bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of bruising in preschool children—a longitudinal study
Authors: Kemp Alison M , Dunstan Frank , Nuttall Diane , Hamilton M , Collins Peter , Maguire Sabine 
Published: January 2015

IntroductionThis study aims to identify the prevalence and pattern of bruises in preschool children over time, and explore influential variablesMethodsProspective longitudinal study of children (<6 years) where bruises were recorded on a body chart, weekly for up to 12 weeks. The number and location of bruises were analysed according to development. Longitudinal analysis was performed using multilevel modelling.Results3523 bruises recorded from 2570 data collections from 328 children (mean age 19 months); 6.7% of 1010 collections from premobile children had at least one bruise (2.2% of babies who could not roll over and 9.8% in those who could), compared with 45.6% of 478 early mobile and 78.8% of 1082 walking child collections. The most common site affected in all groups was below the knees, followed by ‘facial T’ and head in premobile and early mobile. The ears, neck, buttocks, genitalia and hands were rarely bruised (<1% of all collections). None of gender, season or the level of social deprivation significantly influenced bruising patterns, although having a sibling increased the mean number of bruises. There was considerable variation in the number of bruises recorded between different children which increased with developmental stage and was greater than the variation between numbers of bruises in collections from the same child over time.ConclusionsThese data should help clinicians understand the patterns of ‘everyday bruising’ and recognise children who have an unusual numbers or distribution of bruises who may need assessment for physical abuse or bleeding disorders.
Epidemiology of psoriasis and palmoplantar pustulosis: a nationwide study using the Japanese national claims database
Authors: Kubota Kiyoshi , Kamijima Yukari , Sato Tsugumichi , Ooba Nobuhiro , Koide Daisuke , Iizuka Hajime , Nakagawa Hidemi 
Published: January 2015

ObjectiveThe primary objective was to estimate the national prevalence of psoriasis and palmoplantar pustulosis (PPP) in Japan. Secondary objectives were to determine (1) whether psoriasis and PPP disease activity varies by season, and (2) whether disease severity is associated with concurrent diabetes mellitus, hyperlipidaemia and hypertension.SettingsPatients with a psoriasis or PPP diagnosis code between April 2010 and March 2011 were identified using a Japanese national database.Participants565 903 patients with psoriasis or PPP were identified. No patient was excluded.Primary and secondary outcome measuresNational prevalence was calculated using census data. We estimated the difference in the proportion of patients who used healthcare services, as a proxy for disease activity, between the hot and cold seasons and the difference in the standardised prevalence of comorbidities between severe and mild disease. The measures were estimated separately for the two broad disease categories of psoriasis and PPP but not in all patients as planned because the two disease categories had major differences.ResultsThe national prevalence of psoriasis and PPP was 0.34% (95% CI 0.34% to 0.34%) and 0.12% (0.12% to 0.12%), respectively. The difference in the proportion of patients who used healthcare services in the hot compared to the cold season was −0.3% (−0.5% to −0.1%) for psoriasis and 10.0% (9.8% to 10.3%) for PPP. The difference in the standardised prevalence between severe and mild psoriasis was 3.1% (2.7% to 3.4%), 3.2% (2.8% to 3.6%) and 5.1% (4.7% to 5.6%) for concurrent diabetes mellitus, hyperlipidaemia and hypertension, respectively. No significant difference in the prevalence of comorbidity was observed for PPP.ConclusionsThe national prevalence, seasonal variation in disease activity and prevalence of comorbidities in Japanese patients with psoriasis and PPP estimated in this descriptive study may be used as basic information for future studies.
Low-dose dexamethasone as a treatment for women with heavy menstrual bleeding: protocol for response-adaptive randomised placebo-controlled dose-finding parallel group trial (DexFEM)
Authors: Warner P , Weir C J , Hansen C H , Douglas A , Madhra M , Hillier S G , Saunders P T K , Iredale J P , Semple S , Walker B R , Critchley H O D 
Published: January 2015

IntroductionHeavy menstrual bleeding (HMB) diminishes individual quality-of-life and poses substantial societal burden. In HMB endometrium, inactivation of cortisol (by enzyme 11β hydroxysteroid dehydrogenase type 2 (11βHSD2)), may cause local endometrial glucocorticoid deficiency and hence increased angiogenesis and impaired vasoconstriction. We propose that ‘rescue’ of luteal phase endometrial glucocorticoid deficiency could reduce menstrual bleeding.Methods and analysisDexFEM is a double-blind response-adaptive parallel-group placebo-controlled trial in women with HMB (108 to be randomised), with active treatment the potent oral synthetic glucocorticoid dexamethasone, which is relatively resistant to 11βHSD2 inactivation. Participants will be aged over 18 years, with mean measured menstrual blood loss (MBL) for two screening cycles ≥50 mL. The primary outcome is reduction in MBL from screening. Secondary end points are questionnaire assessments of treatment effect and acceptability. Treatment will be for 5 days in the mid-luteal phases of three treatment menstrual cycles. Six doses of low-dose dexamethasone (ranging from 0.2 to 0.9 mg twice daily) will be compared with placebo, to ascertain optimal dose, and whether this has advantage over placebo. Statistical efficiency is maximised by allowing randomisation probabilities to ‘adapt’ at five points during enrolment phase, based on the response data available so far, to favour doses expected to provide greatest additional information on the dose–response. Bayesian Normal Dynamic Linear Modelling, with baseline MBL included as covariate, will determine optimal dose (re reduction in MBL). Secondary end points will be analysed using generalised dynamic linear models. For each dose for all end points, a 95% credible interval will be calculated for effect versus placebo.Ethics and disseminationDexamethasone is widely used and hence well-characterised safety-wise. Ethical approval has been obtained from Scotland A Research Ethics Committee (12/SS/0147). Trial findings will be disseminated via open-access peer-reviewed publications, conferences, clinical networks, public lectures, and our websites.Trial registration numberClinicalTrials.govNCT01769820; EudractCT 2012-003405-98.
Increasing the number of patients receiving information about transition to end-of-life care: the effect of a half-day physician and nurse training
Authors: Martinsson L , Heedman P-A , Eriksson M , Tavelin B , Axelsson B 
Published: January 2015

IntroductionHonest prognostication and information for patients are important parts of end-of-life care. This study examined whether an educational intervention could increase the proportion of patients who received information about the transition to end-of-life (ITEOL care).MethodTwo municipalities (in charge of nursing homes) and two hospitals were randomised to receive an interactive half-day course about ITEOL for physicians and nurses. The proportion of patients who received ITEOL was measured with data from the Swedish Register of Palliative Care (SRPC). Patients were only included if they died an expected death and maintained their ability to express their will until days or hours before their death. Four hospitals and four municipalities were assigned controls, matched by hospital size, population and proportion of patients receiving ITEOL at baseline.ResultsThe proportion of patients in the intervention group who received ITEOL increased from 35.1% (during a 6-month period before the intervention) to 42% (during a 6-month period after the intervention). The proportion in the control group increased from 30.4% to 33.7%. The effect of the intervention was significant (p=0.005) in a multivariable model adjusted for time, age, gender and cause of death.ConclusionMore patients at end-of-life received ITEOL after an educative half-day intervention directed to physicians and nurses.
A panel of nine cerebrospinal fluid biomarkers may identify patients with atypical parkinsonian syndromes
Authors: Magdalinou N K , Paterson R W , Schott J M , Fox N C , Mummery C , Blennow K , Bhatia K , Morris H R , Giunti P , Warner T T , de Silva R , Lees A J , Zetterberg H 
Published: January 2015

BackgroundPatients presenting with parkinsonian syndromes share many clinical features, which can make diagnosis difficult. This is important as atypical parkinsonian syndromes (APSs) such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal syndrome (CBS) carry a poor prognosis, compared with patients with Parkinson's disease (PD). In addition, there is overlap between APS and dementia diseases, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD).ObjectiveTo use a panel of cerebrospinal fluid (CSF) biomarkers to differentiate patients with APS from PD and dementia.MethodsA prospective cohort of 160 patients and 30 control participants were recruited from a single specialist centre. Patients were clinically diagnosed according to current consensus criteria. CSF samples were obtained from patients with clinical diagnoses of PD (n=31), PSP (n=33), CBS (n=14), MSA (n=31), AD (n=26) and FTD (n=16). Healthy, elderly participants (n=30) were included as controls. Total τ (t-τ), phosphorylated τ (p-τ), β-amyloid 1–42 (Aβ42), neurofilament light chain (NFL), α-synuclein (α-syn), amyloid precursor protein soluble metabolites α and β (soluble amyloid precursor protein (sAPP)α, sAPPβ) and two neuroinflammatory markers (monocyte chemoattractant protein-1 and YKL-40) were measured in CSF. A reverse stepwise regression analysis and the false discovery rate procedure were used.ResultsCSF NFL (p<0.001), sAPPα (p<0.001) and a-syn (p=0.003) independently predicted diagnosis of PD versus APS. Together, these nine biomarkers could differentiate patients with PD from APS with an area under the curve of 0.95 and subtypes of APS from one another. There was good discriminatory power between parkinsonian groups, dementia disorders and healthy controls.ConclusionsA panel of nine CSF biomarkers was able to differentiate APS from patients with PD and dementia. This may have important clinical utility in improving diagnostic accuracy, allowing better prognostication and earlier access to potential disease-modifying therapies.
The smooth surfaces in ℙ4 with few apparent triple points
Authors: Sierra José Carlos 
Published: January 2015

We classify smooth complex projective surfaces in [Formula: see text] with [Formula: see text] apparent triple points, thus recovering and extending the results of Ascione [Sulle superficie immerse in un [Formula: see text], le cui trisecanti costituiscono complessi di [Formula: see text] ordine, Atti Accad. Naz. Lincei Rend. Cl. Sci. Fis. Mat. Natur.[Formula: see text]5[Formula: see text] 6 (1897) 162–169] and Severi [Intorno ai punti doppi impropri di una superficie generale dello spazio a quattro dimensioni, e a’ suoi punti tripli apparenti, Rend. Circ. Mat. Palermo 15 (1901) 33–51] for [Formula: see text], Marletta [Le superficie generali dell’ [Formula: see text] dotate di due punti tripli apparenti, Rend. Circ. Mat. Palermo 34 (1912) 179–186] for [Formula: see text], and Aure [The smooth surfaces in [Formula: see text] without apparent triple points, Duke Math. J. 57 (1988) 423–430] for [Formula: see text]. This is done thanks to a new projective character that can be introduced as a consequence of the main result of [K. Ranestad, On smooth plane curve fibrations in [Formula: see text], in Geometry of Complex Projective Varieties, Sem. Conf., Vol. 9 (Mediterranean, 1993), pp. 243–255; J. C. Sierra and A. L. Tironi, Some remarks on surfaces in [Formula: see text] containing a family of plane curves, J. Pure Appl. Algebra 209 (2007) 361–369; V. Beorchia and G. Sacchiero, Surfaces in [Formula: see text] with a family of plane curves, J. Pure Appl. Algebra 213 (2009) 1750–1755]. Going a bit further, we obtain some bounds on the Euler characteristic [Formula: see text] in terms of the degree [Formula: see text] and the sectional genus [Formula: see text] of a smooth surface in [Formula: see text]. For [Formula: see text], these bounds were first obtained in [A. B. Aure and K. Ranestad, The smooth surfaces of degree [Formula: see text] in [Formula: see text], in Complex Projective Geometry, London Mathematical Society Lecture Note Series, Vol. 179 (Cambridge University Press, Cambridge, 1992), pp. 32–46; K. Ranestad, On smooth surfaces of degree [Formula: see text] in the projective fourspace, Ph.D. thesis, Oslo (1988); S. Popescu, On smooth surfaces of degree [Formula: see text] in the projective fourspace, Dissertation, Saarbrücken (1993)]. Here we give a different argument based on liaison that works also for [Formula: see text] and that allows us to determine the triples [Formula: see text] of the smooth surfaces with [Formula: see text] apparent triple points.
Blow-up for sign-changing solutions of the critical heat equation in domains with a small hole
Authors: Ianni Isabella , Musso Monica , Pistoia Angela 
Published: January 2015

We consider the critical heat equation [Formula: see text] in [Formula: see text] where [Formula: see text] is a smooth bounded domain in [Formula: see text] and [Formula: see text] is a ball of [Formula: see text] of center [Formula: see text] and radius [Formula: see text] small. We show that if [Formula: see text] is small enough, then there exists a sign-changing stationary solution [Formula: see text] of (CH) such that the solution of (CH) with initial value [Formula: see text] blows up if [Formula: see text] is sufficiently small. This shows, in particular, that the set of the initial conditions for which the solution of (CH) is global and bounded is not star-shaped.
Lysophosphatidic Acid Receptor LPAR6 Supports the Tumorigenicity of Hepatocellular Carcinoma
Authors: Mazzocca Antonio , Dituri Francesco , De Santis Flavia , Filannino Addolorata , Lopane Chiara , Betz Regina C. , Li Ying-Yi , Mukaida Naofumi , Winter Peter , Tortorella Cosimo , Giannelli Gianluigi , Sabbà Carlo 
Published: January 2015

Abstract
The aberrant processes driving hepatocellular carcinoma (HCC) are not fully understood. Lysophosphatidic acid receptors (LPAR) are commonly overexpressed in HCC, but their contributions to malignant development are not well established. In this report, we show that aberrant expression of LPAR6 sustains tumorigenesis and growth of HCC. Overexpression of LPAR6 in HCC specimens associated with poor survival in a cohort of 128 patients with HCC. We took a genetic approach to elucidate how LPAR6 sustains the HCC tumorigenic process, including through an expression profiling analysis to identify genes under the control of LPAR6. RNAi-mediated attenuation of LPAR6 impaired HCC tumorigenicity in tumor xenograft assays. Expression profiling and mechanistic analyses identified Pim-3 as a pathophysiologically relevant LPAR6 target gene. In nonmalignant cells where LPAR6 overexpression was sufficient to drive malignant character, Pim-3 was upregulated at the level of transcription initiation through a STAT3-dependent mechanism. A further analysis of HCC clinical specimens validated the connection between overexpression of LPAR6 and Pim-3, high proliferation rates, and poorer survival outcomes. Together, our findings establish LPAR6 as an important theranostic target in HCC tumorigenesis. Cancer Res; 75(3); 532–43. ©2014 AACR.
Colorectal Cancer Heterogeneity and Targeted Therapy: A Case for Molecular Disease Subtypes
Authors: Linnekamp Janneke F. , Wang Xin , Medema Jan Paul , Vermeulen Louis 
Published: January 2015

Abstract
Personalized cancer medicine is becoming increasingly important in colorectal cancer treatment. Especially for targeted therapies, large variations between individual treatment responses exist. Predicting therapy response is of utmost significance, as it prevents overtreatment and adverse effects in patients. For EGFR-targeted therapy, many mechanisms of resistance have been uncovered, for example, mutations in KRAS and BRAF, and upregulation of alternative receptors. Currently, routine testing for all known modifiers of response is unpractical, and as a result, decision-making for anti-EGFR therapy is still largely based on assessing the mutation status of an individual gene (KRAS). Recently, comprehensive classifications of colorectal cancer have been presented that integrate many of the (epi-)genetic and microenvironmental factors that contribute to colorectal cancer heterogeneity. These classification systems are not only of prognostic value but also predict therapy efficacy, including the response to anti-EGFR agents. Therefore, molecular subtype–based stratification to guide therapeutic decisions is a promising new strategy that might overcome the shortcomings of single gene testing in colorectal cancer as well as in other malignancies. Furthermore, the development of new agents in a disease subtype–specific fashion has the potential to transform drug-discovery studies and generate novel, more effective therapies. Cancer Res; 75(2); 245–9. ©2014 AACR.
Single-Strand DNA-Binding Protein SSB1 Facilitates TERT Recruitment to Telomeres and Maintains Telomere G-Overhangs
Authors: Pandita Raj K. , Chow Tracy T. , Udayakumar Durga , Bain Amanda L. , Cubeddu Liza , Hunt Clayton R. , Shi Wei , Horikoshi Nobuo , Zhao Yong , Wright Woodring E. , Khanna Kum Kum , Shay Jerry W. , Pandita Tej K. 
Published: January 2015

Abstract
Proliferating mammalian stem and cancer cells express telomerase [telomerase reverse transcriptase (TERT)] in an effort to extend chromosomal G-overhangs and maintain telomere ends. Telomerase-expressing cells also have higher levels of the single-stranded DNA-binding protein SSB1, which has a critical role in DNA double-strand break (DSB) repair. Here, we report that SSB1 binds specifically to G-strand telomeric DNA in vitro and associates with telomeres in vivo. SSB1 interacts with the TERT catalytic subunit and regulates its interaction with telomeres. Deletion of SSB1 reduces TERT interaction with telomeres and leads to G-overhang loss. Although SSB1 is recruited to DSB sites, we found no corresponding change in TERT levels at these sites, implying that SSB1–TERT interaction relies upon a specific chromatin structure or context. Our findings offer an explanation for how telomerase is recruited to telomeres to facilitate G-strand DNA extension, a critical step in maintaining telomere ends and cell viability in all cancer cells. Cancer Res; 75(5); 858–69. ©2015 AACR.
Bruton Tyrosine Kinase Is a Therapeutic Target in Stem-like Cells from Multiple Myeloma
Authors: Yang Ye , Shi Jumei , Gu Zhimin , Salama Mohamed E. , Das Satyabrata , Wendlandt Erik , Xu Hongwei , Huang Junwei , Tao Yi , Hao Mu , Franqui Reinaldo , Levasseur Dana , Janz Siegfried , Tricot Guido , Zhan Fenghuang 
Published: January 2015

Abstract
Ibrutinib (Imbruvica), a small-drug inhibitor of Bruton tyrosine kinase (BTK), is currently undergoing clinical testing in patients with multiple myeloma, yet important questions on the role of BTK in myeloma biology and treatment are outstanding. Using flow-sorted side population cells from human myeloma cell lines and multiple myeloma primary samples as surrogate for the elusive multiple myeloma stem cell, we found that elevated expression of BTK in myeloma cells leads to AKT/WNT/β-catenin–dependent upregulation of key stemness genes (OCT4, SOX2, NANOG, and MYC) and enhanced self-renewal. Enforced transgenic expression of BTK in myeloma cells increased features of cancer stemness, including clonogenicity and resistance to widely used myeloma drugs, whereas inducible knockdown of BTK abolished them. Furthermore, overexpression of BTK in myeloma cells promoted tumor growth in laboratory mice and rendered side population–derived tumors that contained high levels of BTK more sensitive to the selective, second-generation BTK inhibitor, CGI1746, than side population–derived tumors that harbored low levels of BTK. Taken together, these findings implicate BTK as a positive regulator of myeloma stemness and provide additional support for the clinical testing of BTK-targeted therapies in patients with myeloma. Cancer Res; 75(3); 594–604. ©2014 AACR.
Novel Insights into Head and Neck Cancer using Next-Generation “Omic” Technologies
Authors: Sepiashvili Lusia , Bruce Jeff P. , Huang Shao Hui , O'Sullivan Brian , Liu Fei-Fei , Kislinger Thomas 
Published: January 2015

Abstract
Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous disease that develops via one of the two primary carcinogenic routes: chemical carcinogenesis through exposure to tobacco and alcohol or virally induced tumorigenesis. Human papillomavirus (HPV)–positive (HPV+) and HPV-negative (HPV−) HNSCCs represent distinct clinical entities, with the latter associated with significantly inferior outcome. The biologic basis of these different outcomes is an area of intense investigation; their therapeutic regimens are currently also being reevaluated, which would be significantly facilitated by reliable biomarkers for stratification. With the advent of the omics era and accelerated development of targeted therapies, there are unprecedented opportunities to address the challenges in the management of HNSCC. As summarized herein, side-by-side molecular characterization of HPV+ versus HPV− HNSCC has revealed distinct molecular landscapes, novel prognostic signatures, and potentially targetable biologic pathways. In particular, we focus on the evidence acquired from genome-wide omics pertinent to our understanding of the clinical behavior of HNSCC and on insights into personalized treatment opportunities. Integrating, mining, and validating these data toward clinically meaningful outcomes for patients with HNSCC in conjunction with systematic verification of the functional relevance of these findings are critical steps toward the design of personalized therapies. Cancer Res; 75(3); 480–6. ©2014 AACR.