Digital Commons Network^™

Assessing Hypersight Iterative Cbct For Dose Calculation In Online Adaptive Radiotherapy For Pelvis And Breast Patients Compared To Synthetic Ct, Jingwei Duan, Joel A Pogue, Dennis N Stanley, Sui Shen, Natalie N Viscariello, Carlos E Cardenas, Richard A Popple, Joseph Harms

2020-Current year OA Pubs

PURPOSE/OBJECTIVES: Recent technological advancements have increased efficiency for clinical deliverability of online-adaptive-radiotherapy (oART). Previous cone-beam-computed-tomography (CBCT) generations lacked the ability to provide reliable Hounsfield-units (HU), thus requiring oART workflows to rely on synthetic-CT (sCT) images derived through deformable-image-registration (DIR) between the planning CT (pCT) and the daily CBCT. These sCTs are prone to errors stemming from DIR, potentially contributing to dosimetric errors. This study aims to evaluate the capability of direct dose calculation using a novel CBCT platform, HyperSight (Varian-Medical-Systems), as an alternative for sCT.

METHODS/MATERIALS: To validate the HyperSight iterative CBCT (HS-iCBCT) HU accuracy, 125 kV and 140 kV …

Brain Morphometry In Infants Later Diagnosed With Autism Is Related To Later Language Skills, Luke E Moraglia, Kelly N Botteron, Natasha Marrus, Et Al.

2020-Current year OA Pubs

Autism spectrum disorder (ASD) presents early in life with distinct social and language differences. This study explores the association between infant brain morphometry and language abilities using an infant-sibling design. Participants included infants who had an older sibling with autism (high likelihood, HL) who were later diagnosed with autism (HL-ASD; n = 31) and two non-autistic control groups: HL-Neg (HL infants not diagnosed with autism; n = 126) and LL-Neg (typically developing infants who did not have an older sibling with autism; n = 77). Using a whole-brain approach, we measured cortical thickness and surface area at 6 and 12 …

Vascular Rings - What Has Changed, And What Do I Need To Know As A Practitioner?, Sarah Madira, William B Orr, Joshua M Rosenblum, Ryan Pitman, Quang-Tuyen Nguyen, David Molter, Ashley Lloyd, Julie Glickstein, Markus Renno, Pirooz Eghtesady, Jacob R Miller

2020-Current year OA Pubs

Vascular rings represent a heterogeneous set of aberrant great vessel anatomic configurations which can cause respiratory symptoms or dysphagia due to tracheal or oesophageal compression. These symptoms can be subtle and may present at varied ages. More recently, many have been identified in patients without symptoms, including fetal echocardiogram, resulting in a conundrum for practitioners when attempting to determine who will benefit from surgical correction. Here, we provide a review of vascular rings and a guide to the practitioner on when to consider additional imaging or referral. Additionally, we discuss the changing landscape regarding asymptomatic patients and fetal echocardiogram.

Trends In Urology Residency Applications: Results From The American Urological Association Medical Student Survey From 2022 To 2024, Michael Creswell, Kirsten Greene, Lee Richstone, Simone Thavaseelan, Erica Traxel, Aaron Tverye, Casey Kowalik, Gina Badalato, Thomas Jarrett, Kate Kraft, Mathew Sorensen, Moben Mirza

2020-Current year OA Pubs

OBJECTIVE: To provide a comprehensive overview of the American Urological Association Medical Student Surveys and includes data 2022, 2023, and 2024.

METHODS: Data collected through surveys distributed prior to match day and were distributed to all medical students who submitted a rank list for urology residency. Questions consisted of various topics, including applicant demographics, application metrics, and experiences with preference signals and virtual interviews.

RESULTS: 440 (79%), 428 (84%), and 387 (77%) applicants participated in surveys for the years 2022, 2023, and 2024, respectively. Applicants continue to participate in research at a high level. Additionally, United States Medical Licensing Exam …

Fpl Reconstruction After Rupture Following Volar Plate Fixation Of Distal Radius Fractures: A Case Series, Arakua N Welbeck, Brendan J Navarro, Ndéye F Guissé, Charles A Goldfarb, Ryan P Calfee, Christopher J Dy

2020-Current year OA Pubs

PURPOSE: Volar locking plate (VLP) of distal radius fractures (DRF) carries a number of surgical risks including flexor pollicis longus (FPL) rupture secondary to irritation from prominent hardware. This study reviews FPL reconstruction (with interposition graft or tendon transfer) after VLP-related rupture.

METHODS: This retrospective case series reports the experience at one tertiary center with FPL reconstruction after DRF. Patients treated between January 1, 2013, and June 12, 2023, were eligible for inclusion. Preoperative radiographs were analyzed for Soong grading and fracture reduction parameters. Accessible patients (n = 7) were examined to evaluate long-term success of reconstruction.

RESULTS: Fifteen patients …

Sensitivity Of Lung Point-Of-Care Ultrasound (Pocus) To Predict Oxygen Requirements In Emerging Viral Infections, Daniel L Theodoro, Di Coneybeare, Penelope Lema, Nicholas Renz, Laura Wallace, Enyo Ablordeppey, Sean Stickles, Alek Rosenthal, Ian Holley, Sirivalli Chamarti, Josie Acuña, James Patterson, Rachel Ancona, Srikar Adhikari

2020-Current year OA Pubs

OBJECTIVES: The prognostic characteristics of lung point-of-care ultrasound (L-POCUS) to predict respiratory decompensation in patients with emerging infections remains unstudied. Our objective was to examine whether scored lung ultrasounds predict hypoxia among a nonhypoxic, ambulatory population of patients with COVID-19.

METHODS: This was a diagnostic case-control study. Three academic emergency departments across the United States collected a convenience sample of nonhypoxic subjects with COVID-19, scored subjects' hemithorax at 7 locations using lung ultrasound, and followed outcomes for 40 days. We defined cases as hypoxia (≤91% by pulse oxygenation) from 2 hours after index presentation to day 40. Follow-up was by …

An Asymmetric Nautilus-Like Hflk/C Assembly Controls Ftsh Proteolysis Of Membrane Proteins, Alireza Ghanbarpour, Bertina Telusma, Barrett M Powell, Jia Jia Zhang, Isabella Bolstad, Carolyn Vargas, Sandro Keller, Tania A Baker, Robert T Sauer, Joseph H Davis

2020-Current year OA Pubs

The AAA protease FtsH associates with HflK/C subunits to form a megadalton-size complex that spans the inner membrane and extends into the periplasm of E. coli. How this bacterial complex and homologous assemblies in eukaryotic organelles recruit, extract, and degrade membrane-embedded substrates is unclear. Following the overproduction of protein components, recent cryo-EM structures showed symmetric HflK/C cages surrounding FtsH in a manner proposed to inhibit the degradation of membrane-embedded substrates. Here, we present structures of native protein complexes, in which HflK/C instead forms an asymmetric nautilus-shaped assembly with an entryway for membrane-embedded substrates to reach and be engaged by FtsH. …

Introducing A New Polymerase Chain Reaction Panel–Based Cerebrospinal Fluid Evaluation For Encephalitis And Meningitis: Does It Influence Empiric Treatment Duration, Length Of Hospital Stay, And Pathogen-Specific Diagnoses?, Fabian Sidler, Pascal Bittel, Jonas Marschall, Philipp Jent

2020-Current year OA Pubs

We analyzed the impact of a diagnostic meningitis/encephalitis polymerase chain reaction panel. Introducing the test resulted in no significantly shortened empiric antibiotic streptococcal/meningococcal treatment (-1 day [95% confidence interval {CI}, 0-3 days];

High-Dimensional Mediation Analysis For Longitudinal Mediators And Survival Outcomes, Lili Liu, Haixiang Zhang, Yinan Zheng, Tao Gao, Cheng Zheng, Kai Zhang, Lifang Hou, Lei Liu

2020-Current year OA Pubs

Mediation analysis with high-dimensional mediators is crucial for identifying epigenetic pathways linking environmental exposures to health outcomes. However, high-dimensional mediation analysis methods for longitudinal mediators and a survival outcome remain underdeveloped. This study fills that gap by introducing a method that captures mediation effects over time using multivariate, longitudinally measured time-varying mediators. Our approach uses a longitudinal mixed effects model to examine the relationship between the exposure and the mediating process. We connect the mediating process to the survival outcome using a Cox proportional hazards model with time-varying mediators. To handle high-dimensional data, we first employ a mediation-based sure independence …

Research Participant Interest In Learning Results Of Biomarker Tests For Alzheimer Disease, Spondita Goswami, Sarah M Hartz, Amy Oliver, Sacha Jackson, Tomi Ogungbenle, Alissa Evans, Erin Linnenbringer, Krista L Moulder, John C Morris, Jessica Mozersky

2020-Current year OA Pubs

IMPORTANCE: While available evidence suggests there are not major psychosocial harms of return of research results, there are limited data on uptake of Alzheimer disease (AD) research results or reasons for declining to learn results among participants in AD research studies.

OBJECTIVES: To quantitatively and qualitatively evaluate who declines to learn individual AD biomarker research results and what factors are associated with the decision.

DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study was conducted between November 1, 2020, and April 15, 2024, among participants aged 65 years or older with unimpaired cognition and available biomarker data (apolipoprotein E genotype and …

Combining Exercise Training And Testosterone Therapy In Older Women After Hip Fracture: The Step-Hi Randomized Clinical Trial, Ellen F Binder, Peter M Doré, Camelia Guild, Kelly M Monroe, Dominic Reeds, Kenneth B Schechtman, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Despite receiving postacute rehabilitation services, many older women with a recent hip fracture repair are unable to return to their prefracture level of function. Whether testosterone therapy can enhance recovery after hip fracture in older women with persistent mobility impairments has not been fully examined.

OBJECTIVE: To evaluate the effects of a supervised exercise program combined with topical testosterone therapy on functional outcomes in older women with a recent hip fracture.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3 double-blind, placebo-controlled randomized clinical trial, Starting a Testosterone and Exercise Program After Hip Injury (STEP-HI), was conducted at 8 US sites …

Early-Life Factors And Body Mass Index Trajectories Among Children In The Echo Cohort, Chang Liu, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Identifying atypical body mass index (BMI) trajectories in children and understanding associated, modifiable early-life factors may help prevent childhood obesity.

OBJECTIVE: To characterize multiphase BMI trajectories in children and identify associated modifiable early-life factors.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included longitudinal data obtained from January 1997 to June 2024, from the Environmental influences on Child Health Outcomes (ECHO) cohort, which included children aged 1 to 9 years with 4 or more weight and height assessments. Analyses were conducted from January to June 2024.

EXPOSURES: Prenatal exposure to substances and stress (smoking, alcohol, depression, anxiety), maternal characteristics (prepregnancy …

Treatment Patterns And Survival Among Veterans With De Novo Metastatic Hormone-Sensitive Prostate Cancer, Martin W Schoen, Saira Khan, Eric M Knoche, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Combination therapy for metastatic hormone-sensitive prostate cancer (mHSPC) has been widely adopted, yet clinical use and outcomes are unknown. Furthermore, optimal therapy is uncertain due to lack of direct comparison of androgen receptor pathway inhibitors (ARPIs) and docetaxel in high-volume disease.

OBJECTIVE: To evaluate the use of combination therapy and its association with overall survival among patients with mHSPC and to compare ARPIs vs docetaxel doublet therapy by volume of disease.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study was conducted in the US Veterans Health Administration among 6216 US veterans with de novo mHSPC from January 1, 2013, …

Impact Of Chatgpt And Large Language Models On Radiology Education: Association Of Academic Radiology-Radiology Research Alliance Task Force White Paper, David H Ballard, Alexander Antigua-Made, Emily Barre, Elizabeth Edney, Emile B Gordon, Linda Kelahan, Taha Lodhi, Jonathan G Martin, Melis Ozkan, Kevin Serdynski, Bradley Spieler, Daphne Zhu, Scott J Adams

2020-Current year OA Pubs

Generative artificial intelligence, including large language models (LLMs), holds immense potential to enhance healthcare, medical education, and health research. Recognizing the transformative opportunities and potential risks afforded by LLMs, the Association of Academic Radiology-Radiology Research Alliance convened a task force to explore the promise and pitfalls of using LLMs such as ChatGPT in radiology. This white paper explores the impact of LLMs on radiology education, highlighting their potential to enrich curriculum development, teaching and learning, and learner assessment. Despite these advantages, the implementation of LLMs presents challenges, including limits on accuracy and transparency, the risk of misinformation, data privacy issues, …

Three-Year Analysis Of Adult Patients With Relapsed Or Refractory B-Cell Acute Lymphoblastic Leukemia Treated With Brexucabtagene Autoleucel In Zuma-3, Bijal D Shah, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 CAR T-cell therapy approved in the US to treat adults aged ≥18 years (≥26 years in the EU) with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Brexu-cel showed an overall complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate of 73% (CR rate 60%) and median overall survival (OS) of 25.4 months in 78 patients with R/R B-ALL after 2 years in ZUMA-3. Here, we report updated outcomes after >3 years median follow-up. As of July 23, 2022, median follow-up in all patients (N = 78) was 41.6 months. Median OS (95% CI) …

Multiregional Implementation Initiative's Impact On Guideline-Based Performance Measures For Patients Hospitalized With Heart Failure: Implement-Hf, Andrew J. Sauer, Nancy Sweitzer, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite randomized data for survival benefit (with class 1 recommendations) for treating heart failure (HF) with reduced ejection fraction using quadruple medical therapy (QMT)-defined as evidence-based β-blockers, sodium-glucose cotransporter 2 inhibitor, preferably angiotensin receptor/neprilysin inhibitor, and mineralocorticoid receptor antagonist-it is underutilized. IMPLEMENT-HF is a multiregional HF quality improvement initiative to improve care and outcomes for patients with HF by enhancing the use of QMT in routine practice.

METHODS: This analysis of HF with reduced ejection fraction treatment in patients from hospitals participating in the American Heart Association's Get With The Guidelines-HF who volunteered to participate in IMPLEMENT-HF in 7 …

Widespread Pain Phenotypes Impact Treatment Efficacy Results In Randomized Clinical Trials For Interstitial Cystitis/Bladder Pain Syndrome: A Multidisciplinary Approach To The Study Of Chronic Pelvic Pain Network Study, John T. Farrar, Siobhan Sutcliffe, Et Al.

2020-Current year OA Pubs

Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the likelihood of response to therapy, but it has not been tested in clinical trials for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). We explored this hypothesis using data from 3 previously published trials testing treatments for IC/BPS, which suggested modest benefits but did not meet a priori …

A Standardized Nomenclature For The Rods And Cones Of The Vertebrate Retina, Tom Baden, Takeshi Yoshimatsu, Joseph C. Corbo, Et Al.

2020-Current year OA Pubs

Vertebrate photoreceptors have been studied for well over a century, but a fixed nomenclature for referring to orthologous cell types across diverse species has been lacking. Instead, photoreceptors have been variably-and often confusingly-named according to morphology, presence/absence of 'rhodopsin', spectral sensitivity, chromophore usage, and/or the gene family of the opsin(s) they express. Here, we propose a unified nomenclature for vertebrate rods and cones that aligns with the naming systems of other retinal cell classes and that is based on the photoreceptor type's putative evolutionary history. This classification is informed by the functional, anatomical, developmental, and molecular identities of the neuron …

Automated Extraction Of Functional Biomarkers Of Verbal And Ambulatory Ability From Multi-Institutional Clinical Notes Using Large Language Models, Levi Kaster, Ethan Hillis, Inez Y Oh, Bhooma R Aravamuthan, Virginia C Lanzotti, Casey R Vickstrom, Brain Gene Registry Consortium, Christina A Gurnett, Philip R O Payne, Aditi Gupta

2020-Current year OA Pubs

BACKGROUND: Functional biomarkers in neurodevelopmental disorders, such as verbal and ambulatory abilities, are essential for clinical care and research activities. Treatment planning, intervention monitoring, and identifying comorbid conditions in individuals with intellectual and developmental disabilities (IDDs) rely on standardized assessments of these abilities. However, traditional assessments impose a burden on patients and providers, often leading to longitudinal inconsistencies and inequities due to evolving guidelines and associated time-cost. Therefore, this study aimed to develop an automated approach to classify verbal and ambulatory abilities from EHR data of IDD and cerebral palsy (CP) patients. Application of large language models (LLMs) to clinical …

Synergies, Partnership Outcomes, And Lessons Learned: A Qualitative Evaluation Of Cancer Center-Coalition Engagement, Aubrey Villalobos, Sarah Chavez, Bettina Drake, Et Al.

2020-Current year OA Pubs

BACKGROUND: Nine National Cancer Institute-Designated Cancer Centers received supplemental funding to expand community outreach and engagement activities through a partnership with Centers for Disease Control and Prevention-funded comprehensive cancer control coalitions. This article reports on an evaluation of these awards focused on organizational relationships and partnership outcomes.

METHODS: The National Cancer Institute, community outreach and engagement, and coalition representatives co-designed the evaluation, which involved document review and 18 semistructured interviews with 16 community outreach and engagement and 19 coalition representatives. Artificial intelligence-generated interview transcripts were dual-coded in NVivo, version 20/R1, software.

RESULTS: The funding generated a diverse collection of projects …

Histidine-Rich Enantiomeric Peptide Coacervates Enhance Antigen Sequestration And Presentation To T Cells, Ushasi Pramanik, Anirban Das, Elise M Brown, Heather L Struckman, Huihao Wang, Samuel Stealey, Macy L Sprunger, Abdul Wasim, Jonathan Fascetti, Jagannath Mondal, Jonathan R Silva, Silviya P Zustiak, Meredith E Jackrel, Jai S Rudra

2020-Current year OA Pubs

Peptides and peptidomimetics that self-assemble through LLPS have recently emerged as vital building blocks for creating functional biomaterials, thanks to their unique physicochemical properties and dynamic nature. One of life's most distinctive features is its selectivity for chiral molecules. To date, coacervates comprised of d-amino acids have not been reported. Here, we demonstrate that histidine-rich repeats of (GHGXY)

A Secretome Atlas Of Cardiac Fibroblasts From Healthy And Infarcted Mouse Hearts, Jasmin Bahr, Junedh M Amrute, Kory J Lavine, Et Al.

2020-Current year OA Pubs

Cardiac fibroblasts (CF) are key players after myocardial infarction (MI), but their signaling is only incompletely understood. Here we report a first secretome atlas of CF in control (cCF) and post-MI mouse hearts (miCF), combining a rapid cell isolation technique with SILAC and click chemistry. In CF, numerous paracrine factors involved in immune homeostasis are identified. Comparing secretome, transcriptome (SLAMseq), and cellular proteome disclose protein turnover. In miCF at day 5 post-MI, significantly upregulated proteins include SLIT2, FN1, and CRLF1 in mouse and human samples. Comparing the miCF secretome at days 3 and 5 post-MI reveals the dynamic nature of …

Distinct Oxytocin Signaling Pathways Synergistically Mediate Rescue-Like Behavior In Mice, Feng-Rui Zhang, Juan Liu, Jieqi Wen, Zi-Yan Zhang, Yijia Li, Eric Song, Li Hu, Zhou-Feng Chen

2020-Current year OA Pubs

Spontaneous rescue behavior enhances the well-being and survival of social animals, yet the neural mechanisms underlying the recognition and response to conspecifics in need remain unclear. Here, we report that observer mice experience distress when encountering anesthetized conspecifics, prompting spontaneous rescue-like behavior toward the unconscious mice. This behavior facilitates the earlier awakening of anesthetized mice while simultaneously alleviating stress in the helper mice. Our findings reveal that endogenous oxytocin (OXT) release from the hypothalamic paraventricular nucleus (PVN) to the oxytocin receptor (OXTR) in the central nucleus of the amygdala (CeA) regulates the emotional component of rescue-like behavior. In contrast, OXT …

Place-Based Harms And Hidden Strengths: A Qualitative Study Exploring Facets Of Neighborhood Disinvestment Driving Opioid Overdose Among Black Individuals, Kaytryn D Campbell, Rachel P Winograd, Maria E Paschke, Alex Duello, Devin E Banks

2020-Current year OA Pubs

BACKGROUND: Despite significant efforts to address the opioid overdose crisis, Black people who use drugs (PWUD) face unabating, disproportionate increases in opioid overdose death (OOD) rates. These inequities persist in treatment admissions, utilization of medication for opioid use disorder, and treatment retention. Research has linked neighborhood disinvestment - a process of urban decline driven by policy-related changes in neighborhood demand and desirability leading to decreased population, physical and economic erosion, and poorer quality of life for residents - to increased rates of OOD. However, given recent increases in OOD inequities, more research is needed to determine the specific aspects of …

Patient-Generated Health Data: Impact On Promoting Patient-Centered Point Of Care Tobacco Treatment In Patients With Cancer, Jessica Liu, Jingling Chen, Nina Smock, Nicholas B Griffith, Ramaswamy Govindan, Paula Goldberg, Jodi Thole, Kristin Daly, James Reddy, Alex T Ramsey, Laura J Bierut, Aimee James, Robert A Schnoll, Ross C Brownson, Li-Shiun Chen, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Guideline-based tobacco treatment is infrequently offered. Electronic health record-enabled patient-generated health data (PGHD) has the potential to increase patient treatment engagement and satisfaction.

METHODS: We evaluated outcomes of a strategy to enable PGHD in a medical oncology clinic from July 1, 2021 to December 31, 2022. Among 12,777 patients, 82.1% received a tobacco screener about use and interest in treatment as part of eCheck-in via the patient portal.

RESULTS: We attained a broad reach (82.1%) and moderate response rate (30.9%) for this low-burden PGHD strategy. Patients reporting current smoking (

DISCUSSION: PGHD via patient portal appears to be a …

Functional Connectivity Between The Visual And Salience Networks And Autistic Social Features At School-Age, Jessica B Girault, Tomoyuki Nishino, Muhamed Talović, Margaret Reynolds, Abraham Z Snyder, Kelly N Botteron, Natasha Marrus, Robert C Mckinstry, Alexandre A Todorov, John R Pruett Jr, Et Al.

2020-Current year OA Pubs

BACKGROUND: Autism spectrum disorder (ASD) is highly heritable and phenotypically variable. Neuroimaging markers reflecting variation in behavior will provide insights into circuitry subserving core features. We examined functional correlates of ASD symptomology at school-age, while accounting for associated behavioral and cognitive domains, in a longitudinal sample followed from infancy and enriched for those with a genetic liability for ASD.

METHODS: Resting state functional connectivity MRIs (fcMRI) and behavioral data were analyzed from 97 school-age children (8.1-12.0 years, 55 males, 15 ASD) with (n = 63) or without (n = 34) a family history of ASD. fcMRI enrichment analysis (EA) was …

Perspectives On The Current Diagnostic And Treatment Paradigms In Secondary Hemophagocytic Lymphohistiocytosis (Hlh), Leonard Naymagon, Jeffrey Bednarski, Et Al.

2020-Current year OA Pubs

Improved awareness of hemophagocytic lymphohistiocytosis (HLH) among clinicians has led to an increase in its diagnosis. Often diagnosis is made based on the HLH- 2004 criteria. While these criteria have considerable strengths, they lack specificity and may be fulfilled in the setting of many pro-inflammatory disorders. Genetic defects affecting cellular cytotoxicity cause familial (primary) HLH. On the other hand, secondary HLH is more a pathophysiologic process common to many conditions, rather than a singular disease entity. Improved genetic, immunologic, and functional testing have changed not only the way we diagnose HLH, but also how we treat it. In 2004, there …

Adipose-Derived Leptin And Complement Factor D Mediate Osteoarthritis Severity And Pain, Kelsey H Collins, Kristin L Lenz, Hope D Welhaven, Erica Ely, Luke E Springer, Sophie Paradi, Ruhang Tang, Lauryn Braxton, Antonina Akk, Huimin Yan, Bo Zhang, Xiaobo Wu, John P Atkinson, Arin K Oestreich, Ron K June, Christine T N Pham, Farshid Guilak

2020-Current year OA Pubs

Obesity is a risk factor for osteoarthritis (OA), and leptin is among the adipokines implicated in obesity-induced OA. However, the specific role of leptin in OA severity and pain is not known. Using lipodystrophic (LD) mice, we show that fat-secreted factors are required for knee OA development, implicating a fat-cartilage cross-talk. Fat pad implantation or systemic leptin restoration in LD mice reintroduced structural OA and pain, whereas implantation of leptin-deficient fat pad did not change OA susceptibility. Isochronic parabiosis and spatial transcriptomics confirmed that a fat-joint cross-talk likely occurred via soluble mediators. Global unsupervised multiomics of conditioned media from fat …

Functional Screening Identifies Kinesin Spindle Protein Inhibitor Filanesib As A Potential Treatment Option For Hepatoblastoma, Ruth Nousiainen, Katja Eloranta, Jani Saarela, Antti Hassinen, Tamara J Luck, Stefano Cairo, Emilie Indersie, Swapnil Potdar, Michaela J Feodoroff, Jouko Lohi, Lassi Paavolainen, David B Wilson, Vilja Pietiäinen, Markku Heikinheimo, Marjut Pihlajoki

2020-Current year OA Pubs

Hepatoblastoma is a rare pediatric liver malignancy usually treated with surgery and chemotherapy. To explore new treatment options for hepatoblastoma, drug screening was performed using six cell models established from aggressive hepatoblastoma tumors and healthy pediatric primary hepatocytes. Of the 527 screened compounds, 98 demonstrated cancer-selective activity in at least one hepatoblastoma model. The kinesin spindle protein (KSP) inhibitor filanesib was effective in all models and was further evaluated. Filanesib induced G2/M arrest and apoptosis in hepatoblastoma cells at concentrations tolerable to primary hepatocytes. Prominent nuclear fragmentation was observed in filanesib-treated hepatoblastoma cells. Genes participating in cell cycle regulation were …

Development And Evaluation Of A Non-Invasive Brain-Spine Interface Using Transcutaneous Spinal Cord Stimulation, Carolyn Atkinson, Lorenzo Lombardi, Meredith Lang, Rodolfo Keesey, Rachel Hawthorn, Zachary Seitz, Eric C Leuthardt, Peter Brunner, Ismael Seáñez

2020-Current year OA Pubs

Motor rehabilitation is a therapeutic process to facilitate functional recovery in people with spinal cord injury (SCI). However, its efficacy is limited to areas with remaining sensorimotor function. Spinal cord stimulation (SCS) creates a temporary prosthetic effect that may allow further rehabilitation-induced recovery in individuals without remaining sensorimotor function, thereby extending the therapeutic reach of motor rehabilitation to individuals with more severe injuries. In this work, we report our first steps in developing a non-invasive brain-spine interface (BSI) based on electroencephalography (EEG) and transcutaneous spinal cord stimulation (tSCS). The objective of this study was to identify EEG-based neural correlates of …