tbuckley/cabot-search huggingface dataset:
Development of Early Adiposity in Infants of Mothers With Gestational Diabetes Mellitus
Authors: Karen M. Logan, Robby J. Emsley, Suzan Jeffries, Izabela Andrzejewska, Matthew J. Hyde, Chris Gale, Karyn Chappell, Sundhiya Mandalia, Shalini Santhakumaran, James R.C. Parkinson, Luke Mills, Neena Modi
Journal: Diabetes Care (2016)

Infants born to mothers with gestational diabetes mellitus (GDM) are at greater risk of later adverse metabolic health. We examined plausible candidate mediators, adipose tissue (AT) quantity and distribution and intrahepatocellular lipid (IHCL) content, comparing infants of mothers with GDM and without GDM (control group) over the first 3 postnatal months.We conducted a prospective longitudinal study using MRI and spectroscopy to quantify whole-body and regional AT volumes, and IHCL content, within 2 weeks and 8-12 weeks after birth. We adjusted for infant size and sex and maternal prepregnancy BMI. Values are reported as the mean difference (95% CI).We recruited 86 infants (GDM group 42 infants; control group 44 infants). Mothers with GDM had good pregnancy glycemic control. Infants were predominantly breast-fed up to the time of the second assessment (GDM group 71%; control group 74%). Total AT volumes were similar in the GDM group compared with the control group at a median age of 11 days (-28 cm(3) [95% CI -121, 65], P = 0.55), but were greater in the GDM group at a median age of 10 weeks (247 cm(3) [56, 439], P = 0.01). After adjustment for size, the GDM group had significantly greater total AT volume at 10 weeks than control group infants (16.0% [6.0, 27.1], P = 0.002). AT distribution and IHCL content were not significantly different at either time point.Adiposity in GDM infants is amplified in early infancy, despite good maternal glycemic control and predominant breast-feeding, suggesting a potential causal pathway to later adverse metabolic health. Reduction in postnatal adiposity may be a therapeutic target to reduce later health risks.
188P Modified FOLFOX-6 as 1st line therapy for adenocarcinoma of unknown primary: a multicenter phase II study
Authors: D.-Y. Shin, H.-R. Lee, I.I. Na, Y.J. Yuh, B.S. Kim, I.J. Chung, W.-K. Bae, H.-J. Shim, E.-K. Song, S.H. Yang, H.J. Kang
Journal: Annals of Oncology (2015)
Thermostabilization of inactivated polio vaccine in PLGA-based microspheres for pulsatile release
Authors: Stephany Y. Tzeng, Rohiverth Guarecuco, Kevin J. McHugh, Sviatlana Rose, Evan M. Rosenberg, Yingying Zeng, Robert Langer, Ana Jaklenec
Journal: Journal of Controlled Release (2016)

Vaccines are a critical clinical tool in preventing illness and death due to infectious diseases and are regularly administered to children and adults across the globe. In order to obtain full protection from many vaccines, an individual needs to receive multiple doses over the course of months. However, vaccine administration in developing countries is limited by the difficulty in consistently delivering a second or third dose, and some vaccines, including the inactivated polio vaccine (IPV), must be injected more than once for efficacy. In addition, IPV does not remain stable over time at elevated temperatures, such as those it would encounter over time in the body if it were to be injected as a single-administration vaccine. In this manuscript, we describe microspheres composed of poly(lactic-co-glycolic acid) (PLGA) that can encapsulate IPV along with stabilizing excipients and release immunogenic IPV over the course of several weeks. Additionally, pH-sensitive, cationic dopants such as Eudragit E polymer caused clinically relevant amounts of stable IPV release upon degradation of the PLGA matrix. Specifically, IPV was released in two separate bursts, mimicking the delivery of two boluses approximately one month apart. In one of our top formulations, 1.4, 1.1, and 1.2 doses of the IPV serotype 1, 2, and 3, respectively, were released within the first few days from 50 mg of particles. During the delayed, second burst, 0.5, 0.8, and 0.6 doses of each serotype, respectively, were released; thus, 50 mg of these particles released approximately two clinical doses spaced a month apart. Immunization of rats with the leading microsphere formulation showed more robust and long-lasting humoral immune response compared to a single bolus injection and was statistically non-inferior from two bolus injections spaced 1 month apart. By minimizing the number of administrations of a vaccine, such as IPV, this technology can serve as a tool to aid in the eradication of polio and other infectious diseases for the improvement of global health.
Reciprocal interplay between thyroid hormone and microRNA-21 regulates hedgehog pathway–driven skin tumorigenesis
Authors: Daniela Di Girolamo, Raffaele Ambrosio, Maria A. De Stefano, Giuseppina Mancino, Tommaso Porcelli, Cristina Luongo, Emery Di Cicco, Giulia Scalia, Luigi Del Vecchio, Annamaria Colao, Andrzej A. Dlugosz, Caterina Missero, Domenico Salvatore, Monica Dentice
Journal: Journal of Clinical Investigation (2016)

The thyroid hormone–inactivating (TH-inactivating) enzyme type 3 iodothyronine deiodinase (D3) is an oncofetal protein that is rarely expressed in adult life but has been shown to be reactivated in the context of proliferation and neoplasms. D3 terminates TH action within the tumor microenvironment, thereby enhancing cancer cell proliferation. However, the pathological role of D3 and the contribution of TH metabolism in cancer have yet to be fully explored. Here, we describe a reciprocal regulation between TH action and the cancer-associated microRNA-21 (miR21) in basal cell carcinoma (BCC) skin tumors. We found that, besides being negatively regulated by TH at the transcriptional level, miR21 attenuates the TH signal by increasing D3 levels. The ability of miR21 to positively regulate D3 was mediated by the tumor suppressor gene GRHL3, a hitherto unrecognized D3 transcriptional inhibitor. Finally, in a BCC mouse model, keratinocyte-specific D3 depletion markedly reduced tumor growth. Together, our results establish TH action as a critical hub of multiple oncogenic pathways and provide functional and mechanistic evidence of the involvement of TH metabolism in BCC tumorigenesis. Moreover, our results identify a miR21/GRHL3/D3 axis that reduces TH in the tumor microenvironment and has potential to be targeted as a therapeutic approach to BCC.
Abstract 455: Peri-interventional Antiplatelet Effect of Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention is Attenuated by Cytochrome P450 2C19*2 Polymorphism
Authors: Dietmar Trenk, Willibald Hochholzer, Herz-Zentrum Bad Krozingen, Martin F Fromm, Ligia Chialda, Andreas Pahl, Franz-Josef Neumann
Journal: Circulation (2007)

The thienopyridine derivative clopidogrel is an inactive pro-drug requiring biotransformation by cytochrome P450 isoenzymes (CYP) in order to generate an active metabolite. This metabolite inhibits irreversibly the platelet P2Y12 receptor, thereby exerting the antiplatelet effect of the drug. The EXCELSIOR study showed a 7-fold 30-day risk of major adverse cardiac events in patients with inadequate peri-interventional platelet response to loading with clopidogrel 600 mg. Studies in healthy volunteers on the impact of the CYP2C19 genotype to the interindividual variability in antiplatelet effect of clopidogrel showed conflicting results. The EXCELSIOR study enrolled 802 patients undergoing elective percutaneous coronary intervention (PCI) with stent implantation. The antiplatelet effect of a loading dose of clopidogrel 600 mg was determined by optical aggregometry (5μM ADP) before administration of clopidogrel, at the time of PCI and pre-discharge at day 1after PCI. CYP2C19 genotype (681G&gt;A) was analyzed in 697 patients by real-time PCR. Antiplatelet efficacy of clopidogrel was determined for the different genotypes. Within the subset of the EXCELSIOR cohort, 485 patients (69.6%) were CYP2C19 wild-type homozygous (*1/*1), 199 (28.6%) were CYP2C19*1/*2 and 13 (1.9%) were CYP2C19*2/*2 carrying two allelic variants encoding a deficient CYP2C19 enzyme. Residual platelet aggregation (median; interquartile ranges) determined 5 minutes after addition of ADP 5μM is summarized in relation to the CYP2C19 genotypes in the Table below. These results indicate that the antiplatelet response to a loading dose of clopidogrel 600 mg is substantially attenuated in patients carrying at least one CYP2C19*2 allele. It seems that the CYP2C19 genotype is a major factor contributing to the observed variability in the antiplatelet effect of clopidogrel and might therefore affect clinical outcome of patients undergoing PCI. Relationship Between Genotype and ADP-induced Platelet Aggregation (%)
Biologic Therapies and Risk of Infection and Malignancy in Patients With Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis
Authors: Stefanos Bonovas, Gionata Fiorino, Mariangela Allocca, Theodore Lytras, Georgios K. Nikolopoulos, Laurent Peyrin-Biroulet, Silvio Danese
Journal: Clinical Gastroenterology and Hepatology (2016)
Dynamics of the erythropoiesis stimulating agent resistance index in incident hemodiafiltration and high-flux hemodialysis patients
Authors: Daniele Marcelli, Inga Bayh, José I. Merello, Pedro Ponce, Alex Heaton, Fatih Kircelli, Charles Chazot, Attilio Di Benedetto, Cristina Marelli, Erzsebet Ladanyi, Miroslaw Kroczak, Stefano Stuard, Aileen Grassmann, Laura Scatizzi, Katharina Brand, Bernard Canaud
Journal: Kidney International (2016)
329P Afatinib activity against head-and-neck or esophageal squamous cell carcinoma: Significance of activating oncogenic HER4 mutations in head-and-neck squamous cell carcinoma
Authors: Y. Togashi, Y. Nakamura, S. Tomida, H. Hayashi, M.A. de Velasco, K. Sakai, Y. Fujita, S. Hamada, K. Nishio
Journal: Annals of Oncology (2015)
Family or individual therapy: the ethics of modality choice
Authors: R C Sider, C Clements
Journal: American Journal of Psychiatry (1982)

The authors examine the ethical issues in choosing between individual and social unit (marital and family) therapies. Although usually neglected in the literature, these ethical questions are important and complex. A general systems perspective is used to provide a framework for ethical analysis. The core of the ethical problem is shown to be the interdependence and irreducible conflict inherent between the individual and social unit levels. The authors outline a general systems approach to identification and consideration of these ethical issues in clinical practice.
Family Caregivers’ Awareness of Illness and Attitude Toward Disclosure During Chemotherapy for Advanced Cancer
Authors: S.H. Byun, S. Kim, Y. Ko, S.Y. Kwon, J.H. Cheon, D.Y Shin, C.H. Kim, S.H. Yang, S.J Cho, I.I. Na
Journal: Annals of Oncology (2014)
Erratum to: A quantitative literature-curated gold standard for kinase-substrate pairs
Authors: Sara Sharifpoor, Alex N Nguyen Ba, Ji-Young Youn, Dewald van Dyk, Helena Friesen, Alison C Douglas, Christoph F Kurat, Yolanda T Chong, Karen Founk, Alan M Moses, Brenda J Andrews
Journal: Genome biology (2012)
Evaluating Cancer of the Central Nervous System Through Next-Generation Sequencing of Cerebrospinal Fluid
Authors: Elena I. Pentsova, Ronak H. Shah, Jiabin Tang, Adrienne Boire, Daoqi You, Samuel Briggs, Antonio Omuro, Xuling Lin, Martin Fleisher, Christian Grommes, Katherine S. Panageas, Fanli Meng, S. Duygu Selcuklu, Shahiba Ogilvie, Natalie Distefano, Larisa Shagabayeva, Marc Rosenblum, Lisa M. DeAngelis, Agnes Viale, Ingo K. Mellinghoff, Michael F. Berger
Journal: Journal of Clinical Oncology (2016)

Cancer spread to the central nervous system (CNS) often is diagnosed late and is unresponsive to therapy. Mechanisms of tumor dissemination and evolution within the CNS are largely unknown because of limited access to tumor tissue.We sequenced 341 cancer-associated genes in cell-free DNA from cerebrospinal fluid (CSF) obtained through routine lumbar puncture in 53 patients with suspected or known CNS involvement by cancer.We detected high-confidence somatic alterations in 63% (20 of 32) of patients with CNS metastases of solid tumors, 50% (six of 12) of patients with primary brain tumors, and 0% (zero of nine) of patients without CNS involvement by cancer. Several patients with tumor progression in the CNS during therapy with inhibitors of oncogenic kinases harbored mutations in the kinase target or kinase bypass pathways. In patients with glioma, the most common malignant primary brain tumor in adults, examination of cell-free DNA uncovered patterns of tumor evolution, including temozolomide-associated mutations.The study shows that CSF harbors clinically relevant genomic alterations in patients with CNS cancers and should be considered for liquid biopsies to monitor tumor evolution in the CNS.
Blood donation, body iron stores, and risk of myocardial infarction
Authors: H. Hemila, M. Paunio, T.-P. Tuomainen, R. Salonen, K. Nyyssonen, J. T Salonen
Journal: BMJ (1997)

Nicotine replacement therapy should be prescribable on NHSEditor-I welcome the publication of the open letter to the prime minister about tobacco-the most important preventable cause of death in Europe. 1 As Jo E Asvall points out in the letter, tobacco control demands the support of, and action by, the total government, not just the Department of Health.Among the actions Asvall calls for is that "support for smoking cessation is made widely available, particularly through primary health care professionals, including doctors, nurses, pharmacists, and dentists."Nicotine replacement therapy (nicotine gum, patches, nasal spray, and oral inhaler) is now fully established as an effective adjunct to such professional advice and support.Systematic review of many trials has shown a doubling of sustained smoking cessation when nicotine replacement therapy is compared with placebo. 2 The offer of nicotine patches to motivated subjects for a week in the first instance could be a useful policy. 3 But the recommendation of such therapy by health professionals and the use of such therapy by smokers are severely limited by NHS "blacklisting."I can prescribe on the NHS for alcohol problems and even obesity.I can also prescribe for tobacco addiction-but only products of unproved efficacy for this problem, such as tranquillisers and antidepressants, not one of proved effectiveness.Why not nicotine replacement therapy?So much for evidence based medicine.
18F-NaF PET/CT Imaging of Brain Metastases
Authors: Matteo Salgarello, Gianluigi Lunardi, Alessandro Inno, Stefano Pasetto, Fabrizia Severi, Giancarlo Gorgoni, Stefania Gori
Journal: Clinical Nuclear Medicine (2016)

F-NaF is a radiopharmaceutical widely used in PET imaging to detect bone metastases. Several cases of F-NaF uptake from brain metastases have been described, but a specific protocol for the evaluation of brain metastases with F-NaF has not been developed yet. Here we report images of F-NaF PET/CT, standard CT, and MRI of a brain metastasis in a patient with non-small lung cancer. Through a dynamic acquisition procedure, we have identified the first minutes after injection as the preferable time point of imaging acquisition for the study of brain metastases with F-NaF.
Prognostic Significance Of rs6773853 Susceptibility Locus In B-Cell Non-Hodgkin’s Lymphoma
Authors: Joycelyn Jie Xin Lee, Glorijoy Shi En Tan, Chee Hian Tan, Summer Pan, Chiea Chuen Khor, Jianjun Liu, Jia Nee Foo, Soo Yong Tan, Siok Bian Ng, Miriam Tao, Soon Thye Lim, Tiffany Tang
Journal: Blood (2013)
The relationship between biochemical failure and TP53 genetic polymorphism in patients with prostate cancer
Authors: E. Silva, F. M. Calais da Silva, A. Sousa, A. Coelho, R. Medeiros
Journal: Journal of Clinical Oncology (2007)

5133 Background: TP53 is a tumour suppressor gene, located at chromosome 17p13, referred as altered in 50–55% of cancer cases. The p53 protein, encoded by the TP53 gene, is known as the cellular gatekeeper for growth and division, as it plays an essential role in safeguarding the integrity of the genome. This protein is involved in processes as cell cycle arrest, gene transcription, DNA repair and apoptosis and may influence cancer progression. Few studies have been published regarding TP53 codon 72 genetic polymorphism and prostate cancer behaviour. Methods: We analysed the frequency of TP53 codon 72 genetic polymorphism in DNA isolated from blood samples of 265 individuals with prostate cancer using the Real-time PCR methodology. Biochemical failure was defined as two successive post- treatment rises in serum PSA, greater than 50 %. Results: From the 265 prostate cancer cases, we observed that 54.7% were found to be homozygous for the Arg allele (AA), 38.1% were heterozygous (AP) and 7.2% homozygous for the Pro allele (PP). We find that individuals carriers of PP genotype have three fold increased risk of biochemical relapse (OR=3.43, 95% CI 1.31–9.01; p= 0.008). Furthermore, we observed that this genotype was not associated to the gleason score (OR=1.66, 95%CI 0.53–5.13; p=0.372) or the presence of advanced disease (OR=1.69, 95%CI 0.62–4.6; p=0.296). Conclusions: We demonstrate that TP53 codon 72 genetic polymorphism may influence the clinical progression of patients with prostate cancer. Furthermore, our results are consistent with literature regarding other neoplasia suggesting that the Pro allele was associated to a poorer prognosis and survival. No significant financial relationships to disclose.
Original Lithotomy Positioning for Transperineal Extracorporeal Shockwave Lithotripsy for Distal Ureteric Calculi with Tripter X1
Authors: R. Andrianne, C. Vandeberg, P. Bonnet, H. Nicolas, L. Coppens, C. Bouffioux, J. de Leval
Journal: European Urology (1992)
Improved survival with combination oxaliplatin, irinotecan, cetuximab for metastatic pancreatic cancer
Authors: F. Lee, M. Roach, L. Duong, G. Heywood, G. Parasher, K. Rasila
Journal: Journal of Clinical Oncology (2007)

15180 Background: For metastatic pancreatic cancer, no combination chemotherapy has been shown to improve survival significantly in comparison to single agent gemcitabine. A novel combination with oxaliplatin 60 mg/m 2 , irinotecan 90 mg/m 2 , cetuximab 250 mg/m 2 (OIC) given every two weeks appears to produce a high rate of radiographic response. Since our reporting (ASCO 2007 GI Conference), we continue to see a high rate of clinical and radiographic responses (50% by Recist Criteria). We therefore decided to look carefully on the survival data of OIC versus control (mainly gemcitabine single agent or in combination with other agents). Methods: We retrospective reviewed patients seen from 10/2002 to 10/2006 with diagnosis of metastatic pancreatic cancer. The survival duration was calculated from the date of diagnosis to the date of death. We included only patients whose dates of death could be confirmed with death certificates. Results: A total of 37 patients were identified. 11 of those were in the OIC arm and 26 were treated with other regimens (17 with gemcitabine-based regimens, 9 with either capecitabine or 5-FU-based regimens) that function as control. The range of survival duration was 4 - 28 months for OIC arm and 1 - 28 months for the control. Median survival was 10 months for the OIC arm versus 5 months for the control. Conclusions: OIC regimen produces a high rate of tumor response and may have a survival advantage with this retrospective analysis. We believe it is a regimen deserves further evaluation. No significant financial relationships to disclose.
P08.05 * INTRACRANIAL METASTASES IN PATIENTS WITH OVARIAN CARCINOMA
Authors: R. M. Buhl, N. Tiebel
Journal: Neuro-Oncology (2014)

Brain metastases in patients with ovarian carcinoma are extremely rare. Only 1.7% of these patients develop brain metastases. The prognosis in these patients appears to be poor.We report 4 female patients with intracranial single metastase who were treated in our institution within the last 2 years. The age of the patients at time of operation were 43, 66, 74 and 76 years. The interval between diagnosis of ovarian carcinoma and brain metastasis was 3 years in 2 patients, 4 and 7 years. Two patients had supratentorial metastasis in the frontal lobe and the other 2 were located infratentorially in the cerebellum. Histopathological examinations showed typical signs of metastasis of the primary carcinoma. Postoperative outcome was good and further radio- and chemotherapy was performed. Interdisciplinary management with the gynecologists is mandatory. Though brain metastases of ovarian cancer is very rare it has to be kept in mind in the preoperative differential diagnosis and planning of the operation. Mean average age is 54 years and mean interval between diagnosis of ovarian carcinoma and metastases is about 2 years. Median survival time postoperatively is about 6 months.
Routine follow up of breast cancer in primary care
Authors: D. Rainsbury
Journal: BMJ (1996)

Routine follow up ofbreast cancer in primary care Follow up by non-specialists should not be encouraged EDITOR,-While I welcome new initiatives in the management of breast cancer, I believe that the study by Eva Grunfeld and colleagues must be interpreted with caution.'The authors report no delay in the diagnosis of recurrent breast cancer or reduction in the quality of life of patients randomised to follow up by their general practitioner, but their conclusions must be questioned.The data on recurrence are based on a
A Global, Neutral Platform for Sharing Trial Data
Authors: Barbara E. Bierer, Rebecca Li, Mark Barnes, Ida Sim
Journal: New England Journal of Medicine (2016)

ward.Instead of spending time and resources on complicated techniques to try to deidentify and anonymize complex patient data -and risk failing and making populations or patient groups skeptical about the whole concept of data sharing -it may be better to define a core set of data that can be released (and freely accessed) from all trials and to allow sharing of the more complex data only through real and inclusive collaborations, the way successful data sharing related to specific diseases already happens in global health today."It is not only about sharing of the raw data, but sharing of the questions, the problems, and the code that everybody is using," Shasha Jumbe said."It means collaborations throughout the whole process, definition of the goals, framing of the questions -and also thinking about inclusive attribution all the way from subjects that are part of these studies to the data science team.
Teaching interactions are based on motor behavior embodiment
Authors: Ludovic Marin
Journal: Behavioral and Brain Sciences (2015)

Abstract In Kline's target article, the role of motor behavior in teaching is missing. However, it is so important that we cannot avoid taking into account the movements of another person when performing our own movements. Moreover, the state of mind is embodied. Consequently, teaching should integrate the role of motor behavior to enhance teacher/learner social interactions.