bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of once‐weekly dulaglutide versus insulin glargine in mainly Asian patients with type 2 diabetes mellitus on metformin and/or a sulphonylurea: A 52‐week open‐label, randomized phase III trial
Authors: Wang Weiqing , Nevárez Luis , Filippova Ekaterina , Song Ki Ho , Tao Bei , Gu Liqun , Wang Feng , Li Pengfei , Yang Jun
Published: August 2018

Aim

To compare the efficacy and safety of once‐weekly dulaglutide with that of insulin glargine in combination with metformin and/or a sulphonylurea in mainly Asian patients with type 2 diabetes mellitus (T2DM).

Materials and Methods

In this 52‐week, randomized, parallel‐arm open‐label study, we enrolled patients aged ≥18 years with T2DM for at least 6 months and a glycated haemoglobin (HbA1c) concentration ≥53.0 mmol/mol (7.0%) and ≤96.7 mmol/mol (11.0%). The primary outcome was change in HbA1c from baseline to week 26 to determine non‐inferiority of dulaglutide 1.5 mg versus glargine.

Results

A total of 774 patients from China, South Korea, Mexico and Russia were randomly assigned (1:1:1) to dulaglutide 1.5 mg, dulaglutide 0.75 mg or glargine treatment groups. The patients' mean age was 55 years and the average T2DM duration was ~8 years. The least squares mean (SE) changes from baseline in HbA1c at 26 weeks were − 18.9 (0.73) mmol/mol (−1.73 [0.067]%) for dulaglutide 1.5 mg and −14.5 (0.73) mmol/mol (−1.33 [0.067]%) for dulaglutide 0.75 mg, compared with −12.7 (0.73) mmol/mol (−1.16 [0.067]%) for glargine. Statistical criteria for superiority were met with both dulaglutide 1.5 mg and dulaglutide 0.75 mg. More patients in the dulaglutide 1.5 and 0.75 mg groups achieved HbA1c target <53.0 mmol/mol (<7.0%) than in the glargine group at week 26 (P < 0.001 and P = 0.004, respectively). Body weight decreased with dulaglutide and increased with glargine. The incidence and rate of total hypoglycaemia were lower with dulaglutide versus glargine. Gastrointestinal adverse events, including diarrhoea and nausea, were the most frequently reported for patients taking dulaglutide.

Conclusions

Once‐weekly dulaglutide provides greater improvement in HbA1c, with weight loss and less hypoglycaemia, than once‐daily insulin glargine in a population of mainly Asian patients with T2DM who had failed to achieve optimal glycaemic control on metformin and/or a sulphonylurea.
Does future resource input reflect need in first‐episode psychosis: Examining the association between individual characteristics and 5‐year costs
Authors: Hastrup Lene H. , Nordentoft Merete , Gyrd‐Hansen Dorte
Published: August 2018

Aim

Coupling data on future resource consumption with baseline characteristics can provide vital information of future consumption patterns for newly diagnosed patients. This study tested whether higher need (as measured by severity of illness) and other baseline characteristics of newly diagnosed patients were associated with higher future service costs.

Method

Five hundred forty‐seven patients between 18 and 45 years randomized to the OPUS trial was analysed in the study. Multiple regression analysis was applied to estimate the impact of the explanatory variables on mean total costs, which consisted of total health care costs and costs of supportive living facilities.

Results

Lower age, higher level of symptoms (global assessment of functioning), alcohol or cannabis misuse, and being homeless were associated with higher total costs over 5 years, whereas sex, duration of untreated psychosis, and educational level did not show any impact on future resource consumption.

Conclusion

The association between future costs and severity of illness suggests that higher needs among patients were associated with higher resource input level. Our results also indicate that other factors than need might affect future costs, for example, parents who serve as advocates for young patients had impact on future health costs. We also found indications of potential barriers among patients with other citizenship in access to health‐care services. The strength of the study is that resource data were extracted from official Danish registers and interviewers collected information on clinical characteristics. The results are likely to be context‐specific but can be generalized to settings with similar treatment practices.
Diverse student voice approaches across Europe
Authors: Bron Jeroen , Emerson Norman , Kákonyi Lucia
Published: August 2018

The Student voice concept encompasses the right for learners to express their opinions, access people who influence decisions and actively participate in educational decision‐making processes. In this article, three features of a European Erasmus Plus project called “BRIDGE” are presented in a sequence ranging from theoretical considerations for school improvement to an analysis of school contexts and settings, followed by a presentation of results from working with one of the project’s student voice tools. Central in each example is the notion that working in partnership with students will enable students to become more self‐directed learners and active citizens.
Is aided phytostabilization a suitable technique for the remediation of tailings?
Authors: Martínez‐Martínez Silvia , Zornoza Raul , Gabarrón María , Gómez‐Garrido Melisa , Rosales Rosa M. , Muñoz María A. , Gómez‐López María D. , Soriano‐Disla José M. , Faz Angel , Acosta Jose A.
Published: August 2018

Mining activity in Cartagena‐La Union mining district (SE Spain) dates back more than 2500 years. Consequently, large amounts of sterile materials with large metal(loid) contents (mostly Zn and Pb) have accumulated in tailings ponds. A reclamation strategy based on aided phytostabilization was carried out to reclaim one tailings pond to reduce environmental and public health hazards. The main goal of this study was to determine the effectiveness of the aided phytostabilization strategy after 30 months from its implementation in enhancing soil quality and fertility and reducing mobility of the metals. Marble waste, raw pig slurry and its solid phase after physical separation were applied as amendments, and 13 Mediterranean native plant species were planted or sown. Various soil physicochemical and biochemical properties, together with the pseudo‐total and bioavailable fraction of the metal(loid)s, As, Cd, Cu, Pb and Zn, were monitored for 30 months. Results showed that pH, total organic carbon (TOC), total nitrogen (TN), cation exchange capacity (CEC), available phosphorus (P), exchangeable potassium (K), microbial biomass carbon (MBC), basal soil respiration (BSR) and enzyme activities increased with the application of the amendments and development of vegetation. In addition, the available fraction of metals markedly decreased (90–99%). Most plant species present in the area did not transfer large amounts of trace elements to the aerial tissues. The roots ofLygeum spartumloefl. Ex L. andPiptatherum miliaceum(L.) Coss. accumulated the largest amounts of As, Pb and Zn. Thus, the application of marble waste to increase pH and immobilize metal(loid)s, and pig slurry as a source of organic matter and nutrients, together with the development of vegetation to immobilize metal(loid)s in the roots and rhizosphere, and the effect of microbial communities on organic matter stabilization and development, have contributed to improve soil quality and fertility. Once the soil quality of mine tailings was improved, the development of vegetation and microbial colonization increased, promoting integrated reclamation of the area. Therefore, aided phytostabilization was a suitable technique for remediation of this tailings pond.

Highlights

We evaluated effectiveness of mid‐term and large‐scale aided phytostabilization.

Marble waste, pig slurry and native plants were used for reclamation of a tailings pond.

Increased soil quality promoted plant development and microbial colonization.

Lygeum spartumandPiptatherum miliaceumare good candidates to phytostabilize Pb, Zn and As.
Correlates of rate heterogeneity in avian ecomorphological traits
Authors: Chira A. M. , Cooney C. R. , Bright J. A. , Capp E. J. R. , Hughes E. C. , Moody C. J. A. , Nouri L. O. , Varley Z. K. , Thomas G. H.
Published: August 2018

Heterogeneity in rates of trait evolution is widespread, but it remains unclear which processes drive fast and slow character divergence across global radiations. Here, we test multiple hypotheses for explaining rate variation in an ecomorphological trait (beak shape) across a globally distributed group (birds). We find low support that variation in evolutionary rates of species is correlated with life history, environmental mutagenic factors, range size, number of competitors, or living on islands. Indeed, after controlling for the negative effect of species' age, 80% of variation in species‐specific evolutionary rates remains unexplained. At the clade level, high evolutionary rates are associated with unusual phenotypes or high species richness. Taken together, these results imply that macroevolutionary rates of ecomorphological traits are governed by both ecological opportunity in distinct adaptive zones and niche differentiation among closely related species.
Testing Darwin's transoceanic dispersal hypothesis for the inland nettle family (Urticaceae)
Authors: Wu Zeng‐Yuan , Liu Jie , Provan Jim , Wang Hong , Chen Chia‐Jui , Cadotte Marc W. , Luo Ya‐Huang , Amorim Bruno S. , Li De‐Zhu , Milne Richard I.
Published: August 2018

Dispersal is a fundamental ecological process, yet demonstrating the occurrence and importance of long‐distance dispersal (LDD) remains difficult, having rarely been examined for widespread, non‐coastal plants. To address this issue, we integrated phylogenetic, molecular dating, biogeographical, ecological, seed biology and oceanographic data for the inland Urticaceae. We found that Urticaceae originated in Eurasia c. 69 Ma, followed by ≥ 92 LDD events between landmasses. Under experimental conditions, seeds of many Urticaceae floated for > 220 days, and remained viable after 10 months in seawater, long enough for most detected LDD events, according to oceanographic current modelling. Ecological traits analyses indicated that preferences for disturbed habitats might facilitate LDD. Nearly half of all LDD events involved dioecious taxa, so population establishment in dioecious Urticaceae requires multiple seeds, or occasional selfing. Our work shows that seawater LDD played an important role in shaping the geographical distributions of Urticaceae, providing empirical evidence for Darwin's transoceanic dispersal hypothesis.
Interspecific variation in conspecific negative density dependence can make species less likely to coexist
Authors: Stump Simon Maccracken , Comita Liza S.
Published: August 2018

Conspecific negative density dependence (CNDD) is thought to promote plant species diversity. Theoretical studies showing the importance of CNDD often assumed that all species are equally susceptible to CNDD; however, recent empirical studies have shown species can differ greatly in their susceptibility to CNDD. Using a theoretical model, we show that interspecific variation in CNDD can dramatically alter its impact on diversity. First, if the most common species are the least regulated by CNDD, then the stabilising benefit of CNDD is reduced. Second, when seed dispersal is limited, seedlings that are susceptible to CNDD are at a competitive disadvantage. When parameterised with estimates of CNDD from a tropical tree community in Panama, our model suggests that the competitive inequalities caused by interspecific variation in CNDD may undermine many species’ ability to persist. Thus, our model suggests that variable CNDD may make communities less stable, rather than more stable.
Population genetic structure of the deep‐sea mussel Bathymodiolus platifrons (Bivalvia: Mytilidae) in the Northwest Pacific
Authors: Xu Ting , Sun Jin , Watanabe Hiromi K. , Chen Chong , Nakamura Masako , Ji Rubao , Feng Dong , Lv Jia , Wang Shi , Bao Zhenmin , Qian Pei‐Yuan , Qiu Jian‐Wen
Published: August 2018

Studying population genetics of deep‐sea animals helps us understand their history of habitat colonization and population divergence. Here, we report a population genetic study of the deep‐sea mussel Bathymodiolus platifrons (Bivalvia: Mytilidae) widely distributed in chemosynthesis‐based ecosystems in the Northwest Pacific. Three mitochondrial genes (i.e., atp6, cox1, and nad4) and 6,398 genomewide single nucleotide polymorphisms (SNPs) were obtained from 110 individuals from four hydrothermal vents and two methane seeps. When using the three mitochondrial genes, nearly no genetic differentiation was detected for B. platifrons in the Northwest Pacific. Nevertheless, when using SNP datasets, all individuals in the South China Sea (SCS) and three individuals in Sagami Bay (SB) together formed one genetic cluster that was distinct from the remaining individuals. Such genetic divergence indicated a genetic barrier to gene flow between the SCS and the open Northwest Pacific, resulting in the co‐occurrence of two cryptic semi‐isolated lineages. When using 125 outlier SNPs identified focusing on individuals in the Okinawa Trough (OT) and SB, a minor genetic subdivision was detected between individuals in the southern OT (S‐OT) and those in the middle OT (M‐OT) and SB. This result indicated that, although under the influence of the Kuroshio Current and the North Pacific Intermediate Water, subtle geographic barriers may exist between the S‐OT and the M‐OT. Introgression analyses based on these outlier SNPs revealed that Hatoma Knoll in the S‐OT represents a possible contact zone for individuals in the OT‐SB region. Furthermore, migration dynamic analyses uncovered stronger gene flow from Dai‐yon Yonaguni Knoll in the S‐OT to the other local populations, compared to the reverse directions. Taken together, the present study offered novel perspectives on the genetic connectivity of B. platifrons mussels, revealing the potential interaction of ocean currents and geographic barriers with adaption and reproductive isolation in shaping their migration patterns and genetic differentiation in the Northwest Pacific.
The INO80 complex activates the transcription of S‐phase genes in a cell cycle‐regulated manner
Authors: Knezevic Iva , González‐Medina Alberto , Gaspa Laura , Hidalgo Elena , Ayté José
Published: August 2018

Chromatin structure is an essential factor in the proper regulation of DNA repair, DNA replication and transcription. The INO80 complex and the SWR complex have been shown to play a fundamental role in transcription regulation through remodeling chromatin at specific genes and loci. Here, we report that the Schizosaccharomyces pombe INO80 complex physically interacts with the mlui‐binding factor (MBF) complex. Furthermore, we are able to detect the INO80 complex in MBF‐regulated promoters. Binding of INO80 to these genes is cell cycle regulated, with a maximum binding preceding their transcription and accumulation of their mRNAs. In fact, the INO80 complex is required to fully and timely activate the transcription of these genes. We also show that the accumulation of acetylated H2A.Z at the +1 nucleosome is cell cycle regulated. Cells in which H2A.Z acetylation is abolished still have some cell cycle‐regulated transcription of MBF‐dependent genes, although to a much lesser extent.
The effect of dyad type on collaboration: Interactions among heritage and second language learners
Authors: Walls Laura C.
Published: August 2018

This study investigated the dynamics between matched heritage language learner (HLL) dyads, second language learner (L2L) dyads, and mixed HLL‐L2L dyads in the Spanish L2 classroom. Data come from 15‐minute video recordings of 16 dyads, including four HLL–HLL, four L2L–L2L, and eight HLL–L2L dyads that were collected during collaborative writing activities in level 1 and 2 classes at a community college in southern California. Dyads’ interactions were analyzed and then categorized according to the predominant characteristics of each dyad: collaborative, cooperative, dominant–passive, and expert–novice. Key findings demonstrate that matched dyads worked collaboratively and provided more opportunities for language learning than mixed dyads. Pedagogical implications are pinpointed, and possible ways in which dyads can function more effectively are discussed.
Genetic correlations between nicotine reinforcement‐related behaviors and propensity toward high or low alcohol preference in two replicate mouse lines
Authors: Weera Marcus M. , Agim Zeynep S. , Cannon Jason R. , Chester Julia A.
Published: August 2018

Common genetic factors may contribute to the high comorbidity between tobacco smoking and alcohol use disorder. Here, we assessed behavioral and biological effects of nicotine in replicate mouse lines selectively bred for high (HAP2/3) or low alcohol preference (LAP2/3). In Experiment 1, free‐choice (FC) oral nicotine and quinine intake were assessed in HAP2/3 and LAP2/3 mice. Effects of nicotinic acetylcholine receptor blockade by mecamylamine on nicotine intake in HAP2 mice were also examined. In Experiment 2, HAP2/3 and LAP2/3 mice were tested for differences in sensitivity to nicotine‐induced taste conditioning. In Experiment 3, the effects of a single nicotine injection on nucleus accumbens (NAc) and dorsal striatum monoamine levels in HAP2/3 and LAP2/3 mice were tested. In Experiment 1, HAP2/3 mice showed greater nicotine intake and intake ratio than LAP2/3 mice. There were no line differences in quinine intake. Mecamylamine reduced nicotine intake and intake ratio in HAP2 mice. In Experiment 2, HAP2/3 mice showed weaker nicotine‐induced conditioned taste aversion (CTA) compared with LAP2/3 mice. In Experiment 3, nicotine treatment increased NAc dopamine turnover across both HAP2/3 and LAP2/3 mouse lines. These results show that there is a positive genetic correlation between oral alcohol intake (high alcohol intake/preference selection phenotype) and oral nicotine intake and a negative genetic correlation between oral alcohol intake and sensitivity to nicotine‐induced CTA.
Nitrous oxide from chemodenitrification: A possible missing link in the Proterozoic greenhouse and the evolution of aerobic respiration
Authors: Stanton Chloe L. , Reinhard Christopher T. , Kasting James F. , Ostrom Nathaniel E. , Haslun Joshua A. , Lyons Timothy W. , Glass Jennifer B.
Published: August 2018

The potent greenhouse gas nitrous oxide (N2O) may have been an important constituent of Earth's atmosphere during Proterozoic (~2.5–0.5 Ga). Here, we tested the hypothesis that chemodenitrification, the rapid reduction of nitric oxide by ferrous iron, would have enhanced the flux of N2O from ferruginous Proterozoic seas. We empirically derived a rate law, , and measured an isotopic site preference of +16‰ for the reaction. Using this empirical rate law, and integrating across an oceanwide oxycline, we found that low nM NO and μM‐low mM Fe2+ concentrations could have sustained a sea‐air flux of 100–200 Tg N2O–N year−1, if N2 fixation rates were near‐modern and all fixed N2 was emitted as N2O. A 1D photochemical model was used to obtain steady‐state atmospheric N2O concentrations as a function of sea‐air N2O flux across the wide range of possible pO2 values (0.001–1 PAL). At 100–200 Tg N2O–N year−1 and >0.1 PAL O2, this model yielded low‐ppmv N2O, which would produce several degrees of greenhouse warming at 1.6 ppmv CH4 and 320 ppmv CO2. These results suggest that enhanced N2O production in ferruginous seawater via a previously unconsidered chemodenitrification pathway may have helped to fill a Proterozoic “greenhouse gap,” reconciling an ice‐free Mesoproterozoic Earth with a less luminous early Sun. A particularly notable result was that high N2O fluxes at intermediate O2 concentrations (0.01–0.1 PAL) would have enhanced ozone screening of solar UV radiation. Due to rapid photolysis in the absence of an ozone shield, N2O is unlikely to have been an important greenhouse gas if Mesoproterozoic O2 was 0.001 PAL. At low O2, N2O might have played a more important role as life's primary terminal electron acceptor during the transition from an anoxic to oxic surface Earth, and correspondingly, from anaerobic to aerobic metabolisms.
Niche partitioning in carabids: single‐tree admixtures matter
Authors: Wehnert Alexandra , Wagner Sven
Published: August 2018

The importance of tree mixtures to the faunal and floral biodiversity of forests has been documented on many occasions, but little is known about the relationships between single‐tree effects, such as litter distribution and carabid beetles.

The aim of the study was to investigate the relationship between the occurrence of carabid beetles and the locations of admixed oak trees within a Scots pine (Pinus sylvestris L.) stand.

Individuals of four Carabus species were collected in dry pitfall traps in a pine forest with single admixed sessile oaks [Quercus petraea (Matt.) Liebl.]. The capture–mark–recapture technique was used to differentiate carabid beetles by species, gender (female, male), and development stage (imagines, larvae). Three zones of influence were defined according to the distribution of oak leaf litter. The beetle counts from trap data were transformed to a point pattern by means of a random‐field approach where it is assumed that the beetle count per trap is representative of a specified number of single points in the square surrounding the trap.

Spatial patterns specific to species, gender, and development stage were observed relative to the oak tree locations. Females and larvae of C. coriaceus and C. hortensis had a high affinity to the oaks, whereas C. violaceus revealed a negative association to the oak trees. No clear trend could be observed for C. arvensis.

It was concluded that single‐tree admixtures of oaks affect the spatial patterns of mobile organisms (e.g. Coleoptera) serving as ecological niches in pine forests.
Influence of size and taper of basic root canal preparation on root canal cleanliness: a scanning electron microscopy study
Authors: Plotino G. , Özyürek T. , Grande N. M. , Gündoğar M.
Published: August 2018

Aim

To investigate whether a minimally invasive basic root canal preparation technique has an influence on root canal cleanliness in extracted mandibular molar teeth.

Methodology

A total of 80 root canals (40 mesio‐buccal and 40 mesio‐lingual) from 40 mandibular molars were included. The teeth were divided equally into four different experimental groups depending on the subsequently root canal preparation technique: Group 1: a basic preparation was performed up to size 20, .04 taper; Group 2: a basic preparation was performed up to size 2, .06 taper; Group 3: a basic preparation was performed up to size 25, .04 taper; and Group 4: a basic preparation was performed up to size 25, .06 taper. After the use of each instrument, each root canal was irrigated with 2.5 mL of 6% sodium hypochlorite for 30 s. Then, 1 mL NaOCl was activated for 20 s using an EDDY sonic tip. Final irrigation was performed using a total of 5 mL of 17% EDTA solution. The roots were then split longitudinally and all root canal thirds were observed through scanning electron microscopy (SEM) to evaluate the presence of superficial debris and smear layer using a scoring system. Data were statistically analysed using the Kruskal–Wallis and Bonferroni tests with a level of significance set at P < 0.05.

Results

In all groups, there was significantly more residual debris and smear layer in the apical third (P < 0.05), with no differences between the middle and coronal thirds (P > 0.05). For both the parameters analysed, there was no difference amongst the groups in the middle and coronal thirds (P > 0.05), whilst in the apical third significantly less debris and smear layer was found in specimens from groups 3 and 4 than for groups 1 and 2 (P < 0.05).

Conclusion

All basic root canal preparation techniques were associated with less debris and smear layer on the canal walls in the middle and coronal thirds, without differences among them. Even though debris and smear layer were always present in the apical third, an apical size of 25 resulted in significantly cleaner canals walls compared to a size 20.
Cutaneous melioidosis: a review of the literature
Authors: Fertitta Laura , Monsel Gentiane , Torresi Joseph , Caumes Eric
Published: August 2018

Background

Melioidosis is mainly observed in South‐East Asia, where Burkholderia pseudomallei is endemic. Cutaneous melioidosis (CM) has rarely been described and in contrast to systemic forms, there are no therapeutic recommendations to guide management.

Methods

We reviewed the literature published before January 2018, evaluating: dermatological presentation, natural history, diagnostic methods, and treatment options. We also distinguish between primary and secondary CM in which the infection first started in the skin or came from an extracutaneous localization, respectively, and chronic CM when duration exceeded 2 months. The recommended treatment for systemic forms included ceftazidime or meropenem, followed by oral maintenance therapy with cotrimoxazole or amoxicillin – clavulanic acid.

Results

Forty‐three cases were published in 38 articles. Twenty‐nine patients (67.4%) were travelers, including 13 (44.8%) returning from Thailand. Thirty‐eight patients (88%) had primary CM, including nine (29.9%) with chronic infection. All cases of secondary CM first presented with acute infection. The median incubation time was 3 weeks. The most common presentation was cutaneous abscesses (58%). The recommended treatment was administered in 62.7% cases with 37.2% for maintenance therapy. Sixteen patients (37.2%) underwent surgery. Death was reported in less than 5%.

Conclusion

CM should be considered in travelers returning from or residents of endemic countries, particularly Thailand, presenting with cutaneous abscesses, cellulitis, or ulcerations. Surgery may be necessary in a substantial proportion of patients and follow‐up of at least 1 year is essential. Therapeutic recommendations need to be established.
Urinary biomarkers of prostate cancer
Authors: Fujita Kazutoshi , Nonomura Norio
Published: August 2018

The development of more specific biomarkers for prostate cancer and/or high‐risk prostate cancer is necessary, because the prostate‐specific antigen test lacks specificity for the detection of prostate cancer and can lead to unnecessary prostate biopsies. Urine is a promising source for the development of new biomarkers of prostate cancer. Biomarkers derived from prostate cancer cells are released into prostatic fluids and then into urine. Urine after manipulation of the prostate is enriched with prostate cancer biomarkers, which include prostate cancer cells, DNAs, RNAs, proteins and other small molecules. The urinary prostate cancer antigen 3 test is the first Food and Drug Administration‐approved RNA‐based urinary marker, and it helps in the detection of prostate cancer on repeat biopsy. The SelectMDx test is based on messenger RNA detection of DLX1 and HOXC6 in urine after prostate massage, and helps in the detection of high‐risk prostate cancer on prostate biopsy. Exosomes are extracellular vesicles with a diameter of 30–200 nm that are secreted from various types of cells. Urinary prostate cancer‐derived exosomes also contain RNAs and proteins specific for prostate cancer (e.g. PCA3 and TMPRSS2‐ERG), and could be promising sources of novel biomarker discovery. The ExoDx Prostate test is a commercially available test based on the detection of three genes (PCA3, ERG and SPDEF) in urinary exosomes. Advancement of comprehensive analysis (microarray, mass spectrometry and next‐generation sequencing) has resulted in the discovery of several urinary biomarkers. Non‐invasive urinary markers can help in the decision to carry out prostate biopsy or in the design of a therapeutic strategy.
Lenvatinib in combination with everolimus in patients with advanced or metastatic renal cell carcinoma: A phase 1 study
Authors: Matsubara Nobuaki , Naito Yoichi , Nakano Kenji , Fujiwara Yutaka , Ikezawa Hiroki , Yusa Wataru , Namiki Masayuki , Okude Takashi , Takahashi Shunji
Published: August 2018

Objectives

To assess the tolerability, safety, pharmacokinetics and antitumor activities of lenvatinib, an oral inhibitor of multiple receptor tyrosine kinases, in combination with everolimus, an inhibitor of mammalian target of rapamycin, in Japanese patients with advanced or metastatic renal cell carcinoma after disease progression with vascular endothelial growth factor‐targeted therapy.

Methods

Lenvatinib 18 mg and everolimus 5 mg once daily were administered on 28‐day continuous cycles until disease progression or unacceptable toxicity. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 4.03, and tumor response was assessed according to the Response Evaluation Criteria in Solid Tumor version 1.1. Pharmacokinetics sampling was carried out during the first cycle.

Results

Seven patients with clear cell renal cell carcinoma received this combination treatment. Dose‐limiting toxicity was not observed. The most commonly observed adverse events were thrombocytopenia and decreased appetite (100%), followed by hypertriglyceridaemia and palmar‐plantar erythrodysesthesia syndrome (86%). The most common grade 3 adverse event was lymphopenia (43%). No grade 4 or 5 adverse events occurred. The steady‐state mean areas under the concentration–time curves of lenvatinib and everolimus were 3220 and 401 ng·h/mL, respectively. Five patients (71%) had partial response, and one (14%) had stable disease.

Conclusions

Lenvatinib 18 mg and everolimus 5 mg once daily are well tolerated and manageable, and their combined administration has no significant effect on either drug's pharmacokinetics. Overall, this combination therapy shows encouraging antitumor activity in Japanese patients with renal cell carcinoma.
Social Accountability in Diaspora Organizations Aiding Syrian Migrants
Authors: Abdel‐Samad Mounah , Flanigan Shawn Teresa
Published: August 2018

This article presents data from a study of Syrian diaspora organizations providing assistance to conflict‐affected Syrians in Europe, the Middle East, and North America. Using interview data from leaders in four Syrian diaspora non‐profit organizations, this article examines the social mechanisms used to ensure accountability within the challenging environments where the organizations operate. We find that Syrian diaspora organizations benefit from informal social accountability mechanisms that derive from individuals’ social network ties. Personal, social forms of accountability are particularly valuable to these organizations because these mechanisms help circumvent uncertainty and challenges in the operational environment. These findings reflect an important theme in the extant literature on diaspora philanthropy: diaspora members may have an advantage over other actors because of dense personal networks that make them adept at identifying dependable partners and enforcing agreements even in places where banking and legal systems are fragile.
Similar outcomes for general medicine patients discharged on any day of the week
Authors: Au John , Horwood Chris , Hakendorf Paul , Thompson Campbell
Published: August 2018

Background

Hospital congestion is worsened by fewer patients being discharged on the weekend than on weekdays. Weekend admissions fare worse in hospital than weekday admissions. Understanding the fate of patients discharged on the weekend, or any particular weekday, may help optimise hospital discharge processes.

Aim

To determine the effects of weekend and specific weekday discharges on adverse outcomes (mortality and readmission to hospital).

Methods

Electronic records were used to identify unplanned admissions to two large public hospitals across a 5‐year period. Day of week of discharge, the inpatient length of stay, unplanned readmissions and mortality rate were determined.

Results

There was a significant reduction in discharges on the weekend (49%), particularly for patients who were older or with significant comorbidity (P < 0.001). Adjusting for these differences, there was no difference in readmission and mortality between weekday and weekend discharges within two (OR 0.97; 95% CI 0.83–1.14; P < 0.76) or seven (OR 0.91; 95% CI 0.82–1.01; P < 0.07) days of discharge. By 30 days, there were significantly fewer adverse outcomes for those discharged on the weekend (OR 0.89; 95% CI 0.83–0.96; P < 0.001). There was no difference in adverse outcome rates for patients discharged on Mondays, Wednesdays or Fridays.

Conclusion

Fewer patients are discharged on the weekend and these are typically younger, less complex patients. Patients discharged on the weekend fare similarly or better than those discharged on a weekday. Therefore, a push to discharge more patients on the weekend could improve hospital efficiency without compromising patient care.
High‐temperature stable inverse opal photonic crystals via mullite‐sol‐gel infiltration of direct photonic crystals
Authors: Bueno Priscila , Pagnan Furlan Kaline , Hotza Dachamir , Janssen Rolf
Published: August 2018

Three‐dimensionally ordered macroporous materials for photonic or refractory applications have been developed by an innovative approach based on mullite sol‐gel infiltration of direct photonic crystals followed by burn‐out and calcination. Direct photonic crystals were obtained using polystyrene spheres templates either by vertical convective self‐assembly or by drop casting. The samples were then infiltrated by spin coating with mullite sol‐gels prepared with two different compositions (74 wt.% Al2O3, 26 wt.% SiO2and 80 wt.% Al2O3, 20 wt.% SiO2). The inverse opal photonic crystals prepared with both sol‐gels presented a highly ordered porosity and the high‐alumina composition showed stability up to 1500°C. After inversion of the structure (polymeric template burn‐out), the high‐alumina composition showed roundness of thePStemplated pores closer to an ideal sphere (Ø = 0.967) when compared to the low‐alumina composition (Ø = 0.954). Although the inverse opal photonic crystals did not present a photonic bandgap, they showed structural stability at high temperatures, which enable their application as refractory materials.
Structural and physical characteristics of Au2O3‐doped sodium antimonate glasses – Part I
Authors: Ashok Jujjavarapu , Kostrzewa Marek , Srinivasa Reddy Maddireddy , Ravi Kumar Vandana , Venkatramiah Nutalapati , Piasecki Michal , Veeraiah Nalluri
Published: August 2018

Na2O‐Sb2O3 glasses doped with different concentrations of Au2O3 were prepared by melt quenching technique and later were heat treated at 800°C for 6 hours. Structural analysis by XRD, XPS, SEM, EDS, and DSC techniques indicated that the samples are embedded with multiple crystallites composed of Sb3+, Sb5+, Au3+ ions, and Au0 metallic particles. These studies have further demonstrated a gradual increasing fraction of Au0 metallic particles with increasing Au2O3 concentration. IR spectral studies suggested increasing the degree of polymerization of the glass network (due to increasing concentration of Sb5+ ions that participate in the glass network with SbVO4 structural units) with rise in the concentration of Au2O3. Optical absorption spectra of the titled samples have exhibited a broad absorption band at about 530 nm predicted due to the surface plasmon resonance (SPR) and exhibited a spectral red shift with increasing intensity with increase in Au2O3 content. Photoluminescence (PL) spectra of the samples recorded (at λexc = corresponding SPR band position) exhibited an emission peak at about 580 nm (identified as being due to interband transition between sp and d bands of gold particles). Overall, the analysis of these results has confirmed increasing concentration of Au metallic particles with increase in Au2O3 content in the titled material. Finally, it is predicted that the presence of higher concentration of gold particles in the polymerized antimonate glass network makes the materials useful for designing different nano dimensional optoelectronic devices.
In situ study of electric‐field‐induced ferroelectric and antiferromagnetic domain switching in polycrystalline BiFeO3
Authors: Liu Lisha , Hinterstein Manuel , Rojac Tadej , Walker Julian , Makarovic Maja , Daniels John
Published: August 2018

Antiferromagnetic domain switching induced by ferroelectric polarization switching has previously been observed in situ in both multiferroic BiFeO3 single crystals and thin films. Despite a number of reports on macroscopic magnetoelectric measurements on polycrystalline BiFeO3, direct in situ observation of electric‐field‐induced antiferromagnetic domain switching in this material has not been addressed due to the lack of high‐quality samples capable of electrical poling. Here, the electric field control of antiferromagnetic domain texture is identified in polycrystalline BiFeO3 using in situ neutron diffraction, showing the resultant magnetic domain reorientation induced by an electric field. An antiferromagnetic domain reorientation to a value of 2.2‐2.5 multiples of a random distribution (MRD) is found to be induced by an electric field that provides a non‐180° ferroelectric‐ferroelastic domain texture of 2.2‐2.5 MRD along the field direction. The current results show well‐controlled coupling of multiferroic domain texturing in single‐phase polycrystalline BiFeO3.
Influence of lifestyle choices on risks of CYP1B1 polymorphisms for prostate cancer
Authors: Kato Taku , Hashimoto Yutaka , Wong Ryan K. , Mitsui Yozo , Maekawa Shigekatsu , Chang Inik , Shahryari Varahram , Yamamura Soichiro , Majid Shahana , Saini Sharanjot , Tabatabai Z. Laura , Dahiya Rajvir , Deguchi Takashi , Tanaka Yuichiro
Published: August 2018

Cytochrome P450 1B1 (CYP1B1) converts xenobiotics to carcinogens and how lifestyle choices may interact with CYP1B1 polymorphisms and affect prostate cancer risk was assessed. Blood genomic DNA from a Caucasian population was analysed at polymorphic sites of the 5′ untranslated region of CYP1B1 using TaqMan genotyping assays. Overall, drinker status and minor alleles at rs2551188, rs2567206 and rs10175368 were associated with prostate cancer. Linkage was observed between rs2551188, rs2567206, rs2567207 and rs10175368, and the G‐C‐T‐G haplotype (major allele at respective sites) was decreased in cancer. Interestingly when classified by lifestyle factors, no associations of genotypes were found for non‐smokers and non‐drinkers, whereas on the contrary, minor type at rs2567206 and rs10175368 increased and major G‐C‐T‐G decreased risk for cancer among smokers and drinkers. Interestingly, rs2551188, rs2567206 and rs10175368 minor genotypes correlated with increased tissue CYP1B1 as determined by immunohistochemistry. Further, rs10175368 enhanced luciferase activity and mobility shift show stronger binding of nuclear factor for the minor allele. These results demonstrate smoking and alcohol consumption to modify the risks of CYP1B1 polymorphisms for prostate cancer which may be through rs10175368, and this is of importance in understanding their role in the pathogenesis and as a biomarker for this disease.
LINC01287 regulates tumorigenesis and invasion via miR‐298/MYB in hepatocellular carcinoma
Authors: Mo Yichao , He Longguang , Lai Zeru , Wan Zhiheng , Chen Qinshou , Pan Sibo , Li Liangfu , Li Dasheng , Huang Junwei , Xue Fan , Che Siyao
Published: August 2018

Recently, it was reported that long non‐coding RNAs (lncRNAs) participated in promoting hepatocellular carcinoma (HCC) initiation and progression. Herein, we reported that the expression level of LINC01287 was elevated in HCC cell lines and tissues. LINC01287 down‐regulation inhibited HCC cells growth and invasion both in vitro and in vivo. LINC01287 exerted as a ceRNA and negatively regulated miR‐298 expression. MYB was identified as a downstream target of miR‐298. The miR‐298/MYB axis mediated LINC01287's effect on HCC. To the best of our knowledge, our findings provided the first evidence that LINC01287 functioned as an oncogene in HCC. LINC01287 may be a candidate prognostic biomarker and a target for new therapies in HCC patients.
Prognostic value of gastric cancer‐associated gene signatures: Evidence based on a meta‐analysis using integrated bioinformatics methods
Authors: Wang Jun , Gao Peng , Song Yongxi , Sun Jingxu , Chen Xiaowan , Yu Hong , Wang Yu , Wang Zhenning
Published: August 2018

Selecting differentially expressed genes (DEGs) based on integrated bioinformatics analyses has been used in previous studies to explore potential biomarkers in gastric cancer (GC) with microarray and RNA sequencing data. However, the genes obtained may be inaccurate because of noisy data and errors, as well as insufficient clinical sample sizes. Thus, we aimed to find robust and strong DEGs with prognostic value for GC, where the robust rank aggregation method was employed to select significant DEGs from eight Gene Expression Omnibus data sets with a total of 140 up‐regulated and 206 down‐regulated genes. Network data mining was then used to screen hub genes, and 11 genes were filtered using Fisher's exact test. Based on these results, we built a prognostic signature with seven genes (FBN1, MMP1, PLAU, SPARC, COL1A2, COL2A1 and ATP4A) using stepwise multivariate Cox proportional hazard regression. According to the risk score for each patient, we found that high‐risk group patients had significantly worse survival results compared with those in the low‐risk group (log‐rank test P‐value < 0.001). This seven‐gene signature was then validated with an external data set. Thus, we established a signature based on seven DEGs with prognostic value for GC patients using multi‐steps bioinformatics methods, which may provide novel insights and potential biomarkers for prognosis, as well as possibly serving as new therapeutic targets in clinical applications.
LINC00312 represses proliferation and metastasis of colorectal cancer cells by regulation of miR‐21
Authors: Li Gang , Wang Changming , Wang Yongbing , Xu Bin , Zhang Wenzhong
Published: August 2018

Long non‐coding RNAs (lncRNAs) have emerged as important regulators of cancer, including colorectal cancer (CRC). The exact expression pattern of long intergenic noncoding RNA 00312 (LINC00312) in CRC and its mechanisms of action have not been reported. Here, we found that LINC00312 is underexpressed in CRC tissues and cell lines. Functional experiments suggested that LINC00312 suppresses growth, migration and invasion of CRC cells in vitro and attenuates tumour proliferation and metastasis in vivo. Mechanistically, LINC00312 was found to regulate the malignancy of CRC cells by binding to miR‐21 and by functioning as a tumour suppressor targeting PTEN. Overexpression of miR‐21 or knockdown of PTEN attenuated the LINC00312‐mediated inhibition of CRC cell proliferation and invasion. Taken together, our results elucidate the role of the LINC00312–miR‐21–PTEN axis in CRC cell proliferation and tumour progression and may lead to new lncRNA‐based diagnostics or therapeutics for CRC.
Deletion of caveolin‐1 attenuates LPS/GalN‐induced acute liver injury in mice
Authors: Tsai Tsung‐Huang , Tam Kabik , Chen Shu‐Fen , Liou Jun‐Yang , Tsai Yi‐Chen , Lee Yen‐Ming , Huang Tai‐Yu , Shyue Song‐Kun
Published: August 2018

Acute hepatic injury caused by inflammatory liver disease is associated with high mortality. This study examined the role of caveolin‐1 (Cav‐1) in lipopolysaccharide (LPS) and D‐galactosamine (GalN)‐induced fulminant hepatic injury in wild type and Cav‐1‐null (Cav‐1−/−) mice. Hepatic Cav‐1 expression was induced post‐LPS/GalN treatment in wild‐type mice. LPS/GalN‐treated Cav‐1−/− mice showed reduced lethality and markedly attenuated liver damage, neutrophil infiltration and hepatocyte apoptosis as compared to wild‐type mice. Cav‐1 deletion significantly reduced LPS/GalN‐induced caspase‐3, caspase‐8 and caspase‐9 activation and pro‐inflammatory cytokine and chemokine expression. Additionally, Cav‐1−/− mice showed suppressed expression of Toll‐like receptor 4 (TLR4) and CD14 in Kupffer cells and reduced expression of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 in liver cells. Cav‐1 deletion impeded LPS/GalN‐induced inducible nitric oxide synthase expression and nitric oxide production and hindered nuclear factor‐κB (NF‐κB) activation. Taken together, Cav‐1 regulated the expression of mediators that govern LPS‐induced inflammatory signalling in mouse liver. Thus, deletion of Cav‐1 suppressed the inflammatory response mediated by the LPS‐CD14‐TLR4‐NF‐κb pathway and alleviated acute liver injury in mice.
STAT3 promotes tumour progression in glioma by inducing FOXP1 transcription
Authors: Sun Xinlin , Wang Jihui , Huang Min , Chen Taoliang , Chen Jiansheng , Zhang Fabing , Zeng Huijun , Xu Zhimin , Ke Yiquan
Published: August 2018

Objective

This paper investigated the effects of STAT3 through promoting FOXP1 transcription on proliferation, apoptosis and invasion in glioma cells.

Methods

Quantitative real‐time PCR (qRT‐PCR) and Western blot assay were administered to assess the mRNA and protein expression levels of STAT3 and FOXP1 in glioma tissues and cells, respectively. Luciferase reporter and Chromatin Immunoprecipitation (ChIP) assays were implemented to determine the correlation between STAT3 and FOXP1. MTT and colony formation assays were conducted to identify cell growth. Flow cytometry was run to detect the cell apoptosis rate of glioma cells. Transwell assays were conducted to reveal cell invasion ability.

Results

The mRNA and protein expression levels of STAT3 were highly expressed in glioma tissues and cells. After cells transfected with siRNA of STAT3, both STAT3 and FOXP1 were simultaneously downregulated. STAT3 directly regulated FOXP1 transcription. STAT3 promoted cell proliferation, inhibited cell apoptosis and enhanced cell invasion through promoting FOXP1 transcription in glioma cells.

Conclusion

In summary, STAT3 gene was a transcriptional regulator of FOXP1. Depleted STAT3 restrained cell proliferation and invasion, promoted cell apoptosis in glioma cells. This molecular mechanism between STAT3 and FOXP1 can serve as a therapeutic target for glioma treatment.
Identification of pesticide residues in lettuce leaves based on near infrared transmission spectroscopy
Authors: Sun Jun , Ge Xiao , Wu Xiaohong , Dai Chunxia , Yang Ning
Published: August 2018

To explore the nondestructive and accurate qualitative detection method of pesticide residues in vegetables, lettuce leaves were taken as carrier and pesticides (fenvalerate and chlorpyrifos) were taken as research object. The near infrared spectral data of lettuce leaves was collected by using near infrared spectrometer NIRez (950–1,650 nm), then it was preprocessed by SNV algorithm and SG‐SNV combination, respectively. The successive projections algorithm (SPA), competitive adaptive reweighted sampling (CARS), iteratively retaining informative variables (IRIV), and combination of two of them were used to select characteristic wavelengths from the preprocessed spectral data, respectively. In this study, support vector machine (SVM) was used to classify pesticide residues in lettuce leaves. Because the classification performance of SVM was influenced by parameters c (penalty coefficient) and g (kernel function parameter), so the parameters c and g of SVM were optimized by gravitational search algorithm (GSA). Finally, identification models were built on the full wavelengths and the selected characteristic wavelengths, respectively. Final result showed that CARS‐IRIV‐GSA‐SVM model had the best performance, and the classification accuracy of training set and predication set reached 100 and 98.33%. Therefore, near infrared transmission spectroscopy can be applied to the qualitative detection of pesticide residues in lettuce leaves.

Practical applications

Lettuce leaves can be eaten raw, but pesticide residues in lettuce leaves are likely to do harm to human health. Near infrared transmission spectroscopy, a fast and nondestructive technology, can be used to detect pesticide residues in lettuce leaves. Furthermore, the small NIR spectrometer used in this study can also provide some idea for the production of portable pesticide residue detector. This study demonstrated that near infrared transmission spectroscopy can be applied to the qualitative detection of pesticide residues in lettuce leaves.