title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=1913 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Drug delivery systems for ovarian cancer treatment: a systematic review and meta-analysis of animal studies link: https://peerj.com/articles/1489 last-modified: 2015-12-10 description: Current ovarian cancer treatment involves chemotherapy that has serious limitations, such as rapid clearance, unfavorable biodistribution and severe side effects. To overcome these limitations, drug delivery systems (DDS) have been developed to encapsulate chemotherapeutics for delivery to tumor cells. However, no systematic assessment of the efficacy of chemotherapy by DDS compared to free chemotherapy (not in a DDS) has been performed for animal studies. Here, we assess the efficacy of chemotherapy in DDS on survival and tumor growth inhibition in animal studies. We searched PubMed and EMBASE (via OvidSP) to systematically identify studies evaluating chemotherapeutics encapsulated in DDS for ovarian cancer treatment in animal studies. Studies were assessed for quality and risk of bias. Study characteristics were collected and outcome data (survival/hazard ratio or tumor growth inhibition) were extracted and used for meta-analyses. Meta-analysis was performed to identify and explore which characteristics of DDS influenced treatment efficacy. A total of 44 studies were included after thorough literature screening (2,735 studies found after initial search). The risk of bias was difficult to assess, mainly because of incomplete reporting. A total of 17 studies (377 animals) and 16 studies (259 animals) could be included in the meta-analysis for survival and tumor growth inhibition, respectively. In the majority of the included studies chemotherapeutics entrapped in a DDS significantly improved efficacy over free chemotherapeutics regarding both survival and tumor growth inhibition. Subgroup analyses, however, revealed that cisplatin entrapped in a DDS did not result in additional tumor growth inhibition compared to free cisplatin, although it did result in improved survival. Micelles did not show a significant tumor growth inhibition compared to free chemotherapeutics, which indicates that micelles may not be a suitable DDS for ovarian cancer treatment. Other subgroup analyses, such as targeted versus non-targeted DDS or IV versus IP administration route, did not identify specific characteristics of DDS that affected treatment efficacy. This systematic review shows the potential, but also the limitations of chemotherapy by drug delivery systems for ovarian cancer treatment. For future animal research, we emphasize that data need to be reported with ample attention to detailed reporting. creator: René Raavé creator: Rob B.M. de Vries creator: Leon F. Massuger creator: Toin H. van Kuppevelt creator: Willeke F. Daamen uri: https://doi.org/10.7717/peerj.1489 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2015 Raavé et al. title: Low oxygen alters mitochondrial function and response to oxidative stress in human neural progenitor cells link: https://peerj.com/articles/1486 last-modified: 2015-12-10 description: Oxygen concentration should be carefully regulated in all living tissues, beginning at the early embryonic stages. Unbalances in oxygen regulation can lead to cell death and disease. However, to date, few studies have investigated the consequences of variations in oxygen levels for fetal-like cells. Therefore, in the present work, human neural progenitor cells (NPCs) derived from pluripotent stem cells grown in 3% oxygen (v/v) were compared with NPCs cultured in 21% (v/v) oxygen. Low oxygen concentrations altered the mitochondrial content and oxidative functions of the cells, which led to improved ATP production, while reducing generation of reactive oxygen species (ROS). NPCs cultured in both conditions showed no differences in proliferation and glucose metabolism. Furthermore, antioxidant enzymatic activity was not altered in NPCs cultured in 3% oxygen under normal conditions, however, when exposed to external agents known to induce oxidative stress, greater susceptibility to DNA damage was observed. Our findings indicate that the management of oxygen levels should be considered for in vitro models of neuronal development and drug screening. creator: Yury M. Lages creator: Juliana M. Nascimento creator: Gabriela A. Lemos creator: Antonio Galina creator: Leda R. Castilho creator: Stevens K. Rehen uri: https://doi.org/10.7717/peerj.1486 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2015 Lages et al. title: Flood induced phenotypic plasticity in amphibious genus Elatine (Elatinaceae) link: https://peerj.com/articles/1473 last-modified: 2015-12-10 description: Vegetative characters are widely used in the taxonomy of the amphibious genus Elatine L. However, these usually show great variation not just between species but between their aquatic and terrestrial forms. In the present study we examine the variation of seed and vegetative characters in nine Elatine species (E. brachysperma, E. californica, E. gussonei, E. hexandra, E. hungarica, E. hydropiper, E. macropoda, E. orthosperma and E. triandra) to reveal the extension of plasticity induced by the amphibious environment, and to test character reliability for species identification. Cultivated plant clones were kept under controlled conditions exposed to either aquatic or terrestrial environmental conditions. Six vegetative characters (length of stem, length of internodium, length of lamina, width of lamina, length of petioles, length of pedicel) and four seed characters (curvature, number of pits / lateral row, 1st and 2nd dimension) were measured on 50 fruiting stems of the aquatic and on 50 stems of the terrestrial form of the same clone. MDA, NPMANOVA Random Forest classification and cluster analysis were used to unravel the morphological differences between aquatic and terrestrial forms. The results of MDA cross-validated and Random Forest classification clearly indicated that only seed traits are stable within species (i.e., different forms of the same species keep similar morphology). Consequently, only seed morphology is valuable for taxonomic purposes since vegetative traits are highly influenced by environmental factors. creator: Attila Molnár V. creator: János Pál Tóth creator: Gábor Sramkó creator: Orsolya Horváth creator: Agnieszka Popiela creator: Attila Mesterházy creator: Balázs András Lukács uri: https://doi.org/10.7717/peerj.1473 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2015 Molnár et al. title: An evaluation of community pharmacy-based services for type 2 diabetes in an Indonesian setting: patient survey link: https://peerj.com/articles/1449 last-modified: 2015-12-10 description: Background. Diabetes is an emerging chronic disease in developing countries. Its management in developing countries is mainly hospital/clinic based. The increasing diabetes burden in developing countries provides opportunities for community pharmacists to deliver a range of services. Since the management of diabetes requires the patient’s own involvement, it is important to gain their views in order to develop pharmacy-based diabetes services. Studies on diabetes patients’ views have been limited to developed countries.Objectives. To investigate, within a developing country setting (Indonesia), current use of pharmacy services by type 2 diabetes patients, and to evaluate their views regarding community pharmacists’ roles, and the characteristics that influence their views.Methods. A questionnaire survey was conducted within 10 purposefully selected community pharmacies in Surabaya, Indonesia. Each pharmacy recruited approximately 20 patients seeking antidiabetic medications. Usage of pharmacy services was identified using binary responses (‘yes’/‘no’) and views on pharmacists’ roles were rated using Likert scales; an open-ended question was used to identify patient perceived priority roles. Logistic regression models were used to determine characteristics associated with patients’ views.Results. A total of 196 pharmacy patients with type 2 diabetes responded (58.3% response rate). Most patients used community pharmacies for dispensing (100%) and education on how to use medications (79.6%). There were mixed views towards pharmacists providing services beyond dispensing. The highest priorities identified were from the ‘patient education’ domain: education on medications (i.e., directions for use (64.5%), storage (26.6%), common/important adverse effects (25.5%)); and the ‘monitoring’ domain: monitoring medication compliance (37.3%). Patients with higher incomes or who were working were less supportive of these expanded services, whereas patients who previously used a service, those with risk factors for complications or having poor/unknown glycaemic control were more supportive.Conclusions. Community pharmacies in Surabaya, Indonesia in this study were mainly utilised for dispensing. However, many type 2 diabetes patients using these pharmacies report limited monitoring of blood glucose levels and poor glycaemic control, which indicates an opportunity for greater pharmacist involvement. Yet for this to occur, patients’ limited expectations of pharmacists roles will need to be broadened. Characteristics influencing these views should inform the development of pharmacy-based diabetes services in the environment of the burgeoning burden of diabetes. creator: Yosi Wibowo creator: Richard Parsons creator: Bruce Sunderland creator: Jeffery Hughes uri: https://doi.org/10.7717/peerj.1449 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2015 Wibowo et al. title: Baseline seabed habitat and biotope mapping for a proposed marine reserve link: https://peerj.com/articles/1446 last-modified: 2015-12-10 description: Seabed mapping can quantify the extent of benthic habitats that comprise marine ecosystems, and assess the impact of fisheries on an ecosystem. In this study, the distribution of seabed habitats in a proposed no-take Marine Reserve along the northeast coast of Great Barrier Island, New Zealand, was mapped using underwater video combined with bathymetry and substratum data. As a result of the boundary extending to the 12 nautical mile Territorial Limit, it would have been the largest coastal Marine Reserve in the country. Recreational and commercial fisheries occur in the region and would be expected to affect species’ abundance. The seabed of the study area and adjacent coastal waters has been trawled up to five times per year. Benthic communities were grouped by multivariate cluster analysis into four biotope classes; namely (1) shallow water macroalgae Ecklonia sp. and Ulva sp. on rocky substrata (Eck.Ulv); and deeper (2) diverse epifauna of sponges and bryozoans on rocky substrata (Por.Bry), (3) brittle star Amphiura sp. and sea anemone Edwardsia sp. on muddy sand (Amph.Edw), and (4) hydroids on mud (Hyd). In biotopes Por.Bry, Amph.Edw and Hyd, there where boulders and rocks were present, and diverse sponge, bryozoan and coral communities. Fifty species were recorded in the deep water survey including significant numbers of the shallow-water hexactinellid glass sponges Symplectella rowiDendy, 1924 and Rossella ijimaiDendy, 1924, the giant pipe demosponge Isodictya cavicornutaDendy, 1924, black corals, and locally endemic gorgonians. The habitats identified in the waters to the northeast of Great Barrier Island are likely to be representative of similar depth ranges in northeast New Zealand. This study provides a baseline of the benthic habitats so that should the area become a Marine Reserve, any habitat change might be related to protection from fishing activities and impacts, such as recovery of epifauna following cessation of trawling. The habitat map may also be used to stratify future sampling that would aim to collect and identify epifauna and infauna for identification, and thus better describe the biodiversity of the area. creator: Sonny T.M. Lee creator: Michelle Kelly creator: Tim J. Langlois creator: Mark J. Costello uri: https://doi.org/10.7717/peerj.1446 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2015 Lee et al. title: Swarm v2: highly-scalable and high-resolution amplicon clustering link: https://peerj.com/articles/1420 last-modified: 2015-12-10 description: Previously we presented Swarm v1, a novel and open source amplicon clustering program that produced fine-scale molecular operational taxonomic units (OTUs), free of arbitrary global clustering thresholds and input-order dependency. Swarm v1 worked with an initial phase that used iterative single-linkage with a local clustering threshold (d), followed by a phase that used the internal abundance structures of clusters to break chained OTUs. Here we present Swarm v2, which has two important novel features: (1) a new algorithm for d = 1 that allows the computation time of the program to scale linearly with increasing amounts of data; and (2) the new fastidious option that reduces under-grouping by grafting low abundant OTUs (e.g., singletons and doubletons) onto larger ones. Swarm v2 also directly integrates the clustering and breaking phases, dereplicates sequencing reads with d = 0, outputs OTU representatives in fasta format, and plots individual OTUs as two-dimensional networks. creator: Frédéric Mahé creator: Torbjørn Rognes creator: Christopher Quince creator: Colomban de Vargas creator: Micah Dunthorn uri: https://doi.org/10.7717/peerj.1420 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2015 Mahé et al. title: Determinants of antiretroviral therapy coverage in Sub-Saharan Africa link: https://peerj.com/articles/1496 last-modified: 2015-12-08 description: Among 35 million people living with the human immunodeficiency virus (HIV) in 2013, only 37% had access to antiretroviral therapy (ART). Despite global concerted efforts to provide the universal access to the ART treatment, the ART coverage varies among countries and regions. At present, there is a lack of systematic empirical analyses on factors that determine the ART coverage. Therefore, the current study aimed to identify the determinants of the ART coverage in 41 countries in Sub-Saharan Africa. It employed statistical analyses for this purpose. Four elements, namely, the HIV prevalence, the level of national income, the level of medical expenditure and the number of nurses, were hypothesised to determine the ART coverage. The findings revealed that among the four proposed determinants only the HIV prevalence had a statistically significant impact on the ART coverage. In other words, the HIV prevalence was the sole determinant of the ART coverage in Sub-Saharan Africa. creator: Fumitaka Furuoka creator: Mohammad Zahirul Hoque uri: https://doi.org/10.7717/peerj.1496 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2015 Furuoka and Hoque title: De novo clustering methods outperform reference-based methods for assigning 16S rRNA gene sequences to operational taxonomic units link: https://peerj.com/articles/1487 last-modified: 2015-12-08 description: Background. 16S rRNA gene sequences are routinely assigned to operational taxonomic units (OTUs) that are then used to analyze complex microbial communities. A number of methods have been employed to carry out the assignment of 16S rRNA gene sequences to OTUs leading to confusion over which method is optimal. A recent study suggested that a clustering method should be selected based on its ability to generate stable OTU assignments that do not change as additional sequences are added to the dataset. In contrast, we contend that the quality of the OTU assignments, the ability of the method to properly represent the distances between the sequences, is more important.Methods. Our analysis implemented six de novo clustering algorithms including the single linkage, complete linkage, average linkage, abundance-based greedy clustering, distance-based greedy clustering, and Swarm and the open and closed-reference methods. Using two previously published datasets we used the Matthew’s Correlation Coefficient (MCC) to assess the stability and quality of OTU assignments.Results. The stability of OTU assignments did not reflect the quality of the assignments. Depending on the dataset being analyzed, the average linkage and the distance and abundance-based greedy clustering methods generated OTUs that were more likely to represent the actual distances between sequences than the open and closed-reference methods. We also demonstrated that for the greedy algorithms VSEARCH produced assignments that were comparable to those produced by USEARCH making VSEARCH a viable free and open source alternative to USEARCH. Further interrogation of the reference-based methods indicated that when USEARCH or VSEARCH were used to identify the closest reference, the OTU assignments were sensitive to the order of the reference sequences because the reference sequences can be identical over the region being considered. More troubling was the observation that while both USEARCH and VSEARCH have a high level of sensitivity to detect reference sequences, the specificity of those matches was poor relative to the true best match.Discussion. Our analysis calls into question the quality and stability of OTU assignments generated by the open and closed-reference methods as implemented in current version of QIIME. This study demonstrates that de novo methods are the optimal method of assigning sequences into OTUs and that the quality of these assignments needs to be assessed for multiple methods to identify the optimal clustering method for a particular dataset. creator: Sarah L. Westcott creator: Patrick D. Schloss uri: https://doi.org/10.7717/peerj.1487 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2015 Westcott and Schloss title: Intramale variation in sperm size: functional significance in a polygynous mammal link: https://peerj.com/articles/1478 last-modified: 2015-12-08 description: Studies concerning the relationships between sperm size and velocity at the intraspecific level are quite limited and often yielded contradictory results across the animal kingdom. Intramale variation in sperm size may represent a meaningful factor to predict sperm velocity, due to its relationship with the level of sperm competition among related taxa. Because sperm phenotype is under post-copulatory sexual selection, we hypothesized that a reduced intramale variation in sperm size is associated with sperm competitiveness in red deer. Our results show that low variation in sperm size is strongly related to high sperm velocity and normal sperm morphology, which in turn are good predictors of male fertility in this species. Furthermore, it is well known that the red deer show high variability in testicular mass but there is limited knowledge concerning the significance of this phenomenon at intraspecific level, even though it may reveal interesting processes of sexual selection. Thereby, as a preliminary result, we found that absolute testes mass is negatively associated with intramale variation in sperm size. Our findings suggest that sperm size variation in red deer is under a strong selective force leading to increase sperm function efficiency, and reveal new insights into sexual selection mechanisms. creator: José Luis Ros-Santaella creator: Eliana Pintus creator: José Julián Garde uri: https://doi.org/10.7717/peerj.1478 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2015 Ros-Santaella et al. title: Cranial osteology of the ankylosaurian dinosaur formerly known as Minmi sp. (Ornithischia: Thyreophora) from the Lower Cretaceous Allaru Mudstone of Richmond, Queensland, Australia link: https://peerj.com/articles/1475 last-modified: 2015-12-08 description: Minmi is the only known genus of ankylosaurian dinosaur from Australia. Seven specimens are known, all from the Lower Cretaceous of Queensland. Only two of these have been described in any detail: the holotype specimen Minmi paravertebra from the Bungil Formation near Roma, and a near complete skeleton from the Allaru Mudstone on Marathon Station near Richmond, preliminarily referred to a possible new species of Minmi. The Marathon specimen represents one of the world’s most complete ankylosaurian skeletons and the best-preserved dinosaurian fossil from eastern Gondwana. Moreover, among ankylosaurians, its skull is one of only a few in which the majority of sutures have not been obliterated by dermal ossifications or surface remodelling. Recent preparation of the Marathon specimen has revealed new details of the palate and narial regions, permitting a comprehensive description and thus providing new insights cranial osteology of a basal ankylosaurian. The skull has also undergone computed tomography, digital segmentation and 3D computer visualisation enabling the reconstruction of its nasal cavity and endocranium. The airways of the Marathon specimen are more complicated than non-ankylosaurian dinosaurs but less so than derived ankylosaurians. The cranial (brain) endocast is superficially similar to those of other ankylosaurians but is strongly divergent in many important respects. The inner ear is extremely large and unlike that of any dinosaur yet known. Based on a high number of diagnostic differences between the skull of the Marathon specimen and other ankylosaurians, we consider it prudent to assign this specimen to a new genus and species of ankylosaurian. Kunbarrasaurus ieversi gen. et sp. nov. represents the second genus of ankylosaurian from Australia and is characterised by an unusual melange of both primitive and derived characters, shedding new light on the evolution of the ankylosaurian skull. creator: Lucy G. Leahey creator: Ralph E. Molnar creator: Kenneth Carpenter creator: Lawrence M. Witmer creator: Steven W. Salisbury uri: https://doi.org/10.7717/peerj.1475 license: http://creativecommons.org/licenses/by/4.0/ rights: © 2015 Leahey et al.