bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical experience of ingenol mebutate gel for the treatment of Bowen's disease
Authors: Lee Dong Won , Ahn Hyo Hyun , Kye Young Chul , Seo Soo Hong 
Published: January 2018

AbstractThere are only a few anecdotal case reports about Bowen's disease (BD) treated with ingenol mebutate (IM) gel but no clinical study has been published yet. The aim of this study was to evaluate the effectiveness of IM gel in the treatment of BD and to observe the therapeutic efficacy of IM alone or IM with ablative fractional laser pretreatment. Nineteen patients with BD or squamous cell carcinoma in situ confirmed by skin biopsy were enrolled. IM was applied with 0.015% gel on facial lesions for 3 days consecutively and 0.05% gel on other sites for 2 days consecutively, with a 5‐mm application margin around the visible lesion. Nine patients applied IM gel immediately following fractional CO2 laser treatment. Two patients were lost to follow up and a total of 17 patients were enrolled. Nine patients (9/17, 52.9%) had a clinically complete response at 2 months after treatment. Among the patients treated with the fractional CO2 laser before applying IM gel, eight (8/9, 88.9%) showed a complete response and one (1/9, 11.1%) showed partial response. Among the patients treated with IM gel alone, only one patient (1/8, 12.5%) showed a complete response, four (4/8, 50%) showed a partial response and three (3/8, 37.5%) did not respond to therapy. IM gel alone seems to have limited value for treatment of BD; however, a combination therapy with the ablative fractional laser can increase its therapeutic effectiveness.
Mass‐independent maximal metabolic rate predicts geographic range size of placental mammals
Authors: Hayes Jack P. , Feldman Chris R. , Araújo Miguel B. 
Published: January 2018

Abstract

Understanding the mechanisms driving geographic range sizes of species is a central issue in ecology, but remarkably few rules link physiology with the distributions of species. Maximal metabolic rate (MMR) during exercise is an important measure of physiological performance. It sets an upper limit to sustained activity and locomotor capacity, so MMR may influence ability to migrate, disperse and maintain population connectivity. Using both conventional ordinary least squares (OLS) analyses and phylogenetically generalized least squares (PGLS), we tested whether MMR helps explain geographic range size in 51 species of placental mammals.

Log body mass alone (OLS r2 = .074, p = .053; PGLS r2 = .016, p = .373) and log MMR alone (OLS r2 = .140, p = .007; PGLS r2 = .061, p = .081) were weak predictors of log range size.

However, multiple regression of log body mass and log MMR accounted for over half of the variation in log range size (OLS R2 = .527, p < .001). The relationship was also strong after correcting for the phylogenetic non‐independence (PGLS R2 = .417, p < .001).

In analyses restricted to rodents (34 species), neither log body mass alone (OLS r2 = .004, p = .720; PGLS r2 = .003, p = .77) nor log MMR alone was useful in predicting log geographic range size (OLS r2 = .008, p = .626; PGLS r2 = .046, p = .225), but multiple regressions of log body mass and log MMR accounted for roughly a third to a half of the variation in log range size (OLS R2 = .443, p < .001, PGLS R2 = .381, p < .001).

Mass‐independent MMR is a strong predictor of mass‐independent geographic range size in placental mammals. The ability of body mass and MMR to explain nearly 50% of the variation in the geographic ranges of mammals is surprising and powerful, particularly when neither variable alone is strongly predictive.

A better understanding of MMR during exercise may be important to understanding the limits of geographic ranges of mammals, and perhaps other animal groups.

A plain language summary is available for this article.
Hot Spots of Crime and Place‐Based Prevention
Authors: Weisburd David 
Published: January 2018

AbstractThe August Vollmer Award Address is intended to focus on contributions to justice and on the recipient's research and policy experiences. This contribution begins with the recipient recapping his personal journey to recognizing hot spots of crime and their importance for prevention. He then goes on to summarize the “law of crime concentration” and its importance for the logic model underlying this approach. He describes the seminal Minneapolis Hot Spots Patrol Experiment and the subsequent evaluation research in hot‐spots policing and place‐based prevention more generally that led to its broad acceptance as an effective crime prevention strategy. Finally, the author turns to key unanswered questions in place‐based prevention, focusing on police legitimacy, identifying jurisdictional effects, and emphasizing the importance of harnessing informal social controls.
Evidence for selective avoidance of traffic noise by anuran amphibians
Authors: Grace M. K. , Noss R. F. 
Published: January 2018

AbstractRoads create many challenges for conservation, and amphibians are particularly vulnerable to their negative effects. This experiment evaluates the impact that traffic noise has on amphibian populations, specifically anurans (frogs and toads). It is thought that traffic noise may act to reduce population abundances; however, it is difficult to disentangle the impact of noise from other road effects, such as roadkill and chemical pollution. To test this, we created a ‘phantom road’ by playing different traffic noise treatments in three roadless areas and measured resulting anuran abundance using vocalizations as a proxy. We also tested the vocalizations of one species, the Oak Toad Anaxyrus quercicus for changes in response to noise. We found that broadcasting traffic noise caused a significant reduction in vocalizations heard, but, intriguingly, we did not observe this effect when the traffic noise was digitally altered to remove frequencies that overlap with anuran vocalizations. This suggests that avoidance of traffic noise could be a tactic that increases the success of communication with conspecifics. We also found that Oak Toads increase the redundancy of their calls in response to traffic noise, but not in response to the altered noise.
Patterns of care of superficial soft tissue sarcomas: it is not always just a lump
Authors: Tan Mark Ting Le , Thompson Stephen R. , Schipp Diane , Bae Susie , Crowe Philip J. 
Published: January 2018

AbstractAimSuperficial soft tissue sarcomas (S‐STS) are generally considered low‐risk tumors and have an excellent prognosis when treated with appropriate surgery and adjuvant therapy. However, they are often misdiagnosed then mistreated, leading to significant morbidity. This study aims to examine the patterns of care and outcomes of patients with S‐STS, comparing those initially managed through sarcoma units versus elsewhere.MethodsPatients with S‐STS from Prince of Wales Hospital in NSW (1995–2013) and Peter MacCallum Cancer Centre in Victoria (2009–2013) were identified from a national sarcoma database. Baseline variables, treatment and disease outcomes were recorded. Statistical tests performed included univariate and multivariate analyses, chi‐square tests, as well as the Kaplan–Meier method for 5‐year local recurrence and survival rates.ResultsEighty‐nine patients were identified, with 35% initially managed at a sarcoma unit and 65% elsewhere. Patients initially managed at sarcoma units had larger tumors (>5 cm 39% vs 17%; P = 0.036) with a trend to higher grade (61% vs 48%; P = 0.39). Patients that were initially managed outside a sarcoma unit more often underwent open surgical biopsies (P < 0.0005), had multiple operations (P < 0.0005) and had higher rates of local recurrences (24% vs 6.5%, P = 0.038). They also had lower 5‐year local recurrence‐free survival rates (P = 0.022), but had higher metastasis‐free survival (P = 0.014). On multivariate analysis, only larger STS size and male gender predicted for poorer metastasis‐free survival (P = 0.042 and 0.018, respectively).ConclusionPatients with S‐STS initially managed outside specialized sarcoma units undergo more operations, with risk of greater morbidity, and have greater risk of local recurrence.
FLT3‐ITD positive acute myeloid leukemia: A retrospective analysis of the role of allogeneic transplant and allelic ratio in patient management
Authors: Taylor Emma , Morris Kirk , Ellis Marc , Marlton Paula , Baveshi Ketan , Clarey Joseph , Irving Ian , Cochrane Tara , Kennedy Glen 
Published: January 2018

AbstractAimFMS‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD) positive AML is associated with increased relapse risk and reduced overall survival (OS) compared to non‐FLT3‐mutated AML. The aim of this study was to evaluate the impact of allelic ratio and allogeneic transplant on outcomes in FLT3‐ITD+ AML.MethodsA retrospective study across five centers in Queensland, Australia, was conducted to examine survival outcomes and impact of FLT3‐ITD allelic ratio and allograft.ResultsSeventy‐one patients were included in the study. OS was significantly better for patients who were able to be allografted in first complete remission (CR1; 50.1 months vs 8.5 months; P = 0.0002). We did not find allelic ratio to be predictive of outcome.ConclusionTransplantation in first complete remission is associated with improved outcomes for patients with FLT3+ AML. When feasible transplantation in CR1 is recommended. We do not currently recommend using allelic ratio to stratify risk unless this has been validated by local results.
Pacifier use in newborns: related to socioeconomic status but not to early feeding performance
Authors: Pineda Roberta , Luong Anhthi , Ryckman Justin , Smith Joan 
Published: January 2018

AbstractAimMothers are often advised not to use pacifiers until breastfeeding has been well‐established. This study determined the infant and social factors that were related to pacifier use during the first few days of life and whether it led to alterations in feeding performance.MethodsWe enroled 51 full‐term infants and their mothers at Barnes‐Jewish Hospital in urban St. Louis, USA, in 2015. Before they were discharged the mothers completed a questionnaire, and infant feeding was assessed using a standardised assessment.ResultsThere were 24 (47%) infants who used a pacifier during the first few days of life and seven (29%) of these were exclusively breastfed. Pacifier use was less common among mothers who exclusively breastfed (p = 0.04). Pacifier use was more common among mothers whose income was less than 25 000 US dollars (p = 0.02), who were single (p = 0.002) and who did not have a college education (p = 0.03). No associations between pacifier use and feeding performance were observed.ConclusionWhile lower socioeconomic status was related to pacifier use, feeding performance in the first few days of life was no different between those infants who did and did not use pacifiers after a full‐term birth.
Higher Ca2+‐sensitivity of arterial contraction in 1‐week‐old rats is due to a greater Rho‐kinase activity
Authors: Mochalov S. V. , Tarasova N. V. , Kudryashova T. V. , Gaynullina D. K. , Kalenchuk V. U. , Borovik A. S. , Vorotnikov A. V. , Tarasova O. S. , Schubert R. 
Published: January 2018

AbstractAimDuring early post‐natal development, arterial contraction depends less on Ca2+‐signalling pathways but more on changes in Ca2+‐sensitivity compared to adult animals. Whether this difference is related to Rho‐kinase, one of the major players affecting Ca2+‐sensitivity, is unknown for intact vessels. Thus, we tested the hypothesis that Rho‐kinase critically contributes to the higher Ca2+‐sensitivity of contraction in intact arteries of 1‐week‐old rats.MethodsWe studied 1‐week‐old, 4‐ to 5‐week‐old and 10‐ to 12‐week‐old rats performing isometric myography, Ca2+‐fluorimetry and Western blotting using intact saphenous arteries and arterial pressure measurements under urethane anaesthesia.ResultsIn 10‐ to 12‐week‐old rats, methoxamine (MX) produced vasoconstriction associated with an increase in [Ca2+]i and Ca2+‐sensitivity. In contrast, in 1‐week‐old rats these contractions were accompanied only by an increase in Ca2+‐sensitivity. All MX‐induced effects were reduced by the Rho‐kinase inhibitor Y‐27632; this reduction was complete only in 1‐week‐old rats. The Rho‐kinase specific site Thr855 on MYPT1 was increasingly phosphorylated by MX in vessels of 1‐week‐old, but not 10‐ to 12‐week‐old rats; this effect was also inhibited completely by Y‐27632. The Rho‐kinase inhibitor fasudil in a dose not affecting the pressor response to MX in 4‐ to 5‐week‐old rats reduced it considerably in 1‐week‐old rats.ConclusionOur results suggest that the higher Ca2+‐sensitivity of arterial contraction in 1‐week‐old compared to 10‐ to 12‐week‐old rats is due to a greater Rho‐kinase activity. Constitutively active Rho‐kinase contributes to MX‐induced contraction in 10‐ to 12‐week‐old rats. In 1‐week‐old rats, additional Rho‐kinase activation is involved. This remodelling of the Rho‐kinase pathway is associated with its increased contribution to adrenergic arterial pressure responses.
Glutathione‐PEGylated liposomal methylprednisolone in comparison to free methylprednisolone: slow release characteristics and prolonged lymphocyte depression in a first‐in‐human study
Authors: Kanhai K. M. S. , Zuiker R. G. J. A. , Stavrakaki I. , Gladdines W. , Gaillard P. J. , Klaassen E. S. , Groeneveld G. J. 
Published: January 2018

AimsIntravenous high‐dose free methylprednisolone (MP) hemisuccinate is the primary treatment for an acute relapse in relapsing–remitting multiple sclerosis. However, it is inconvenient and its side effects are undesirable. Both dose and dosing frequency can be reduced by incorporating free MP in glutathione‐PEGylated liposomes, creating a slow‐release formulation with reduced toxicity and prolonged peripheral efficacy. This first‐in‐human study was designed to assess the safety, pharmacokinetics and pharmacodynamics of glutathione‐PEGylated liposomes containing MP (2B3–201).MethodsThe first part was a double‐blind, three‐way cross over study in 18 healthy male subjects, receiving ascending doses of 2B3–201, active comparator (free MP) or placebo. Part 2 of the study was an open‐label infusion of 2B3–201 (different doses), exploring pretreatment with antihistamines and different infusion schedules in another 18 healthy male subjects, and a cross‐over study in six healthy female subjects. MP plasma concentrations, lymphocyte counts, adrenocorticotropic hormone, osteocalcin and fasting glucose were determined. Safety and tolerability profiles were assessed based on adverse events, safety measurements and central nervous system tests.ResultsThe most frequent recorded AE related to 2B3–201 was an infusion related reaction (89%). 2B3–201 was shown to have a plasma half‐life between 24 and 37 h and caused a prolonged decrease in the lymphocyte count, adrenocorticotropic hormone and osteocalcin, and a rise in fasting glucose.Conclusion2B3–201 is considered safe, with no clinically relevant changes in central nervous system safety parameters and no serious adverse events. In addition, 2B3–201 shows a long plasma half‐life and prolonged immunosuppressive effects.
Active retreat of a Late Weichselian marine‐terminating glacier: an example from Melasveit, western Iceland
Authors: Sigfúsdóttir Thorbjörg , Benediktsson Ívar Örn , Phillips Emrys 
Published: January 2018

Large and complete glaciotectonic sequences formed by marine‐terminating glaciers are rarely observed on land, hampering our understanding of the behaviour of such glaciers and the processes operating at their margins. During the Late Weichselian in western Iceland, an actively retreating marine‐terminating glacier resulted in the large‐scale deformation of a sequence of glaciomarine sediments. Due to isostatic rebound since the deglaciation, these formations are now exposed in the coastal cliffs of Belgsholt and Melabakkar‐Ásbakkar in the Melasveit district, and provide a detailed record of past glacier dynamics and the inter‐relationships between glaciotectonic and sedimentary processes at the margin of this marine‐terminating glacier. A comprehensive study of the sedimentology and glaciotectonic architecture of the coastal cliffs reveals a series of subaquatic moraines formed by a glacier advancing from Borgarfjörður to the north of the study area. Analyses of the style of deformation within each of the moraines demonstrate that they were primarily built up by ice‐marginal/proglacial thrusting and folding of marine sediments, as well as deposition and subsequent deformation of ice‐marginal subaquatic fans. The largest of the moraines exposed in the Melabakkar‐Ásbakkar section is over 1.5 km wide and 30 m high and indicates the maximum extent of the Borgarfjörður glacier. Generally, the other moraines in the series become progressively younger towards the north, each designating an advance or stillstand position as the glacier oscillated during its overall northward retreat. During this active retreat, glaciomarine sediments rapidly accumulated in front of the glacier providing material for new moraines. As the glacier finally receded from the area, the depressions between the moraines were infilled by continued glaciomarine sedimentation. This study highlights the dynamics of marine‐terminating glaciers and may have implications for the interpretation of their sedimentological and geomorphological records.
Bullying, mental health and friendship in Australian primary school children
Authors: Bayer Jordana K. , Mundy Lisa , Stokes Isobel , Hearps Stephen , Allen Nicholas , Patton George 
Published: January 2018

BackgroundFrequent bullying predicts adolescent mental health problems, particularly depression. This population‐based study with young Australian primary school children aimed to determine the frequency and mental health correlates of bullying, and whether friendship could be protective.MethodParticipants were a population‐based sample of 1221 children aged 8–9 years attending 43 primary schools in metropolitan Melbourne, Australia. Children were taking part in the Childhood to Adolescence Transition Study. Children completed online questionnaires at school to measure peer relations and emotional well‐being. Parents reported on their child's mental health in questionnaires sent to the home.ResultsOne in three children (29.2%) reported experiencing frequent bullying, defined as at least once a week. This included physical bullying alone (13.8%), verbal bullying alone (22.7%) and the combination (7.4%). Children who reported being frequently bullied self‐reported higher internalising symptoms compared with children who did not report frequent bullying (M (SD) 1.6 (0.9) vs. 1.1 (0.8), p < .001). This difference was confirmed by parents' reports of their child's internalising symptoms (M (SD) 2.4 (2.3) vs. 2.1 (2.0), p = .026, respectively). Amongst children who reported frequent bullying, those with a group of friends had better emotional well‐being.ConclusionsA substantial proportion of children report experiencing bullying on a weekly basis early in primary school. Given the prevalence of bullying in primary school and its relationship to children's mental health, we recommend effective school‐wide antibullying programmes. Further research can explore whether intervention to foster a group of friends around bullied children can improve their emotional well‐being.
Long noncoding RNA BC005927 upregulates EPHB4 and promotes gastric cancer metastasis under hypoxia
Authors: Liu Xiangqiang , Wang Yafang , Sun Li , Min Jie , Liu Jiaming , Chen Di , Zhang Hongbo , Zhang Hongwei , Zhang Helong , Zhou Yongan , Liu Lili 
Published: January 2018

Hypoxia plays a critical role in the metastasis of gastric cancer (GC), yet the underlying mechanism remains largely unclear. It is also not known whether long, noncoding RNAs (lncRNAs) are involved in the contribution of hypoxia to GC metastasis. In the present study, we found that lncRNA BC005927 can be induced by hypoxia in GC cells and mediates hypoxia‐induced GC cell metastasis. Furthermore, BC005927 is frequently upregulated in GC samples and increased BC005927 expression was correlated with a higher tumor‐node‐metastasis stage. GC patients with higher BC005927 expression had poorer prognoses than those with lower expression. Additional experiments showed that BC005927 expression is induced by hypoxia inducible factor‐1 alpha (HIF‐1α); ChIP assay and luciferase reporter assays confirmed that this lncRNA is a direct transcriptional target of HIF‐1α. Next, we found that EPHB4, a metastasis‐related gene, is regulated by BC005927 and that the expression of EPHB4 was positively correlated with that of BC005927 in the clinical GC samples assessed. Intriguingly, EPHB4 expression was also increased under hypoxia, and its upregulation by BC005927 resulted in hypoxia‐induced GC cell metastasis. These results advance the current understanding of the role of BC005927 in the regulation of hypoxia signaling and offer new avenues for the development of therapeutic interventions against cancer progression.
Step‐down of inhaled corticosteroids in non‐eosinophilic asthma: A prospective trial in real life
Authors: Demarche S. , Schleich F. , Henket M. , Paulus V. , Louis R. , Van Hees T. 
Published: January 2018

SummaryBackgroundWhile non‐eosinophilic asthmatics are usually considered poorly responsive to inhaled corticosteroids (ICSs), studies assessing a step‐down of ICS in this specific population are currently lacking.ObjectivesTo assess the proportion of non‐eosinophilic asthmatics in whom ICS may be withdrawn without any clinical degradation and to determine the predictive markers of a failure to stop treatment with ICS.MethodsThis prospective study was completed by 36 non‐eosinophilic asthmatics, defined by sputum eosinophils <3% and blood eosinophils <400/μL. In these patients, whichever the baseline asthma control level, the dose of ICS was gradually reduced every 3 months until they met the failure criteria or successfully discontinued ICS for 6 months. The failure criteria were an ACQ score ≥1.5 with an increase from baseline >0.5 or a number of severe exacerbations during the study which was greater than the number during the year prior to the baseline visit. Receiver‐operating characteristic (ROC) curves were constructed to assess predictors of a failure to stop ICS. This study is registered with ClinicalTrials.gov, number NCT02169323.ResultsIn 14 patients (39%), ICSs were completely withdrawn, and in 10 further patients (28%), ICS were stepped‐down to a reduced ICS dose without any deterioration of asthma control and exacerbation rate. Baseline predictors of a failure to stop ICS were a greater age (area under ROC curve [ROC AUC] and [95% CI]: 0.77 [0.62‐0.93]) and elevated blood eosinophils (ROC AUC [95% CI]: 0.77 [0.61‐0.93]). After the first step‐down of ICS, the best predictor was an elevated blood eosinophil count (ROC AUC [95% CI]: 0.85 [0.72‐0.99]).Conclusions & Clinical RelevanceWithdrawing or reducing the dose of ICS is feasible in two‐thirds of non‐eosinophilic asthmatics irrespective of baseline asthma control. An elevated blood eosinophil count may predict the failure to stop ICS.