Medicine and Health Sciences Commons^™

Does Stem Design Affect Primary Stability Of Splined Tapered Fluted Stems? A Biomechanical Cadaver Study, Shuyang Han, Daniel C Mascarenhas, Camryn A Pletka, Jonathan E Gold, Sabir K Ismaily, Matthew Cao, Matthew W Brewer, Robert Frangie, Philip C Noble, David Rodriguez-Quintana

Faculty, Staff and Student Publications

Background: Tapered fluted stems are an excellent solution for revision hip arthroplasty following periprosthetic fractures. However, existing implant designs differ in terms of the number of splines, taper angle, and cross-sectional design, and there is a lack of knowledge on the biomechanical effect of these design variations. Therefore, the objective of this study was to compare the primary stability of two representative stem designs and the extent and distribution of stem-bone contact in a periprosthetic fracture model. It was hypothesized that a greater number of splines would lead to greater stability.

Methods: There were six pairs of cadaver femora included …

Trop2 Expression In Salivary Gland Adenoidcystic Carcinoma (Acc) According To Histologic Subtype: Therapeutic Implications, Juliana Mota Siqueira, Yoshitsugu Mitani, Mario L Marques-Piubelli, Camilla Oliveira Hoff, Flavia Bonini, Luana Guimaraes De Sousa, Mutsumi Mitani, Giovanna Lopes Carvalho, Fabio Daumas Nunes, Leandro Luongo Matos, Shiaw-Yih Lin, Michael T Spiotto, Ehab Y Hanna, Daniel J Mcgrail, Adel K El-Naggar, Renata Ferrarotto

Faculty, Staff and Student Publications

Background: Adenoid cystic carcinoma (ACC) is a common salivary gland carcinoma with high recurrence and distant metastasis rates. Currently, there is no standard systemic treatment available. TROP2 is a transmembrane glycoprotein involved in the oncogenesis of several tumors that can be therapeutically targeted by a TROP2-antibody-drug conjugate (ADC). We aimed to characterize TROP2 expression in ACC and assess TROP2 as a potential therapeutic target.

Methods: TROP2 immunohistochemistry was performed in a tissue microarray including 165 ACC of salivary gland. The tumors were grouped according to the histological pattern as non-solid, solid + non-solid, or solid. TROP2 protein expression in ACC …

Which Score For What? Operationalizing Standardized Cognitive Test Performance For The Assessment Of Change, Cristan Farmer, Audrey Thurm, Tanvi Das, E Martina Bebin, Jonathan A Bernstein, Elizabeth Berry-Kravis, Joseph D Buxbaum, Charis Eng, Thomas Frazier, Antonio Y Hardan, Alexander Kolevzon, Darcy A Krueger, Julian A Martinez-Agosto, Hope Northrup, Craig M Powell, Latha Valluripalli Soorya, Joyce Y Wu, Mustafa Sahin, Developmental Synaptopathies Consortium

Faculty, Staff and Student Publications

Developmental domains, such as cognitive, language, and motor, are key concepts of interest in longitudinal studies of intellectual and developmental disabilities (IDD). Normative scores (e.g., IQ) are often used to operationalize performance on standardized tests of these concepts, but it is the interval-distributed person-ability scores that are intended for the assessment of within-individual change. Here we illustrate the use and interpretation of several Stanford Binet, 5th Edition score types (IQ, extended IQ, Z-normalized raw score, developmental quotient, raw sum score, age equivalent, and ability score) using data from two longitudinal studies of rare genetic conditions associated with IDD. We found …

Auricular Point Acupressure For Older Adults With Chronic Low Back Pain: A Randomized Controlled Trial, Jennifer Kawi, Chao Hsing Yeh, Nada Lukkahatai, Hulin Wu, Natalia E Morone, Ronald Glick, Elizabeth A Schlenk, Claudia Campbell, Johannes Thrul, Xinran Huang, Hongyu Wang, Hejingzi Monica Jia, Paul Christo, Constance Johnson

Faculty, Staff and Student Publications

Objective: Efficacious modalities are limited in chronic low back pain (cLBP). We determined the efficacy of auricular point acupressure (APA) in older adults with cLBP.

Design: 3-arm randomized controlled trial.

Setting: Baltimore, Maryland.

Participants: Participants, ≥60 years with cLBP, were randomized (1:1:1) to APA with ear points targeted to cLBP (T-APA, n = 92), points nontargeted to cLBP (NT-APA, n = 91), or waitlist education control (n = 89), and followed up to 6 months (6M). Participants in the APA groups received 4 weekly APA sessions; the education control group received 4 weekly educational sessions.

Intervention: APA.

Main outcomes and …

The Late Positive Potential Predicts Contingency Management Outcomes For Cocaine Use Disorder, Heather E Webber, Douglas J Calvillo, Francesco Versace, Constanza De Dios, Robert Suchting, Charles E Green, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

Contingency management (CM) relies on motivation and reward processing and is among the most effective treatments available for cocaine use disorder (CUD), yet success rates do not meet desired clinical efficacy. To improve treatment-individual fit, we investigated the late positive potential (LPP), a measure of incentive salience to cues, as a predictor of treatment response. Treatment-seeking adults with CUD (N = 58) completed an EEG task where they viewed pleasant, unpleasant, cocaine, and neutral images. Participants received CM and counseling for four weeks. Urine was collected thrice weekly. We defined incentive salience to cues by A) cluster analyses on LPP …

Launching! To Adulthood, A Culturally Adapted Treatment Program For Military-Dependent Autistic Young Adults And Their Military Parents: A Pilot Study, Antonio F Pagán, Jordan Kenemore, Maj Mark Ahlenius, Linda Hernandez, Stephen Armstrong, Katherine A Loveland, Ron Acierno

Faculty, Staff and Student Publications

Introduction: Military-dependent young adults (17-25 years old) with autism spectrum disorder (ASD) face significant barriers to accessing services during their transition to adulthood. Frequent relocations, disrupted care, and limited ASD-tailored interventions exacerbate the challenges for these families, with many young adults experiencing a "service cliff" as they age out of pediatric care and school-based services. Addressing these gaps is critical, particularly given the rising mental health challenges and executive dysfunction in this population. This study evaluates the preliminary efficacy of an adapted telehealth intervention, the Military-Launching! program, designed to support young adults with ASD and their military families.

Materials and …

Testing Measurement Invariance Of Self-Report And Interview Measures Of Borderline Personality Disorder Across Ethnic/Racial Groups Of Inpatient Adolescents, Salome Vanwoerden, Eric D Sumlin, Veronica Mclaren, Carla Sharp

Faculty, Staff and Student Publications

Borderline personality disorder (BPD) is a severe mental disorder that onsets during adolescence. Research examining sociocontextual differences in BPD presentation is limited and provides mixed results, highlighting the importance of further investigation and the evaluation of potential measure effects. This study assessed measurement invariance of two widely used adolescent measures (self-report—the Borderline Personality Features Scale for Children and semistructured interview—Childhood Interview of Diagnostic and Statistical Manual Borderline Personality Disorder) of BPD. Comparisons across inpatient psychiatric settings (n = 521 at a private inpatient; n = 378 at a public inpatient) and across self-identified Hispanic/Latinx (n = 193), Black …

Beyond Frequency Of Use: Exploring Additional Metrics For Quantifying Cocaine Use And Their Relation To Life Functioning And Treatment Outcome, Samantha Ellis, Rachel Sun, Angela Heads, Jin Ho Yoon, Heather Webber, Joy Schmitz, Margaret Wardle

Faculty, Staff and Student Publications

Background: Frequency of use - the number of days of use - is the most common metric for quantifying cocaine use and the most common target of treatment. However, frequency may not capture all important aspects of cocaine use. This study examined how other aspects of cocaine use (typical amount spent, variability etc.) relate to life functioning and cocaine use disorder (CUD) treatment outcomes.

Method: This is a secondary analysis of 3 clinical trials for CUD, N = 207 for the life functioning analysis and N = 173 for the outcomes analysis. Eight metrics of use were calculated from baseline …

Leveraging Existing Cohort Studies Of Mexican Women To Better Understand Hispanic Health And Cancer Risk, Dalia Stern, Liliana Gomez-Flores-Ramos, Britton Trabert, V Wendy Setiawan, Loïc Le Marchand, Henry Gomez, Paul A Scheet, Humberto Parada, Amber Pirzada, Martin Lajous, Leslie V Farland

Faculty, Staff and Student Publications

Background: Hispanics have been historically underrepresented in epidemiologic cancer research. Existing cohort studies focused on recruiting Hispanic participants have been relatively small, making studying cancer outcomes challenging. Therefore, we aimed to compare the distribution of cancer risk factors among Hispanic women of Mexican heritage (HWMH) participating in existing cohorts to explore the possibility of future data pooling efforts.

Methods: We used baseline data of HWMH from three US-based studies, the Mexican American Cohort (MAC; n = 19,797; 2001-2017), the Multiethnic Cohort (MEC; n = 18,007; 1993-1996), and the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; n = 4,022; 2008-2011), and …

Variants In Cald1, Esrp1, And Rbfox1 Are Associated With Orofacial Cleft Risk, Jenna C Carlson, Xinyi Zhang, Zeynep Erdogan-Yildirim, Terri H Beaty, Azeez Butali, Carmen J Buxó, Lord J J Gowans, Jacqueline T Hecht, Ross E Long, Lina Moreno, Jeffrey C Murray, Ieda M Orioli, Carmencita Padilla, George L Wehby, Eleanor Feingold, Elizabeth J Leslie-Clarkson, Seth M Weinberg, Mary L Marazita, John R Shaffer

Faculty, Staff and Student Publications

Nonsyndromic orofacial clefts (OFCs) are common, heritable birth defects caused by both genetic and environmental risk factors. Despite the identification of many genetic loci harboring OFC-risk variants, there are many unknown genetic determinants of OFC. Furthermore, while the process of embryonic facial development is well characterized, the molecular mechanisms that underly it are not. This represents a major hurdle in understanding how disruptions in these biological processes result in OFC. Thus, we sought to identify novel OFC-risk loci through a genome-wide multi-ancestry study of five nested OFC phenotypes (isolated cleft lip [CLO], isolated cleft palate [CPO], cleft lip and palate …

Eular/Acr Classification Criteria For Paediatric Chronic Nonbacterial Osteomyelitis (Cno)., Yongdong Zhao, Melissa S. Oliver, Anja Schnabel, Eveline Y. Wu, Zhaoyi Wang, Achille Marino, Cassyanne L. Aguiar, Jonathan D. Akikusa, Ummusen Kaya Akca, Beverley Almeida, Simone Appenzeller, Erin Balay-Dustrude, Ozge Basaran, Matthew L. Basiaga, Yelda Bilginer, David A. Cabral, Martina Capponi, Nathan Donaldson, Bugra Han Egeli, Emily Fox, Antonella Insalaco, Ramesh S. Iyer, Annette F. Jansson, Inna Kostik, Mikhail Kostik, Leonard K. Kovalick, Katia Tomie Kozu, Sivia K. Lapidus, Tzielan C. Lee, Aleksander Lenert, Kamran Mahmood, Edoardo Marrani, Doaa Mosad Mosa, Ian Muse, Alexander Mushkin, Katherine D. Nowicki, Farzana Nuruzzaman, Karen Onel, Manuela Pardeo, Trang Sophia Pham, Lauren Potts, Athimalaipet V. Ramanan, Angelo Ravelli, Nathan D. Rogers, Andrew W. Grim, Micol Romano, Natalie Rosenwasser, Takashi Shawn Sato, Gabriele Simonini, Jennifer B. Soep, Sara M. Stern, Timmy Strauss, Angela Taneja Kohli, Alexander C. Theos, Lori B. Tucker, Leslie F. Vogel, Shima Yasin, Stephen C. Wong, Katerina Bouchalova, Alison M. Hendry, Kevin C. Cain, Hermann J. Girschick, Fatma Dedeoglu, Christian M. Hedrich, Ronald M. Laxer, Polly J. Ferguson, Raymond Naden, Seza Ozen

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To develop and validate classification criteria for paediatric chronic nonbacterial osteomyelitis (CNO) jointly supported by the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR).

METHODS: This international initiative had 4 phases: (1) candidate items were proposed in a survey of paediatric rheumatologists, (2) criteria definition and reduction by Delphi and nominal group technique exercises, (3) criteria weighting using multicriteria decision analysis, and (4) refinement of weights and threshold score in a development cohort of 441 patients and validation in another cohort of 514 patients.

RESULTS: The new EULAR/ACR classification criteria for CNO require …

Phenotypic Divergence Of Jag1- And Notch2-Associated Alagille Syndrome & Disease-Specific Notch2 Variant Classification Guidelines., Shannon M. Vandriel, Li-Ting Li, Huiyu She, Jian-She Wang, Kathleen M. Loomes, David A. Piccoli, Irena Jankowska, Piotr Czubkowski, Dorota Gliwicz-Miedzińska, Lorenzo D'Antiga, Emanuele Nicastro, Florence Lacaille, Dominique Debray, Étienne M. Sokal, Tanguy Demaret, Rima L. Fawaz, Silvia Nastasio, Kyung Mo Kim, Seak Hee Oh, Björn Fischler, Henrik Arnell, Catherine Larson-Nath, Winita Hardikar, Sahana Shankar, Shikha S. Sundaram, Alexander Chaidez, Pinar Bulut, Pier Luigi Calvo, Mureo Kasahara, Niviann Blondet, Eberhard Lurz, Anna-Maria Kavallar, Emmanuel M. Gonzales, Emmanuel Jacquemin, Jérôme Bouligand, Noelle H. Ebel, Jeffrey A. Feinstein, Susan M. Siew, Michael O. Stormon, Saul J. Karpen, Rene Romero, M Kyle Jensen, Catalina Jaramillo, James E. Squires, Sarah M. Bedoyan, Deirdre A. Kelly, Jane Hartley, Henkjan J. Verkade, Way Seah Lee, Chatmanee Lertudomphonwanit, Ryan T. Fischer, Henry C. Lin, Nathalie Rock, Yael Mozer-Glassberg, Amin J. Roberts, Helen M. Evans, Wikrom Karnsakul, Gabriella Nebbia, Victorien M. Wolters, Pamela L. Valentino, Jesus Quintero Bernabeu, Amal A. Aqul, Cigdem Arikan, María Legarda Tamara, Cristina Molera Busoms, Thomas Damgaard Sandahl, Giuseppe Indolfi, Andréanne N. Zizzo, Aglaia Zellos, Ruben E. Quiros-Tejeira, Ermelinda Santos-Silva, Kathleen B. Schwarz, Jernej Brecelj, Maria Camila Sanchez, Maria Lorena Cavalieri, Christos Tzivinikos, Sabina Wiecek, John Eshun, Nanda Kerkar, Quais Mujawar, Zerrin Önal, Cristina Gonçalves, Jennifer Garcia, Seema Alam, Carolina Jimenez-Rivera, Luis Bujanda, Richard J. Thompson, Bettina E. Hansen, Nancy B. Spinner, Melissa A. Gilbert, Binita M. Kamath, Global Alagille Alliance (Gala) Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND & AIMS: Alagille syndrome (ALGS) is a rare, autosomal dominant disorder with high phenotypic heterogeneity. Disease-causing variants are primarily identified in Jagged1 (JAG1), with fewer reported in NOTCH2. JAG1 variants cause disease through a mechanism of haploinsufficiency, but the mechanism for NOTCH2 variants is not completely understood, making classification of variants more challenging. Using a large, international patient cohort acquired through the Global ALagille Alliance (GALA) study, we sought to improve classification of NOTCH2 variants and study phenotypic differences between NOTCH2- and JAG1-related disease.

METHODS: Clinical and molecular data from 952 individuals with ALGS in GALA were analysed and …

Mature And Migratory Dendritic Cells Promote Immune Infiltration And Response To Anti-Pd-1 Checkpoint Blockade In Metastatic Melanoma, Jiekun Yang, Cassia Wang, Doris Fu, Li-Lun Ho, Kyriakitsa Galani, Lee Chen, Jose Gonzalez, Jolene Fu, Amy Y Huang, Dennie T Frederick, Liang He, Mukta Asnani, Rahul Tacke, Emily J Robitschek, Sandeep K Yadav, Wentao Deng, Kelly P Burke, Tatyana Sharova, Ryan J Sullivan, Sarah Weiss, Kunal Rai, David Liu, Genevieve M Boland, Manolis Kellis

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, yet most patients fail to achieve durable responses. To better understand the tumor microenvironment (TME), we analyze single-cell RNA-seq (~189 K cells) from 36 metastatic melanoma samples, defining 14 cell types, 55 subtypes, and 15 transcriptional hallmarks of malignant cells. Correlations between cell subtype proportions reveal six distinct clusters, with a mature dendritic cell subtype enriched in immunoregulatory molecules (mregDC) linked to naive T and B cells. Importantly, mregDC abundance predicts progression-free survival (PFS) with ICIs and other therapies, especially when combined with the TCF7 + /- CD8 T cell ratio. Analysis …

Generation Of Human Induced Pluripotent Stem Cell Line From A Familial Alzheimer’S Disease Patient Carrying Missense Mutations In Psen1 And Mapt Genes, Ashaq H Najar, Sofia E Sepulveda, Camila Gherardelli, Fatemeh Elahian, Amber Fontenot-Roberts, Aleksandar Bajic, David H Hunter, Claudio Soto, Paul E Schulz, Abhisek Mukherjee

Faculty, Staff and Student Publications

Alzheimer's disease (AD), pathologically characterized by misfolding and accumulation of amyloid beta (Aβ) and hyperphosphorylated tau, is the leading cause of neurodegenerative dementia, accounting for 60-80 % of cases. The familial form of AD is caused by mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes. Here, we report the generation of an iPSC line from a 39-year-old AD patient carrying a missense mutation in PSEN1 (F177S), leading to very early onset of AD. The patient also carries a rare variant Q49E in the microtubule-associated protein tau gene (MAPT) with an as yet unknown clinical significance.

Secretogranin 2 Binds Lilrb4 Resulting In Immunosuppression, Xing Yang, Ryan Huang, Meng Fang, Yubo He, Jingjing Xie, Xiaoye Liu, Chengcheng Zhang, Qi Lou, Mi Deng, Wei Xiong, Cheryl Lewis, Zade Sadek, Ankit Gupta, Lianqi Chen, Xuewu Zhang, Lei Guo, Lin Xu, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

Faculty, Staff and Student Publications

Immunosuppressive myeloid cells are important in a variety of physiological and pathological contexts, including tumor development, but how hormones might regulate their activity is unclear. Secretogranins, a family of secretory proteins in endocrine and neuronal cells, are proposed to function as prohormones or hormones, but their specific receptors are unknown. Here we show that secretogranin 2 (SCG2), a granin family member, functionally interacts with leukocyte immunoglobulin-like receptor B4 (LILRB4) on monocytic cells. Tumor-derived SCG2 promotes tumor growth in myeloid-specific LILRB4 transgenic mice in a T cell-dependent manner, whereas SCG2 deficiency in host mice impairs tumor progression and reduces infiltration of …

The Brescia International Multidisciplinary Consensus Guidelines On The Optimal Pathology Assessment And Multidisciplinary Pathways Of Non-Pancreatic Neoplasms In And Around The Ampulla Of Vater (Peripan), Mohammad Abu Hilal, Bas A Uijterwijk, Daniël H L Lemmers, Boris V Janssen, Marc G Besselink, Denise Bianchi, Arantza Fariña, Noriyoshi Fukushima, Anthony J Gill, Seung-Mo Hong, Alyssa Krasinskas, Claudio Luchini, Laura Melocchi, Giulio Rossi, Aldo Scarpa, Olca Basturk, Deyali Chatterjee, Angela Chou, Irene Esposito, Roger Feakins, Bas Groot Koerkamp, Ralph H Hruban, Stefano La Rosa, Chanjuan Shi, Aatur Singhi, Joanne Verheij, Huamin Wang, Sergio Alfieri, Fabio Ausania, Adnan Alseidi, Marco J Bruno, Ugo Boggi, Claudio Bnà, Christos Dervenis, Massimo Falconi, Michele Ghidini, Jakob W Kist, Giovanni Marchegiani, Michele Milella, Roberto Salvia, Ajith Siriwardena, Hanneke Wilmink, Alberto Zaniboni, Shaimaa Al-Janabi, Maia Blomhoff Holm, Eva Roos, Naoki Sano, In Hye Song, Zeynep Tarcan, Gianpaolo Balzano, Isabella Frigerio, Alfredo Guglielmi, Giuseppe Malleo, Horacio Asbun, Volkan Adsay, Caroline Verbeke

Faculty, Staff and Student Publications

IMPORTANCE: The lack of multidisciplinary workflow guidelines and clear definitions and classifications for neoplasms in and around the ampulla of Vater results in inconsistencies affecting patient care and research.

OBJECTIVE: The PERIPAN international multidisciplinary consensus group aimed to standardize the multidisciplinary diagnostic workflow and achieve consensus on definitions and classifications in order to ensure proper classification and optimal diagnostic assessment and consequently to improve patient care and future research.

DESIGN: An international team of 43 experts (pathologists, surgeons, radiologists, gastroenterologists, oncologists) from 12 countries identified knowledge gaps, reviewed 37061 articles, and proposed recommendations using the Scottish Intercollegiate Guidelines Network methodology …

Baseline Α-Synuclein Seeding Activity And Disease Progression In Sporadic And Genetic Parkinson’S Disease In The Ppmi Cohort, Jackson G Schumacher, Xinyuan Zhang, Eric A Macklin, Jian Wang, Armin Bayati, Johannes M Dijkstra, Hirohisa Watanabe, Michael A Schwarzschild, Marianna Cortese, Xuehong Zhang, Xiqun Chen

Faculty, Staff and Student Publications

Background: α-Synuclein (α-syn) seed amplification assays (SAAs) have shown remarkable potential in diagnosing Parkinson's disease (PD). Using data from the Parkinson's Progression Markers Initiative (PPMI) cohort, we aimed to test whether baseline α-syn seeding activity and α-syn SAA kinetic parameters are associated with disease progression in sporadic PD, LRRK2-associated PD (LRRK2 PD), and GBA-associated PD (GBA PD).

Methods: We analysed 7 years of motor, non-motor, and cognitive assessments and 5 years of dopamine transporter imaging along with baseline α-syn SAA results from 564 PPMI participants (n = 332 sporadic PD, 162 LRRK2 PD, and 70 GBA PD) using linear mixed-effects …

Isatuximab Plus Bortezomib, Lenalidomide, And Dexamethasone For Transplant-Ineligible Newly Diagnosed Multiple Myeloma Patients: A Frailty Subgroup Analysis Of The Imroz Trial, Salomon Manier, Meletios-Athanasios Dimopoulos, Xavier P Leleu, Philippe Moreau, Michele Cavo, Hartmut Goldschmidt, Robert Z Orlowski, Muriel Tron, Christina Tekle, Marie-France Brégeault, Andrea T Shafer, Meral Beksac, Thierry Facon

Faculty, Staff and Student Publications

Patients with multiple myeloma (MM) meeting frailty criteria have worse outcomes than those identified as non-frail. Here, we present a post hoc subgroup analysis of IMROZ, a global, phase III, open-label study investigating isatuximab (Isa) with bortezomib, lenalidomide, and dexamethasone (VRd) followed by Isa-Rd (N=265) versus VRd followed by Rd (N=181) in newly diagnosed transplant-ineligible MM (Ti NDMM) patients using the simplified International Myeloma Working Group (sIMWG) frailty score. Although patients aged >80 years were excluded, there was no exclusion for patients meeting frailty criteria. All patients received standard VRd/Rd dosing; Isa-VRd patients received intravenous Isa (cycle 1, 10 mg/kg …

Systematic Literature Review Of Intravenous Versus Subcutaneous Administration Of Oncology Therapies: A Clinical, Economic And Patient Perspective, Saby George, Maria T Bourlon, Michael J Overman, Matt Dixon, Karishma Shelley, Kristen J Markus, Rachel M Kewley, Sophie I Pope, Laurence Albigès

Faculty, Staff and Student Publications

Subcutaneous (SC) formulations of oncology therapies offer a potentially less time-consuming and more convenient alternative to intravenous (IV) administration. However, exploring the potential benefits of SC over IV administration from a broader perspective is necessary to understand the larger-scale impact. In this systematic literature review (SLR), we evaluated the efficacy, pharmacokinetics/pharmacodynamics (PK/PD), safety, and patient and healthcare provider (HCP) preference for SC/IV oncology therapies, along with differences in patient outcomes, costs, and time requirements. The SLR was conducted in January 2019 and updated in May 2023, and included 169 publications. Studies providing comparative results between IV and SC formulations regarding …

Exploring Boundaries With Food, Substances, And People In Substance Use Recovery: A Qualitative Analysis, Tiffany Champagne-Langabeer, Audrey Sarah Cohen, Kriti Shrestha, Jie Zhu, Audrey Lopez, Alisha Campbell, Christine Bakos-Block

Faculty, Staff and Student Publications

Background: In the United States, over 47 million youth and adults live with a substance use disorder (SUD). These individuals are frequently malnourished and have metabolic dysregulation as a result. Nutrition interventions incorporating a mindfulness-based approach help recovery efforts that are physical and mental.

Objective: The objective of this study was to explore and analyze the perspectives and experiences of individuals with SUD regarding emotional regulation and nutrition. The study used a mixed methods approach to generate insights for improving recovery support and developing future interventions.

Design: In 2024, an exploratory mixed methods study was conducted based on a large …

Predicting Clinical Success Of Ct-Based Functional Drained Liver Volume Assessment In Malignant Biliary Obstruction, Ethan Y Lin, Bruno C Odisio, Koustav Pal, Iwan Paolucci, Ryan P Kempen, Nicolas Cardenas, Paige Reed, Ketan Y Shah, Ahmed Awad, Rahul A Sheth, David Fuentes, Alda Tam

Faculty, Staff and Student Publications

Purpose

To compare the predictive accuracy of subjective versus objective assessment of three-dimensional functional drained liver volume (fDLV) for clinical success after percutaneous transhepatic biliary drainage (PTBD).

Materials and Methods

This retrospective study included patients with malignant biliary obstruction and hyperbilirubinemia who underwent de novo PTBD between January 2016 and February 2017. Clinical success was defined as achieving total bilirubin level less than 1.8 mg/dL (30.8 μmol/L) within 30 days after PTBD. Seven interventional radiologists independently categorized subjective fDLV into four groups: less than 30%, 30%–50%, 51%–75%, and greater than 75% of the total liver volume. Objective fDLV was calculated …

Using Extension-Based Mrna Display To Design Antibody-Like Proteinogenic Peptides For Human Pd-L1, Justin N Ong, Brian J Grindel, Scott A Rankin, Sarah H Naylon, Anupallavi Srinivasamani, Guillaume J Trusz, Xiaowen Liang, Md Nasir Uddin, Lauren Fuller, Michael Curran, Stephane P Roche, Terry T Takahashi, Richard W Roberts, Steven W Millward

Faculty, Staff and Student Publications

Many peptide drugs rely on nonproteinogenic amino acids and chemical modifications for improved activity and proteolytic stability. However, these features also make drug production expensive and challenging to scale. Here, we engineered small, linear, proteinogenic peptides that bind human programmed death-ligand 1 (hPD-L1) with high affinity and stability using mRNA display affinity maturation. The resulting peptides, SPAM2 and SPAM3, have antibody-like affinities for hPD-L1 (dissociation constants between ~250 and 300 pM) and are selective for hPD-L1. Both SPAM2 and SPAM3 compete with hPD-L1 ligands known to interact with the programmed cell death protein 1 site and are stable in human …

Mechanisms Underlying Treatment-Resistant Depression: Exploring Sex-Based Biological Differences, Francisco E R Da Silva, Atakan Yucel, Antonio P M Menezes, Ana C Ruiz, Marcela C Carbajal Tamez, Tatiana Barichello, Giselli Scaini, Joao Quevedo

Faculty, Staff and Student Publications

Treatment-resistant depression (TRD) represents a severe and complex subtype of major depressive disorder (MDD), affecting approximately 30% of patients who fail to respond adequately to multiple standard antidepressant therapies. While the pathophysiology of TRD remains incompletely understood, emerging evidence suggests that sex-based biological differences might influence its onset, progression, and treatment response. Women are disproportionately affected by depression and are more likely to experience residual symptoms and treatment resistance, potentially due to hormonal fluctuations, immune system differences, and variations in brain circuitry and neuroplasticity. This narrative explores the current literature on the mechanisms underlying TRD, with a particular emphasis on …

Risk Of Second Primary Lung Cancer Among Cancer Survivors Stratified By The Site Of First Primary Cancer And The Lung Cancer Screening Eligibility Status, Sara Nofal, Edwin J Ostrin, Jianjun Zhang, Jia Wu, Paul Scheet, Mara B Antonoff, John V Heymach, Iakovos Toumazis

Faculty, Staff and Student Publications

Personal history of cancer is an independent risk factor for developing lung cancer. However, it is not considered in the current US lung cancer screening (LCS) guidelines. In this study, we assessed the risk of developing lung cancer among cancer survivors across 24 different sites of first primary cancer stratified by their LCS eligibility status. Using data from the Patient History Database at the University of Texas MD Anderson Cancer Center, we calculated and compared the cumulative incidence of second primary lung cancer, the overall and the LCS eligibility status-specific, stratified by the site of first primary cancer among cancer …

Unbound Bilirubin And Risk Of Severe Neurodevelopmental Impairment In Extremely Low Birthweight Newborns, Cody C Arnold, Ivana Maric, Ronald J Wong, Jon E Tyson, David K Stevenson

Faculty, Staff and Student Publications

Background: Unbound bilirubin (UB) was measured on day 5 ± 1 in 1101 ELBW newborns in the Aggressive vs Conservative Phototherapy randomized controlled trial. We accessed this dataset to quantify the UB-mediated risk of severe neurodevelopmental impairment (sNDI) in extremely low birthweight (ELBW) newborns.

Methods: UB levels were standardized within laboratories as z-score percentiles. A dichotomous UB exposure variable was based on sharply increased risk of sNDI at the 85th percentile (UBz>85th). Targeted maximum likelihood estimation with ensemble machine learning (TMLE + ML) and logistic regression (LR) were used to estimate sNDI risk attributable to UBz>85th.

Results: UB …

Utility Of Whole-Slide Imaging For Rapid Evaluation Of Thyroid Fna: A Multireader Prospective Study, Mohammed S Ahmed, Dianna Klippel-Almaraz, Sara E Amin, Gloria H Sura, Uma Rani Kundu, Wendong Yu, Jogn M Stewart, Qiong Gan, Savitri Krishnamurthy

Faculty, Staff and Student Publications

Background: Rapid on-site evaluation (ROSE) of thyroid fine-needle aspiration biopsy (FNAB) improves diagnostic adequacy and facilitates ancillary molecular testing. In this prospective, multireader study, the authors evaluated the feasibility of using whole-slide images (WSIs) for ROSE to determine specimen adequacy and preliminary categorization (according to The Bethesda System for Reporting Thyroid Cytopathology [Bethesda]) of image-guided thyroid FNABs compared with conventional light-microscopic (LM) examination of the same specimens in a referral cancer center.

Methods: The authors evaluated 98 ultrasound-guided thyroid FNAB cases. Smears were stained with Papanicolaou and Diff-Quik and were scanned at ×20 magnification using a Leica Aperio CS2 scanner. …

Spatial Colocalization And Molecular Crosstalk Of Myofibroblastic Cafs And Tumor Cells Shape Lymph Node Metastasis In Oral Squamous Cell Carcinoma, Ken Furudate, Shuya Kasai, Tadashi Yoshizawa, Yuya Sasaki, Kohei Fujikura, Shintaro Goto, Ryohei Ito, Koki Takagi, Tomoyuki Tanaka, Hiroshi Kijima, Kosei Kubota, Ken Itoh, Wataru Kobayashi, Koichi Takahashi

Faculty, Staff and Student Publications

Lymph node metastasis (LNM) is a critical prognostic factor for patients with oral squamous cell carcinoma (OSCC). Previous research has implicated the partial epithelial-to-mesenchymal transition of tumor cells and myofibroblastic cancer-associated fibroblasts (myCAFs) in the LNM process. However, the underlying molecular mechanisms remain poorly understood. Here, we conducted a comprehensive molecular analysis integrating original and publicly available OSCC data from bulk genome and transcriptome, single-cell transcriptome, and spatial transcriptome analyses. We found that myCAFs were quantitatively and functionally activated in LNM-positive samples and spatially colocalized with OSCC cells within the invasive tumor front (ITF), providing a niche that may facilitate …

Dna Methylation Cooperates With Genomic Alterations During Non-Small Cell Lung Cancer Evolution, Francisco Gimeno-Valiente, Carla Castignani, Elizabeth Larose Cadieux, Nana E Mensah, Xiaohong Liu, Kezhong Chen, Olga Chervova, Takahiro Karasaki, Clare E Weeden, Corentin Richard, Siqi Lai, Carlos Martínez-Ruiz, Emilia L Lim, Alexander M Frankell, Thomas B K Watkins, Georgia Stavrou, Ieva Usaite, Wei-Ting Lu, Daniele Marinelli, Sadegh Saghafinia, Gareth A Wilson, Pawan Dhami, Heli Vaikkinen, Jonathan Steif, Selvaraju Veeriah, Robert E Hynds, Martin Hirst, Crispin Hiley, Andrew Feber, Özgen Deniz, Mariam Jamal-Hanjani, Nicholas Mcgranahan, Tracerx Consortium, Stephan Beck, Jonas Demeulemeester, Miljana Tanić, Charles Swanton, Peter Van Loo, Nnennaya Kanu

Faculty, Staff and Student Publications

Aberrant DNA methylation has been described in nearly all human cancers, yet its interplay with genomic alterations during tumor evolution is poorly understood. To explore this, we performed reduced representation bisulfite sequencing on 217 tumor and matched normal regions from 59 patients with non-small cell lung cancer from the TRACERx study to deconvolve tumor methylation. We developed two metrics for integrative evolutionary analysis with DNA and RNA sequencing data. Intratumoral methylation distance quantifies intratumor DNA methylation heterogeneity. MR/MN classifies genes based on the rate of hypermethylation at regulatory (MR) versus nonregulatory (MN) CpGs to identify driver genes exhibiting recurrent functional …

In Situ Programming Of The Tumor Microenvironment To Alleviate Immunosuppression For Pancreatic Cancer Immunotherapy, Man Sun, Huan Zhang, Yarui Ma, Simiao Wang, Jiayi Chen, Yaxin Cui, Yun Zhang, Siyuan Hu, Dan Zhou, Pengchen Zhang, Yahui Liu, Betty Y S Kim, Wen Jiang, Xiaobing Wang, Zhaogang Yang

Faculty, Staff and Student Publications

Recent studies have highlighted the pivotal role of the cGAS‐STING pathway in cancer immunotherapy. However, clinical trials with cGAS‐STING pathway agonists have faced setbacks thanks to their short biological half‐life, lack of tumor specificity, and potential to promote tumor immune evasion. To address these challenges, a novel exosome‐based drug delivery platform, termed cmExoaCD11b is developed, designed to precisely target and reprogram the tumor microenvironment (TME) in situ for pancreatic cancer immunotherapy. cmExoaCD11b is engineered to encapsulate high copy numbers of IL‐12 mRNA and 2′3’‐cGAMP (cGAMP) and is functionalized with CD11b antibodies for targeted delivery to macrophages. Notably, cmExoaCD11b facilitated the …

Sex Disparities In Chlamydia And Gonorrhea Treatment In Us Adult Emergency Departments: A Systematic Review And Meta-Analysis, Rachel E Solnick, Rahi Patel, Ethan Chang, Carmen Vargas-Torres, Maaz Munawar, Carlin Pendell, Judith E Smith, Ethan Cowan, Keith E Kocher, Roland C Merchant

Faculty, Staff and Student Publications

BACKGROUND: Empiric antibiotic treatment for gonorrhea (GC) and chlamydia (CT) is common in U.S. emergency departments (EDs) due to the delayed availability of test results. Local studies have identified sex-based disparities in sexually transmitted infection (STI) care, with females potentially receiving less empiric treatment than males. This study evaluates how STI treatment aligns with laboratory-confirmed results to quantify potential overtreatment and undertreatment rates and investigates sex differences for these outcomes.

METHODS: We conducted a preregistered (PROSPERO #241429) systematic review and meta-analysis of studies published between January 2010 and January 2025 in U.S. EDs, excluding studies conducted exclusively in pediatric settings. …