bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer: PEGASUS‐PC Study
Authors: Yamaue Hiroki , Tsunoda Takuya , Tani Masaji , Miyazawa Motoki , Yamao Kenji , Mizuno Nobumasa , Okusaka Takuji , Ueno Hideki , Boku Narikazu , Fukutomi Akira , Ishii Hiroshi , Ohkawa Shinichi , Furukawa Masayuki , Maguchi Hiroyuki , Ikeda Masafumi , Togashi Yosuke , Nishio Kazuto , Ohashi Yasuo 
Published: April 2015

Gemcitabine is a key drug for the treatment of pancreatic cancer; however, with its limitation in clinical benefits, the development of another potent therapeutic is necessary. Vascular endothelial growth factor receptor 2 is an essential target for tumor angiogenesis, and we have conducted a phase I clinical trial using gemcitabine and vascular endothelial growth factor receptor 2 peptide (elpamotide). Based on the promising results of this phase I trial, a multicenter, randomized, placebo‐controlled, double‐blind phase II/III clinical trial has been carried out for pancreatic cancer. The eligibility criteria included locally advanced or metastatic pancreatic cancer. Patients were assigned to either the Active group (elpamotide + gemcitabine) or Placebo group (placebo + gemcitabine) in a 2:1 ratio by the dynamic allocation method. The primary endpoint was overall survival. The Harrington–Fleming test was applied to the statistical analysis in this study to evaluate the time‐lagged effect of immunotherapy appropriately. A total of 153 patients (Active group, n = 100; Placebo group, n = 53) were included in the analysis. No statistically significant differences were found between the two groups in the prolongation of overall survival (Harrington–Fleming P‐value, 0.918; log–rank P‐value, 0.897; hazard ratio, 0.87, 95% confidence interval [CI], 0.486–1.557). Median survival time was 8.36 months (95% CI, 7.46–10.18) for the Active group and 8.54 months (95% CI, 7.33–10.84) for the Placebo group. The toxicity observed in both groups was manageable. Combination therapy of elpamotide with gemcitabine was well tolerated. Despite the lack of benefit in overall survival, subgroup analysis suggested that the patients who experienced severe injection site reaction, such as ulceration and erosion, might have better survival.
A systematic review on the correlation between skeletal and jawbone mineral density in osteoporotic subjects
Authors: Calciolari Elena , Donos Nikolaos , Park Jung‐Chul , Petrie Aviva , Mardas Nikos 
Published: April 2015

AbstractObjectivesThe aim of this systematic review was to assess whether the systemic skeletal reduction of bone mineral density (BMD) that characterizes osteoporotic subjects is also associated with a reduction of BMD in the jawbones.Material and methodsTwo reviewers searched independently and in duplicate three databases up to May 2014 and assessed the risk of bias using a tailored version of the Newcastle–Ottawa scale (NOS). Only papers reporting either Pearson's correlation coefficient or Spearman's rank correlation coefficient between skeletal and jawbone mineral density in more than five osteoporotic subjects were selected.ResultsFrom 1763 citations, 64 full‐text papers were screened and five papers that met the inclusion criteria were included in the final analysis. None of the included studies complied with all NOS criteria, and as only two studies were eligible for meta‐analysis, this was not performed.ConclusionsOnly limited conclusions can be drawn from this systematic review, due to the small number of studies included, their heterogeneity, and their high risk of bias. Future studies that take into consideration both upper and lower jaws, that use the same technique to measure skeletal and jaw BMD (ideally dual‐energy X‐ray absorptiometry, DXA), and that account for confounding variables (such as medications/diseases affecting bone metabolism and demographics) are needed to provide more robust conclusions.
Patient‐centered outcomes comparing digital and conventional implant impression procedures: a randomized crossover trial
Authors: Joda Tim , Brägger Urs 
Published: April 2015

AbstractObjectivesThe aim of this randomized controlled trial was to compare patient‐centered outcomes during digital and conventional implant impressions.Material and methodsIn a crossover study design, intraoral scanning (IOS) [test] as well as classical polyether impressions [control] were both performed on 20 patients for single‐tooth replacement with implant‐supported crowns. The sequential distribution of either starting with the test or the control procedure was randomly selected. Patients' perception and satisfaction on the level of convenience‐related factors were assessed with visual analogue scale (VAS) questionnaires. In addition, clinical work time was separately recorded for test and control procedures. Statistical analyses were performed with Wilcoxon signed‐rank tests and corrected for multiple testing by the method of Holm.ResultsOn VAS ranging from 0 to 100, patients scored a mean convenience level of 78.6 (SD ± 14.0) in favor of IOS compared to conventional impressions with 53.6 (SD ± 15.4) [P = 0.0001]. All included patients would prefer the digital workflow if in the future they could choose between the two techniques. Secondary, IOS was significantly faster with 14.8 min (SD ± 2.2) compared to the conventional approach with 17.9 min (SD ± 1.1) [P = 0.0001].ConclusionBased on the findings of this investigation, both impression protocols worked successfully for all study participants capturing the 3D implant positions. However, the digital technique emerges as the most preferred one according to patient‐centered outcomes and was more time‐effective compared to conventional impressions.
Age‐Related Changes in Resting‐State Networks of A Large Sample Size of Healthy Elderly
Authors: Huang Chun‐Chao , Hsieh Wen‐Jin , Lee Pei‐Lin , Peng Li‐Ning , Liu Li‐Kuo , Lee Wei‐Ju , Huang Jon‐Kway , Chen Liang‐Kung , Lin Ching‐Po 
Published: April 2015

SummaryAimsPopulation aging is burdening the society globally, and the evaluation of functional networks is the key toward understanding cognitive changes in normal aging. However, the effect of age on default mode subnetworks has not been documented well, and age‐related changes in many resting‐state networks remain debatable. The purpose of this study was to propose more precise results for these issues using a large sample size.MethodsWe used group‐level meta‐ICA analysis and dual regression approach for identifying resting‐state networks from functional magnetic resonance imaging data of 430 healthy elderly participants. Partial correlation was used to observe age‐related correlations within and between resting‐state networks.ResultsIn the default mode network, only the ventral subnetwork negatively correlated with age. Age‐related decrease in functional connectivity was also noted in the auditory, right frontoparietal, sensorimotor, and visual medial networks. Further, some age‐related increases and decreases were observed for between‐network correlations.ConclusionThe results of this study suggest that only the ventral default mode subnetwork had age‐related decline in functional connectivity and several reverse patterns of resting‐state networks for network development. Understanding age‐related network changes may provide solutions for the impact of population aging and diagnosis of neurodegenerative diseases.
Cross‐Situational Learning of Minimal Word Pairs
Authors: Escudero Paola , Mulak Karen E. , Vlach Haley A. 
Published: April 2015

AbstractCross‐situational statistical learning of words involves tracking co‐occurrences of auditory words and objects across time to infer word‐referent mappings. Previous research has demonstrated that learners can infer referents across sets of very phonologically distinct words (e.g., WUG, DAX), but it remains unknown whether learners can encode fine phonological differences during cross‐situational statistical learning. This study examined learners’ cross‐situational statistical learning of minimal pairs that differed on one consonant segment (e.g., BON–TON), minimal pairs that differed on one vowel segment (e.g., DEET–DIT), and non‐minimal pairs that differed on two or three segments (e.g., BON–DEET). Learners performed above chance for all pairs, but performed worse on vowel minimal pairs than on consonant minimal pairs or non‐minimal pairs. These findings demonstrate that learners can encode fine phonetic detail while tracking word‐referent co‐occurrence probabilities, but they suggest that phonological encoding may be weaker for vowels than for consonants.
TGF‐β signalling prevents pancreatic beta cell death after proliferation
Authors: Lei Chen , Zhou Xiaoling , Pang Yi , Mao Yuanyuan , Lu Xixuan , Li Meijuan , Zhang Jie 
Published: April 2015

AbstractObjectivesMaintenance of functional beta cell mass is critical for prevention of diabetes. The transforming growth factor‐beta (TGF‐β) receptor signalling pathway plays an essential role in pancreatic development. However, its involvement in control of post‐natal beta cell growth has only been recently reported.Materials and methodsHere, we studied the role of TGF‐β receptor signalling in beta cell proliferation after 50% partial pancreatectomy (PPx), using beta cell‐specific TGF‐β receptor II (TBR2)‐mutated mice.ResultsConsistent with previous reports, we found that inhibition of TGF‐β receptor signalling in beta cells resulted in slightly higher beta cell mass 1 week after PPx, due to greater beta cell proliferation. However, beta cell mass in these beta cell‐specific TBR2‐mutated mice significantly decreased by 12 weeks after PPx, resulting from increase in beta cell apoptosis.ConclusionsOur data thus suggest that TGF‐β receptor signalling may be required for prevention of beta cell death after proliferation, and highlight this pathway as an essential regulator during post‐natal beta cell homoeostasis.
Icariin induces osteogenic differentiation of bone mesenchymal stem cells in a MAPK‐dependent manner
Authors: Wu Yuqiong , Xia Lunguo , Zhou Yuning , Xu Yuanjin , Jiang Xinquan 
Published: April 2015

AbstractObjectivesIcariin, a flavonoid isolated from Epimedium pubescens, has previously been identified to exert beneficial effects on preventing bone loss and promoting bone regeneration. However, molecular mechanisms for its anabolic action have, up to now, remained largely unknown.Materials and methodsEffects of icariin on cell proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs) were systematically evaluated. To characterize underlying mechanisms, its effects on mitogen‐activated protein kinase (MAPK) signalling pathways were determined.ResultsResults showed that icariin might not have enhanced effects on cell proliferation. However, it seemed to significantly enhance osteogenic differentiation of BMSCs, demonstrated by increasing alkaline phosphatase (ALP) activity and gene expression of collagen type I (Col I), osteocalcin (OCN) and osteopotin (OPN). It was demonstrated that icariin rapidly phosphorylated extracellular signal‐regulated kinase (ERK), p38 kinase and c‐Jun N terminal kinase (JNK). Furthermore, icariin‐stimulated osteogenic effects on BMSCs were dramatically attenuated by treatment with either specific ERK inhibitor of PD98059, p38 inhibitor of SB202190 or JNK inhibitor SP600125.ConclusionsThese results provide a potential mechanism of anabolic activity of icariin on BMSCs involving ERK, p38 and JNK MAPK pathways.
Perceived barriers to utilise methadone maintenance therapy among male injection drug users in rural areas of southern Thailand
Authors: Khampang Roongnapa , Assanangkornchai Sawitri , Teerawattananon Yot 
Published: April 2015

AbstractIntroduction and AimsMethadone maintenance therapy (MMT) has been proven to be effective and cost‐effective in treating dependence on opioids. However, concerns remain that geographical, financial and other hidden barriers may hinder access to MMT, especially in rural areas where health services are limited. The objective of this study was to determine factors associated with utilisation of MMT by injection drug users (IDUs) living in Songkhla province.Design and MethodsA cross‐sectional study among 159 IDUs in Songkhla province of southern Thailand was conducted. Participants were recruited using a snowball technique. Data were collected from July 2013 to January 2014 via face‐to‐face interviews.ResultsAround one‐forth (24.5%) of participants had difficulties travelling to MMT clinics because of the long distance, long travelling time and lack of a private vehicle. Twenty‐four percent faced difficulties with the clinic's opening hours and 28% faced difficulties paying for the cost of travel. IDUs who utilised the MMT perceived risks of injection drug use differently compared with those who did not. Younger or Muslim IDUs were less likely to attend MMT. IDUs who perceived that MMT was effective were more likely to utilise MMT.Discussion and ConclusionsPhysical accessibility, affordability and acceptability play an essential role in MMT utilisation. Developing alternatives that reduce the travelling time, costs for IDUs and more convenient operation hours to suit their lifestyles may increase the utilisation of MMT. Intensive consultation before starting MMT is highly recommended. [Khampang R, Assanangkornchai S, Teerawattananon Y. Perceived barriers to utilise methadone maintenance therapy among male injection drug users in rural areas of southern Thailand. Drug Alcohol Rev 2015;34:645–53]
Toxicity profile and treatment delays in NOPHO ALL2008—comparing adults and children with Philadelphia chromosome‐negative acute lymphoblastic leukemia
Authors: Toft Nina , Birgens Henrik , Abrahamsson Jonas , Griškevičius Laimonas , Hallböök Helene , Heyman Mats , Klausen Tobias Wirenfeldt , Jónsson Ólafur Gísli , Palk Katrin , Pruunsild Kaie , Quist‐Paulsen Petter , Vaitkeviciene Goda , Vettenranta Kim , Asberg Ann , Helt Louise Rold , Frandsen Thomas , Schmiegelow Kjeld 
Published: April 2015

AbstractObjectivesCure rates improve when adolescents and young adults with acute lymphoblastic leukemia (ALL) are treated according to pediatric protocols. Assumed risks of toxicities and associated delays in treatment have played a role in setting upper age limits. The aim of this study was to examine the toxicity profile and treatment delays in NOPHO ALL2008 comparing children and adults.MethodsWe collected information on 19 treatment‐related toxicities, systematically captured at 3‐month intervals throughout therapy, and time intervals between 12 consecutive treatment phases for 1076 patients aged 1–45 yrs treated according to the Nordic/Baltic ALL2008 protocol.ResultsNo adults died during induction. The duration of induction therapy and postinduction treatment phases did not differ between children and adults, except for patients 18–45 yrs being significantly delayed during two of nine high‐risk blocks (median number of days for patients 1–9, 10–17, and 18–45 yrs; the glucocorticosteroid/antimetabolite‐based block B1: 24, 26, and 29 d, respectively, P = 0.001, and Block 5 (in most cases also a B block): 29, 29, and 37 d, respectively, P = 0.02). A higher incidence of thrombosis with increasing age was found; highest odds ratio 5.4 (95% CI: (2.6;11.0)) for patients 15–17 yrs compared with children 1–9 yrs (P < 0.0001). Risk of avascular osteonecrosis was related to age with the highest OR for patients 10–14 yrs (OR = 10.4 (95% CI: (4.4;24.9)), P < 0.0001).ConclusionAdults followed and tolerated the NOPHO ALL2008 protocol virtually as well as children, although thrombosis and avascular osteonecrosis was most common among adolescents.
Mean reticulocyte volume: a specific parameter to screen for hereditary spherocytosis
Authors: Xu Yuchan , Yang Wang , Liao Lin , Deng Zengfu , Qiu Yuling , Chen Wenqiang , Lin Faquan 
Published: April 2015

AbstractThis study assessed the value of mean reticulocyte volume (MRV) for differential diagnosis of hereditary spherocytosis (HS) so as to develop conventional and new specific screen indexes. Subjects in this study were divided into three groups: 53 cases in HS group, 217 cases in hemolytic anemia control group (109 cases of thalassemia (THAL), 56 cases of glucose‐6‐phosphate dehydrogenase G6PD deficiency anemia, and 52 cases of autoimmune hemolytic anemia (AIHA)), and 100 cases in healthy control group. We analyzed erythrocyte and reticulocyte parameters including MRV, mean sphered corpuscular volume, mean corpuscular hemoglobin concentration, and immature reticulocyte fraction. Results demonstrated that MRV was significantly lower in the HS group but significantly higher in the AIHA and G6PD deficiency anemia groups than that in the healthy control group (P = 0.000). MRV was not significantly different between the AIHA and G6PD deficiency anemia groups (P = 0.977) and between the healthy control and THAL groups (P = 0.168). The area under the ROC curve of MRV for diagnosis of HS was 0.942, with a standard error of 0.019, 95% confidence interval of 0.905–0.979, and optimal critical diagnosis point of 95.77 fL. When the MRV was ≤95.77 fL, the sensitivity and specificity for diagnosis of HS were 86.80% and 91.20%, respectively. Therefore, MRV is a general and specific new index for screening HS and important for differential diagnosis of different types of hemolytic anemia.
Reelin supplementation recovers synaptic plasticity and cognitive deficits in a mouse model for Angelman syndrome
Authors: Hethorn Whitney R. , Ciarlone Stephanie L. , Filonova Irina , Rogers Justin T. , Aguirre Daniela , Ramirez Raquel A. , Grieco Joseph C. , Peters Melinda M. , Gulick Danielle , Anderson Anne E. , L. Banko Jessica , Lussier April L. , Weeber Edwin J. 
Published: April 2015

AbstractThe Reelin signaling pathway is implicated in processes controlling synaptic plasticity and hippocampus‐dependent learning and memory. A single direct in vivo application of Reelin enhances long‐term potentiation, increases dendritic spine density and improves associative and spatial learning and memory. Angelman syndrome (AS) is a neurological disorder that presents with an overall defect in synaptic function, including decreased long‐term potentiation, reduced dendritic spine density, and deficits in learning and memory, making it an attractive model in which to examine the ability of Reelin to recover synaptic function and cognitive deficits. In this study, we investigated the effects of Reelin administration on synaptic plasticity and cognitive function in a mouse model of AS and demonstrated that bilateral, intraventricular injections of Reelin recover synaptic function and corresponding hippocampus‐dependent associative and spatial learning and memory. Additionally, we describe alteration of the Reelin profile in tissue from both the AS mouse and post‐mortem human brain.
Insect life history and the evolution of bacterial mutualism
Authors: Henry Lee M. , Maiden Martin C. J. , Ferrari Julia , Godfray H. Charles J. 
Published: April 2015

AbstractBacterial symbiosis has played a fundamental role in the evolution of eukaryotes. However, we still know little about how cooperative relationships with bacteria originate, and why they form in some host species but not others. Facultative symbionts that are beneficial, but not essential, provide unique insights into these processes. We use data from over a hundred aphid species to test if host life history is associated with the presence of facultative symbionts. We find that aphid species that have mutualistic associations with ants that protect them from natural enemies are less likely to carry symbionts that provide similar benefits. We also find one symbiont species occurs more frequently in unrelated aphid species that specialise on certain plant genera. In addition, aphid species that attack multiple plants often carry different symbiont complements. Our findings provide evidence of the ecological conditions that facilitate stable, mutually beneficial relationships between microbes and eukaryotic hosts.
How far to go? Determinants of migration distance in land mammals
Authors: Teitelbaum Claire S. , Fagan William F. , Fleming Chris H. , Dressler Gunnar , Calabrese Justin M. , Leimgruber Peter , Mueller Thomas 
Published: April 2015

AbstractAnimal migration is a global phenomenon, but few studies have examined the substantial within‐ and between‐species variation in migration distances. We built a global database of 94 land migrations of large mammalian herbivore populations ranging from 10 to 1638 km. We examined how resource availability, spatial scale of resource variability and body size affect migration distance among populations. Resource availability measured as normalised difference vegetation index had a strong negative effect, predicting a tenfold difference in migration distances between low‐ and high‐resource areas and explaining 23% of the variation in migration distances. We found a weak, positive effect of the spatial scale of resource variability but no effect of body size. Resource‐poor environments are known to increase the size of mammalian home ranges and territories. Here, we demonstrate that for migratory populations as well, animals living in resource‐poor environments travel farther to fulfil their resource needs.
Mixed effects of effluents from a wastewater treatment plant on river ecosystem metabolism: subsidy or stress?
Authors: Aristi Ibon , von Schiller Daniel , Arroita Maite , Barceló Damià , Ponsatí Lídia , García‐Galán María J. , Sabater Sergi , Elosegi Arturo , Acuña Vicenç 
Published: April 2015

Summary

The effluents of wastewater treatment plants (WWTPs) include a complex mixture of nutrients and pollutants. Nutrients can subsidise autotrophic and heterotrophic organisms, while toxic pollutants can act as stressors, depending, for instance, on their concentration and interactions in the environment. Hence, it is difficult to predict the overall effect of WWTP effluents on river ecosystem functioning.

We assessed the effects of WWTP effluents on river biofilms and ecosystem metabolism in one river segment upstream from a WWTP and three segments downstream from the WWTP and following a pollution gradient.

The photosynthetic capacity and enzymatic activity of biofilms showed no change, with the exception of leucine aminopeptidase, which followed the pollution gradient most likely driven by changes in organic matter availability. The effluent produced mixed effects on ecosystem‐scale metabolism. It promoted respiration (subsidy effect), probably as a consequence of enhanced availability of organic matter. On the other hand, and despite enhanced nutrient concentrations, photosynthesis–irradiance relationships showed that the effluent partly decoupled primary production from light availability, thus suggesting a stress effect.

Overall, WWTP effluents can alter the balance between autotrophic and heterotrophic processes and produce spatial discontinuities in ecosystem functioning along rivers as a consequence of the mixed contribution of stressors and subsidisers.