedural ability, and clinical reasoning; yet it is often delivered in brief, standalone activities that lack longitudinal structure or integration within the broader curriculum. Few programs have a longitudinal simulation curriculum that spans the academic year and incorporates multiple modalities and topics. We developed a novel simulation-based curriculum intentionally integrated into the existing resident academic schedule to provide structured hands-on learning across multiple domains. Sessions focused on procedural and …

Muc15 Ectodomain Architecture Regulates Integrin Clustering To Control Cancer Metastasis, Simei Zhang, Guy M Genin, Et Al.

2020-Current year OA Pubs

Cancer metastasis is governed by physical cues at the cell-matrix interface, with matrix stiffness, ligand density, and topography established as key determinants. Here, a fourth critical factor in cancer metastasis, the architecture of the cell-surface glycocalyx is identified. Using MUC15 as a representative small glycoprotein, mathematical modeling and domain truncation experiments are combined to show that glycoprotein size distribution governs integrin adhesion states and metastatic outcomes. MUC15 localizes to focal adhesions and interact with integrins, while larger glycoproteins such as MUC1 are sterically excluded. These physical effects, rather than intracellular signaling, dictate adhesion state transitions: removing MUC15's ectodomain eliminated its …

Renal Replacement Therapy In Lupus Nephritis-Related End-Stage Kidney Disease: A Systematic Review And Meta-Analysis, Hassan Kawtharany, Jessica N Williams, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To assess the impact of renal replacement therapy in people with lupus nephritis (LN)-associated end-stage kidney disease (ESKD) and support the development of the 2024 American College of Rheumatology LN treatment guidelines.

METHODS: We conducted a systematic literature review and meta-analysis to address three Population, Intervention, Comparison, and Outcome (PICO) questions related to renal replacement therapy for ESKD due to LN, including comparisons of kidney transplant versus dialysis, hemodialysis versus peritoneal dialysis, and preemptive kidney transplant versus no preemptive kidney transplant. Outcomes of interest included mortality, cardiovascular (CV) events, infections, lupus flares, disease-related damage, graft failure, and quality of …

Fast And Accurate Measurement Of Small Field Dosimetry Using A Novel Scintillation Detector, Yiding Han, Jingzhu Xu, Yao Hao, Baozhou Sun

2020-Current year OA Pubs

BACKGROUND: The most used instruments for small-field dosimetry have notable limitations, including the need for correction of output factors, limited scanning speeds, and challenges in alignment for percentage depth dose (PDD) measurements, particularly for extremely small fields. However, plastic scintillation detectors (PSDs) are an attractive alternative for small-field dosimetry due to their correction-free nature, linear dose response, and fast response time.

PURPOSE: This study evaluates the robustness and accuracy of the dosimetric measurements using a new water-equivalent PSD in small-field dosimetry. The study also aims to report accurate measurements of output factors, profiles, and an indirect method for measuring PDD …

Black Women’S Experiences Accessing Health Care And Law Enforcement After Intimate Partner Violence: A Qualitative Pilot Study, Kaylen M. Moore, Linda M. Wesp, Jeneile Luebke, Peninnah M. Kako

College of Nursing Faculty Research and Publications

Background:

Intimate partner violence (IPV) is a global public health issue impacting millions of people each year. Black women constitute 14% of the US population but alarmingly comprise 31% of homicides resulting from IPV. African American women survivors of IPV experience intersecting impacts of racism, sexism, and historical mistrust. This research aimed to raise awareness about their experiences of violence and perceptions of institutional support.

Objective:

This study sought to explore African American women’s experiences with IPV and navigation of health care and law enforcement after experiences of violence.

Method:

Critical ethnography was used as an approach for this qualitative …

Benzodioxane-Benzamides Targeting Bacterial Cell Division Protein Ftsz Potentially Disrupt Slma-Mediated Nucleoid Occlusion And Reversible Biomolecular Condensation, Marta Sobrinos-Sanguino, Inés Barros-Medina, Lorenzo Suigo, Alessia Lanzini, Ermanno Valoti, William Margolin, Valentina Straniero, Begoña Monterroso, Silvia Zorrilla

Faculty, Staff and Student Publications

New strategies are urgently needed against antimicrobial resistance, a major health threat, and the different mechanisms regulating the bacterial cell division machinery offer multiple opportunities for developing novel therapeutics. FtsZ, an essential protein of this process, is targeted by multiple small molecules, and benzodioxane-benzamides (BDOBs) are among the most potent inhibitors in several bacterial species. BDOBs mechanisms are however poorly understood, particularly their impact on FtsZ's interplay with partners and ability to assemble phase-separated biomolecular condensates potentially involved in stress sensing. We show that certain BDOBs shielded FtsZ against depolymerization induced by the nucleoprotein complexes of SlmA, which inhibit Z-ring …

Breakwater Phase Iii: Results For Encorafenib And Cetuximab Plus Mfolfox6 In First-Line Braf V600e-Mutant Metastatic Colorectal Cancer, Scott Kopetz, Josep Tabernero, Elena Élez

Faculty, Staff and Student Publications

The BREAKWATER Phase III study investigated encorafenib and cetuximab plus mFOLFOX6 versus chemotherapy with or without bevacizumab for the treatment of patients with previously untreated BRAF V600E – mutant metastatic colorectal cancer. The study showed significantly improved objective response rate by blinded independent central review, and significantly longer progression-free survival by blinded independent central review and overall survival in patients treated with first-line encorafenib and cetuximab plus mFOLFOX6 compared with chemotherapy with or without bevacizumab. The safety profiles were consistent with those known for each agent. These results led to the approval of encorafenib and cetuximab plus mFOLFOX6 for the …

Caspase 3-Specific Cleavage Of Ubiquitin-Specific Peptidase 48 Enhances Drug-Induced Apoptosis In Aml, Zhanglin Zhang, Xiang Lin, Yaling Yang, Xuemei Wang, Yi Wang, Xianbao Huang, Miao Hong, Wei Gao, Hua He, M James You, Yi Yang, Guangyao Kong

Faculty, Staff and Student Publications

Dysfunction or dysregulation of deubiquitination is closely related to the initiation and development of multiple cancers. Targeted regulation of deubiquitination has been recognized as an important strategy in tumor therapy. However, the mechanism by which drugs regulate deubiquitinase is not clear. Here, we identified ubiquitin-specific peptidase 48 (USP48), a member of the ubiquitin-specific protease family highly expressed in various tumors, as a specific substrate for the activated caspase-3. During drug induced apoptosis of AML cells, activated caspase-3 cleaves USP48 through recognizing the conservative motif DEQD located at 611-614 sites of human USP48. Subsequent analysis showed that the cleavage USP48 N-terminal …

Impact Of Peripheral Circadian Misalignment And Alcohol On The Resiliency Of Intestinal Barrier And Microbiota, Laura Tran, Maliha Shaikh, Phillip A Engen, Ankur Naqib, Dulce M Frausto, Vivian Ramirez, Malia Gasteier, Zlata Bogin, Kristi Lawrence, Lijuan Zhang, Shiwen Song, Stefan J Green, Faraz Bishehsari, Christopher B Forsyth, Ali Keshavarzian, Garth R Swanson

Faculty, Staff and Student Publications

Circadian organization is involved in many gastrointestinal tract (GIT) functions such as the maintenance of intestinal barrier integrity. There is compelling evidence that perturbation of the circadian clock decreases intestinal epithelial cells' resiliency to alcohol-induced injury. One of the most common causes of circadian misalignment is wrong-time eating (largest meal at dinner) in modern societies. Yet, few studies have examined the importance of peripheral circadian rhythms of the GIT to alcohol consumption. Eating patterns during physiologic rest time, defined as wrong-time eating (WTE), misalign the peripheral circadian clock of the GIT and the body's central clock. This study aims to …

Molecular And Immunological Features Associated With Long-Term Benefits In Metastatic Nsclc Patients Undergoing Immune Checkpoint Blockade, Pedro Rocha, Rafael Bach, Laura Masfarré, Sharia Hernandez, Nil Navarro-Gorro, Adrià Rossell, Xavier Villanueva, Mario Giner, Ignacio Sanchéz, Miguel Galindo, Raúl Del Rey-Vergara, Albert Iñañez, Beatriz Sanchéz-Espiridion, Wei Lu, Ariadna Acedo-Terrades, Pau Berenguer-Molins, Albert Sánchez-Font, Roberto Chalela, Victor Curull, Álvaro Taus, Max Hardy-Werbin, Mark Sausen, Andrew Georgiadis, James White, Jennifer B Jackson, Laura Moliner, Sergi Clavé, Beatriz Bellosillo, Ana Rovira, Ignacio Wistuba, Luisa M Solis Soto, Júlia Perera-Bel, Edurne Arriola

Faculty, Staff and Student Publications

Introduction: Immunotherapy is firmly established as a treatment regimen in various solid tumors, driven by its exceptional benefits in a selected group of patients. Despite widespread adoption of immune checkpoint blockade (ICB) across diverse solid tumors, the quest for a clinically informative biomarker for long-term benefit remains unmet.

Methods: A total of 49 patients with metastatic NSCLC treated with ICB were included. Long-term (LTR) and short-term responders (STR) were defined as those with a response to ICB lasting more than 24 months or less than 6 months, respectively. Longitudinal blood specimens were collected before ICB treatment initiation and early-on treatment. …

Functional Connectivity Associations With Markers Of Disease Progression In Grn Pathogenic Variant Carriers, Taru M Flagan, Nupur Ghoshal, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Autosomal dominant progranulin (GRN) pathogenic variants are a genetic cause of frontotemporal lobar degeneration. Though clinical trials for GRN-related therapies are underway, there is an unmet need for biomarkers that can predict symptom onset and track disease progression. We previously showed that asymptomatic GRN variant carriers exhibit thalamocortical hyperconnectivity that increases with age, presumably as they are approaching symptom onset. Whether hyperconnectivity arises concomitantly with markers of neurodegeneration remains unclear.

METHODS: Utilizing T1 and task-free functional magnetic resonance imaging from 49 asymptomatic and 26 symptomatic GRN variant carriers, we determined the relationships between functional connectivity, as measured by voxelwise …

A Roadmap To Scale Up Person-Centred Care In The Hiv Response: Recommendations From A Global Consensus-Building Process, Lina Golob, Elvin H Geng, Et Al.

2020-Current year OA Pubs

INTRODUCTION: World Health Organization global normative guidance recommends person-centred care (PCC) approaches to reduce HIV-related mortality and morbidity and to improve health-related quality of life (HrQoL). However, consensus on the priority PCC elements and guidance on how different stakeholders can realize PCC principles at the health systems, service delivery and individual client-healthcare worker (HCW) levels are lacking. We conducted a global consensus-building process to define core PCC elements and develop recommendations for implementation at scale.

METHODS: We used a multi-phase process to build consensus and prioritize recommendations, consisting of a literature review, five stakeholder consultations (34-43 participants each) between July …

A Guide For Initiating And Managing Chimeric Antigen Receptor T Cell Therapy Clinical Trials In Autoimmune Rheumatic Diseases, Roberto Caricchio, Stacie Bell, Sasha Bernatsky, Maria Dall'era, David Goddard, Kenneth Kalunian, Alfred H J Kim, Fotios Koumpouras, Jose Rubio, Amit Saxena, Saira Sheikh, Lupus Clinical Investigators Network

2020-Current year OA Pubs

Chimeric antigen receptor (CAR) T-cell therapy, long transformative in oncology, is now rapidly emerging as a frontier in autoimmune rheumatic diseases, particularly systemic lupus erythematosus (SLE), driven by accumulating evidence of deep B-cell depletion, immune "resetting," and durable drug-free remission in early studies, yet its translation into rheumatology demands mastery of formidable logistical, regulatory, clinical, and ethical complexities that span institutional readiness, multidisciplinary team formation, stringent regulatory compliance, sophisticated operational workflows, comprehensive patient selection and education, meticulous clinical management of both classical toxicities (CRS, ICANS, ICAHT) and autoimmune-specific reactions such as LICATS, robust financial and resource planning, and long-term follow-up …

Bilateral Breast Treatment In A Single Arc Using Rapidarc Dynamic: A Planning Comparison With Conventional Volumetric Modulated Arc Therapy, Taoran Li, Luca Cozzi, Lesley Rosa, Ryan Clark, Priyanka Agarwal, Yin Gao, Yun Yang, Boon-Keng Kevin Teo, Anthony Magliari, Himank Kalra, Francisco Reynoso, Patrick Kupelian, Sushil Beriwal

2020-Current year OA Pubs

PURPOSE: Synchronous bilateral breast cancer (SBBC) presents significant radiotherapy planning challenges due to complex target volumes near critical organs. This study evaluated RapidArc Dynamic (RAD), a novel technique integrating dynamic arcs with static angle modulated ports (STAMPs) via simultaneous GPU-accelerated optimization, against conventional volumetric modulated arc therapy (VMAT) for SBBC treatment planning and delivery efficiency.

METHODS: Ten retrospective SBBC cases involving comprehensive nodal irradiation were planned using both multi-arc VMAT (six arcs) and RAD (one arc plus six STAMPs) in Eclipse (v18.1) with AcurosXB. A prescription dose of 40.05 Gy in 15 fractions was normalized to PTV D95% = 95%. …

Brain Functional Connectivity, But Not Neuroanatomy, Captures The Interrelationship Between Sex And Gender In Preadolescents, Athanasia Metoki, Roselyne J Chauvin, Evan M Gordon, Timothy O Laumann, Benjamin P Kay, Babatunde Adeyemo, Samuel R Krimmel, Scott Marek, Anxu Wang, Andrew N Van, Noah J Baden, Vahdeta Suljic, Kristen M Scheidter, Julia Monk, Forrest I Whiting, Nadeshka J Ramirez-Perez, Deanna M Barch, Aristeidis Sotiras, Nico U F Dosenbach

2020-Current year OA Pubs

Understanding sex differences in the adolescent brain is crucial, as they relate to sex-specific neurological and psychiatric conditions. Predicting sex from adolescent brain data may reveal how these differences influence neurodevelopment. Recently, attention has shifted toward socially-identified gender (distinct from sex assigned at birth) recognizing its explanatory power. This study evaluates whether resting-state functional connectivity (rsFC), cortical thickness, or cortical volume better predicts sex and sex/gender alignment (congruence between sex and gender) in preadolescents. Using Adolescent Brain Cognitive Development (ABCD) Study data and machine learning, rsFC predicted sex more accurately (85 %) than cortical thickness (76 %) and cortical volume …

Novel Leadless Atrial And Ventricular Pacing System With Subcutaneous Implantable Cardiac Defibrillator: A Case Of Cross-Platform Device Compatibility., Nicholas Bradley, Ankur Shah, Anish Amin

Heart and Vascular Articles

No abstract provided.

From Standard To Stratified: Modeling Ntcp And Ear To Personalize Daily Mv-Cbct In Radiotherapy., Duong Thanh Tai, Luong Tien Phat, Tran Trung Kien, Duong Tuan Linh, Nguyen Ngoc Anh, Nguyen Quang Hung, Peter Sandwall, Parham Alaei, David Bradley, James C L Chow

Oncology Articles

PURPOSE: To evaluate the cumulative radiobiological impact of daily megavoltage cone-beam computed tomography (MV-CBCT) imaging dose based on normal tissue complication probability (NTCP) and excess absolute risk (EAR) of secondary malignancies among radiotherapy patients treated for breast, pelvic, and head & neck cancers. This study investigated whether MV-CBCT imaging dose warrants protocol personalization according to patient age, anatomical treatment site, and organ-specific radiosensitivity.

METHODS: This retrospective study included cohorts of breast (n = 30), pelvic (n = 17), and head & neck (n = 20) cancer patients undergoing radiotherapy with daily MV-CBCT. Imaging dose distributions employing two common MV-CBCT protocols …

Meniscal Repair In The Setting Of Revision Anterior Cruciate Ligament Reconstruction: 6-Year Follow-Up Results From The Mars Cohort, Jake A Fox, Laura J Huston, Amanda K Haas, Jacquelyn S Pennings, Christina R Allen, Daniel E Cooper, Thomas M Deberardino, Warren R Dunn, Brett Brick A Lantz, Kurt P Spindler, Michael J Stuart, Annunziato Ned Amendola, Christopher C Annunziata, Robert A Arciero, Bernard R Bach, Champ L Baker, Arthur R Bartolozzi, Keith M Baumgarten, Jeffrey H Berg, Geoffrey A Bernas, Stephen F Brockmeier, Robert H Brophy, Charles A Bush-Joseph, J Brad Butler V, James L Carey, James E Carpenter, Brian J Cole, Jonathan M Cooper, Charles L Cox, R Alexander Creighton, Tal S David, David C Flanigan, Robert W Frederick, Theodore J Ganley, Charles J Gatt, Steven R Gecha, James Robert Giffin, Sharon L Hame, Jo A Hannafin, Christopher D Harner, Norman Lindsay Harris, Keith S Hechtman, Elliott B Hershman, Rudolf G Hoellrich, David C Johnson, Timothy S Johnson, Morgan H Jones, Christopher C Kaeding, Ganesh V Kamath, Thomas E Klootwyk, Bruce A Levy, C Benjamin Ma, G Peter Maiers, Robert G Marx, Matthew J Matava, Gregory M Mathien, David R Mcallister, Eric C Mccarty, Robert G Mccormack, Bruce S Miller, Carl W Nissen, Daniel F O'Neill, Brett D Owens, Richard D Parker, Mark L Purnell, Arun J Ramappa, Michael A Rauh, Arthur C Rettig, Jon K Sekiya, Kevin G Shea, Orrin H Sherman, James R Slauterbeck, Matthew V Smith, Jeffrey T Spang, Col Ret Steven J Svoboda, Timothy N Taft, Joachim J Tenuta, Edwin M Tingstad, Armando F Vidal, Darius G Viskontas, Richard A White, James S Williams, Michelle L Wolcott, Brian R Wolf, James J York, Rick W Wright

Faculty, Staff and Student Publications

Background: Meniscal preservation has been demonstrated to contribute to long-term knee health and has been a successful intervention in isolation and in patients with anterior cruciate ligament reconstruction (ACLR). The long-term results of meniscal repair in the setting of revision ACLR have yet to be documented.

Purpose: To report the incidence of meniscal repair failures at the 6-year follow-up in a cohort of patients who underwent concurrent revision ACLR and primary meniscal repair.

Study design: Prospective cohort study; Level of evidence, 2.

Methods: All revision ACLRs with concomitant primary meniscal repair cases from a multicenter group between 2006 and 2011 …

Tubulin Regulates Stability And Localization Of Stmn2 By Binding Preferentially To Its Soluble Form, Xiang Deng, Gary A Bradshaw, Marian Kalocsay, Timothy Mitchison

Faculty, Staff and Student Publications

The small, tubulin-binding protein STMN2 is highly expressed in neurons and is implicated in amyotrophic lateral sclerosis. STMN2 degrades rapidly and accumulates at axotomy sites, suggesting fast turnover is crucial for its neuroprotective function. We show that STMN2 was primarily degraded by the ubiquitin-proteasome system. Its membrane-targeting N-terminal domain promoted fast turnover, whereas its tubulin-binding domain promoted stabilization. Proximity labeling and imaging showed that tubulin binding reduced STMN2 targeting to trans-Golgi network membranes. Pull-down assays showed that tubulin binds preferentially to soluble over membrane-bound STMN2. Our observations suggest that STMN2 interconverts between a soluble, tubulin-bound form and a membrane-bound, tubulin-free …

Smags-Lasso: A Novel Feature Selection Method For Sensitivity Maximization In Early Cancer Detection, Hamid Khoshfekr Rudsari, Sara Khorami-Sarvestani, Johannes F Fahrmann, James P Long, Samir Hanash, Kim-Anh Do, Ehsan Irajizad

Faculty, Staff and Student Publications

Background: Sensitivity and specificity are foundational metrics for cancer detection tools. However, most machine learning algorithms prioritize overall accuracy during optimization, which fails to align with clinical priorities of early detection. We aim to develop a feature selection machine learning algorithm while maximizing sensitivity at a given specificity.

Methods: We developed SMAGS-LASSO, a machine learning algorithm that combines our developed Sensitivity Maximization at a Given Specificity (SMAGS) framework with L1 regularization for feature selection. This approach simultaneously optimizes sensitivity at user-defined specificity thresholds while performing feature selection. SMAGS-LASSO utilizes a custom loss function with L1 regularization and multiple parallel optimization …

The Revised Risk Analysis Index Outperforms The 5-Factor Modified Frailty Index In Predicting Postoperative Morbidity After Pilon Fracture Fixation., Gabriel Deoliveira, Amber Park, Arsalaan Sayyed, Aruni Areti, Nithin Gupta, Taylor Manes, Morgan Turnow, Benjamin Taylor, Jack W Weick

Trauma and Acute Care Articles

BACKGROUND: Pilon fractures often result from high energy mechanisms resulting in long-term morbidity and postoperative complications. While there is extensive literature investigating frailty scales as tools for preoperative risk stratification in orthopedic surgery, there is no literature regarding their use in fixation of pilon fractures. The objective of this study was to compare the predictive ability and discriminative accuracy of the Revised Risk Analysis Index (RAI-rev) and the 5-Item Modified Frailty (mFI-5) in 30-day postoperative outcomes following surgical fixation of pilon fractures.

METHODOLOGY: The ACS-NSQIP database was used to identify patients undergoing surgical fixation of pilon fractures from 2015 to …

Long-Term Illness In Adults Hospitalized For Respiratory Syncytial Virus Disease, United States, February 2022-September 2023, Aleda M Leis, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

Respiratory syncytial virus (RSV) can cause severe illness, but little is known about long-term consequences in hospitalized adults. We surveyed adults (>18 years of age) who survived hospitalization for RSV or COVID-19 during February 2022-September 2023 about physical functioning and quality of life; surveys were conducted 6-12 months after hospitalization. We compared outcomes after RSV hospitalization by age (< 60 vs. >60 years) and to those hospitalized for COVID-19 by using multivariable regression models. Among 146 adults hospitalized with RSV, 27.4% reported severe breathlessness and 21.9% poor quality of life at follow-up. Few differences were seen in posthospital illness by age. …

Rhinovirus C15 Infection Induces Airway Epithelial Cell Remodeling And Robust Inflammatory Responses: Potential Implications For Airway Obstruction In Children, Yiran Li, Shilpi Singh, Hannah L Briggs, Jordan E Kreger, Alex L Sliwicki, Emily L Eberhardt, Shiuhyang Kuo, Jessica A Czapla, J Kelley Bentley, Heidi R Flori, Amjad Horani, Steven L Brody, Marc B Hershenson

2020-Current year OA Pubs

Despite recognition of rhinovirus-C (RV-C) as a cause of severe respiratory exacerbations, little is known about the pathogenesis of RV-C infections. We infected mucociliary-differentiated primary tracheobronchial epithelial cells with RV-C15 or RV-A16. Initial RNASeq data showed that, compared to RV-A16, RV-C15 decreased expression of genes related to ciliary function while increasing expression of genes associated with mucus secretion and inflammation. Using different airway epithelial cell isolates, we confirmed greater reduction in DNAI2 and FOXJ1 (regulates production of motile cilia) and increased FOXA3 (regulates mucin -related gene expression) after RV-C15 infection compared to RV-A16. Similarly, nasal swab samples from children with …

Genetic Predisposition To Persistent Fatigue After A Diagnosis Of Colorectal Cancer, Elham Kazemian, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cancer-related fatigue (fatigue) is a common and persistent symptom after cancer treatment, yet the role of genetic susceptibility remains unclear.

METHODS: We used data from a prospective cohort study called the ColoCare Study, conducted over 5 US sites and Germany. Fatigue was assessed at 5 time points using the European Organisation for the Research and Treatment of Cancer Core Quality of Life Questionnaire fatigue subscale and analyzed as (1) a binary summary measure of the trajectory from diagnosis into survivorship (defined as severe: yes/no), (2) a mean score across all time points, and (3) the highest (ie, worst) score …

Telemedicine Preexposure Prophylaxis Prescribing From A Large Online Us Company, Aaron J Siegler, Shi Hao Ernest Koh, Tristan Schukraft, Simon Mazzoni, Edwin Corbin-Gutierrez, Rupa R Patel, Patrick S Sullivan, Wenting Huang

2020-Current year OA Pubs

IMPORTANCE: HIV preexposure prophylaxis (PrEP) is highly effective in HIV prevention; telemedicine is a promising avenue for delivering PrEP care.

OBJECTIVE: To explore telemedicine delivery of PrEP care (telePrEP) by the largest telePrEP company in the US.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, single-arm cohort study used health record data of patients receiving telePrEP from MISTR LLC, a for-profit telehealth company, from November 27, 2018, to March 5, 2025. Patient characteristics and AIDSVu data were assessed to determine levels of PrEP use nationally. Retention in care was assessed for persons initiating PrEP in 2020, 2021, and 2022. Data were analyzed …