tbuckley/cabot-search huggingface dataset:
Development of a 4-aminopyrazolo[3,4-d]pyrimidine-based dual IGF1R/Src inhibitor as a novel anticancer agent with minimal toxicity
Authors: Ho Jin Lee, Phuong Chi Pham, Seung Yeob Hyun, Byungyeob Baek, Byungjin Kim, Yunha Kim, Hye-Young Min, Jeeyeon Lee, Ho-Young Lee
Journal: Molecular Cancer (2018)

Abstract Background Both the type I insulin-like growth factor receptor (IGF1R) and Src pathways are associated with the development and progression of numerous types of human cancer, and Src activation confers resistance to anti-IGF1R therapies. Hence, targeting both IGF1R and Src concurrently is one of the main challenges in combating resistance to the currently available anti-IGF1R-based anticancer therapies. However, the enhanced toxicity from this combinatorial treatment could be one of the main hurdles for this strategy, suggesting the necessity of developing a novel strategy for co-targeting IGF1R and Src to meet an urgent clinical need. Methods We synthesized a series of 4-aminopyrazolo[3,4- d ]pyrimidine-based dual IGF1R/Src inhibitors, selected LL28 as an active compound and evaluated its potential antitumor effects in vitro and in vivo using the MTT assay, colony formation assays, flow cytometric analysis, a tumor xenograft model, and the Kras G12D/+ -driven spontaneous lung tumorigenesis model. Results LL28 markedly suppressed the activation of IGF1R and Src and significantly inhibited the viability of several NSCLC cell lines in vitro by inducing apoptosis. Administration of mice with LL28 significantly suppressed the growth of H1299 NSCLC xenograft tumors without overt toxicity and substantially reduced the multiplicity, volume, and load of lung tumors in the Kras G12D/+ -driven lung tumorigenesis model. Conclusions The present results suggest the potential of LL28 as a novel anticancer drug candidate targeting both IGF1R and Src, providing a new avenue to efficient anticancer therapies. Further investigation is warranted in advanced preclinical and clinical settings.
Assisted Reproductive Technology Surveillance — United States, 2015
Authors: Saswati Sunderam, Dmitry M. Kissin, Sara B. Crawford, Suzanne G. Folger, Sheree L. Boulet, Lee Warner, Wanda D. Barfield
Journal: MMWR Surveillance Summaries (2018)

Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks for both mothers and infants, including obstetric complications, preterm delivery (<37 weeks), and low birthweight (<2,500 g) infants. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2015 and compares birth outcomes that occurred in 2015 (resulting from ART procedures performed in 2014 and 2015) with outcomes for all infants born in the United States in 2015.
Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma
Authors: Valeria Spina, Alessio Bruscaggin, Annarosa Cuccaro, Maurizio Martini, Martina Di Trani, Gabriela Forestieri, Martina Manzoni, Adalgisa Condoluci, Alberto Arribas, Lodovico Terzi-Di-Bergamo, Silvia Laura Locatelli, Elisa Cupelli, Luca Ceriani, Alden A. Moccia, Anastasios Stathis, Luca Nassi, Clara Deambrogi, Fary Diop, Francesca Guidetti, Alessandra Cocomazzi, Salvatore Annunziata, Vittoria Rufini, Alessandro Giordano, Antonino Neri, Renzo Boldorini, Bernhard Gerber, Francesco Bertoni, Michele Ghielmini, Georg Stüssi, Armando Santoro, Franco Cavalli, Emanuele Zucca, Luigi Maria Larocca, Gianluca Gaidano, Stefan Hohaus, Carmelo Carlo-Stella, Davide Rossi
Journal: Blood (2018)
Effects of Early life Factors on the Incidence of Allergic diseases in an Asian Birth cohort
Authors: Anchalee Senavonge, Pantipa Chatchatee, Kanlada Wongworapat, Yong Poovorawan, Nasamon Wanlapakorn, Pierre Van Damme, Camille Locht, Surasith Chaithongwongwatthana, Pathareeyawan Srimuan, Jarungchit Ngamphaiboon, Narissara Suratannon
Journal: Journal of Allergy and Clinical Immunology (2018)
Paid Family and Childbearing Leave Policies at Top US Medical Schools
Authors: Nicholas S. Riano, Eleni Linos, Erin C. Accurso, Dawn Sung, Elizabeth Linos, Julia F. Simard, Christina Mangurian
Journal: JAMA (2018)

Of the 32 829 research articles published from 2005 through 2014 among 10 journals with high impact factors, 3706 (11.3%) credited multiple authors as equal contributors.After inspecting the bylines of these articles, 2250 (6.9%) had exactly 2 co-first authors.We excluded 1260 with co-first authors of the same gender and 128 with at least 1 co-first author of uncertain gender, leaving 862 eligible articles with co-first authors of different genders.Overall, the proportion of female authors listed first in the byline was 0.50 (95% CI, 0.46 to 0.53; P = .92).However, among articles published in clinical journals, the proportion of female authors listed first was 0.37 (95% CI, 0.30 to 0.45; P < .001).Table 1 summarizes the tests of proportions for all categorical independent variables.The median (interquartile range [IQR]) total number of authors did not differ between articles with a female author listed first (9 [IQR, 6-14]) or a male author listed first (10 [IQR, 6-14]; P = .56).In the adjusted analysis (Table 2), compared with publication in a basic science journal, publication in a clinical research journal was inversely associated with female first authorship (aRR, 0.69 [95% CI, 0.56-0.85];P < .001).Also, a female (vs male) last author was associated with a female co-first author listed first in the byline (aRR, 1.18 [95% CI, 1.00-1.39];P = .04).Discussion | Overall and among articles published in basic science journals, co-first author gender was not associated with byline position.However, female co-first authors of articles published in clinical journals were less likely than their male counterparts to be listed first in the
Intragastric sensitization to peanut in the absence of a Th2-skewing adjuvant in mice genetically predisposed to food allergy
Authors: Johanna Smeekens, Kelly Orgel, Martin T. Ferris, Darla Miller, A. Wesley Burks, Fernando Pardo-Manuel de Villena, Mike D. Kulis
Journal: Journal of Allergy and Clinical Immunology (2018)
Eight-year survival in chronic hepatitis B patients under long-term entecavir or tenofovir therapy is similar to the general population
Authors: George V. Papatheodoridis, Vana Sypsa, George Dalekos, Cihan Yurdaydin, Florian van Boemmel, Maria Buti, John Goulis, Jose Luis Calleja, Heng Chi, Spilios Manolakopoulos, Alessandro Loglio, Spyros Siakavellas, Nikolaos Gatselis, Onur Keskın, Maria Lehretz, Savvoula Savvidou, Juan de la Revilla, Bettina E. Hansen, Anastasia Kourikou, Ioannis Vlachogiannakos, Kostantinos Galanis, Ramazan Idilman, Massimo Colombo, Rafael Esteban, Harry L.A. Janssen, Thomas Berg, Pietro Lampertico
Journal: Journal of Hepatology (2018)
Abstract 13269: The Tyrosine Kinase Inhibitor Nilotinib Induces Vascular Adverse Events in Patients With Chronic Myeloid Leukemia and Inhibits Endothelial Function and Angiogenesis
Authors: Rudolf Kirchmair, Karin Albrecht-Schgoer, Willfried Schgoer, Markus Theurl, Emir Hadzijusufovic, Gregor Eisenwort, Susanne Herndlhofer, Sabine Cerny-Reiterer, Wolfgang Sperr, Dominik Wolf, Peter Valent
Journal: Circulation (2013)

The second-generation BCR/ABL tyrosine kinase inhibitor nilotinib (nilo) is used for treatment of patients (pts) with chronic myeloid leukemia. Nilo has been considered a well-tolerated drug howeve...
Fast direct neuronal signaling via the IL-4 receptor as therapeutic target in neuroinflammation
Authors: Christina F. Vogelaar, Shibajee Mandal, Steffen Lerch, Katharina Birkner, Jerome Birkenstock, Ulrike Bühler, Andrea Schnatz, Cedric S. Raine, Stefan Bittner, Johannes Vogt, Jonathan Kipnis, Robert Nitsch, Frauke Zipp
Journal: Science Translational Medicine (2018)

Ongoing axonal degeneration is thought to underlie disability in chronic neuroinflammation, such as multiple sclerosis (MS), especially during its progressive phase. Upon inflammatory attack, axons undergo pathological swelling, which can be reversible. Because we had evidence for beneficial effects of T helper 2 lymphocytes in experimental neurotrauma and discovered interleukin-4 receptor (IL-4R) expressed on axons in MS lesions, we aimed at unraveling the effects of IL-4 on neuroinflammatory axon injury. We demonstrate that intrathecal IL-4 treatment during the chronic phase of several experimental autoimmune encephalomyelitis models reversed disease progression without affecting inflammation. Amelioration of disability was abrogated upon neuronal deletion of IL-4R. We discovered direct neuronal signaling via the IRS1-PI3K-PKC pathway underlying cytoskeletal remodeling and axonal repair. Nasal IL-4 application, suitable for clinical translation, was equally effective in improving clinical outcome. Targeting neuronal IL-4 signaling may offer new therapeutic strategies to halt disability progression in MS and possibly also neurodegenerative conditions.
So you think you can return to sport?
Authors: Trevor A Lentz, Mark V Paterno, Jonathan C Riboh
Journal: British Journal of Sports Medicine (2018)

‘Within the next two years, you will have another ACL tear’. This statement is true for one out of every three young athletes who undergo ACL reconstruction and return to cutting and pivoting sports.1 2 Understandably, this high rate of reinjury has led to questions about the effectiveness of current rehabilitation programmes and return-to-sport decision-making tools. In this editorial, we suggest psychological readiness for return to sport as a contributing, yet overlooked risk factor for reinjury in young athletes.

Psychological readiness for return to sport has been associated with the ability to achieve preinjury levels of sports participation following surgery.3 However, characteristics of psychological readiness, like self-efficacy (ie, confidence) and fear of reinjury, might be equally important indicators for risk of reinjury, although for very different reasons. The fear avoidance model has been applied to postoperative recovery following ACL reconstruction to describe how high fear of reinjury and low self-efficacy can lead to poor function.4 But this model also describes a mechanism where low fear and high self-efficacy can facilitate …
Mechanical circulatory support device-heart hysteretic interaction can predict left ventricular end diastolic pressure
Authors: Brian Y. Chang, Steven P. Keller, Sonya S. Bhavsar, Noam Josephy, Elazer R. Edelman
Journal: Science Translational Medicine (2018)

Variations in the driving motor current of a percutaneous ventricular assist device can be used to predict left ventricular end diastolic pressure.
Alcohol labels should include information on calorie content, public health doctors say
Authors: Anne Gulland
Journal: BMJ (2018)

Calorie content and health warnings should appear on the labels of alcoholic drinks, a report by public health doctors has urged.1

The Royal Society of Public Health has said that calorie content and a warning not to drink and drive should appear on the front of alcohol packaging, and health warnings, such as the risk of breast and bowel cancer, should appear on the rear.

The society warns of an “alcohol health awareness vacuum” with just 16% of people aware of the government’s alcohol guidelines, just one in 10 aware of the link between alcohol and cancer, …
Place de la cholangio-pancréatografie rétrograde endoscopique dans la prise en charge des complications biliaires du kyste hydatique du foie
Authors: H Hassine, M Sabbah, N Bibani, D Trad, H Elloumi, D Gargouri, A Ouakaa-Kchaou, J Kharrat
Journal: Endoscopy (2018)

Le kyste hydatique du foie (KHF) constitue encore un problème de santé publique en Tunisie. Ses complications biliaires inaugurales sont fréquentes variant entre 3 et 17%. La fistule biliaire externe (FBE) constitue la complication post-opératoire la plus commune. Ces deux situations requièrent un drainage biliaire endoscopique.
Contraceptive use by Palestine refugee mothers of young children attending UNRWA clinics: a cross-sectional follow-up study
Authors: Majed Hababeh, Wafaa Zeidan, Mariam Abdel El-Kader, Anwar Al Thaher, Nimer Kassim, Elias Habash, Hasan Arab, Ali Khader, Akihiro Seita
Journal: The Lancet (2018)
Endoscopies digestives basses (ECB) en réanimation: Quelle indication et pour quel bénéfice? une étude observationnelle rétrospective bicentrique
Authors: T Issoufaly, H Duboc, B Sztrymf, D Prat, D Roux, S Gaudry, D Dreyfuss, B Coffin, JD Ricard, J Messika
Journal: Endoscopy (2018)

L'endoscopie digestive basse (EDB) est indispensable dans l'investigation de certaines pathologies digestives basses, mais son bénéfice reste discuté chez les patients de réanimation, en raison de la complexité de la préparation colique. La rentabilité des coloscopies a été très peu étudiée dans ce contexte, c'est pourquoi nous avons voulu étudier les indications et la rentabilité diagnostique des EDB réalisées dans ces conditions.
An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans
Authors: Adil Mardinoglu, Hao Wu, Elias Bjornson, Cheng Zhang, Antti Hakkarainen, Sari M. Räsänen, Sunjae Lee, Rosellina M. Mancina, Mattias Bergentall, Kirsi H. Pietiläinen, Sanni Söderlund, Niina Matikainen, Marcus Ståhlman, Per-Olof Bergh, Martin Adiels, Brian D. Piening, Marit Granér, Nina Lundbom, Kevin J. Williams, Stefano Romeo, Jens Nielsen, Michael Snyder, Mathias Uhlén, Göran Bergström, Rosie Perkins, Hanns-Ulrich Marschall, Fredrik Bäckhed, Marja-Riitta Taskinen, Jan Borén
Journal: Cell Metabolism (2018)
Dysregulated invertebrate tropomyosin–dectin-1 interaction confers susceptibility to allergic diseases
Authors: Naina Gour, Stephane Lajoie, Ursula Smole, Marquitta White, Donglei Hu, Pagé Goddard, Scott Huntsman, Celeste Eng, Angel Mak, Sam Oh, Jung-Hyun Kim, Annu Sharma, Sophie Plante, Ikhlass Haj Salem, Yvonne Resch, Xiao Xiao, Nu Yao, Anju Singh, Susanne Vrtala, Jamila Chakir, Esteban G. Burchard, Andrew P. Lane, Marsha Wills-Karp
Journal: Science Immunology (2018)

Invertebrate tropomyosin homologs are ligands for dectin-1.
P091 Clusterin is increased in early rheumatoid arthritis and predicts disease activity and treatment response
Authors: T Lennerová, H Mann, O Ruickov, O Šléglová, L Vernerová, B Šumová, K Pavelka, J Vencovský, L Šenolt
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Clusterin (apolipoprotein J) is a molecular chaperone involved in a number of biological processes, such as inflammation and apoptosis. Recent data suggest its role in the development of autoimmune diseases and bone erosions. <h3>Objectives</h3> The aim of this study was to analyse the serum levels of clusterin in patients with early rheumatoid arthritis (RA) and in healthy controls, and to investigate the association of clusterin with disease activity and treatment response. <h3>Methods</h3> Clusterin serum levels were measured by ELISA (BioVendor) in 56 patients with early RA before and three months after treatment initiation, and in 56 age-/sex-matched healthy individuals. Disease activity was assessed by 28-joint Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI). Treatment response was calculated based on the SDAI/CDAI definition. Receiver operating characteristic (ROC) curve analysis was performed to predict disease activity and treatment response after six months of therapy. Data are presented as mean ±SD. <h3>Results</h3> Concentrations of clusterin at baseline were significantly higher in patients with early RA compared with healthy controls (75.1±12.4 vs 56.7±9.7, p&lt;0.001). After three months of therapy, clusterin levels decreased and were comparable to those in healthy subjects (57.7±9.7 vs 56.7±9.7, p&gt;0.05). Although clusterin levels did not correlate with disease activity at baseline, they positively correlated with CDAI and SDAI at month 3 (r=0.294, p=0.030 and r=0.269, p=0.047, respectively) and at month 6 after treatment initiation (r=0.318, p=0.021 and r=0.339, p=0.013, respectively). Using ROC analysis, clusterin baseline levels predicted moderate to high disease activity according to CDAI (AUC=0.829 (95% CI: 0.721 to 0.937), p&lt;0.001) and SDAI (AUC=0.709 (95% CI: 0.548 to 0.869), p=0.019), and major treatment response after 6 months of therapy (AUC=0.696 (95% CI: 0.549 to 0.842), p=0.015 for both). <h3>Conclusions</h3> We demonstrate here for the first time increased clusterin levels in patients with early rheumatoid arthritis and propose clusterin as a predictive biomarker for assessing disease activity and treatment response. <h3>Acknowledgements</h3> Supported by the project of MHCR for conceptual development of research organisation 00023728, research project SVV 260 373 and project GAUK No. 5 34 217. <h3>Disclosure of interest</h3> None declared
Place de la CPRE dans le traitement de l'angiocholite «Expérience d'un centre universitaire marocain»
Authors: I Nakhcha, A Essaid El Feydi, I Benelbarhdadi, FZ Ajana
Journal: Endoscopy (2018)

L'angiocholite est une urgence thérapeutique. Le traitement endoscopique s'impose pour effectuer un bon drainage et lever l'obstacle existant. Le but de notre travail est d'évaluer l'efficacité de ce traitement et partager notre expérience dans le traitement de l'angiocholite.
A New Year’s Wish on Opioids
Authors: Joshua M. Sharfstein
Journal: JAMA (2018)

It's a lot more cost effective and more readily available and you can get a feel for what would be the potential of a compound in multiple types of ALS," she said."There is a lot of power in the simple models that is not utilized to its maximum extent."In addition to pimozide, there are other compounds entering the early stages of the drug pipeline, Bruijn said."This is an incredibly robust time for ALS research," she said."There's such an energy in the community and so many advances scientifically that I am very hopeful that we will find better treatments and more treatments in the years to come."The FDA approved edaravone in May 2017.It was the first drug approved specifically for ALS in 22 years, according to the ALS
A novel splice variant of human Ep-CAM as a potential therapeutic antibody target for epithelial cell-based cancers
Authors: Shu-Hui Liu, Kristen Michelson, Maria Rodriguez, Roberto A. Macina, Jackie Papkoff
Journal: Cancer Research (2005)

2706  Ep-CAM is a 40kDa transmembrane glycoprotein expressed on the basolateral surface of normal epithelia. Ep-CAM protein is significantly upregulated on the cell surface of a variety of carcinomas and consequently is being developed as a therapeutic target for both active and passive immunotherapy. Through internal efforts to find alternative transcripts associated with cancer, we identified a novel splice variant of Ep-CAM, named DD-O232v3. We validated the expression of this novel mRNA in human cancer tissues. The mRNA expression of DD-O232v3 is more cancer-specific than Ep-CAM, using real-time quantitative RT-PCR. For example, Ep-CAM mRNA exhibits significant expression in normal colon tissue, whereas DD-O232v3 mRNA is largely undetected in such samples. Aligning the coding region of Ep-CAM with that of DD-O232v3 shows that DD-O232v3 has 76 additional amino acids within the extracellular domain, a region thought to be important for the cell-cell adhesion function of Ep-CAM. In addition, there are potential integrin-binding and arginine-rich domains within the novel DD-O232v3 coding regions. We are investigating the functional significance of these regions, especially with respect to their potential role in cell-to-cell or cell-matrix adhesion. DD-O232v3 is expressed as a 48 kDa glycoprotein in transiently transfected 293T cells. Cell surface biotinylation and immunofluorescence experiments with live cells confirm that the exogenously-expressed DD-O232v3 predominantly localizes to the plasma membrane. Furthermore, cells overexpressing Ep-CAM or DD-O232v3 are efficiently killed by incubation first with a specific monoclonal antibody, followed by a toxin-conjugated secondary antibody. These data suggest that both proteins are capable of internalizing bound antibodies. Literature reports have shown that overexpression of Ep-CAM enhances cell proliferation and promotes colony formation in transfected cells. Experiments to better understand the role of DD-O232v3 in cell growth and transformation are underway. Taken together, the cancer-specific overexpression, cell surface localization and the potential to internalize, make DD-O232v3 a promising target for therapeutic antibodies. We are currently generating and testing specific monoclonal antibodies against the novel regions of DD-O232v3 to validate their potential as anti-tumor agents.
Galectin-3 Promotes Vascular Remodeling and Contributes to Pulmonary Hypertension
Authors: Scott A. Barman, Feng Chen, Xueyi Li, Stephen Haigh, David W. Stepp, Dmitry Kondrikov, Keyvan Mahboubi, Zsuzsanna Bordan, Peter Traber, Yunchao Su, David J. R. Fulton
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

0.727-0.840),but mortality in women who used CPAP increased (odds ratio, 1.320; 95% confidence interval, 1.151-1.515).In men, significant interactions were found for cerebrovascular disease, diabetes mellitus, and hypertension, but patients treated with CPAP had a lower probability of death than control subjects in all scenarios (Table 1).On the other hand, CPAP treatment was associated with lower mortality in women with cerebrovascular disease but had a neutral or detrimental effect on mortality in other scenarios (Table 1).Overall, the population of patients treated with CPAP in Catalonia had lower mortality rates than age-, sex-, and regionmatched control subjects, despite a higher prevalence of most comorbidities among patients treated with CPAP.However, this finding was driven by the 74% of men in the population, because CPAP was associated with increased mortality among women.These population-based findings contrast with the less positive findings of the randomized SAVE study (3).In contrast, our results are consistent with recently published data from a Danish historical cohort (22,135 patients with OSA), which showed that CPAP treatment was associated with lower mortality rates in middle-aged and elderly men after adjustment for multiple comorbidities, but not in women (5).Although in our population sex differences in the results seem to be related to a high heart failure prevalence among women using CPAP, further research is needed on the potentially different characteristics of OSA, and associated comorbidities, among women and men.Finally, several potential limitations should be noted.First, the data used in this study lack information about CPAP adherence.Second, it was not possible to control for undiagnosed OSA in control subjects, and, finally, the observational design means that potential confounding from uncontrolled factors such as socioeconomic status, level of health literacy and self-care, or level of delivered health care cannot be avoided.In conclusion, these findings suggest that CPAP treatment is associated with reductions in mortality at the population level, although only in men.Therefore, further analyses should be planned within the frame of precision medicine (6) to clarify which patients with OSA could benefit the most from CPAP treatment and whether CPAP might be detrimental in some specific patient subgroups.