bluuebunny/crossref_metadata_2025_split huggingface dataset:
Next-Generation Sequencing Reveals Pathway Activations and New Routes to Targeted Therapies in Cutaneous Metastatic Melanoma
Authors: Carlson J. Andrew , Caldeira Xavier Jose Candido , Tarasen Ashley , Sheehan Christine E. , Otto Geoff , Miller Vincent A. , Stephens Philip J. , Elvin Julia A. , Vergilio Jo-Anne , Suh James , Gay Laurie M. , Ross Jeffrey S. 
Published: December 2016

Background:
Comprehensive genomic profiling of clinical samples by next-generation sequencing (NGS) can identify one or more therapy targets for the treatment of metastatic melanoma (MM) with a single diagnostic test.

Methods:
NGS was performed on hybridization-captured, adaptor ligation–based libraries using DNA extracted from 4 formalin-fixed paraffin-embedded sections cut at 10 microns from 30 MM cases. The exons of 182 cancer-related genes were fully sequenced using the Illumina HiSeq 2000 at an average sequencing depth of 1098X and evaluated for genomic alterations (GAs) including point mutations, insertions, deletions, copy number alterations, and select gene fusions/rearrangements. Clinically relevant GAs (CRGAs) were defined as those identifying commercially available targeted therapeutics or therapies in registered clinical trials.

Results:
The 30 American Joint Committee on Cancer Stage IV MM included 17 (57%) male and 13 (43%) female patients with a mean age of 59.5 years (range 41–83 years). All MM samples had at least 1 GA, and an average of 2.7 GA/sample (range 1–7) was identified. The mean number of GA did not differ based on age or sex; however, on average, significantly more GAs were identified in amelanotic and poorly differentiated MM. GAs were most commonly identified in BRAF (12 cases, 40%), CDKN2A (6 cases, 20%), NF1 (8 cases, 26.7%), and NRAS (6 cases, 20%). CRGAs were identified in all patients, and represented 77% of the GA (64/83) detected. The median and mean CRGAs per tumor were 2 and 2.1, respectively (range 1–7).

Conclusion:
Comprehensive genomic profiling of MM, using a single diagnostic test, uncovers an unexpectedly high number of CRGA that would not be identified by standard of care testing. Moreover, NGS has the potential to influence therapy selection and can direct patients to enter relevant clinical trials evaluating promising targeted therapies.
Efficacy and Safety of Novel Oral P2Y12 Receptor Inhibitors in Patients With ST-Segment Elevation Myocardial Infarction Undergoing PCI: A Systematic Review and Meta-Analysis
Authors: Sun Jianjun , Xiang Qian , Li Chao , Wang Zining , Hu Kun , Xie Qiufen , Cui Yimin 
Published: December 2016

Abstract:
The efficacy and safety of novel oral P2Y12 receptor inhibitors (prasugrel and ticagrelor) are subjects of contention in patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI, and the optimal duration of therapy remains uncertain. We searched PubMed, Embase, Cochrane Library, CNKI, VIP, and WanFang Data to identify randomized controlled trials comparing novel oral P2Y12 receptor inhibitors with clopidogrel in patients with STEMI undergoing PCI until February 2016. The primary efficacy and safety endpoint were all-cause mortality and major/minor bleeding. Twelve studies were included. Novel oral P2Y12 inhibitors significantly reduced the incidence of all-cause death (relative risk: 0.65, 95% confidence interval, 0.53–0.78), major adverse cardiac events [0.68 (0.56–0.83)], and stent thrombosis [0.56 (0.43–0.75)] without significant difference in bleeding (P = 0.11) compared with clopidogrel. Identical results were observed in the longer dual antiplatelet therapy (DAPT) and shorter-DAPT subgroups, albeit Chinese patients with ticagrelor treatment had a slight increase in bleeding (P = 0.08). Furthermore, the pooled relative risk ratio for each endpoint showed no significant difference between the longer-DAPT and shorter-DAPT subgroups. In conclusion, prasugrel and ticagrelor decreased the risk of all-cause death, major adverse cardiac events, and stent thrombosis without causing more bleeding events compared with clopidogrel in patients with STEMI undergoing PCI.
Bleeding Risk of Antithrombotic Treatment in Patients on Hemodialysis
Authors: Vázquez Eduardo , Sánchez-Perales Carmen , Ortega Sonia , Vázquez-Sánchez Teresa , Quesada Enrique , Salas Daniel , Fernández-Guerrero Juan Carlos 
Published: December 2016

Background:
The risk–benefit of antithrombotic treatment (ATT) has not been established in patients on dialysis. Our objective was to determine the influence of ATT on the risk of hemorrhage in patients on hemodialysis.

Methods:
We included patients who began dialysis between 2003 and 2007. We determined the rates of fatal bleeding or bleeding leading to hospitalization or transfusion.

Results:
Two hundred twenty-one patients were included. Over the follow-up period (45.5 ± 34 months), there were 76 hemorrhages in 52 patients. There were 10 fatal bleedings. The annual incidence of patients presenting with hemorrhagia was 6.2%. Bleeding occurred in 5.2% of those being treated with aspirin, 7% with acenocumarol, 12.3% with clopidogrel, 15.2% with aspirin + clopidogrel, 45.9% with anticoagulants + antiplatelets, 49.6% with low-molecular-weight heparin, and 3.9% without ATT. On multivariate analysis, masculine gender [hazard ratio (HR): 2.421; 95% confidence interval (CI), 1.261–4.650; P = 0.003], treatment with dicumarins (HR: 2.406; 95% CI, 1.013–5.718; P = 0.047), treatment with clopidogrel (HR: 2.697; 95% CI, 1.440–5.051; P = 0.002), and treatment with low-molecular-weight heparin (HR: 21.463; 95% CI, 9.067–50.806; P = 0.001) were independent predictors of bleeding.

Conclusions:
ATT increases the risk of bleeding in patients on hemodialysis. The incidence of hemorrhage varies with the type of antithrombotics used.
Quantitative Method for Simultaneous Analysis of Acetaminophen and 6 Metabolites
Authors: Lammers Laureen A. , Achterbergh Roos , Pistorius Marcel C. M. , Romijn Johannes A. , Mathôt Ron A. A. 
Published: December 2016

Background:
Hepatotoxicity after ingestion of high-dose acetaminophen [N-acetyl-para-aminophenol (APAP)] is caused by the metabolites of the drug. To gain more insight into factors influencing susceptibility to APAP hepatotoxicity, quantification of APAP and metabolites is important. A few methods have been developed to simultaneously quantify APAP and its most important metabolites. However, these methods require a comprehensive sample preparation and long run times. The aim of this study was to develop and validate a simplified, but sensitive method for the simultaneous quantification of acetaminophen, the main metabolites acetaminophen glucuronide and acetaminophen sulfate, and 4 Cytochrome P450–mediated metabolites by using liquid chromatography with mass spectrometric (LC-MS) detection.

Methods:
The method was developed and validated for the human plasma, and it entailed a single method for sample preparation, enabling quick processing of the samples followed by an LC-MS method with a chromatographic run time of 9 minutes. The method was validated for selectivity, linearity, accuracy, imprecision, dilution integrity, recovery, process efficiency, ionization efficiency, and carryover effect.

Results:
The method showed good selectivity without matrix interferences. For all analytes, the mean process efficiency was >86%, and the mean ionization efficiency was >94%. Furthermore, the accuracy was between 90.3% and 112% for all analytes, and the within- and between-run imprecision were <20% for the lower limit of quantification and <14.3% for the middle level and upper limit of quantification.

Conclusions:
The method presented here enables the simultaneous quantification of APAP and 6 of its metabolites. It is less time consuming than previously reported methods because it requires only a single and simple method for the sample preparation followed by an LC-MS method with a short run time. Therefore, this analytical method provides a useful method for both clinical and research purposes.
IMAGING AND MEASUREMENT OF THE PRERETINAL SPACE IN VITREOMACULAR ADHESION AND VITREOMACULAR TRACTION BY A NEW SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY ANALYSIS
Authors: Stopa Marcin , Marciniak Elżbieta , Rakowicz Piotr , Stankiewicz Agnieszka , Marciniak Tomasz , Dąbrowski Adam 
Published: December 2016

Purpose:
To evaluate a new method for volumetric imaging of the preretinal space (also known as the subhyaloid, subcortical, or retrocortical space) and investigate differences in preretinal space volume in vitreomacular adhesion (VMA) and vitreomacular traction (VMT).

Methods:
Nine patients with VMA and 13 with VMT were prospectively evaluated. Automatic inner limiting membrane line segmentation, which exploits graph search theory implementation, and posterior cortical vitreous line segmentation were performed on 141 horizontal spectral domain optical coherence tomography B-scans per patient. Vertical distances (depths) between the posterior cortical vitreous and inner limiting membrane lines were calculated for each optical coherence tomography B-scan acquired. The derived distances were merged and visualized as a color depth map that represented the preretinal space between the posterior surface of the hyaloid and the anterior surface of the retina. The early treatment d retinopathy study macular map was overlaid onto final virtual maps, and preretinal space volumes were calculated for each early treatment diabetic retinopathy study map sector.

Results:
Volumetric maps representing preretinal space volumes were created for each patient in the VMA and VMT groups. Preretinal space volumes were larger in all early treatment diabetic retinopathy study map macular regions in the VMT group compared with those in the VMA group. The differences reached statistical significance in all early treatment diabetic retinopathy study sectors, except for the superior outer macula and temporal outer macula where significance values were P = 0.05 and P = 0.08, respectively. Overall, the relative differences in preretinal space volumes between the VMT and VMA groups varied from 2.7 to 4.3 in inner regions and 1.8 to 2.9 in outer regions.

Conclusion:
Our study provides evidence of significant differences in preretinal space volume between eyes with VMA and those with VMT. This may be useful not only in the investigation of preretinal space properties in VMA and VMT, but also in other conditions, such as age-related macular degeneration, diabetic retinopathy, and central retinal vein occlusion.
STAINING-ASSISTED REMOVAL OF SILICONE OIL FOR THE IDENTIFICATION OF SUBCLINICAL PROLIFERATIVE VITREORETINOPATHY
Authors: Rizzo Stanislao , Barca Francesco , Faraldi Francesco , Caporossi Tomasso , Virgili Gianni 
Published: December 2016

Purpose:
Retinal detachment is a frequent complication after removal of silicone oil (ROSO). A retrospective study was conducted to determine whether staining-assisted removal of silicone oil (st-ROSO) allowed better identification and removal of proliferative vitreoretinopathy (PVR) processes compared with a conventional removal of silicone oil technique.

Methods:
All individuals underwent pars plana vitrectomy (PPV) and silicone oil fill-in for complicated retinal detachments. In conventional removal of silicone oil (Group 1), no staining was used. In staining-assisted removal of silicone oil (Group 2), a mixture of trypan blue and brilliant blue G dyes was used to identify proliferative vitreoretinopathy and subclinical epiretinal membrane.

Results:
After the first 3-month follow-up, 15.9% of patients (N = 608) developed a retinal detachment. Retinal detachment occurred in 22.8% of patients in Group 1 (n = 284) and 9.8% of patients in Group 2 (n = 324; P < 0.001). In Group 2, proliferative vitreoretinopathy removal was performed in 153 eyes (47.2%).

Conclusion:
The incidence of retinal redetachment was significantly lower after staining-assisted removal of silicone oil compared with a conventional technique. Staining-assisted removal of silicone oil allowed better identification and removal of proliferative vitreoretinopathy processes.
LATE-ONSET CHOROIDAL METASTASIS FROM BREAST CANCER
Authors: Levison Ashleigh L. , Erenler Feyza , Zhao Yue , Martin Daniel F. , Lowder Careen , Budd G. Thomas , Singh Arun D. 
Published: December 2016

Purpose:
Report occurrence of late-onset choroidal metastasis from breast cancer.

Methods:
Retrospective chart review.

Results:
The authors report 3 patients with choroidal metastasis from breast cancer that presented more than 20 years after diagnosis of the primary tumor. The choroidal metastases were the presenting feature of metastatic disease in all three patients, but after imaging, all patients had metastasis elsewhere as well. Two of the patients' tumors were known, ER+, and the hormone receptor status of the third patient was unknown. All three patients were treated with aromatase inhibitors with good response.

Conclusion:
Late onset of metastatic disease, an excellent response to hormonal therapy, and a prolonged survival despite presence of systemic disease suggests a milder variant within the broad category of breast cancer patients with uveal metastases. Awareness of this entity can minimize the risk of misdiagnosis and avoid potentially toxic local therapy.
Implementation and Quality Improvement of a Screening and Counseling Program for Unhealthy Alcohol Use in an Academic General Internal Medicine Practice
Authors: Jonas Daniel E. , Miller Thomas , Ratner Shana , McGuirt Brooke , Golin Carol E. , Grodensky Catherine , Sturkie Emily , Kinley Jennifer , Dale Maureen , Pignone Michael 
Published: December 2016

Abstract:
Unhealthy alcohol use is the third leading cause of preventable death in the United States. The U.S. Preventive Services Task Force (USPSTF) recommends screening for unhealthy alcohol use but little is known about how best to do so. We used quality improvement techniques to implement a systematic approach to screening and counseling primary care patients for unhealthy alcohol use. Components included use of validated screening and assessment instruments; an evidence-based two-visit counseling intervention using motivational interviewing techniques for those with risky drinking behaviors who did not have an alcohol use disorder (AUD); shared decision making about treatment options for those with an AUD; support materials for providers and patients; and training in motivational interviewing for faculty and residents. Over the course of one year, we screened 52% (N = 5,352) of our clinic's patients and identified 294 with positive screens. Of those 294, appropriate screening-related assessments and interventions were documented for 168 and 72 patients, respectively. Although we successfully implemented a systematic screening program and structured processes of care, ongoing quality improvement efforts are needed to screen the rest of our patients and to improve the consistency with which we provide and document appropriate interventions.
Body Composition Trajectories From Infancy to Preschool in Children Born Premature Versus Full‐term
Authors: Scheurer Johannah M. , Zhang Lei , Gray Heather L. , Weir Katherine , Demerath Ellen W. , Ramel Sara E. 
Published: December 2016

ABSTRACTObjectives:The aim of the study was to longitudinally characterize infancy to preschool body composition trajectories and the association of early fat and fat‐free mass gains with preschool age body composition in children born premature versus full‐term.Methods:A cohort of appropriate‐for‐gestational age preterm (n = 20) and term (n = 51) infants were followed at 3 visits: “neonatal” visit 1 at 2 weeks of age for term and near term corrected age for preterm; “infancy” visit 2 at 3 to 4 months (preterm corrected age); “preschool” visit 3 at 4 years. Body composition via air displacement plethysmography and anthropometrics were measured at all visits. Tracking of infancy weight and body composition with preschool measurements was tested using Pearson partial correlation coefficients. Associations between serial body composition measurements were assessed using multiple linear regression.Results:Early differences in body composition between premature (mean gestational age 31.9 weeks, mean birth weight 1843 g) and full‐term (mean gestational age 39.8 weeks) infants were not present at preschool age. Visit 1 body composition was not correlated with preschool measurements in the preterm infants. Visit 2 measurements were correlated with preschool measures. Fat‐free mass accretion from visit 1 to visit 2 was positively associated with preschool lean mass (β = 0.038, P = 0.049) in preterm children, whereas fat accretion was not associated with preschool body composition.Conclusions:Children born prematurely and full‐term have similar body composition at preschool age. For preterms infancy fat‐free mass gains, and not adiposity gains, are positively associated with preschool fat‐free mass; this may be associated with lower risk of later obesity and adverse metabolic outcomes.
The Association Between Celiac Disease and Eosinophilic Esophagitis
Authors: Hommeida Salim , Alsawas Mouaz , Murad Mohammad H. , Katzka David A. , Grothe Rayna M. , Absah Imad 
Published: December 2016

ABSTRACTBackground:The association between celiac disease (CD) and eosinophilic esophagitis (EoE) has been the focus of multiple studies with variable results. Both diseases are immune mediated, and dietary triggers play a role in their pathogenesis.Objectives:The aim of the study was to analyze the risk of EoE in children with CD, assess the magnitude of association between CD and EoE in children, and report the characteristics and outcomes of children with both conditions.Methods:We conducted a retrospective study of the Mayo Clinic Electronic medical records between January 1, 1998 and December 31, 2015. Systematic review and meta‐analysis of multiple databases was conducted to include studies reporting on the same association. Random‐effects model was used to report pooled odds ratio (OR) and 95% confidence interval (CI).Results:In this cohort study, of 10,201 children who underwent at least 1 endoscopy, 595 had EoE, and 546 had CD. The risk of having EoE was not increased in children with CD compared to those without CD (OR, 0.29; 95% CI, 0.154–0.545). Nine of 10 children improved with gluten‐free diet, topical glucocorticosteroid, and/or elimination diet. One child lost to follow‐up.Meta‐analysis of 5 studies showed similar results (OR, 0.525; 95% CI, 0.364–0.797). A total of 45 cases in the literature had both CD and EoE (mean age, 10 years; 64% boys; majority presenting with abdominal pain, vomiting, and diarrhea).Conclusions:Based on our cohort and the observational data, the diagnosis of CD in children is not associated with increased risk of EoE.
Agenda for Sleep Research in Older Adults With Cancer
Authors: Matthews Ellyn E. , Hacker Eileen Danaher , Otte Julie L. , Dean Grace E. 
Published: December 2016

Background:
Sleep problems are common but often neglected in older adults, particularly in the context of cancer. Underlying mechanisms are poorly understood and interventions frequently lack a clear scientific basis.

Objective:
The objective of this report was to examine scientific content presented at a National Institutes of Health–sponsored U13 “Bedside to Bench” conference using a qualitative and iterative review procedure. Analysis of current scientific issues regarding sleep in older adults with cancer is needed to direct nurse scientists and clinicians toward research opportunities.

Methods:
A multistep review procedure for the analysis/synthesis of knowledge gaps and research opportunities was undertaken by oncology nurse scientists in attendance.

Results:
Conceptual problems in this area include the lack of standard sleep terminology and absence of an overarching conceptual model. Methodological problems are inconsistent sleep/napping measurement and complex operational challenges in designing comprehensive yet feasible studies in older adults. Knowledge gaps in basic and clinical science relate to cellular and molecular mechanisms that underlie sleep and circadian rhythm disturbances, contribution of sleep to adverse outcomes, and impact of disturbed sleep during hospitalization and the transition from hospital to home.

Conclusions:
Focused and interdisciplinary research that advances conceptual and operational understanding of biological and behavioral determinants of sleep health in the aging cancer population can lead to more effective, safe, and targeted interventions for those with cancer-related sleep-circadian disturbances.

Implications for Practice:
Research that addresses current conceptual, methodological, and physiological issues can lead to more effective, safe, and targeted care for older adults with cancer-related sleep-circadian disturbances.
Exploring Meaning in the Life of Chinese Breast Cancer Survivors
Authors: Xia Hao-Zhi , Gao Lei , Yue Hong , Shi Bao-Xin 
Published: December 2016

Background:
Breast cancer is the most common cancer among women worldwide, and spiritual fulfillment such as experiencing meaning in life plays an important role in coping with the disease.

Objective:
The objectives of this study were to explore and understand Chinese breast cancer survivors’ perspective on meaning in life.

Methods:
This study used Grounded Theory; 23 participants were recruited using convenience sampling, purposive sampling, and theoretical sampling. Semistructured interviews were conducted, and the data were analyzed using open coding, axial coding, and selective coding.

Results:
A core category emerged as “satisfaction with my life” to explain Chinese breast cancer survivors’ perspective of meaning in life, and 4 subcategories described the core category including (1) living a healthy and peaceful life, (2) having a good relationship with others, (3) achieving purpose in life, and (4) fulfilling responsibility.

Conclusion:
Chinese breast cancer survivors value physical health as well as spiritual fulfillment. The experience of adapting to life with cancer, having a good relationship with others, pursuing life goals, and fulfilling responsibility consists of a satisfying life, which makes life more meaningful.

Implications for Practice:
Health providers should pay more attention to survivors’ experience of meaning in life and help them enhance meaning in life and improve their quality of life through building good relationship with others, achieving purpose in life, and fulfilling responsibility for family and society.