bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Strategies Utilized in the Setting of Acquired Resistance to EGFR Tyrosine Kinase Inhibitors
Authors: Yu Helena A. , Riely Gregory J. , Lovly Christine M. 
Published: October 2014

Abstract
Patients with EGFR-mutant lung cancer derive significant therapeutic benefit from treatment with EGFR tyrosine kinase inhibitors (TKI). Unfortunately, acquired resistance is an inevitable consequence of this treatment strategy, with a broad variety of resistance mechanisms including acquired EGFR mutations (e.g., T790M) and activation of bypass signaling pathways, such as MET and HER2. Several therapeutic strategies hypothesized to delay or overcome resistance have been tested in clinical trials, including “next-generation” EGFR TKIs and rational combinations of targeted agents. However, to date, there are no FDA-approved therapies for patients with acquired resistance to first-line EGFR TKI therapy. There remains a critical need for more effective and better tailored treatments in this setting to match treatments to the individual patient and specific resistance mechanism at hand. In this review, we discuss known mechanisms of resistance to first-line EGFR TKI therapy and describe previous and ongoing strategies to overcome resistance. Clin Cancer Res; 20(23); 5898–907. ©2014 AACR.
Mutational Landscape of Aggressive Cutaneous Squamous Cell Carcinoma
Authors: Pickering Curtis R. , Zhou Jane H. , Lee J. Jack , Drummond Jennifer A. , Peng S. Andrew , Saade Rami E. , Tsai Kenneth Y. , Curry Jonathan L. , Tetzlaff Michael T. , Lai Stephen Y. , Yu Jun , Muzny Donna M. , Doddapaneni Harshavardhan , Shinbrot Eve , Covington Kyle R. , Zhang Jianhua , Seth Sahil , Caulin Carlos , Clayman Gary L. , El-Naggar Adel K. , Gibbs Richard A. , Weber Randal S. , Myers Jeffrey N. , Wheeler David A. , Frederick Mitchell J. 
Published: October 2014

Abstract
Purpose: Aggressive cutaneous squamous cell carcinoma (cSCC) is often a disfiguring and lethal disease. Very little is currently known about the mutations that drive aggressive cSCC.
Experimental Design: Whole-exome sequencing was performed on 39 cases of aggressive cSCC to identify driver genes and novel therapeutic targets. Significantly, mutated genes were identified with MutSig or complementary methods developed to specifically identify candidate tumor suppressors based upon their inactivating mutation bias.
Results: Despite the very high-mutational background caused by UV exposure, 23 candidate drivers were identified, including the well-known cancer-associated genes TP53, CDKN2A, NOTCH1, AJUBA, HRAS, CASP8, FAT1, and KMT2C (MLL3). Three novel candidate tumor suppressors with putative links to cancer or differentiation, NOTCH2, PARD3, and RASA1, were also identified as possible drivers in cSCC. KMT2C mutations were associated with poor outcome and increased bone invasion.
Conclusions: The mutational spectrum of cSCC is similar to that of head and neck squamous cell carcinoma and dominated by tumor-suppressor genes. These results improve the foundation for understanding this disease and should aid in identifying and treating aggressive cSCC. Clin Cancer Res; 20(24); 6582–92. ©2014 AACR.
A Tale of Two Receptors: Insulin and Insulin-Like Growth Factor Signaling in Cancer
Authors: Yee Douglas 
Published: October 2014

Abstract
Inhibition of the type I IGF receptor (IGF1R) has been the focus of numerous clinical trials. Two reports in this issue describe the results of phase I trials of an IGF1R tyrosine kinase inhibitor OSI-906. This commentary will describe the complex endocrine changes induced by these types of agents. Clin Cancer Res; 21(4); 667–9. ©2014 AACR.
See related articles by Jones et al., p. 693, and Puzanov et al., p. 701
Clinically Relevant microRNAs in Ovarian Cancer
Authors: Zhang Shu , Lu Zhen , Unruh Anna K. , Ivan Cristina , Baggerly Keith A. , Calin George A. , Li Zongfang , Bast Robert C. , Le Xiao-Feng 
Published: October 2014

Abstract
microRNAs (miRNAs/miRs) belong to a class of small noncoding RNAs that can negatively regulate messenger RNA (mRNA) expression of target genes. miRNAs are involved in multiple aspects of ovarian cancer cell dysfunction and the phenotype of ovarian cancer cells can be modified by targeting miRNA expression. miRNA profiling has detected a number of candidate miRNAs with the potential to regulate many important biologic functions in ovarian cancer, but their role still needs to be clarified, given the remarkable heterogeneity among ovarian cancers and the context-dependent role of miRNAs. This review summarizes the data collected from The Cancer Genome Atlas (TCGA) and several other genome-wide projects to identify dysregulated miRNAs in ovarian cancers. Copy number variations (CNVs), epigenetic alterations, and oncogenic mutations are also discussed that affect miRNA levels in ovarian disease. Emphasis is given to the role of particular miRNAs in altering expression of genes in human ovarian cancers with the potential to provide diagnostic, prognostic, and therapeutic targets. Particular attention has been given to TP53, BRCA1/2, CA125 (MUC16), HE4 (WFDC2), and imprinted genes such as ARHI (DIRAS3). A better understanding of the abnormalities in miRNA expression and downstream transcriptional and biologic consequences will provide leads for more effective biomarkers and translational approaches in the management of ovarian cancer. Mol Cancer Res; 13(3); 393–401. ©2014 AACR.
Trends in Early Aspirin Use Among Patients With Acute Myocardial Infarction in China, 2001–2011: The China PEACE‐Retrospective AMI Study
Authors: Gao Yan , Masoudi Frederick A. , Hu Shuang , Li Jing , Zhang Haibo , Li Xi , Desai Nihar R. , Krumholz Harlan M. , Jiang Lixin ,   the China PEACE Collaborative Group
Published: October 2014

Background

Aspirin is an effective, safe, and inexpensive early treatment of acute myocardial infarction (
AMI
) with few barriers to administration, even in countries with limited healthcare resources. However, the rates and recent trends of aspirin use for the early treatment of
AMI
in China are unknown.

Methods and Results

Using data from the China Patient‐centered Evaluative Assessment of Cardiac Events Retrospective Study of Acute Myocardial Infarction (China
PEACE
‐Retrospective
AMI
Study), we identified a cohort of 14 041 patients with
AMI
eligible for early aspirin therapy. Early use of aspirin for
AMI
increased over time (78.4% in 2001, 86.5% in 2006, and 90.0% in 2011). However, about 15% of hospitals had a rate of use of <80% in 2011. Treatment was less likely in patients who were older, presented with cardiogenic shock at admission, presented without chest discomfort, had a final diagnosis of non‐
ST
‐segment elevation acute myocardial infarction, or did not receive reperfusion therapy. Hospitalization in rural regions was also associated with aspirin underuse.

Conclusions

Despite improvements in early use of aspirin for
AMI
in China, there remains marked variation in practice and opportunities for improvement that are concentrated in some hospitals and patient groups.

Clinical Trial Registration

URL:
ClinicalTrials.gov
Unique identifier: NCT01624883.
Tracheal Size Variability Is Associated With Sex
Authors: Karmakar Arunabha , Pate Mariah B. , Solowski Nancy L. , Postma Gregory N. , Weinberger Paul M. 
Published: October 2014

Purpose: Whereas selection of endotracheal tube (ETT) size in pediatric patients benefits from predictive nomograms, adult ETT sizing is relatively arbitrary. We sought to determine associations between cervical tracheal cross-sectional area (CTCSA) and clinical variables. Methods: One hundred thirty-two consecutive patients undergoing noncontrasted chest computed tomography (CT) at a single tertiary care institution from January 2010 to June 2011 were reviewed. Patients with improper CT technique, endotracheal intubation, and pulmonary/tracheal pathology were excluded. Tracheal luminal diameters in anteroposterior (D1) and transverse (D2) were measured 2 cm inferior to the cricoid and used to determine CTCSA = π*D1*D2*¼. The demographic variables of age, height, weight, and body mass index (BMI) were tested for association with CTCSA by Spearman correlation. Wilcoxon rank-sum test was used to compare CTCSA by race and sex. Multivariate linear regression was performed including all clinical variables. Results: There were 91 patients who met inclusion criteria. There was no correlation between age, weight, or BMI and CTCSA. There was a significant positive correlation between patient height and CTCSA ( P = .001, R = 0.35); however, this was confounded by sex. Female patients had significantly smaller CTCSA (mean = 241 mm2) compared to male patients (mean = 349 mm2, P < .001). Multivariate linear regression stratified by sex revealed that height is correlated with CTCSA only in males ( P = .028). Males also had more variability in CTCSA (SD 118.6) compared to females (SD 65.5). Conclusion: Our data suggest that selection of ETT size in male patients should include height as a predictive factor. For female patients, it may be appropriate to select a uniformly smaller diameter ETT size.
Analysis of the barriers of mental distress disclosure in medical inpatients in Taiwan
Authors: Han Der-Yan , Lin Yi-Yin , Liao Shih-Cheng , Lee Ming-Been , Thornicroft Graham , Wu Chia-Yi 
Published: October 2014

Background: Disclosure of mental distress to physicians is important for mental illness identification, early referrals and proper treatment to prevent suicide. Little is known about what affects mental health communication in the clinical settings in the Chinese societies. Aims: The study aimed to identify the demographic, psychosocial and medical factors related to people with non-disclosure of their mental distress. Methods: We interviewed a series of consecutive inpatients from two medical wards of a general hospital in northern Taiwan. We collected depressive symptoms (the Patient Health Questionnaire, PHQ-9), living arrangement, threatening life events, suicide risks (i.e. past self-harm history, lifetime suicide ideas and hopelessness) and recent experience of mental distress disclosure. Furthermore, we explored the reasons of non-disclosure. Results: A total of 230 medical inpatients agreed to participate (53.5% males). The results indicated that only 5.7% actually communicated their mental health concerns, and that 12.3% were willing to talk about their mental health problems. Among the 69 (30%) depressed participants (PHQ-9 score ≥ 10 points), the disclosure rate was low (8.7%) and the wish to talk about mental distress was also low (10.3%). After adjustment, living alone (OR = 7.58, 95% CI = 1.56–36.91) and having stressful life events (OR = 3.68, 95% CI = 1.09–12.46) remained significant in predicting disclosure of mental distress. The 109 participants attributed their refusal of communicating mental distress as medical-related attributes, subjective perceptions or sociocultural factors. Conclusion: Communication of mental distress in medical settings was uncommon due to medical or psychosocial barriers in Taiwan. Skill training to facilitate disclosure in medical education and public campaigns to improve knowledge of depression and enhance help-seeking deserve more attention, particularly under the influence of stigma in the Chinese societies.
Hikikomori in Spain: A descriptive study
Authors: Malagón-Amor Ángeles , Córcoles-Martínez David , Martín-López Luis M , Pérez-Solà Víctor 
Published: October 2014

Background: Social withdrawal behaviour is a major health problem that is becoming increasingly important, being necessary studies that investigate its psychopathology and existence in different cultures. Aims: To describe the clinical and socio-demographic characteristics of hikikomori individuals in Spain. Method: Participants were 200 subjects referred to the Crisis Resolution Home Treatment (CRHT) because of social isolation. The definition of hikikomori was the state of avoiding social engagement with generally persistent withdrawal into one’s residence for at least 6 months. Socio-demographic and clinical data were analysed, including Severity of Psychiatric Illness (SPI), Global Assessment of Functioning (GAF), Clinical Global Impression (CGI) and World Health Organization Disability Assessment (WHODAS) scales. Results: A total of 164 cases were evaluated. Hikikomori were predominantly young male, with the mean age at onset of hikikomori of 40 years old and a mean socially withdrawn period of 3 years. Only three people had no symptoms suggestive of mental disorder. Psychotic and anxiety were the most common comorbid disorders. The scales administered describe the presence of serious symptoms and impairment in social functioning, with a high prevalence of poor collaboration with treatment. Conclusion: This study shows the existence of hikikomori in Spain. Its difficult detection and treatment highlights the need for specialized domiciliary teams. The high comorbidity leads us to conclude that it may not be a new diagnosis, but rather a severe syndrome associated with multiple mental illnesses. Primary hikikomori also exist, but less commonly. Future cross-national studies are needed in order to describe its definition and psychopathology.
Amartya Sen on human rights in The Idea of Justice
Authors: Macleod Alistair M. 
Published: October 2014

In section I, I identify several mini-theses embedded in Amartya Sen’s theory of human rights – such theses as (1) that human rights are moral, not legal, rights, (2) that nevertheless they are not rights that are awaiting transformation into legal rights, (3) that an expansive doctrine of human rights can incorporate a broad swath of rights (civil, political, economic, social and cultural) without merely mimicking the catalogues in post-Second World War declarations and covenants, and (4) that not all the obligations generated by human rights are (in Kant’s language) ‘perfect’ obligations. In section II, I argue that, both because ‘freedom’ has many interpretations and because not all human freedoms, even when they are life-enhancing, are to be protected as human rights, the distinctive features of Sen’s version of a freedom-emphasizing doctrine would be clearer if the preferred interpretation of ‘freedom’ and the particular human freedoms to be protected were more explicitly identified. While Sen’s doctrine of human rights is a freedom-emphasizing doctrine, its distinctive features – vis-à-vis competing freedom-focused accounts – would be more clearly etched if it were made clearer what the sense is in which it stresses protection of important human freedoms, especially since he concedes that not all freedoms, even when they are life-enhancing for human beings, should be protected as human rights.
Manifest injustice from the (de)colonial matrix
Authors: Sanín-Restrepo Ricardo , Méndez-Hincapié Gabriel 
Published: October 2014

Amartya Sen’s theory of enhancement of justice bears an insurmountable blind side that impairs and makes it incomplete, if not parochial. It dismisses coloniality as the veiled face of modernity (and of capitalism) without which any understanding of a theory of justice in a globalized world is impossible. Constructing a theory outside the complex frame of coloniality makes the theory vulnerable to severe hindrances. The duality (coloniality/modernity) produces a twofold but interdependent reality: for the western world it means the achievement of values such as liberty and prosperity; for the non-western world, racism, extraction and exclusion. Since colonialism has been rearticulated into coloniality, these two categories cannot be isolated for they presuppose one another. Democracy remains a fallacy as long as real power depends on capitalism, which is the inextricable way of coloniality itself. Henceforth, free public discussion and free social choice remain chimerical, obtainable only when democracy as a true, unresolved conflict is a reality through the destruction of coloniality. Finally we propose a third principle of justice that would correct both Rawls’ and Sen’s conceptions of justice. Such corrections pinpoint the void in their approaches thus inverting the panoptic.
Evaluation of Voice Quality after Supraglottic Laryngectomy
Authors: Topaloğlu İlhan , Salturk Ziya , Atar Yavuz , Berkiten Güler , Büyükkoç Onur , Çakır Ozan 
Published: October 2014

ObjectiveSupraglottic laryngectomy is a surgical procedure that preserves laryngeal functions. This technique allows extensions including removal of tongue base or 1 arytenoid. We aimed to compare vocal results of supraglottic laryngectomy and extended procedures.Study DesignCross‐sectional study.SettingTertiary care hospital.Subjects and MethodsThirty‐three males who underwent supraglottic laryngectomy were included in the study. Fifteen patients (45.5%) were applied standard supraglottic laryngectomy (standard supraglottic laryngectomy group). In 11 patients (33.3%), unilateral arytenoid cartilage was totally resected by separation at the cricoarytenoid joint (laterally extended group), and the tongue base was removed in 7 patients (anteriorly extended group) (21.2%). Twenty male smokers constituted control group. Acoustic and aerodynamic voice analyses were performed for the assessment of objective results. Grade, roughness, breathiness, asthenia, and strain scale (GRBAS) scores were analyzed for perceptual assessment. Voice Handicap Index‐30 was used to evaluate subjective results.ResultsThe comparison of supraglottic laryngectomy group with the control group revealed that the mean maximum phonation time and fundamental frequency were significantly lower in the supraglottic laryngectomy group (P <. 001), and the mean jitter, shimmer, and noise‐to‐harmonics ratio were significantly higher in the supraglottic laryngectomy group (P <. 001). Maximum phonation time and fundamental frequency were higher in the standard supraglottic laryngectomy group in comparison to extended groups. Jitter value was also lower in the standard supraglottic laryngectomy group compared to extended groups. Perceptual and subjective analyses revealed no difference among standard supraglottic laryngectomy and extended groups.ConclusionThe results of this study indicate that supraglottic laryngectomy patients have acceptable voice quality, as determined by perceptual and subjective assessment.
Contribution of verbal suggestion to the therapeutic efficacy of an analgesic agent for acute primary headache
Authors: Oktay Cem , Eken Cenker , Goksu Erkan , Dora Babur 
Published: October 2014

Objective The therapeutic response of a patient cannot purely be explained by the method of therapy or the efficacy of a drug. Clinician-patient interaction, psychosocial factors, patients’ expectations, hopes, beliefs and fears are all related to the healing outcome. Malleability and suggestibility are also important in the placebo or nocebo effect. The purpose of this study was to evaluate whether adding brief verbal suggestions for pain relief could change the magnitude of an analgesic’s efficacy. Methods This prospective study was performed in the emergency department of a university hospital. Patients who were ordered analgesia with diclofenac sodium for primary headache were divided into three groups. All groups were informed that they would be administered a pain killer by intramuscular injection. The second and third groups were given positive and reduced treatment expectations about the therapeutic efficacy, respectively. Patients were asked to rate their pain on a VAS at 0 and 45 minutes and if they needed any additional analgesic 45 minutes after the injection. Results A total of 153 patients were included in the study. The paired univariate analyses showed significant differences for all groups between 0- and 45-minute VAS scores. However, there was no difference between the three groups according to the differences in VAS scores between 45 and 0 minutes and according to the administration of an additional drug. Conclusion Simple verbal suggestions did not alter the efficacy of an analgesic agent for headache in an emergency setting. The contributions of suggestibility, desire and expectation in acute primary headache patients should be further investigated.
Low cognitive reserve is associated with chronic migraine with medication overuse and poor quality of life
Authors: Gómez-Beldarrain Marian , Anton-Ladislao Ane , Aguirre-Larracoechea Urko , Oroz Isabel , García-Moncó Juan Carlos 
Published: October 2014

Objective The objective of this article is to test the hypothesis that cognitive reserve (CR) is related to migraine chronification, medication overuse and poor quality of life in migraineurs. Design/methods A cross-sectional study on patients with chronic migraine with medication overuse (CM-MOH), episodic migraine (EM), and controls, matched by sex, age and education, was carried out. CR was assessed by a specific questionnaire, and quality of life was measured by general and specific questionnaires (SF-36 and MSQoL). Migraine Disability Assessment Scale and Beck questionnaires for depression and anxiety were used. Medication dependence was evaluated by the medication-dependence questionnaire in headache (MDQ-H). Results Fifty-five individuals were enrolled: 18 CM-MOH patients (32.73%), 22 EM patients (40%) and 15 controls (27.27%). Fifty (90.91%) of them were females and aged 43.53 (7.54) years. Univariate analysis showed a significant association between the study group and CR, and all items of the SF-36, anxiety and depression questionnaires, MSQoL and MDQ-H. The lower CR and CM-MOH group were related to a worse quality of life, more anxiety and depression and the highest medication dependence scores. Multivariate analysis showed that higher CR scores were related to higher quality of life as measured by the physical and mental composite scores of the SF-36, and to lower anxiety (beta = −1.08, p = 0.001) and depression (beta = −0.56, p = 0.03) levels. Focusing on MSQoL, the increase in CR was predictive of a better quality of life (beta = 1.88, p < 0.0001). By all the models, the explained variance of the sample ranged from 39% (mental composite score) to 58% (MSQoL). Conclusions Low CR appears to be an independent factor associated with the deterioration of quality of life, the presence of anxiety and depression, and drug dependence and medication overuse in CM-MOH.
Migraine, cardiovascular disease, and stroke during pregnancy: Systematic review of the literature
Authors: Wabnitz Ashley , Bushnell Cheryl 
Published: October 2014

Objective The objective of this article is to review the literature relating migraine, cardiovascular disease, and stroke during pregnancy in order to better define the relationship between migraines and vascular disease. Methods We conducted a systematic review of the literature using Medline and Cochrane Review with the following search terms: migraine AND pregnancy and vascular disease OR myocardial infarction OR heart disease OR stroke OR cerebrovascular disease OR hypertension in pregnancy. We also reviewed the bibliographies of papers identified in this search to obtain additional relevant studies. Results Of the 219 papers obtained with the primary search, we found 17 that were topically relevant. Altogether, there is an increased risk both of gestational hypertension (OR range from 1.23 to 1.68) and preeclampsia (OR range 1.08 to 3.5) in migraineurs compared to nonmigraineurs. In addition, there is an association between an increased risk of ischemic stroke in pregnancy (OR range 7.9 to 30.7), particularly with active migraine. There is also an association between migraine and increased risk of acute myocardial infarction and heart disease (OR 4.9; 95% CI 1.7, 14.2), and thromboembolic events during pregnancy (deep venous thrombosis OR 2.4; 95% CI 1.3, 4.2 and pulmonary embolus OR 3.1; 95% CI 1.7, 5.6). Conclusion In this review, we summarized the association between migraine and risk of vascular disease during pregnancy, based on the available literature. Given the limited amount of data, more research on these associations is needed to determine which women with migraine may be at risk while pregnant.