bluuebunny/crossref_metadata_2025_split huggingface dataset:
IGF signalling in germ cells and testicular germ cell tumours: roles and therapeutic approaches
Authors: Selfe J. , Shipley J. M. 
Published: June 2019

AbstractThe insulin‐like growth factor (IGF) axis plays key roles in normal tissue growth and development as well as in the progression of several tumour types and their subsequent growth and progression to a metastatic phenotype. This review explores the role of IGF system in normal germ cell development and function in addition to examining the evidence for deregulation of IGF signalling in cancer, with particular relevance to evidence supporting a role in testicular germ cell tumours (TGCTs). Despite the clear preclinical rationale for targeting the IGF axis in cancer, there has been a lack of progress in identifying which patients may benefit from such therapy. Future employment of agents targeting the IGF pathway is expected to concentrate on their use in combination with other treatments to prevent resistance and exploit their potential as chemo‐ and radiosensitizers.
Longitudinal pathways between perceived oral health and regular service use of adult Finns
Authors: Torppa‐Saarinen Eeva , Suominen Anna L. , Lahti Satu , Tolvanen Mimmi 
Published: June 2019

AbstractObjectivesOur aim was to evaluate changes in and pathways between different measures of perceived oral health (POH) and regular oral health service use between the years 2000 and 2011 among Finnish adults. POH was measured by means of oral health‐related quality of life (OHRQoL) and subjective oral health (SOH).MethodsThe study was based on a longitudinal sample (n = 5525) of adults having participated both in the Health 2000 and 2011 Surveys (BRIF 8901). OHRQoL was measured with the Oral Health Impact Profile 14‐item questionnaire and SOH with a single question. Path analyses were used to determine whether SOH or OHRQoL affected service use or vice versa, grouped by age groups and self‐assessed treatment need.ResultsThe path analyses indicate that good OHRQoL leads to regular service use and regular service use leads to better SOH. The first path was stronger among the elderly (0.10) and the second among the younger age group (0.07). Both paths were stronger (0.12 and 0.06) among those who reported no treatment need in 2000.ConclusionsGood OHRQoL, indicated by a lack of perceived problems or symptoms, leads to regular service use. Our findings indicate that poor OHRQoL leads to nonregular service use, and nonregular service use leads to poor SOH.
How do paediatricians use and monitor antithyroid drugs in the UK? A clinician survey
Authors: Lawrence Neil , Cheetham Tim , Elder Charlotte 
Published: June 2019

AbstractObjectiveWe aimed to document current practice in the medical management of paediatric hyperthyroidism in the UK and compare to international recommendations.DesignA 27‐question online survey distributed via an electronic newsletter in August 2018.ParticipantsResponses from 48 members (11%) of the British Society for Paediatric Endocrinology and Diabetes.MeasurementsInformation about antithyroid drug (ATD) preference, treatment duration, monitoring of full blood count (FBC), management of neutropaenia, agranulocytosis screening and patient education.ResultsCarbimazole is favoured by 98% of respondents and a “dose titration” regimen preferred over “block and replace” (65% vs 29%). TRAbs (thyroid‐stimulating hormone receptor antibodies) are used for diagnostic purposes by 85% and by 33% to look for evidence of disease remission. The majority (81%) treat for a minimum of 2 years before considering a trial off ATD. All respondents reported that they “always/usually” warn their patients about the risk of agranulocytosis before starting ATD, but written information is “rarely/never” provided by 63%. Sore throat (98%) and fever (92%) are the most commonly cited symptoms used to alert a patient to possible agranulocytosis. FBC is measured prior to treatment by 65% and measured periodically during treatment by 70%.ConclusionsThe management of paediatric hyperthyroidism with ATDs in the UK is not consistent with all international recommendations because a block and replace ATD regimen remains widely used. TRAbs are utilized at presentation, but underused for detecting disease remission. National consensus guidelines and written patient information may refine the management of paediatric patients on ATDs.
Anticonvulsant and antiepileptogenic effects of system xc− inactivation in chronic epilepsy models
Authors: Leclercq Karine , Liefferinge Joeri Van , Albertini Giulia , Neveux Michel , Dardenne Sylvia , Mairet‐Coello Georges , Vandenplas Catherine , Deprez Tania , Chong Seon‐Ah , Foerch Patrik , Bentea Eduard , Sato Hideyo , Maher Pamela , Massie Ann , Smolders Ilse , Kaminski Rafal M. 
Published: June 2019

AbstractObjectiveThe cystine/glutamate antiporter system could represent a new target for antiepileptogenic treatments due to its crucial roles in glutamate homeostasis and neuroinflammation. To demonstrate this, we compared epilepsy development and seizure susceptibility in xCT knockout mice (xCT−/−) and in littermate controls (xCT+/+) in different chronic models of epilepsy.MethodsMice were surgically implanted with electrodes in the basolateral amygdala and chronically stimulated to develop self‐sustained status epilepticus (SSSE); continuous video‐electroencephalography monitoring was performed for 28 days after SE and hippocampal histopathology was assessed. Corneal kindling was induced by twice daily electrical stimulation at 6 Hz and maintenance of the fully kindled state was evaluated. Next, messenger RNA (mRNA) and protein levels of xCT and of the proteins involved in the phosphoinositide 3‐kinase (PI3K)/Akt/glycogen synthase kinase 3β (GSK‐3β)/eukaryotic initiation factor 2α (eIF2α)/activating transcription factor 4 (ATF4) signaling pathway were measured at different time points during epileptogenesis in NMRI mice treated with pilocarpine. Finally, the anticonvulsant effect of sulfasalazine (SAS), a nonselective system inhibitor, was assessed against 6 Hz‐evoked seizures in pilocarpine‐treated mice.ResultsIn the SSSE model, xCT−/− mice displayed a significant delayed epileptogenesis, a reduced number of spontaneous recurrent seizures, and less pronounced astrocytic and microglial activation. Moreover, xCT−/− mice showed reduced seizure severity during 6 Hz kindling development and a lower incidence of generalized seizures during the maintenance of the fully kindled state. In pilocarpine‐treated mice, protein levels of the PI3K/Akt/GSK‐3β/eIF2α/ATF4 pathway were increased during the chronic phase of the model, consistent with previous findings in the hippocampus of patients with epilepsy. Finally, repeated administration of SAS protected pilocarpine‐treated mice against acute 6 Hz seizure induction, in contrast to sham controls, in which system is not activated.SignificanceInhibition of system could be an attractive target for the development of new therapies with a potential for disease modification in epilepsy.
Transcriptomic response to aquaculture intensification in Nile tilapia
Authors: Rodriguez‐Barreto Deiene , Rey Olivier , Uren‐Webster Tamsyn M. , Castaldo Giovanni , Consuegra Sonia , Garcia de Leaniz Carlos 
Published: June 2019

AbstractTo meet future global demand for fish protein, more fish will need to be farmed using fewer resources, and this will require the selection of nonaggressive individuals that perform well at high densities. Yet, the genetic changes underlying loss of aggression and adaptation to crowding during aquaculture intensification are largely unknown. We examined the transcriptomic response to aggression and crowding in Nile tilapia, one of the oldest and most widespread farmed fish, whose social structure shifts from social hierarchies to shoaling with increasing density. A mirror test was used to quantify aggression and skin darkening (a proxy for stress) of fish reared at low and high densities, and gene expression in the hypothalamus was analysed among the most and least aggressive fish at each density. Fish reared at high density were darker, had larger brains, were less active and less aggressive than those reared at low density and had differentially expressed genes consistent with a reactive stress‐coping style and activation of the hypothalamus–pituitary–interrenal (HPI) axis. Differences in gene expression among aggressive fish were accounted for by density and the interaction between density and aggression levels, whereas for nonaggressive fish differences in gene expression were associated with individual variation in skin brightness and social stress. Thus, the response to crowding in Nile tilapia is context dependent and involves different neuroendocrine pathways, depending on social status. Knowledge of genes associated with the response to crowding may pave the way for more efficient fish domestication, based on the selection of nonaggressive individuals with increasing tolerance to chronic stress necessary for aquaculture intensification.
Mapping the global network of fisheries science collaboration
Authors: Syed Shaheen , ní Aodha Lia , Scougal Callum , Spruit Marco 
Published: June 2019

AbstractAs socio‐environmental problems have proliferated over the past decades, one narrative which has captured the attention of policymakers and scientists has been the need for collaborative research that spans traditional boundaries. Collaboration, it is argued, is imperative for solving these problems. Understanding how collaboration is occurring in practice is important, however, and may help explain the idea space across a field. In an effort to make sense of the shape of fisheries science, here we construct a co‐authorship network of the field, from a data set comprising 73,240 scientific articles, drawn from 50 journals and published between 2000 and 2017. Using a combination of social network analysis and machine learning, the work first maps the global structure of scientific collaboration amongst fisheries scientists at the author, country and institutional levels. Second, it uncovers the hidden subgroups—here country clusters and communities of authors—within the network, detailing also the topical focus, publication outlets and relative impact of the largest fisheries science communities. We find that whilst the fisheries science network is becoming more geographically extensive, it is simultaneously becoming more intensive. The uncovered network exhibits characteristics suggestive of a thin style of collaboration, and groupings that are more regional than they are global. Although likely shaped by an array of overlapping micro‐ and macro‐level factors, the analysis reveals a number of political–economic patterns that merit reflection by both fisheries scientists and policymakers.
Slime travelers: Early evidence of animal mobility and feeding in an organic mat world
Authors: Evans Scott D. , Gehling James G. , Droser Mary L. 
Published: June 2019

AbstractMobility represents a key innovation in the evolution of complex animal life. The ability to move allows for the exploration of new food sources, escapes from unfavorable environmental conditions, enhanced ability to exchange genetic material, and is one of the major reasons for the diversity and success of animal life today. The oldest widely accepted trace fossils of animal mobility are found in Ediacaran‐aged rocks (635–539 Ma). The earliest definitive evidence for movement associated with exploitation of resources for feeding occurs in the White Sea assemblage of the Ediacara Biota—macroscopic, soft‐bodied fossils of Ediacaran age. Here, we evaluate potential support for mobility in dickinsoniomorphs, presenting new data regarding abundant Dickinsonia and associated trace fossils from the Ediacara Member, South Australia. Results quantitatively demonstrate that Dickinsonia was capable of mobility on relatively short, ecological timescales. This organism was bilaterally symmetrical, likely moved via muscular peristalsis, and left trace fossils due to active removal of the organic mat related to feeding. Analogous structures associated with Yorgia indicate that it was also mobile and fed in a similar manner. Morphological evidence suggests that two other modular taxa, Andiva and Spriggina, were able to move but did not feed in a manner that impacted the organic mat. Together, these data suggest that mobility was present in multiple disparate bilaterally symmetrical Ediacaran taxa.
Integrating anthropogenic factors into regional‐scale species distribution models—A novel application in the imperiled sagebrush biome
Authors: Requena‐Mullor Juan M. , Maguire Kaitlin C. , Shinneman Douglas J. , Caughlin Timothy Trevor 
Published: June 2019

AbstractSpecies distribution models (SDMs) that rely on regional‐scale environmental variables will play a key role in forecasting species occurrence in the face of climate change. However, in the Anthropocene, a number of local‐scale anthropogenic variables, including wildfire history, land‐use change, invasive species, and ecological restoration practices can override regional‐scale variables to drive patterns of species distribution. Incorporating these human‐induced factors into SDMs remains a major research challenge, in part because spatial variability in these factors occurs at fine scales, rendering prediction over regional extents problematic. Here, we used big sagebrush (Artemisia tridentata Nutt.) as a model species to explore whether including human‐induced factors improves the fit of the SDM. We applied a Bayesian hurdle spatial approach using 21,753 data points of field‐sampled vegetation obtained from the LANDFIRE program to model sagebrush occurrence and cover by incorporating fire history metrics and restoration treatments from 1980 to 2015 throughout the Great Basin of North America. Models including fire attributes and restoration treatments performed better than those including only climate and topographic variables. Number of fires and fire occurrence had the strongest relative effects on big sagebrush occurrence and cover, respectively. The models predicted that the probability of big sagebrush occurrence decreases by 1.2% (95% CI: −6.9%, 0.6%) when one fire occurs and cover decreases by 44.7% (95% CI: −47.9%, −41.3%) if at least one fire occurred over the 36 year period of record. Restoration practices increased the probability of big sagebrush occurrence but had minimal effect on cover. Our results demonstrate the potential value of including disturbance and land management along with climate in models to predict species distributions. As an increasing number of datasets representing land‐use history become available, we anticipate that our modeling framework will have broad relevance across a range of biomes and species.
An update on the new classification of Ehlers‐Danlos syndrome and review of the causes of bleeding in this population
Authors: Jesudas Rohith , Chaudhury Ateefa , Laukaitis Christina M. 
Published: June 2019

AbstractIt has long been hypothesized that bleeding symptoms in people with hypermobility occur as a result of abnormalities in the collagen of the vessel wall or the connective tissues. The bleeding symptoms, particularly in the skin, have been attributed to the fragility of skin and blood vessels caused by “defective collagen wickerwork” of the reticular layer of the skin. Collagen, which forms the framework of vessel walls, is altered in many patients with Ehlers‐Danlos syndrome (EDS) leading to weakening of the vessel wall or the supporting tissues. Another important function of subendothelial collagen is its interaction with platelets and von Willebrand factor, which results in the propagation of a platelet plug. Thus, abnormalities in subendothelial collagen may alter its interaction with platelets and VWF. More recently, hypermobile‐EDS (hEDS) has been associated with mast cell disorders, a condition independently associated with bleeding symptoms. It has also been observed that patients with mild bleeding disorders have a more severe bleeding phenotype when they have co‐existing joint hypermobility.
A mutation analysis of the EGFR pathway genes, RAS, EGFR, PIK3CA, AKT1 and BRAF, and TP53 gene in thymic carcinoma and thymoma type A/B3
Authors: Sakane Tadashi , Murase Takayuki , Okuda Katsuhiro , Saida Kosuke , Masaki Ayako , Yamada Takeshi , Saito Yushi , Nakanishi Ryoichi , Inagaki Hiroshi 
Published: June 2019

AimsThymic carcinoma is rare and usually has a fatal outcome. Gene mutations in the epidermal growth factor receptor (EGFR) signalling pathway and TP53 have not been well analysed in thymic carcinoma.Methods and resultsWe examined a large cohort of thymic carcinoma and thymoma type A/B3 and looked for gene mutations in the RAS family, EGFR, PIK3CA, AKT1, BRAF and TP53. Among 54 thymic carcinoma cases, RAS family mutations were detected in 10 cases, EGFR in two, PIK3CA in one, AKT1 in one, BRAF in none and TP53 in five. Among 33 thymoma type A/B3 cases, HRAS gene mutation were found in one, PIK3CA in two and AKT1 in one. All these mutations were those of missense type activating mutations. RAS family mutations were significantly more frequent in thymic carcinoma than in thymoma type A/B3 (P = 0.0461). A prognostic analysis focusing on thymic squamous cell carcinoma cases (n = 44) showed that the overall survival was significantly shorter in patients with EGFR pathway mutations (n = 9) than in those without in a univariate analysis (P = 0.0173). Subsequently, EGFR pathway mutations were selected as an independent factor for a poor overall survival in a multivariate analysis (P = 0.0389).ConclusionsMutations in the EGFR pathway and TP53 in thymic carcinoma may be frequent, and the EGFR pathway mutations may be associated with a poor prognosis in thymic squamous cell carcinoma patients. The therapeutic significance of gene mutations in thymic carcinoma should be further clarified.
Extracellular matrix dynamics in cell migration, invasion and tissue morphogenesis
Authors: Yamada Kenneth M. , Collins Joshua W. , Cruz Walma David A. , Doyle Andrew D. , Morales Shaimar Gonzalez , Lu Jiaoyang , Matsumoto Kazue , Nazari Shayan S. , Sekiguchi Rei , Shinsato Yoshinari , Wang Shaohe 
Published: June 2019

SummaryThis review describes how direct visualization of the dynamic interactions of cells with different extracellular matrix microenvironments can provide novel insights into complex biological processes. Recent studies have moved characterization of cell migration and invasion from classical 2D culture systems into 1D and 3D model systems, revealing multiple differences in mechanisms of cell adhesion, migration and signalling—even though cells in 3D can still display prominent focal adhesions. Myosin II restrains cell migration speed in 2D culture but is often essential for effective 3D migration. 3D cell migration modes can switch between lamellipodial, lobopodial and/or amoeboid depending on the local matrix environment. For example, “nuclear piston” migration can be switched off by local proteolysis, and proteolytic invadopodia can be induced by a high density of fibrillar matrix. Particularly, complex remodelling of both extracellular matrix and tissues occurs during morphogenesis. Extracellular matrix supports self‐assembly of embryonic tissues, but it must also be locally actively remodelled. For example, surprisingly focal remodelling of the basement membrane occurs during branching morphogenesis—numerous tiny perforations generated by proteolysis and actomyosin contractility produce a microscopically porous, flexible basement membrane meshwork for tissue expansion. Cells extend highly active blebs or protrusions towards the surrounding mesenchyme through these perforations. Concurrently, the entire basement membrane undergoes translocation in a direction opposite to bud expansion. Underlying this slowly moving 2D basement membrane translocation are highly dynamic individual cell movements. We conclude this review by describing a variety of exciting research opportunities for discovering novel insights into cell‐matrix interactions.
Reinvigorating Research on Gender in the Workplace Using a Positive Work and Organizations Perspective*
Authors: Warren Meg A. , Donaldson Scott I. , Lee Joo Young , Donaldson Stewart I. 
Published: June 2019

AbstractGender inequality is a widespread organizational challenge, however, research on gender in the workplace suffers from stagnation in mainstream management research. A positive work and organizations perspective has the capacity to augment problem‐focused gender research with new approaches to boosting gender equity. Yet, contributions that utilize such a perspective are sparsely spread across nearly two decades’ time and dozens of journals with differing disciplinary foci. This paper aims to reinvigorate gender research in management research by consolidating insights that have emerged through the application of a positive perspective. Therefore, we systematically review articles published in 21 management and psychological journals between 2001 and 2016. Four main themes emerged as drivers of gender research from a positive perspective: performance, social integration, well‐being, and justice/moral matters. The contributions within these themes highlight pathways to organizational flourishing through positive diversity and inclusion behaviors and practices. Thus, this paper provides a conceptual map for navigating and planning further research.
A 14‐year retrospective analysis of indications and outcomes of autologous haemopoietic stem cell transplantation in regional Queensland: a single‐centre experience
Authors: Hamilton Elizabeth M. , Nath Karthik D. , Vangaveti Venkat N. , McCutchan Andrew D. , Marsh Jodie L. , Birchley Andrew J. , Casey John M. , McNamara Caroline , Lai Hock C. , Morris Edward S. , Hodges Georgina , Irving Ian M. 
Published: June 2019

AbstractBackgroundThe Townsville Hospital is a tertiary hospital in North Queensland with one of the largest regional transplant centres in Australia, performing primarily autologous haemopoietic stem cell transplants (HSCT) for various haematological malignancies.AimsThis single‐centre, retrospective, observational study aims to describe the activity and outcomes of autologous HSCT at The Townsville Hospital between 2003 and 2017 to verify safety standards.MethodsPatient‐level data were collected, including demographics, frequency and indication for transplant, conditioning, current clinical status and cause of death. Key outcomes included overall survival, non‐relapse mortality, incidence of therapy‐related neoplasm and causes of death. Progression‐free survival in the multiple myeloma (MM) subgroup was also assessed.ResultsThere were 319 autologous HSCT in 286 patients, with a median age of 58 years (range 14–71 years); 62% of patients were male. Indications for transplantation were: MM 53.7%, non‐Hodgkin lymphoma 29.4%, Hodgkin lymphoma 5.0% and other 11.9%. Causes of death were: disease progression/relapse (65.2%), second malignancy (17.0%), infection (9.8%) and other (8.0%). Non‐relapse mortality was 1.2% (95% confidence interval 0.4–3.0) and 3.2% (1.7–5.7) at 100 days and 1 year, respectively, post‐HSCT. Overall survival at 2 years was 81.0% (73.8–86.4) for MM and 69.6% (58.8–78.1) for non‐Hodgkin lymphoma. The median progression‐free survival in the MM cohort was 3.3 years.ConclusionThe Townsville Hospital transplant centre provides an important transplant service in regional Queensland, with outcomes comparable to national data. We reported a relatively high rate of second malignancy as a cause of death.