Digital Commons Network^™

The Impact Of Sleep In High-Risk Infants, Ann-Cathrine Neukamm, Mirja Quante, Christian F Poets, Renée A Shellhaas, “Neonatal Sleep Talks (Nest)” Group

2020-Current year OA Pubs

Most of an infant's day is devoted to sleep - and normal sleep is vital to normal brain development. Sleep disruptions may impair overall health, well-being, and neurodevelopment. Disruptors of sleep and circadian health, such as noise, light, respiratory support, and clinical interventions, are highly prevalent in hospital and nursing care facilities. These factors particularly affect infants who already have an increased risk of sleep disorders and their consequences due to an underlying disease. Preterm infants and infants with disorders such as neonatal abstinence syndrome, craniofacial malformations, congenital heart disease, hypoxic-ischemic encephalopathy, Chiari-malformation/myelomeningocele, congenital musculoskeletal disease, and Down syndrome are …

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 …

The Influence Of Body Mass Index On Tumor Treating Fields Therapy In Patients With Metastatic Non-Small Cell Lung Cancer: A Post-Hoc And Simulation Analysis From The Phase Iii Lunar Study, Christian Rolfo, David E Gerber, Rupesh Kotecha, Jeffrey P Ward, Wallace Akerley, Lukas Weiss, Ariel Naveh, Nadav Shapira, Ticiana Leal, Corey J Langer, Lunar Study Investigators

2020-Current year OA Pubs

INTRODUCTION: In the phase III LUNAR study, overall survival (OS) with PD-(L)1 inhibitor or docetaxel was improved by adding Tumor Treating Fields (TTFields) therapy in patients with metastatic non-small cell lung cancer progressing on/after platinum-based therapy. This post-hoc analysis evaluated the effects of body mass index (BMI) on TTFields delivery.

METHODS: OS was assessed in LUNAR patients with BMI <  25 kg/m

RESULTS: In the BMI <  25 kg/m

CONCLUSIONS: In this post-hoc analysis, we found no difference in OS benefit of TTFields therapy between patients with BMI <  25 kg/m

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 …

Trainee Perspectives On Diversity, Equity, And Inclusion: A Group Concept Mapping Study, Nicholas Szoko, Ana Radovic, Jennifer E Wolford, Loreta Matheo, Orquidia Torres

2020-Current year OA Pubs

Growing work highlights the importance of diversity, equity, and inclusion (DEI) initiatives in graduate medical education. Few studies have employed participatory research approaches to solicit trainee perspectives related to DEI. Our goal was to utilize group concept mapping (GCM), a mixed-methods participatory research approach, to describe resident perspectives on DEI within a large pediatric residency program. To organize and represent their perspectives on DEI, trainees completed brainstorming, sorting/rating, and interpretation activities in accordance with GCM methodology. Activities occurred via two synchronous discussion sessions (brainstorming and interpretation) and an electronic survey (sorting/rating). Items from the brainstorming session were sorted (i.e. grouped …

A Multi-Center Retrospective Cohort Study Of Neurosarcoidosis Myelitis: Current Observations And Future Directions, Giovanna S Manzano, David B Clifford, Steven Richard Dunham, Masoud Majed, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The optimal treatment for neurosarcoidosis myelitis is uncertain. We characterize incident neurosarcoidosis myelitis and assess treatment response by MRI and clinical scales.

METHODS: Incident probable or definite neurosarcoidosis myelitis in adults was retrospectively identified from 13 academic medical centers. Cases were analyzed by initial treatment. The primary outcome was T1 post-contrast gadolinium enhancement resolution at 6 months post-treatment. Secondary outcomes were changes in modified Rankin scale (mRS) and Expanded Disability Status Scale (EDSS) from nadir to final follow-up.

RESULTS: Two hundred two patients were identified (median diagnosis age: 47 years (IQR 39-55); male: female 1.3:1). Median nadir mRS and …

Peptide Vaccines For Pediatric High-Grade Glioma And Diffuse Midline Glioma: Current Progress And Future Perspectives, Aron K Mebrahtu, Vatsal Jain, Eliese M Moelker, Alexandra M Hoyt-Miggelbrink, Katayoun Ayasoufi, Eric M Thompson

2020-Current year OA Pubs

High-grade gliomas (HGGs) and diffuse midline gliomas (DMGs) in pediatric patients carry a poor prognosis, necessitating the rapid development of novel therapies. Peptide vaccines represent a safe, repeatable, and rational immunotherapeutic modality aimed at inducing potent, tumor-specific T-cell responses. In this review, we define the scope of current progress by arguing that immunogenicity in children with HGG/DMG hinges on three factors: appropriate antigen class (neoantigen vs. TAA), the use of potent immunoadjuvants, and successful navigation of immune suppression. To address the gap between biological promise and clinical reality, we analyze clinical trials targeting shared tumor-associated antigens (e.g., CMV pp65, Survivin) …

Early And Mid-Term Outcomes Of Mitral Annular Calcification And Transcatheter Mitral Therapy: A Systematic Review, Yosuke Sakurai, Ashton Mcdonald, Tsuyoshi Kaneko

2020-Current year OA Pubs

BACKGROUND: Mitral annular calcification (MAC) poses technical and clinical challenges in patients undergoing mitral valve intervention. Patients with severe MAC were excluded from major previous randomized controlled trials evaluating mitral therapies. Consequently, outcomes following mitral transcatheter edge-to-edge repair (M-TEER) in this population remain controversial.

METHODS: MEDLINE and EMBASE were searched through June 2025 to identify studies reporting outcomes after M-TEER in patients with MAC. This systematic review assessed the difference in MAC grading and M-TEER eligibility across studies. The definition of procedural success was documented to highlight inconsistencies. The primary endpoint was all-cause mortality during follow-up. Secondary endpoints included procedural …

Implementing And Evaluating Visual Key Information Pages Compared To Text-Based Key Information: Protocol For A Stepped-Wedge Cluster Randomized Trial, Krista E Cooksey, Eliana C Goldstein, Clara N Lee, Jessica Mozersky, Kimberly A Kaphingst, Jingxia Liu, Shuang Wu, Molly Volkmar, Victor Catalan-Gallegos, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Informed consent is a key aspect of conducting research studies, yet many participants do not understand critical study details after reviewing long, complex consent documents. The 2018 Common Rule aimed to address this challenge by requiring a key information section, a "concise and focused" presentation of important and relevant study information. In our ongoing work, we developed a template and toolkit to improve the presentation of key information by incorporating health literacy best practices, including color and visual icons. The goal of this study is to assess the impact of the visual key information (KI) pages at both the …

Participatory Implementation Science To Enhance Knowledge And Build The Capacity To Increase The Uptake And Sustainability Of Hpv Vaccination Among Girls In Nigeria, Peter Kalulu, Olufunto A Olusanya, Nkiruka Obodoechina, Maria A Afadapa, Temitope Ojo, Priscilla A Kabutey, Caven N Ngoe, Ashley Bardon, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Human papillomavirus (HPV) vaccination can prevent cancer in low- and middle-income countries (LMICs), but its uptake remains low, especially in Nigeria. Understanding participatory approaches can help identify local strategies to increase, build capacity for, and sustain vaccine uptake. This study evaluated the effectiveness of an innovation bootcamp in enhancing the knowledge and skills of youth implementers about HPV and cervical cancer as a strategy to increase vaccine uptake among Nigerian girls aged 9-14 years. An innovation bootcamp is an intensive training program that engages end users to build capacity and skills.

METHODS: This was a five-week hybrid bootcamp guided …

Development Of Intestinal Tissue-Resident T Cells In Early-Life Mice Before And After Weaning, Catherine Montenegro, Siyuan Ding, Federico Perdomo-Celis, Manuel A Franco

2020-Current year OA Pubs

Intestinal tissue-resident T cells have been poorly characterized during early-life. Here, we phenotypically characterized tissue-resident (intravascular staining negative) CD4

Structure Of An Lgr Dimer, An Evolutionary Predecessor Of Glycoprotein Hormone Receptors, Zhen Gong, Shuobing Chen, Ziao Fu, Brian Kloss, Chi Wang, Jonathan Kim, Oliver B Clarke, Qing R Fan, Wayne A Hendrickson

2020-Current year OA Pubs

Glycoprotein hormones (GpHs) produced in the human pituitary act through receptors (GpHRs) in the gonads to support reproduction and in the thyroid for metabolism. GpHs are heterodimeric cystine-knot proteins; their receptors bind cognate hormones at an extracellular domain and signal through a transmembrane domain to heterotrimeric G proteins. GpHs and GpHRs have co-evolved from invertebrate counterparts. Structures of the human receptors as isolated for cryogenic electron microscopy (cryo-EM) are all monomeric despite compelling evidence for their functioning as dimers. Here we characterize the homologous receptor from Caenorhabditis elegans. Its biochemical properties are notably similar to those of the thyroid stimulating …

Variation In State Policies On Sideline Medical Coverage Of High School Athletic Events, Marcus Allen, Aravind Athiviraham, Darlington Nwaudo, Lutul D Farrow, Aossm Bold Study Group, Matthew Matava

2020-Current year OA Pubs

BACKGROUND: Certified athletic trainers (ATs) are the primary source of sideline coverage for high school athletic events, providing an essential role in student-athlete health. However, there is a paucity of literature evaluating the existence of state requirements regarding the presence of ATs and mandatory sideline medical coverage of high school athletic events.

HYPOTHESIS: It was hypothesized that there is significant variation among state policies on sideline medical coverage and AT requirements for high school athletic events.

STUDY DESIGN: Cross-sectional study.

METHODS: A 17-question survey was emailed to the executive directors (or analogous position) of the state high school athletic associations …

So What? Elevating The Impact Of Implementation Science, Ross C Brownson, Juliet Iwelunmor, Thomas A Odeny, Enola K Proctor, Elvin H Geng

2020-Current year OA Pubs

BACKGROUND: Given the substantial public funding of health-related research, tangible benefits of this support must be demonstrated. Implementation science provides actionable methods to enhance population health, reduce health inequities, and guide effective public health and clinical practices and policies. We must elevate the notion of impact (the "so-what gap") and the role of implementation science, particularly in university settings.

MAIN TEXT: We distinguish between scientific output and impacts. Impacts in implementation science are commonly defined as improvements in health outcomes, quality of life, quality of services, or policy change. In contrast, traditional academic outputs, such as citation counts and grant …

Successful Implementation Of Stroke Risk Screening For Sickle Cell Anemia In The Displace Study: Results Of A Cluster Randomized Trial, Alyssa M Schlenz, Monica L Hulbert, Et Al.

2020-Current year OA Pubs

BACKGROUND: Stroke risk screening using transcranial Doppler (TCD) is a critical evidence-based tool for children with sickle cell anemia (SCA) that has been poorly implemented in the United States. The Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) study was designed to improve rates of stroke risk screening for SCA using interventions informed by an extensive multi-level barriers and facilitators assessment. This report describes the final outcomes of a large, randomized implementation trial comparing two intervention arms: 1) an application designed to track TCD implementation, ProviderMinder™, versus 2) ProviderMinder™ plus a single coordinator intervention. All sites …

Implementation Outcomes From The Hypertension Treatment In Nigeria Program: Results From A Type 2 Hybrid Interrupted Time Series Trial, Jiancheng Ye, Erica L Jamro, Guhan Iyer, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Hypertension Treatment in Nigeria Program was implemented across 60 primary healthcare centers (PHCs) in Nigeria to improve hypertension treatment and control using the World Health Organization's HEARTS package. This study reports the program's implementation outcomes.

METHODS: The Hypertension Treatment in Nigeria Program used a type 2 hybrid interrupted time series design, and data were collected from January 2020 to December 2023. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework guided the evaluation, focusing on key metrics such as patients' and clinics' characteristics, prescription rate of fixed dose combination (FDC) drugs, medication availability, and retention.

RESULTS: Among 21,922 …

Molecular Basis Of Nfib-Mediated Regulation Of Oncogenic Transcription, Ci Zhu, Ding Xiao, Yueyu Wang, Hong Han, Chengxiao Qin, Shuang Liu, Xi Chen, Hejin Xiao, Xin Chen, Junfeng Shi, Juyu Tang, Jie Shen, He Song

2020-Current year OA Pubs

The Nuclear Factor I (NFI) family of transcription factors orchestrates key regulatory programs in development, differentiation, and metabolism, with dysregulation implicated in diverse pathological conditions, including cancer. Among the paralogs, NFIB has emerged as an oncogenic driver in multiple tumor types, yet the mechanisms through which it engages DNA and directs oncogenic transcriptional programs remain undefined. Here, using cancer cells with high NFIB expression, we demonstrate that NFIB promotes malignant phenotypes, as CRISPR-Cas9 knockout impairs proliferation, migration, and invasion. Transcriptomic profiling reveals that NFIB regulates a cancer-enriched gene network that includes FGFR3 and PDGFRB. Biophysical analyses show that NFIB, including …

The Pitfalls Of Multiple-Choice Questions In Generative Ai And Medical Education, Shrutika Singh, Anton Alyakin, Daniel Alexander Alber, Jaden Stryker, Ai Phuong S Tong, Karl Sangwon, Nicolas Goff, Mathew De La Paz, Miguel Hernandez-Rovira, Ki Yun Park, Eric Claude Leuthardt, Eric Karl Oermann

2020-Current year OA Pubs

The performance of Large Language Models (LLMs) on multiple-choice question (MCQ) benchmarks is frequently cited as proof of their medical capabilities. We hypothesized that LLM performance on medical MCQs may in part be illusory and driven by factors beyond medical content knowledge and reasoning capabilities. To assess this, we created a novel benchmark of free-response questions with paired MCQs (FreeMedQA). Using this benchmark, we evaluated three state-of-the-art LLMs (GPT-4o, GPT-3.5, and LLama-3-70B-instruct) and found an average absolute deterioration of 39.43% in performance on free-response questions relative to multiple-choice (p = 1.3 * 10

Maternal Obesogenic Diet Exposure Regulates The Offspring Gut Liver Axis And Fibroinflammatory Liver Disease, Naresh Naik Ramavath, Oğuz Özler, Holly Hinrichs, Francisco R Victorino, Vung Lian, Monica Young, Tarin M Bigley, Michael D Thompson

2020-Current year OA Pubs

Maternal obesogenic diet exposure (MODE) promotes fibroinflammatory liver disease in offspring via vertical transfer of an altered microbiome. The mechanism for how an altered offspring microbiome increases susceptibility to liver disease is not clear. A critical early life event termed the 'weaning reaction' is dependent on the early microbiome and when altered, results in worse pathologic inflammation. MODE attenuates the weaning reaction promoting worse liver disease in mice in an early microbiome-dependent manner. Using our MODE model and cross-fostering approaches we assessed the effect of MODE on neonatal gut-liver axis development. MODE shifts the bile acid (BA) profile, expression of …

Oligomerisation Of Ku From Mycobacterium Tuberculosis Promotes Dna Synapsis, Sayma Zahid, Ankita Chadda, Eric Galburt, Et Al.

2020-Current year OA Pubs

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is estimated to infect nearly one-quarter of the global population. A key factor in its resilience and persistence is its robust DNA repair capacity. Non-homologous end joining (NHEJ) is the primary pathway for repairing DNA double-strand breaks (DSBs) in many organisms, including Mtb, where it is mediated by the Ku protein and the multifunctional LigD enzyme. In this study, we demonstrate that Ku is essential for mycobacterial survival under DNA-damaging conditions. Using cryogenic electron microscopy (cryo-EM), we solved high-resolution structures of both the apo and DNA-bound forms of the Ku-Mtb homodimer. …

Strengthening Implementation Science Research To Improve Adolescent And Young Adult Hiv-Prevention And Care In Sub-Saharan Africa: Patc3h-In, Geri R Donenberg, Ucheoma Nwaozuru, Sylvia Adebajo, Joseph D Tucker, Juliet Iwelunmor, Lisa M Kuhns, Brenda Gati Mirembe, Lisa Hightow-Weidman, Brian Zanoni, Tapiwa A Tembo, Maria Felix Lupogo, Franklin Yates

2020-Current year OA Pubs

BACKGROUND: Despite significant progress in HIV prevention and treatment, uptake of evidence-based interventions among adolescents and young adults (AYA), particularly in low- and middle-income countries (LMICs), remains low. Implementation research can optimize strategies to enhance reach, uptake, and equitable access to these innovations. The Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource-Constrained Settings Implementation Science Network (PATC

METHODS: The PATC

RESULTS: The PATC

CONCLUSIONS: The PATC

CLINICAL TRIAL NUMBER: Not Applicable.

Clinical And Implementation Outcomes Of An Antimicrobial Stewardship Intervention For Rapid Blood Culture Diagnostics, Monica Abdelnour, Christine R Lockowitz, Evan E Facer, Andrew Atkinson, Sara Malone, Virginia R Mckay, Rebekah E Dumm, Alexander S Plattner, Matthew M Sattler, Jason G Newland

2020-Current year OA Pubs

OBJECTIVE: To evaluate the clinical and implementation outcomes of an antimicrobial stewardship program (ASP) intervention to improve antibiotic therapy for a rapid diagnostic test (RDT) for bloodstream infections (BSIs).

DESIGN: Retrospective pre and postintervention study.

SETTING: Single pediatric tertiary center from August 2022 to May 2024.

PARTICIPANTS: Patients presenting with a positive blood culture accompanied by the Verigene (VG) Gram-positive Blood Culture Nucleic Acid (BC-GP) assay. Implementation outcomes surveys were completed by infectious diseases (ID) clinicians and non-ID clinicians.

METHODS: We implemented a 24 hours a day, 7 days a week (24/7) ASP intervention to improve response to BC-GP assay …

Prospective Sars-Cov-2 Additional Vaccination In Immunosuppressant-Treated Individuals With Autoimmune Diseases In A Randomized Controlled Trial, Meggan Mackay, Alfred Hj Kim, Et Al.

2020-Current year OA Pubs

BACKGROUND: Individuals with autoimmune diseases (AD) on immunosuppressants often have suboptimal responses to COVID-19 vaccine. We evaluated the efficacy and safety of additional COVID-19 vaccines in those treated with mycophenolate mofetil/mycophenolic acid (MMF/MPA), methotrexate (MTX), and B cell-depleting therapy (BCDT), including the impact of withholding MMF/MPA and MTX.

METHODS: In this open-label, multicenter, randomized trial, 22 participants taking MMF/MPA, 26 taking MTX, and 93 treated with BCDT who had suboptimal antibody responses to initial COVID-19 vaccines (2 doses of BNT162b2 or mRNA-1273 or 1 dose of AD26.COV2.S) received an additional homologous vaccine. Participants taking MMF/MPA and MTX were randomized (1:1) …

Mitochondrial Iron Transport Via Mfrn1 Is Required For Erythroid Cell Cycle Progression, Mark Perfetto, Aidan Danoff, Muhammad Ishfaq, Heidi Monroe, Aiden Mohideen, Meilin Chen, Jesus Tejero, Amber N Stratman, Satoshi Okawa, Yvette Y Yien

2020-Current year OA Pubs

Iron metabolism drives key erythropoietic processes, including hemoglobinization, survival, and proliferation. Here, we developed in vivo methods to interrogate how iron regulates erythropoiesis and report that mitochondrial iron transport via mitoferrin-1 (MFRN1) is essential for erythroid cell cycle progression. mfrn1 embryos had severely decreased erythroid cell number caused by cell cycle arrest at G2/M. They had enlarged nuclei, suggesting a mitotic defect. Iron supplementation rescued the cell cycle defect, implicating mitochondrial iron deficiency as its cause. In contrast, fpn1 mutants, anemic from systemic iron deficiency, had less severe decreases in erythroid mitochondrial iron than mfrn1 mutants and no proliferative defects. …

Deep Learning Reveals How Cells Pull, Buckle, And Navigate Fibrous Environments, Abinash Padhi, Arka Daw, Atharva Agashe, Medha Sawhney, Maahi M Talukder, Mehran M H Pour, Mohammad Jafari, Guy M Genin, Farid Alisafaei, Sohan Kale, Anuj Karpatne, Amrinder S Nain

2020-Current year OA Pubs

Cells in tissues navigate fibrous environments fundamentally differently than they do on flat substrates, but the establishment of cell forces in physiological fibrous settings remains poorly understood. Although factors such as the stiffness of the extracellular matrix (ECM) are known to drive behaviors, including cell motility on flat nonfibrous substrates, the interplay between fiber architecture and stiffness in fibrous ECM is not known. Here, we find that in fibrous environments, the directionality of mechanical forces overrides ECM stiffness as the primary regulator of contractility in migrating cells. Using an approach combining phase microscopy with deep learning to map forces in …

Cpx-351 Vs. Conventional Chemotherapy Cardiotoxicity In High-Risk Aml: A Post Hoc Phase Iii Trial Analysis, Joshua D Mitchell, Michael Pfeiffer, John Boehmer, John Gorcsan, Shunsuke Eguchi, Yoshiyuki Orihara, Nalina Dronamraju, Sonja Dhani, Stefan Faderl, Tara L Lin, Geoffrey L Uy, Jeffrey E Lancet, Jorge E Cortes

2020-Current year OA Pubs

BACKGROUND: CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, has demonstrated significantly improved overall survival in acute myeloid leukemia (AML) compared with 7 + 3, but its impact on cardiac function remains unclear. In a post hoc analysis of the pivotal clinical trial, we sought to determine the relative cardiotoxicity of CPX-351 vs. 7 + 3 in high-risk AML.

METHODS: We evaluated cardiotoxicity in 102 patients with AML (CPX-351, n = 57; 7 + 3, n = 45) who had normal baseline left ventricular ejection fraction (LVEF) ≥ 53% and at least one …

Cohort Profile: The Pharmacogenomics And Pharmacokinetics Study In Ghanaian Hiv Patients (Genopharm-Gh), Nicholas Ekow Thomford, Oksana Ryabinina, Joel Adu Twum, John Anyimadu, Samuel Badu Nyarko, Akwasi Anyanful, Martins Ekor, George Boateng Kyei

2020-Current year OA Pubs

BACKGROUND: The GenoPharm-GH project initiated in 2019, as a longitudinal, multi-site observational cohort study aimed at bridging gaps in understanding the influence of host genetics, pharmacokinetics and comorbidities on treatment outcome among persons living with HIV (PLWH) in Ghana.

METHODS: The study is ongoing prospective, longitudinal, multi-site cohort associated with diverse projects being conducted throughout health facilities across Ghana. So far 2044 persons living with HIV (PLWH) aged ≥ 8 years have been registered. These participants are on treatment with antiretroviral therapies (ART). Viral suppression, treatment adherence (self-reported and pill count), clinical data, genetic variations, coinfections, and comorbidities are being …

Single-Cell Transcriptomic Analysis Of Hpv-Related Multiphenotypic Sinonasal Carcinoma Uncovers Myb-Hpv Association, Avishai Wizel, Matthew D A Spence, Michael Mints, William Britton, Ogoegbunam Okolo, Victoria Yu, Isabel Cioffi, Salvatore Caruana, Scott H Troob, William C Faquin, Derrick T Lin, Itay Tirosh, Sidharth V Puram, Anuraag S Parikh, Yotam Drier

2020-Current year OA Pubs

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a rare tumor that morphologically resembles high-grade adenoid cystic carcinoma (ACC) but exhibits indolent clinical behavior. Both demonstrate MYB proto-oncogene upregulation, though HMSC lacks the MYB translocation characteristic of ACC. We performed single-cell RNA sequencing on an HMSC tumor and compared expression patterns with published ACC and oropharyngeal squamous cell carcinoma (OPSCC) datasets. Malignant HMSC cells clustered separately from ACC and lacked bicellular luminal and myoepithelial differentiation. A greater proportion of HMSC cells expressing HPV-related genes (HPVon) expressed MYB (83% vs. 62%, p = 0.022) and MYB targets (p = 6.4 × …

Multidomain Therapy For Alzheimer's Disease: A Scoping Review Of Cognitive Decline Trials, Jared C Roach, Cyrus A Raji, Et Al.

2020-Current year OA Pubs

BACKGROUND: Alzheimer’s disease (AD) leading to cognitive decline and dementia results from the interplay of multiple interacting dysfunctional biological systems. These systems can be categorized by domain, such as inflammation, cardiovascular health, proteostasis, or metabolism. Specific causes of AD differ between individuals, but each individual is likely to have causes stemming from multiple domains. Personalized multidomain therapy has been proposed as a standard of care for AD. OBJECTIVES: We sought to enumerate and describe prospective randomized controlled trials (RCTs) for multidomain interventions for AD, and to extract their inclusion criteria, trial design parameters (length, number of participants), and outcome measures. …