bluuebunny/crossref_metadata_2025 huggingface dataset:
Replanting reduces frog diversity in oil palm
Authors: Kurz David J. , Turner Edgar C. , Aryawan Agung A. , Barkley Hannah C. , Caliman Jean‐Pierre , Konopik Oliver , Ps. Sudharto , Foster William A.
Published: March 2016

A growing body of literature has demonstrated significant biodiversity losses for many taxa when forest is converted to oil palm. However, no studies have directly investigated changes to biodiversity throughout the oil palm life cycle, in which oil palm matures for 25–30 yr before replanting. This process leads to major changes in the oil palm landscape that likely influence species assemblages and ecosystem function. We compare frog assemblages between mature (21–27‐yr old) and recently replanted (1–2‐yr old) oil palm in Sumatra, Indonesia. Across eighteen 2.25‐ha oil palm plots, we found 719 frogs from 14 species. Frog richness was 31 percent lower in replanted oil palm (nine species) than mature oil palm (13 species). Total frog abundance was 47 percent lower in replanted oil palm, and frog assemblage composition differed significantly between the two ages of oil palm. The majority of frog species were disturbance‐tolerant, although we encountered four forest‐associated frog species within mature oil palm despite a distance of 28 km between our study sites and the nearest extensive tract of forest. Although it is clear that protection of forest is of paramount importance for the conservation of tropical fauna, our results indicate that management decisions within tropical agricultural landscapes also have a profound impact on biodiversity. Practices such as staggered replanting or maintenance of connectivity among mature oil palm patches could help maintain frog diversity in the oil palm landscape.
Can wing morphology inform conservation priorities for Southeast Asian cave bats?
Authors: Furey Neil M. , Racey Paul A.
Published: March 2016

Adaptations for foraging in the complex airspaces of forest interiors may make bat species in the Asian tropics particularly susceptible to forest loss. However, ecomorphological analysis of Vietnamese bat assemblages challenges the hypothesis that, due to their greater vagility, cave‐roosting bats are less vulnerable to habitat fragmentation than foliage‐roosting species. Of the 13 most highly adapted forest‐interior species in our study, eight were cave‐roosting members of the Rhinolophidae and Hipposideridae and had wing morphologies closely resembling five foliage‐roosting members of the Murininae and Kerivoulinae—species typically thought to have low vagility. Overall, both cave‐roosting and foliage‐roosting bats exhibited a wide range of flight indices and species' wing designs corresponded with preferred foraging habitats, suggesting that foraging strategy may outweigh roost preference as a determinant of bat wing morphology and flight performance. Consequently, where such variation occurs, cave‐roosting bat ensembles are likely to include species with low vagility and similar sensitivity to habitat fragmentation. This could have important conservation implications as Asian karst formations support high cave densities and important bat diversity yet increasingly represent forest refugia in anthropogenic landscapes. We, therefore, advocate greater consideration of species vagility in determining conservation priorities for the region's bat fauna.
Selective Inhibition of PTP1B by Vitalboside A from Syzygium cumini Enhances Insulin Sensitivity and Attenuates Lipid Accumulation Via Partial Agonism to PPARγ: In Vitro and In Silico Investigation
Authors: Thiyagarajan Gopal , Muthukumaran Padmanaban , Sarath Kumar Baskaran , Muthusamy Velusamy Shanmuganathan , Lakshmi Baddireddi Subhadra
Published: March 2016

Although antidiabetic drugs show good insulin‐sensitizing property for T2DM, they also exhibit undesirable side‐effects. Partial peroxisome proliferator‐activated receptor γ agonism with protein tyrosine phosphatase 1B inhibition is considered as an alternative therapeutic approach toward the development of a safe insulin sensitizer. Bioactivity‐based fractionation and purification of Syzygium cumini seeds led to the isolation and identification of bifunctional Vitalboside A, which showed antidiabetic and anti‐adipogenic activities, as measured by glucose uptake in L6 and 3T3‐L1 adipocytes and Nile red assay. A non‐competitive allosteric inhibition of protein tyrosine phosphatase 1B by Vitalboside A was observed, which was confirmed by docking studies. Inhibitor studies with wortmannin and genistein showed an IRTK‐ and PI3K‐dependent glucose uptake. A PI3K/AKT‐dependent activation of GLUT4 translocation and an inactivation of GSK3β were observed, confirming its insulin‐sensitizing potential. Vitalboside A exhibited partial transactivation of peroxisome proliferator‐activated receptor γ with an increase in adiponectin secretion, which was confirmed using docking analysis. Vitalboside A is a bifunctional molecule derived from edible plant showing inhibition of PTP1B and partial agonism to peroxisome proliferator‐activated receptor γ which could be a promising therapeutic agent in the management of obesity and diabetes.
“I think they're all basically the same”: parents' perceptions of human papilloma virus (HPV) vaccine compared with other adolescent vaccines
Authors: Ogunbajo A. , Hansen C. E. , North A. L. , Okoloko E. , Niccolai L. M.
Published: March 2016

Background

Human papillomavirus (HPV) vaccination is recommended for routine administration at ages 11–12 years. However, uptake is lower than for other vaccines that are also routinely recommended for adolescents (MCV4 and Tdap). Understanding parental perceptions of HPV vaccine compared with other vaccines may help to inform strategies to increase uptake.

Methods

Parents and caregivers (n = 45) of adolescents ages 10–18 years from a low‐income, ethnic minority population participated in a qualitative study. Interviews were transcribed verbatim and coded for emergent themes.

Results

Many participants perceived the HPV vaccine to be similar to other routine vaccines. Noted similarities included the vaccines' ability to prevent disease, similar methods of administration and belief in health care providers' recommendation. Some parents noted the greater benefit of HPV vaccine in preventing cancer, which was viewed as a serious disease. Parents also noted the different mode of transmission (sexual) for HPV, which evoked mixed opinions.

Conclusion

Overall, most participants viewed the HPV vaccine in a positive light and similar to other adolescent vaccines with the added benefit of cancer prevention. Strategies that treat all three vaccines equally such as presenting them similarly as a ‘bundle’ to parents or considering policy initiatives such as school entry requirements might help increase raise coverage for HPV vaccine.
A model for measuring the health burden of classic congenital adrenal hyperplasia in adults
Authors: Hummel Silvia R. , Sadler Susannah , Whitaker Martin J. , Ara Roberta M. , Dixon Simon , Ross Richard J.
Published: March 2016

Aim

Patients with classic congenital adrenal hyperplasia (CAH) have poor health outcomes. In the absence of a comprehensive observational study, this manuscript provides a model to estimate the lifetime disease burden of adults with classic CAH.

Methods

The model, built in Excel, comprises subdomains addressing the health consequences of CAH and synthesises evidence from clinical and epidemiological studies on health outcomes.

Results

The model estimates that adults with classic CAH will implement ‘sick day rules’ (doubling or tripling glucocorticoid and/or use of parenteral therapy) 171 times over their lifetime and attend hospital for adrenal crisis on 11 occasions. In a population of 1000, over 200 will die of a condition complicated by adrenal crisis resulting, on average, in a loss of 7 years of life. Patients with CAH may also suffer from excess CVD events. Treatment with glucocorticoids almost doubles the risk of bone fractures in patients with CAH compared to the general population, leading on average to an additional 0·8 fractures per patient with CAH over their lifetime.

Conclusions

The disease burden model highlights gaps in evidence, particularly regarding intensity of care and adrenal crisis, and the relationship between control of CAH and risks of CVD, osteoporosis, diabetes and infertility. The model can be used for research on the impact of new clinical pathways and therapeutic interventions in terms of clinical events and cost.
Addressing risk factors, screening, and preventative treatment for diabetic retinopathy in developing countries: a review
Authors: Lin Stephanie , Ramulu Pradeep , Lamoureux Ecosse L , Sabanayagam Charumathi
Published: March 2016

The number of people with diabetic retinopathy (DR) has increased with the increasing prevalence of diabetes mellitus worldwide, especially in developing countries. In recent years, the successful implementation of public health programs in developed countries has been thought to contribute to decreases in blindness from DR. Developing countries, however, have not seen the same improvements, and their public health interventions still face significant challenges. In this review we describe the current state of public health approaches including risk factor control, screening and treatment techniques for DR in developing countries, and suggest recommendations. While the awareness of DR is variable, specific knowledge about DR is low, such that many patients have already experienced vision loss by the time they are screened. Attempts to improve rates of screening, in particular through non‐mydriatic cameras and tele‐screening, are ongoing and promising, although challenges include collaboration with healthcare systems and technology failures. Laser treatment is the most readily available, with anti‐VEGF therapy and vitreo‐retinal surgery increasingly sought after and provided. Recommendations include the use of ‘targeted mydriasis’ for fundus imaging to address high rates of ungradable images, increased communication with diabetes management services to improve patient retention and mobilization of access to DR treatments.
Hardware complications and failure of three‐unit zirconia‐based and porcelain‐fused‐metal implant‐supported fixed dental prostheses: a retrospective cohort study with up to 8 years
Authors: Shi Jun‐Yu , Zhang Xiao‐Meng , Qiao Shi‐Chong , Qian Shu‐Jiao , Mo Jia‐Ji , Lai Hong‐Chang
Published: March 2016

Objective

The aim of the present study was to assess the hardware complications and survival of three‐unit implant‐supported zirconia‐based fixed dental prostheses (IZ) and implant‐supported porcelain‐fused‐metal fixed dental prostheses (IP).

Material and methods

The study is a retrospective cohort study with up to 8 years (mean 4.8 years) follow‐up. Patients with conventional three‐unit implant‐supported fixed dental prostheses (without cantilever) in posterior area were reviewed. Hardware complications and survival rate were evaluated. Chi‐Square test was used to test the difference between IZ and IP groups.

Results

Two hundred and thirty‐seven patents (IZ : 112, IP : 125) with 279 three‐unit restorations (IZ : 127, IP : 152) participated in the study. The overall survival rate was 95.3% in IZ group and 94.7% in IP group at implant‐level and 94.6% in IZ group and 94.4% in IP group at subject‐level. Veneer chipping was the most frequently seen complication (20.1%). Significant higher minor veneer chipping rate (Grade 1) was found in IZ group (P = 0.04). No significant difference of veneer chipping rate (Grade 2 and Grade 3) was found between the two groups. The overall hardware complication rates of IZ were significantly higher than IP (33.07% and 18.42%, P = 0.01).

Conclusion

High survival rate of zirconia‐base and Porcelain‐fused‐to‐metal (PFM) restorations can be achieved with up to 8 years follow‐up. The zirconia‐based restorations need more polishing procedures, maintenance, and professional care than PFM restorations. The number of implants supporting a fixed dental prosthesis did not influence the implant survival and hardware complications. Well‐designed studies with high evidence level are still needed to further explore the hardware complications and clinical survival of IZ and IP.
Economic evaluation of a computed tomography directed referral strategy for chronic rhinosinusitis
Authors: Kilty S.J. , Leung R. , Rudmik L.
Published: March 2016

Background

Chronic rhinosinusitis (CRS) is a prevalent chronic inflammatory disease. The basis of a clinical diagnosis of CRS for primary care physicians (PCPs) is based upon the recognition of a symptom constellation that manifests with the disease. However, because the symptomatology of CRS may overlap with other diagnoses, the referral of patient to the most appropriate specialist may not always occur, leading to further delays in evaluation and treatment.

Methods

Given the emphasis on improving the value of health care in Canada, a decision tree model was designed to evaluate whether an upfront computed tomography (CT) scan of the paranasal sinuses ordered by the PCP for a suspected case of CRS would be more cost‐effective when compared to symptom‐based specialist referral practice.

Results

The CT‐based strategy resulted in the patient arriving at the most appropriate specialist 95% (±5%) of the time while the symptom‐based referral strategy resulted in the patient arriving at the correct specialist 77% (±18%) of the time. The incremental cost effectiveness ratio (ICER) for the CT‐based strategy was $1522 per patient arriving at the correct specialist.

Conclusion

These results suggest that PCPs can improve the effectiveness of their referrals for CRS by utilising an upfront CT referral strategy. However, it would create an additional cost of approximately $1500 per patient referred. Given these findings, the potential clinical benefits of using an upfront CT scan in the Canadian primary care setting should be further studied to determine the value of the additional money spent to improve the effectiveness of CRS referral.
Expanding marine protected areas to include degraded coral reefs
Authors: Abelson A. , Nelson P.A. , Edgar G.J. , Shashar N. , Reed D.C. , Belmaker J. , Krause G. , Beck M.W. , Brokovich E. , France R. , Gaines S.D.
Published: March 2016

Marine protected areas (MPAs) are a commonly applied solution to coral reef degradation, yet coral reefs continue to decline worldwide. We argue that expanding the range of MPAs to include degraded reefs (DR‐MPA) could help reverse this trend. This approach requires new ecological criteria for MPA design, siting, and management. Rather than focusing solely on preserving healthy reefs, our approach focuses on the potential for biodiversity recovery and renewal of ecosystem services. The new criteria would help identify sites with the highest potential for recovery and the greatest resistance to future threats (e.g., increased temperature and acidification) and sites that contribute to MPA connectivity. The DR‐MPA approach is a compliment rather than a substitute for traditional MPA design approaches. We believe that the DR‐MPA approach can enhance the natural, or restoration‐assisted, recovery of DRs and their ecosystem services; increase total reef area available for protection; promote more resilient and better‐connected MPA networks; and improve conditions for human communities dependent on MPA ecosystem services.
Distribution of donor lungs in the United States: a case for broader geographic sharing
Authors: Iribarne Alexander , Meltzer David O. , Chauhan Dhaval , Sonett Joshua R. , Gibbons Robert D. , Vigneswaran Wickii , Russo Mark J.
Published: March 2016

Objectives

To evaluate the association between allocation of donor lungs by geographic sharing type (GST) and lung allocation score (LAS).

Methods

UNOS data included lung transplant recipients between 5/4/05 and 09/30/15 (n = 17 416) grouped by GST of donor lungs: local, regional, or national. Recipients were stratified by LAS <50, 50–75, and >75. Kaplan–Meier analysis was used to assess five‐yr survival.

Results

The majority of lungs were shared locally (n = 9200; 52.8%) followed by nationally (n = 5356; 30.8%) and regionally (n = 2860; 16.4%). There was a significant difference in the mean LAS at transplant (local: 43.7 ± 15; regional: 49.5 ± 18.8; national 51 ± 19.4; p < 0.001). There was a significant association between GST and LAS (p < 0.001). The majority (n = 7431; 58.2%) of recipients with LAS <50 received local lungs. Recipients with LAS >75 received a majority of their organs from national (n = 881; 45.4%) and regional (n = 414; 21.6%) donors. Although statistically significant (p = 0.024), absolute decline in five‐yr survival by GST in the national GST was only 1.1% compared to the local GST.

Conclusions

Nearly half of all lungs in the United States are allocated locally to recipients with an LAS <50. Additional studies should determine if organ sharing over broader geographies would improve waitlist outcomes.
Ultrasound‐guided fine needle aspiration cytology of gallbladder lesions: a study of 596 cases
Authors: Rana C. , Krishnani N. , Kumari N.
Published: March 2016

Objective

Fine needle aspiration (FNA) is not a commonly performed procedure for gallbladder lesions for fear of causing biliary peritonitis; hence data on gallbladder cytology is scarce. The aims of the present study were to evaluate the diagnostic application of ultrasound‐guided (US) FNA cytology in the pre‐operative diagnosis of neoplastic as well as non‐neoplastic lesions of the gallbladder and to review the cytomorphological spectrum of gallbladder lesions encountered along with various diagnostic difficulties that can arise during reporting.

Methods

The study was carried out on 596 patients with gallbladder lesions in whom US‐guided FNA was performed over a 5‐year period. In 130 cases, simultaneous aspirations from other organs were done. The histological correlation was available in 32 cases. No major complications such as haemorrhage, peritonitis, etc. were encountered related to the procedure.

Results

The majority were mass lesions whereas in 73 cases (12.2%) only focal or diffuse gallbladder wall thickening was present. Cytological examination of 596 cases revealed malignancy in 462 (77.6%), 26 (4.4%) suspicious of malignancy, 23 (3.8%) inflammatory lesion, 29 negative (4.8%) and 56 cases showed necrosis only or were inadequate for any definite opinion. The lesions diagnosed on FNA cytology included carcinoma (predominantly adenocarcinoma), xanthogranulomatous cholecystitis (XGC), acute suppurative inflammation and tuberculosis. Of 26 with adequate cytology, 24 were accurate with respect to malignant (including one suspicious FNA) versus benign: one false positive and one false negative both involved xanthogranulomatous change.

Conclusion

The present study is the largest series evaluating the role of US‐guided FNA in the diagnosis of gallbladder lesions. It is a safe, rapid, reliable, cost‐effective and reasonably accurate method for diagnosing gallbladder lesions. FNA should always be attempted in cases with a mass lesion.
Obstructive sleep apnea in children with cerebral palsy and epilepsy
Authors: Garcia John , Wical Beverly , Wical William , Schaffer Leah , Wical Thomas , Wendorf Heather , Roiko Samuel
Published: March 2016

Aim

To examine the risk of obstructive sleep apnea (OSA) in children with cerebral palsy (CP) and/or epilepsy.

Method

This cross‐sectional study employs the Pediatric Sleep Questionnaire (PSQ), the Gross Motor Function Classification System (GMFCS), and chart review to identify symptoms of OSA in children presenting to a multi‐specialty pediatric healthcare institution.

Results

Two‐hundred and fifteen patients were grouped into those with epilepsy (n=54), CP (n=18), both (n=55), and neither (comparison group, n=88). The comparison group comprised children with developmental disabilities but not children with typical development. Significantly increased PSQ scores (indicating increased risk of OSA) were found among children with CP (58%) and CP with epilepsy (67%) than among the comparison group (27%; p<0.001 and p<0.0001 respectively). Children with both CP and epilepsy had a greater number of increased PSQ scores compared with CP alone (p<0.05). Increased PSQ scores were observed with increasing CP severity as measured using the GMFCS. The PSQ identified more children at risk of OSA (46%) than did the medical record review for symptoms of OSA (8.2%, p<0.001).

Interpretation

Children with CP of greater severity or comorbid epilepsy are at increased risk of OSA. This study supports the routine questionnaire‐based assessment for OSA as a regular part of the care of all children with CP, especially in those with more severe CP and those with epilepsy.
Growth during infancy and early childhood in children with cerebral palsy: a population‐based study
Authors: Strand Kristin Melheim , Dahlseng Magnus O , Lydersen Stian , Rø Torstein B , Finbråten Ane‐Kristine , Jahnsen Reidun B , Andersen Guro L , Vik Torstein
Published: March 2016

Aim

To describe growth in infancy and early childhood in children with cerebral palsy (CP).

Method

One hundred and four children with CP born at minimum 36 weeks' gestation in 2002 to 2010 were included. Prospectively collected growth data were requested from public health clinics. We calculated standard deviation (SD) scores (z‐scores) for weight and height for 12 set age points for each child from birth to 5 years, and for head circumference from birth to 12 months.

Results

Children with CP had normal growth in weight and height if they were born non‐small for gestational age (non‐SGA) or had mild motor impairments (i.e. Gross Motor Function Classification System [GMFCS] I–II), whereas children born SGA or with severe motor impairments (GMFCS III–V) had reduced growth (p<0.001). Children with feeding difficulties in infancy had reduced growth in weight and height throughout early childhood, while children without feeding difficulties had normal growth. Head circumference growth decreased most severely among children born SGA, who had mean z‐scores of −3.0 (95% confidence interval [CI] −3.7 to −2.2) at 1 year.

Interpretation

Children with mild CP had normal growth in weight and height until 5 years, and in head circumference during infancy. Feeding difficulties in infancy and being born SGA were strongly associated with reduced growth.
Intermittent Malfunction of a Prosthetic Valve—A Diagnostic Challenge
Authors: Fadel Bahaa M. , Alassas Khadija , Dahdouh Ziad , Pergola Valeria , Galzerano Domenico , Di Salvo Giovanni
Published: March 2016

Intermittent malfunction of a mechanical valve prosthesis is a rare condition that carries serious clinical implications. It results from the periodic entrapment of a prosthetic disk in either an open or closed position leading to transient intravalvular regurgitation or obstruction to flow. The intermittent nature of the malfunction poses a diagnostic challenge, particularly in the era of digital echocardiography. In this manuscript, we describe the Doppler and two‐dimensional echocardiographic findings in a patient with intermittent prosthetic mitral valve malfunction.
CONGLOMERATES AND REGULATION
Authors: Calzolari Giacomo , Scarpa Carlo
Published: March 2016

Conglomerates operating integrated productions in different regulated and unregulated sectors may benefit of scope economies. However, the precise size of these synergies is often unknown to both rival firms and regulators. We show that the conglomerate's private information on scope economies may negatively affect both the regulated and the unregulated sectors depending on the precise nature of competition (strategic substitutes or complements). We also unveil a novel effect of regulation that involves an informational externality to the conglomerate's rivals. Notwithstanding these complications, and independently of the nature of competition, we show that in our model it is desirable, as for welfare, to let the firm run integrated productions, unless diseconomies of scope may realize. (JEL L51, L43, L52)
Mutual interference reduces offspring production in a brood‐guarding bethylid wasp
Authors: Sreenivas A.G. , Hardy Ian C.W.
Published: March 2016

Parasitoids have the potential to suppress populations of their hosts and thus may play an important role in influencing the temporal and spatial dynamics of pest arthropods. Behavioural interactions between foraging females, collectively constituting ‘mutual interference’, can reduce host suppression. We use laboratory microcosms to assess the prevalence and consequences of mutual interference behaviour in a bethylid wasp,Goniozus nephantidis(Muesebeck) (Hymenoptera: Bethylidae), which is known to brood guard and to engage in agonistic contests for individual hosts and which is also an agent of biological pest control. We hold host and parasitoid numbers constant and vary the degree of female–female contact that can occur. Mutual interference is manifest in a considerable reduction in the number of offspring produced when females are not fully isolated from each other, due to effects operating at the early stages of offspring production. This mutual interference may contribute towards the limited degree of host population suppression achieved when some species of bethylids are deployed as agents of biological pest control and also has clear potential to influence the efficiency of mass rearing of parasitoids prior to field release.
Ordinal species richness in insects—a preliminary study of the influence of morphology, life history, and ecology
Authors: Ferns P.N. , Jervis M.A.
Published: March 2016

In an effort to understand why some groups of insects, especially beetles, are much more diverse than others, analyses were carried out on the role of morphological, life‐history, and ecological factors on the species richness of various orders, as quantified by the number of extant species they each contain. The influence of body size, the form of the wings and thorax, the mode of development, parasitism, the ability to accumulate resources for egg laying at both juvenile and adult stages (ovigenic flexibility), diet range, and habitat choice were examined using comparative methods that control for phylogeny. Hierarchical multiple regression revealed that about 10% of the variance in insect species richness occurred within subclasses, 34% within superorders, and 54% within or below ordinal level. The evolution of wings and mode of development were key differences between the subclasses, and two superorders, each containing a single species‐rich order and several species‐poor ones, were responsible for most of the variation at superordinal level. After controlling for phylogeny, and on the basis of minimal adequate statistical models, the rate of cladogenesis declined with time, and was higher in orders with a broad range of larval diets. The number of species in each order was most closely correlated with larval diet breadth, the proportion of species able to fly, physical protection of the hindwings by the forewings at rest, the proportion of species that are parasitic, and the age of the order. Evidence from the literature on adult diet and ovigeny index, supported by measurements of the width of the thoracico‐abdominal junction, indicates that the food processing ability of adultDiptera,Lepidoptera, andHymenoptera is subject to morphological constraints limiting the contribution that the adult diet makes to the accumulation of the protein reserves needed for egg formation. AdultColeoptera are free of such constraints, and thus exhibit the broadest range of both larval and adult diets and inhabit the widest range of habitats. Beetles can thus accumulate resources for egg production as larvae, adults, or both, as a consequence of their unique adult morphology. The key adult features involved are (1) the protective elytra and thickened exoskeleton, (2) the flexible jointing of the prothorax with the pterothorax, (3) the wide, rigid post‐thoracic junction with the abdomen allowing enlargement of the gut for the storage, passage, and efficient digestion of a wide range of particulate foods, and (4) the biting mouthparts with which to process them.
Histiocytic sarcoma as a secondary malignancy: pathobiology, diagnosis, and treatment
Authors: Ansari Junaid , Naqash Abdul Rafeh , Munker Reinhold , El‐Osta Hazem , Master Samip , Cotelingam James D. , Griffiths Elizabeth , Greer Adam H. , Yin Hong , Peddi Prakash , Shackelford Rodney E.
Published: March 2016

Histiocytic sarcoma (HS) is an extremely rare non‐Langerhans cell disorder with an aggressive course and limited treatment options. Recent advances in molecular/genetic sequencing have suggested a common clonal origin between various hematolymphoid disorders and cases of secondary HS. Deriving conclusions from previously reported cases of HS arising secondarily to certain hematolymphoid disorders, here we have tried to provide insight into the mechanisms influencing this evolution. We also discuss a clinical case of a 72‐year‐old man with a diagnosis of chronic myeloid leukemia (CML), presenting subsequently with a heterogeneous liver mass positive with a diagnosis of HS. The liver mass showed a retained BCR‐ABL1 translocation suggesting clonality between the CML and HS. As seen in our case and other reported cases of HS derived secondarily, the concurrent expression of immunoglobulin heavy (IGH)‐/light‐chain rearrangements or cytogenetic markers common to the primary malignancy suggests an evolutionary mechanism involving lineage switching that could potentially be influenced by genetic or epigenetic cues which may occur at the level of a progenitor or the malignant cell itself.
Environmental layout complexity affects neural activity during navigation in humans
Authors: Slone Edward , Burles Ford , Iaria Giuseppe
Published: March 2016

Navigating large‐scale surroundings is a fundamental ability. In humans, it is commonly assumed that navigational performance is affected by individual differences, such as age, sex, and cognitive strategies adopted for orientation. We recently showed that the layout of the environment itself also influences how well people are able to find their way within it, yet it remains unclear whether differences in environmental complexity are associated with changes in brain activity during navigation. We used functional magnetic resonance imaging to investigate how the brain responds to a change in environmental complexity by asking participants to perform a navigation task in two large‐scale virtual environments that differed solely in interconnection density, a measure of complexity defined as the average number of directional choices at decision points. The results showed that navigation in the simpler, less interconnected environment was faster and more accurate relative to the complex environment, and such performance was associated with increased activity in a number of brain areas (i.e. precuneus, retrosplenial cortex, and hippocampus) known to be involved in mental imagery, navigation, and memory. These findings provide novel evidence that environmental complexity not only affects navigational behaviour, but also modulates activity in brain regions that are important for successful orientation and navigation.
Muscarinic control of rostromedial tegmental nucleus GABA neurons and morphine‐induced locomotion
Authors: Wasserman David I. , Tan Joel M. J. , Kim Jun Chul , Yeomans John S.
Published: March 2016

Opioids induce rewarding and locomotor effects by inhibiting rostromedial tegmental GABA neurons that express μ‐opioid and nociceptin receptors. These GABA neurons then strongly inhibit dopamine neurons. Opioid‐induced reward, locomotion and dopamine release also depend on pedunculopontine and laterodorsal tegmental cholinergic and glutamate neurons, many of which project to and activate ventral tegmental area dopamine neurons. Here we show that laterodorsal tegmental and pedunculopontine cholinergic neurons project to both rostromedial tegmental nucleus and ventral tegmental area, and that M4 muscarinic receptors are co‐localized with μ‐opioid receptors associated with rostromedial tegmental GABA neurons. To inhibit or excite rostromedial tegmental GABA neurons, we utilized adeno‐associated viral vectors and DREADDs to express designed muscarinic receptors (M4D or M3D respectively) in GAD2::Cre mice. In M4D‐expressing mice, clozapine‐N‐oxide increased morphine‐induced, but not vehicle‐induced, locomotion. In M3D‐expressing mice, clozapine‐N‐oxide blocked morphine‐induced, but not vehicle‐induced, locomotion. We propose that cholinergic inhibition of rostromedial tegmental GABA neurons via M4 muscarinic receptors facilitates opioid inhibition of the same neurons. This model explains how mesopontine cholinergic systems and muscarinic receptors in the rostromedial tegmental nucleus and ventral tegmental area are important for dopamine‐dependent and dopamine‐independent opioid‐induced rewards and locomotion.
The ventromedial hypothalamus mediates predator fear memory
Authors: Silva Bianca A. , Mattucci Camilla , Krzywkowski Piotr , Cuozzo Rachel , Carbonari Laura , Gross Cornelius T.
Published: March 2016

The amygdala has been shown to be essential for the processing of acute and learned fear across animal species. However, the downstream neural circuits that mediate these fear responses differ according to the nature of the threat, with separate pathways having been identified for predator, conspecific and physically harmful threats. In particular, the dorsomedial part of the ventromedial hypothalamus (VHMdm) is critical for the expression of defensive responses to predators. Here, we tested the hypothesis that this circuit also participates in predator fear memory by transient pharmacogenetic inhibition of the VMHdm and its downstream effector, the dorsal periaqueductal grey, during predator fear learning in the mouse. Our data demonstrate that neural activity in the VMHdm is required for both the acquisition and recall of predator fear memory, whereas that of its downstream effector, the dorsal periaqueductal grey, is required only for the acute expression of fear. These findings are consistent with a role for the medial hypothalamus in encoding an internal emotional state of fear.
Patient Parents: Do Offspring Decide on the Timing of Fledging in Zebra Finches?
Authors: Trillmich Fritz , Spiller Inka , Naguib Marc , Krause Eike Tobias
Published: March 2016

Parent–offspring conflict over parental care is predicted to become most pronounced during offspring transition to independence when offspring are predicted to attempt to extend care for longer than parents are selected to provide it. However, on the proximate level, it is difficult to determine who plays the most important role in this process, parents or offspring. For several vertebrate taxa, it has been documented that parents end brood care by abandoning offspring after a fixed period or else show high flexibility in the duration of care, but teasing apart the role of offspring and parents underlying this flexibility has been difficult. Here, we studied the decision to fledge in captive zebra finches (Taeniopygia guttata), an altricial songbird. We experimentally delayed the time of fledging to determine who decides about the end of feeding inside the nest, parents or offspring. The experiment indicates that parents do not primarily rely on phenotypic offspring traits in their decision to feed offspring in the nest, but appear to adjust the duration of parental care as long as offspring are in the nest which parents may take as an indicator of offspring need and locomotor abilities. Delayed‐fledging offspring appeared not to suffer a disadvantage in terms of age at the onset of independent feeding. Our study suggests that, in zebra finches, offspring play a major role in determining the time of fledging and leave the nest on their own, possibly to reduce the risk of nest predation, or to evade sibling competition in the nest.
Levobupivacaine attenuates lipopolysaccharide‐induced acute lung injury
Authors: Guo Dan , Li Kehan , Yang Muqiang , Zhang Hongjun , Miao Yafei
Published: March 2016

Levobupivacaine (LB), a kind of local anesthetic, possesses anti‐inflammatory properties. High‐mobility group box 1 (HMGB1), a nuclear DNA‐binding protein, plays a key role in the development of acute lung injury (ALI). The aim of this study was to investigate whether LB attenuates ALI by the inhibition of HMGB1 expression and to investigate the molecular mechanisms. ALI in male rats was induced by an intratracheal instillation of LPS (5 mg/kg), and male rats received mini‐osmotic pumps containing LB 30 min after LPS exposure. A549 alveolar epithelial cells were incubated with LPS in the presence or absence of LB. An enzyme‐linked immunosorbent assay was used to detect the levels of inflammatory cytokines. Western blotting was used to detect the changes in the expression of toll‐like receptor 2/4 (TLR2/4) and the activation of NF‐κB. The results showed that LB significantly protected animals from LPS‐induced ALI as evidenced by a decrease in the ratio of lung wet to dry weight, total cells, neutrophils, macrophages, and myeloperoxidase activity, associated with a reduced lung histological damage. We also found that LB post‐treatment markedly inhibited the release of HMGB1 and other pro‐inflammatory cytokines. Furthermore, LB significantly inhibited LPS‐induced TLR2/4 protein overexpression and NF‐κB activation in the lung tissues and in LPS‐stimulated A549 alveolar epithelial cells in vitro. These data indicate that LB attenuated LPS‐induced ALI by the inhibition of HMGB1 expression in rats. These benefits were associated with the inhibition of TLR2/4‐NF‐κB pathway by LB.
To deliver or to degrade – an interplay of the ubiquitin–proteasome system, autophagy and vesicular transport in plants
Authors: Zientara‐Rytter Katarzyna , Sirko Agnieszka
Published: March 2016

The efficient utilization and subsequent reuse of cell components is a key factor in determining the proper growth and functioning of all cells under both optimum and stress conditions. The process of intracellular and intercellular recycling is especially important for the appropriate control of cellular metabolism and nutrient management in immobile organisms, such as plants. Therefore, the accurate recycling of amino acids, lipids, carbohydrates or micro‐ and macronutrients available in the plant cell becomes a critical factor that ensures plant survival and growth. Plant cells possess two main degradation mechanisms: a ubiquitin–proteasome system and autophagy, which, as a part of an intracellular trafficking system, is based on vesicle transport. This review summarizes knowledge of both the ubiquitin–proteasome system and autophagy pathways, describes the cross‐talk between the two and discusses the relationships between autophagy and the vesicular transport systems.
Modelling marine community responses to climate‐driven species redistribution to guide monitoring and adaptive ecosystem‐based management
Authors: Marzloff Martin Pierre , Melbourne‐Thomas Jessica , Hamon Katell G. , Hoshino Eriko , Jennings Sarah , van Putten Ingrid E. , Pecl Gretta T.
Published: March 2016

As a consequence of global climate‐driven changes, marine ecosystems are experiencing polewards redistributions of species – or range shifts – across taxa and throughout latitudes worldwide. Research on these range shifts largely focuses on understanding and predicting changes in the distribution of individual species. The ecological effects of marine range shifts on ecosystem structure and functioning, as well as human coastal communities, can be large, yet remain difficult to anticipate and manage. Here, we use qualitative modelling of system feedback to understand the cumulative impacts of multiple species shifts in south‐eastern Australia, a global hotspot for ocean warming. We identify range‐shifting species that can induce trophic cascades and affect ecosystem dynamics and productivity, and evaluate the potential effectiveness of alternative management interventions to mitigate these impacts. Our results suggest that the negative ecological impacts of multiple simultaneous range shifts generally add up. Thus, implementing whole‐of‐ecosystem management strategies and regular monitoring of range‐shifting species of ecological concern are necessary to effectively intervene against undesirable consequences of marine range shifts at the regional scale. Our study illustrates how modelling system feedback with only limited qualitative information about ecosystem structure and range‐shifting species can predict ecological consequences of multiple co‐occurring range shifts, guide ecosystem‐based adaptation to climate change and help prioritise future research and monitoring.
High and dry: post‐fire tree seedling establishment in subalpine forests decreases with post‐fire drought and large stand‐replacing burn patches
Authors: Harvey Brian J. , Donato Daniel C. , Turner Monica G.
Published: March 2016

AimClimate warming and increased wildfire activity are hypothesized to catalyse biogeographical shifts, reducing the resilience of fire‐prone forests world‐wide. Two key mechanisms underpinning hypotheses are: (1) reduced seed availability in large stand‐replacing burn patches, and (2) reduced seedling establishment/survival after post‐fire drought. We tested for regional evidence consistent with these mechanisms in an extensive fire‐prone forest biome by assessing post‐fire tree seedling establishment, a key indicator of forest resilience.

LocationSubalpine forests, US Rocky Mountains.

MethodsWe analysed post‐fire tree seedling establishment from 184 field plots where stand‐replacing forest fires were followed by varying post‐fire climate conditions. Generalized linear mixed models tested how establishment rates varied with post‐fire drought severity and distance to seed source (among other relevant factors) for tree species with contrasting post‐fire regeneration adaptations.

ResultsTotal post‐fire tree seedling establishment (all species combined) declined sharply with greater post‐fire drought severity and with greater distance to seed sources (i.e. the interior of burn patches). Effects varied among key species groups. For conifers that dominate present‐day subalpine forests (Picea engelmannii,Abies lasiocarpa), post‐fire seedling establishment declined sharply with both factors. One exception was serotinousPinus contorta, which did not vary with either factor. For montane species expected to move upslope under future climate change (Larix occidentalis, Pseudotsuga menziesii,Populus tremuloides) and upper treeline species (Pinus albicaulis), establishment was unrelated to either factor. Greater post‐fire tree seedling establishment on cooler/wetter aspects suggested local topographic refugia during post‐fire droughts.

Main conclusionsIf future drought and wildfire patterns manifest as expected, post‐fire tree seedling establishment of species that currently characterize subalpine forests could be substantially reduced. Compensatory increases from lower montane and upper treeline species may partially offset these reductions, but our data suggest important near‐ to mid‐term shifts in the composition and structure of high‐elevation forests under continued climate warming and increased wildfire activity.
Diuretic usage for protection against end‐organ damage in liver cirrhosis and heart failure
Authors: Mori Takefumi , Ohsaki Yusuke , Oba‐Yabana Ikuko , Ito Sadayoshi
Published: March 2016

Volume overload is common in liver cirrhosis, heart failure, and chronic kidney disease, being an independent risk factor for mortality. Loop diuretics have been widely used for treating volume overload in these patients. However, there is a tendency to increase the dose of loop diuretics partly because of diuresis resistance. Neurohormonal factors are also enhanced in these patients, which play a role in volume overload and organ ischemia. Loop diuretics cannot improve neurohormonal factors and could result in end‐organ damage. The water diuretic tolvaptan has been approved for use for volume overload in heart failure and liver cirrhosis. Despite causing similar increases in urine volume, its characteristics differ from those of loop diuretics. Renal blood flow is maintained with tolvaptan but decreased with furosemide in heart failure patients. Neurohormonal factors and blood pressure are not markedly altered by tolvaptan administration. It is expected that these mechanisms of tolvaptan can protect against worsening renal function by volume overload diseases compared with loop diuretics. It has also been reported that some patients do not respond well to tolvaptan. Loop diuretics and tolvaptan share the same mechanism with regard to decreasing renal interstitial osmolality, which plays a fundamental role in water diuresis. Thus, a high dose of loop diuretics could result in resistance to tolvaptan, so tolvaptan should be administered before increasing the loop diuretic dose. Therefore, volume control without enhancing end‐organ damage can be achieved by adding tolvaptan to a tolerable dose of Na‐sparing diuretics.
Pathophysiology of recurrent hepatocellular carcinoma after radiofrequency ablation
Authors: Ikemoto Tetsuya , Shimada Mitsuo , Yamada Shinichiro
Published: March 2016

Radiofrequency ablation (RFA) is effective for the local control of hepatocellular carcinoma (HCC), particularly when a patient's liver functional reserve does not allow radical resection. There is controversy regarding the superiority of surgical resection compared with RFA for such patients, particularly those with three or fewer tumors with diameters ≤3 cm. Moreover, HCC often recurs after RFA, and the tumor cells show distinct phenotypic changes. Incomplete ablation accounts for tumor recurrence, and recent studies provide new insights into the biological mechanisms responsible for the pathological changes of HCC after RFA. This review focuses on the roles of epithelial–mesenchymal transition and cancer stemness that are driven by a mechanism that involves microRNA‐mediated upregulation of hypoxia‐inducible factor‐1. The studies reviewed here provide compelling evidence that complete ablation of HCC is required to prevent recurrence and indicate that further research is urgently required to develop a new systematic strategy to prevent tumor recurrence by targeting hypoxia‐inducible factor‐1.
The application of next‐generation sequencing‐based molecular diagnostics in endometrial stromal sarcoma
Authors: Li Xiaodong , Anand Mona , Haimes Josh D , Manoj Namitha , Berlin Aaron M , Kudlow Brian A , Nucci Marisa R , Ng Tony L , Stewart Colin J R , Lee Cheng‐Han
Published: March 2016

Aims

Endometrial stromal sarcomas (ESSs) are divided into low‐grade and high‐grade subtypes, with the latter showing more aggressive clinical behaviour. Although histology and immunophenotype can aid in the diagnosis of these tumours, genetic studies can provide additional diagnostic insights, as low‐grade ESSs frequently harbour fusions involving JAZF1/SUZ12 and/or JAZF1/PHF1, whereas high‐grade ESSs are defined by YWHAE–NUTM2A/B fusions. The aim of this study was to evaluate the utility of a next‐generation sequencing (NGS)‐based assay in identifying ESS fusions in archival formalin‐fixed paraffin‐embedded tumour samples.

Methods and results

We applied an NGS‐based fusion transcript detection assay (Archer FusionPlex Sarcoma Panel) that targets YWHAE and JAZF1 fusions in a series of low‐grade ESSs (n = 11) and high‐grade ESSs (n = 5) that were previously confirmed to harbour genetic rearrangements by fluorescence in‐situ hybridization (FISH) and/or reverse transcription polymerase chain reaction (RT‐PCR) analyses. The fusion assay identified junctional fusion transcript sequences that corresponded to the known FISH/RT‐PCR results in all cases. Four low‐grade ESSs harboured JAZF1–PHF1 fusions with different junctional sequences, and all were correctly identified because of the open‐ended nature of the assay design, using anchored multiplex polymerase chain reaction. Seven non‐ESS sarcomas were also included as negative controls, and no strong ESS fusion candidates were identified in these cases.

Conclusions

Our findings demonstrate good sensitivity and specificity of an NGS‐based gene fusion assay in the detection of ESS fusion transcripts.