tbuckley/cabot-search huggingface dataset:
First results from the phase III ALTTO trial (BIG 2-06; NCCTG [Alliance] N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T→L), or their combination (T+L) in the adjuvant treatment of HER2-positive early breast cancer (EBC).
Authors: Martine J. Piccart-Gebhart, Andrew Peter Holmes, Jose Baselga, Evandro De Azambuja, Amylou C. Dueck, Giuseppe Viale, Jo Anne Zujewski, Aron Goldhirsch, Sergio Santillana, Kathleen I. Pritchard, Antonio C. Wolff, Christian Jackisch, Istvan Lang, Michael Untch, Ian E. Smith, Frances Boyle, Binghe Xu, Henry Leonidas Gomez, Richard D. Gelber, Edith A. Perez
Journal: Journal of Clinical Oncology (2014)

LBA4 Background: Lapatinib (L) is a HER1-HER2 tyrosine kinase inhibitor. The Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) Trial is a randomised, phase III trial comparing 3 oral L-containing regimens with T, each given for 1 year. Methods: From June 2007 to July 2011, 8381 patients (pts) were randomised from 946 sites in 44 countries to receive either L+T, T→L, L, or T. Anti-HER2 therapy was initiated after completing all chemotherapy (N=4613), concurrently with a taxane following anthracycline (N=3337), or concurrently with a non-anthracycline, platinum-containing regimen (N=431). The L arm was closed in Aug 2011 for futility and is not presented. The primary endpoint is invasive disease-free survival (DFS). L+T vs. T is tested for superiority and T→L vs. T is tested for non-inferiority at 1.11 margin. P≤0.025 is required for statistical significance. 850 DFS events in the L+T vs. T comparison would provide 80% power to detect a true hazard ratio (HR) of 0.80 with experiment-wide alpha=0.05. The current analysis was planned to occur either after observing these 850 events or at 4.5 yrs median follow up (MFU). Results: Pt and disease characteristics were well balanced. 40% were node-negative and 57% were hormone receptor positive. Only 555 DFS events for the L+T vs. T comparison were observed at 4.5 years MFU. HR for DFS was 0.84 (97.5% CI, 0.70-1.02; P=0.048; 4-yr DFS%=88% vs. 86%) for L+T vs. T and 0.93 (97.5% CI, 0.76-1.13; non-inferiority P=0.044; 4-yr DFS%=87% vs. 86%) for T→L vs. T. Diarrhoea (75% vs. 20%), rash (55% vs. 20%) and hepatobiliary (23% vs. 16%) adverse events were more frequent in L+T vs. T. Primary cardiac endpoints were infrequent (&lt;1%) in all arms. Conclusions: L+T has lower risk of a DFS event compared with T, and T→L appeared non-inferior to T, but neither finding was statistically significant. The first DFS results of dual HER2 blockade in the adjuvant ALTTO at 4.5 years MFU are unexpected considering the effect shown by doubling the pCR rate with L+T vs. T in the NeoALLTO trial. Follow up continues. Clinical trial information: NCT00490139.
Use of a video decision tool to improve informed decision making in hospitalized patients considering palliative radiation therapy.
Authors: Kavita Vyas Dharmarajan, Beryl McCormick, Chasity Walters, Christopher Monether, Tomer Levin, CarolAnn Milazzo, Robin Rawlins-Duell, Gina Giannantoni-Ibelli
Journal: Journal of Clinical Oncology (2013)

29 Background: Substantial evidence exists to suggest improved patient outcomes when oncologic patients are involved in making treatment decisions. Tools have been shown to facilitate the decision-making process for patients, yet aids to support decision making in radiation therapy (RT) are scarce. Given RT is one of the more difficult modalities for patients to conceptualize, there is a pressing need to develop and test decision aids, particularly in patients with incurable cancers. Methods: In this study, a video decision tool was developed and tested with 42 inpatients referred for palliative RT. Participants completed questionairres measuring their knowledge regarding palliative RT, treatment preferences and readiness, and decisional uncertainty before and after viewing the video. An additional 5-item tool was administered to participants after watching the video to assess their impression of the tool. Results: The mean percent of patients answering knowledge-assessing questions correctly increased 46.5% after viewing the video. Thirty-three percent (n=13) of patients rated their willingness to start palliative RT as 2 or greater (1= very ready; 10= not ready at all). Of these, 84.6% (n=11) showed improved scores in regard to their willingness to consent to palliative RT. Mean patient willingness scores improved 44% after watching the video. Decisional uncertainty scores changed minimally. Conclusions: Overall, participants' knowledge of palliative RT increased after viewing the video decision aid. With improved knowledge, there was a trend in increased willingness to begin RT. The next phase of this study will be a randomized trial to assess for differences in decisional uncertainty, knowledge of palliative RT, and treatment preferences for palliation. Clinical trial information: NCT01667965.
Competency building for self-management and self-care: evidence informed development of an empowerment course for breast cancer survivors
Authors: J. Nyhof-Young, M. Regehr, S. Secord, A. Jusko Friedman, P. Catton
Journal: Journal of Clinical Oncology (2006)

18626 Purpose: To improve survivorship outcomes by empowering and preparing survivors to self- manage their health. We describe the evidence-informed development of a patient empowerment course “Managing Your Cancer Journey” offered in the Breast Cancer Survivorship Program at Princess Margaret Hospital in Toronto, Canada. Methods: Audio-taped and transcribed focus groups (3; n = 16 patients, August 2004), interviews (n = 8 lymphedema patients, spring 2004, n = 8 patients, spring 2005) were held for patient directed guidance in survivorship course and program development. A comprehensive literature review was conducted to develop a theoretical framework for empowerment. Three main competencies: knowing, navigating and negotiating emerged and were developed into 5 ×1.5 hour classes facilitated by two social workers in collaboration with health professionals and community organizations. Feedback from survivors in a community forum (n = 40) and during piloting with survivors (n = 10) and educators was solicited. Analysis of transcripts and observer/consultant debriefings were analyzed for emergent themes. Results: Respondents recommended program interventions that allowed people to gain mastery or a perceived sense of control over their lives with cancer. Survivors and expert consultants prioritized 3 major domains for the survivorship program: psychosocial support, information provision, and support for dealing with the physical effects of breast cancer. In response, outcome measures for empowerment will include: patient satisfaction, cancer knowledge, self-efficacy in disease management, empowerment, and depression. Conclusions: Ongoing iterative feedback from and piloting with the survivor target audience and embedding the course within the hospital’s strategic plan for patient centred care and competency building are keys to successful course implementation. No significant financial relationships to disclose.
Prognostic Significance of Jab1 Expression in Laryngeal Squamous Cell Carcinomas
Authors: Youyi Dong, Li Sui, Yasuo Watanabe, Fuminori Yamaguchi, Naoya Hatano, Masaaki Tokuda
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Jun activation domain-binding protein 1 (Jab1) is known as a coactivator of AP1 transcription factor, which contributes to tumor progression by degrading the p27kip1 protein. The purpose of this study is to investigate whether Jab1 expression is correlated with p27kip1 level and cell proliferation, as well as whether Jab1 expression is associated with clinicopathologic variables and prognosis of laryngeal squamous cell carcinoma (LSCC). Experimental Design: Immunohistochemical and/or Western blot analysis was done in HEp-2 cells and 102 cases of LSCCs. Results: Jab1 expression was negatively associated with p27kip1 expression and was positively associated with cell proliferation both in HEp-2 cells and LSCCs. Jab1 overexpression was detected in 51% LSCCs and was significantly associated with unfavorable clinicopathologic variables. Survival analysis revealed that Jab1 overexpression is significantly associated with short disease-free and overall survival (P = 0.0036 and P = 0.0001, respectively). When Jab1 and p27kip1 are combined, patients with Jab1(+)/p27kip1(−) revealed poor disease-free and overall survival (P= 0.0008 and P &amp;lt; 0.0001, respectively). When Jab1 expression and lymph node status are combined, patients with Jab1(+)/lymph node(+) revealed poorer disease-free andoverall survival than others (P &amp;lt; 0.0001 and P &amp;lt; 0.0001, respectively). Furthermore, patients with the phenotype of Jab1(+)/p27kip1(−)/lymph node(+) revealed the worst disease-free and overall survival (P &amp;lt; 0.0001 and P &amp;lt; 0.0001, respectively). Multivariate analysis revealed that Jab1 protein is an independent prognostic indicator for overall survival. Conclusions: These findings suggested that Jab1 protein may contribute to the tumor progression and represent a novel prognostic indicator for LSCCs.
C/EBPβ and GATA-1 Synergistically Regulate Activity of the Eosinophil Granule Major Basic Protein Promoter: Implication for C/EBPβ Activity in Eosinophil Gene Expression
Authors: Yuji Yamaguchi, Hitoshi Nishio, Kenji Kishi, Steven J. Ackerman, Toshio Suda
Journal: Blood (1999)
Clintrial Refer- a Mobile App To Connect Patients With Local Clinical Trials
Authors: Judith Trotman, Xavier Badoux, Admir Huseincehajic, Michele Gambrill, Anais LeGall, Michelle Daly, Mark Lacey, Sonia Byrne, Jennifer Aung, Shashi Nair, Penny Mahairas, Cheryl Rine, Karen McCardie, Yvonne Cheung, Molly Forbes, Rebecca Meti, Patricia Plenge, Sharon Clark, Angela Bayley, Roslyn Ristuccia
Journal: Blood (2013)
High fluorescence cells in pleural fluid. Association with pleural malignancy
Authors: Diana Badenes, August Supervía, Francisco Del Baño, Sabina Herrera, Carles Vilaplana, Teresa Torrella, Isabel Cirera, Oriol Pallás
Journal: European Respiratory Journal (2013)

Background : High fluorescence cells (HFC) are cells that are not sorted by the automatic cell counter Sysmex XT 4000®. The significance of HFC in pleural fluid (PF) is not well known, but they could be related with non-haematological cells, including neoplasms.   Aims and objective:  To evaluate if the presence of HFC in PE is associated with neoplasms.   Methods:  Retrospective study carried out between February-May 2012. Cell count, total protein, glucose, pH, microbiology and cytology were determined in PF. Hospital records of all patients were reviewed, and clinical, pathological, diagnostic and mortality data were recorded. X 2 , Fisher’s exact and Mann-Whitney U tests were used for statistical analysis. A cut-off point to discriminate neoplasms from other causes of pleural disease was carried out (ROC curves).   Results:  148 samples of PF from 113 patients were analyzed. Age: 67 (20) years. 60% male. 44% of PF were transudates. 48 patients (32%) had an active neoplasm but a pleural cytology confirmed neoplasm in only 12 (8%). Main etiology of pleural disease: 30.6% infection; 26% heart failure; 8% pleural malignancy. The number of HFC in PE was associated with a pleural cytology of malignancy (p=0.003). A cut-off point of 64 HFC in PF is proposed to discriminate neoplasm: only 4 % of positive cytologies for malignancy had  64 HFC (p=0.001). The number of HFC in pleura was also related with in-hospital mortality (p=0.02) and 30 th  day mortality (p=0.03).   Conclusions:  There is an association between the number of HFC and the cytology confirming malignancy in PF. In addition, less than 64 HFC are seldom associated with pleural malignancy.
Clinical and functional assessment according to the exacerbating phenotype in COPD
Authors: Virginia Almadana, Agustin Valido, Rodrigo Tallόn, Jesús Sánchez, Concepciόn Romero, Teodoro Montemayor
Journal: European Respiratory Journal (2011)

Objective:  To establish the differences regarding effort test, lung function and quality of life questionnaires depending on the exacerbations.   Methods:  A prospective study of patients, who were evaluated to be included in a Respiratory Rehabilitation (RR) programme, was carried out. We analyzed age, gender, BMI, smoking history, symptoms, comorbidities, quality of life questionnaires: St George9s Respiratory Questionnaire (SGRQ) and Chronic Respiratory Questionnaire (CRQ) and anxiety-depression (HADS); spirometric values, 6 minutes walking test, maximal effort test, submaximal test, and the number and characteristics of the exacerbations during the previous year. We distinguished 2 groups: Frecuent exacerbating patients (>2 exacerbations per year) and non-exacerbating patients (≤2).   Results:  We included 41 patients: 20 showed ≤2 exacerbation per year vs 21 showing >2. By comparing both groups, we coudn9t find differences regarding age, gender, smoking history, BMI, symptoms, comorbidities or COPD severity classification (GOLD). There were no significant differences in HADS, although there were some in SGRQ (45.27±18.27 vs 65.76±14.48, p   Conclusions:  1. About half of patients who assisted our RR practice were frequent exacerbating patients.  2. Showing more exacerbations does not imply a worse tolerance to effort or a different clinical and functional profile, although it affects directly their quality of life.
Renal tubular transport of proline, hydroxyproline, and glycine
Authors: Charles R. Scriver
Journal: Journal of Clinical Investigation (1968)

Impaired renal tubular transport of proline, hydroxyproline, and glycine was inherited as an autosomal recessive trait in two Ashkenazi-Jewish pedigrees and one French-Canadian family; the heterozygotes for the trait exhibited hyperglycinuria only. Intestinal transport of imino acids and glycine was not impaired in homozygotes. It is possible that more than one mutant allele may occur at a locus controlling tubular transport of the imino acids and glycine, since one subject with the imino-glycinuric phenotype had one parent who was not hyperglycinuric. More than 60% of the specific tubular transport function is still available in homozygotes for absorption of imino acids and glycine at endogenous substrate concentrations; however, this persistent transport is already saturated at these concentrations in contrast to the large capacity available in normal subjects. Furthermore, the glycine portion of this persistent transport is noninhibitable by imino acids in contrast to the normal situation. The imino acids can inhibit each other's uptake in mutant and normal phenotypes. Two modes of transport for the imino acids and glycine are proposed to explain these observations: (1) a common system with high capacity, and (2) two additional systems, each with low capacity (one-tenth or less of the common system). One of these systems is apparently shared by proline and hydroxyproline. The mutant allele(s) observed in this investigation occur at the locus for the common system.
Interleukin-18 levels in induced sputum of stable and exacerbated COPD patients
Authors: Ingvild Haaland, Marianne Aanerud, Solveig Tangedal, Louise J. Persson, Per S. Bakke, Tomas M. Eagan
Journal: European Respiratory Journal (2014)

Background:  The pro-inflammatory cytokine Interleukin-18 (IL-18) is increased in blood and sputum from COPD patients, and may be further upregulated through inflammasome activation during acute exacerbations of COPD (AECOPD). The role of IL-18 in AECOPD is however largely unknown.   Aims: In this study, we aimed to compare levels of soluble IL-18 in induced sputum between healthy controls and stable COPD patients, between COPD patients with high and low exacerbation frequency, and between stable COPD and AECOPD.   Methods:  Induced sputum samples were collected from 43 healthy individuals, 253 stable COPD patients and 56 patients during AECOPD. Patients were recruited from Bergen COPD Cohort Study and Bergen COPD Exacerbation Study (aged 40-76, GOLD stage II-IV). IL-18 levels were measured by a bead-based immunoassay.   Results:  Induced sputum IL-18 levels were significantly higher in stable COPD patients compared to healthy controls (mean 11.3 vs 3.3 pg/ml;  p l0.01), and in GOLD stage IV compared to II (mean 30.7 vs 8.5 pg/ml;  p l0.01). Patients with frequent exacerbations (≥2/year) expressed higher IL-18 levels than low frequency exacerbators (l2/year), both in stable COPD (mean 15.8 vs 10.3 pg/ml) and AECOPD (mean 12.6 vs 9.3 pg/ml), although differences were not statistically significant. Finally, there was no difference in IL-18 levels between COPD patients at the stable state and during AECOPD (mean 11.3 vs 10.0 pg/ml;  p =0.5).   Conclusions:  IL-18 is increased in induced sputum of COPD patients, with a tendency to elevated levels in patients with frequent exacerbations. The lack of difference in IL-18 levels between stable and exacerbated COPD suggests that AECOPD mechanisms are independent of IL-18 activation.
Mental disorders and homicidal behavior in female subjects
Authors: M Eronen
Journal: American Journal of Psychiatry (1995)

Although violent behavior is one of the most important factors that have a detrimental effect on quality of life, there are very few quantitative epidemiological studies published on this issue. In particular, female homicidal behavior has remained poorly studied. This study reveals the association between some specific DSM-III-R disorders and female homicidal behavior.The author reviewed forensic psychiatric examination of 127 female homicide offenders in Finland over a 13-year period.Female homicide offenders had about a 10-fold higher odds ratio than the general female population for having schizophrenia or a personality disorder. The disorders with the most substantially higher odds ratios were alcohol abuse/dependence and antisocial personality disorder.Mental disorders appear to have a statistical relationship with homicidal behavior in countries with relatively low crime rates. On the basis of the data, there may be special subgroups of women among whom the risk of homicidal behavior is very high.
John Hunter's Teachings on Gunshot Wounds
Authors: J Rosenberg
Journal: Journal of the Royal Society of Medicine (2001)

Professor Ellis (January 2001 JRSM, pp. 43-45) quotes from Sir Everard Home that Hunter's poor health led to his enlisting in the Army in 1760. This is the popular view also cited by Beasley1. It is possible that this is an erroneous opinion akin to that previously perpetuated regarding the cause of Hunter's death—as syphilitic aortitis acquired in the dissecting room, when in fact he died of ischaemic heart disease. An alternative view proposed by Dobson2 is that Hunter enlisted in the Army primarily to advance his career. This seems more plausible considering the great risks from both injury and disease attendant on military service—a topic considered by Dr Gordon Cook in the subsequent issue of the JRSM.

Another point, as discussed by Oppenheimer3, is the controversy surrounding the relationship between Home and Hunter. Home, who destroyed Hunter's manuscripts and has been accused of plagiarism, might well have had nefarious reasons for impugning Hunter's health.
NeuroStation – Statistical software based on artificial intelligence and pattern recognition for NSCLC development prediction through comprehensive biomarker analysis
Authors: Nikola Minic, Svetlana Zunic, Snezana Zunic
Journal: European Respiratory Journal (2011)

A feed-forward artificial neural network is the perfect way to organize gathered information into precisely defined categories regardless blurred borders among them. Well-trained neural network with sufficient number of neurons in processing layer will act as an expert with highly increased learning and data processing skills and reduced error possibility below 0.001.  NeuroStation statistical software is uniquely made for analysis of three biomarker categories: apoptotic, cytological and cytochemical parameters. Initial learning database contains 24 patients (9 non-smokers, 6 smokers and 9 NSCLC patients), plotted into 21-dimensional space neural network based on observed biomarkers. After thorough analysis and testing, the system offers a reliable prediction in percentages what is the probability of NSCLC development based on any collected biomarker for a new person.  An analyst can further adjust statistical factors, such as influence ratio diameter and dispersion formula. Although the sample of 24 patients usually does not fulfill requirements for standard statistic tests, this network demonstrated significant results both in sense of reliability and mean squared error reduction.  Software NeuroStation has remarkable potential in becoming essential tool both for in scientific purposes and for medical staff who work with NSCLC endangered patients.
Obstructive sleep apnea syndrome and insomnia: The development of insomnia symptoms with CPAP treatment
Authors: Xuân-Lan Nguyên, Dominique Rakotonanahary, Joël Chaskalovic, Bernard Fleury
Journal: European Respiratory Journal (2011)

Rationale:  Insomnia is frequently reported in obstructive sleep apnoea syndrome (OSAS) patients due to the high prevalence of both diseases and, potentially, a causal relationship between them.   Objective:  To assess the evolution of insomnia under long-term continuous positive airway pressure (CPAP) treatment.   Methods:  Eighty apneic patients (age = 54.9±10.6 years, respiratory disturbance index = 45.0±24.6/h) on CPAP were followed prospectively for 24 months. Depression was assessed at baseline (T0) with the QD2A scale, and assessment of insomnia and sleep quality used the Insomnia Severity Index (ISI) (an ISI ≥ 14 defining insomnia) and the Pittsburgh Sleep Quality Index (PSQI) at T0 and T24. A multivariate correlation analysis identified the major explanatory factors for the ISI at T24.   Results:  The median ISI was 14 at T0 and 6 at T24. The ISI (13.7±5.7 vs. 8.2±6.3) and PSQI (8.2±3.7 vs. 5.9±3.8) significantly decreased at T24 (p = 0.0001) for the patients as a group. Forty-three subjects (54%) had insomnia at T0, and 14 (17.5%) were still insomniac at T24 (p = 0.0001). The ISI T0  (ρ = 0.41), PSQI T0  (ρ = 0.40), antidepressant use  T0  (ρ = 0.36), depression score  T0  (ρ = 0.33) and female gender (ρ = 0.28) correlated with ISI T24  (p   T24  did not.   Conclusion:  Insomnia was no longer measurable with CPAP treatment in two-thirds of initially insomniac patients. Residual insomnia was associated with high levels of initial insomnia and depressive symptoms.