tbuckley/cabot-search huggingface dataset:
ANGI-11. SEX DIFFERENCES IN IMAGING-BASED ASSESSMENT OF GLIOBLASTOMA INVASION
Authors: Susan Christine Massey, Andrea Hawkins-Daarud, Pamela Jackson, Rebecca Grove, Katrina Bakken, Lihong He, Ann Mladek, Ashley Stokes, Ashlyn Gonzalez, Ashley Nespodzany, Jenny Eschbacher, Leslie Baxter, Kris Smith, Peter Nakaji, Samuel McGee, Bernard Bendok, Terence Burns, Jann Sarkaria, Leland Hu, Kristin Swanson
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Neuroimaging dogma for glioblastoma asserts that hyperintensity on T1Gd MRI reveals the bulk of the tumor, while T2/FLAIR signal indicates edema. However, it is unclear whether this edema results from immune response or increased tumor cells. Further, one significant driver of the known sex differences in glioblastoma may be differences in immune response, due to the X-linkage of many immune genes. Based on this, we hypothesized that assumptions regarding tumor cellularity in T2/FLAIR images should be tailored to the biological sex of the patient. METHODS Using a retrospective cohort of 18 primary glioblastoma patients receiving multiple image-localized biopsies (82 total) and standard MRI, we assessed: distance of biopsy from T1Gd and T2 areas; a pathologist’s score of percent tumor cell density; and an imaging-based invasion metric, D/ρ. This metric is derived from the biomathematical Proliferation-Invasion model of glioma growth, which features two parameters, net growth rate (ρ) and net invasion rate (D). Their ratio D/ρ is related to degree of invasion, and is estimated from volumetric measurements of MRI abnormalities. Additionally, 25 patient-derived xenograft models implanted in females were grown until moribund, at which point brains were excised and stained for DAPI (to show all cells) and Lamin (to highlight tumor cells). Image processing of lamin-stained sections defines contours of intensity correlating with cell density. RESULTS Outside both the T1Gd and T2 region, male patient biopsies had higher tumor cell densities than females. Males also tended to have higher invasion metrics. Although each set derived from different patients, preclinical metrics of invasion were positively correlated with clinical invasion in females but negatively correlated in males. CONCLUSION Our preliminary finding that cell distribution patterns correlate with imaging metrics differently between the sexes supports the hypothesis that the degree of tumor cell density represented on certain MRI sequences may be sex-specific.
The Relationship between Transplant Status and Patient-Reported Outcomes in Patients with FLT3-Mutated Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML): Results from the Phase 3 Admiral Study
Authors: David Cella, Ellen K. Ritchie, Francesco Fabbiano, Arnaud Pigneux, Yoshinobu Kanda, Cristina Ivanescu, Bhavik J. Pandya, Manasee V Shah
Journal: Blood (2019)
Treatment of Heart Failure
Authors: S. Whittaker
Journal: BMJ (1955)

HIATUS HERNIAIn the present investigation, though many of the patients were elderly, none of the 70 from whom the first series is taken had pain which could be confused with that of myo- cardial ischaemia.The seven patients in the second series were referred privately to a cardiologist, as their symptoms were thought to be due to heart disease.In Case 1 pain and " wind in the chest " on walking, and relieved by stopping to belch, was suggestive of cardiac effort pain.However, the exertion necessary to provoke an attack varied consider- ably from day to day.This with the history of dyspepsia and the normal cardiological finding led to the correct diag- nosis.Pain in the chest (Case 5), in the chest and left arm (Case 4), and at the xiphisternum (Case 6) could have been mistaken for the pain of myocardial ischaemia, had the patient been seen in the first attack only.Again, diagnosis was assisted by the variation of the attacks over a period of time, the dyspeptic symptoms, and absence of significant cardiac disease.In Case 7 a history of genuine cardiac effort pain was related to anaemia and disappeared following iron treatment.No confusion arose in Cases 2 and 3.It would appear, therefore, from the present study and from the literaturereviewed here that hiatus hernia (in the absence of associated anaemia) may only rarely be responsible for pain in, or spreading to, the chest, arms, neck, and jaw.When this does occur it may have the same distribution as the pain of cardiac ischaemia, and the type of pain may be similar.Direct relationship to exertion, however, is very inconstant, and when present the effort required to produce the pain varies much more than in myocardial disease.Furthermore, it often lasts for hours.The pre- dominant aggravating factors are the taking of food, the horizontal position, and, as most authors stress, anxiety.Its relief with belladonna and antacids is usually better than with nitroglycerin.
Inhibition of Anti-Apoptotic Mcl-1 Exerts Anti-Leukemia Activity through Modulation of Leukemia-Stromal Interactions and Metabolic Functions in AML
Authors: Bing Z Carter, Po Yee Mak, Marc Warmoes, Wenjing Tao, Philip Lorenzi, Vivian Ruvolo, Lin Tan, Justin Cidado, Lisa Drew, Michael Andreeff
Journal: Blood (2019)
Policy Recommendations for Public Health Plans to Stem the Escalating Costs of Prescription Drugs: A Position Paper From the American College of Physicians
Authors: Hilary Daniel, Sue S. Bornstein
Journal: Annals of Internal Medicine (2019)

The increasing price of prescription drugs is an ongoing concern for Medicare and Medicaid, particularly for patients with chronic health conditions who are using multiple medications and patients in these programs taking high-priced brand-name specialty drugs. Shifts in benefit design, including higher deductibles and a movement away from copayments to coinsurance, have increased patient out-of-pocket costs and put pressure on program budgets. In this paper, the American College of Physicians expands on its position paper from 2016 and offers additional recommendations to decrease out-of-pocket costs for patients, enhance the government's purchasing power, and address existing policies that add costs to the health care system.
Tobacco Product Use and Cessation Indicators Among Adults — United States, 2018
Authors: MeLisa R. Creamer, Teresa W. Wang, Stephen Babb, Karen A. Cullen, Hannah Day, Gordon Willis, Ahmed Jamal, Linda Neff
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

an estimated 49.1 million U.S. adults (19.7%) reported currently using any tobacco product, including cigarettes (13.7%), cigars (3.9%), e-cigarettes (3.2%), smokeless tobacco (2.4%), and pipes* (1.0%).Most tobacco product users (83.8%) reported using combustible products (cigarettes, cigars, or pipes), and 18.8% reported using two or more tobacco products.The prevalence of any current tobacco product use was higher in males; adults aged ≤65 years; non-Hispanic American Indian/Alaska Natives; those with a General Educational Development certificate (GED); those with an annual household income <$35,000; lesbian, gay, or bisexual adults; uninsured adults; those with a disability or limitation; and those with serious psychological distress.The prevalence of e-cigarette and smokeless tobacco use increased during 2017-2018.During 2009-2018, there were significant increases in all three cigarette cessation indicators (quit attempts, recent cessation, and quit ratio).Implementing comprehensive populationbased interventions in coordination with regulation of the manufacturing, marketing, and distribution of all tobacco products can reduce tobacco-related disease and death in the United States (1,4).NHIS is an annual, nationally representative, household survey of the noninstitutionalized U.S. civilian population.† The 2018 NHIS Sample Adult component included 25,417 adults aged * The use of regular pipe, water pipe, or hookah was assessed together using a single question.
ATIM-03. ANTI-TGFß2 RNA THERAPEUTIC OT-101 INDUCES DURABLE OBJECTIVE RESPONSES IN PATIENTS WITH RECURRENT/REFRACTORY (R/R) GLIOBLASTOMA MULTIFORME (GBM, WHO GRADE 4) OR ANAPLASTIC ASTROCYTOMA (AA, WHO GRADE 3)
Authors: Fatih Uckun, Sanjive Qazi, Larn Hwang, David Nam, Vuong Trieu
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND High-grade gliomas (HGG) are characterized by a T-cell exhaustion signature and pronounced T-cell hyporesponsiveness of their tumor microenvironment (TME). Transforming growth factor beta 2 (TGF-ß2) has been implicated as a key contributor to the immunosuppressive landscape of the TME in HGG. OT-101 is a first-in-class RNA therapeutic designed to abrogate the immunosuppressive actions of TGF-ß2. Here we report the single-agent activity of OT-101 in adult patients with R/R HGG. METHODS In this phase 2 clinical trial (NCT00431561), OT-101 was administered with an intratumoral catheter using a convection enhanced delivery (CED) system. 77 patients received 4–11 cycles of OT-101 via continuous infusion over 7d. Response determinations were based on central review of MRI scans by an independent review committee according to standard and modified McDonald criteria. Standard statistical methods were applied for the analysis of data. RESULTS The median progression-free survival (PFS) and overall survival (OS) were 86d and 432d, respectively. 26 patients (33.8%) had marked reductions of their tumor volume after receiving OT-101: 19 achieved durable objective responses (CR: 3, PR: 16). The median time for 90% reduction of the baseline tumor volume was 11.7 months (Range: 4.9–57.7 months). The mean log reduction of the tumor volume was 2.2 ± 0.4 (Median = 1.4: Range: 0.4–4.5) logs. 7 had stable disease (SD) lasting &gt; 6 months. The median PFS (1109d [95% CI: 992 - &gt; 1423] vs. 37d [95% CI: 35 – 59] (Log-rank Chi Square = 69.9, P-value &lt; 0.0001) and OS (1280d [95% CI: 1116- &gt; 1743] vs. 240d [95% CI: 169 – 361] (Log-rank Chi Square = 47.0, P-value &lt; 0.0001) of these 26 patients was significantly better than the PFS or OS of the remaining 51 patients. CONCLUSION Anti-TGFß2 RNA therapeutic OT-101 exhibits clinically meaningful single-agent activity and induces durable CR/PR/SD in R/R HGG patients.
Associations Between Screen-Based Media Use and Brain White Matter Integrity in Preschool-Aged Children
Authors: John S. Hutton, Jonathan Dudley, Tzipi Horowitz-Kraus, Tom DeWitt, Scott K. Holland
Journal: JAMA Pediatrics (2019)

The American Academy of Pediatrics (AAP) recommends limits on screen-based media use, citing its cognitive-behavioral risks. Screen use by young children is prevalent and increasing, although its implications for brain development are unknown.To explore the associations between screen-based media use and integrity of brain white matter tracts supporting language and literacy skills in preschool-aged children.This cross-sectional study of healthy children aged 3 to 5 years (n = 47) was conducted from August 2017 to November 2018. Participants were recruited at a US children's hospital and community primary care clinics.Children completed cognitive testing followed by diffusion tensor imaging (DTI), and their parent completed a ScreenQ survey.ScreenQ is a 15-item measure of screen-based media use reflecting the domains in the AAP recommendations: access to screens, frequency of use, content viewed, and coviewing. Higher scores reflect greater use. ScreenQ scores were applied as the independent variable in 3 multiple linear regression models, with scores in 3 standardized assessments as the dependent variable, controlling for child age and household income: Comprehensive Test of Phonological Processing, Second Edition (CTOPP-2; Rapid Object Naming subtest); Expressive Vocabulary Test, Second Edition (EVT-2; expressive language); and Get Ready to Read! (GRTR; emergent literacy skills). The DTI measures included fractional anisotropy (FA) and radial diffusivity (RD), which estimated microstructural organization and myelination of white matter tracts. ScreenQ was applied as a factor associated with FA and RD in whole-brain regression analyses, which were then narrowed to 3 left-sided tracts supporting language and emergent literacy abilities.Of the 69 children recruited, 47 (among whom 27 [57%] were girls, and the mean [SD] age was 54.3 [7.5] months) completed DTI. Mean (SD; range) ScreenQ score was 8.6 (4.8; 1-19) points. Mean (SD; range) CTOPP-2 score was 9.4 (3.3; 2-15) points, EVT-2 score was 113.1 (16.6; 88-144) points, and GRTR score was 19.0 (5.9; 5-25) points. ScreenQ scores were negatively correlated with EVT-2 (F2,43 = 5.14; R2 = 0.19; P < .01), CTOPP-2 (F2,35 = 6.64; R2 = 0.28; P < .01), and GRTR (F2,44 = 17.08; R2 = 0.44; P < .01) scores, controlling for child age. Higher ScreenQ scores were correlated with lower FA and higher RD in tracts involved with language, executive function, and emergent literacy abilities (P < .05, familywise error-corrected), controlling for child age and household income.This study found an association between increased screen-based media use, compared with the AAP guidelines, and lower microstructural integrity of brain white matter tracts supporting language and emergent literacy skills in prekindergarten children. The findings suggest further study is needed, particularly during the rapid early stages of brain development.
ASXL1 Mutations Are Associated with Widespread and Distinct DNA Methylation Alterations
Authors: Nora E Rahmani, Nandini Ramachandra, Tushar D Bhagat, Shanisha Gordon, Kith Pradhan, Bianca Rivera Pena, Mohammad Kazemi, Orsi Giricz, Shahina Maqbool, Raul Olea, Hamid Dolatshad, Vickram Tittrea, Dharamveer Tatwavedi, Shalini Singh, Andrea Pellagatti, Jacqueline Boultwood, Amit Verma
Journal: Blood (2019)
Characterization of the "Immune Evasion" Phenotype of Richter Syndrome and the Implications for Immune-Checkpoint Inhibitor Therapy
Authors: Clare Gould, Jennifer Lickiss, Yamuna Kankanige, Satwica Yerneni, John Markham, Costas K. Yannakou, Diego Villa, Graham W Slack, Collin Chin, Constantine S. Tam, Stephen Lade, Niles Elizabeth Nelson, Paul J Neeson, John F. Seymour, Michael Dickinson, David Alan Westerman, Piers Blombery
Journal: Blood (2019)
CSIG-17. SIGNALING PATHWAY-BASED CLUSTERING OF MASS CYTOMETRY DATA UNCOVERS CELLS ASSOCIATED WITH CLINICAL PROGRESSION IN GLIOBLASTOMA
Authors: Alvaro Alvarado, Tyler Alban, Ichiro Nakano, Justin Lathia, Steven Goldman, Harley Kornblum
Journal: Neuro-Oncology (2019)

Abstract Recent advances in single cell expression technology have allowed us to appreciate the complexity in tumoral heterogeneity of solid tumors such as glioblastoma (GBM), which remains uniformly fatal despite aggressive therapies. Currently, there is no knowledge about cell identities and functional characteristics of the different tumoral populations. To this end, we created a 28-marker mass cytometry panel composed of signaling markers, including phospho-proteins, and lineage markers that have been associated with GBM or are considered putative cancer stem cell markers. We evaluated lines established from core and edge (periphery) areas from the same patient and validated to be functionally different with RNA expression and in vivo experiments. We first clustered the cells from all samples using the signaling markers in order to establish differences based on pathway utilization, and then we evaluated the expression of all markers. We found clusters shared by cells from both regions as well as region-specific ones. In order to better characterize these, we used marker enrichment modeling (MEM) and generated machine-readable labels. These were compared to MEM labels generated after using the same signaling markers to cluster primary samples from newly diagnosed or recurrent patients. Similarly, MEM labels were obtained from patients in a clinical trial treated with capecitabine that had positive or negative responses. Clusters from edge cells were found in higher proportion in recurrent tumors and were correlated with negative responses to the chemotherapeutic agent. Initial analyses have also been done correlating immune clusters with tumor clusters in the same samples. We are currently conducting in vitro studies and analyzing additional lines from other patients in order to validate these findings. Our studies exploit single cell cytometry to underscore pathways that are preferentially use by different cell populations with the ultimate goal of establishing therapeutic efforts to extend patient survival.
Plasmodium vivax Malaria Viewed through the Lens of an Eradicated European Strain
Authors: Lucy van Dorp, Pere Gelabert, Adrien Rieux, Marc de Manuel, Toni de-Dios, Shyam Gopalakrishnan, Christian Carøe, Marcela Sandoval-Velasco, Rosa Fregel, Iñigo Olalde, Raül Escosa, Carles Aranda, Silvie Huijben, Ivo Mueller, Tomàs Marquès-Bonet, François Balloux, M Thomas P Gilbert, Carles Lalueza-Fox
Journal: Molecular Biology and Evolution (2019)

The protozoan Plasmodium vivax is responsible for 42% of all cases of malaria outside Africa. The parasite is currently largely restricted to tropical and subtropical latitudes in Asia, Oceania, and the Americas. Though, it was historically present in most of Europe before being finally eradicated during the second half of the 20th century. The lack of genomic information on the extinct European lineage has prevented a clear understanding of historical population structuring and past migrations of P. vivax. We used medical microscope slides prepared in 1944 from malaria-affected patients from the Ebro Delta in Spain, one of the last footholds of malaria in Europe, to generate a genome of a European P. vivax strain. Population genetics and phylogenetic analyses placed this strain basal to a cluster including samples from the Americas. This genome allowed us to calibrate a genomic mutation rate for P. vivax, and to estimate the mean age of the last common ancestor between European and American strains to the 15th century. This date points to an introduction of the parasite during the European colonization of the Americas. In addition, we found that some known variants for resistance to antimalarial drugs, including Chloroquine and Sulfadoxine, were already present in this European strain, predating their use. Our results shed light on the evolution of an important human pathogen and illustrate the value of antique medical collections as a resource for retrieving genomic information on pathogens from the past.
Neddylation Pathway Regulates Treg Differentiation and T Cell Function in Chronic Lymphocytic Leukemia (CLL) Ex Vivo and Murine In Vivo Studies
Authors: Scott R Best, Vi Lam, Nur Bruss, Taylor Hashiguchi Rowland, Adam S. Kittai, Tingting Liu, Allison J Berger, Alexey Danilov
Journal: Blood (2019)
HOUT-09. DEVELOPING OMMAYA CLINICS FOR LEPTOMENINGEAL CARCINOMATOSIS (LMC): STANDARDIZED TREATMENT, IMPACT ON SURVIVAL/NEUROLOGIC DISABILITY AND ROLE FOR ADVANCED PRACTITIONERS
Authors: Erika Leese, Jesse Manikowski, Anand Mahadevan, Andrew Conger, Gino Mongelluzzo, Na Tosha Gatson
Journal: Neuro-Oncology (2019)

Abstract Leptomeningeal carcinomatosis (LMC), first described in 1870, involves leptomeningeal and CSF invasion by neoplastic cells and portends poor survival. Among solid tumor LMC, breast cancer is the most common followed by lung and melanoma. With an estimated 100,000+ new cases yearly, the dual-edged sword of systemic treatment drives the increasing incidence as cancer patients live longer and on non-CNS penetrating therapies. Addition of immuno-oncotherapies has impacted LMC survival. At time of diagnosis, most patients have multiple neurologic disabilities. Multiple reports on the topic have not yielded consistent treatment standards to extend patient survival. Most agree that local CNS control coupled with systemic therapy offers the best survival. Still, there are few established Ommaya clinics (OC). Importantly, LMC is a common exclusionary criterion for clinical trials. A single institutional evaluation of 147 patients (2012–2019) with a diagnosis of LMC was completed. 69 of 147 were excluded, leaving 48 pre-OC and 30 OC patients. The mOS (weeks) of those treated with intrathecal chemotherapy (ITC) versus no ITC was compared between cohorts: pre-OC and OC (3.36, 15.29****). Average KPS at time of diagnosis in pre-OC and OC was 70–80 (ECOG 2–3). The mOS was compared between breast (5, 28*), lung (3, 3) and melanoma (5,10*) in the pre-OC and OC respectively. The treatment standardized for the OC includes whole-brain radiation, Ommaya reservoir placement, systemic treatment, treatment with ITC (2x weekly – q other month) and MR imaging every 3 months. Breast cancer patients fared the best followed by melanoma and lung patients in the OC. With use of advanced practitioners (APs), standardization of treatment and surveillance is achievable. Patients treated according to a standardized OC regimen experienced longer overall survival along with a 10% improvement in KPS after two months of treatment. Development of institutional OCs reduces treatment variability and increases clinical surveillance.
Application of a new methodology and R package reveals a high burden of healthcare-associated infections (HAI) in Germany compared to the average in the European Union/European Economic Area, 2011 to 2012
Authors: Benedikt Zacher, Sebastian Haller, Niklas Willrich, Jan Walter, Muna Abu Sin, Alessandro Cassini, Diamantis Plachouras, Carl Suetens, Michael Behnke, Petra Gastmeier, Lothar H. Wieler, Tim Eckmanns
Journal: Eurosurveillance (2019)

BackgroundHealthcare-associated infections (HAIs) pose a major challenge to health systems. Burden of disease estimations in disability-adjusted life years (DALYs) are useful for comparing and ranking HAIs.AimTo estimate the number of five common HAIs, their attributable number of deaths and burden for Germany.MethodsWe developed a new method and R package that builds on the approach used by the Burden of Communicable Diseases in Europe (BCoDE) project to estimate the burden of HAIs for individual countries. We used data on healthcare-associated Clostridioides difficile infection, healthcare-associated pneumonia, healthcare-associated primary bloodstream infection, healthcare-associated urinary tract infection and surgical-site infection, which were collected during the point prevalence survey of HAIs in European acute-care hospitals between 2011 and 2012.ResultsWe estimated 478,222 (95% uncertainty interval (UI): 421,350-537,787) cases for Germany, resulting in 16,245 (95% UI: 10,863-22,756) attributable deaths and 248,920 (95% UI: 178,693-336,239) DALYs. Despite the fact that Germany has a relatively low hospital prevalence of HAIs compared with the European Union/European Economic Area (EU/EEA) average, the burden of HAIs in Germany (308.2 DALYs/100,000 population; 95% UI: 221.2-416.3) was higher than the EU/EEA average (290.0 DALYs/100,000 population; 95% UI: 214.9-376.9). Our methodology is applicable to other countries in or outside of the EU/EEA. An R package is available from https://CRAN.R-project.org/package=BHAI.ConclusionThis is the first study to estimate the burden of HAIs in DALYs for Germany. The large number of hospital beds may be a contributing factor for a relatively high burden of HAIs in Germany. Further focus on infection prevention control, paired with reduction of avoidable hospital stays, is needed to reduce the burden of HAIs in Germany.
Weekly Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab (wKRd-D) Combination Therapy Provides Unprecedented MRD Negativity Rates in Newly Diagnosed Multiple Myeloma: A Clinical and Correlative Phase 2 Study
Authors: Ola Landgren, Malin Hultcrantz, Alexander M. Lesokhin, Sham Mailankody, Hani Hassoun, Eric L Smith, Urvi A Shah, Sydney X Lu, Donna Mastey, Meghan Salcedo, Victoria Diab, Kelly Werner, Jenna Rispoli, Allison Sams, Dennis Verducci, Katie Jones, Angela Harrison, Aisara Chansakul, Even H Rustad, Venkata Yellapantula, Francesco Maura, Heather J Landau, Michael Scordo, David J. Chung, Gunjan Shah, Oscar B Lahoud, Katie Thoren, Kazunori Murata, Lakshmi Ramanathan, Maria E Arcila, Caleb Ho, Mikhail Roshal, Ahmet Dogan, Sean M. Devlin, Sergio Giralt, Neha Korde
Journal: Blood (2019)