tbuckley/cabot-search huggingface dataset:
Randomized phase II study of carboplatin plus either docetaxel (CbD) or paclitaxel (CbP) in Japanese patients with advanced non-small cell lung cancer (NSCLC): JMTO LC07-01.
Authors: M. Kawahara, K. Komuta, H. Yoshioka, M. Kawasaki, Y. Fujita, T. Yonei, F. Ogushi, K. Kubota, T. Yamanaka, K. Furuse
Journal: Journal of Clinical Oncology (2010)

e18069 Background: Platinum-based taxane chemotherapy has become a standard in the treatment of advanced NSCLC. However, no randomized data of CbD versus CbP have been available to date in Asian patients (pts). We report the analysis of a randomized phase II study comparing these two regimens. Methods: Chemotherapy-naive, ECOG PS 0-1, advanced NSCLC pts were enrolled. Carboplatin was administered at a fixed dose of AUC 6 on day1. Pts were randomized to either CbD (docetaxel 60 mg/m2 on day1, q3 wks) or CbP (paclitaxel 200 mg/m2 3h on day1, q3 wks) × 6 cycles in a ratio of 2 to 1, where the planned accrual was 90 pts (60/30 for CbD/CbP). Primary endpoint was PFS rate at 6 months (mo). Results: Ninety-one pts were enrolled and 90 pts were evaluable: median age 67 (range 37-82); M/F, 77/23%; cStage IIIB/IV/Relapse, 34/54/12%; Ad/Sq/Others, 59/26/16%; 6% had received prior RT. Demographics were well balanced between the two arms. Of the planned 360/180 cycles, 64/77% of those were administered in CbD/CbP. Median follow-up time was 15.8 mo. Data for survival, response rate, and toxicity in both arms are presented in the Table. PFS rate at 6 mo and median PFS were 41% and 4.8 mo in CbD and 37% and 5.1 mo in CbP. Although summary statistics for efficacy were similar in both arms, survival (OS and PFS) curves crossed each other. There was one treatment-related death due to pneumonitis in CbD. Conclusions: Two taxane drugs were tolerated and showed a similar activity in combination with carboplatin. Besides CbP, one of the current standard, CbD can be an alternative platform regimen in the first-line treatment of advanced NSCLC. Regimen CbD CbP N 60 30 Response rate, 90% CI 22% (13-32%) 33% (19-50%) PFS, % at 6 mo (90% CI) median (90% CI) 41% (30-52%) 4.8 mo (4.1-6.9 mo) 37% (22-51%) 5.1 mo (4.4-6.1 mo) OS, % at 12 mo (90% CI) median (90% CI) 60% (48-69%) 18 mo (12-23 mo) 60% (44- 73%) 15 mo (10-18 mo) Gr ≥3 neutropenia 75% 87% Gr ≥3 anemia 10% 10% Gr ≥3 thrombocytopenia 5% 3% Gr ≥3 febrile neutropenia 15% 17% Gr ≥3 nausea 5% 3% Gr ≥3 vomiting 5% 0% Gr ≥2 sensory neuropathy 17% 13% Gr ≥2 myalgias 7% 0% Treatment-related death 1 case 0 case No significant financial relationships to disclose.
Does bacterial colonisation potentiate granulation tissue formation post endobronchial stenting
Authors: Dinesh Krishnamoorthy, Brendan Madden
Journal: European Respiratory Journal (2012)

Background  Following endobronchial stent insertion granulation tissue formation may occur, which can occlude the airway. It has been postulated that bacterial colonisation causes granulation tissue formation and its subsequent proliferation.  Aim  To study whether specific microorganisms are associated with granulation tissue formation in patients post endobronchial stent deployment.  Methods  We conducted a retrospective review of all endobronchial stent insertions performed for benign conditions between January 2005- November 2011. Stents used in the procedure were covered and uncovered Ultraflex expandable metallic stents(Micro-invasive, Boston Scientific, Watertown, MA). Follow up bronchoscopies determined which patients had developed granulation tissue formation. Biopsies, sputum and lavage were then taken for microbiological anaylsis. Microsoft excel was used to collect and analyse data.  Results  Thirty patients had endobronchial stents deployed. Ten patients developed granulation tissue proliferation and all of these had bacterial colonisation of the stent with at least one pathogen. A total of 11 different pathogens where found; Staphylococcus aureus (6), Alpha haemolytic streptococci (5), Pseudomonas aeruginosa (3), Haemophilus influenza (2), Coagulase negative staphylococcus (2), Moraxella catarrhalis (1), Non haemolytic streptococcus (2), MRSA (1), Neisseria (1), Coliform (1), Corynebacterium striatum (1).  Conclusion  Prophylactic control in the form of antibiotic-impregnated stents and nebulised antibiotics post stent deployment targeting specific microorganisms may be beneficial in reducing granulation tissue formation.
T-box Transcription Factors Combine with the Cytokines TGF-β and IL-15 to Control Tissue-Resident Memory T Cell Fate
Authors: Laura K. Mackay, Erica Wynne-Jones, David Freestone, Daniel G. Pellicci, Lisa A. Mielke, Dane M. Newman, Asolina Braun, Frederick Masson, Axel Kallies, Gabrielle T. Belz, Francis R. Carbone
Journal: Immunity (2015)
Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial
Authors: Gérard Zalcman, Julien Mazieres, Jacques Margery, Laurent Greillier, Clarisse Audigier-Valette, Denis Moro-Sibilot, Olivier Molinier, Romain Corre, Isabelle Monnet, Valérie Gounant, Frédéric Rivière, Henri Janicot, Radj Gervais, Chrystèle Locher, Bernard Milleron, Quan Tran, Marie-Paule Lebitasy, Franck Morin, Christian Creveuil, Jean-Jacques Parienti, Arnaud Scherpereel
Journal: The Lancet (2015)
Stem cell-derived tissue- associated regulatory T cells ameliorate the development of autoimmune arthritis
Authors: Mohammad Haque, Kristin Fino, Jianxun Song
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Embryonic stem cells have the ability to grow indefinitely while maintaining pluripotency. Under the right circumstance, pluripotent stem cells (PSC) can produce almost all of the cells in the body including regulatory T cell (Tregs). Tregs are essential for normal immune
Efficacy of Mirtazapine in Patients With Functional Dyspepsia and Weight Loss
Authors: Jan Tack, Huynh Giao Ly, Florencia Carbone, Hanne Vanheel, Tim Vanuytsel, Lieselot Holvoet, Guy Boeckxstaens, Philip Caenepeel, Joris Arts, Lukas Van Oudenhove
Journal: Clinical Gastroenterology and Hepatology (2015)
O079 : Calr somatic mutations in a prospective cohort of 308 patients with splanchnic vein thrombosis
Authors: C. Marzac, A. Plessier, J.-J. Kiladjian, A. Andreoli, E. De Raucourt, O. Goria, K. Zekrini, C. Bureau, F. Lorre, F. Durand, N. Casadevall, D.-C. Valla, P.-E. Rautou
Journal: Journal of Hepatology (2015)
Boston Type 1 Keratoprosthesis versus Repeat Donor Keratoplasty for Corneal Graft Failure
Authors: Sumayya Ahmad, Priya M. Mathews, Kristina Lindsley, Majed Alkharashi, Frank S. Hwang, Sueko M. Ng, Anthony J. Aldave, Esen Karamursel Akpek
Journal: Ophthalmology (2015)
Oncovex MGM-CSF –mediated regression of contralateral (non-injected) tumors in the A20 murine lymphoma model does not involve direct viral oncolysis
Authors: Keegan Cooke, James Rottman, Jinghui Zhan, Petia Mitchell, Oluwatayo Ikotun, Brittany Yerby, Angela Chong, Charles Glaus, Achim K Moesta, Beltran Pedro
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Talimogene laherparepvec (T-VEC) is an injectable modified oncolytic herpes simplex virus type-1 (HSV-1) hypothesized to be efficacious by at least two complimentary mechanisms of action: a) direct oncolysis of the injected tumor and b) elicitation of a systemic anti-tumor immune
3CPET: finding co-factor complexes from ChIA-PET data using a hierarchical Dirichlet process
Authors: Mohamed Nadhir Djekidel, Zhengyu Liang, Qi Wang, Zhirui Hu, Guipeng Li, Yang Chen, Michael Q. Zhang
Journal: Genome biology (2015)

Various efforts have been made to elucidate the cooperating proteins involved in maintaining chromatin interactions; however, many are still unknown. Here, we present 3CPET, a tool based on a non-parametric Bayesian approach, to infer the set of the most probable protein complexes involved in maintaining chromatin interactions and the regions that they may control, making it a valuable downstream analysis tool in chromatin conformation studies. 3CPET does so by combining data from ChIA-PET, transcription factor binding sites, and protein interactions. 3CPET results show biologically significant and accurate predictions when validated against experimental and simulation data.
Why shocking might be not shocking enough
Authors: J DEGROOT
Journal: Cardiovascular Research (2004)

See article by Chattipakorn et al. [10] in this issue.

Sudden cardiac death remains the single most frequent cause of mortality in the industrialized world [1]. Indeed, approximately every 100 s somebody dies suddenly in the United States alone [2]. Most frequently, ventricular fibrillation (VF) associated with acute myocardial ischemia or infarction is the cause of circulatory collapse [1].

When untreated, VF is lethal within minutes because the arrhythmia precludes coordinated contraction of the ventricles and thus causes circulatory arrest. The electrophysiologic mechanism of VF is reentry. Reentrant activation was first described by George Ralph Mines who showed in 1914 that an impulse can travel around a ring of excitable heart tissue and can re-excite tissue that is no longer refractory, thus giving rise to continuous circus movement of activation [3]. Mines defined three main requirements for reentry: slow conduction, a short refractory period, and a zone of unidirectional block [3]. Slow conduction is necessary because the revolution time of the impulse should allow the tissue where the impulse started to recover from refractoriness. The shorter the refractory period, the earlier the tissue can be re-excited. Unidirectional block prevents the impulse from traveling in both directions of the tissue ring and dying out opposite from where it started. Under normal circumstances both factors are absent, but a timely delivered premature beat can initiate reentry in normal hearts.

Consequently, the wavelength … 

*Tel.: +31-20-566-3266; fax: +31-20-697-5458. j.r.degroot{at}amc.uva.nl
A randomized, double-blinded, pilot trial of aprepitant added to standard antiemetics during conditioning therapy for hematopoietic stem cell transplant (HSCT)
Authors: J. S. Bubalo, J. F. Leis, P. T. Curtin, R. T. Maziarz, T. J. Kovascovics, G. Meyers, J. S. McCune, M. Y. Munar, B. Hayes-Lattin, N. Jones
Journal: Journal of Clinical Oncology (2007)

9112 Background: Antiemetic prophylaxis for standard dose chemotherapy has improved while that for high dose chemotherapy ± total body irradiation (TBI) has not. Aprepitant (A), a neurokinin-1 antagonist, was added to standard antiemetic therapy for planned conventional HSCT to test for improved emesis control. Methods: During cyclophosphamide (Cy)-based conditioning therapy patients were randomized to receive ondansetron (O) ± dexamethasone plus A or a placebo (P) on days of chemo/radiotherapy. The primary aim was to reduce N/V during and after HSCT conditioning. Nausea, emesis, and nutritional intake were evaluated from the onset of therapy through day +7. Busulfan doses were targeted to disease appropriate AUCs and pharmacokinetic (PK) analysis was performed on Cy, Cy- metabolites (HCY &amp; CEPM), and A. Responses were defined as Complete (CR) - no emesis, mild-moderate nausea, and Major (MR) - 1–2 emesis on only 1 day with any level nausea or no emesis with severe nausea. Results: Fifteen patients have been randomized per arm. Eleven patients received TBI (1,200 cGy) CY (120 mg/kg) and 19 received Bu (16 mg/kg) CY (120 mg/kg). A/P was begun on Day -7 (125 mg) with the first O dose and given daily (80 mg) through day +4 (alone on days +1 through +4). Overall responses (CR + MR) were seen in 14/15 A patients and 7/15 P patients. (p=0.014) No emesis occurred in 10/15 A patients and 5/15 P patients (p=0.143). Preliminary PK show the observed AUCs of CY, HCY and CEPM, for both regimens and PK differences between the 2 regimens, were consistent with previously published data. Most busulfan patients, 87%, required dose adjustments (primarily reductions) to stay within target AUCs. Anti-seizure prophylaxis with phenytoin may significantly decrease A levels, but this didn't appear to be clinically relevant. Adverse effects were similar between arms. One case of sinusoidal obstruction syndrome occurred in the P arm. Conclusions: In this interim analysis, aprepitant added to standard antiemetics improved emesis prevention during Cy-containing conditioning therapy prior to HSCT, without significant changes in Cy pharmacokinetics or increased toxicity. Data on the target accrual of 40 patients will be presented. [Table: see text]
The role of Notch3 signaling pathway in pancreatic cancer
Authors: T. Dang, k. Vo, K. Washington, J. Berlin
Journal: Journal of Clinical Oncology (2007)

21049 Background: Given the extremely poor prognosis of patients diagnosed with pancreatic cancer, identifying new targets for therapeutic intervention is crucial in improving clinical outcome. Existing data support a role for Notch3 pathway in human cancer, pancreas cancer in specific and in normal pancreas development. Method: We developed a pancreatic tissue array. An antibody targeting the extracellular domain of Notch3 was used to evaluate expression levels, grading from 0 to 4+ to determine the prevalence of Notch3 in pancreatic cancer. Notch3 expression was used to correlate with clinical data (IRB approved). Using small interfering RNA (siRNA) we tested the downstream effects of Notch3 in pancreatic cancer cell line BxP3 in vitro. Furthermore, to study pharmacologic inhibition of Notch3 processing and activation we exposed Panc-1, HPAF II and BxP3 pancreas cancer cell lines to γ-secretase inhibitors (previously demonstrated to block upstream of Notch3 thereby inhibiting Notch3). Results: Strong staining (+2 or greater) for Notch3 was seen in 50 of 72 (69%) resected specimens. No correlation with survival or tumor grade was seen. Using siRNA, we demonstrated that inhibiting Notch3 downregulated the antiapoptotic protein Bcl-xL but not Bcl-2. When γ-secretase inhibitors (GSI and L-685,458) were used, the previously mentioned pancreatic cell lines demonstrated reduction in proliferation rates. Conclusion: Notch3 overexpression is common in pancreas cancer. While Notch 3 expression does not clearly correlate with survival, our in vitro data suggest that Notch3 affects apoptotic pathways and may represent a potential target for intervention in patients with pancreatic cancer. No significant financial relationships to disclose.
Calcium antagonists and renal hemodynamics
Authors: M Epstein
Journal: Journal of the American Society of Nephrology (1991)

During the past decade, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of this preparation to vasoconstrictor agents. Our recent studies with the isolated perfused hydronephrotic rat kidney model, which permits visualization of afferent and efferent arterioles, have demonstrated that the augmentation of glomerular filtration rate observed in the isolated perfused kidney is attributable to preferential vasodilation of preglomerular vessels. Although the clinical implications of such observations have not been fully delineated, the results of recent studies indicate that calcium antagonists exert salutary effects on renal function in patients with impaired renal hemodynamics. Such disorders include radiocontrast-induced nephrotoxicity and transplant-associated acute renal insufficiency. It is apparent, however, that the effects of calcium antagonists on renal blood flow commend their use in the management of essential hypertension.
Who reviews the reviewers? Who edits the editors? Many avenues for you to hold<i>BJSM</i>accountable
Authors: Karim M Khan, Babette M Pluim
Journal: British Journal of Sports Medicine (2015)

Being open and transparent creates trust is one of the BMJ Publishing Group's nine values. Does the BJSM leadership team act openly and transparently to deserve the trust of our community? We put our case here but we leave the verdict to our valued readers and respected communities (including our 19 member societies who total over 12 000 subscribers).

When we consider ‘ BJSM ’ we refer to the broad range of content that can be considered to start from bjsm.bmj.com. In addition to our 24 annual issues, BJSM is a dynamic, versatile contributor to health education and debate via >200 podcasts, 60 YouTube videos and >300 blog posts. We engage with a vast community on Facebook and Twitter—and these are two-way media where BJSM content can rapidly be tagged, trolled or trumpeted. In total, 4.5 million BJSM pages are viewed each year. If this volume of content did not generate debate and criticism it would be time to sack the Editorial team.

Peer review of around 1200 papers/year …
Licorice in prevention of radiation induced mucositis
Authors: A. A. Ismail, A. A. Behkite, F. M. Badria, A. A. Guemei
Journal: Journal of Clinical Oncology (2004)

8268 Background: Complementary and alternative medicine (CAM) had proven efficacy in pain relief, correction of nutritional status and improving the performance status. However, lack of standardization is the major obstacle for any scientific evaluation of any CAM trial. Mucositis is a major complication of irradiation in head and neck (H&N) tumors, the addition of chemotherapy to irradiation may enhance this dose limiting problem. Licorice is a strong demulcent that had been effectively used in treatment of peptic ulcer.Methods: We had prepared a standard concentration from lyophilized licorice extract (5%w/v) and use it as a mouth wash before and immediately after each session of radiation therapy. We encouraged the patients to repeat this mouthwash and swallow it several times throughout the day. The mucositis grade is reported according to WHO grading system. Six weeks after the end of radiation the flow of saliva in 5 min was measured for the flow in response to citric acid stimulation within 5min and the Na, Cl, and bicarbonate content will be measured. Results: Out of 45 patients with H&N tumors of different sites all treated with irradiation. Tumor stage T2–4, N0–3, M0; 17 of them were treated by combination of concomitant RT and CT, 10 were treated by additional concomitant boost to tumor site. And 29 treated with conventional RT. The mean radiation dose was 60 Gy (range 50–71 Gy) The mean overall treatment time was 6.4 wks. Only 7 pts suffer from grade III mucositis that require treatment interruption. Seven pts. Evaluated for salivary secretion; 2 were comparable to normal control, 3 had[tmsnew]63[/tmsnew] 15% reduction in the volume and 2 had 40 % reduction of the volume of saliva. Conclusions: The use of Licorice in H&N tumors is safe and prevents radiation-induced mucositis that may result in better outcome of the results, further evaluation in randomized study is urgently required to conclude in this new modality. No significant financial relationships to disclose.
Association Between β-Genus Human Papillomavirus and Cutaneous Squamous Cell Carcinoma in Immunocompetent Individuals—A Meta-analysis
Authors: Jad Chahoud, Adele Semaan, Yong Chen, Ming Cao, Alyssa G. Rieber, Peter Rady, Stephen K. Tyring
Journal: JAMA Dermatology (2015)

<h3>Importance</h3> Existing epidemiological evidence remains controversial regarding the association between β-genus human papillomavirus (β-HPV) and cutaneous squamous cell carcinoma (cSCC) in immunocompetent individuals. <h3>Objective</h3> We aimed to clarify this association and evaluate type-specific β-HPV involvement. <h3>Data Sources</h3> We performed a systematic literature search of MEDLINE and EMBASE for studies in humans through June 18, 2014, with no restriction on publication date or language. The following search terms were used: "human papillomavirus" and "cutaneous squamous cell carcinoma or skin squamous cell carcinoma or cSCC or nonmelanoma skin neoplasms." <h3>Study Selection</h3> Articles were independently assessed by 2 reviewers. We only included case-control or cohort studies, in immunocompetent individuals, that calculated the odds ratio (OR) for cSCC associated with overall and type-specific β-HPV. <h3>Data Extraction and Synthesis</h3> We first assessed the heterogeneity among study-specific ORs using the Q statistic and<i>I</i><sup>2</sup>statistic. Then, we used the random-effects model to obtain the overall OR and its 95% CI for all studies as well as for each type of HPV. We also tested and corrected for publication bias by 3 funnel plot–based methods. The quality of each study was assessed with the Newcastle Ottawa Scale. <h3>Main Outcomes and Measures</h3> Pooled ORs and 95% CIs for overall β-HPV and HPV types 5, 8, 15, 17, 20, 24, 36, and 38 association with skin biopsy proven cSCC. <h3>Results</h3> Seventy-nine articles were assessed for eligibility; 14 studies met inclusion criteria for the meta-analysis and included 3112 adult immunocompetent study participants with cSCC and 6020 controls. For all detection methods, the overall association between β-HPV and cSCC was significant with an adjusted pooled OR (95% CI) of 1.42 (1.18-1.72). As for the type-specific analysis, types 5, 8, 15, 17, 20, 24, 36, and 38 showed a significant association with adjusted pooled ORs (95% CIs) of 1.4 (1.18-1.66), 1.39 (1.16-1.66), 1.25 (1.04-1.50), 1.34 (1.19-1.52), 1.38 (1.21-1.59), 1.26 (1.09-1.44), 1.23 (1.01-1.50), and 1.37 (1.13-1.67) respectively. Our subgroup analysis in studies using only serology for HPV detection showed a significant association between overall β-HPV and HPV subtypes 5, 8, 17, 20, 24, and 38 with an increased risk of cSCC development. <h3>Conclusions and Relevance</h3> This study serves as added evidence supporting β-HPV as a risk factor for cSCC in healthy individuals. The subgroup analysis highlights this significant association for HPV 5, 8, 17, 20, and 38, which may help to direct future prevention efforts.
High-dose melphalan and cyclophosphamide with autologous bone marrow rescue for recurrent/progressive malignant brain tumors in children: a pilot pediatric oncology group study.
Authors: D H Mahoney, D Strother, B Camitta, T Bowen, T Ghim, T Pick, D Wall, L Yu, J J Shuster, H Friedman
Journal: Journal of Clinical Oncology (1996)

PURPOSE To determine the maximum-tolerated dose of cyclophosphamide (CTX) when administered sequentially with melphalan 60 mg/m2/d for 3 days, followed by autologous bone marrow rescue (ABMR), in children with recurrent or progressive malignant brain tumors, and to make preliminary observations on efficacy. PATIENTS AND METHODS Nineteen patients between the ages of 2 and 21 years were enrolled and 18 were assessable for effects of therapy. CTX was administered to seven patients at 750 mg/m2/d for 4 days, to five patients at 975 mg/m2/d, to three patients at 1,200 mg/m2/d, and to three patients at 1,500 mg/m2/d. All patients received ABMR. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used in 15 patients. Toxicity, response to therapy, time to progression, and survival and monitored. RESULTS The median time to a granulocyte count more than 500/dL was 19 days (range, 11 to 39), and for a platelet count more than 50,000/dL was 33 days (range, 16 to 60). Four heavily pretreated patients (22%) died of transplant-related complications. No dose-limiting, non-hematologic toxicities were defined for the study. Seven of 18 patients (39%) had a complete response (CR) or a partial response (PR). These included four patients with medulloblastoma (CR and three PRs), two with germinomas (two CRs), and one with ependymoma (one CR). The estimated 1-year survival rate was 39% (SE 12%). CONCLUSION CTX, at a maximum total dose of 6,000 mg/m2, administered sequentially with melphalan and followed by ABMR was tolerable in children with recurrent brain tumors who had not been heavily pretreated. Responses were seen in patients with medulloblastoma and germinomas. Further trials in children with chemosensitive tumors, with minimal residual disease, are planned.