tbuckley/cabot-search huggingface dataset:
Abstract 955: Transformation from NSCLC to SCLC in EGFR mutant lung cancers with acquired resistance to EGFR inhibitors
Authors: Matthew J. Niederst, Lecia V. Sequist, Elizabeth L. Lockerman, Angel R. Garcia, Carlotta Costa, Farhiya Mohamoud, Darrell R. Borger, Toshi Shioda, Gad Getz, Anthony J. Iafrate, Mari Mino-Kenudson, Jeffrey A. Engelman
Journal: Cancer Research (2014)

Abstract Epidermal growth factor receptor (EGFR) mutant non-small cell lung cancers (NSCLCs) are sensitive to the EGFR inhibitors erlotinib and gefitinib. In the majority of patients with this type of cancer, EFGR inhibition leads to a dramatic reduction in tumor size coupled with an abatement of symptoms. These responses are temporary, and in most cases the cancers become resistant after an average of one year. Recently, we and others have found that a subset of these cancers transform from NSCLC to SCLC as they acquire resistance to EGFR TKI. Details underlying this novel resistance mechanism are largely undiscovered. To assess the genetic changes associated with NSCLC to SCLC transformation, we carried out next generation sequencing analysis on NSCLC and SCLC resistant tumors. The sequencing results revealed that Rb, along with p53 and PIK3CA were specifically altered in the SCLC transformed tumors. An IHC assay to detect Rb indicated that while 10 out of 10 SCLC transformed cases have loss of Rb, resistant cancers that maintained an NSCLC histology largely retained Rb. To address the mechanism underlying the resistance to EGFR inhibition in these tumors, we demonstrated that upon the transformation to SCLC there is a marked reduction in EGFR expression, suggesting that in transforming to SCLC these cells become a cell type that no longer requires EGFR for their survival. Finally, utilizing cell lines generated from biopsies taken from resistant cancers, we identify the Bcl-2/Bcl-XL inhibitor Abt-263 as a potential therapeutic approach to treat these resistant patients. Together, our results provide details underlying this novel mechanism of resistance to targeted therapy. Citation Format: Matthew J. Niederst, Lecia V. Sequist, Elizabeth L. Lockerman, Angel R. Garcia, Carlotta Costa, Farhiya Mohamoud, Darrell R. Borger, Toshi Shioda, Gad Getz, Anthony J. Iafrate, Mari Mino-Kenudson, Jeffrey A. Engelman. Transformation from NSCLC to SCLC in EGFR mutant lung cancers with acquired resistance to EGFR inhibitors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 955. doi:10.1158/1538-7445.AM2014-955
Stent Thrombosis in New-Generation Drug-Eluting Stents in Patients With STEMI Undergoing Primary PCI
Authors: Giovanna Sarno, Bo Lagerqvist, Johan Nilsson, Ole Frobert, Kristina Hambraeus, Christoph Varenhorst, Ulf J. Jensen, Tim Tödt, Matthias Götberg, Stefan K. James
Journal: Journal of the American College of Cardiology (2014)
The psychological sequelae of therapeutic abortion--denied and completed
Authors: P K Dagg
Journal: American Journal of Psychiatry (1991)

The purpose of this article is to review the available literature on the psychological sequelae of therapeutic abortion, addressing both the issue of the effects of the abortion on the woman involved and the effects on the woman and on the child born when abortion is denied.Papers reviewed were initially selected by using a Medline search. This procedure resulted in 225 papers being reviewed, which were further selected by limiting the papers to those reporting original research. Finally, studies were assessed as to whether or not they used control groups or objective, validated symptom measures.Adverse sequelae occur in a minority of women, and when such symptoms occur, they usually seem to be the continuation of symptoms that appeared before the abortion and are on the wane immediately after the abortion. Many women denied abortion show ongoing resentment that may last for years, while children born when the abortion is denied have numerous, broadly based difficulties in social, interpersonal, and occupational functions that last at least into early adulthood.With increasing pressure on access to abortion services in North America, nonpsychiatrist physicians and mental health professionals need to keep in mind the effects of both performing and denying therapeutic abortion. Increased research into these areas, focusing in particular on why some women are adversely affected by the procedure and clarifying the relationship issues involved, continues to be important.
The Clinical Use of Operant Learning Approaches: Some Complex Issues
Authors: STANLEY I. GREENSPAN
Journal: American Journal of Psychiatry (1974)

The clinical use of operant learning approaches demands a full understanding of a patient's behavioral organization and the many experiences that constitute reinforcement. This involves considering the appropriate functional response classes, the "core" functional response classes, the integration of precursor and end goal behaviors (as seen in the natural development of complex behavior patterns in children), program flexibiity, and the variety of stimulus configurations a patient may experience as reinforcing. The author raises a basic question regarding the value of changing behaviors versus changing the patient's experience of reinforcement.
Prognostic Significance of Extent of Disease in Bone in Patients With Androgen-Independent Prostate Cancer
Authors: P. Sabbatini, S. M. Larson, A. Kremer, Z.-F. Zhang, M. Sun, H. Yeung, M. Imbriaco, I. Horak, M. Conolly, C. Ding, P. Ouyang, W. K. Kelly, H. I. Scher
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate the prognostic significance of a bone scan index (BSI) based on the weighted proportion of tumor involvement in individual bones, in relation to other factors and to survival in patients with androgen-independent prostate cancer. PATIENTS AND METHODS: Baseline radionuclide bone scans were reviewed in 191 assessable patients with androgen-independent disease who were enrolled onto an open, randomized trial of liarozole versus prednisone. The extent of skeletal involvement was assessed by scoring each scan using the BSI and independently according to the number of metastatic lesions. The relationship of the scored bone involvement to other known prognostic factors was explored in single- and multiple-variable analyses. RESULTS: In single-variable analyses, the pretreatment factors found to be associated with survival were age (P = .0446), performance status (P = .0005), baseline prostate-specific antigen (P = .0001), hemoglobin (P = .0001), alkaline phosphatase (P = .0002), AST (P = .0021), lactate dehydrogenase (P = .0001), and treatment (P = .0098). The extent of osseous disease was significant using both the BSI (P = .0001) and the number of lesions present (P = .0001). In multiple-variable proportional hazards analyses, only BSI, age, hemoglobin, lactate dehydrogenase, and treatment arm were associated with survival. When the patient population was divided into three equal groups, with BSI values of &lt; 1.4%, 1.4% to 5.1%, and &gt; 5.1%, median survivals of 18.3, 15.5, and 8.1 months, respectively, were observed (P = .0079). CONCLUSION: The BSI quantifies the extent of skeletal involvement by tumor. It allows the identification of patients with distinct prognoses for stratification in clinical trials. Further study is needed to assess the utility of serial BSI determinations in monitoring treatment effects. The BSI may be particularly useful in the evaluation of agents for which prostate-specific antigen changes do not reflect clinical outcomes accurately.
Bupropion: a new treatment for smokers
Authors: J. Britton
Journal: BMJ (2000)

Bupropion was licensed in June by the Medicines Control Agency for use in the United Kingdom to help patients stop smoking. Bupropion is the first new pharmacological treatment for smokers to be introduced since nicotine replacement therapy 20 years ago. Bupropion can potentially have a huge impact on public health not only through the efficacy of the drug itself but also by making smoking cessation services more widely available.

There are about 13 million regular smokers in the United Kingdom.1 One in every two lifelong smokers will die prematurely from tobacco related causes.2 Interventions to help people stop smoking are cost effective in preventing that premature loss of life, and nicotine replacement products are the most effective treatment available.3 4 About 20% of those given nicotine replacement with support from specialist counsellors will remain non-smokers for one year and up to about 10% will remain non-smokers if given brief advice from a health professional in addition to nicotine replacement.3 This latter approach may potentially have a far greater impact on public health because wider coverage of the population can be achieved. It is also cost effective.5 However, nicotine replacement and counselling services …
Would a Breakthrough Therapy by Any Other Name Be as Promising?
Authors: Joseph S. Ross, Rita F. Redberg
Journal: JAMA Internal Medicine (2015)

patients with atrial fibrillation with high global cardiovascular risk, the yield for detecting ischemia was 5.2%, and ischemia was not associated with increased mortality in this population.These findings suggest that these asymptomatic patients do not benefit from MPI. Harms of MPI include increased cancer risk from the high radiation burden (6-37 mSv depending on protocol, which is equivalent to hundreds or thousands of chest radiographs).These findings support a change in the AUC rating to the rarely appropriate category for this indication, and because MPI has definite harms without benefits for asymptomatic patients with atrial fibrillation this Research Letter merits the Less is More designation.
Air Pollution Exposure during Pregnancy and Childhood Autistic Traits in Four European Population-Based Cohort Studies: The ESCAPE Project
Authors: Mònica Guxens, Akhgar Ghassabian, Tong Gong, Raquel Garcia-Esteban, Daniela Porta, Lise Giorgis-Allemand, Catarina Almqvist, Aritz Aranbarri, Rob Beelen, Chiara Badaloni, Giulia Cesaroni, Audrey de Nazelle, Marisa Estarlich, Francesco Forastiere, Joan Forns, Ulrike Gehring, Jesús Ibarluzea, Vincent W.V. Jaddoe, Michal Korek, Paul Lichtenstein, Mark J. Nieuwenhuijsen, Marisa Rebagliato, Rémy Slama, Henning Tiemeier, Frank C. Verhulst, Heather E. Volk, Göran Pershagen, Bert Brunekreef, Jordi Sunyer
Journal: Environmental Health Perspectives (2015)

Prenatal exposure to air pollutants has been suggested as a possible etiologic factor for the occurrence of autism spectrum disorder.We aimed to assess whether prenatal air pollution exposure is associated with childhood autistic traits in the general population.Ours was a collaborative study of four European population-based birth/child cohorts-CATSS (Sweden), Generation R (the Netherlands), GASPII (Italy), and INMA (Spain). Nitrogen oxides (NO2, NOx) and particulate matter (PM) with diameters of ≤ 2.5 μm (PM2.5), ≤ 10 μm (PM10), and between 2.5 and 10 μm (PM(coarse)), and PM2.5 absorbance were estimated for birth addresses by land-use regression models based on monitoring campaigns performed between 2008 and 2011. Levels were extrapolated back in time to exact pregnancy periods. We quantitatively assessed autistic traits when the child was between 4 and 10 years of age. Children were classified with autistic traits within the borderline/clinical range and within the clinical range using validated cut-offs. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis.A total of 8,079 children were included. Prenatal air pollution exposure was not associated with autistic traits within the borderline/clinical range (odds ratio = 0.94; 95% CI: 0.81, 1.10 per each 10-μg/m3 increase in NO2 pregnancy levels). Similar results were observed in the different cohorts, for the other pollutants, and in assessments of children with autistic traits within the clinical range or children with autistic traits as a quantitative score.Prenatal exposure to NO2 and PM was not associated with autistic traits in children from 4 to 10 years of age in four European population-based birth/child cohort studies.Guxens M, Ghassabian A, Gong T, Garcia-Esteban R, Porta D, Giorgis-Allemand L, Almqvist C, Aranbarri A, Beelen R, Badaloni C, Cesaroni G, de Nazelle A, Estarlich M, Forastiere F, Forns J, Gehring U, Ibarluzea J, Jaddoe VW, Korek M, Lichtenstein P, Nieuwenhuijsen MJ, Rebagliato M, Slama R, Tiemeier H, Verhulst FC, Volk HE, Pershagen G, Brunekreef B, Sunyer J. 2016. Air pollution exposure during pregnancy and childhood autistic traits in four European population-based cohort studies: the ESCAPE Project. Environ Health Perspect 124:133-140; http://dx.doi.org/10.1289/ehp.1408483.
Abstract 3917: The Toronto Risk Score for Major Adverse Cardiovascular Events Following Percutaneous Coronary Intervention
Authors: Joan Ivanov, Saqib Chowdhary, Eric Horlick, Peter Seidelin, Karen Mackie, Vlad Dzavik
Journal: Circulation (2006)

Objective: To develop and internally validate an objective, contemporary risk index for major adverse cardiovascular events (MACE) following percutaneous coronary intervention (PCI) which facilitat...
50-year trends in the incidence of anorexia nervosa in Rochester, Minn.: a population-based study
Authors: A R Lucas, C M Beard, W M O'Fallon, L T Kurland
Journal: American Journal of Psychiatry (1991)

The aim of the study was to determine incidence and prevalence rates and long-term trends in incidence of anorexia nervosa by identifying all persons residing in the community of Rochester, Minn., during the 50-year period 1935 through 1984 who had the disorder.From a community-based epidemiologic resource, 13,559 medical records with diagnoses of amenorrhea, starvation, weight loss, anorexia nervosa, or other conditions were screened to identify true cases of anorexia nervosa determined by using standard diagnostic criteria.One hundred eighty-one residents (166 female and 15 male) fulfilled the diagnostic criteria for anorexia nervosa; these were the incidence cases. Due to a quadratic trend in the rates for girls 10-19 years old, the incidence rate among female residents fell from 16.6 per 100,000 person-years in the 1935-1939 period to a low of 7.0 in 1950-1954 and increased to 26.3 in 1980-1984. The incidence rates for women 20 years old and older and for males remained constant. For females 15-24 years old, there was a linear increase. The overall age-adjusted incidence rate per 100,000 person-years was 14.6 for females and 1.8 for males. The prevalence rate per 100,000 population was 269.9 for females and 22.5 for males.Anorexia nervosa is more common than previously recognized. Among girls 15-19 years old it is a very common chronic illness. Its incidence has increased among females 15-24 years old but not among older women or among males.
Asymptomatic haematuria
Authors: J. Reynard
Journal: BMJ (2000)

Asymptomatic haematuria All patients with haematuria should undergo cystoscopyEditor-Having just performed cystoscopy on a man of 36 who presented with bladder cancer five years ago, I am not reassured by Del Mar's so called evidence based survey of the likely diagnoses associated with occult haematuria. 1 The quoted studies are likely to have missed cases of bladder cancer because not all patients underwent cystoscopy.Only 24 of 255 subjects in Ritchie et al's study underwent both upper tract imaging and cystoscopy. 2 Among these, two cases of bladder cancer and one of bladder dysplasia (a premalignant condition) were found.The other 231 patients had not been adequately screened to exclude the presence of bladder cancer.There was no mention of long term follow up to confirm the absence of urological cancer in those who did not undergo initial cystoscopy.Similarly, not all of Hiatt and Ordonez's patients underwent a full urological evaluation, 3 which prompts doubts about the accuracy of the performance statistics quoted in this paper.Sultana et al performed cystoscopy and upper tract imaging in all patients referred over one year with microscopic haematuria. 4 In those aged over 50, five bladder cancers and one renal cancer were diagnosed in 126 patients.More recently Khadra et al performed full urological evaluation of 982 patients with occult haematuria. 5 Altogether 5% had bladder cancer, 4% stone disease, and 0.3% renal cancer.Current urological training emphasises the importance of obtaining a midstream specimen of urine, upper tract imaging, and particularly cystoscopy in all patients who have haematuria, whether microscopic or macroscopic and whether persistent or not.Flexible cystoscopy can now be performed in minutes under local anaesthesia.I believe that there has to be a very good reason for not performing cystoscopy in patients with occult haematuria as this is likely to lead to missed diagnoses of bladder and renal cancer.
Dehydroepiandrosterone prevents linoleic acid-induced endothelial cell senescence by increasing autophagy
Authors: Min Jung Lee, Eun Hee Kim, Sang Ah. Lee, Yu Mi Kang, Chang Hee Jung, Hae Kyeong Yoon, So Mi Seol, Yoo La Lee, Woo Je Lee, Joong-Yeol Park
Journal: Metabolism (2015)
Adverse clinical outcome in Hodgkin's disease is associated with loss of retinoblastoma protein expression, high Ki67 proliferation index, and absence of Epstein-Barr virus-latent membrane protein 1 expression.
Authors: Manuel M. Morente, Miguel A. Piris, Victor Abraira, Agustin Acevedo, Beatriz Aguilera, Carmen Bellas, Máximo Fraga, Raimundo Garcia-Del-Moral, Francisco Gomez-Marcos, Javier Menarguez, Horacio Oliva, Margarita Sanchez-Beato, Carlos Montalban
Journal: Blood (1997)
Abstract 3219: Curcumin Prevents the Development of Hypertension-induced Left Ventricular Hypertrophy in Rats
Authors: Yoichi Sunagawa, Tatsuya Morimoto, Teruhisa Kawamura, Tomohide Takaya, Hiromichi Wada, Kazuhide Uemura, Akira Shimatsu, Tadashi Kimura, Masatoshi Fujita, Koji Hasegawa
Journal: Circulation (2009)

Background:  Hypertension causes left ventricular hypertrophy (LVH) with a preserved systolic function. While LVH might be a compensatory process, its presence of LVH is associated with an increased incidence of cardiovascular events and heart failure. Recently, we found that curcumin, a major curcumanoid isolated from  Curcuma longa , inhibits the histone acetyltransferase (HAT) activity of p300 as well as the p300-induced acetylation of histones and a hypertrophy-responsive transcription factor,GATA-4, in cultured cardiomyocytes. Furthermore, curcumin prevents deterioration of the systolic function in rat heart failure models  in vivo . However, whether curcumin prevents the development of hypertension-induced LHV at an early stage of hypertension is unclear.   Objective:  To solve this problem, we have utilized a salt-sensitive Dahl rat (DS) model of hypertension.   Methods:  We randomized 6-week-old DS (n=19) and control salt-resistant Dahl rats (DR, n=10) to a curcumin (Curc) or the vehicle (Veh) group. Then, these rats were given a high-salt diet and subjected to daily oral treatment with 50 mg/kg/day of curcumin or its vehicle for 5 weeks.   Results:  There were no differences between Curc and Veh in any data examined before treatment (6 weeks of age). The high-salt diet induced a similar degree of hypertension in these two groups of DS compared with DR. At 11 weeks of age, transthoracic echocardiography in Veh showed that the LV wall thickness (DS:2.0 mm, DR:1.0 mm), LV mass (DS:1.06 g/m 2 , DR:0.64 g/m 2 ), and LV fractional shortening (DS: 60%, DR:50%) were significantly higher in DS compared with DR, and the LV systolic and diastolic dimensions were significantly smaller in DS than DR. Curcumin treatment significantly (p 2 , Veh:1.06 g/m 2 ), but not in DR. However, LV fractional shortening in DS was similar between the two groups (Curc:57%, Veh:60%).   Conclusions:  The natural compound curcumin inhibits the development of hypertension-induced concentric LVH without affecting the systolic function. Thus, this compound might be applicable to patients with early-stages hypertensive heart diseases.
Characteristics of subjects susceptible to exacerbation-like respiratory events in a population-based cohort: Canadian cohort obstructive lung disease (CanCOLD) study
Authors: Laura Labonté, Palmina Mancino, Wan Tan, Robert Cowie, Paul Hernandez, Kenneth Chapman, Pei Li, Shawn Aaron, Andrea Benedetti, Mark Fitzgerald, François Maltais, Darcy Marciniuk, Denis O'Donnell, Don Sin, Jean Bourbeau
Journal: European Respiratory Journal (2014)

Rationale: There is no information on the characteristics of subjects sampled from the general population with mild to moderate COPD who are susceptible to exacerbation-like respiratory events.  Objective: Assess in a population-based sample, if there are differences between the characteristics of subjects with COPD who report exacerbation-like events and those who do not.  Methods: Canadian Cohort Obstructive Lung Disease (CanCOLD) is a longitudinal, multi-center study, 1400 subjects, ≥40 years old, identified by random digit dialling from the general population. Subjects are sex- and age-matched, and grouped:1) COPD moderate+ (GOLD≥2); 2) COPD mild (GOLD1); 3) at risk (ever smoker); 4) healthy (never smoker, no obstruction). An exacerbation questionnaire is administered at baseline and every 3 months to detect changes in respiratory symptoms, medication, work and health service use.  Results: In a preliminary analysis of 372 subjects with COPD, 73 reported having an exacerbation-like event during a 6-month follow-up, 299 did not. Subjects who reported at least 1 event had greater BODE scores, a 2-fold increase in respiratory medication, and decreased lung function and health status. Smoking, MRC dyspnea score and co-morbidities were not associated with exacerbation events. Frequency of exacerbations increased with disease severity.  Conclusions: From a population-sampling based cohort that mirrors the population of COPD patients at large,exacerbation-like respiratory events are associated with worsening disease manifestation in subjects with mild or moderate COPD. Longitudinal evaluation will allow for phenotype analysis.
Structured light plethysmography as an assessment tool for dysfunctional breathing in children
Authors: Nicki Barker, Laurie Smith, Willem De Boer, Mark Everard
Journal: European Respiratory Journal (2014)

Background   Dysfunctional breathing (DB) is a respiratory disorder characterised by abnormal breathing patterns. Currently there is no comprehensive method available for objectively measuring these patterns.   Aim   The aim of this study was to investigate whether structured light plethysmography (SLP) can be used for the objective measurement of breathing patterns in children with DB.   Methods   Tidal breathing was recorded, using the Thora3Di TM  SLP device, in 41 children (20 with DB and 21 healthy controls). Measured parameters included overall phase, principle angle, breath phase, inspiratory time and expiratory time.   Results   No significant difference was found in the measured parameters between healthy children and those with DB, when comparing periods of settled tidal breathing (p>0.19). However, when comparing all tidal breaths recorded for each child, a significant difference (p=0.03) in breath phase was found between the 2 groups. Breath phase is the difference in phase angle between the thorax and abdomen signals and was closer to zero in the DB group, indicating a more synchronous pattern than the control group.   Conclusion   SLP can be used to objectively measure breathing patterns in children with DB, but longer captures may be required to achieve more reliable data.