tbuckley/cabot-search huggingface dataset:
Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial
Authors: Ian J Jacobs, Usha Menon, Andy Ryan, Aleksandra Gentry-Maharaj, Matthew Burnell, Jatinderpal K Kalsi, Nazar N Amso, Sophia Apostolidou, Elizabeth Benjamin, Derek Cruickshank, Danielle N Crump, Susan K Davies, Anne Dawnay, Stephen Dobbs, Gwendolen Fletcher, Jeremy Ford, Keith Godfrey, Richard Gunu, Mariam Habib, Rachel Hallett, Jonathan Herod, Howard Jenkins, Chloe Karpinskyj, Simon Leeson, Sara J Lewis, William R Liston, Alberto Lopes, Tim Mould, John Murdoch, David Oram, Dustin J Rabideau, Karina Reynolds, Ian Scott, Mourad W Seif, Aarti Sharma, Naveena Singh, Julie Taylor, Fiona Warburton, Martin Widschwendter, Karin Williamson, Robert Woolas, Lesley Fallowfield, Alistair J McGuire, Stuart Campbell, Mahesh Parmar, Steven J Skates
Journal: The Lancet (2015)

Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality.
Abstract 124: An AED Is Not an AED: Extreme Variation in No-Flow Fraction, Perishock Pause and Time to First Shock Among Different Commercially Available Public Access Defibrillators
Authors: Cynthia Poenicke, Maxi Kurth, Tobias Neidel, Benjamin Lauterwald, Norbert Papkalla, Adrian Pfältzer, Thea Koch, Michael P Müller
Journal: Circulation (2014)

Out of hospital cardiac arrest (OHCA) requires immediate basic life support (BLS) to prevent death and permanent brain damage. Patients suffering a shockable cardiac rhythm need early defibrillation. In many countries public access defibrillators are established. However, no studies have investigated differences in the no-flow fraction (NFF) and the peri-shock pause between PAD.   Objective:  To evaluate the NFF, peri-shock pause, and time to 1st shock in a five minutes simulated cardiac arrest scenario with persistent shockable rhythm.   Methods:  We evaluated seven commercially available PAD (Heartsave PAD, Metrax/Germany; Heartstart HS1, Philips/The Netherlands; Lifeline VIEW AED, defibtech/USA; Powerheart G5 AED, Cardiac Science/USA; FRED easy Life, Schiller/Switzerland; AED plus, Zoll/USA; LIFEPAK CR Plus, Medtronic/USA). In this pilot study an instructor in BLS/PAD performed single rescuer BLS using a Code Blue III advanced life support manikin (Gaumard Scientific/USA). The pre-scripted scenario was an adult patient with OHCA and persistent shockable rhythm. We measured the time to 1st shock, the NFF (fraction of time without chest compressions divided by the time without perfusing rhythm) and the peri-shock pause. The results were compared to a standard BLS scenario without the use of an AED.   Results:  We found considerable differences among the tested AEDs regarding the CPR quality. Furthermore, many of the devices did not meet the demands of the current international guidelines (table 1).   Conclusion:  The algorithms and user guidance of the AEDs should be reconsidered to reduce the NFF and to allow high quality BLS. Further research is necessary to study the usability of AEDs when used by lay rescuers.
GATA2 deficiency underlying severe blastomycosis and fatal herpes simplex virus–associated hemophagocytic lymphohistiocytosis
Authors: Michael A. Spinner, Jennifer P. Ker, Charles J. Stoudenmire, Oluwole Fadare, Emily M. Mace, Jordan S. Orange, Amy P. Hsu, Steven M. Holland
Journal: Journal of Allergy and Clinical Immunology (2015)
Biological Soft Robotics
Authors: Adam W. Feinberg
Journal: Annual Review of Biomedical Engineering (2015)

In nature, nanometer-scale molecular motors are used to generate force within cells for diverse processes from transcription and transport to muscle contraction. This adaptability and scalability across wide temporal, spatial, and force regimes have spurred the development of biological soft robotic systems that seek to mimic and extend these capabilities. This review describes how molecular motors are hierarchically organized into larger-scale structures in order to provide a basic understanding of how these systems work in nature and the complexity and functionality we hope to replicate in biological soft robotics. These span the subcellular scale to macroscale, and this article focuses on the integration of biological components with synthetic materials, coupled with bioinspired robotic design. Key examples include nanoscale molecular motor-powered actuators, microscale bacteria-controlled devices, and macroscale muscle-powered robots that grasp, walk, and swim. Finally, the current challenges and future opportunities in the field are addressed.
Evaluation of bronchoscopic findings and bronchoalveolar lavage (BAL) fluid cytology with regard to BAL fluid microbiology in critically ill patients
Authors: Pavlos Venikos, Christos Kampolis, Konstantinos Konstantopoulos, Apostolos Armaganides, Petros Karakitsos
Journal: European Respiratory Journal (2014)

Introduction: Bronchoscopy may be a useful diagnostic tool in critically ill patients with evolving pulmonary infiltrates and respiratory failure, especially when quick and exact diagnostic answers are required.  Objectives: To evaluate a possible association between macroscopic appearance of respiratory secretions or BAL fluid cytology and BAL fluid microbiology, in mechanically ventilated (MV) patients with deterioration on chest radiography.  Methods and patients: This prospective study included 52 consecutive MV patients (median age 72 yrs/ IQR:58-80) admitted to intensive care unit (ICU). Bronchoscopy and BAL was performed in all immunocompromised patients upon admission and in immunocompetent patients when diagnosis was uncertain.  Results: Purulence of respiratory secretions was more frequent in patients with positive BAL cultures (for either one or more microbial pathogens), compared to patients with negative cultures (80% or 81.8% vs 46.2%) (p=0.060), and in patients with BAL cultures positive for Acinetobacter baumani or Pseudomonas aeruginosa compared to other pathogens (92.3% or 84.6% vs 62.5%) (p=0.045).The percentage of BAL fluid neutrophils did not seem to differ among patients with negative cultures, one or more isolated bacteria (p=0.435), or among patients with BAL cultures positive for different specific pathogens (p=0.352).  Conclusions: In MV patients with radiologic deterioration, presence of purulent secretions revealed by bronchoscopy is associated with positive BAL cultures and isolation of specific gram negative pathogens. BAL differential cell profile does not differ according to BAL microbiology findings.
Rising CA-125 levels within the normal range in patients with uterine papillary serous cancer.
Authors: M. Frimer, J. Y. Hou, L. Riemers, G. L. Goldberg, S. Shahabi
Journal: Journal of Clinical Oncology (2010)

e15510 Background: Rising serum cancer antigen 125 (CA-125) trends within the “normal range” have been reported to be predictive of disease recurrence in patients with epithelial ovarian carcinoma. Pre-operative levels of CA-125 have been shown to correlate with disease stage and prognosis in uterine papillary serous carcinoma (UPSC). The clinical significance of CA-125 as a tumor marker in UPSC is unclear. We hypothesize that rising CA-125 levels that remain below the upper limit of normal (< 35 U/mL) may predict recurrence in patients with UPSC. Methods: All patients that underwent surgical staging and treatment for UPSC between 1999-2008 were reviewed for the following: 1) CA-125 > 35 u/mL at time of diagnosis defining marker positive (MP) and marker negative (MN) status, 2) complete clinical and/or radiographic response to initial treatment with normalization of serum CA-125, and 3) clinical and/or radiographic detection and confirmation of recurrence. All CA-125 values from diagnosis to recurrence or the last follow-up were reviewed. Baseline CA-125 level was defined as the nadir level in remission. Chi-Square test was used to examine the association between CA-125 trends and disease status. Results: Fifty-six patients with UPSC were evaluable with a mean follow-up of 51 months. Twenty-three patients (41%) developed recurrence at a median interval of 21 months, of these, 11 patients (19%) had serial CA-125 levels measured in remission. Of the 14 MP patients, 10 (71.4%) had stage III/IV disease. Of the 42 MN patients, 34 (80.9%) were stage I/II, and 8 (19%) had stage III/IV disease. Elevated CA-125 levels at diagnosis were significantly associated with recurrence and advanced stage (p = 0.012, p = 0.0004 respectively). The rise in CA-125 above 15 U/mL during remission was significantly associated with recurrence (p < 0.001). An absolute value increase in CA-125 level by 5 U/mL and 10 U/mL from baseline was also independently associated with disease recurrence (p < 0.001, p = 0.0024 respectively). Conclusions: Rising CA-125 levels within the normal range is highly predictive of disease recurrence. The potential impact of these findings and early management and therapy may affect progression-free survival and overall survival. No significant financial relationships to disclose.
MiR-214 increases the sensitivity of breast cancer cells to tamoxifen and fulvestrant through inhibition of autophagy
Authors: Xinfeng Yu, Aiping Luo, Yicong Liu, Shuqing Wang, Ye Li, Wenna Shi, Zhihua Liu, Xianjun Qu
Journal: Molecular Cancer (2015)

Tamoxifen (TAM) and fulvestrant (FUL) are the major drugs for patients with estrogen receptor-positive (ER+) breast cancers. However, the development of endocrine resistance is the impediment for successful treatment. We aimed to explore the mechanisms of endocrine resistance and therapeutic strategy for overcoming resistance against TAM and FUL. Experiments were performed in ER+ and estrogen/TAM-sensitive MCF7 cells and antiestrogen-resistant MCF7/LCC9 cells. The expression of miR-214 and uncoupling protein 2 (UCP2) was determined by RT-qPCR and Western blot in breast cancer cells and human breast cancer tissue specimens. Cell autophagy was examined by fluorescent probe monodansyl cadaverine (MDC) and GFP-LC3-II-positive punctate identified by confocal microscopy. Apoptotic cells were determined by Annexin V-FITC/PI staining. The potential regulatory target of miR-214 was determined by prediction tool, target protein expression and luciferase reporter assay. 4-OHT/FUL treatment resulted in induction of apoptosis as well as autophagy in breast cancer cells. Autophagy might be the major cause of endocrine resistance to 4-OHT or FUL. MiR-214 increased the sensitivity of breast cancer cells to the 4-OHT/FUL-induced apoptosis through inhibition of autophagy. Importantly, a negative correlation was established between miR-214 and UCP2 in human breast cancer tissue specimens assayed by RT-qPCR. UCP2 was identified to be a direct target of miR-214. Further study in MCF7/LCC9 cells indicated that endocrine resistance might arise from activation of the PI3K-Akt-mTOR pathway, thereby inducing autophagy by overexpression of UCP2. MiR-214 increased the sensitivity of breast cancer cells to TAM and FUL through inhibition of autophagy by targeting UCP2. MiR-214 shows potential as a novel therapeutic strategy for overcoming endocrine resistance in ER+ breast cancers.
Race, socioeconomic status and survival difference in cutaneous melanoma patients in California
Authors: M. Mobasher, J. A. Zell, F. L. Meyskens, H. Anton-Culver
Journal: Journal of Clinical Oncology (2006)

8023 Background: Survival data for malignant melanoma patients of various ethnic backgrounds are lacking. Furthermore, the modifying effect of socioeconomic status (SES) on survival in melanoma patients is unknown. This study was performed to analyze survival differences for cutaneous melanoma patients of each major ethnicity, including analysis of the effect of SES on outcomes, using a statewide cancer registry. Methods: A case-only analysis of data from the California Cancer Registry database during 1992–2002 was conducted. The primary outcome measured was overall survival for each ethnic group. Univariate survival analyses were conducted using the Kaplan-Meier method and log-rank test; multivariate survival analyses were performed using Cox proportional hazards ratios. Results: 46,218 incident cases of invasive cutaneous melanoma were identified, including 39,741 Caucasians (93.47%), 2263 (5.32%) Hispanics, 331(0.78%) Asians, 172 (0.40%) African-Americans, and 12 (0.03%) Native Americans (P&lt;0.0001). On univariate survival analysis, improved 10-year overall survival rates were noted for Hispanics (63.2%) and Caucasians (60.9%) compared to Asians (51.1%), African-Americans (39.8%), and Native Americans (30.6%) (P&lt;0.0001). A statistically significant survival difference was observed for melanoma patients based on SES (P&lt;0.0001), favoring those with high SES. Multivariate survival analysis revealed an increased hazard ratio (HR) for African-Americans (HR=1.594; P=0.0023) compared to Caucasians, after adjustment for age, sex, stage, Breslow depth, histologic subtype,location, and SES. Increased age, male sex, regional and remote stages, melanoma of the head/face, Breslow depth categories 2, 3, and 4, nodular melanoma, melanoma-NOS, and lowest SES quartile were independently associated with poor survival (P&lt;0.0001). Conclusions: Among patients with invasive cutaneous melanoma, survival is significantly decreased for African-Americans compared to Caucasians. This is not explained by differences in SES, stage, Breslow depth, age, sex, histological subtype, and location. Our epidemiologic observations suggest that intrinsic differences may exist for African-American melanoma patients, adversely affecting survival. No significant financial relationships to disclose.
Abdominal malrotation overlooked at extensive cross-sectional imaging and leading to life-threatening gastrointestinal bleeding
Authors: Alexander Arlt, Dörthe Schuldt, Susanna Nikolaus, Clemens Schafmayer, Witig von Schoenfels, Stefan Schreiber, Mark Ellrichmann
Journal: Endoscopy (2015)

A 34-year-old woman presented with recurrent abdominal discomfort that had started in early childhood. External ileocolonoscopy showing inflammatory alterations of the ileum and colon led to the suspicion of inflammatory bowel disease. Treatment with mesalazine or corticosteroids had no beneficial effects. Initial magnetic resonance enterography (MRE) and diagnostic laparoscopy revealed no pathological findings.
Aerobic Glycolysis and the Warburg Effect. An Unexplored Realm in the Search for Fibrosis Therapies?
Authors: Toby M. Maher
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

as we have progressed technically, our tools for detecting subtle changes resulting from defective CFTR activity or expression have been refined, including the use of cell-specific knockouts, siRNAs, genomics, proteomics, and transcriptomic and genome editing.These tools have allowed the role of CFTR-deficient macrophages in the context of CF pathophysiology to be delineated (6,(15)(16)(17).However, several questions remain: What do these changes really mean?How does a new "set-point" or altered XBP-1 activity affect the cell's response to the environment?How important is the immune response beyond the contributions of the airway epithelium in CF?Is the contribution of the immunologic response to CF pathophysiology of a magnitude that it can be manipulated to significantly affect CF lung disease?Why is the concept of "specific" immune involvement so hard to embrace as an important focus?Whether you agree that intrinsic CFTR defects directly alter macrophage responses or that the observed differences are the result of the response to the altered CFTR milieu, what difference does it make?Therapeutic interventions aimed at XBP-1 or other molecules associated with sustaining the proinflammatory phenotype in the CF lung, in combination with antimicrobials and CFTR modulators, may provide improved resolution of infection and inflammation.The difference may not lie with only correcting CFTR function in airway epithelial cells and providing improved airway surface hydration, but also with providing supportive immunology, so that patients can aide in their own fight against infection and inflammation.This will ultimately improve quality of life, and hopefully survival, in patients with CF.
Effect of 3 Years of Treatment With Exenatide on Postprandial Glucagon Levels
Authors: Mark M. Smits, Mathijs C. Bunck, Michaela Diamant, Anja Corner, Bjorn Eliasson, Robert J. Heine, Ulf Smith, Hannele Yki-Järvinen, Daniël H. van Raalte
Journal: Diabetes Care (2015)

α-Cell dysfunction contributes to hyperglycemia in type 2 diabetes and is characterized by inappropriately increased basal and postprandial glucagon levels (1). The regulation of glucagon secretion remains poorly understood. Glucagon-like peptide 1 (GLP-1), a gut-derived hormone with glucose-dependent insulinotropic effects, has been shown, albeit mostly in short-term studies, to reduce fasting and postprandial glucagon levels. Thus, the glucagonostatic effect of GLP-1 receptor agonists has been considered as one of the key mechanisms by which they improve glycemia (2). However, in a recent 48-week study with the GLP-1 receptor agonist liraglutide, a paradoxical postprandial increase in glucagon levels was observed (3). This study challenged our understanding of the effects of GLP-1 receptor agonists on glucagon.

We assessed the effects of 3-year treatment with the GLP-1 receptor agonist exenatide (EXE) versus insulin glargine (GLAR) on fasting and postprandial glucagon levels. Details of the study design were reported previously (4). In short, 36 …
Adjuvant capecitabine and oxaliplatin for gastric cancer: Results of the phase III CLASSIC trial.
Authors: Y. Bang, Y. W. Kim, H. Yang, H. C. Chung, Y. Park, K. Lee, K. H. Lee, Y. H. Kim, S. Noh, J. Ji, M. Johnston, F. Sirzen, S. H. Noh
Journal: Journal of Clinical Oncology (2011)

LBA4002 Background: Surgical resection is a recommended treatment for operable gastric cancer (GC) in general, despite high recurrence rates (40%–80%). Adjuvant chemotherapy aims to reduce recurrences; however, there is currently no universally accepted adjuvant regimen for GC. Methods: CLASSIC is a randomized, open-label, multicenter, international (South Korea, China, and Taiwan) study of XELOX (capecitabine 1000mg/m 2 bid, d1–14, q3w and oxaliplatin 130mg/m 2 , d1, q3w x 8 cycles) vs observation, following D2 gastrectomy. Eligible patients were chemotherapy- and radiotherapy-naive, with stage II (T2N1, T1N2, T3N0), IIIa (T3N1, T2N2, T4N0), or IIIb (T3N2) GC resected within 6 weeks prior to randomization. The primary endpoint is 3-year disease-free survival (DFS). A sample size of 512 patients per arm was planned to observe the 385 DFS events required to provide 80% power at a 5% significance level for the hypothesized treatment effect (hazard ratio [HR] 0.75). The Independent Data Monitoring Committee recommended full evaluation and reporting of results following a positive pre-planned interim analysis at 266 events. Results: The XELOX and observation arms (ITT populations of 520 and 515 patients, respectively) were well balanced for baseline characteristics. The median duration of follow-up was 34.4 (16–51) months. XELOX-related grade 3/4 adverse events (AEs) occurred in 244/496 patients (49%) of the safety population. Neutropenia was the only AE observed in &gt;10% of patients (21%, n=106/496). Serious XELOX-related grade 3/4 AEs occurred in 34/496 patients (7%). There were 62/496 (13%) and 80/476 (17%) deaths on study in the safety populations of XELOX and observation arms, respectively, mostly due to disease progression. Efficacy results in the ITT population are summarized below. Conclusions: This study demonstrates the superior efficacy of adjuvant XELOX vs observation alone following D2 gastrectomy. Although OS data are still immature, there is a trend towards superiority of XELOX. These data support the use of adjuvant XELOX for GC. [Table: see text]
Regulatory and effector T cell subsets and dendritic cells in breast cancer
Authors: S. Y. Chui, M. A. Morse, T. Doldo, T. Osada, T. M. Clay, H. K. Lyerly, S. Khan, A. Gattis, A. C. Hobeika
Journal: Journal of Clinical Oncology (2004)

9697 Background: Successful immune responses against breast cancer may depend on the balance between immune stimulation mediated through dendritic cells (DC) & cytolytic T cells, and immune inhibition mediated in part by CD4+CD25+ regulatory T cells (Treg) and CTLA4 expression on T cells. We hypothesized that low anti-tumor immunity in breast cancer patients might be partially explained by aberrations in the frequencies of these different components of the immune response compared with healthy individuals. Methods: We analyzed whole blood from 26 breast cancer patients (9 stage I, 8 stage II, 3 stage III, 6 stage IV) for Treg, DC subsets, CD8+CD45RA+CCR7- cytolytic effectors, and CTLA4 expressing T cells. Controls were 41 healthy volunteers. Results: Breast cancer patients overall had higher levels of Treg (37+/−14% of CD4+ T cells) than controls (26.3 +/− 9%; p=0.002). Treg were higher in patients with stage II-IV disease, positive lymph nodes, and age < 65. Patients <65 also tended to have higher levels of CTLA4 on both CD4 and CD8+ T cells. Across all patients, there was a high positive correlation (0.82) of CTLA4 expression on Treg and CD8+ T cells, suggesting that the presence of this suppressive molecule may be a more generalized phenomenon in some individuals. The only groups that differed in CD8+CD45RA+CCR7- cytolytic effectors were premenopausal patients who had lower levels than post-menopausal women (37 vs 54%, p=0.04). Across all the patients, there was a modest negative correlation (−0.44) between Treg and CD8+ CD45RA+CCR7- suggesting that Treg may inhibit development of cytotoxic effector T cells. Finally, patients receiving chemotherapy and those with Stage IV disease had lower levels of immunostimulatory CD11c+ DC and higher levels of immunomodulatory CD123+ DC than other patients suggesting a possible negative impact of chemotherapy and advanced disease on stimulatory DC. Conclusions: This data highlights the inhibitory environment of the immune system in breast cancer patients, particularly those with advanced disease and younger age. Modification of this inhibitory environment will be needed to increase the activity of immunotherapy interventions in these patients. No significant financial relationships to disclose.
Prospective, Observational Study To Assess The Safety Of Rituximab In Combination With Chemotherapy In Patients With Previously-Untreated Or Relapsed Or Refractory B Cell-Lineage Chronic Lymphocytic Leukaemia (B-CLL): Preliminary Results
Authors: Andres Lopez, Eduardo Rios, Javier De la Serna, Felix Carbobnell, Cristina Garcia Bernaldez, Isabel Gonzalez-Grande, Pilar Giraldo
Journal: Blood (2013)
Guidelines for Reporting Estimates of Probability of Paternity
Authors: R H Walker
Journal: JAMA (1985)

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