bluuebunny/crossref_metadata_2025_split huggingface dataset:
How adolescents experience and cope with pain in daily life: a qualitative study on ways to cope and the use of over-the-counter analgesics
Authors: Lagerløv Per , Rosvold Elin Olaug , Holager Tanja , Helseth Sølvi 
Published: March 2016

ObjectiveThe aim of this study was to describe how different adolescents experience and manage pain in their daily life, with a focus on their use of over-the-counter analgesics. More specifically, the aim was to explore different patterns among the adolescents in pain descriptions, in the management of pain, in relationships with others, and in their daily life.DesignQualitative semistructured interviews on experiences with pain, pain management and involvement of family and friends during pain. Pain and stress management strategies and attachment theory will be in focus for interpretations.Participants and setting25 participants aged 15–16-years from six different junior high schools, both genders, with and without immigrant background were interviewed at their local schools in Norway.ResultsWe identified 4 groups of adolescents with similarities in attitudes and management strategies to pain: ‘pain is manageable’, ‘pain is communicable’, ‘pain is inevitable’ and ‘pain is all over’. The participants within each group differed in how they engaged their parents in pain; how they perceived, communicated and managed pain; and how they involved emotions and used over-the-counter analgesics.ConclusionsThe adolescents’ different involvement with the family during pain related to their pain perception and management. Knowledge of the different ways of approaching pain is important when supporting adolescents and may be a subject for further research on the use of over-the-counter analgesics in the family.
Evaluation of cardiovascular risk-lowering health benefits accruing from laboratory-based, community-based and exercise-referral exercise programmes
Authors: Webb R , Thompson J E S , Ruffino J-S , Davies N A , Watkeys L , Hooper S , Jones P M , Walters G , Clayton D , Thomas A W , Morris K , Llewellyn D H , Ward M , Wyatt-Williams J , McDonnell B J 
Published: March 2016

BackgroundTo evaluate the ability of community-based exercise programmes to facilitate public participation in exercise and hence improved cardiovascular health, we assessed the respective impacts of: a continuously monitored exercise programme based within our university (study 1); a Valleys Regional Park-facilitated community-based outdoor exercise programme (study 2); a Wales National Exercise Referral Scheme-delivered exercise-referral programme (study 3).MethodsBiomolecular (monocytic PPARγ target gene expression), vascular haemodynamic (central/peripheral blood pressure, arterial stiffness), clinical (insulin sensitivity, blood lipids) and anthropometric (body mass index, waist circumference, heart rate) parameters were investigated using RT-PCR, applanation tonometry, chemical analysis and standard anthropometric techniques.ResultsIn studies 1–3, 22/28, 32/65 and 11/14 participants adhered to their respective exercise programmes, and underwent significant increases in physical activity levels. Importantly, beneficial effects similar to those seen in our previous studies (eg, modulations in expression of monocytic PPARγ target genes, decreases in blood pressure/arterial stiffness, improvements in blood lipids/insulin sensitivity) were observed (albeit to slightly differing extents) only in participants who adhered to their respective exercise programmes. While study 1 achieved more intense exercise and more pronounced beneficial effects, significant cardiovascular risk-lowering health benefits related to biomolecular markers, blood pressure, arterial stiffness and blood lipids were achieved via community/referral-based delivery modes in studies 2 and 3.ConclusionsBecause cardiovascular health benefits were observed in all 3 studies, we conclude that the majority of benefits previously reported in laboratory-based studies can also be achieved in community-based/exercise-referral settings. These findings may be of use in guiding policymakers with regard to introduction and/or continued implementation of community/referral-based exercise programmes.
Carl Wiman and the foundation of Mesozoic vertebrate palaeontology in Sweden
Authors: Ebbestad Jan Ove R. 
Published: March 2016

Abstract
In 1908, Carl Wiman of Uppsala University, Sweden, discovered rich horizons with Triassic vertebrate remains in Spitsbergen on Svalbard, Norway. This marked the beginning of vertebrate palaeontology as a science in Sweden, subsequently developed mainly through the collection and study of non-Swedish fossil remains. Wiman's accomplishments, resolute personality and a tight network of influential friends and supporters enabled him to become the first person in Sweden to hold a university chair in Palaeontology and Historical Geology. He also managed to amass large numbers of unique fossil vertebrate specimens culminating in an extensive Chinese collection of both world famous dinosaurs and Neogene mammals deposited at Uppsala University. Joint scientific Sino-Swedish collaboration and a deliberate Swedish scientific agenda ensured this unprecedented situation in an opportune moment. Governmental support and initiative allowed Uppsala University and Carl Wiman's Palaeontological Institute to erect a museum building dedicated foremost to the Chinese material, now known as the Lagrelius Collection in recognition of the patron behind Wiman's ambitious endeavours. In addition, the museum served as a permanent repository for seminal collections of Mesozoic fossils from Svalbard and North America. Collectively, these represent a landmark research and teaching resource that remains of intense scientific interest even today.
Identification of RNA-Binding Protein LARP4B as a Tumor Suppressor in Glioma
Authors: Koso Hideto , Yi Hungtsung , Sheridan Paul , Miyano Satoru , Ino Yasushi , Todo Tomoki , Watanabe Sumiko 
Published: March 2016

Abstract
Transposon-based insertional mutagenesis is a valuable method for conducting unbiased forward genetic screens to identify cancer genes in mice. We used this system to elucidate factors involved in the malignant transformation of neural stem cells into glioma-initiating cells. We identified an RNA-binding protein, La-related protein 4b (LARP4B), as a candidate tumor-suppressor gene in glioma. LARP4B expression was consistently decreased in human glioma stem cells and cell lines compared with normal neural stem cells. Moreover, heterozygous deletion of LARP4B was detected in nearly 80% of glioblastomas in The Cancer Genome Atlas database. LARP4B loss was also associated with low expression and poor patient survival. Overexpression of LARP4B in glioma cell lines strongly inhibited proliferation by inducing mitotic arrest and apoptosis in four of six lines as well as in two patient-derived glioma stem cell populations. The expression levels of CDKN1A and BAX were also upregulated upon LARP4B overexpression, and the growth-inhibitory effects were partially dependent on p53 (TP53) activity in cells expressing wild-type, but not mutant, p53. We further found that the La module, which is responsible for the RNA chaperone activity of LARP4B, was important for the growth-suppressive effect and was associated with BAX mRNA. Finally, LARP4B depletion in p53 and Nf1-deficient mouse primary astrocytes promoted cell proliferation and led to increased tumor size and invasiveness in xenograft and orthotopic models. These data provide strong evidence that LARP4B serves as a tumor-suppressor gene in glioma, encouraging further exploration of the RNA targets potentially involved in LARP4B-mediatd growth inhibition. Cancer Res; 76(8); 2254–64. ©2016 AACR.
Rab11-FIP1C Is a Critical Negative Regulator in ErbB2-Mediated Mammary Tumor Progression
Authors: Boulay Pierre-Luc , Mitchell Louise , Turpin Jason , Huot-Marchand Julie-Émilie , Lavoie Cynthia , Sanguin-Gendreau Virginie , Jones Laura , Mitra Shreya , Livingstone Julie M. , Campbell Shirley , Hallett Michael , Mills Gordon B. , Park Morag , Chodosh Lewis , Strathdee Douglas , Norman Jim C. , Muller William J. 
Published: March 2016

AbstractRab coupling protein (FIP1C), an effector of the Rab11 GTPases, including Rab25, is amplified and overexpressed in 10% to 25% of primary breast cancers and correlates with poor clinical outcome. Rab25 is also frequently silenced in triple-negative breast cancer, suggesting its ability to function as either an oncogene or a tumor suppressor, depending on the breast cancer subtype. However, the pathobiologic role of FIP family members, such as FIP1C, in a tumor-specific setting remains elusive. In this study, we used ErbB2 mouse models of human breast cancer to investigate FIP1C function in tumorigenesis. Doxycycline-induced expression of FIP1C in the MMTV-ErbB2 mouse model resulted in delayed mammary tumor progression. Conversely, targeted deletion of FIP1C in the mammary epithelium of an ErbB2 model coexpressing Cre recombinase led to accelerated tumor onset. Genetic and biochemical characterization of these FIP1C-proficient and -deficient tumor models revealed that FIP1C regulated E-cadherin (CDH1) trafficking and ZONAB (YBX3) function in Cdk4-mediated cell-cycle progression. Furthermore, we demonstrate that FIP1C promoted lysosomal degradation of ErbB2. Consistent with our findings in the mouse, the expression of FIP1C was inversely correlated with ErbB2 levels in breast cancer patients. Taken together, our findings indicate that FIP1C acts as a tumor suppressor in the context of ErbB2-positive breast cancer and may be therapeutically exploited as an alternative strategy for targeting aberrant ErbB2 expression. Cancer Res; 76(9); 2662–74. ©2016 AACR.
Oncogenic ALK Fusion in Rare and Aggressive Subtype of Colorectal Adenocarcinoma as a Potential Therapeutic Target
Authors: Yakirevich Evgeny , Resnick Murray B. , Mangray Shamlal , Wheeler Michael , Jackson Cynthia L. , Lombardo Kara A. , Lee Jeeyun , Kim Kyoung-Mee , Gill Anthony J. , Wang Kai , Gowen Kyle , Sun James , Miller Vincent A. , Stephens Philip J. , Ali Siraj M. , Ross Jeffrey S. , Safran Howard 
Published: March 2016

Abstract
Purpose: Chromosomal translocations in the anaplastic lymphoma kinase (ALK) gene have been identified as oncogenic drivers in lung adenocarcinomas and other tumors, recently including rare cases of colorectal carcinoma. We identified a patient with refractory metastatic colorectal carcinoma harboring a STRN–ALK gene fusion who achieved an exceptional clinical benefit to the ALK inhibitor ceritinib. Our goal was to further define the clinicopathologic features of ALK-rearranged colorectal carcinoma in a large cohort.
Experimental Design: Clinical cases of colorectal carcinoma evaluated by comprehensive genomic profiling (CGP) or by ALK immunohistochemistry (IHC) were reviewed retrospectively. FISH and microsatellite instability (MSI) analyses were performed.
Results: Nine colorectal carcinoma cases harbored ALK gene fusions. Six cases were identified by CGP of 3,157 colorectal carcinoma (0.2%) and three by IHC of 2,980 colorectal carcinoma (0.1%). The ALK fusions involved known ALK partners EML4, C2orf44, CAD, and the novel STRN, PPP1R21, SENPF, MAPRE3, and PRKAP1B partners. These advanced-stage colorectal carcinomas lacked mutations in other oncogenic drivers, predominantly involved the proximal colon, and often exhibited MSI and mucinous phenotype. The index patient was treated with the ALK inhibitor ceritinib, resulting in a marked decrease in size of a skin metastasis, and resolution by computerized tomography of all contrast enhancing tumor. After 9 months of treatment, biopsy of progressive disease demonstrated a KRAS mutation, consistent with acquired resistance to ceritinib.
Conclusions: Colorectal carcinoma harboring ALK fusions represent a rare aggressive subtype of colorectal carcinoma with distinct clinicopathologic features. This report provides the first clinical evidence that such patients may benefit from targeted monotherapy with ALK inhibitors. Clin Cancer Res; 22(15); 3831–40. ©2016 AACR.
Limitations of the Driver/Passenger Model in Cancer Prevention
Authors: Kuhner Mary K. , Kostadinov Rumen , Reid Brian J. 
Published: March 2016

Abstract
Mutations detected in cancers are often divided into “drivers” and “passengers.” We suggest that this classification is potentially misleading for purposes of early detection and prevention. Specifically, some mutations are frequent in tumors and thus appear to be drivers, but are poor predictors of cancer; other mutations are individually rare and thus appear to be passengers, but may collectively explain a large proportion of risk. The assumptions bundled into the terms “driver” and “passenger” can lead to misunderstandings of neoplastic progression, with unintended consequences including overdiagnosis, overtreatment, and failure to identify the true sources of risk. We argue that samples from healthy, benign, or neoplastic tissues are critical for evaluating the risk of future cancer posed by mutations in a given gene. Cancer Prev Res; 9(5); 335–8. ©2016 AACR.
Exome Sequencing Identified a Splice Site Mutation in
FHL1
that Causes Uruguay Syndrome, an X-Linked Disorder With Skeletal Muscle Hypertrophy and Premature Cardiac Death
Authors: Xue Yuan , Schoser Benedikt , Rao Aliz R. , Quadrelli Roberto , Vaglio Alicia , Rupp Verena , Beichler Christine , Nelson Stanley F. , Schapacher-Tilp Gudrun , Windpassinger Christian , Wilcox William R. 
Published: March 2016

Background—
Previously, we reported a rare X-linked disorder, Uruguay syndrome in a single family. The main features are pugilistic facies, skeletal deformities, and muscular hypertrophy despite a lack of exercise and cardiac ventricular hypertrophy leading to premature death.

Methods and Results—

An ≈19 Mb critical region on X chromosome was identified through identity-by-descent analysis of 3 affected males. Exome sequencing was conducted on one affected male to identify the disease-causing gene and variant. A splice site variant (c.502-2A>G) in the
FHL1
gene was highly suspicious among other candidate genes and variants. FHL1A is the predominant isoform of FHL1 in cardiac and skeletal muscle. Sequencing cDNA showed the splice site variant led to skipping of exons 6 of the FHL1A isoform, equivalent to the FHL1C isoform. Targeted analysis showed that this splice site variant cosegregated with disease in the family. Western blot and immunohistochemical analysis of muscle from the proband showed a significant decrease in protein expression of FHL1A. Real-time polymerase chain reaction analysis of different isoforms of FHL1 demonstrated that the FHL1C is markedly increased.

Conclusions—

Mutations in the
FHL1
gene have been reported in disorders with skeletal and cardiac myopathy but none has the skeletal or facial phenotype seen in patients with Uruguay syndrome. Our data suggest that a novel
FHL1
splice site variant results in the absence of FHL1A and the abundance of FHL1C, which may contribute to the complex and severe phenotype. Mutation screening of the
FHL1
gene should be considered for patients with uncharacterized myopathies and cardiomyopathies.
Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction
Authors: Henri Orianne , Pouehe Chris , Houssari Mahmoud , Galas Ludovic , Nicol Lionel , Edwards-Lévy Florence , Henry Jean-Paul , Dumesnil Anais , Boukhalfa Inès , Banquet Sébastien , Schapman Damien , Thuillez Christian , Richard Vincent , Mulder Paul , Brakenhielm Ebba 
Published: March 2016

Background—
The lymphatic system regulates interstitial tissue fluid balance, and lymphatic malfunction causes edema. The heart has an extensive lymphatic network displaying a dynamic range of lymph flow in physiology. Myocardial edema occurs in many cardiovascular diseases, eg, myocardial infarction (MI) and chronic heart failure, suggesting that cardiac lymphatic transport may be insufficient in pathology. Here, we investigate in rats the impact of MI and subsequent chronic heart failure on the cardiac lymphatic network. Further, we evaluate for the first time the functional effects of selective therapeutic stimulation of cardiac lymphangiogenesis post-MI.

Methods and Results—

We investigated cardiac lymphatic structure and function in rats with MI induced by either temporary occlusion (n=160) or permanent ligation (n=100) of the left coronary artery. Although MI induced robust, intramyocardial capillary lymphangiogenesis, adverse remodeling of epicardial precollector and collector lymphatics occurred, leading to reduced cardiac lymphatic transport capacity. Consequently, myocardial edema persisted for several months post-MI, extending from the infarct to noninfarcted myocardium. Intramyocardial-targeted delivery of the vascular endothelial growth factor receptor 3–selective designer protein VEGF-C
C152S
, using albumin-alginate microparticles, accelerated cardiac lymphangiogenesis in a dose-dependent manner and limited precollector remodeling post-MI. As a result, myocardial fluid balance was improved, and cardiac inflammation, fibrosis, and dysfunction were attenuated.

Conclusions—
We show that, despite the endogenous cardiac lymphangiogenic response post-MI, the remodeling and dysfunction of collecting ducts contribute to the development of chronic myocardial edema and inflammation-aggravating cardiac fibrosis and dysfunction. Moreover, our data reveal that therapeutic lymphangiogenesis may be a promising new approach for the treatment of cardiovascular diseases.
An update of the UK’s design summer years: Probabilistic design summer years for enhanced overheating risk analysis in building design
Authors: Eames ME 
Published: March 2016

Overheating is increasingly becoming a key issue for building design across the world. In the UK, better building fabric performance and warmer weather can increase the risk of overheating events in badly designed buildings. The impacts of these overheating events could be reduced by adapting building designs at an early design stage using building thermal models using appropriate weather data such as a design summer year. In this work, a method to determine probabilistic design summer years will be presented. These years take into account the return periods of actual events, are presented within a probabilistic framework and therefore include a description of the severity of the year at each location. Practical application: Design summer years are designed to be used to optimise building performance in terms of thermal comfort at design stage. This paper demonstrates a method to create probabilistic design summer years which contain a range of overheating events which can be used to inform designers of the overheating risk to occupants. The proposed method is then used to generate new near extreme weather files for the UK.
Reoperation following Adult Tonsillectomy
Authors: Brant Jason A. , Bur Andrés M. , Chai Raymond , Hatten Kyle , Nicolli Elizabeth A. , Fischer John P. , Cannady Steven B. 
Published: March 2016

ObjectiveTonsillectomy remains a common procedure in adults; however, there are few population‐level data evaluating risk factors for reoperation.Study DesignRetrospective review of national database.SettingAmerican College of Surgeons National Surgical Quality Improvement Program (ACS‐NSQIP), 2005‐2013.Subjects and MethodsThe ACS‐NSQIP was queried for patients undergoing tonsillectomy ± adenoidectomy as their primary procedure (CPT 42821 or 42826). Demographic information and indications were reviewed along with complications and reoperation rates.ResultsIn total, 12,542 cases met inclusion criteria. Patients were predominantly female (66.4%) and white (70.8%), with mean age of 30 ± 12 years (range: 16‐90+). Thirty‐day mortality was 0.03%, and 4.8% of patients experienced at least 1 complication, including reoperation (3.6%). Risk of complications was associated with male sex (P <. 0001; odds ratio [OR], 1.7), diabetes (P =. 0002; OR, 2.1), and presence of a bleeding disorder (P =. 002; OR, 3.2). Risk factors for reoperation were similar, in addition to older age (P =. 002; OR, 0.986). Complications other than reoperation were correlated with older age (P =. 001; OR, 1.02) and diabetes (P =. 001; OR, 2.59). Procedures were done mostly for infectious/inflammatory (70.4%) versus hypertrophic (16.4%) indications. Indication had no significant effect on the rate of reoperation. Most reoperations occurred after postoperative day 1 (86%; mean, 6.4 ± 4.2 days).ConclusionThis review of a large validated surgical database provides an overview of the rates of, and risk factors for, complications and reoperations following tonsillectomy in the adult population.
Orbital Decompression in the Endoscopic Age
Authors: Yao William C. , Sedaghat Ahmad R. , Yadav Prashant , Fay Aaron , Metson Ralph 
Published: March 2016

ObjectivePostoperative diplopia occurs in up to 45% of patients following orbital decompression for exophthalmos associated with Graves’ orbitopathy. We sought to describe outcomes of our balanced orbital decompression strategy that includes the preservation of a modified inferomedial orbital strut (mIOS).Study DesignCase series with chart review.SettingAcademic medical center.Subjects and MethodsA total of 115 consecutive orbital decompressions were performed on 73 patients (42 bilateral) with Graves’ orbitopathy. All patients underwent (1) a balanced decompression technique incorporating an endoscopic medial and external lateral decompression and (2) a mIOS technique with preservation of the anterior half of the inferomedial orbital strut. A periorbital periosteal (orbital) sling was utilized in patients (n = 54) without threatened vision loss, proptosis >28 mm, or periorbital disruption to prevent prolapse of the medial rectus muscle.ResultsUtilization of the mIOS technique with or without a sling did not adversely affect the reduction in proptosis (5.1 mm with sling vs 5.0 mm without sling; P =. 85).The incidence of new‐onset postoperative diplopia was 17% (n = 6). The sling was not associated with postoperative diplopia (odds ratio = 0.54, 95% confidence interval: 0.08‐3.40, P =. 51), while it was associated with resolution of preexisting diplopia (odds ratio = 6.67, 95% confidence interval: 1.06‐42.06, P =. 04). No intraoperative complications occurred, and no patients suffered a decrement in visual acuity.ConclusionBalanced orbital decompression utilizing a mIOS in patients with Graves’ orbitopathy provides a safe and effective reduction in proptosis with a low rate of new‐onset diplopia as compared with historical values. Utilization of an orbital sling may be beneficial in reducing postoperative diplopia in select patients.