tbuckley/cabot-search huggingface dataset:
Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial
Authors: Noriyuki Katsumata, Makoto Yasuda, Seiji Isonishi, Fumiaki Takahashi, Hirofumi Michimae, Eizo Kimura, Daisuke Aoki, Toshiko Jobo, Shoji Kodama, Fumitoshi Terauchi, Toru Sugiyama, Kazunori Ochiai
Journal: The Lancet Oncology (2013)
Seven-year follow-up after dobutamine stress echocardiography
Authors: Elena Biagini, Abdou Elhendy, Jeroen J. Bax, Vittoria Rizzello, Arend F.L. Schinkel, Ron T. van Domburg, Miklos D. Kertai, Boudewijn J. Krenning, Manolis Bountioukos, Claudio Rapezzi, Angelo Branzi, Maarten L. Simoons, Don Poldermans
Journal: Journal of the American College of Cardiology (2004)
AT13148 Is a Novel, Oral Multi-AGC Kinase Inhibitor with Potent Pharmacodynamic and Antitumor Activity
Authors: Timothy A. Yap, Mike I. Walton, Kyla M. Grimshaw, Robert H. te Poele, Paul D. Eve, Melanie R. Valenti, Alexis K. de Haven Brandon, Vanessa Martins, Anna Zetterlund, Simon P. Heaton, Kathrin Heinzmann, Paul S. Jones, Ruth E. Feltell, Matthias Reule, Steven J. Woodhead, Thomas G. Davies, John F. Lyons, Florence I. Raynaud, Suzanne A. Eccles, Paul Workman, Neil T. Thompson, Michelle D. Garrett
Journal: Clinical Cancer Research (2012)

Deregulated phosphatidylinositol 3-kinase pathway signaling through AGC kinases including AKT, p70S6 kinase, PKA, SGK and Rho kinase is a key driver of multiple cancers. The simultaneous inhibition of multiple AGC kinases may increase antitumor activity and minimize clinical resistance compared with a single pathway component.We investigated the detailed pharmacology and antitumor activity of the novel clinical drug candidate AT13148, an oral ATP-competitive multi-AGC kinase inhibitor. Gene expression microarray studies were undertaken to characterize the molecular mechanisms of action of AT13148.AT13148 caused substantial blockade of AKT, p70S6K, PKA, ROCK, and SGK substrate phosphorylation and induced apoptosis in a concentration and time-dependent manner in cancer cells with clinically relevant genetic defects in vitro and in vivo. Antitumor efficacy in HER2-positive, PIK3CA-mutant BT474 breast, PTEN-deficient PC3 human prostate cancer, and PTEN-deficient MES-SA uterine tumor xenografts was shown. We show for the first time that induction of AKT phosphorylation at serine 473 by AT13148, as reported for other ATP-competitive inhibitors of AKT, is not a therapeutically relevant reactivation step. Gene expression studies showed that AT13148 has a predominant effect on apoptosis genes, whereas the selective AKT inhibitor CCT128930 modulates cell-cycle genes. Induction of upstream regulators including IRS2 and PIK3IP1 as a result of compensatory feedback loops was observed.The clinical candidate AT13148 is a novel oral multi-AGC kinase inhibitor with potent pharmacodynamic and antitumor activity, which shows a distinct mechanism of action from other AKT inhibitors. AT13148 will now be assessed in a first-in-human phase I trial.
One-Year Reductions in Body Weight and Blood Pressure, but Not in Visceral Fat Accumulation and Adiponectin, Improve Urinary Albumin-to-Creatinine Ratio in Middle-Aged Japanese Men
Authors: Hideaki Nakatsuji, Ken Kishida, Tohru Funahashi, Midori Noguchi, Tomoko Ogawa, Yukiyoshi Okauchi, Hitoshi Nishizawa, Tadashi Nakamura, Yuji Matsuzawa, Iichiro Shimomura
Journal: Diabetes Care (2010)

Microalbuminuria has been recognized recently as a risk factor for cardiovascular diseases as well as renal failure and is often found in subjects with metabolic syndrome. The relationship between visceral fat accumulation and microalbuminuria, urinary albumin-to-creatinine ratio (UACR), has not been fully clarified. Our cross-sectional study demonstrated that visceral fat accumulation is associated with increases in UACR. However, the accompanying obesity-related risk factors, especially hemoglobin A1c (HbA1c) and elevated blood pressure, strongly increased the risk of UACR (1). We have reported that reductions in both body weight and estimated visceral fat area (eVFA) measured by the bioelectrical impedance analysis method (2) were accompanied by reductions in the number of obesity-related cardiovascular risk factors (3) and increases in serum levels of adiponectin (4) in our longitudinal Amagasaki Visceral Fat Study, in which intensive risk factor–oriented health promotion programs were …
Abnormal in vitro proliferation and differentiation of T cell colony-forming cells in patients with tropical spastic paraparesis/human T lymphocyte virus type I (HTLV-I)-associated myeloencephalopathy and healthy HTLV-I carriers.
Authors: Y Lunardi-Iskandar, A Gessain, V H Lam, R C Gallo
Journal: The Journal of Experimental Medicine (1993)

T cell colonies were generated from the peripheral blood mononuclear cells (PBMC) of 10 patients with tropical spastic paraparesis/human T lymphocyte virus type I (HTLV-I)-associated myeloencephalopathy (TSP/HAM), two healthy HTLV-I carriers, and 17 healthy HTLV-I-seronegative subjects. PBMC were cultured in methylcellulose in the absence of added growth factors (spontaneous T cell colonies), or in the presence of phorbol myristate acetate and interleukin 2 (induced T cell colonies). PBMC T cell colony-forming cells (T-CFC) from all TSP/HAM patients and HTLV-I carriers were able to grow in the absence of added growth factors and/or mitogenic stimulation. Pooled spontaneous and induced colonies were composed of cells bearing CD3+, CD4+, CD8+, and CD1+ antigens. Colonies from normal HTLV-I-seronegative subjects displayed mature cells bearing the CD3+, CD4+, CD8+, and CD1- surface phenotype. In addition, spontaneous and induced T cell colonies expressed HTLV-I antigens in 18-38% of the cells from TSP/HAM patients and HTLV-I carriers. These results demonstrate that HTLV-I infection is associated with an abnormal proliferation and differentiation of T cell progenitors in vitro and that the T-CFC from HTLV-I-seropositive individuals are infected, suggesting that T-CFC abnormalities may play a predominant role in the pathophysiology of HTLV-I.
NORMATIVE VALUES FOR THE SCAT3 IN ADOLESCENT ATHLETES
Authors: A Brooks, K MacDonald, N Wasylyk, S Hetzel, T McGuine
Journal: British Journal of Sports Medicine (2014)

Background Sport Concussion Assessment Tool (SCAT3) was published March 2013 to allow more complete clinical assessment of concussed athletes. Objective Establish normative SCAT3 values in adolescent athletes. Design Prospective cohort. Setting 7 Wisconsin high schools. Participants 758 (187 Female, 571 Male) athletes (age 15.9±1.1 yrs.) in 19 sports. Risk factor assessment SCAT3 administered summer 2013. Subjects reported previous SRC history in past 12 months. Main outcome measurements Total symptoms (TS, 0–22), symptom severity (SS, 0–132), total Standardized Assessment of Concussion (SAC, 0–30), Orientation (OR, 0–5), Immediate Memory (IM, 0–15), Concentration (CO, 0–5), Delayed Recall (DR, 0–5), Balance Error Scoring System (BESS, 0–20). T-tests (P&lt;.05) used to test for differences based on sex and previous history of SRC. Results Mean scores (95% CI) were: TS 1.32 (1.31–1.33); SS 2.15 (1.80–2.48); total SAC 26.12 (25.90–26.26); OR 4.69 (4.64–4.72); IM 14.25 (14.15–14.31); CO 3.25 (3.15–3.33); DR 3.93 (3.85–3.99); BESS 13.46 (13.05–13.79). No difference in baseline scores by sex: SS (P=.51), IM (P=.37), CO (P=.30), DR (P=.19), BESS (P=.98). Males had higher TS (1.41 vs 1.04, P=.05) and lower total SAC (26.02 vs 26.4, P=.03), and OR (4.66 vs 4.76, P=.02). No difference in baseline scores by previous SRC history for total SAC (P=.18), OR (P=.57), IM (P=.13), CO (P=.69), DR (P=.53), BESS (P=.06). Athletes with previous SRC reported higher TS (1.91 vs 1.25, P=.01) and SS (3.33 vs 2.0, P=.02). Conclusions Normative SCAT3 values in adolescent athletes vary by gender and previous SRC history.
Premature mortality in people with epilepsy in rural China: a prospective study
Authors: Ding Ding, Wenzhi Wang, Jianzhong Wu, Guangyu Ma, Xiuying Dai, Bin Yang, Taiping Wang, Chenglin Yuan, Zhen Hong, Hanneke M de Boer, Leonid Prilipko, Josemir W Sander
Journal: The Lancet Neurology (2006)
MicroRNA Expression in Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus: Associations with Survival
Authors: Ewy A. Mathé, Giang Huong Nguyen, Elise D. Bowman, Yiqiang Zhao, Anuradha Budhu, Aaron J. Schetter, Rosemary Braun, Mark Reimers, Kensuke Kumamoto, Duncan Hughes, Nasser K. Altorki, Alan G. Casson, Chang-Gong Liu, Xin Wei Wang, Nozomu Yanaihara, Nobutoshi Hagiwara, Andrew J. Dannenberg, Masao Miyashita, Carlo M. Croce, Curtis C. Harris
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The dismal outcome of esophageal cancer patients highlights the need for novel prognostic biomarkers, such as microRNAs (miRNA). Although recent studies have established the role of miRNAs in esophageal carcinoma, a comprehensive multicenter study investigating different histologic types, including squamous cell carcinoma (SCC) and adenocarcinoma with or without Barrett's, is still lacking. Experimental Design: miRNA expression was measured in cancerous and adjacent noncancerous tissue pairs collected from 100 adenocarcinoma and 70 SCC patients enrolled at four clinical centers from the United States, Canada, and Japan. Microarray-based expression was measured in a subset of samples in two cohorts and was validated in all available samples. Results: In adenocarcinoma patients, miR-21, miR-223, miR-192, and miR-194 expression was elevated, whereas miR-203 expression was reduced in cancerous compared with noncancerous tissue. In SCC patients, we found elevated miR-21 and reduced miR-375 expression levels in cancerous compared with noncancerous tissue. When comparing cancerous tissue expression between adenocarcinoma and SCC patients, miR-194 and miR-375 were elevated in adenocarcinoma patients. Significantly, elevated miR-21 expression in noncancerous tissue of SCC patients and reduced levels of miR-375 in cancerous tissue of adenocarcinoma patients with Barrett's were strongly associated with worse prognosis. Associations with prognosis were independent of tumor stage or nodal status, cohort type, and chemoradiation therapy. Conclusions: Our multicenter-based results highlight miRNAs involved in major histologic types of esophageal carcinoma and uncover significant associations with prognosis. Elucidating miRNAs relevant to esophageal carcinogenesis is potentially clinically useful for developing prognostic biomarkers and identifying novel drug targets and therapies. (Clin Cancer Res 2009;15(19):6192–200)
Type A Aortic Dissection After Nonaortic Cardiac Surgery
Authors: Olaf Stanger, Thomas Schachner, Brigitta Gahl, Peter Oberwalder, Lars Englberger, Markus Thalmann, Debbie Harrington, Dominik Wiedemann, Michael Südkamp, Mary N. Sheppard, Mark Field, Bartosz Rylski, Mario Petrou, Thierry Carrel, Johannes Bonatti, John Pepper
Journal: Circulation (2013)

Background— Cardiac surgery with cardiopulmonary bypass is associated with mechanical manipulation of the ascending aorta that occasionally leads to type A aortic dissection (AAD). Methods and Results— One hundred three patients with surgical repair for AAD following nonaortic cardiac surgery were identified. With the use of logistic regression modeling, coronary artery bypass surgery (CABG), either isolated or combined with another procedure in the initial operation, was associated with significantly higher operative mortality in comparison with patients with non-CABG procedures at the time of AAD repair both for all patients (odds ratio, 2.90; 95% confidence interval, 1.09–7.72; P =0.033) and for patients with acute and chronic AAD ≥30 days after the initial operation (odds ratio, 3.62; 95% confidence interval, 1.13–11.54; P =0.03). In patients who developed AAD late after the initial operation, operative mortality was highest in patients without preoperative coronary angiography and appropriate management of their native coronary artery disease and graft disease (odds ratio, 5.36; 95% confidence interval, 1.68–17.0; P =0.002). Nearly all the intimal dissection tears were located at sites of previous surgical trauma. Most of the ascending aortas that had dissected initially had a diameter ≥40 mm with histological evidence of medial degeneration in resected tissue samples. Conclusions— In patients who have undergone previous cardiac surgery, preexisting aortic wall pathology contributes to AAD with typical intimal damage at sites of mechanical trauma. The operative mortality was the highest in patients with previous CABG in comparison with patients with non-CABG procedures. Preoperative coronary angiography and operative management of native coronary and graft disease were significantly associated with outcome in patients with previous CABG.
134 EVALUATION OF GENOME-WIDE LOCI OF IRON METABOLISM IN HEREDITARY HEMOCHROMATOSIS IDENTIFIES PCSK7 AS A PREDICTOR OF LIVER CIRRHOSIS
Authors: F. Stickel, S. Buch, H. Zoller, S. Gallati, C. (Österreicher, A. Finkenstedt, A. Stadlmayr, E. Aigner, E. Sahinbegovic, C. Sarrazin, C. Schafmayer, H. Hinrichsen, F. Braun, M. Nothnagel, M.M. Lerch, J. Mayerle, H. Vozker, W. Kratzer, B.O. Boehm, A. Arlt, A. Franke, S. Schreiber, T. Becker, M. Krawczak, T. Berg, R. Hultcrantz, J. Zwerlina, C. Datz, J. Hampe
Journal: Journal of Hepatology (2012)
Longer Repolarization in the Epicardium at the Right Ventricular Outflow Tract Causes Type 1 Electrocardiogram in Patients With Brugada Syndrome
Authors: Satoshi Nagase, Kengo Fukushima Kusano, Hiroshi Morita, Nobuhiro Nishii, Kimikazu Banba, Atsuyuki Watanabe, Shigeki Hiramatsu, Kazufumi Nakamura, Satoru Sakuragi, Tohru Ohe
Journal: Journal of the American College of Cardiology (2008)
Influence of prior and subsequent pregnancy on breast cancer prognosis.
Authors: E von Schoultz, H Johansson, N Wilking, L E Rutqvist
Journal: Journal of Clinical Oncology (1995)

PURPOSE AND METHODS The prognostic influence of pregnancies 5 years before (n = 173) and after (n = 50) breast cancer diagnosis was investigated in 2,119 women less than 50 years of age with a primary operable breast cancer. The main end point was distant metastasis. Univariate and multivariate analyses were performed using the Cox proportional hazards model. In the analyses of the effect of pregnancy after diagnosis of breast cancer, a Cox model with a time-dependent covariate was applied. RESULTS Women with a pregnancy before diagnosis had slightly larger tumors than the control group. However, they did not differ with respect to nodal status and estrogen receptor (ER) status. There was no evidence that women with a pregnancy during the 5-year period preceding breast cancer diagnosis had a worse prognosis compared with women without pregnancy during the same period. Similarly, there was no evidence that women with a pregnancy after breast cancer diagnosis had a worse prognosis. CONCLUSION The hormonal changes associated with pregnancy thus seem to have little, if any, influence on the prognosis of breast cancer. In the present study, at least, there was no indication of a worse prognosis. In fact, the relative hazard for women who became pregnant after diagnosis of breast cancer in comparison with women without a subsequent pregnancy was 0.48 (P = .14), which suggested a possible decreased risk of distant dissemination.
The Stress-Responsive Gene <i>GADD45G</i> Is a Functional Tumor Suppressor, with Its Response to Environmental Stresses Frequently Disrupted Epigenetically in Multiple Tumors
Authors: Jianming Ying, Gopesh Srivastava, Wen-Son Hsieh, Zifen Gao, Paul Murray, Shuen-Kuei Liao, Richard Ambinder, Qian Tao
Journal: Clinical Cancer Research (2005)

The CpG island of GADD45G was identified as a target sequence during the identification of hypermethylated genes using methylation-sensitive representational difference analysis combined with 5-aza-2'-deoxycytidine demethylation. Located at the commonly deleted region 9q22, GADD45G is a member of the DNA damage-inducible gene family. In response to stress shock, GADD45G inhibits cell growth and induces apoptosis. Same as other GADD45 members, GADD45G is ubiquitously expressed in all normal adult and fetal tissues. However, its transcriptional silencing or down-regulation and promoter hypermethylation were frequently detected in tumor cell lines, including 11 of 13 (85%) non-Hodgkin's lymphoma, 3 of 6 (50%) Hodgkin's lymphoma, 8 of 11 (73%) nasopharyngeal carcinoma, 2 of 4 (50%) cervical carcinoma, 5 of 17 (29%) esophageal carcinoma, and 2 of 5 (40%) lung carcinoma and other cell lines but not in any immortalized normal epithelial cell line, normal tissue, or peripheral blood mononuclear cells. The silencing of GADD45G could be reversed by 5-aza-2'-deoxycytidine or genetic double knockout of DNMT1 and DNMT3B, indicating a direct epigenetic mechanism. Aberrant methylation was further frequently detected in primary lymphomas although less frequently in primary carcinomas. Only one single sequence change in the coding region was detected in 1 of 25 cell lines examined, indicating that genetic inactivation of GADD45G is very rare. GADD45G could be induced by heat shock or UV irradiation in unmethylated cell lines; however, this stress response was abolished when its promoter becomes hypermethylated. Ectopic expression of GADD45G strongly suppressed tumor cell growth and colony formation in silenced cell lines. These results show that GADD45G can act as a functional new-age tumor suppressor but being frequently inactivated epigenetically in multiple tumors.
Pulmonary Spirochaetosis: A Preliminary Note on Spirochaetes in the Sputum of Soldiers admitted to Special Malaria Wards
Authors: J. A. Thomson
Journal: BMJ (1918)

PULMONARY SPIROCHAETOSIS.r TuB lR 709 actually suffering tlhe acute phases of tlhe disease but rarely consult us.There are othler infective persons whlo never consult us at all.For the question arises: By wlhom is !gonorrljoea spread abroad?There may be persons in whom gonococei can live for a long time witlhout cau.sing any svmptoms, just as there "are "carriers " of thje organism of enteric fever-tlhey lhave not "typlhoid" tlhemselves, but tlhey can give it to otlhers.Carriers are not said to lhave "clhroniie enteric fever," and possibly it wouild be wise to drop tlle termn "chronic gonorrhoea."It is probable that miiost of the persons wlho transmuit gonorrhjoea are frequently reinifected witlh freslh strains of 0,onococei, anid really are tlle subjects of reneated inild attaclks of acute gonorrhoea.Man and wife, for exanmple, may continue to reinifect one anotlher time after time, so that it is only after separation that eitlher of tlhem ceases to be infective.After you lhave entered upon the practice of nmedicine you will avoid maniy comxiplications if you always tlhink at least tlhree timies before stating that a perso'i is free from venereal disease.It can be acquired again so quickly.Thjere is not muclh gained by seeitng an hliabitual drunjkard through one driikling bout, and it is ratlher futile to attack venereal diseatse by founding clinics wlhere all comners can be treated at the public expense.You cannot cure drunklienness unless you can keep people fromn drinking.
Is daily walking when living in the Paralympic village different to the typical home environment?
Authors: Brendan Burkett
Journal: British Journal of Sports Medicine (2010)

Background Life within the Paralympic village is exciting, and the preparation for competition of upmost importance. Due to the shear geographic size of the Paralympic village and associated competition venues, the amount of incidental walking could be different to an athlete's home environment, and any extra walking could potentially diminish athletic performance. Objectives To quantify the change (if any) in the amount of daily walking an athlete does during a typical day at home, when compared with when they are preparing for competition and competing. Methods The total number of steps per day was quantified using calibrated pedometers for 31 participants in four environments: at home, within a home-based national training camp, while abroad for an international training camp and when in the Paralympic village. Results There was a significant change in the daily step count with an average increase of 947 steps (or 13%) while in the national training camp, an increase of 3488 steps (or 53%) when in the international camp and an increase of 5472 steps (or 83%) when in the Paralympic village. Conclusion To enable the maximum possible sporting performance at the 2012 London Olympic and Paralympic Games and beyond, athletes should monitor their incidental walking and adjust levels of activity accordingly. The layout and design of the Olympic and Paralympic village should consider the significant increase in incidental walking and provide improved mechanisms to avoid this unwanted issue.
Genomic instability influences the transcriptome and proteome in endometrial cancer subtypes
Authors: Jens K Habermann, Nana K Bündgen, Timo Gemoll, Sampsa Hautaniemi, Caroline Lundgren, Danny Wangsa, Jana Doering, Hans-Peter Bruch, Britta Nordstroem, Uwe J Roblick, Hans Jörnvall, Gert Auer, Thomas Ried
Journal: Molecular Cancer (2011)

In addition to clinical characteristics, DNA aneuploidy has been identified as a prognostic factor in epithelial malignancies in general and in endometrial cancers in particular. We mapped ploidy-associated chromosomal aberrations and identified corresponding gene and protein expression changes in endometrial cancers of different prognostic subgroups. DNA image cytometry classified 25 endometrioid cancers to be either diploid (n = 16) or aneuploid (n = 9), and all uterine papillary serous cancers (UPSC) to be aneuploid (n = 8). All samples were subjected to comparative genomic hybridization and gene expression profiling. Identified genes were subjected to Ingenuity pathway analysis (IPA) and were correlated to protein expression changes. Comparative genomic hybridization revealed ploidy-associated specific, recurrent genomic imbalances. Gene expression analysis identified 54 genes between diploid and aneuploid endometrioid carcinomas, 39 genes between aneuploid endometrioid cancer and UPSC, and 76 genes between diploid endometrioid and aneuploid UPSC to be differentially expressed. Protein profiling identified AKR7A2 and ANXA2 to show translational alterations consistent with the transcriptional changes. The majority of differentially expressed genes and proteins belonged to identical molecular functions, foremost Cancer, Cell Death, and Cellular Assembly and Organization. We conclude that the grade of genomic instability rather than the histopathological subtype correlates with specific gene and protein expression changes. The identified genes and proteins might be useful as molecular targets for improved diagnostic and therapeutic intervention and merit prospective validation.