bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical experiences with molecular targeted therapy in lung cancer in China
Authors: Wang Yan , Sun Yan 
Published: April 2015

AbstractIn the past decade, a dramatic shift has been witnessed in cancer therapy in China. Although traditional cytotoxic chemotherapy still remains the treatment of choice for many malignancies, targeted therapies are now a component of treatment for many types of cancer, including lung cancer. As molecular target agents are widely used in clinical practice and relevant studies have been conducted, we have accumulated valuable experience in the treatment strategy for advanced non‐small cell lung cancer. On this basis we have successfully developed our Class‐I new drug through independent research, which significantly accelerates the clinical development of targeted therapy for lung cancer. This article summarizes the clinical practice and relevant studies of current targeted therapies for lung cancer in China.
Intraarrest Rhythms and Rhythm Conversion in Asphyxial Cardiac Arrest
Authors: Varvarousi Giolanda , Chalkias Athanasios , Stefaniotou Antonia , Pliatsika Paraskevi , Varvarousis Dimitrios , Koutsovasilis Anastasios , Xanthos Theodoros 
Published: April 2015

AbstractObjectivesThe objective was to analyze the cardiac arrest rhythms presenting during asphyxial cardiac arrest (ACA).MethodsAsphyxial cardiac arrest was induced in 30 Landrace large white piglets, aged 12 to 15 weeks and with a mean (±SD) weight of 20 (±2) kg. After the onset of cardiac arrest, the animals were left untreated for 4 minutes, after which cardiopulmonary resuscitation was commenced. Heart rhythms were monitored from the onset of asphyxia until return of spontaneous circulation or death.ResultsAfter endotracheal tube clamping and prior to cardiac arrest, normal sinus rhythm was noted in 14 animals, atrial fibrillation in two animals, Mobitz II atrioventricular block in 10 animals, and third‐degree atrioventricular block in four animals. At the onset of cardiac arrest, seven animals had ventricular fibrillation (VF), two had asystole, and 21 had pulseless electrical activity (PEA). During the 4‐minute period of untreated arrest, however, significant changes in the monitored rhythm were noted; at the end of the fourth minute, 19 animals had VF, two animals had asystole, and nine animals had PEA.ConclusionsThe most common rhythm after 4 minutes of untreated ACA was VF, while in 57% of animals, PEA was spontaneously converted to VF during the cardiac arrest interval.
Radiographic Evaluation of Carotid Artery Compression in Patients With Extraglottic Airway Devices in Place
Authors: White Jenna M. B. , Braude Darren A. , Lorenzo Gamaliel , Hart Blaine L. 
Published: April 2015

AbstractObjectivesExtraglottic airway devices (EADs) are now commonly placed for airway management of critically ill or injured patients, particularly by emergency medical services providers in the out‐of‐hospital setting. Recent literature has suggested that EADs may cause decreased cerebral blood flow due to compression of the arteries of the neck by the devices’ inflated cuffs.MethodsThe authors identified a cohort of 17 patients presumed to be hemodynamically stable with EADs in place who underwent radiographic imaging of the neck. These studies were reviewed by a neuroradiologist to determine if mechanical compression of the carotid arteries was present.ResultsNone of the 17 cases reviewed had radiographically evident mechanical compression of the carotid artery.ConclusionsUntil further studies are performed in which cerebral perfusion is evaluated prospectively in both hemodynamically stable and unstable human subjects, there is insufficicent evidence to recommend against the use of extraglottic airways in the emergency setting on the basis of carotid artery compression.
The “5Es” of Emergency Physician–performed Focused Cardiac Ultrasound: A Protocol for Rapid Identification of Effusion, Ejection, Equality, Exit, and Entrance
Authors: Kennedy Hall M. , Coffey E. C. , Herbst Meghan , Liu Rachel , Pare Joseph R. , Andrew Taylor R. , Thomas Sheeja , Moore Chris L. 
Published: April 2015

AbstractEmergency physician (EP)‐performed focused cardiac ultrasound (EP FOCUS) has been increasingly recognized as a crucial tool to help clinicians diagnose and treat potentially life‐threatening conditions. The existing literature demonstrates a variety of EP FOCUS applications and protocols; however, EP FOCUS is not taught, practiced, or interpreted consistently between institutions. Drawing on over 12 years of experience in a large‐volume, high‐acuity academic emergency department, we have developed a protocol for teaching and performing EP FOCUS known as “The 5Es,” where each E represents a specific assessment for immediately relevant clinical information. These include pericardial effusion, qualitative left ventricular ejection, ventricular equality, exit (aortic root diameter), and entrance (inferior vena cava diameter and respirophasic variation). Each of these assessments has been well described in the emergency medicine literature and is within the scope of EP‐performed echocardiography. This approach provides a reliable and easily recalled framework for assessing, teaching, and communicating EP FOCUS findings that are essential in caring for the patient in the emergency setting.
Clinical Risk Factors for In‐hospital Adverse Cardiovascular Events After Acute Drug Overdose
Authors: Manini Alex F. , Hoffman Robert S. , Stimmel Barry , Vlahov David 
Published: April 2015

AbstractObjectivesIt was recently demonstrated that adverse cardiovascular events (ACVE) complicate a high proportion of hospitalizations for patients with acute drug overdoses. The aim of this study was to derive independent clinical risk factors for ACVE in patients with acute drug overdoses.MethodsThis prospective cohort study was conducted over 3 years at two urban university hospitals. Patients were adults with acute drug overdoses enrolled from the ED. In‐hospital ACVE was defined as any of myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest.ResultsThere were 1,562 patients meeting inclusion/exclusion criteria (mean age, 41.8 years; female, 46%; suicidal, 38%). ACVE occurred in 82 (5.7%) patients (myocardial injury, 61; shock, 37; dysrhythmia, 23; cardiac arrests, 22) and there were 18 (1.2%) deaths. On univariate analysis, ACVE risk increased with age, lower serum bicarbonate, prolonged QTc interval, prior cardiac disease, and altered mental status. In a multivariable model adjusting for these factors as well as patient sex and hospital site, independent predictors were: QTc > 500 msec (3.8% prevalence, odds ratio [OR] = 27.6), bicarbonate < 20 mEq/L (5.4% prevalence, OR = 4.4), and prior cardiac disease (7.1% prevalence, OR = 9.5). The derived prediction rule had 51.6% sensitivity, 93.7% specificity, and 97.1% negative predictive value, while presence of two or more risk factors had 90.9% positive predictive value.ConclusionsThe authors derived independent clinical risk factors for ACVE in patients with acute drug overdose, which should be validated in future studies as a prediction rule in distinct patient populations and clinical settings.
Chronic Ethanol‐Induced Impairment of Wnt/β‐Catenin Signaling is Attenuated by PPAR‐δ Agonist
Authors: Xu Chelsea Q. , de la Monte Suzanne M. , Tong Ming , Huang Chiung‐Kuei , Kim Miran 
Published: April 2015

BackgroundThe Wnt/β‐catenin pathway regulates liver growth, repair, and regeneration. Chronic ethanol (EtOH) exposure blunts normal liver regenerative responses, in part by inhibiting insulin/IGF signaling, and correspondingly, previous studies showed that EtOH‐impaired liver regeneration could be restored by insulin sensitizer (proliferator‐activated receptor [PPAR]‐δ agonist) treatment. As Wnt/β‐catenin functions overlap and cross talk with insulin/IGF pathways, we investigated the effects of EtOH exposure and PPAR‐δ agonist treatment on Wnt pathway gene expression in relation to liver regeneration.MethodsAdult male Long Evans rats were fed with isocaloric liquid diets containing 0 or 37% EtOH for 8 weeks and also treated with vehicle or a PPAR‐δ agonist during the last 3 weeks of the feeding regimen. The rats were then subjected to 70% partial hepatectomy (PH) and livers harvested at various post‐PH time points were used to quantitate expression of 19 Wnt pathway genes using Quantigene 2.0 Multiplex Assay.ResultsEtOH broadly inhibited expression of Wnt/β‐catenin signaling‐related genes, including down‐regulation of Wnt1, Fzd3, Lef1, and Bcl9 throughout the post‐PH time course (0 to 72 hours), and suppression of Wnt7a, Ccnd1, Fgf4, Wif1, Sfrp2, and Sfrp5 at 18‐ and 24‐hour post‐PH time points. PPAR‐δ agonist treatments rescued the EtOH‐induced suppression of Wnt1, Wnt7a, Fzd3, Lef1, Bcl9, Ccnd1, and Sfrp2 gene expression in liver, corresponding with the improvements in DNA synthesis and restoration of hepatic architecture.ConclusionsChronic high‐dose EtOH exposures inhibit Wnt signaling, which likely contributes to the impairments in liver regeneration. Therapeutic effects of PPAR‐δ agonists extend beyond restoration of insulin/IGF signaling mechanisms and are mediated in part by enhancement of Wnt pathway signaling. Future studies will determine the degree to which targeted restoration of Wnt signaling is sufficient to improve liver regeneration and remodeling in the context of chronic EtOH exposure.
Analysis of Human Triallelic SNPs by Next‐Generation Sequencing
Authors: Cao Min , Shi Juan , Wang Jiqiu , Hong Jie , Cui Bin , Ning Guang 
Published: April 2015

SummaryAlthough single‐nucleotide polymorphisms (SNPs) have become extremely useful in the study of geneticvariation, triallelic SNPs are still not fully understood. Next‐generation sequencing (NGS) is a promising approach to identify triallelic sites in large populations. In this study, we explored exome sequencing data from 221 Chinese individuals, with an average depth of 70‐fold. We identified 382,901 SNPs in the study samples, including 2,002 (0.52%) triallelic sites. Among the triallelic SNPs, 17.3% were coding SNPs (cSNPs) and 78.3% were novel. Comparison and analysis revealed that the variant alleles were more likely to result in nonsynonymous variation at triallelic sites. In addition, natural selection seemed to influence triallelic SNPs. However, with the limited sample size assessed, more studies will be required in order to fully characterize the features of triallelic SNPs.
Lipid transfer protein sensitization: reactivity profiles and clinical risk assessment in an Italian cohort
Authors: Scala E. , Till S. J. , Asero R. , Abeni D. , Guerra E. C. , Pirrotta L. , Paganelli R. , Pomponi D. , Giani M. , De Pità O. , Cecchi L. 
Published: April 2015

AbstractBackgroundNonspecific lipid transfer proteins (nsLTPs) represent a major cause of systemic food allergic reactions in the Mediterranean area. This study investigate hierarchical patterns and cluster relationships of IgE sensitization to different nsLTPs, and the relationship to clinical allergy in a large Italian cohort.MethodsA total of 568 nsLTP‐positive subjects after IgE ImmunoCAP‐ISAC microarray analysis with Ara h 9, Art v 3, Cor a 8, Jug r 3, Pla a 3, Pru p 3 and Tri a 14 allergens were studied. IgE inhibition experiments were carried out with mugwort and plane tree pollen extracts.ResultsEighty‐two per cent of nsLTP‐positive participants (94% if <6 years old) were Pru p 3pos, and 71% were Jug r 3pos. Participants who reacted to >5 nsLTPs reported a higher incidence of food‐induced systemic reactions. Only Art v 3 and Pla a 3 (mugwort and plane tree nsLTPs, respectively) were associated with respiratory symptoms, and a correlation was observed between sensitization to pollen and plant food nsLTPs, particularly between Pla a 3 and tree nut/peanut nsLTPs. Co‐sensitization to Par j 2 and PR‐10 or profilin pan‐allergens was associated with a lower prior prevalence of severe food‐induced reactions. In inhibition assays, plane and mugwort pollen extracts inhibited 50–100% of IgE binding to food nsLTPs in microarrays.ConclusionsTesting IgE reactivity to a panel of nsLTP allergens unveils important associations between nsLTP sensitization profiles and clinical presentation and allows the identification of novel cluster patterns indicating likely cross‐reactivities and highlighting potential allergens for nsLTP immunotherapy.
Malignant glomus tumor with oncocytic features: an unusual presentation of dysphagia
Authors: Ugras Nesrin , Yercİ Ömer , Yalçınkaya Ulviye , Gülcü Barış , Öztürk Ersin , Yıldırım Çınar , Çavuşoğlu İlkin 
Published: April 2015

Glomus tumors in the gastrointestinal tract are unusual, as the previous series in the literature have been mainly limited to the stomach. Less than 10 cases of esophageal glomus tumors have been described in the literature. Oncocytic glomus tumors are a recently identified, rare variant of the glomus tumor. We report a 47‐year‐old female who presented with an approximately 3‐month history of dysphagia and weight loss. Upper gastrointestinal endoscopy showed a black‐purple, hypervascular, protruding lesion measuring approximately 65 mm at the 37th cm of the esophagus. The patient underwent an Ivor Lewis operation via open thoracotomy. The resected specimen had a protuberant, ulcerated mass measuring 80 × 35 mm in the posterior wall of the esophagus. Based on the histopathological, immunohistochemical and electron microscope findings, the final diagnosis was a malignant glomus tumor with oncocytic features. To our knowledge, this is the first report of a malignant glomus tumor with oncocytic features in an esophageal location.
Systematic review and meta‐analysis: opportunistic infections and malignancies during treatment with anti‐integrin antibodies in inflammatory bowel disease
Authors: Luthra P. , Peyrin‐Biroulet L. , Ford A. C. 
Published: April 2015

SummaryBackgroundAnti‐integrin antibodies are effective therapies for Crohn's disease (CD) and ulcerative colitis (UC). However, these drugs carry theoretical risks of opportunistic infection and malignancy.AimTo pool data from all placebo‐controlled studies, to estimate risk of opportunistic infection or malignancy with anti‐integrin antibodies.MethodsMEDLINE, EMBASE and the Cochrane central register of controlled trials were searched (up to December 2014). Randomised placebo‐controlled trials of anti‐integrin antibodies in adults with active or quiescent CD or UC were eligible. Dichotomous data were pooled to obtain a relative risk (RR) of opportunistic infection or malignancy, with 95% confidence intervals (CIs).ResultsThe search strategy identified 1579 citations, 12 of which were eligible (four trials of natalizumab, six of vedolizumab and two of etrolizumab). The RR of developing an opportunistic infection was not significantly higher with non‐gut specific (2.34; 95% CI 0.05–108.72) or gut specific anti‐integrin antibodies (1.55; 95% CI 0.16–14.83). The RR was generally higher in trials of non‐gut specific anti‐integrin antibodies with duration of therapy ≥52 weeks (RR = 15.00; 95% CI 0.86–261), but remained non‐significant. The RR of malignancy was not elevated with non‐gut specific (1.57; 95% CI 0.19–12.74) or gut specific anti‐integrin antibodies (0.78; 95% CI 0.15–4.02).ConclusionsAbsolute numbers of opportunistic infections were higher with anti‐integrin antibodies, but this difference is not statistically significant. There was no increased risk of malignancy detected. Long‐term data in large prospective cohorts are needed to further assess this issue.
Freedom of Choice About Incidental Findings Can Frustrate Participants' True Preferences
Authors: Viberg Jennifer , Segerdahl Pär , Langenskiöld Sophie , Hansson Mats G. 
Published: April 2015

AbstractEthicists, regulators and researchers have struggled with the question of whether incidental findings in genomics studies should be disclosed to participants. In the ethical debate, a general consensus is that disclosed information should benefit participants. However, there is no agreement that genetic information will benefit participants, rather it may cause problems such as anxiety. One could get past this disagreement about disclosure of incidental findings by letting participants express their preferences in the consent form. We argue that this freedom of choice is problematic.In transferring the decision to participants, it is assumed that participants will understand what they decide about and that they will express what they truly want. However, psychological findings about people's reaction to probabilities and risk have been shown to involve both cognitive and emotional challenges. People change their attitude to risk depending on what is at stake. Their mood affects judgments and choices, and they over‐ and underestimate probabilities depending on whether they are low or high. Moreover, different framing of the options can steer people to a specific choice.Although it seems attractive to let participants express their preferences to incidental findings in the consent form, it is uncertain if this choice enables people to express what they truly prefer. In order to better understand the participants' preferences, we argue that future empirical work needs to confront the participant with the complexity of the uncertainty and the trade‐offs that are connected with the uncertain predictive value of genetic risk information.
Establishing a Clinically Relevant Large Animal Model Platform for TBI Therapy Development: Using Cyclosporin A as a Case Study
Authors: Margulies Susan S. , Kilbaugh Todd , Sullivan Sarah , Smith Colin , Propert Kathleen , Byro Melissa , Saliga Kristen , Costine Beth A. , Duhaime Ann‐Christine 
Published: April 2015

AbstractWe have developed the first immature large animal translational treatment trial of a pharmacologic intervention for traumatic brain injury (TBI) in children. The preclinical trial design includes multiple doses of the intervention in two different injury types (focal and diffuse) to bracket the range seen in clinical injury and uses two post‐TBI delays to drug administration. Cyclosporin A (CsA) was used as a case study in our first implementation of the platform because of its success in multiple preclinical adult rodent TBI models and its current use in children for other indications. Tier 1 of the therapy development platform assessed the short‐term treatment efficacy after 24 h of agent administration. Positive responses to treatment were compared with injured controls using an objective effect threshold established prior to the study. Effective CsA doses were identified to study in Tier 2. In the Tier 2 paradigm, agent is administered in a porcine intensive care unit utilizing neurological monitoring and clinically relevant management strategies, and intervention efficacy is defined as improvement in longer term behavioral endpoints above untreated injured animals. In summary, this innovative large animal preclinical study design can be applied to future evaluations of other agents that promote recovery or repair after TBI.
Lack of weight gain after angiotensin AT1 receptor blockade in diet‐induced obesity is partly mediated by an angiotensin‐(1–7)/Mas‐dependent pathway
Authors: Schuchard Johanna , Winkler Martina , Stölting Ines , Schuster Franziska , Vogt Florian M , Barkhausen Jörg , Thorns Christoph , Santos Robson A , Bader Michael , Raasch Walter 
Published: April 2015

Background and PurposeAngiotensin AT1 receptor antagonists induce weight loss; however, the mechanism underlying this phenomenon is unknown. The Mas receptor agonist angiotensin‐(1‐7) is a metabolite of angiotensin I and of angiotensin II . As an agonist of Mas receptors, angiotensin‐(1‐7) has beneficial cardiovascular and metabolic effects.Experimental ApproachWe investigated the anti‐obesity effects of transgenically overexpressed angiotensin‐(1‐7) in rats. We secondly examined whether weight loss due to telmisartan (8 mg·kg−1·d−1) in diet‐induced obese Sprague Dawley (SD) rats can be blocked when the animals were co‐treated with the Mas receptor antagonist A779 (24 or 72 μg·kg−1·d−1).Key ResultsIn contrast to wild‐type controls, transgenic rats overexpressing angiotensin‐(1‐7) had 1.) diminished body weight when they were regularly fed with chow; 2.) were protected from developing obesity although they were fed with cafeteria diet (CD); 3.) showed a reduced energy intake that was mainly related to a lower CD intake; 5.) remained responsive to leptin despite chronic CD feeding; 6.) had a higher, strain‐dependent energy expenditure, and 7.) were protected from developing insulin resistance despite CD feeding. Telmisartan‐induced weight loss in SD rats was partially antagonized after a high, but not a low dose of A779.Conclusions and ImplicationsAngiotensin‐(1‐7) regulated food intake and body weight and contributed to the weight loss after AT1 receptor blockade. Angiotensin‐(1‐7)‐like agonists may be drug candidates for treating obesity.
Measurement Issues: Measures of infant mental health
Authors: Szaniecki Eduardo , Barnes Jacqueline 
Published: April 2015

BackgroundEmotional and behavioural problems emerging in very young children can represent a challenge to the child and family and warrant early identification and appropriate support or intervention. Diagnostic systems are being developed that allow for specific difficulties to be identified and this review summarizes them.ScopeThis evidenced based review describes the psychometric properties and potential for use in clinical practice of a range of instruments and methods that are available to identify infant mental health difficulties, and which may be suitable for use in primary care settings, including observations, questionnaires and checklists.Findings and ConclusionWhile debate continues about whether infant mental health problems can or should be identified, the use of standardized tools may help clinicians to compare observations of infants so that those emerging as atypical can receive additional attention, reflecting a more targeted approach to primary care services.
An Up to 12‐Year Retrospective Follow‐Up on Immediately Loaded, Surface‐Modified Implants in the Edentulous Mandible
Authors: Vandeweghe Stefan , Hawker Peter , De Bruyn Hugo 
Published: April 2015

AbstractPurposeThe study aims to evaluate the long‐term clinical outcome of immediate loading of implants in the edentulous mandible.Materials and MethodsPatients were treated at least 1 year prior to evaluation, with four to five implants and an immediate provisional bridge in the edentulous mandible. They were invited for a clinical examination, which included the removal of the bridge, probing, perio‐testing, clinical photographs, and a new radiograph to determine the bone level. Also, patients were requested to answer theOHIP‐14 questionnaire to rate their satisfaction with the treatment.ResultsForty‐six patients (21 men, 25 women), mean age 60 years (SD8.5, range 43–77), were treated with 211 implants. One implant failed to integrate, resulting in a survival rate of 99.5%. After a mean follow‐up of 90 months (SD45, range 17–143), the mean bone level was 1.17 mm (SD0.49, range 0.36–4.88). The mean Periotest value was −5.48 (SD0.883, range −2 to −7). The mean probing depth was 2.04 mm (SD0.71, range 1.00–8.25). There were 83.3% of the implants that demonstrated no bleeding at probing. Calculus was observed at 13.9% of the abutments. Around one implant (0.5%), suppuration was seen after probing. There was a highly significant correlation between bone loss and probing depth (p < .001). Overall, patients were very satisfied, with 69.6% scoring their treatment as excellent.ConclusionImmediate loading of surface‐enhanced implants is a highly predictable and successful treatment modality in the edentulous mandible.