tbuckley/cabot-search huggingface dataset:
DNA Methylation Score as a Biomarker in Newborns for Sustained Maternal Smoking during Pregnancy
Authors: Sarah E. Reese, Shanshan Zhao, Michael C. Wu, Bonnie R. Joubert, Christine L. Parr, Siri E. Håberg, Per Magne Ueland, Roy M. Nilsen, Øivind Midttun, Stein Emil Vollset, Shyamal D. Peddada, Wenche Nystad, Stephanie J. London
Journal: Environmental Health Perspectives (2016)

Maternal smoking during pregnancy, especially when sustained, leads to numerous adverse health outcomes in offspring. Pregnant women disproportionately underreport smoking and smokers tend to have lower follow-up rates to repeat questionnaires. Missing, incomplete, or inaccurate data on presence and duration of smoking in pregnancy impairs identification of novel health effects and limits adjustment for smoking in studies of other pregnancy exposures. An objective biomarker in newborns of maternal smoking during pregnancy would be valuable.We developed a biomarker of sustained maternal smoking in pregnancy using common DNA methylation platforms.Using a dimension reduction method, we developed and tested a numeric score in newborns to reflect sustained maternal smoking in pregnancy from data on cotinine, a short-term smoking biomarker measured mid-pregnancy, and Illumina450K cord blood DNA methylation from newborns in the Norwegian Mother and Child Cohort Study (MoBa).This score reliably predicted smoking status in the training set (n = 1,057; accuracy = 96%, sensitivity = 80%, specificity = 98%). Sensitivity (58%) was predictably lower in the much smaller test set (n = 221), but accuracy (91%) and specificity (97%) remained high. Reduced birth weight, a well-known effect of maternal smoking, was as strongly related to the score as to cotinine. A three-site score had lower, but acceptable, performance (accuracytrain = 82%, accuracytest = 83%).Our smoking methylation score represents a promising novel biomarker of sustained maternal smoking during pregnancy easily calculated with Illumina450K or IlluminaEPIC data. It may help identify novel health impacts and improve adjustment for smoking when studying other risk factors with more subtle effects.
Valve Weight and Severity of Valve Calcification are less in Paradoxical Low Gradient than in High Gradient Severe Aortic Stenosis
Authors: Jamila Boulif, Bernhard Gerber, Siham Lazam, Fabian Demeure, Christophe de Meester de Ravenstein, Agnes Pasquet, David Vancraeynest, Jean-Louis Vanoverschelde
Journal: Circulation (2014)

Background: Paradoxical low gradient (PLG) severe aortic stenosis (SAS) is a recently described subset of SAS, whose exact clinical significance is a matter of intense debate. Some authors indeed consider this new entity as a more advanced form of SAS, whereas others believe it represents a relatively benign form of AS. To get further insight into the pathophysiology of PLG SAS, we compared the weight of the valves explanted at the time of surgery (AVR) and the degree of valve calcification, two surrogates markers of the true stenosis severity, among consecutive patients with PLG SAS and high-gradient (HG) SAS. Methods: We prospectively recruited 38 consecutive patients (20 men; mean age: 73 yrs) with isolated non-rheumatic SAS (indexed aortic valve area (AVAi)  0.90) and in-vivo (r2=0.71) Agatston scores. Interestingly, valves explanted from patients with PLG SAS were lighter (1.58±0.65 vs 2.65±1.24 g, p=0.001) and showed lower ex-vivo Agatston scores (363±282 vs 1211±840, p<0.001) than HG SAS valves. These differences remained significant after adjustment for gender (1.58±0.65 vs 2.36±0.88 g, p=0.011 for valves weight and 363±282 vs 1023±597, p=0.002 for ex-vivo Agatston score). Conclusion: The valves weight and degree of valve calcification reported in our study indicate that PLG SAS valves are less severely affected than HG SAS valves. These data thus reinforce the hypothesis that PLG SAS is a lesser advanced form of aortic stenosis than HG SAS.
Expression Profiling of a Panel of Apoptosis Related Micrornas in Patients with Acute Myeloid Leukemia
Authors: Eleftheria Hatzimichael, Aggeliki Dasoula, Maria Igglezou, Andreas Katsenos, Ioannis Sainis, Isidore Rigoutsos, Evangelos Briasoulis
Journal: Blood (2015)
A halfway house for mentally ill offenders
Authors: J Goldmeier, R H Sauer, E V White
Journal: American Journal of Psychiatry (1977)

The authors describe the resocialization of recovering mentally ill male offenders through the halfway house program to which they were released. A number of guiding principles are discussed in connection with the care of this high-risk population. Partial residence for those about tp be discharged from the hospital was one feature of the program. Evaluation of the program after three years showed a lower than average rate of recidivism and relatively low operating costs; in addition, it appeared that predictions regarding possible dangerousness can be made with greater confidence when halfway house residence is part of the treatment plan for this type of population.
Targeted disruption of guanosine diphosphate-dissociation inhibitor for Rho-related proteins, GDID4: normal hematopoietic differentiation but subtle defect in superoxide production by macrophages derived from in vitro embryonal stem cell differentiation
Authors: JC Guillemot, BA Kruskal, CN Adra, S Zhu, JL Ko, P Burch, K Nocka, K Seetoo, E Simons, B Lim
Journal: Blood (1996)
A Patient With Metastatic Sarcoma was Successfully Treated With Radiolabeled Somatostatin Analogs
Authors: Aurora Crespo-Jara, Ramón González Manzano, Maribel Lopera Sierra, María Carmen Redal Peña, Antonio Brugarolas Masllorens
Journal: Clinical Nuclear Medicine (2016)

We present a sarcoma patient with a tumor reduction of more than 50% in lung metastasis after 2 single courses of the investigational medical product Lutathera (177Lu-DOTA0-Tyr3-octreotate). She was resistant to more than 6 lines of therapy including all the available active drugs in soft tissue sarcomas. The high expression of somatostatin receptors was shown by microarrays and Octreoscan. The overall duration of response exceeded 1 year.
BMA annual meeting: What Chaand Nagpaul said on seven day GP services
Authors: Abi Rimmer
Journal: BMJ (2016)

Speaking at the BMA’s annual representatives meeting in Belfast on 20 June, the chair of the association’s General Practitioners Committee described a new type of “weekend effect”



BMA’s Chaand Nagpaul: “We’re seeing GPs who would have worked out-of-hours urgent care shifts choosing instead to work in new seven day routine access clinics” 



“I want to raise the issue of a new weekend effect in general practice of the government’s …
The Iks
Authors: Lewis Thomas
Journal: New England Journal of Medicine (1973)

THE small tribe of Iks, formerly nomadic hunters and gatherers in the mountain valleys of northern Uganda, have become celebrities in the past year, literary symbols for the ultimate fate of disheartened, heartless mankind at large. Two disastrously conclusive things happened to them: the government decided to have a national park, so they were compelled by law to give up hunting in the valleys and become farmers on poor hillside soil, and then they were visited for two years by an anthropologist who detested them and wrote a book about them.*The message of the book is that the Iks . . .
Objective response rate in a phase II multicenter trial of pertuzumab (P), a HER2 dimerization inhibiting monoclonal antibody, in combination with trastuzumab (T) in patients (pts) with HER2-positive metastatic breast cancer (MBC) which has progressed during treatment with T
Authors: J. Baselga, D. Cameron, D. Miles, S. Verma, M. Climent, G. Ross, V. Gimenez, K. Gelmon
Journal: Journal of Clinical Oncology (2007)

1004 Background: T and P bind to different epitopes on the extra cellular domain of HER2. Unlike T, P binds to the dimerization domain and blocks homo- and hetero-dimerization of HER2 with other HER kinase family members. Xenograft models support the hypothesis that the complementary mechanisms of action could result in augmented efficacy when T and P are combined. Methods: Two-stage design, criteria to proceed to the 2 nd stage were: ≥ 2 partial responses (PR) or 1 PR and 12 stable disease (SDs) or 13 SDs. Eligibility included: measurable, centrally-tested HER2 positive breast cancer; up to 3 lines of prior chemotherapy plus T (including adjuvant chemotherapy plus T); disease progression during T as most recent treatment for metastatic disease; baseline left ventricular ejection fraction (LVEF) ≥ 55% and no decrease of LVEF to below 50% during prior T treatment. Consenting Pts received T i.v. weekly or every 3 weeks at 2 mg/kg or 6 mg/kg respectively (with re-loading dose if required) plus 420mg fixed dose of P i.v. every 3 weeks following loading dose 840mg. Study treatment was initiated within 9 weeks of the last dose of T given as most recent therapy. An independent data safety monitoring board has overseen the 1 st stage safety data. Results: Recruitment into 1 st stage is complete. The main adverse events were diarrhea (71%), fatigue (46%), nausea/vomiting (38%) and rash (25%). Most AE’s were mild to moderate (there was 1 case of Grade 3 diarrhea) and none was treatment-limiting. There were no clinical cardiac events, and central review revealed no case of fall in LVEF of ≥10% and to ≤50%. Response status: 5 confirmed PR (21%); 12 SD (50%). Responses have been observed in lymph node and liver metastases. Recruitment into the 2 nd stage of the trial has commenced. Conclusions: The combination of the P and T is active and well tolerated in patients with pre-treated HER2 positive breast cancer which has progressed during treatment with T. No significant financial relationships to disclose.
Preaching to the choir: new voices in the end of life discussion.
Authors: J A Jacobson
Journal: Journal of Clinical Oncology (1997)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1997.15.2.413 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9053459 Preaching to the choir: new voices in the end of life discussion. J A JacobsonxJ A JacobsonSearch for articles by this author https://doi.org/10.1200/JCO.1997.15.2.413 First Page PDF © 1997 by American Society of Clinical OncologyKeywords: Death and Euthanasia... Show All
ECG Challenge: November 3, 2015
Authors: Philip Podrid
Journal: Circulation (2015)

ECG Challenge 1743A 67-year-old man with prostate cancer currently being treated with radiation therapy presents to the hospital with concerns about the inability to urinate for the past 2 days.It is noted that his urinary tract is obstructed and a Foley catheter is inserted with difficulty.Several hours later the patient develops shaking chills and diaphoresis and has a blood pressure of 89/60 mm Hg.It is believed that he has urosepsis, and he is started on antibiotics and pressors for early septic shock.As a result, he develops a tachycardia and an ECG (ECG A) is obtained.
A Worldwide Map of<i>Plasmodium falciparum</i>K13-Propeller Polymorphisms
Authors: Didier Ménard, Nimol Khim, Johann Beghain, Ayola A. Adegnika, Mohammad Shafiul-Alam, Olukemi Amodu, Ghulam Rahim-Awab, Céline Barnadas, Antoine Berry, Yap Boum, Maria D. Bustos, Jun Cao, Jun-Hu Chen, Louis Collet, Liwang Cui, Garib-Das Thakur, Alioune Dieye, Djibrine Djallé, Monique A. Dorkenoo, Carole E. Eboumbou-Moukoko, Fe-Esperanza-Caridad J. Espino, Thierry Fandeur, Maria-Fatima Ferreira-da-Cruz, Abebe A. Fola, Hans-Peter Fuehrer, Abdillahi M. Hassan, Socrates Herrera, Bouasy Hongvanthong, Sandrine Houzé, Maman L. Ibrahim, Mohammad Jahirul-Karim, Lubin Jiang, Shigeyuki Kano, Wasif Ali-Khan, Maniphone Khanthavong, Peter G. Kremsner, Marcus Lacerda, Rithea Leang, Mindy Leelawong, Mei Li, Khin Lin, Jean-Baptiste Mazarati, Sandie Ménard, Isabelle Morlais, Hypolite Muhindo-Mavoko, Lise Musset, Kesara Na-Bangchang, Michael Nambozi, Karamoko Niaré, Harald Noedl, Jean-Bosco Ouédraogo, Dylan R. Pillai, Bruno Pradines, Bui Quang-Phuc, Michael Ramharter, Milijaona Randrianarivelojosia, Jetsumon Sattabongkot, Abdiqani Sheikh-Omar, Kigbafori D. Silué, Sodiomon B. Sirima, Colin Sutherland, Din Syafruddin, Rachida Tahar, Lin-Hua Tang, Offianan A. Touré, Patrick Tshibangu-wa-Tshibangu, Inès Vigan-Womas, Marian Warsame, Lyndes Wini, Sedigheh Zakeri, Saorin Kim, Rotha Eam, Laura Berne, Chanra Khean, Sophy Chy, Malen Ken, Kaknika Loch, Lydie Canier, Valentine Duru, Eric Legrand, Jean-Christophe Barale, Barbara Stokes, Judith Straimer, Benoit Witkowski, David A. Fidock, Christophe Rogier, Pascal Ringwald, Frederic Ariey, Odile Mercereau-Puijalon
Journal: New England Journal of Medicine (2016)

Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)–propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale.
Reduced epithelial suppressor of cytokine signalling 1 in severe eosinophilic asthma
Authors: Emma Doran, David F. Choy, Aarti Shikotra, Claire A. Butler, Declan M. O'Rourke, James A. Johnston, Adrien Kissenpfennig, Peter Bradding, Joseph R. Arron, Liam G. Heaney
Journal: European Respiratory Journal (2016)

Severe asthma represents a major unmet clinical need. Eosinophilic inflammation persists in the airways of many patients with uncontrolled asthma, despite high-dose inhaled corticosteroid therapy. Suppressors of cytokine signalling (SOCS) are a family of molecules involved in the regulation of cytokine signalling via inhibition of the Janus kinase-signal transducers and activators of transcription pathway. We examined SOCS expression in the airways of asthma patients and investigated whether this is associated with persistent eosinophilia.Healthy controls, mild/moderate asthmatics and severe asthmatics were studied. Whole genome expression profiling, quantitative PCR and immunohistochemical analysis were used to examine expression of SOCS1, SOCS2 and SOCS3 in bronchial biopsies. Bronchial epithelial cells were utilised to examine the role of SOCS1 in regulating interleukin (IL)-13 signalling in vitroSOCS1 gene expression was significantly lower in the airways of severe asthmatics compared with mild/moderate asthmatics, and was inversely associated with airway eosinophilia and other measures of T-helper type 2 (Th2) inflammation. Immunohistochemistry demonstrated SOCS1 was predominantly localised to the bronchial epithelium. SOCS1 overexpression inhibited IL-13-mediated chemokine ligand (CCL) 26 (eotaxin-3) mRNA expression in bronchial epithelial cells.Severe asthma patients with persistent airway eosinophilia and Th2 inflammation have reduced airway epithelial SOCS1 expression. SOCS1 inhibits epithelial IL-13 signalling, supporting its key role in regulating Th2-driven eosinophilia in severe asthma.
A Diffusion Tensor Imaging Study in Children With ADHD, Autism Spectrum Disorder, OCD, and Matched Controls: Distinct and Non-Distinct White Matter Disruption and Dimensional Brain-Behavior Relationships
Authors: Stephanie H. Ameis, Jason P. Lerch, Margot J. Taylor, Wayne Lee, Joseph D. Viviano, Jon Pipitone, Arash Nazeri, Paul E. Croarkin, Aristotle N. Voineskos, Meng-Chuan Lai, Jennifer Crosbie, Jessica Brian, Noam Soreni, Russell Schachar, Peter Szatmari, Paul D. Arnold, Evdokia Anagnostou
Journal: American Journal of Psychiatry (2016)

Neurodevelopmental disorders (NDDs) (attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) share genetic vulnerability and symptom domains. The authors present direct comparison of structural brain circuitry in children and adolescents with NDDs and control subjects and examine brain circuit-behavior relationships across NDDs using dimensional measures related to each disorder.Diffusion imaging and behavioral measures were acquired in 200 children and adolescents (ADHD: N=31; OCD: N=36; ASD: N=71; controls: N=62; mean age range: 10.3-12.6 years). Following Tract-Based Spatial Statistics, multigroup comparison of white matter indices was conducted, followed by pairwise comparisons. Relationships of fractional anisotropy with dimensional measures of inattention, social deficits, obsessive-compulsive symptoms, and general adaptive functioning were conducted across the NDD sample.Lower fractional anisotropy within the splenium of the corpus callosum was found in each NDD group, compared with the control group. Lower fractional anisotropy in additional white matter tracts was found in the ASD and ADHD groups, compared with the control group, but not in the OCD group. Fractional anisotropy was lower in the ASD and ADHD groups compared with the OCD group but was not different in ADHD participants compared with ASD participants. A positive relation between fractional anisotropy (across much of the brain) and general adaptive functioning across NDDs was shown.This study identified disruption in interhemispheric circuitry (i.e., fractional anisotropy alterations in the corpus callosum) as a shared feature of ASD, ADHD, and OCD. However, fractional anisotropy alterations may be more widespread and severe in ASD and ADHD than in OCD. Higher fractional anisotropy throughout the brain appears to be related to better adaptive function across NDDs.
Some Epidemiological Aspects of Leukemia in Children
Authors: Miriam D. Manning, M.D., M.P.H., Benjamin E. Carroll, M.A.
Journal: JNCI Journal of the National Cancer Institute (1957)

Journal Article Some Epidemiological Aspects of Leukemia in Children Get access Miriam D. Manning, M.D., M.P.H., Miriam D. Manning, M.D., M.P.H. Children's Cancer Research Foundation, Boston, Massachusetts, and National Cancer Institute,4Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Benjamin E. Carroll, M.A. Benjamin E. Carroll, M.A. Children's Cancer Research Foundation, Boston, Massachusetts, and National Cancer Institute,4Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 19, Issue 6, December 1957, Pages 1087–1094, https://doi.org/10.1093/jnci/19.6.1087 Published: 01 December 1957 Article history Received: 18 June 1957 Published: 01 December 1957
Abstract 15747: Over-Expression of Insulin-Like Growth Factor-1 by Human Cardiac Stem Cells Enhances Long-Term Retention of Transplanted Cells While Promoting Salvage of Injured Myocardium
Authors: Robyn Jackson, Everad L Tilokee, Nicholas Latham, Bin Ye, Munir Boodhwani, Vincent Chan, Marc Ruel, Erik J Suuronen, Duncan J Stewart, Darryl R Davis
Journal: Circulation (2014)

Background: Insulin-like growth factor (IGF-1) is a potent pro-survival cytokine that is not robustly expressed by human cardiac stem cells (CSCs). Previously, we have shown that paracrine engineering of CSCs with IGF-1 improves cell-mediated cardiac repair. Here, we explore the mechanisms underlying IGF-1 enhanced cardiac repair by CSCs. Methods/Results: Sub-culture of isolated c-Kit+, CD90+ and lineage negative cells (c-Kit-/CD90-) demonstrated that the natural low level production of IGF-1 by CSCs (149±16 pg/ml*mg) is secreted by all 3 sub-populations. After culture in hypoxic reduced serum media, lentiviral mediated over-expression of IGF-1 enhanced proliferation (population doubling time: 1.4±1.7 vs.-0.9±1.2 and -1.9±2.4 days, respectively; p≤0.01), expression of pro-survival transcripts (AKT, ERK and MAPK pathways) and pro-survival proteins (Bcl-2, Bcl-x, HIF-1a; p≤0.01) while decreasing expression of apoptotic markers (3.5±0.9 and 3.7±0.9 fold less annexin V; p≤0.01) as compared to GFP- and non-transduced CSCs. The high expression of the IGF-1 (79±3%) or the insulin receptor (61±5%) on CSCs suggests that autocrine pro-survival pre-conditioning underlies these effects. Direct and indirect co-culture of CSCs with neonatal rat ventricular cardiomyocytes (NRVMs) within hypoxic conditions demonstrated that IGF-1 promoted indirect myocardial repair by increasing NRVM viability and pro-survival signaling (Bcl2+; p≤0.01) while reducing apoptosis (annexin V+; p≤0.05) as compared GFP- or non-transduced CSCs. Transplant of CSCs genetically engineered to over-express IGF-1 into immunodeficient mice one week after infarction boosted IGF-1 content within infarcted tissue by 2.9±0.2 fold (p=0.004) and long-term engraftment (+4 weeks human alu content increased by 9.1±4 fold; p=0.05) while reducing myocardial apoptosis (3.4±0.3 and 2.5±0.5 fold reduction expression of Bax and p53, respectively; p&lt;0.05) and long-term myocardial scarring (+ 4 weeks 2.2±0.4 fold less; p=0.01) as compared to GFP-transduced CSCs. Conclusions: Transplantation of IGF-1 enriched CSCs enhances cardiac repair by boosting transplant cell survival and reducing myocardial apoptosis to improve myocardial function and salvage of damaged myocardium.
Nerve growth factor inhibition with tanezumab influences weight-bearing and subsequent cartilage damage in the rat medial meniscal tear model
Authors: Timothy P LaBranche, Alison M Bendele, Brian C Omura, Kathryn E Gropp, Susan I Hurst, Cedo M Bagi, Thomas R Cummings, Lonnie E Grantham, David L Shelton, Mark A Zorbas
Journal: Annals of the Rheumatic Diseases (2016)

Objective To investigate whether the effects of nerve growth factor (NGF) inhibition with tanezumab on rats with medial meniscal tear (MMT) effectively model rapidly progressive osteoarthritis (RPOA) observed in clinical trials. Methods Male Lewis rats underwent MMT surgery and were treated weekly with tanezumab (0.1, 1 or 10 mg/kg), isotype control or vehicle for 7, 14 or 28 days. Gait deficiency was measured to assess weight-bearing on the operated limb. Joint damage was assessed via histopathology. A second arm, delayed onset of treatment (starting 3–8 weeks after MMT surgery) was used to control for analgesia early in the disease process. A third arm, mid-tibial amputation, evaluated the dependency of the model on weight-bearing. Results Gait deficiency in untreated rats was present 3–7 days after MMT surgery, with a return to normal weight-bearing by days 14–28. Prophylactic treatment with tanezumab prevented gait deficiency and resulted in more severe cartilage damage. When onset of treatment with tanezumab was delayed to 3–8 weeks after MMT surgery, there was no increase in cartilage damage. Mid-tibial amputation completely prevented cartilage damage in untreated MMT rats. Conclusions These data suggest that analgesia due to NGF inhibition during the acute injury phase is responsible for increased voluntary weight-bearing and subsequent cartilage damage in the rat MMT model. This model failed to replicate the hypotrophic bone response observed in tanezumab-treated patients with RPOA.
Correlations Between TET2 Mutation and Clinicohematologic Parameters in Myeloproliferative Neoplasms
Authors: Jung Sook Ha, Jae Hee Lee, Sung Gyun Park, Nam Hee Ryoo, Dong Suk Jeon, Jae Ryong Kim, Young Rok Do, Jin Young Kim, Ki Young Kwon, Ji Yoon Kim, Jang Soo Suh
Journal: Blood (2012)
Continued Treatment Duration, Drug dosing and Health-Related Quality Of Life (HRQoL) Of Patients With Relapsed/Refractory Multiple Myeloma (RRMM) Receiving 2nd and 3rd Line Treatments: Results From a European Multicentre Study
Authors: Maria Teresa Petrucci, Xavier Leleu, Charalampia Kyriakou, Isabelle Vande Broek, Philip T Murphy, Philip Lewis, Pamela Bacon, Benoit Arnould, Manfred Welslau
Journal: Blood (2013)
A family cluster of imported ZIKV cases: Viremia period may be longer than previously reported
Authors: De Wu, Jiufeng Sun, Haojie Zhong, Dawei Guan, Huan Zhang, Qiqi Tan, Huiqiong Zhou, Dan Ning, Changwen Ke, Tie Song, Jinyan Lin, Yonghui Zhang, Marion Koopmans, George F. Gao
Journal: Journal of Infection (2016)