tbuckley/cabot-search huggingface dataset:
EPID-19. SHARED GENOMIC ARCHITECTURE OF GLIOMA AND NEURO-COGNITIVE AND NEURO-PSYCHIATRIC TRAITS REVEALED BY LD-SCORE REGRESSION
Authors: Kyle Walsh, Quinn Ostrom, Chenan Zhang, Jacob Edelson, Erica Shen, Jinyoung Byun, Younghun Han, Christopher Amos, Melissa Bondy
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Genome-wide analyses estimate glioma heritability at 25%, yet known risk loci account for just one-third of this risk and suggest that sporadic glioma is a highly polygenic disease with hitherto unaccounted for genomic architecture. LD-score regression leverages results from genome-wide association studies (GWAS) and known patterns of linkage disequilibrium (LD) to estimate correlation between the genetic architecture of multiple phenotypes. We applied LD-score regression to identify associations with neuro-cognitive and neuro-psychiatric traits not amenable to study in prior glioma case-control analyses. METHODS GWAS summary statistics were obtained from the Glioma International Case-Control Consortium (GICC) meta-analysis (Melin, et al. 2017) and for 64 neuro-cognitive and neuro-psychiatric traits primarily from the UK Biobank. Included SNPs had quality scores ≥0.70 and minor allele frequency ≥0.01. Pairwise genetic correlations between traits were estimated using the LDSC package. P-values &lt; 7.8x10-4 (i.e. 0.05/64) were considered significant. RESULTS Significant negative correlations were identified between the genetic architectures of glioma and bipolar disorder (Rg=-0.41, P=1.4x10-9) and schizophrenia (Rg=-0.29, P=7.1x10-9), consistent in both GBM and LGG. Significant positive correlations were identified with measures of educational attainment, including age at educational completion (Rg=0.11, P=2.0x10-4), obtaining a college degree (Rg=0.086, P=4.9x10-4), college attendance (Rg=0.086, P=5.9x10-4), and years of education (Rg=0.081, P=7.7x10-4). These associations were notably stronger with LGG. A number of additional nominal associations were observed, including with anorexia (anti-correlated) and performance on a pair-matching cognitive test (positively correlated). Importantly, LD-score regression did not identify an association between glioma risk in GICC data and Townsend deprivation index in UK Biobank data. CONCLUSIONS These results implicate a shared genetic basis for glioma and several psychiatric and cognitive traits. Further research is needed to understand these associations and to explore underlying mechanisms, including the mediating effects of neuro-inflammation, developmental differences in neural‒glial cell circuitry, and inter-individual variation in myelination.
Rapid Personalized Manufacture (RPM) of Sleeping Beauty System-Generated NY-ESO-1-Specific TCR-T Cells Co-Expressing Membrane-Bound IL-15 Yields Anti-Tumor Responses
Authors: Lenka V Hurton, Tiejuan Mi, Kirsten C Switzer, Ling Zhang, Cuiping Dai, Misun Kim, Karishma R Bavisi, Matthew J Figliola, Vazquez M Lydia, Sourindra N Maiti, Shihuang Su, Drew C Deniger, Simon Olivares, Laurence J N Cooper, Harjeet Singh
Journal: Blood (2019)
Against the Odds: Risk Stratification with Cardiac Magnetic Resonance Imaging in Pulmonary Arterial Hypertension
Authors: Manuel J. Richter, Khodr Tello
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

reported comparisons: when adjusted for HIV-infected status, and when adjusted for current smoking, reduced FEV 1 /FVC, or reduced DL CO within HIV-infected subjects, saliva samples were less diverse and were enriched with three or four main bacterial genera.Although the authors adjusted for smoking in their multivariate analysis, the potential effect of active smoking cannot be fully discounted, given its direct impact on airway dysfunction and mucosal inflammation.Moreover, cigarette smoke can induce intestinal inflammation and has been associated with altered intestinal microbiota patterns (13-15) (somewhat surprisingly, the latter was not observed here, which may relate to insufficient statistical power).Nonetheless, returning to the oral cavity, it is important to consider the oral mucosa as an immunologically very active interface.Thus, dysbiotic oral microbiota signatures could exert significant distant effects, constituting a potential "oral-lung axis."Although more experimental work will be needed to discern these causal scenarios, the current investigation invites us to consider that when we look for pulmonary disease, we should think beyond a single site of microbial-host interaction.
Clinicians’ Perspectives on Barriers to Discussing Infertility and Fertility Preservation With Young Women With Cancer
Authors: Andrea Covelli, Marcia Facey, Erin Kennedy, Christine Brezden-Masley, Abha A. Gupta, Ellen Greenblatt, Nancy N. Baxter
Journal: JAMA Network Open (2019)

Infertility can be a devastating adverse effect of cancer treatment for young women. Fertility preservation may be an important and influential factor in treatment decisions. Despite American Society of Clinical Oncology guidelines recommending discussion around potential infertility with patients, nearly 50% of young women with cancer remain uninformed.
Robert McClelland: surgeon who tried to help save both President John F Kennedy and Lee Harvey Oswald
Authors: Rebecca Wallersteiner
Journal: BMJ (2019)

Picture credit: University of Texas South-western Medical Centre, Dallas, USA

Robert McClelland was born in the small town of Gilmer in east Texas, to Robert, a butcher, and Verna (nee Nelson), a government welfare officer. He was educated at a local high school—where he read prodigiously and developed a lifelong interest in history—followed by medical school at the University of Texas Medical Branch in Galveston. He had been eager to be a doctor, like his grandfather whom he admired. After qualifying he served as a medical officer for the US Air Force in Germany, before joining the University of Texas South-western Medical faculty in 1962. At the age of 34, he was thrown into the historical spotlight forever.

At around 12 30 pm on 22 November 1963, Robert McClelland was showing a film on how to repair a hiatus hernia to a group of surgery graduates at the Parkland Memorial Hospital in Dallas, Texas, when there was a loud knock on the door. McClelland was called away to the emergency department to deal with a “terrible” situation two floors down. He made his way down, grumbling on the way as he was often called out to deal with “terrible” injuries that turned out not to be that bad. 

In this case, the US president, John F Kennedy, had been shot as his motorcade travelled through Dallas and had been brought to Parkland, …
Thyroid Hormone Transporters
Authors: Stefan Groeneweg, Ferdy S van Geest, Robin P Peeters, Heike Heuer, W Edward Visser
Journal: Endocrine Reviews (2019)

Abstract Thyroid hormone transporters at the plasma membrane govern intracellular bioavailability of thyroid hormone. Monocarboxylate transporter (MCT) 8 and MCT10, organic anion transporting polypeptide (OATP) 1C1, and SLC17A4 are currently known as transporters displaying the highest specificity toward thyroid hormones. Structure-function studies using homology modeling and mutational screens have led to better understanding of the molecular basis of thyroid hormone transport. Mutations in MCT8 and in OATP1C1 have been associated with clinical disorders. Different animal models have provided insight into the functional role of thyroid hormone transporters, in particular MCT8. Different treatment strategies for MCT8 deficiency have been explored, of which thyroid hormone analogue therapy is currently applied in patients. Future studies may reveal the identity of as-yet-undiscovered thyroid hormone transporters. Complementary studies employing animal and human models will provide further insight into the role of transporters in health and disease.
RTHP-43 (LTBK-02). MULTI-TIME POINT EVALUATION OF PERIPHERAL BLOOD MYELOID-DERIVED SUPPRESSOR CELL AND LYMPHOCYTE POPULATIONS IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA RECEIVING ADJUVANT THERAPY
Authors: Lindsey Sloan, Rupashree Sen, Michele Doucet, Lee Blosser, Ilya Shpitser, Eli Sherman, Numair San, Zhi Cheng, Lisa Katulis, Jan Wemmer, David Kamson, Christina Jackson, Chen Hu, Todd McNutt, Stuart Grossman, Matthias Holdhoff, Michael Lim, Kristin J Redmond, Charles Eberhart, Harry Quon, Drew Pardoll, Sudipto Ganguly, Lawrence Kleinberg
Journal: Neuro-Oncology (2019)

Abstract Alterations in peripheral blood cell populations, including myeloid cell subsets and lymphocytes, have been associated with poor prognostic outcomes in patients with glioblastoma (GBM). To date, evaluation of these populations has largely been on freeze-thawed samples at a limited number of time points. The purpose of our study is to identify the frequency and activation status of tumor-supportive myeloid and lymphocyte subsets during the course of standard adjuvant therapy in patients with GBM in fresh peripheral blood samples. We hypothesize that dysfunctional myeloid and lymphocyte populations expand during standard care temozolomide (TMZ)/radiation therapy (RT). We prospectively enrolled 16 patients with a new diagnosis of GBM that underwent maximal safe surgical resection. Twelve received standard adjuvant therapy consisting of six weeks of TMZ/RT. Four received alternative therapies: one experimental chemotherapeutic/three alternative radiation schemes. Peripheral blood was obtained seven times over the course of adjuvant therapy: prior to starting adjuvant therapy, five during treatment, and once one month after completion of therapy. Eleven patients completed all seven time points. Peripheral blood samples were analyzed by flow cytometry, focusing on immune checkpoints and critical markers of activation of systemic immunity. Available preliminary data demonstrate a median increase of 2.1% (-21.2–27.4%) in the frequency (%fx) of myeloid-derived suppressor cells (MDSC) after commencement of adjuvant therapy at time point 2 (TP2), compared to baseline. To date, 7/16 patients are alive and without evidence of recurrent disease on imaging. The majority of these patients had a decrease in %fx of MDSC at TP2, after starting adjuvant therapy, compared to baseline. The %fx of CD8+ T cells was greatest at TP7 (range: 21.7%-67.0%), one month after TMZ/RT, for most patients. PD-1 and FOXP3 expression by lymphocytes was variable across time points, suggesting the importance of additional factors which will be explored through future analyses. These early findings suggest that the immune response changes throughout the course of TMZ/RT. An understanding of these changes in the peripheral blood, termed immunodynamics in the context of our studies, may be valuable future tool to aid in optimizing immunity in patients with GBM.
Development and validation of a risk model integrating plasma Epstein-Barr virus DNA (EBV DNA) level and TNM stage for stratification of nasopharyngeal cancer (NPC) to adjuvant therapy
Authors: E.P. Hui, W.F. Li, B.B.Y. Ma, F. Mo, W.K.J. Lam, K.C.A. Chan, Q.H. Ai, A.D. King, C.H. Wong, R. Guo, D.M.C. Poon, M. Tong, L. Li, T.K.H. Lau, K.C.W. Wong, D.C.M. Lam, Y.M.D. Lo, J. Ma, A.T.C. Chan
Journal: Annals of Oncology (2019)
Outcomes Following Early Relapse in Patients with Mantle Cell Lymphoma
Authors: David A. Bond, Jeffrey M. Switchenko, Kami J. Maddocks, Michael C. Churnetski, Subir Goyal, Krithika Shanmugasundaram, Oscar Calzada, Bhaskar Kolla, Veronika Bachanova, James N. Gerson, Stefan K. Barta, Yazeed Sawalha, Brian T. Hill, Peter Martin, Max J. Gordon, Alexey Danilov, Natalie S Grover, Stephanie Mathews, Madelyn Burkart, Reem Karmali, Nilanjan Ghosh, Steven I Park, Narendranath Epperla, Talha Badar, Jin Guo, Mehdi Hamadani, Timothy S. Fenske, Mary-Kate Malecek, Brad S. Kahl, Christopher R. Flowers, Kristie A. Blum, Jonathon B. Cohen
Journal: Blood (2019)
A New Era for Cyborg Science Is Emerging: The Promise of Cyborganic Beings
Authors: Gorka Orive, Nayere Taebnia, Alireza Dolatshahi‐Pirouz
Journal: Advanced Healthcare Materials (2019)

Abstract Living flesh, hacked beyond known biological borders, and sophisticated machineries, made by humans, are currently being united to address some of the impending challenges in medicine. Imagine biological systems made from smart biomaterials with the capacity to operate like smart machines to regulate insulin production in diabetic patients, or cardiac patches that can monitor and release important biological factors, on demand, to optimize the mending of broken hearts. It sounds like something from the realm of science fiction; however, this big gap between the real world and the world of fantasy and fiction is slowly being bridged. This piece sheds a much‐needed light on this emerging area, as this futuristic concept is gaining momentum, at a speed, that soon will ignite a paradigm shift in disease management and the healthcare sector as an entirety.
Introducing a Predictive Score for Successful Treatment Free Remission in Chronic Myeloid Leukemia (CML)
Authors: Simone Claudiani, Silvia Metelli, Rafiee Kamvar, Richard Szydlo, Afzal Khan, Jenny Byrne, Paolo Gallipoli, Simon J Bulley, Gillian A. Horne, Kate Rothwell, Mhairi Copland, Richard E. Clark, Jamshid S Khorashad, Letizia Foroni, Dragana Milojkovic, Jane F. Apperley
Journal: Blood (2019)
Growth differentiation factor 11 attenuates liver fibrosis via expansion of liver progenitor cells
Authors: Zhen Dai, Guangqi Song, Asha Balakrishnan, Taihua Yang, Qinggong Yuan, Selina Möbus, Anna-Carina Weiss, Martin Bentler, Jimin Zhu, Xuemei Jiang, Xizhong Shen, Heike Bantel, Elmar Jaeckel, Andreas Kispert, Arndt Vogel, Anna Saborowski, Hildegard Büning, Michael Manns, Tobias Cantz, Michael Ott, Amar Deep Sharma
Journal: Gut (2019)

Objective Liver fibrosis and cirrhosis resulting from chronic liver injury represent a major healthcare burden worldwide. Growth differentiation factor (GDF) 11 has been recently investigated for its role in rejuvenation of ageing organs, but its role in chronic liver diseases has remained unknown. Here, we investigated the expression and function of GDF11 in liver fibrosis, a common feature of most chronic liver diseases. Design We analysed the expression of GDF11 in patients with liver fibrosis, in a mouse model of liver fibrosis and in hepatic stellate cells (HSCs) as well as in other liver cell types. The functional relevance of GDF11 in toxin-induced and cholestasis-induced mouse models of liver fibrosis was examined by in vivo modulation of Gdf11 expression using adeno-associated virus (AAV) vectors. The effect of GDF11 on leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5)+ liver progenitor cells was studied in mouse and human liver organoid culture. Furthermore, in vivo depletion of LGR5+ cells was induced by injecting AAV vectors expressing diptheria toxin A under the transcriptional control of Lgr5 promoter. Results We showed that the expression of GDF11 is upregulated in patients with liver fibrosis and in experimentally induced murine liver fibrosis models. Furthermore, we found that therapeutic application of GDF11 mounts a protective response against fibrosis by increasing the number of LGR5+ progenitor cells in the liver. Conclusion Collectively, our findings uncover a protective role of GDF11 during liver fibrosis and suggest a potential application of GDF11 for the treatment of chronic liver disease.
Microenvironmental Signatures Reveal Biological Subtypes of Diffuse Large B-Cell Lymphoma (DLBCL) Distinct from Tumor Cell Molecular Profiling
Authors: Leandro Cerchietti, Giorgio Inghirami, Nikita Kotlov, Viktor Svekolkin, Alexander Bagaev, Felix Frenkel, Maria Victoria Revuelta, Jude M Phillip, Maria Teresa Cacciapuoti, Sarah C. Rutherford, Peter Martin, John P. Leonard
Journal: Blood (2019)
Symptom burden and characteristics of patients who die in the acute palliative care unit of a tertiary cancer center.
Authors: YuJung Kim, Grace S. Ahn, Hak Ro Kim, Beodeul Kang, Sung Soun Hur, Ji-Won Kim, Se Hyun Kim, Jin Won Kim, Jeong-Ok Lee, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong Seok Lee
Journal: Journal of Clinical Oncology (2019)

53 Background: Acute Palliative Care Units (ACPUs) are novel inpatient programs in tertiary care centers that provide aggressive symptom management and assist transition to hospice. However, patients often die in the APCU before successfully transferring to hospice. The aim of this study was to evaluate the symptom burden and characteristics of advanced cancer patients who die in the APCU. Methods: We retrospectively reviewed the medical records of all advanced cancer patients admitted to the APCU between April, 2015 and March, 2016 at a tertiary cancer center in Korea. Basic characteristics and symptom burden assessed by the Edmonton Symptom Assessment System (ESAS) were obtained from consultation upon APCU admission. Statistical analyses were conducted to compare patients who died in the APCU with those who were discharged alive. Results: Of the 267 patients analyzed, 87 patients (33%) died in the APCU. The median age of patients was 66 (range, 23-97). Patients who died in the APCU had higher ESAS scores of drowsiness (6 vs 5, P = 0.002), dyspnea (4 vs 2, P = 0.001), anorexia (8 vs 6, P = 0.014) and insomnia (6 vs 4, P = 0.001) compared to patients who discharged alive. Total symptom distress scores (SDS) were also significantly higher (47 vs 40, P = 0.001). Patients who died in the APCU were more likely to be male (odds ratio [OR] for female patients 0.38, 95% confidence interval [CI] 0.22-0.67, P &lt; 0.001) and have higher ESAS scores of drowsiness (OR 2.08, 95% CI, 1.08-3.99, P = 0.029) and dyspnea (OR 2.19, 95% CI 1.26-3.80, P = 0.005). These patients showed significantly shorter survival after APCU admission (7 days vs 31 days, P &lt; 0.001). Conclusions: Advanced cancer patients who die in the APCU are more likely to be male and have significantly higher symptom burden that include drowsiness and dyspnea. These patients show rapid clinical deterioration after APCU admission. More proactive and timely end-of-life care is needed for these patients.
A prototype mobile application to improve communication about symptom management.
Authors: Matthew Roger LeBlanc, Thomas William LeBlanc, Sophia Kustas Smith
Journal: Journal of Clinical Oncology (2019)

27 Background: Cancer patients report many physical and emotional symptoms which can go unreported and underestimated resulting in unmet needs. Research suggests systematic collection of symptom data is associated with decreased emergency department use, increased quality of life, treatment toleration and overall survival. The multiple myeloma (MM) patient population is noted to have high symptom burden and represent an important target for intervention. This project aimed to develop a prototype app to facilitate MM patient/clinician communication about symptom management. Methods: 15 MM patients and 11 MM clinicians were interviewed to better understand patients’ symptom experience and management practices and preferences. Insights gained guided development of a prototype MM Coach mobile app. The think aloud protocol and cognitive interviewing were used to test usability and the prototype was iteratively refined. Results: Subjects highlighted a need for better symptom tracking over time, medication adherence tools, and real-time feedback to help patients self-manage symptoms. Our prototype app contains several modules designed to facilitate MM patient symptom management. 1) Track Symptoms; Using the Edmonton Symptom Assessment Scale patients track bothersome symptoms whenever they occur. 2) Track Medications; Patients can set up medication alerts and log medication use. 3) Track Mood; Patients record and track their distress level using the Distress Thermometer. 4) Relaxation Tools; This module contains a number of useful mind body activities such as guided imagery. 5) Get Support; Links to MM and non-MM related sources of support. 6) Prepare for Appointments; This module facilitates patients’ prioritizing issues to facilitate productive clinical encounters. 7) Insights; Patients and clinicians can review trends in symptom burden and medication adherence. 8) Learn; Educational content on topics relevant to MM symptoms such as pain, fatigue, depression. Conclusions: Our team is currently working with mobile app developers to build a version for the iOS AppStore and Android GooglePlay store. A pilot will be conducted to evaluate acceptability and feasibility in preparation for a clinical trial.
Co-Expression of SYK and ZAP70 Subverts Negative B-Cell Selection and Enables Oncogenic Signaling in Multiple B-Cell Malignancies
Authors: Teresa Sadras, Mickaël Martin, Lauren Kim-Sing, Jevon Cutler, Gal Lenz, Anne Marie Knapp, Dana Ghergus, Fabien Delmotte, Cédric Schleiss, Anne-Sophie Korganow, Pauline Soulas-Sprauel, Zhengshan Chen, Akhilesh Pandey, David M. Weinstock, Hassan Jumaa, Eric Meffre, Thierry Martin, Markus Müschen
Journal: Blood (2019)
Comparison of Outcome Between Refractory/Relapsed De Novo Diffuse Large B-Cell and Transformed Lymphoma Using Related and Unrelated Allogeneic Hematopoietic SCT.
Authors: Khaled M Ramadan, Kevin W. Song, Joseph M. Connors, Abdul Al-Tourah, Randy D. Gascoyne, Michael J. Barnett, Stephen H. Nantel, Thomas J. Nevill, John D. Shepherd, Heather J. Sutherland, Julye Lavoie, Donna L. Forrest, Donna E. Hogge, Nicholas Voss, Ryan Brinkman, Yasser R. Abou Mourad, Maryse M. Power, Sujaatha Narayanan, Clayton A. Smith, Cynthia L. Toze
Journal: Blood (2008)
Azacitidine (AZA) with Nivolumab (Nivo), and AZA with Nivo + Ipilimumab (Ipi) in Relapsed/Refractory Acute Myeloid Leukemia: A Non-Randomized, Prospective, Phase 2 Study
Authors: Naval G. Daver, Guillermo Garcia-Manero, Marina Y Konopleva, Mansour Alfayez, Naveen Pemmaraju, Tapan M. Kadia, Courtney D. DiNardo, Jorge E. Cortes, Farhad Ravandi, Hussein Abbas, Sreyashi Basu, Elias Jabbour, Sherry A. Pierce, Zeev E. Estrov, Koichi Takahashi, Jing Ning, Steven M. Kornblau, Koji Sasaki, Lucia Masarova, Wilmer Flores, James P Allison, Padmanee Sharma, Hagop M. Kantarjian
Journal: Blood (2019)
Fenfluramine for Treatment-Resistant Seizures in Patients With Dravet Syndrome Receiving Stiripentol-Inclusive Regimens
Authors: Rima Nabbout, Arun Mistry, Sameer Zuberi, Nathalie Villeneuve, Antonio Gil-Nagel, Rocio Sanchez-Carpintero, Ulrich Stephani, Linda Laux, Elaine Wirrell, Kelly Knupp, Catherine Chiron, Gail Farfel, Bradley S. Galer, Glenn Morrison, Michael Lock, Anupam Agarwal, Stéphane Auvin
Journal: JAMA Neurology (2019)

Fenfluramine treatment may reduce monthly convulsive seizure frequency in patients with Dravet syndrome who have poor seizure control with their current stiripentol-containing antiepileptic drug regimens.
EP300 Suppresses Leukemia Development in Myelodysplastic Syndrome through Myb Repression
Authors: Na Man, Gloria Mas Martin, Daniel Karl, Jun Sun, Fan Liu, Miguel Torres-Martin, Hidehiro Itonaga, Concepcion Martinez, Shi Chen, Stephanie Duffort, Pierre-Jacques Hamard, Ye Xu, Luisa Cimmino, Feng-Chun Yang, Philip A. Cole, Mingjiang Xu, Maria E. Figueroa, Stephen Nimer
Journal: Blood (2019)
Multistate Outbreak of <i>Salmonella</i> Infections Linked to Raw Turkey Products — United States, 2017–2019
Authors: Rashida Hassan, Sean Buuck, Douglas Noveroske, Carlota Medus, Alida Sorenson, Jessica Laurent, David Rotstein, Linda Schlater, Jennifer Freiman, Aphrodite Douris, Mustafa Simmons, Danielle Donovan, Justin Henderson, Mackenzie Tewell, Kaitlyn Snyder, Oluwakemi Oni, Diana Von Stein, Kossia Dassie, Molly Leeper, Azizat Adediran, Natasha Dowell, Laura Gieraltowski, Colin Basler
Journal: MMWR Morbidity and Mortality Weekly Report (2019)