Digital Commons Network^™

Stable Isotope Labelling Kinetics Of Neurofilament Light, Claire A Leckey, Tatiana A Giovannucci, John B Coulton, Yingxin He, Chihiro Sato, Nupur Ghoshal, Tharini Vignarajah, Zane Jaunmuktane, Nicolas R Barthélemy, Henrik Zetterberg, Donald L Elbert, Kevin Mills, Selina Wray, Randall J Bateman, Ross W Paterson

2020-Current year OA Pubs

This study provides the first quantification of neurofilament light chain (NfL) kinetics in the human CNS using stable isotope labelling kinetics. NfL is elevated in CSF and blood across a range of traumatic, inflammatory and neurodegenerative diseases of the CNS, and has been increasingly included in clinical trials as a secondary or exploratory outcome measure of target engagement. Interpreting trajectories of NfL post-treatment has been challenging, prompting a greater need and focus on understanding its pathophysiology. We set out to measure NfL kinetics in the human CNS using stable isotope labelling kinetics. In human neurons derived from induced pluripotent stem …

Effectiveness And Implementation Of A Multi-Faceted Intervention To Facilitate Adoption Of Asthma Self-Management Practices In Peruvian Children And Adolescents: A Hybrid Type 2 Individually Randomized Controlled Trial, Alejandro Zevallos-Morales, Elisa Romani-Huacani, Kevin J Psoter, Oscar Flores-Flores, David Reif, Trishul Siddharthan, Mariona Portell, Maria Teresa Anguera, Lindsay J Underhill, Suzanne L Pollard

2020-Current year OA Pubs

BACKGROUND: Peru has one of the highest burdens of asthma in the world, as well as large gaps in access to evidence-based treatments. Studies often overlook the ways in which the research context and data collection activities interact and influence the experience of a research participant, their perception of an intervention, and, by extension, study outcomes.

METHODS: We conducted an individually randomized type 2 hybrid-implementation trial to evaluate the implementation and effectiveness of a locally adapted, multi-faceted intervention package to improve adherence to self-management practices. We enrolled 110 children with physician-diagnosed asthma living in nine urban districts Lima, Peru, and …

Evolution And Recent Radiation Therapy Advancement In Uganda: A Precedent On How To Increase Access To Quality Radiotherapy Services In Low- And Middle-Income Countries, Awusi Kavuma, Solomon Kibudde, Daniel Kanyike, Joseph Kigula-Mugambe, Tianyu Zhao, Hiram Gay, Baozhou Sun, Jackson Orem

2020-Current year OA Pubs

The evolution of radiation therapy in Uganda has been a journey marked by significant milestones and persistent challenges. Since the inception of radiotherapy services in 1988-1989, there has been a concerted effort to enhance cancer treatment services. The early years were characterized by foundational developments, such as the installation of the first teletherapy units, low-dose-rate brachytherapy units, and conventional simulators, and the recognition of radiation oncologists and medical physicist professionals laid the groundwork for radiotherapy treatment modalities. With more support from the International Atomic Energy Agency, the acquisition of dosimetry equipment, treatment planning systems, and additional professional training signaled a …

Sensorimotor Faculties Bias Choice Behavior, Jan Kubanek, Lawrence H Snyder, Richard A Abrams

2020-Current year OA Pubs

Decision-making is a deliberate process that seemingly evolves under our own volition. Yet, research on embodied cognition has demonstrated that higher-order cognitive processes may be influenced, in unexpected ways, by properties of motor and sensory systems. Here we tested whether and how decisions are influenced by handedness and by asymmetries in the auditory system. Right- and left- handed participants performed an auditory decision task. In the task, subjects decided whether they heard more click sounds in the right ear or in the left ear, and pressed a key with either their right or left index finger, according to an instructed …

Physical Activity As A Resistance Or Resilience Mechanism In Down Syndrome Alzheimer's Disease, Victoria L Fleming, Beau M Ances, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Adults with Down syndrome (DS) are at risk for Alzheimer's disease (AD). Lifestyle factors such as engagement in moderate-to-vigorous physical activity (MVPA) reduce risk or delay the onset of AD. This study aimed to determine whether MVPA confers a

METHODS: Analyses included 69 adults with DS (aged 26-58) who participated in a longitudinal study across 3.29 years. An actigraphy accelerometer assessed MVPA across 7 days. Directly administered and informant-reported measures assessed cognitive functioning, specifically memory and dementia symptoms. Neuroimaging biomarkers quantified amyloid beta (Aβ) burden, as assessed via positron emission tomography imaging.

RESULTS: In regression models, baseline MVPA was …

Abdominal Versus Femoral Subcutaneous Fat Gene Expression In Non-Obese Insulin Resistant Individuals, Saif Badran, Shamma Almuraikhy, Maha Alser, Khaled Naja, Najeha Anwardeen, Hanan H Abunada, Mohamed Badie Ahmed, Salma Jarrar, Ghanem Aljassem, Sara Iskeirjeh, Atalla Hammouda, Suhail A Doi, Layla Al-Mansoori, Mohamed A Elrayess

2020-Current year OA Pubs

INTRODUCTION: Adipose tissue, once viewed primarily as an energy reservoir, is now recognized as an endocrine organ involved in various physiological functions, including energy balance and immune responses. Interestingly, recent insights suggest that not all overweight or obese individuals exhibit insulin resistance, guiding the focus towards depot-specific adipose gene expression and its metabolic implications. This pilot study investigates adipose depot-specific differences in gene expression in abdominal versus femoral subcutaneous adipose tissue (SAT) among non-obese, insulin-sensitive (IS) and insulin-resistant (IR) individuals, aiming to elucidate underlying mechanisms of metabolic dysfunction.

METHODS: Seventeen non-obese participants scheduled for body contouring surgery provided paired SAT …

The Role Of Impaired Adipogenesis In Insulin Resistance Among Non-Obese Individuals, Shamma Almuraikhy, Maha Alser, Khaled Naja, Najeha Anwardeen, Samir Taha, Jomon John, Sharique Halim, Saif Badran, Mohamed Badie Ahmed, Salma Jarrar, Ghanem Aljassem, Fatima Saoud Al-Mohannadi, Suhail Doi, Asmaa Abdel-Aziz, Yousra Jalal Elaf, Mohamed A Elrayess

2020-Current year OA Pubs

INTRODUCTION: Adipogenesis is an essential process for energy storage, hormone regulation, and overall metabolic health. Previous work showed that impaired adipogenesis plays an important role in the development of obesity-associated insulin resistance. This project investigates the role of impaired adipogenesis in the development of insulin resistance among non-obese (lean/overweight) individuals under physiological and pathological microenvironments.

METHODS: Subcutaneous adipose tissue samples were obtained from insulin-sensitive and insulin-resistant non-obese cohorts undergoing maxillofacial or body contouring surgeries. Preadipocytes were isolated and examined for proliferation and adipogenic capacity, insulin signaling, and inflammatory markers. These assessments were conducted under basal conditions and following treatment with …

Il-7: A Potential Next-Generation Adjuvant For Immune Cell Therapies, Richard S Hotchkiss, John F Dipersio, Cassian Yee, Russell K Pachynski, Marcel R M Van Den Brink

2020-Current year OA Pubs

Cell-based immune therapies ranging from CAR-T cells to tumor infiltrating lymphocytes (TILs) and endogenous T-cell products, have produced unprecedented clinical responses in hematologic malignancies and are currently under active investigation for solid tumors. Nevertheless, several key challenges continue to limit the durability and breadth of clinical benefit. IL-7 is a pleiotropic cytokine that increases both the number and function of lymphocytes. Although not yet clinically approved, IL-7 has been used in over 620 adult and pediatric patients for a variety of reasons including, for example, to hasten bone marrow recovery after allogenic stem cell transplantation, to reverse lymphopenia due to …

"I Feel Like People Would Look At Me Like I'M Dirty Or Like I'M A Thief:" A Qualitative Exploration Of Interpersonal And Intrapersonal Experiences That Influence Recovery Among Adults At Risk Of Opioid-Related Overdose, Hannah S Szlyk, Sara Jones, Jordan Michener, Zhuoran Zhang, Nina Kaiser, Heidi Holtz, Melody Rachel Konadu Frempong, Husain Lateef, William Hutson, Patricia Cavazos-Rehg

2020-Current year OA Pubs

OBJECTIVE: Due to the nature of early termination of treatment and the transient lifestyles of many people who use substances, many providers are unaware of the factors that may have contributed to their client's engagement in treatment. Treatment providers and researchers need a better understanding of intrapersonal and interpersonal factors that impact recovery from the clients' perspective. This study uses qualitative methods to explore these factors.

METHODS: Eligible participants were adults who had used opioids and/or stimulants and were receiving treatment at a consenting facility. Participants completed one-month follow-up interviews after using a mobile health intervention. Transcripts were analyzed using …

Association Of Item-Level Responses To Cognitive Function Index With Tau Pathology And Hippocampal Volume In The A4 Study, Idris Demirsoy, Elham Ghanbarian, Babak Khorsand, Bhargav T Nallapu, Kellen K Petersen, Richard B Lipton, S Ahmad Sajjadi, Laura A Rabin, Ali Ezzati

2020-Current year OA Pubs

INTRODUCTION: Alzheimer's disease (AD) has a long preclinical phase in which individuals may accumulate amyloid beta (Aβ) and tau pathology without noticeable cognitive impairment. Subjective cognitive impairment reports can provide early insights into cognitive decline.

METHODS: In the A4 Study, 339 cognitively unimpaired, Aβ-positive individuals underwent tau positron emission tomography imaging. Tau status was classified based on medial temporal lobe tau standardized uptake value ratios (tau

RESULTS: Higher tau

DISCUSSION: These findings support the utility of participant- and study partner-reported concerns as early indicators of preclinical AD pathology, with potential value for early detection and trial enrichment strategies.

HIGHLIGHTS: Higher …

Mechanosensitivity Of Macrophage Polarization: Comparing Small Molecule Leukadherin-1 To Substrate Stiffness, Hemant Joshi, Edgar Anaya, Anvitha Addanki, Alison Almgren-Bell, Elizabeth M Todd, Sharon Celeste Morley

2020-Current year OA Pubs

Macrophages sustain tissue homeostasis through host defense and wound repair. To promote host defense, macrophages upregulate surface markers associated with antigen processing and secrete pro-inflammatory mediators such as IL-6 and IL-1β. After pathogen clearance, macrophages shift phenotype to promote wound repair. Shifts in phenotypes are termed "polarization" and have historically been modeled by exposure to soluble mediators such as LPS+IFNγ (host defense) or IL-4+IL-13 (tissue repair). Greater emphasis is now being placed on understanding how the mechanical environment of macrophages, such as tissue compliance, regulates macrophages responses. Here, we compare incubation of primary macrophages on collagen-coated silica gels of varying …

Visual Outcomes In A Series Of Patients With Papilledema And Comorbid Nutritional Deficiency, Dan V Spiegelman, John Burkland, Evan Jameyfield, Gregory P Van Stavern, Leanne Stunkel

2020-Current year OA Pubs

BACKGROUND: Fulminant papilledema is a neuro-ophthalmologic emergency that can lead to permanent vision loss as a result of optic neuropathy. Despite appropriate treatment of intracranial hypertension and improvement of papilledema, some patients continue to experience worsening vision. In some cases, comorbid micronutrient deficiencies, which are an additional cause of optic neuropathy, may contribute to this decline. This case series highlights patients with papilledema whose vision worsened despite improvement in papilledema and who were found to have comorbid nutritional deficiencies.

METHODS: A retrospective case series of three patients with papilledema were seen between 2019 and 2022 at Washington University in St. …

Tourette Syndrome Research Highlights From 2024 [Version 3; Peer Review: 2 Approved, 1 Approved With Reservations], Andreas Hartmann, Per Andrén, Cyril Atkinson-Clement, Virginie Czernecki, Cécile Delorme, Simon Morand-Beaulieu, Nanette Mol Debes, Kirsten Müller-Vahl, Peristera Paschou, Natalia Szejko, Apostolia Topaloudi, Kevin J Black

2020-Current year OA Pubs

We summarize research reports from 2024 relevant to Tourette syndrome, which the authors consider the most important or interesting. This working draft aims to submit this content for publication around the beginning of 2025 in the yearly Tourette Syndrome Research Highlights series on F1000Research. The authors welcome article suggestions and thoughtful feedback from readers, who can add a comment by clicking on the rectangular comment box icon to the left of the LOG IN link at the top of this page. For private comments, you can reach us by email ( [email protected] or [email protected]).

Tracking The Evolving Role Of Artificial Intelligence In Implementation Science: Protocol For A Living Scoping Review Of Applications, Evaluation Approaches And Outcomes [Version 2; Peer Review: 2 Approved], Guillaume Fontaine, Byron J Powell, Et Al.

2020-Current year OA Pubs

BACKGROUND: Artificial intelligence (AI) offers significant opportunities to improve the field of implementation science by supporting key activities such as evidence synthesis, contextual analysis, and decision-making to promote the adoption and sustainability of evidence-based practices. This living scoping review aims to: (1) map applications of AI in implementation research and practice; (2) identify evaluation approaches, reported outcomes, and potential risks; and (3) synthesize reported research gaps and opportunities for advancing the use of AI in implementation science.

METHODS: This scoping review will follow the Joanna Briggs Institute (JBI) methodology and the Cochrane guidance for living systematic reviews. A living scoping …

Automated Differentiation Of Wide Qrs Complex Tachycardia Using Qrs Complex Polarity, Adam M May, Bhavesh B Katbamna, Preet A Shaikh, Sarah Lococo, Elena Deych, Ruiwen Zhou, Lei Liu, Krasimira M Mikhova, Rugheed Ghadban, Phillip S Cuculich, Daniel H Cooper, Thomas M Maddox, Peter A Noseworthy, Anthony Kashou

2020-Current year OA Pubs

BACKGROUND: Wide QRS complex tachycardia (WCT) differentiation into ventricular tachycardia (VT) and supraventricular wide complex tachycardia (SWCT) remains challenging despite numerous 12-lead electrocardiogram (ECG) criteria and algorithms. Automated solutions leveraging computerized ECG interpretation (CEI) measurements and engineered features offer practical ways to improve diagnostic accuracy. We propose automated algorithms based on (i) WCT QRS polarity direction (WCT Polarity Code [WCT-PC]) and (ii) QRS polarity shifts between WCT and baseline ECGs (QRS Polarity Shift [QRS-PS]).

METHODS: In a three-part study, we derive and validate machine learning (ML) models-logistic regression (LR), artificial neural network (ANN), Random Forests (RF), support vector machine (SVM), …

Saponin Tql1055 Adjuvant-Containing Vaccine Confers Protection Upon Mycobacterium Tuberculosis Challenge In Mice, Mushtaq Ahmed, Eric Farris, Rosemary V Swanson, Shibali Das, Yan Yang, Tyler Martin, Shabaana A Khader

2020-Current year OA Pubs

Tuberculosis (TB), caused by the intracellular pathogen

The Association Of Caregiver Attitudes, Information Sources, And Trust With Hpv Vaccine Initiation Among Adolescents, Akila Anandarajah, Thembekile Shato, Sarah Humble, Alan R Barnette, Heather M Brandt, Lisa M Klesges, Vetta L Sanders Thompson, Michelle I Silver

2020-Current year OA Pubs

This study described caregiver attitudes and the information sources they access about HPV vaccination for adolescents and determined their influence on human papillomavirus (HPV) vaccination initiation. An online survey was administered to 1,016 adults in July 2021. Participants were eligible if they were the caregiver of a child aged 9-17 residing in Mississippi, Arkansas, Tennessee, Missouri, and select counties in Southern Illinois. Multivariate logistic regression was used to estimate the association of caregiver attitudes and information sources with HPV vaccination. Information from doctors or healthcare providers (87.4%) and internet sources other than social media (31.0%) were the most used sources …

Supporting Teams With Designing For Dissemination And Sustainability: The Design, Development, And Usability Of A Digital Interactive Platform, Maura M Kepper, Allison J L'Hotta, Thembekile Shato, Bethany M Kwan, Russell E Glasgow, Douglas Luke, Andrea K Graham, Ana A Baumann, Ross C Brownson, Brad Morse

2020-Current year OA Pubs

BACKGROUND: Designing for Dissemination and Sustainability (D4DS) principles and methods can support the development of research products (interventions, tools, findings) that match well with the needs and context of the intended audience and setting. D4DS principles and methods are not well-known or used during clinical and public health research; research teams would benefit from applying D4DS. This paper presents the development of a new digital platform for research teams to learn and apply a D4DS process to their work.

METHODS: A user-centered design (UCD) approach engaged users (n = 14) and an expert panel (n = 6) in an iterative …

Head-To-Head Comparison Of Aptamer- And Antibody-Based Proteomic Platforms In Human Cerebrospinal Fluid Samples From A Real-World Memory Clinic Cohort, Raquel Puerta, Yun Ju Sung, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

High-throughput proteomic platforms are crucial to identify novel Alzheimer's disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan

Oxidized Phospholipid And Transcriptomic Signatures Of Thc-Related Vaping Associated Lung Injury, Tomeka L Suber, Zeyu Xiong, Janet S Lee, Et Al.

2020-Current year OA Pubs

E-cigarette/vaping-associated lung injury (EVALI) is strongly associated with vitamin E acetate and often occurs with concomitant tetrahydrocannabinol (THC) use. To uncover pathways associated with EVALI, we examined cytokines, transcriptomic signatures, and lipidomic profiles in bronchoalveolar lavage fluid (BALF) from THC-EVALI patients. At a single center, we prospectively enrolled mechanically ventilated patients with EVALI from THC-containing products (N = 4) and patients with non-vaping acute lung injury and airway controls (N = 5). BALF samples were analyzed by Luminex multiplex assay, RNA sequencing, and mass spectrometry. After treating BEAS-2B lung epithelial cells with vaping and non-vaping BALF, LDH release was quantified. …

Hiding In Plain Sight: Eating Disorders In Diverse Populations - A Case For Comprehensive Medical Education, Tashalee R Brown, Madeline O Jansen, Drew Hirsch, Habiba Amir, Alexis E Duncan, Ginger E Nicol

2020-Current year OA Pubs

BACKGROUND: Training gaps regarding the diagnosis and management of eating disorders in diverse populations, including racial, ethnic, sexual, and gender minoritized groups, have not been thoroughly examined.

OBJECTIVE: This study aimed to examine resident physicians' knowledge and attitudes regarding eating disorders in diverse populations, with a focus on areas for improved training and intervention.

METHODS: Ninety-two resident physicians in internal medicine, emergency medicine, obstetrics/gynecology, psychiatry, and surgery at an academic center completed an online survey from 12/1/2020-3/1/2021, which comprised multiple choice and vignette-style open-ended questions to assess knowledge and attitudes toward the management and clinical presentations of eating disorders. Overall, …

Approaches And Outcomes Of Adalimumab Discontinuation In Patients With Well-Controlled Inflammatory Arthritis: A Systematic Search And Review, Erin Balay-Dustrude, Jessica Fennell, Kevin Baszis, Y Ingrid Goh, Daniel B Horton, Tzielan Lee, Chloe Rotman, Anna Sutton, Marinka Twilt, Olha Halyabar, Carra Jia Inactive Disease Workgroup

2020-Current year OA Pubs

OBJECTIVE: This systematic search and review aimed to evaluate the available literature on discontinuation of adalimumab and other tumor necrosis factor inhibitors (TNFi) for patients with well-controlled chronic inflammatory arthritides.

METHODS: We conducted a publication search on adalimumab discontinuation from 2000-2023 using PubMed, CINAHL, EMBASE, and Cochrane Library. Included studies evaluated adalimumab discontinuation approaches, tapering schemes, and outcomes including successful discontinuation and recapture after flare, in patients with well-controlled disease. Studies included evaluated rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA).

RESULTS: Forty-nine studies were included. Studies evaluating adalimumab alone were limited, and many reported TNFi outcomes …

Effectiveness Of An Online Food Shopping Intervention To Reduce Salt Purchases Among Individuals With Hypertension - Findings Of The Saltswitch Online Grocery Shopping (Ogs) Randomised Trial, Jason Hy Wu, Damian Maganja, Liping Huang, Kathy Trieu, Fraser Taylor, Eden M Barrett, Clare Arnott, Xiaoqi Feng, Aletta E Schutte, Gian Luca Di Tanna, Cliona Ni Mhurchu, Adrian J Cameron, Mark D Huffman, Bruce Neal

2020-Current year OA Pubs

BACKGROUND: Online grocery shopping is a growing source of food purchases in many countries. We investigated the effect of nudging consumers towards purchases of lower sodium products using a web browser extension.

METHODS: This trial was conducted among individuals with hypertension who shopped for their groceries online in Australia. From July 2021 to June 2023, participants were randomised to use the SaltSwitch Online Grocery Shopping web browser extension or continue their usual grocery shopping for 12 weeks. The SaltSwitch extension modified a retailer's online shopping interface to suggest similar but lower sodium alternative products to those initially selected. The primary …

Carboxyl Ester Lipase Hybrid 1 (Cel-Hyb1) Haplotypes Confer Varying Risk For Chronic Pancreatitis, Gergő Berke, Xunjun K Xiao, Mark E Lowe, Et Al.

2020-Current year OA Pubs

The CEL-HYB1 hybrid allele of the carboxyl ester lipase (CEL) gene and its pseudogene (CELP) has been associated with chronic pancreatitis (CP). Recent work indicated that amino acid positions 488 and 548 in CEL-HYB1 determined pathogenicity. Haplotype Thr488-Ile548 was associated with CP while haplotypes Thr488-Thr548 and Ile488-Thr548 were benign. However, functional analysis revealed that Thr488 is the primary determinant of CEL-HYB1 misfolding and associated endoplasmic reticulum (ER) stress. To address this contradiction, we analyzed a cohort from Hungary and found significantly increased CEL-HYB1 carrier frequency in CP cases (9/319, 2.8%) versus controls (5/618, 0.8%), yielding an odds ratio of 3.6 …

Refinement Of An Algorithm To Detect And Predict Freezing Of Gait In Parkinson Disease Using Wearable Sensors, Allison M Haussler, Lauren E Tueth, David S May, Gammon M Earhart, Pietro Mazzoni

2020-Current year OA Pubs

Freezing of gait (FOG) is a debilitating symptom of Parkinson disease (PD). It is episodic and variable in nature, making assessment difficult. Wearable sensors used in conjunction with specialized algorithms, such as our group's pFOG algorithm, provide objective data to better understand this phenomenon. While these methods are effective at detecting FOG retrospectively, more work is needed. The purpose of this paper is to explore how the existing pFOG algorithm can be refined to improve the detection and prediction of FOG. To accomplish this goal, previously collected data were utilized to assess the prediction ability of the current algorithm, the …

Stereotactic Cardiac Radiotherapy For Refractory Ventricular Tachycardia In Structural Heart Disease Patients: A Systematic Review, Amulya Gupta, Zeeshan Sattar, Nourhan Chaaban, Sagar Ranka, Cameron Carlson, Farhad Sami, Clifford G Robinson, Phillip S Cuculich, Seth H Sheldon, Madhu Reddy, David Akhavan, Amit Noheria

2020-Current year OA Pubs

AIMS: Among patients with structural heart disease with ventricular tachycardia (VT) refractory to medical therapy and catheter ablation, cardiac stereotactic body radiotherapy (SBRT) is a paradigm-changing treatment option. This study aims to assess the efficacy of cardiac SBRT in refractory VT by comparing the rates of VT episodes, anti-tachycardia pacing (ATP) therapies, and implantable cardioverter-defibrillator (ICD) shocks post-SBRT with pre-SBRT.

METHODS AND RESULTS: We performed a comprehensive literature search and included all clinical studies reporting outcomes on cardiac SBRT for VT. Treatment efficacy was evaluated as random-effects pooled rate-ratios of VT episodes, ATP therapies and ICD shocks post-SBRT (after 6-week …

Cochlear Mechanics Are Preserved After Inner Ear Delivery Of Gold Nanoparticles, Dorothy W Pan, Jinkyung Kim, Patricia M Quiñones, Anthony J Ricci, Brian E Applegate, John S Oghalai

2020-Current year OA Pubs

Novel therapeutic delivery systems and delivery methods to the inner ear are necessary to treat hearing loss and inner ear disorders. However, numerous barriers exist to therapeutic delivery into the bone-encased and immune-privileged environment of the inner ear and cochlea, which makes treating inner ear disorders challenging. Nanoparticles (NPs) are a type of therapeutic delivery system that can be engineered for multiple purposes, and posterior semicircular canal (PSCC) infusion is a method to directly deposit them into the cochlea. We sought to assess PSCC infusion of gold NPs into the cochlea, including the NPs' distribution and effect on cochlear mechanics. …

Lower-Intensity Cpx-351 Plus Venetoclax Induction For Adults With Newly Diagnosed Aml Unfit For Intensive Chemotherapy, Geoffrey L Uy, Vinod Pullarkat, Praneeth Baratam, Robert K Stuart, Roland B Walter, Eric S Winer, Qi Wang, Stefan Faderl, Divya Chakravarthy, Diane Menno, Ronald S Cheung, Tara L Lin

2020-Current year OA Pubs

Preclinical data suggest a rationale for combining CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine, with venetoclax, a B-cell lymphoma-2 inhibitor. This phase 1b study evaluated lower-intensity CPX-351 combined with venetoclax in adults with acute myeloid leukemia (AML) considered unfit/ineligible for intensive chemotherapy. In a dose-exploration phase using a 3+3 design, patients received stepwise dosing of CPX-351 IV on days 1 and 3 plus venetoclax 400 mg orally on days 2 to 21 per cycle to determine the recommended phase 2 dose (RP2D) for this combination. During the expansion phase, additional patients received CPX-351 plus venetoclax at the identified …

Emata: A Toolbox For The Automatic Extraction And Modeling Of Arterial Inputs For Tracer Kinetic Analysis In [18f]Fdg Brain Studies, Mattia De Francisci, Erica Silvestri, Andrea Bettinelli, Tommaso Volpi, Manu S Goyal, Andrei G Vlassenko, Diego Cecchin, Alessandra Bertoldo

2020-Current year OA Pubs

PURPOSE: PET imaging is a pivotal tool for biomarker research aimed at personalized medicine. Leveraging the quantitative nature of PET requires knowledge of plasma radiotracer concentration. Typically, the arterial input function (AIF) is obtained through arterial cannulation, an invasive and technically demanding procedure. A less invasive alternative, especially for [

METHODS: To assess the toolbox generalizability and present example outputs, EMATA was applied to brain [

RESULTS: EMATA consistently performs IDIF extraction across all datasets, despite differences in scanners and acquisition protocols. Remarkably high agreement is observed when comparing Patlak's K

CONCLUSION: EMATA proved adaptability to different datasets characteristics and …

Loss Of Chop Prevents Joint Degeneration And Pain In A Mouse Model Of Pseudoachondroplasia, Jacqueline T Hecht, Alka C Veerisetty, Mohammad G Hossain, Debabrata Patra, Michele Carrer, Frankie Chiu, Dorde Relic, Paymaan Jafar-Nejad, Karen L Posey

2020-Current year OA Pubs

Pseudoachondroplasia (PSACH), a severe dwarfing condition characterized by impaired skeletal growth and early joint degeneration, results from mutations in cartilage oligomeric matrix protein (COMP). These mutations disrupt normal protein folding, leading to the accumulation of misfolded COMP in chondrocytes. The MT-COMP mouse is a murine model of PSACH that expresses D469del human COMP in response to doxycycline and replicates the PSACH chondrocyte and clinical pathology. The basis for the mutant-COMP pathology involves endoplasmic reticulum (ER) stress signaling through the PERK/eIF2α/CHOP pathway. C/EBP homologous protein (CHOP), in conjunction with a TNFα inflammatory process, upregulates mTORC1, hindering autophagy clearance of mutant COMP …