tbuckley/cabot-search huggingface dataset:
Effect of Repeated Low-Level Red-Light Therapy for Myopia Control in Children
Authors: Yu Jiang, Zhuoting Zhu, Xingping Tan, Xiangbin Kong, Hui Zhong, Jian Zhang, Ruilin Xiong, Yixiong Yuan, Junwen Zeng, Ian G. Morgan, Mingguang He
Journal: Ophthalmology (2021)

To assess the efficacy and safety of repeated low-level red-light (RLRL) therapy in myopia control in children.Multicenter, randomized, parallel-group, single-blind clinical trial.Two hundred sixty-four eligible children 8 to 13 years of age with myopia of cycloplegic spherical equivalent refraction (SER) of -1.00 to -5.00 diopters (D), astigmatism of 2.50 D or less, anisometropia of 1.50 D or less, and best-corrected visual acuity (BCVA) of 0.0 logarithm of the minimum angle of resolution or more were enrolled in July and August 2019. Follow-up was completed in September 2020.Children were assigned randomly to the intervention group (RLRL treatment plus single-vision spectacle [SVS]) and the control group (SVS). The RLRL treatment was provided by a desktop light therapy device that emits red light of 650-nm wavelength at an illuminance level of approximately 1600 lux and a power of 0.29 mW for a 4-mm pupil (class I classification) and was administered at home under supervision of parents for 3 minutes per session, twice daily with a minimum interval of 4 hours, 5 days per week.The primary outcome and a key secondary outcome were changes in axial length and SER measured at baseline and the 1-, 3-, 6-, and 12-month follow-up visits. Participants who had at least 1 postrandomization follow-up visit were analyzed for treatment efficacy based on a longitudinal mixed model.Among 264 randomized participants, 246 children (93.2%) were included in the analysis (117 in the RLRL group and 129 in the SVS group). Adjusted 12-month axial elongation and SER progression were 0.13 mm (95% confidence interval [CI], 0.09-0.17mm) and -0.20 D (95% CI, -0.29 to -0.11D) for RLRL treatment and 0.38 mm (95% CI, 0.34-0.42 mm) and -0.79 D (95% CI, -0.88 to -0.69 D) for SVS treatment. The differences in axial elongation and SER progression were 0.26 mm (95% CI, 0.20-0.31 mm) and -0.59D (95% CI, -0.72 to -0.46 D) between the RLRL and SVS groups. No severe adverse events (sudden vision loss ≥2 lines or scotoma), functional visual loss indicated by BCVA, or structural damage seen on OCT scans were observed.Repeated low-level red-light therapy is a promising alternative treatment for myopia control in children with good user acceptability and no documented functional or structural damage.
Association Between Social Media Use and Self-reported Symptoms of Depression in US Adults
Authors: Roy H. Perlis, Jon Green, Matthew Simonson, Katherine Ognyanova, Mauricio Santillana, Jennifer Lin, Alexi Quintana, Hanyu Chwe, James Druckman, David Lazer, Matthew A. Baum, John Della Volpe
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Some studies suggest that social media use is associated with risk for depression, particularly among children and young adults. <h3>Objective</h3> To characterize the association between self-reported use of individual social media platforms and worsening of depressive symptoms among adults. <h3>Design, Setting, and Participants</h3> This survey study included data from 13 waves of a nonprobability internet survey conducted approximately monthly between May 2020 and May 2021 among individuals aged 18 years and older in the US. Data were analyzed in July and August 2021. <h3>Main Outcomes and Measures</h3> Logistic regression was applied without reweighting, with a 5 point or greater increase in 9-item Patient Health Questionnaire (PHQ-9) score as outcome and participant sociodemographic features, baseline PHQ-9, and use of each social media platform as independent variables. <h3>Results</h3> In total, 5395 of 8045 individuals (67.1%) with a PHQ-9 score below 5 on initial survey completed a second PHQ-9. These respondents had a mean (SD) age of 55.8 (15.2) years; 3546 respondents (65.7%) identified as female; 329 respondents (6.1%) were Asian, 570 (10.6%) Black, 256 (4.7%) Hispanic, 4118 (76.3%) White, and 122 (2.3%) American Indian or Alaska Native, Pacific Islander or Native Hawaiian, or other. Among eligible respondents, 482 (8.9%) reported 5 points or greater worsening of PHQ-9 score at second survey. In fully adjusted models for increase in symptoms, the largest adjusted odds ratio (aOR) associated with social media use was observed for Snapchat (aOR, 1.53; 95% CI, 1.19-1.96), Facebook (aOR, 1.42; 95% CI, 1.10-1.81), and TikTok (aOR, 1.39; 95% CI, 1.03-1.87). <h3>Conclusions and Relevance</h3> Among survey respondents who did not report depressive symptoms initially, social media use was associated with greater likelihood of subsequent increase in depressive symptoms after adjustment for sociodemographic features and news sources. These data cannot elucidate the nature of this association, but suggest the need for further study to understand how social media use may factor into depression among adults.
Abstract 11699: Angiographic Coronary Artery Disease (CAD) and Outcomes in Acute Heart Failure (HF)
Authors: Leah B Kosyakovsky, Heather Ross, Shaun G Goodman, Xuesong Wang, Husam Abdel Qadir, Peter Austin, Patrick R Lawler, Eric Horlick, Andrew Czarnecki, Ismail Raslan, Barbara Doumouras, Michael E Farkouh, John Spertus, Douglas S Lee
Journal: Circulation (2021)

Introduction: The association between CAD severity and long-term outcomes in patients admitted with acute HF has not been determined. We characterized the angiographic burden of CAD in patients with acute HF and determined the association between CAD severity and mortality and readmission outcomes. Methods: In a multicenter registry of 70 hospitals in Ontario, Canada, we identified acute HF patients who underwent coronary angiography within 14 days of hospitalization (April 2010-March 2013) using stratified random sampling. We selected a cohort of HF patients with a higher a priori risk of CAD, defined inclusively as those with at least one of the following features: previous myocardial infarction (MI), troponin elevation, or angina on presentation. Using angiographic data, we defined obstructive CAD as the presence of &gt; 70% stenosis in at least one epicardial vessel or &gt; 50% left main (LM) stenosis. Multivessel disease (MVD) was defined as the presence of obstructive disease in 2 or more vessels. We determined adjusted associations between coronary anatomy and the rate of cardiovascular (CV) death and readmissions over two years. Results: Of 1772 patients undergoing angiography who met inclusion criteria (median age 71 [IQR 62-79] years; 38.5% women), 1039 patients had CAD and 683 had MVD. Increasing CAD burden was associated with higher CV death (Figure). CV death was significantly increased in those with any CAD and HFpEF (HR 2.27, 95%CI; 1.12, 4.59, p=0.023). The rate of CV death was increased in MVD (HR 1.91, 95% CI; 1.32, 2.75, p&lt;0.001) but not single-vessel disease (HR 1.15, 95%CI; 0.75, 1.77, p=0.516), compared to no obstructive CAD. There was no interaction between MVD and HFpEF or HFrEF status for the outcome of CV death (p=0.690). CV readmission was also significantly higher only in MVD (HR 1.28, 95%CI; 1.07, 1.54, p=0.008). Conclusion: In patients presenting with acute HF, angiographic MVD is associated with an increased rate of CV death and readmissions over 2 years.
Assessing the Potential for Patient-led Surveillance After Treatment of Localized Melanoma (MEL-SELF)
Authors: Deonna M. Ackermann, Mbathio Dieng, Ellie Medcalf, Marisa C. Jenkins, Cathelijne H. van Kemenade, Monika Janda, Robin M. Turner, Anne E. Cust, Rachael L. Morton, Les Irwig, Pascale Guitera, H. Peter Soyer, Victoria Mar, Jolyn K. Hersch, Donald Low, Cynthia Low, Robyn P. M. Saw, Richard A. Scolyer, Dorothy Drabarek, David Espinoza, Anthony Azzi, Alister M. Lilleyman, Amelia K. Smit, Peter Murchie, John F. Thompson, Katy J. L. Bell
Journal: JAMA Dermatology (2021)

Patient-led surveillance is a promising new model of follow-up care following excision of localized melanoma.
Abstract 10485: Case Fatality and Prior Anticoagulation in Patients with Atrial Fibrillation and First-Ever Ischemic Stroke
Authors: Paula Tiili, Jukka Putaala, Olli Halminen, Janne Kinnunen, Jari Haukka, Miika Linna, Pirjo Mustonen, Juhani Airaksinen, Mika Lehto
Journal: Circulation (2021)

Introduction: Thromboprophylaxis of patients with atrial fibrillation (AF) has changed in the past decade. How the changes manifest in real life is yet less studied. This study describes 30-day case fatality and prior anticoagulation in a nationwide cohort of patients with AF and first-ever ischemic stroke during the past decade. Methods: FinACAF (Finnish Anticoagulation in Atrial Fibrillation) is a registry-linkage study. Data were collected from several nationwide registries. We followed patients with incident AF between 2009 and 2017 with first-ever ischemic stroke between January 2009 and November 2018. Cox regression model was used to estimate the associations between 30-day case fatality and oral anticoagulation (OAC) if purchased 90 days preceding the stroke, adjusting for age, sex, time of AF diagnosis relative to stroke (new-onset AF vs. prior diagnosis), and stroke year. Results: Altogether, 17,924 patients (55% female, median age 79 years with interquartile range 71-86) suffered from first-ever ischemic stroke. Crude 30-day case fatality was 15.4% (95% confidence interval 14.9-15.9, p=0.037). Prior NOAC (hazard ratio 0.69, 0.57-0.84, p&lt;0.001) and prior warfarin (0.78, 0.71-0.86, p&lt;0.001) usage were both associated with lower case fatality compared to those without any OAC in use. There was no significant difference between previous warfarin and NOAC usage. Older age and AF diagnosis registered before the stroke, as opposed to AF diagnosis first recognized together with stroke, were associated with higher case fatality. There was no significant difference between 30-day case fatality when comparing cases by the event year (1.00, 0.98-1.01, p=0.739). Conclusion: Previously recorded AF diagnosis was associated with higher 30-day case fatality, although prior use of warfarin and NOAC were associated with decreased mortality compared to no prior OAC use.
Abstract 9971: Longitudinal Lipoprotein(a) Concentrations and Cardiovascular Risk: A Prospective Cohort Study
Authors: Mark Trinder, Kaavya Paruchuri, Sara Haidermota, Rachel Bernardo, Seyedeh Zekavat, Thomas C Gilliland, James L Januzzi, Pradeep Natarajan
Journal: Circulation (2021)

Introduction: When indicated, current guidelines recommend a single measurement of lipoprotein(a) for cardiovascular risk assessment. However, temporal variability in lipoprotein(a) concentration is not well understood, and it is unclear if repeat testing may help refine risk prediction of coronary artery disease (CAD). Hypothesis: We examined the longitudinal stability of lipoprotein(a) measurements and tested whether instability in lipoprotein(a) molar concentration was associated with incident CAD. Methods: We assessed the correlation between baseline and first follow-up measurements of lipoprotein(a) in the UK Biobank (molar concentration n=16,017) and Mass General Brigham cohorts (molar concentration n=271; mass n=1,748; cholesterol n=1,237). The association between change in lipoprotein(a) molar concentration and incident CAD was assessed among 15,432 UK Biobank participants using Cox proportional-hazards models. Results: Baseline and follow-up lipoprotein(a) molar concentration were significantly correlated in the UK Biobank over a median 4.42 years (IQR: 1.24 years) and Mass General Brigham cohorts over a median 0.94 years (IQR: 0.60 years) (Spearman correlations: 0.96 and 0.92, respectively; p-values &lt;0.0001). Similar results were observed for lipoprotein(a) mass and cholesterol. Follow-up lipoprotein(a) molar concentration was significantly associated with risk of incident CAD (HR [95% CI] per 120 nmol/L: 1.31 [1.14-1.51], p-value=0.0002). However, delta lipoprotein(a) was not significantly associated with incident CAD independent of follow-up lipoprotein(a) (p-value=0.98). Conclusions: These findings suggest that, in the absence of therapies substantially altering lipoprotein(a) measures, longitudinal assessments of lipoprotein(a) are likely unnecessary for CAD risk assessment in the context of primary prevention.
CTIM-30. PHASE II TRIAL OF PEMBROLIZUMAB IN RECURRENT AND RESIDUAL HIGH-GRADE MENINGIOMAS
Authors: Priscilla Brastianos, Albert Kim, Anita Giobbie-Hurder, Eudocia Quant Lee, Nancy Wang, April Eichler, Ugonma Chukwueke, Deborah Forst, Isabel Arrillaga-Romany, Jorg Dietrich, Kevin Lou, Juliana Larson, Joana Mora, Naema Nayyar, Jay Loeffler, Kevin Oh, Helen Shih, William Curry, Daniel Cahill, Fred Barker, Elizabeth Gerstner, Sandro Santagata
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION High-grade meningiomas are associated with significant neuro-cognitive morbidity and a poor prognosis. Systemic therapies, to date, have demonstrated minimal efficacy. We recently found that high-grade meningiomas harbor an immunosuppressive tumor microenvironment and that programmed cell death-ligand 1 (PD-L1) expression may contribute to the aggressive phenotype of these tumors. Therefore, we conducted a single-arm, open-label phase II trial evaluating efficacy of pembrolizumab, a PD-1 inhibitor, in a cohort of 24 patients with recurrent and progressive grade II and III meningiomas. METHODS The primary endpoint was the rate of progression-free survival at 6 months. The trial distinguished between 6-month PFS (PFS-6) rates of 26% vs. 52%. If at least 10 patients demonstrated a 6-month PFS, among the 24 patients, the agent would be considered worthy of further study. This design has at least 88% power using an exact binomial test with a one-sided significance level of 0.1. RESULTS Between November 2017 to December 2019, twenty-four patients were enrolled. The majority of the patients in our cohort were heavily pre-treated; prior to enrolling to the study, twenty patients underwent more than one surgical resection and twelve patients had received more than one round of radiotherapy. Our study met its primary endpoint and achieved a 6-month progression-free survival rate of 0.50 (90% exact CI: 0.32-0.68) and a median PFS of 8.3 months (90% CI: 4.1-12.9 months). For the twelve patients who achieved the PFS-6 primary endpoint, median PFS from the start of treatment was 17.3 months (90% CI: 9.7 – 24.3 months). Four patients had grade-3 or higher adverse events that were at least possibly treatment-related, including colitis, skin infection, encephalopathy and transaminitis. CONCLUSION Our study achieved its primary endpoint. These results suggest that pembrolizumab exerts promising activity on these tumors and results in prolonged PFS compared to historical controls.
EPID-23. THE PAKISTAN BRAIN TUMOR EPIDEMIOLOGY STUDY: PAVING THE WAY FOR A NATIONAL BRAIN TUMOR REGISTRY
Authors: Mashal Shah, Erum Baig, Mohammad Hamza Bajwa, Altaf Ali Laghari, Saad Bin-Anis, Naveed Zaman Akhunzada, Jaleed Gilani, Noyan Jawed, Usman Khalid, Namra Qadeer, Areeb Lutfi, Izza Tahir, Rameen Bajwa, Huzaifa Rashid, Haleema Sadia, Kinzah Ghazi, Mishal Gillani, Iqbal Azam, Uzma Shamsi, Pakistan Brain Tumor Consortium, Sameen Siddiqi, Syed Ather Enam
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION In Pakistan, brain tumor epidemiology has been examined in single-centre studies or as part of general cancer registries, which are limited by catchment area, age group, or are not specific to brain tumors. The Pakistan Society of Neuro-Oncology conducted a nationwide study to assess the distribution of brain tumor distribution and associated risk factors. This unfunded study explores data from across Pakistan and serves as a potential model for LMICs to emulate. METHODS A cross-sectional study was designed to include patients diagnosed with brain tumors in major neurosurgical centers in Pakistan retrospectively from January-December 2019. Patients, both alive and deceased, with a radiological diagnosis of a brain tumor were included. Data were recorded on a comprehensive online form from 35 centers, encompassing an estimated 85% of all the brain tumor patients seeking initial treatment by a neurosurgeon from the public and private sectors. Data collection was split into three regions: Sindh and Balochistan; Punjab; and Khyber Pakhtunkhwa and Islamabad. Data collection occurred between August 2020 and January 2021. RESULTS A total of 2750 brain tumor cases were recorded of which 1897 (69%) were diagnosed in the private sector hospitals. MRIs were a more common radiological study compared to CT scans. 2666 surgeries were performed, 174 individuals underwent chemotherapy and 479 underwent radiation therapy; approximately two-thirds of the patients that require adjuvant treatment are not able to receive it. Gliomas were the most common tumor, while pineal tumors were the least common. Findings indicate a low metastasis frequency and few females seeking care. CONCLUSION The study shows that brain tumors are mostly diagnosed and operated on in the private sector; the public sector should be more engaged. The study also highlights that despite inconsistencies in hospital records for brain tumor patients, reliable information can be collected in LMIC settings.
BIOM-45. CHARACTERIZATION OF EVs RELEASED FROM 5-ALA DOSED GLIAL AND EXTRA-AXIAL TUMORS
Authors: Tiffaney Hsia, Anudeep Yekula, Bob Carter, Leonora Balaj
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION The administration of 5-Aminolevunlinic acid (5-ALA) in the context of fluorescence-guided surgery is contingent on the highly selective accumulation of PpIX in tumor cells. PpIX is a precursor in the heme pathway that naturally exhibits fluorescent and phototoxic properties upon excitation. We have previously reported evidence of PpIX fluorescence in tumor-specific extracellular vesicles (EVs). Here, we explore the implications of exogenous 5-ALA on cellular function, EV characteristics, and gene expression. METHODS We have characterized a range of glioblastoma, meningioma, and healthy cell lines (Gli36 EGFRvIII, Gli36 EGFR WT, U87, CH-157, IOMM-Lee, and HBMVEC). At equal confluency, cells were dosed with 0.8 mM 5-ALA or mock dosed. Media was collected and processed to eliminate debris after 24 hours. Analysis of cells and EVs was conducted using Amnis ImageStream (IFC) and Nanoparticle Tracking Analysis. EV subpopulations were analyzed with IFC following antibody staining. RNA was extracted using Qiagen exoRNeasy and RNeasy. Libraries were prepared via Qiagen UPX 3’ Transcriptome kit and sequenced using Illumina MiSeq. Data analysis was carried out via GeneGlobe, CLC workbench, and MATLAB. RESULTS Following 5-ALA dosing, all tumor cells and their derived EVs exhibit significant levels of fluorescence. Analysis of EV subpopulations demonstrated a general decrease in tetraspanin-positive EVs following 5-ALA dosing. At 24 hours, Gli36 cell lines exhibited increased EV release post 5-ALA whereas U87 and meningioma lines resulted in a decreased EV release rate. This clustering is also reflected in EV size distributions and in cellular and EV differential gene expression analysis. Gene ontology analysis of common genes from mock and dosed EVs demonstrated high counts of genes controlling biological regulation as well as cellular and metabolic processes. CONCLUSION Collection and characterization of cancer specific EVs may be advantageous to liquid biopsy development.
Abstract 13748: Feasibility Of Quantitation Coronary And Aortic Valve Calcification In Virtual Non-contrast Images From Dual-energy Delayed Ct Scans In Patients With Severe Aortic Stenosis
Authors: Donghee Han, Balaji Tamarappoo, Alan C Kwan, Raj Makkar, Damini Dey, John Friedman, Daniel S Berman
Journal: Circulation (2021)

Introduction: Increased extracellular volume (ECV), is a prognostically important marker of myocardial fibrosis in patients with severe aortic stenosis (AS). ECV can be assessed during transcatheter aortic valve replacement planning CT (TAVR CT) scan by adding a dual-energy CT (DECT) delayed image. TAVR CT scans routinely include a traditional non-contrast scan (TNC) for coronary artery calcium (CAC) and aortic valve calcium (AVC) scoring. Virtual non-contrast (VNC) images, derived from the DECT could replace TNC for CAC and AVC scoring, and reducing radiation and scan time. We examined the adaptability of VNC as a substitute for TNC by comparing CAC and AVC scoring based on VNC from delayed DECT scans compared to TNC in severe AS patients. Methods: We enrolled 27 severe AS patients who underwent TNC CAC scan and delayed DECT scan as part of TAVR CT using a dual-source scanner (Somatom Flash, Siemens). VNC was reconstructed with postprocessing software (Syngo Dual Energy, Siemens). CAC was categorized as 0, 1-99, 100-399, 400-999 and ≥1,000. Severe AVC was defined as &gt;2,200 for men and &gt;1,200 for women. Results: Both CAC and AVC scores in VNC demonstrated excellent correlation with TNC (r=0.975 and 0.982). The CAC score was significantly lower in VNC compare to TNC (745.2 ± 923.6 vs. 1006.4 ± 1116.9, p&lt;0.001). AVC score did not significantly differ between VNC and TNC (2000.8 ± 2791.6 vs. 1911.5 ± 2186.8, p=0.567). Three patients (3/27) were categorized to a CAC category one grade lower than TNC by VNC DECT (Figure). One patient with non-severe AVC by TNC was misclassified as having severe AVC by VNC (1/27) (Figure). Conclusions: VNC DECT underestimates CAC compared to TNC, but the differences in CAC score rarely resulted in categorical discordance in severe AS patients. VNC from DECT delayed scan for ECV assessment can assign patients to the correct cardiovascular risk categories based on CAC and performs adequately for clinically meaningful AVC scoring in severe AS patients.
IMMU-32. IDENTIFICATION OF TUMOR-ANTIGEN SPECIFIC T CELLS AND THE EFFICACY OF IMMUNOTHERAPY VACCINES FOR GLIOBLASTOMA ANTIGENS DETERMINED USING CANCER IMMUNOGENOMICS APPROACH
Authors: Vrunda Trivedi, Changlin Yang, Oleg Yegorov, Kyle Dyson, Duane Mitchell
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastoma multiforme (GBM) remains a disease with debilitating survival outcomes. Owing to the heterogeneous nature and low mutation burden, identifying multiple antigens inherent to GBM that may serve as targets for immune-based therapies is attractive. Our aim is to develop a personalized immunotherapy approach using cancer immunogenomics for prospectively identifying neoantigens and uniquely expressed tumor proteins and then selectively expanding T cells against these truly tumor-specific antigens and dendritic cell vaccines to boost the T cell responses. METHODS RNAseq and WES was performed for murine KR158-luc GBM tumor. Using a cancer immunogenomics approach that we developed, called the O pen R eading Frame A ntigen N etwork (O.R.A.N.), we identified the immunogenic neoantigens and tumor-associated antigens (TAAs) including cancer testis and developmental antigens, that are aberrantly over-expressed in KR158-luc tumor. All predicted genes were subjected to a gene enrichment strategy and an mRNA library was generated containing predominantly only the target genes but had some background non-specific genes (validated by RNAseq). KR158-luc tumor bearing animals were then treated with dendritic cells loaded with the tumor antigen specific mRNA library. Tumor volume and thus progress was determined using in vivo luciferase imaging technique. Additionally, tetramers specific to several of the predicted antigens were manufactured and the frequency of antigen specific T cells was determined using flow cytometry. RESULTS The dendritic cell vaccines were effective in delaying the progression of KR158-luc tumors and we identified T cells targeting several of our predicted antigens in the tumor bearing animals. The antigen specific T cells were detected in the tumor infiltrating lymphocytes as well as in the peripheral lymph organs. CONCLUSION We developed a dendritic cell-based vaccination approach targeting all neoantigens and TAAs identified as being tumor-specific and validated our developed immunogenomics pipeline by identifying antigen-specific T cells in the tumor bearing animals against novel GBM antigens.