tbuckley/cabot-search huggingface dataset:
Neoadjuvant chemotherapy for resectable oesophageal and junctional adenocarcinoma: Results from the UK Medical Research Council randomised OEO5 trial (ISRCTN 01852072).
Authors: Derek Alderson, Ruth E Langley, Matthew Guy Nankivell, Jane M. Blazeby, Michael Griffin, Adrian Crellin, Heike I. Grabsch, Alicia Frances Clare Okines, Cindy Goldstein, Stephen Falk, Joyce Thompson, Richard Krysztopik, Fareeda Y. Coxon, Susan Pritchard, Rupert Langer, Sally Patricia Stenning, David Cunningham
Journal: Journal of Clinical Oncology (2015)

4002 Background: Neoadjuvant chemotherapy (2 cycles cisplatin/5 fluorouracil) (CF) followed by surgery is a standard of care for locally advanced oesophageal cancer. We investigated whether more chemotherapy (4 cycles epirubicin/cisplatin /capecitabine (ECX)) would improve outcomes. Methods: A multi-centre, randomised, phase III trial comparing 2 cycles of CF with 4 cycles of ECX followed by oesophagectomy with 2-field lymphadenectomy for lower oesophageal and junctional (Types I and II) adenocarcinoma. Primary outcome was overall survival (OS); 842 patients (677 deaths) would detect an increase in 3-year survival from 30% to 38% (or 37%) with 82% (or 70%) power with 2α = 5%. Deaths accrued more slowly than anticipated but the Independent Data Monitoring Committee considered the data sufficiently robust for release. Secondary outcomes include disease-free (DFS) and progression-free survival (PFS), pathological R0 resection rate, Mandard grade and quality of life. Results: From 2005-2011, 897 patients (451 CF, 446 ECX) from 72 UK centres were randomly allocated (1:1). Baseline characteristics were similar between the groups (overall, male 90%, median age 62 (IQR 56-67), staging included PET 60%, T3 N0 22%, T3 N1 65%). 96% CF received 2 cycles, 89% ECX > 3 cycles. Grade 3/4 toxicity was lower with CF (30% v 47% p < 0.001.) Of those patients having a resection R0 rates were CF 60%, ECX 66% with a Mandard grade ≤ 3 achieved in CF 15% v ECX 32% with 3 and 11% achieving complete response. Post-operative complications were similar (CF 57%, ECX 62%) as were deaths at 30 (CF 2%, ECX 2%) and 90 days post-surgery (CF 4%, ECX 5%). PFS and DFS favoured ECX, hazard ratio (HR, 95% CI) PFS 0.86 (0.74-1.01), DFS 0.88 (0.75-1.03). HR for OS was 0.92 (0.79-1.08, p = 0.3017) based on 315 CF and 298 ECX deaths, with similar 3 year survival rates CF 39% (35-44%) vs ECX 42% (37-46%). Conclusions: There is some evidence of a benefit from the prolonged ECX regimen, in terms of PFS, DFS and tumour regression at resection, but this does not translate into a survival benefit. Overall chemotherapy toxicity was higher with 4 cycles of ECX compared to 2 cycles of CF but surgical morbidity was not increased. Clinical trial information: 01852072.
Changes in lung function on ascent to altitude
Authors: A J Pollard, D Collier, N P Mason, P W Barry
Journal: Thorax (1997)

Ascent to high altitude leads to a number of changes in lung function. We studied 55 subjects at sea level and as they ascended from 2600m to 5300m over 8 to 14 days to investigate the possible time course of these changes. Using a turbine spirometer, previously validated at simulated altitude, subjects recorded their peak expiratory flow (PEF), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) on arrival at each new attitude and again the next morning. Compared to sea level, PEF rose by 4.7% (95% confidence intervals (CI) 4.4-5.0, p=0.007), and FVC fell by 0.54% (95% CI 0.4-0.7, p=0.034), for every 1000m gain in altitude. FEV1 was unaffected by altitude change. These observations are in line with our previous findings (Pollard et al, Thorax, 1996;51:175-8). There was no significant change in lung function or acute mountain sickness (AMS) scores between arrival at each altitude and the next morning. Subjects with a greater fall in FVC on arrival at each attitude had higher AMS scores both on arrival and the next morning (Mood's median test, p=0.017). Furthermore, those with higher AMS scores had lower FVC at sea level (mean sea level FVC 4.81 (sd1.1) in those with AMS scores >4, vs. 5.51 (sd 0.9) in those with AMS scores <4 (p=0.018). Subjects with higher AMS scores had a smaller rise in PEF, although this did not reach significance (p=0.068). These results suggest that the fall in FVC may be related to acute mountain sickness, and that acute mountain sickness may be predicted from sea level FVC. The rise in PEF continued in two subjects studied after acclimatisation as they ascended to 6,400m, supporting the hypothesis that it is due to changes in air density. The fall in FVC was not progressive with further ascent, suggesting that it may be due to transient changes in the lung, such as sub-clinical pulmonary oedema, which resolved with acclimatisation.
Combined copy number and mutation analysis identifies oncogenic pathways associated with transformation of follicular lymphoma
Authors: A Bouska, W Zhang, Q Gong, J Iqbal, A Scuto, J Vose, M Ludvigsen, K Fu, D D Weisenburger, T C Greiner, R D Gascoyne, A Rosenwald, G Ott, E Campo, L M Rimsza, J Delabie, E S Jaffe, R M Braziel, J M Connors, C-I Wu, L M Staudt, F D‘Amore, T W McKeithan, W C Chan
Journal: Leukemia (2016)
Low α-defensin gene copy number increases the risk for IgA nephropathy and renal dysfunction
Authors: Zhen Ai, Ming Li, Wenting Liu, Jia-Nee Foo, Omniah Mansouri, Peiran Yin, Qian Zhou, Xueqing Tang, Xiuqing Dong, Shaozhen Feng, Ricong Xu, Zhong Zhong, Jian Chen, Jianxin Wan, Tanqi Lou, Jianwen Yu, Qin Zhou, Jinjin Fan, Haiping Mao, Daniel Gale, Jonathan Barratt, John A. L. Armour, Jianjun Liu, Xueqing Yu
Journal: Science Translational Medicine (2016)

Although a major source of genetic variation, copy number variations (CNVs) and their involvement in disease development have not been well studied. Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. We performed association analysis of the DEFA1A3 CNV locus in two independent IgAN cohorts of southern Chinese Han (total of 1189 cases and 1187 controls). We discovered three independent copy number associations within the locus: DEFA1A3 [P = 3.99 × 10(-9); odds ratio (OR), 0.88], DEFA3 (P = 6.55 × 10(-5); OR, 0.82), and a noncoding deletion variant (211bp) (P = 3.50 × 10(-16); OR, 0.75) (OR per copy, fixed-effects meta-analysis). While showing strong association with an increased risk for IgAN (P = 9.56 × 10(-20)), low total copy numbers of the three variants also showed significant association with renal dysfunction in patients with IgAN (P = 0.03; hazards ratio, 3.69; after controlling for the effects of known prognostic factors) and also with increased serum IgA1 (P = 0.02) and galactose-deficient IgA1 (P = 0.03). For replication, we confirmed the associations of DEFA1A3 (P = 4.42 × 10(-4); OR, 0.82) and DEFA3 copy numbers (P = 4.30 × 10(-3); OR, 0.74) with IgAN in a Caucasian cohort (531 cases and 198 controls) and found the 211bp variant to be much rarer in Caucasians. We also observed an association of the 211bp copy number with membranous nephropathy (P = 1.11 × 10(-7); OR, 0.74; in 493 Chinese cases and 500 matched controls), but not with diabetic kidney disease (in 806 Chinese cases and 786 matched controls). By explaining 4.96% of disease risk and influencing renal dysfunction in patients with IgAN, the DEFA1A3 CNV locus may be a potential therapeutic target for developing treatments for this disease.
Rapidly Cycling Auras and Episodic Focal Dystonia in Anti-LGI1 Autoimmune Encephalitis
Authors: Tadeu A. Fantaneanu, Shamik Bhattacharyya, Tracey A. Milligan, Page B. Pennell
Journal: JAMA Neurology (2016)

This case report describes a 57-year-old man with hemochromatosis and panhypopituitarism who presented with a 6-month history of word-finding difficulty, short-term memory loss, and rapidly cycling symptoms.
Management of Community-Acquired Pneumonia—Reply
Authors: Jonathan S. Lee, Daniel L. Giesler, Michael J. Fine
Journal: JAMA (2016)

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Barriers to Quality End-of-Life Care for Patients With Blood Cancers
Authors: Oreofe O. Odejide, Angel M. Cronin, Nolan B. Condron, Sean A. Fletcher, Craig C. Earle, James A. Tulsky, Gregory A. Abel
Journal: Journal of Clinical Oncology (2016)

Purpose Patients with blood cancers have been shown to receive suboptimal care at the end of life (EOL) when assessed with standard oncology quality measures (eg, no chemotherapy ≤ 14 days before death). As they were developed primarily for solid tumors, it is unclear if these measures are appropriate for patients with hematologic malignancies. Moreover, barriers to high-quality EOL care for this specific patient population are largely unknown. Methods In 2015, we asked a national cohort of hematologic oncologists about the acceptability of eight standard EOL quality measures. Building on prior qualitative work, we prespecified that measures achieving agreement among at least 55% of respondents would be considered acceptable. We also explored perspectives regarding barriers to quality EOL care. Results We received 349 surveys (response rate = 57.3%). Six of the standard measures met the threshold of acceptability, and four were acceptable to &gt; 75% of respondents: hospice admission &gt; 7 days before death, no chemotherapy ≤ 14 days before death, no intubation in the last 30 days of life, and no cardiopulmonary resuscitation in the last 30 days of life. The highest-ranked barriers to quality EOL care reported were “unrealistic patient expectations” (97.3%), “clinician concern about taking away hope” (71.3%), and “unrealistic clinician expectations” (59.0%). Conclusion In this large national cohort of hematologic oncologists, standard EOL quality measures were highly acceptable. The top barrier to quality EOL care reported was unrealistic patient expectations, which may be best addressed with more timely and effective advance care discussions.
Phase 1/2 Trial Of Lenalidomide In Combination With Cyclophosphamide and Prednisone (REP) In Patients With Lenalidomide-Refractory Multiple Myeloma (REPEAT-study)
Authors: Inger S. Nijhof, Sonja Zweegman, Mark-David Levin, Harry R. Koene, Aart Beeker, Andries C. Bloem, Gerard M.J. Bos, Laura M. Faber, Saskia K. Klein, Evert-Jan F.M. de Kruijf, Ellen van der Spek, Shulamiet Wittebol, Jeroen F. van Velzen, Berris van Kessel, Tuna Mutis, Pieter Sonneveld, Henk Lokhorst, Niels W.C.J. van de Donk
Journal: Blood (2013)
Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy
Authors: E. Ben-Ami, C.M. Barysauskas, M. von Mehren, M.C. Heinrich, C.L. Corless, J.E. Butrynski, J.A. Morgan, A.J. Wagner, E. Choy, J.T. Yap, A.D. Van den Abbeele, S.M. Solomon, J.A. Fletcher, G.D. Demetri, S. George
Journal: Annals of Oncology (2016)
Pleural Effusion of Patients with Malignant Mesothelioma Induces Macrophage-Mediated T Cell Suppression
Authors: Lysanne A. Lievense, Robin Cornelissen, Koen Bezemer, Margaretha E.H. Kaijen-Lambers, Joost P.J.J. Hegmans, Joachim G.J.V. Aerts
Journal: Journal of Thoracic Oncology (2016)
Physical activity prescription: a critical opportunity to address a modifiable risk factor for the prevention and management of chronic disease: a position statement by the Canadian Academy of Sport and Exercise Medicine
Authors: Jane S Thornton, Pierre Frémont, Karim Khan, Paul Poirier, Jonathon Fowles, Greg D Wells, Renata J Frankovich
Journal: British Journal of Sports Medicine (2016)

Non-communicable disease is a leading threat to global health. Physical inactivity is a large contributor to this problem; in fact, the WHO ranks it as the fourth leading risk factor for overall morbidity and mortality worldwide. In Canada, at least 4 of 5 adults do not meet the Canadian Physical Activity Guidelines of 150 min of moderate-to-vigorous physical activity per week. Physicians play an important role in the dissemination of physical activity (PA) recommendations to a broad segment of the population, as over 80% of Canadians visit their doctors every year and prefer to get health information directly from them. Unfortunately, most physicians do not regularly assess or prescribe PA as part of routine care, and even when discussed, few provide specific recommendations. PA prescription has the potential to be an important therapeutic agent for all ages in primary, secondary and tertiary prevention of chronic disease. Sport and exercise medicine (SEM) physicians are particularly well suited for this role and should collaborate with their primary care colleagues for optimal patient care. The purpose of this Canadian Academy and Sport and Exercise Medicine position statement is to provide an evidence-based, best practices summary to better equip SEM and primary care physicians to prescribe PA and exercise, specifically for the prevention and management of non-communicable disease. This will be achieved by addressing common questions and perceived barriers in the field. Author note This position statement has been endorsed by the following nine sport medicine societies: Australasian College of Sports and Exercise Physicians (ACSEP), American Medical Society for Sports Medicine (AMSSM), British Association of Sports and Exercise Medicine (BASEM), European College of Sport &amp; Exercise Physicians (ECOSEP), Norsk forening for idrettsmedisin og fysisk aktivite (NIMF), South African Sports Medicine Association (SASMA), Schweizerische Gesellschaft für Sportmedizin/Swiss Society of Sports Medicine (SGSM/SSSM), Sport Doctors Australia (SDrA), Swedish Society of Exercise and Sports Medicine (SFAIM), and CASEM.
68P Color Doppler parameters as non invasive prognostic marker in breast carcinoma. Result of 4 year prospective analysis
Authors: G. Hb, S. Pradhan, R. Jain, I. Khaleel, B.L. Nabiza, N. T
Journal: Annals of Oncology (2015)

Aim/Background: In this study we are correlating Color Doppler parameters (PI, RI and Vmax) with that of the different prognostic factors and association of these findings with that of 4 years Disease Free Survival (DFS) and Overall Survival (OS).Methods: The present prospective clinical study conducted during December 2009 to May 2011 includes 92 patients of breast cancer. All patients were undergone Color Doppler examination before treatment and parameters RI, PI and Vmax were recorded. Out of 92 patients, 15 patients were incomplete treatment or not taken standard treatment. 17 patients were lost to follow up. Follow Up as per standard protocol. Taken from registry or telephonic interview. DFS and OS calculated from the time of completion of treatment. Appropriate statistics used for analysis.Tabled 1N= 60DFS % (4 years)OS % (4 years)Stage T1T2T3T44122222100.083.3068.1063.60P < 0.05100.091.6686.3686.36P < 0.05Hiostology Grade 1Grade 2Grade 3Grade 41027140980.0077.7764.2855.55P < 0.0590.0092.5985.7177.77P < 0.05Lymph NodeN0N1N2N31528130486.6071.4261.5375.00P > 0.0593.3389.2884.6175.00P > 0.05PI Grade 1Grade 2Grade 3Grade 40251817- 80.0061.1170.58P > 0.05- 84.0088.8894.11P > 0.05RI Grade 1Grade 2Grade 3Grade 40371310- 72.9776.9260.00P < 0.05- 91.8984.6180.00P < 0.05Vmax Grade 1Grade 2Grade 3Grade 42282010100.071.4270.0070.00P < 0.05100.089.2890.0080.00P < 0.05 Open table in a new tab Conclusions: Doppler Parameters can be correlated with other prognostic indicator like tumor size and grade of the tumor and Lymph nodes. These can be used as prognostic indicator but further follow up large sample with multicentre trials is needed.Disclosure: All authors have declared no conflicts of interest. Aim/Background: In this study we are correlating Color Doppler parameters (PI, RI and Vmax) with that of the different prognostic factors and association of these findings with that of 4 years Disease Free Survival (DFS) and Overall Survival (OS). Methods: The present prospective clinical study conducted during December 2009 to May 2011 includes 92 patients of breast cancer. All patients were undergone Color Doppler examination before treatment and parameters RI, PI and Vmax were recorded. Out of 92 patients, 15 patients were incomplete treatment or not taken standard treatment. 17 patients were lost to follow up. Follow Up as per standard protocol. Taken from registry or telephonic interview. DFS and OS calculated from the time of completion of treatment. Appropriate statistics used for analysis. Conclusions: Doppler Parameters can be correlated with other prognostic indicator like tumor size and grade of the tumor and Lymph nodes. These can be used as prognostic indicator but further follow up large sample with multicentre trials is needed. Disclosure: All authors have declared no conflicts of interest.
The melatonin-sensitive circadian clock of the enteric bacterium<i>Enterobacter aerogenes</i>
Authors: Jiffin K. Paulose, Vincent M. Cassone
Journal: Gut Microbes (2016)

Circadian clocks are fundamental properties of all eukaryotic organisms and at least some prokaryotic organisms. Recent studies in our laboratory have shown that the gastrointestinal system contains a circadian clock that controls many, if not all, aspects of gastrointestinal function. We now report that at least one species of intestinal bacteria, Enterobacter aerogenes, responds to the pineal and gastrointestinal hormone melatonin by an increase in swarming activity. This swarming behavior is expressed rhythmically, with a period of approximately 24 hrs. Transformation of E. aerogenes to express luciferase with a MotA promoter reveals circadian patterns of bioluminescence that are synchronized by melatonin and whose periods are temperature compensated from 26°C to 40°C. Bioinformatics suggest similarities between the E. aerogenes and cyanobacterial clocks, suggesting the circadian clock may have evolved very early in the evolution of life. They also point to a coordination of host circadian clocks with those residing in the microbiota themselves.
Vitamin D3 Analog Inecalcitol Synergizes Vith Imatinib To Inhibit Selectively The Growth Of Chronic Myeloid Leukemia (CML) Progenitors and Stem Cells
Authors: Ali G Turhan, Marie Laure Bonnet, Bouneau Clementine, Remi Delansorne, Jean-François Dufour-Lamartinie, Agnès Guerci-Bresler, Hyacinthe A. Johnson-Ansah, Annelise Bennaceur-Griscelli
Journal: Blood (2013)
IMAGE, a randomized phase Ib/II study of elisidepsin in pretreated advanced gastroesophageal cancer.
Authors: S. A. Szyldergemajn, A. Gonçalves, J. P. Metges, K. Gunzer, C. Montagut, R. Salazar, M. Alsina, T. R. J. Evans, D. Swinson, R. D. Petty, H. Singer, C. M. Kahatt
Journal: Journal of Clinical Oncology (2011)

TPS169 Background: Elisidepsin (E) is a new marine compound with broad in vitro/in vivo antitumor activity. Cell exposure at low μM concentration results in rapid morphological changes and membrane permeabilization leading to cell-death. Phase I studies in cancer patients (pts) showed lack of hematologic toxicity, and transient transaminases increase to be E dose-limiting toxicity, the severity being related both to E dose and infusion times. E body clearance is independent of body surface area. E tolerance depends on whether it is infused over 3 hours (h) or 24 h, although not greatly on the schedule: weekly (q1wk), fortnightly or every 3 weeks. Gastroesophageal (GE) cancer is the 2nd leading cause of cancer-related deaths. Despite recent advances, no standard options are available once pts fail first-line combination chemotherapy regimens. E has shown promising activity in unselected pretreated GE pts in phase I, including 1 complete response and 2 prolonged disease stabilizations of around 12 months each. Methods: To determine the tolerability and efficacy of E in pts with GE after 1-2 prior chemotherapy lines. Pts were initially randomized in Spain, France or UK to: E 8.0 mg 24-h fortnightly (Arm A, dose intensity) vs E 3.0 mg. 3-h q1wk (Arm B, dose density). Dose will be optimized with a 25% initial dose increase or 20% initial dose decrease according to the toxicity observed in Cycle 1. After dose optimization, up to 40 pts per arm will be randomized (stratified by histology) to 1 of the optimal doses previously defined. Eligible adult pts must have advanced or metastatic GE cancer (squamous or adenocarcinoma), have failed 1-2 lines of prior chemotherapy, adequate major organ function, no CNS involvement, PS 0 or 1, no relevant non-neoplastic liver or cardiac condition, no high transfusion or parenteral nutrition requirements. Primary endpoint is progression-free survival at wk 16 ± 1 (PFS-4), at least 2 pts per arm within the first 15 pts must reach the endpoint in order to continue recruitment in that specific arm, up to a maximum of 40. The study was initiated in October 2010. As of December 2010, the first cohort has been completed for both arms.
22. The impact of “Development of the polymer micelles carrier system for doxorubicin” on the nanomedicine realm
Authors: Nicholas A. Peppas, Ruth Duncan, Gary E. Wnek, Allan S. Hoffman, Guang Hui Gao, Sung Wan Kim, Doo Sung Lee, Michael Hadjiargyrou, Elka Touitou, Denize Ainbinder, Russell Mumper, Alain Rolland, Takuro Niidome, Vinod Labhasetwar, Shi Liu, Guangyuan Zhou, Yubin Huang, Zhigang Xie, Xiabin Jing, Noemi Csaba
Journal: Journal of Controlled Release (2014)