tbuckley/cabot-search huggingface dataset:
Dennis Searle Smith: pioneer in stroke management and rehabilitation
Authors: Amy Coopes
Journal: BMJ (2019)

Dennis Searle Smith, a survivor of the Blitz who passed long childhood nights in air raid shelters and watched his father recover from injuries sustained by unexploded ordnance, devoted his life to rehabilitation medicine and was instrumental in the emerging specialism’s development.

Smith was born to Walter and Doris Smith in working class Coventry, the older of two boys. He showed academic aptitude from a young age, particularly in the sciences, where he revelled in the study of chemistry as a scholarship pupil at Bablake Grammar School.

During the second world war the school was relocated to a disused campus in Lincoln, and Smith’s younger brother, Tony, was evacuated to Solihull, where he lived away from the family for several years. Smith’s medical clerk father was hurt by unexploded ordnance while inspecting bomb sites in Coventry.

It was his wartime experiences, surviving some of the worst air raids of the Blitz, whichsparked Smith’s lifelong interest in the determinants of disability and recovery from …
Targeting compensatory MEK/ERK activation increases JAK inhibitor efficacy in myeloproliferative neoplasms
Authors: Simona Stivala, Tamara Codilupi, Sime Brkic, Anne Baerenwaldt, Nilabh Ghosh, Hui Hao-Shen, Stephan Dirnhofer, Matthias S. Dettmer, Cedric Simillion, Beat A. Kaufmann, Sophia Chiu, Matthew Keller, Maria Kleppe, Morgane Hilpert, Andreas S. Buser, Jakob R. Passweg, Thomas Radimerski, Radek C. Skoda, Ross L. Levine, Sara C. Meyer
Journal: Journal of Clinical Investigation (2019)

Constitutive JAK2 signaling is central to myeloproliferative neoplasm (MPN) pathogenesis and results in activation of STAT, PI3K/AKT, and MEK/ERK signaling. However, the therapeutic efficacy of current JAK2 inhibitors is limited. We investigated the role of MEK/ERK signaling in MPN cell survival in the setting of JAK inhibition. Type I and II JAK2 inhibition suppressed MEK/ERK activation in MPN cell lines in vitro, but not in Jak2V617F and MPLW515L mouse models in vivo. JAK2 inhibition ex vivo inhibited MEK/ERK signaling, suggesting that cell-extrinsic factors maintain ERK activation in vivo. We identified PDGFRα as an activated kinase that remains activated upon JAK2 inhibition in vivo, and PDGF-AA/PDGF-BB production persisted in the setting of JAK inhibition. PDGF-BB maintained ERK activation in the presence of ruxolitinib, consistent with its function as a ligand-induced bypass for ERK activation. Combined JAK/MEK inhibition suppressed MEK/ERK activation in Jak2V617F and MPLW515L mice with increased efficacy and reversal of fibrosis to an extent not seen with JAK inhibitors. This demonstrates that compensatory ERK activation limits the efficacy of JAK2 inhibition and dual JAK/MEK inhibition provides an opportunity for improved therapeutic efficacy in MPNs and in other malignancies driven by aberrant JAK-STAT signaling.
CD133-negative glioblastoma cancer stem cells represent the ‘mesenchymal’ subclass of glioblastoma
Authors: Kyeung Min Joo, Shi Yeon Kim, Mi Hyun Kim, Yong Jung, Bong Gu Kang, Ji Won Jeon, Doo-Sik Kong, Do-Hyun Nam
Journal: Cancer Research (2008)

3786  Whether CD133-positive (CD133(+)) cells are the only cancer stem cells of glioblastoma (GBM) is a hot issue these days. We isolated CD133(+) and CD133-negative (CD133(-)) cells from one GBM patient (total 6 GBM patients) and found that both can produce tumor mass in the mouse brain. However, tumor masses produced by CD133(-) cells had more vessels and PCNA-positive proliferating cells. Akt was activated more in the tumor masses produced by CD133(+) cells. These results suggested that there are cancer stem cells in CD133(-) cell population, however, they have different characteristics compared with CD133(+) cells. To analyze different characteristics of CD133(-) cells further, we gathered 20 GBM patients, analyzed their CD133(+) cell ratios using FACS analysis method and divided them into two groups according to CD133(+) cell ratio (CD133(+) cell ratio high (≥3%, n=10) and low (
Predictors of Relapse and Efficacy of Rituximab in Autoimmune Thrombotic Thrombocytopenic Purpura (TTP): A Multi-Institutional Registry-Based Analysis
Authors: Lova Sun, Johnathan P. Mack, Ang Li, Justine Ryu, Vivek A Upadhyay, Robert Makar, Pavan Bendapudi
Journal: Blood (2018)
The efficacy of splenic hilar lymph node dissection in advanced gastric cancer.
Authors: Tetsuro Toriumi, Rie Makuuchi, Satoshi Kamiya, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Masanori Terashima
Journal: Journal of Clinical Oncology (2019)

112 Background: Total gastrectomy with splenectomy for splenic hilar lymph node (No.10 LN) dissection had been a standard treatment for proximal advanced gastric cancer in Japan. The efficacy of No. 10 LN dissection with splenectomy for advanced gastric cancer without the greater curvature invasion was denied by a randomized controlled trial, JCOG0110. However, JCOG0110 did not include the patients with greater curvature invasion. Therefore, we aimed to clarify the role of No. 10 LN dissection in patients with proximal advanced gastric cancer invading the greater curvature. Methods: A total of 273 patients with proximal advanced gastric cancer who underwent curative total gastrectomy with splenectomy from 2002 to 2013 were included. We reviewed esophagogastroduodenoscopy and upper gastrointestinal series for evaluation of clinical tumor localization and classified the patients into with greater curvature invasion group (G group, n = 108) or without invasion group (NG group, n = 165). The incidence and therapeutic value index (TVI) of No. 10 LN were compared between the groups. Results: Patients in the G group had more advanced T stage, undifferentiated histology, and larger tumor size than those in the NG group. However, there was no difference in survival between the groups; 5-year overall survival (5-OS) was 66.3% in the G group and 69.1% in the NG group (p = 0.570). The incidence of No.10 LN metastasis was significantly higher in the G group (10.2%) than that in the NG group (3.0%) (p = 0.028). TVI for No.10 LN dissection was higher in the G group (5.6) than that in the NG group (0.6). The survival of the patients with No.10 LN metastasis tended to be better in the G group, although it did not reach statistical significance (5-OS: 54.5% in G group vs. 20.0% in NG group, p = 0.336). Conclusions: It is suggested that splenic hilar LN dissection has a favorable effect on survival in patients with proximal gastric cancer invading the greater curvature.
Ocular Prophylaxis for Gonococcal Ophthalmia Neonatorum: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force
Authors: Janelle M. Guirguis-Blake, Corinne V. Evans, Megan Rushkin
Journal: JAMA (2019)

US Preventive Services Task Force; Susan J. Curry, PhD; Alex H. Krist, MD, MPH; Douglas K. Owens, MD, MS; Michael J. Barry, MD; Aaron B. Caughey, MD, PhD; Karina W. Davidson, PhD, MASc; Chyke A. Doubeni, MD, MPH; John W. Epling Jr, MD, MSEd; Alex R. Kemper, MD, MPH, MS; Martha Kubik, PhD, RN; C. Seth Landefeld, MD; Carol M. Mangione, MD, MSPH; Michael Silverstein, MD, MPH; Melissa A. Simon, MD, MPH; Chien-Wen Tseng, MD, MPH, MSEE; John B. Wong, MD
Platelet decoys inhibit thrombosis and prevent metastatic tumor formation in preclinical models
Authors: Anne-Laure Papa, Amanda Jiang, Netanel Korin, Michelle B. Chen, Erin T. Langan, Anna Waterhouse, Emma Nash, Jildaz Caroff, Amanda Graveline, Andyna Vernet, Akiko Mammoto, Tadanori Mammoto, Abhishek Jain, Roger D. Kamm, Matthew J. Gounis, Donald E. Ingber
Journal: Science Translational Medicine (2019)

Human platelet decoys prevented thrombosis in rabbits and inhibited cancer cell aggregation and extravasation in vitro and in a mouse model.
Health Related Quality of Life Remains Stable over Time in Myelodysplastic Syndrome: An MDS-CAN Prospective Study
Authors: Danielle N. Blunt, Richard A. Wells, Martha Lenis, Lisa Chodirker, Michelle Geddes, Nancy Zhu, Jill Fulcher, Mitchell Sabloff, Mary-Margaret Keating, Brian Leber, Heather A. Leitch, Karen W.L. Yee, Eve St-Hilaire, Nicholas G. Finn, April Shamy, Mohamed Elemary, Robert Delage, Ken Rockwood, Versha Banerji, Alexandre Mamedov, Liying Zhang, Rena Buckstein
Journal: Blood (2018)
Advancing Frontiers in Bone Bioprinting
Authors: Nureddin Ashammakhi, Anwarul Hasan, Outi Kaarela, Batzaya Byambaa, Amir Sheikhi, Akhilesh K. Gaharwar, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2019)

Abstract Three‐dimensional (3D) bioprinting of cell‐laden biomaterials is used to fabricate constructs that can mimic the structure of native tissues. The main techniques used for 3D bioprinting include microextrusion, inkjet, and laser‐assisted bioprinting. Bioinks used for bone bioprinting include hydrogels loaded with bioactive ceramics, cells, and growth factors. In this review, a critical overview of the recent literature on various types of bioinks used for bone bioprinting is presented. Major challenges, such as the vascularity, clinically relevant size, and mechanical properties of 3D printed structures, that need to be addressed to successfully use the technology in clinical settings, are discussed. Emerging approaches to solve these problems are reviewed, and future strategies to design customized 3D printed structures are proposed.
Total neoadjuvant therapy with short course radiation compared to concurrent chemoradiation in rectal cancer.
Authors: William Chapman, Hyun Kim, Philip Bauer, Bilal Makhdoom, Nikolaos Trikalinos, Katrina Pedersen, Sean Glasgow, Amit Roy, Michael Charles Roach, Matthew G Mutch, Parag Parikh, Steven Hunt
Journal: Journal of Clinical Oncology (2019)

486 Background: Total Neoadjuvant Therapy (TNT), or delivery of all radiation and chemotherapy prior to surgery, has improved complete response and downstaging rates compared to adjuvant therapy in patients with rectal cancer. Data regarding the use of short course radiation in the setting of TNT (SC-TNT) are limited. This study compares the pathologic complete response rate (pCR), Neoadjuvant Rectal (NAR) Score – a validated predictor of outcome based on tumor downstaging, and recurrence rates for patients receiving SC-TNT versus chemoradiation (CRT). Methods: Patients who underwent neoadjuvant therapy followed by total mesorectal excision for Stage II or III rectal cancer from 2009 to 2018 were included in this retrospective cohort study. CRT recipients (50-55Gy/25-28 fx with concurrent 5-FU or capecitabine) comprised one cohort; the other included SC-TNT recipients (25-35Gy/5 fx followed by CAPOX or FOLFOX chemotherapy). The primary outcome of pCR rate was assessed in univariate analysis; the secondary outcome of NAR score was calculated and categorized as “Low” ( &lt; 8), “Intermediate” (8–16), and “High” ( &gt; 16). Finally, recurrence rates were measured and classified as local, distant, or both. Results: Of 388 eligible patients, 236 (60.8%) were treated with CRT and 152 (39.2%) underwent SC-TNT. On univariate analysis, the SC-TNT cohort had more advanced disease (77% Stage III disease vs. 67%, p = 0.04) and longer elapsed time between radiation completion and surgery (Median 131 vs. 63 days; p &lt; 0.01). SC-TNT achieved a numerically higher pCR rate compared to CRT (25.0% vs. 19.1%, p = 0.16). Odds of achieving a “low” NAR Score trended higher among the SC-TNT cohort (OR 1.49, 95% CI 0.96 – 2.31). Recurrence rates were also similar (14.3% vs. 14.9%, p = 0.87) over comparable follow-up (CRT = 30.5 months [IQR 11.1 – 49.0]; SC-TNT = 22.3 months [IQR 10.8 – 61.0]; p = 0.82). Conclusions: SC-TNT yielded a pCR rate of 25% and overall recurrence rate of 14.9% among patients with locally advanced rectal cancer. Short course radiation with neoadjuvant multiagent chemotherapy is at least as effective as long-course CRT. [Table: see text]
Mira Hazel Farquharson
Authors: Marie Freel
Journal: BMJ (2019)

Mira Hazel Farquharson held several posts in clinical medicine in Glasgow before starting her training in haematology in Edinburgh in 2004. She made friends easily, and her chatty, easygoing nature, as well as her flaming red hair, meant that she made a memorable impression wherever she worked.

Mira was appointed to a consultant post in haematology in the Western General and St John’s hospitals in Edinburgh in 2010. She was well respected in all areas of her specialty, and …
Predicting Patient Response To Pneumococcal 23-vaccine (PPV23) Using Age, Baseline Immunoglobulins, and Pneumococcal Serotypes
Authors: Rayna J. Doll, David McGarry, Nancy Joseph, Jack Jeskey, Linda Quinn, Devi Jhaveri, Haig Tcheurekdjian, Robert W. Hostoffer
Journal: Journal of Allergy and Clinical Immunology (2019)
Brazil’s Fight against Hepatitis C — Universalism, Local Production, and Patents
Authors: Elize M. da Fonseca, Kenneth Shadlen, Francisco I. Bastos
Journal: New England Journal of Medicine (2019)

Brazil's strategy for addressing hepatitis C, which combines evidence-based treatment protocols and innovative initiatives for local production of generic direct-acting antiviral drugs, needs to be considered in light of ongoing conflicts over pharmaceutical patents.
Abstract P366: Fasting Glucose and Insulin Resistance Trajectories in Young Adulthood and Cognitive Function in Middle Adulthood: the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Michael P Bancks, Mercedes Carnethon, David R Jacobs, Lenore Launer, Jared Reis, Pamela J Schreiner, Ravi Shah, Steve Sidney, Kristine Yaffe, Yuichiro Yano, Norrina B Allen
Journal: Circulation (2017)

Introduction: Whether multiple unique trajectories in fasting glucose (FG) and insulin resistance (HOMA-IR) are present during young adulthood and if such trajectories are associated with cognitive function in middle adulthood is unclear. Hypothesis: We hypothesized that a high-increasing trajectory of FG and HOMA-IR in the absence of diabetes during young adulthood would be associated with lower level of cognitive function in midlife compared to a low trajectory. Methods: We studied 2,650 CARDIA participants, age 18 to 30 years (1985-1986) to determine FG and HOMA-IR at baseline and 7, 10, 15, and 20 year follow-up exams (≥ 8 hours fasting and not pregnant). Using latent class analysis (SAS Proc Traj), we determined trajectory groups for FG and HOMA-IR through year 20. Cognitive function was assessed at year 25 (2010-2011) with three cognitive tests including the Digit Symbol Substitution Test (DSST; a test of sustained attention, psychomotor speed, working memory, and executive function), Rey-Auditory Verbal Learning Test (RAVLT; verbal memory), and Stroop Test (executive function). We used multivariable linear regression to estimate adjusted means for each cognitive test according to trajectory group for both FG and HOMA-IR for individuals free from diabetes during follow-up, after adjustment for potential confounding factors. Results: We identified three trajectory groups for FG and HOMA-IR for individuals free from diabetes in middle adulthood, qualitatively low-stable to increasing, moderate-increasing, and high-increasing. Compared to the low FG trajectory group, the high FG trajectory group had significantly lower mean score for the RAVLT, shown in the Table . Otherwise, cognitive test scores generally did not differ according to FG or HOMA-IR trajectory group. Conclusion: In this community-based sample of individuals free from diabetes, a high-increasing FG trajectory through young adulthood was associated with worse memory in midlife.
Extreme self-sacrifice beyond fusion: Moral expansiveness and the special case of allyship
Authors: Daniel Crimston, Matthew J. Hornsey
Journal: Behavioral and Brain Sciences (2018)

Abstract As a general theory of extreme self-sacrifice, Whitehouse's article misses one relevant dimension: people's willingness to fight and die in support of entities not bound by biological markers or ancestral kinship ( allyship ). We discuss research on moral expansiveness, which highlights individuals’ capacity to self-sacrifice for targets that lie outside traditional in-group markers, including racial out-groups, animals, and the natural environment.
Sixty seconds on . . . genome mapping
Authors: Ann Robinson
Journal: BMJ (2019)

Hilarious. When the Department of Health and Social Care says that every NHS patient will have the opportunity to have their whole genome sequenced for a fee through Genomics England, it’s considering the future. England’s health secretary, Matt Hancock, thinks population genetic testing can save lives, prevent illness, and reduce demand on the NHS.

No, it’s genomics not fortune telling. And clinical geneticist Anneke Lucassen thinks it …
Toward Broader Genetic Contextualism: Genetic Testing Enters the Age of Evidence-Based Medicine
Authors: Anne-Marie Laberge, Julie Richer, Vardit Ravitsky
Journal: The American Journal of Bioethics (2019)

In “Genomic Contextualism: Shifting the Rhetoric of Genetic Exceptionalism,” Garrison and colleagues (2019) criticize genetic exceptionalism as a reductive argument that has recently led to counter...
Book reviewIslands as individualsRobert J. Whittaker, Island Biogeography: Ecology, Evolution and Conservation, Oxford University Press (1998), £50.00 hbk, £19.50 pbk (xi 1 278 pages), ISBN: 0 19 850021 2 / 0 19 850020 3
Authors: Quentin Cronk
Journal: Trends in Ecology & Evolution (1999)
Abstract 2424: Reducing Myofibroblast Arrhythmogenicity by Pharmacological Targeting of Their Cytoskeleton
Authors: Christian Rosker, Nicolo Salvarani, Stephan Rohr
Journal: Circulation (2009)

Introduction: Slow conduction and ectopic activity are key elements of cardiac arrhythmogenesis. Both anomalies can be caused by myofibroblasts (MFBs) following establishment of heterocellular gap ...
CKS1B/CDKN2C Copy Number Ratio : A New Predictor of Survival in Transplant- and Non Transplant-Eligible Multiple Myeloma Patients
Authors: Stéphanie Dos Santos, Laura Herbreteau, Christophe Nicol, Vincent Rebière, Hubert Galinat, Jean-Christophe Ianotto, Jean-Richard Eveillard
Journal: Blood (2018)
Abstract MP67: Pregnancy Outcomes in Women With Congenital Heart Defects in Colorado: Results From the Colorado CHD Surveillance System in Adolescents and Adults (COCHD)
Authors: Tessa Crume, Lindsey Duca, Christopher Rausch, Amber Khanna
Journal: Circulation (2018)

Introduction: The normal hemodynamic changes of pregnancy can trigger cardiac dysfunction in women with congenital heart defects (CHD), leading to an increased risk of cardiac events. Further, utero-placental flow is impaired in women with CHD which can result in higher risk of adverse offspring outcomes. Hypothesis: Severity of maternal CHD is associated with adverse maternal cardiovascular events and offspring events by severity of CHD in 1074 pregnancies that resulted in a live birth in Colorado between 2011-13. Methods: Using data from the Colorado CHD Surveillance System in Adolescents and Adults, 926 pregnant women with CHD were identified that resulted in 1074 live births between 2011-2013. Maternal CHD type was dichotomized as severe (n=149) and moderate (total n=882). The risk of adverse maternal cardiac and offspring events were calculated out of the total number of pregnancies in each severity category. Results: Primary maternal cardiac events including cardiovascular mortality, arrhythmia, heart failure, thromboembolic events (pulmonary embolism, valve thrombosis or deep venous thrombosis), vascular events (stroke, myocardial infarction or dissection) and endocarditis occurred in 15% and 7% of women with severe and moderate CHD, respectively. Premature birth (delivery &lt;37 weeks) and/or low birth weight (&lt;2,500 grams) occurred in &gt;18% of the women with severe CHD and 17% of women with moderate CHD. The risk of offspring congenital anomalies among women with severe CHD was extremely high for circulatory/respiratory, musculoskeletal/integumentary, cyanotic congenital heart disease and Down syndrome. The risk of infant congenital anomalies was lower for women with moderate CHD, with the most common being circulatory/respiratory, urogenital, Down syndrome and cyanotic congenital heart disease. Conclusions: Population-level surveillance system of CHD in Colorado provides novel assessment of the substantial risk of maternal and neonatal cardiac events associated with pregnancy in women with CHD.
hnRNP K Overexpression Drives Myeloid Malignancy Via Interaction with RUNX1
Authors: Marisa J Hornbaker, Prerna Malaney, Xiaorui Zhang, Ruizhi Duan, Vrutant Shah, Shelley Herbrich, Miguel Gallardo, Rodrigo Jacamo, Todd Link, Huaxian Ma, Sanzhar Alybayev, Steven M. Kornblau, Peter Hu, Dos Sarbassov, Rashmi Kanagal-Shamanna, Carlos E. Bueso-Ramos, Sean M Post
Journal: Blood (2018)
Abstract 4731: Impaired Right Ventricular Contraction and Relaxation in Patients with Left Ventricular Hypertrophy and Preserved Left Ventricular Ejection Fraction Quantified by Speckle-Tracking Strain and Strain Rate Imaging
Authors: Emiyo Ogawa, Kaoru Dohi, Katsuya Onishi, Takeshi Takamura, Hiroshi Nakajima, Masaki Tanabe, Hiroya Tamada, Norikazu Yamada, Masatoshi Miyahara, Mashio Nakamura, Masaaki Ito
Journal: Circulation (2008)

Background: It has not been fully investigated whether right ventricular (RV) contraction and relaxation were impaired in patients with left ventricular hypertrophy (LVH) and normal left ventricular ejection fraction (LVEF). Methods: To quantify longitudinal RV function, 30 patients with hypertensive LVH (LVH group: mean age 59 ± 15 years, LVEF 64 ± 5 %), 25 patients with hypertrophic cardiomyopathy (HCM group: mean age 60 ± 14 years, LVEF 71 ± 10 %) and 50 age matched normal controls (Control group: mean age 56 ± 15 years, LVEF 65 ± 5 %) had echo-study with speckle-tracking strain and strain rate imaging (Vivid 7 and EchoPAC, GE Electronic) from apical 4 chamber view. RV peak systolic strain (PSS) and peak relaxation rate (PRR) were used as indices of global RV contraction and relaxation, respectively. RV fractional area change was also analyzed. Results: Both PSS and PRR were significantly reduced in LVH group compared to Control group and were further impaired in HCM group (PSS: −20 ± 4 %* in LVH group...
Tumor mutational burden and other predictive immunotherapy markers in histiocytic neoplasms
Authors: Gaurav Goyal, Denise Lau, Alison M. Nagle, Robert Vassallo, Karen L. Rech, Jay H. Ryu, Caroline J. Davidge-Pitts, W. Oliver Tobin, Matthew J. Koster, N. Nora Bennani, Mithun V. Shah, Minetta C. Liu, Ronald S. Go
Journal: Blood (2019)