bluuebunny/crossref_metadata_2025 huggingface dataset:
A virtualized infrastructure to offer network mapping functionality in SDN networks
Authors: Manzanares‐Lopez Pilar , Muñoz‐Gea Juan Pedro , Malgosa‐Sanahuja Josemaria , Flores‐de la Cruz Adrian
Published: April 2019

The separation of control and forwarding planes in software‐defined networking (SDN) networks is a key issue of the SDN technology. This feature and the existence of the SDN controller allow the developing of dynamic, adaptable and manageable networks, networks that require adequate services, and applications. However, the separation of these planes prevents the use of existing powerful tools that were coded considering traditional networks. In this paper, we make use of the potential of network virtualization (NV) technologies to propose the use of a virtualized infrastructure that makes possible the incorporation of these existing services and/or applications to an SDN network, without the need for programming additional and complex software modules in the SDN controller. Thus, in this paper, NV is not employed to develop a network managed by SDN but to broaden and give support to the SDN control layer. As an example, we describe the incorporation of nmap (a versatile and powerful tool widely used by security experts for network exploration) into the SDN framework. It is only necessary to develop a simple control plane service that thanks to the proposed virtualized infrastructure allows the inclusion of this powerful management application. The result offers the complete functionality of the nmap utility to the network administrators, who control the SDN network through the out‐of‐band control plane. In addition, a northbound REST API has been defined to offer the main functionality of the tool (host discovery, port scanning, and operating system detection) to the application layer.
An eigenvalue‐based edge infrastructure for cloud‐based CDN
Authors: Sahoo Sampa , Sahoo Bibhudatta , Turuk Ashok Kumar
Published: April 2019

In today's dynamic video landscape, an end user needs services to be delivered to any devices anytime with less delay over the Internet. Now users' expectation has changed; they want faster time‐to‐market, cost reduction, and the ability to adjust according to the evolving requirements, which are a limit for the traditional server‐based approach. The explosive growth of the internet multimedia application needs a new approach to content delivery to overcome the limitations of server‐based techniques. Cloud‐based content delivery networks (CCDNs) have recently started to emerge where contents are cached from the cloud storage and delivered through the distribution service to meet quality of services (QoS) of requested services. In this paper, we dealt with CCDN deployment problem and proposed a new eigenvalue‐based edge infrastructure for a network service provider to serve the users with a variation on proximity interest concerning operational cost and user QoS satisfaction. The edge infrastructure designing is a two‐step process: (a) ideal location search for placing edge server and (b) edge server placement and capacity provisioning. The performance of the proposed approach is appraised via modeling and simulation. Performance evaluation outcomes are exhibited to manifest the effectiveness and competitiveness of our approach when compared with existing algorithms.
Adaptable mesocosm facility to study oil spill impacts on corals
Authors: Silva Denise P. , Duarte Gustavo , Villela Helena D.M. , Santos Henrique F. , Rosado Phillipe M. , Rosado João Gabriel , Rosado Alexandre S. , Ferreira Edir M. , Soriano Adriana U. , Peixoto Raquel S.
Published: April 2019

Although numerous studies have been carried out on the impacts of oil spills on coral physiology, most have relied on laboratory assays. This scarcity is partly explained by the difficulty of reproducing realistic conditions in a laboratory setting or of performing experiments with toxic compounds in the field. Mesocosm systems provide the opportunity to carry out such studies with safe handling of contaminants while reproducing natural conditions required by living organisms. The mesocosm design is crucial and can lead to the development of innovative technologies to mitigate environmental impacts. Therefore, this study aimed to develop a mesocosm system for studies simulating oil spills with several key advantages, including true replication and the use of gravity to control flow‐through that reduces reliance on pumps that can clog thereby decreasing errors and costs. This adaptable system can be configured to (a) have continuous flow‐through; (b) operate as an open or closed system; (c) be fed by gravity; (d) have separate mesocosm sections that can be used for individual and simultaneous experiments; and (e) simulate the migration of oil from ocean oil spills to the nearby reefs. The mesocosm performance was assessed with two experiments using the hydrocoral Millepora alcicornis and different configurations to simulate two magnitudes of oil spills. With few exceptions, physical and chemical parameters remained stable within replicates and within treatments throughout the experiments. Physical and chemical parameters that expressed change during the experiment were still within the range of natural conditions observed in Brazilian marine environments. The photosynthetic potential (Fv/Fm) of the algae associated with M. alcicornis decreased in response to an 1% crude‐oil contamination, suggesting a successful delivery of the toxic contaminant to the targeted replicates. This mesocosm is customizable and adjustable for several types of experiments and proved to be effective for studies of oil spills.
A meta‐analysis of herbivore effects on plant attractiveness to pollinators
Authors: Moreira Xoaquín , Castagneyrol Bastien , Abdala‐Roberts Luis , Traveset Anna
Published: April 2019

Herbivores may directly or indirectly affect plant attractiveness to pollinators. Although several studies have reported on these effects, there is yet no general consensus on the strength and sign of such interactions or their contingency on herbivory features such as the plant tissue attacked. We performed a meta‐analysis of studies testing for effects of herbivores on floral traits, plant attractiveness to pollinators, and plant reproductive success. We also assessed whether herbivore effects depended on the plant tissue attacked by herbivores and if real or simulated herbivory was used. We found an overall significant negative effect of herbivores on floral traits, plant attractiveness to pollinators, and plant reproductive success. These effects were, however, contingent on the plant tissue attacked and on whether real or simulated damage was used. Real floral and leaf, but not root, herbivores showed detrimental effects on floral traits and plant attractiveness to pollinators. In addition, real leaf, but not floral or root herbivory, lowered plant reproductive success. Contrastingly, simulated leaf and floral herbivory showed no effect on any of the response variables. These findings help move forward our understanding of the strength and directionality of herbivore effects on plant attractiveness to pollinators and their underlying mechanisms.
Evaluation of bias on the probability of collapse from amplitude scaling using spectral‐shape‐matched records
Authors: Dávalos Héctor , Miranda Eduardo
Published: April 2019

Although for many years it was thought that amplitude scaling of acceleration time series to reach a target intensity did not introduce any bias in the results of nonlinear response history analyses, recent studies have showed that scaling can lead to an overestimation of deformation demands with increasing scale factors. Some studies have suggested that the bias can be explained by differences in spectral shape between the response spectra of unscaled and scaled records. On the basis of these studies, some record selection procedures assume that if records are selected using spectral‐shape‐matching procedures, amplitude scaling does not induce any bias on the structural response. This study evaluates if bias is introduced on lateral displacement demands and seismic collapse risk estimates even when spectral shape is carefully taken into consideration when selecting ground motions. Several single‐degree‐of‐freedom and multiple‐degree‐of‐freedom systems are analyzed when subjected to unscaled and scaled ground motions selected to approximately match the mean and the variance of the conditional spectrum at the target level of intensity. Results show that an explicit consideration of spectral shape is not enough to avoid a systematic overestimation of lateral displacement demands and collapse probabilities as the scale factor increases. Moreover, the bias is observed in practically all cases for systems with strength degradation and it increases with decreasing period and decreasing lateral strength relative to the strength required to remain elastic. Key reasons behind the bias are presented by evaluating input energy, causal parameters, and damaging pulse distributions in unscaled and scaled ground motion sets.
A Re-Evaluation of Chironomid Deformities as an Environmental Stress Response: Avoiding Survivorship Bias and Testing Noncontaminant Biological Factors
Authors: Gagliardi Bryant , Long Sara M. , Pettigrove Vincent J. , Griffin Philippa C. , Hoffmann Ary A.
Published: April 2019

Larval deformities have been observed in chironomids, and are thought to be associated with aquatic contaminant exposure. However, in laboratory assays, deformities have not been linked with contaminants in the absence of potential confounding variables including mortality, which introduces a survivorship bias. There is also a paucity of data on noncontaminant causes. In addition, power analyses are rarely undertaken, meaning that effect sizes detectable are usually uncertain. We therefore aimed to clarify factors associated with deformities, by running survivorship bias–free (i.e., sublethal) assays, assessing contaminant (copper and imidacloprid) and noncontaminant (malnutrition) stressors, and considering natural biological (metamorphosis) factors in Chironomus tepperi. We included a posteriori power analyses for all tests. Our assays found no significant association between tested factors and deformity rate. Power analyses indicated that the stressor experiment had moderate power to detect deformity effects. The metamorphosis assay had relatively lower power (due to an unexpectedly high control deformity rate), highlighting the importance of power tests in these types of evaluations. These results, in conjunction with others recently published, raise doubts as to the causal effects of environmental stressors on deformity incidence. By avoiding survivorship bias, and by testing noncontaminant factors and statistical power, we present a more holistic methodology, to resolve ongoing uncertainty in this area. We also discuss possible future directions for chironomid deformity research, and concerns regarding survivorship bias in ecotoxicology. Environ Toxicol Chem 2019;38:1658–1667. © 2019 SETAC
Empathetic Practice: The Struggle and Virtue of Empathizing with a Patient's Suffering
Authors: Campelia Georgina , Tate Tyler
Published: April 2019

In this article, our analysis of empathy in the clinical context hinges on the complexities of patients who are acutely suffering. Using a case concerning a heart transplant patient with Duchenne muscular dystrophy, Alex, and his nurse, Joe, we investigate how empathy’s phenomenological nebulousness can generate doubts about its virtue. Even when asking, “How are you, Alex?” Joe hates the question; it seems empty, silly. Cases like this show both that the enactment of empathy is sometimes challenging and that it can be reasonable to wonder if empathy is a virtue at all. Perhaps Alex’s suffering is simply too massive: Joe cannot possibly know how he feels, so why try? Perhaps empathy would only cause Joe to suffer along with Alex. Not only is empathy difficult to produce in the context of Alex’s suffering; it may not even be possible; and if we simply cannot muster empathy, what is the point of morally demanding it?

In response, we distinguish different kinds of empathic engagements from one another and offer separate counsel. We argue that it is important to understand empathy as something that must be honed across varied contexts before it can be called a virtue. Conceptualizing and operationalizing empathy in this way helps to ground its possibility and virtue even in the most challenging and complex clinical encounters.
The Critical Role of Medical Institutions in Expanding Access to Investigational Interventions
Authors: Spector‐Bagdady Kayte , Weatherwax Kevin J. , Gravelin Misty , Shuman Andrew G.
Published: April 2019

The U.S. federal government provides two tracks for eligible patients to obtain access outside clinical trials to investigational interventions currently under study for potential clinical benefits: the Food and Drug Administration’s expanded access pathway and the pathway created by the more recent Right to Try Act. In this issue of the Hastings Center Report, with a critical focus on patients, industry, and the research enterprise, Kelly Folkers and colleagues frame the inherent challenges that these pathways are meant to solve and have also inadvertently created. But an additional key focus is how the relevant situations should be managed at the bedside and how the system risks both inefficient and inequitable access to options at the institutional level. Although either pathway could be helpful to patients, the challenges of having the pathways coexist are greater than the sum of their parts. Individual clinicians represent the front line of the regulatory and eligibility challenges of expanded access and right to try, making clinical education a critical component of a comprehensive approach to using them well. But it is medical institutions that must take the lead on supporting access to investigational options in the most equitable and effective manner possible.
Danielle M. Wenner Replies
Authors: Wenner Danielle M.
Published: April 2019

The author replies to a letter to the editor from Felicitas Sofia Holzer concerning Wenner’s article “The Social Value Requirement in Research: From the Transactional to the Basic Structure Model of Stakeholder Obligations,” in the Hastings Center Report’s January‐February 2019 issue.
ΔFosB Requires Galanin, but not Leptin, to Increase Bone Mass via the Hypothalamus, but both are needed to increase Energy expenditure
Authors: Idelevich Anna , Sato Kazusa , Nagano Kenichi , Rowe Glenn , Gori Francesca , Baron Roland
Published: April 2019

Energy metabolism and bone homeostasis share several regulatory pathways. The AP1 transcription factor ΔFosB and leptin both regulate energy metabolism and bone, yet whether their pathways intersect is not known. Transgenic mice overexpressing ΔFosB under the control of the Enolase 2 (ENO2) promoter exhibit high bone mass, high energy expenditure, low fat mass, and low circulating leptin levels. Because leptin is a regulator of bone and ΔFosB acts on leptin-responsive ventral hypothalamic (VHT) neurons to induce bone anabolism, we hypothesized that regulation of leptin may contribute to the central actions of ΔFosB in the VHT. To address this question, we used adeno-associated virus (AAV) expression of ΔFosB in the VHT of leptin-deficient ob/ob mice and genetic crossing of ENO2-ΔFosB with ob/ob mice. In both models, leptin deficiency prevented ΔFosB-triggered reduction in body weight, increase in energy expenditure, increase in glucose utilization, and reduction in pancreatic islet size. In contrast, leptin deficiency failed to prevent ΔFosB-triggered increase in bone mass. Unlike leptin deficiency, galanin deficiency blocked both the metabolic and the bone ΔFosB-induced effects. Overall, our data demonstrate that, while the catabolic energy metabolism effects of ΔFosB require intact leptin and galanin signaling, the bone mass–accruing effects of ΔFosB require galanin but are independent of leptin. © 2019 American Society for Bone and Mineral Research.
Retracted: A feed‐forward regulatory network lncPCAT1/miR‐106a‐5p/E2F5 regulates the osteogenic differentiation of periodontal ligament stem cells
Authors: Jia Bo , Qiu Xiaoling , Chen Jun , Sun Xiang , Zheng Xianghuai , Zhao Jianjiang , Li Qin , Wang Zhiping
Published: April 2019

Periodontal ligament stem cells (PDLSCs) are characterized by multiple differentiation potential and potent self‐renewal ability, yet much remains to be elucidated that what determines these properties. Long noncoding RNAs (lncRNAs) have been suggested to involve in multiple biological process under physiological and pathological conditions, including osteogenic differentiation. In the present study, we performed comprehensive lncRNA profiling by lncRNA microarray analysis and identified prostate cancer‐associated ncRNA transcript‐1 (lncPCAT1) was gradually increased in PDLSCs during consecutive osteogenic induction, and it could further positively regulate the osteogenic differentiation both in vitro and in vivo, whereas lncPCAT1 inhibition led to suppressed osteogenic differentiation. Thereafter, we inferred a predicted interaction between lncPCAT1 and miR‐106a‐5p and then confirmed the direct binding sites of miR‐106a‐5p on lncPCAT1. Although miR‐106a‐5p upregulation led to decreased osteogenic differentiation, lncPCAT1 overexpression could reverse its suppression, indicating that lncPCAT1 act as a competing endogenous RNA for miR‐106a‐5p. Moreover, lncPCAT1 could sponge miR‐106a‐5p to upregulate miR‐106a‐5p‐targeted gene BMP2, which was a crucial gene involved in osteogenic differentiation. Interestingly, we found that E2F5, another target of miR‐106a‐5p, could bind to the promoter of lncPCAT1 and then form a feed‐forward regulatory network targeting BMP2. In conclusion, our study provided a novel lncRNA‐miRNA feed‐forward regulatory network and a promising target to modulate the osteogenic differentiation of PDLSCs.
Protein kinase D1 inhibition interferes with mitosis progression
Authors: Martínez-León Eduardo , Amable Gastón , Jácamo Rodrigo , Picco María Elisa , Anaya Laura , Rozengurt Enrique , Rey Osvaldo
Published: April 2019

Protein kinase D1 (PKD1) plays a vital role in signal transduction, cell proliferation, membrane trafficking, and cancer; however, the majority of the studies up to date had centered primarily on PKD1 functions in interphase, very little is known about its role during cell division. We previously demonstrated that during mitosis PKD1 is activated and associated with centrosomes, spindles, and midbodies. However, these observations did not address whether PKD1 was associated with mitosis regulation. Accordingly, we used rapidly acting PKD‐specific inhibitors to examine the contribution of PKD1 the sequence of events in mitosis. We found that although PKD1 overexpression did not affect mitosis progression, suppression of its catalytic activity by two structurally unrelated inhibitors (kb NB 142‐70 and CRT 0066101) induced a significant delay in metaphase to anaphase transition time. PKD1 inhibition during mitosis also produced the appearance of abnormal spindles, defects in chromosome alignment, and segregation as well as apoptosis. Thus, these observations indicate that PKD1 activity is associated with mitosis regulation.
Ketoacidosis in Euglycemic Patients With Type 2 Diabetes After Abdominal Surgery
Authors: Segebrecht Ray , Moncure Michael , Bennett Ashley , Geehan Douglas , Van Way Charles W. , Weide Lamont
Published: April 2019

Diabetic ketoacidosis is defined as hyperglycemia >250 mg/dL with metabolic acidosis of arterial pH <7.3, serum bicarbonate <18 mEq/L with positive urine and serum ketones and an anion gap >10. Euglycemic ketoacidosis has been reported in patients with type 2 diabetes and in patients with type 1 diabetes. However, as a surgical complication, euglycemic ketoacidosis has not been reported. We report 2 cases from 2 teaching tertiary care centers of patients with type 2 diabetes who developed high‐gap ketoacidosis in an intensive care unit while recovering from emergent abdominal surgery. Both patients developed altered mental status, metabolic acidosis with a bicarbonate level as low as 14 mEq/L, and an anion gap > 18, without hyperglycemia. Both patients had β‐hydroxybutyrate levels > 5 mmol/L.
Measuring near‐saturated hydraulic conductivity of soils by quasi unit‐gradient percolation—2. Application of the methodology
Authors: Sarkar Subharthi , Germer Kai , Maity Rajib , Durner Wolfgang
Published: April 2019

Sarkar et al. (this issue) proposed a laboratory measurement method for obtaining the hydraulic conductivity of soil at near‐saturated moisture conditions, bridging the gap between measurements that can be obtained with the evaporation method in the medium dry region, and measurements of the saturated conductivity by traditional methods. The method is based on a tension infiltration on a limited part of the surface of a soil sample and drainage of the sample at the same tension, leading to a divergent flow field. Despite equal tensions at top and bottom of the sample (“unit gradient”), the water flux in the sample is smaller than the corresponding value of the soil hydraulic conductivity at the applied tension. From numerical analysis of the flow problem, they concluded that unsaturated conductivity can be obtained with an accuracy of 10% for all texture classes of the USDA soil texture triangle. In this paper, we test the methodology for three different soil types using an appropriate apparatus. The results match well with independent saturated conductivity measurements on the wet side, and with unsaturated conductivity measurements in the medium moisture range that were obtained with the evaporation method.
Mechanical properties, corrosion behavior, and microstructure of Sr modified Al–9.2Mg–0.7Mn alloys
Authors: Zhang Peng , Xia Weijun , Yan Hongge , Chen Jihua , Su Bin , Li Xinyu , Li Xinlei
Published: April 2019

The influence of strontium (Sr) additions in the form of Mg–Sr master alloys from 0 to 0.6 wt% on the mechanical properties, corrosive nature, and microstructure of Al–9.2Mg–0.7Mn alloys is investigated. The material is studied in a fully annealed (O‐temper) and a sensitizing treatment at 150°C for 7 days. Here we demonstrate that there will be a new phase which might be (Al, Mg)17Sr2 formed in the as‐cast microstructure. When the Sr content is 0.2 wt%, under the premise that the mechanical properties of completely annealed alloy change little (relative to the matrix: the ultimate tensile strength increases by 8 MPa and the elongation only decrease by 1.6%), the intergranular corrosion resistance is significantly improved. The specific performance is that the mass loss from intergranular corrosion decreases by more than 53% from the addition of 0.2 wt% Sr after sensitizing.
Senescence as a main mechanism of Ritonavir and Ritonavir‐NO action against melanoma
Authors: Paskaš Svetlana , Krajnović Tamara , Basile Maria S. , Dunđerović Duško , Cavalli Eugenio , Mangano Katia , Mammana Santa , Al‐Abed Yousef , Nicoletti Ferdinando , Mijatović Sanja , Maksimović‐Ivanić Danijela
Published: April 2019

The main focus of this study is exploring the effect and mechanism of two HIV‐protease inhibitors: Ritonavir and Ritonavir‐nitric oxide (Ritonavir‐NO) on in vitro growth of melanoma cell lines. NO modification significantly improved the antitumor potential of Ritonavir, as the IC50 values of Ritonavir‐NO were approximately two times lower than IC50 values of the parental compound. Our results showed for the first time, that both compounds induced senescence in primary and metastatic melanoma cell lines. This transformation was manifested as a change in cell morphology, enlargement of nuclei, increased cellular granulation, upregulation of β‐galactosidase activity, lipofuscin granules appearance, higher production of reactive oxygen species and persistent inhibition of proliferation. The expression of p53, as one of the key regulators of senescence, was upregulated after 48 hours of Ritonavir‐NO treatment only in metastatic B16F10 cells, ranking it as a late‐response event. The development of senescent phenotype was consistent with the alteration of the cytoskeleton—as we observed diminished expression of vinculin, α‐actin, and β‐tubulin. Permanent inhibition of S6 protein by Ritonavir‐NO, but not Ritonavir, could be responsible for a stronger antiproliferative potential of the NO‐modified compound. Taken together, induction of senescent phenotype may provide an excellent platform for developing therapeutic approaches based on selective killing of senescent cells.
Exosome‐transmitted p120‐catenin suppresses hepatocellular carcinoma progression via STAT3 pathways
Authors: Cheng Zhangjun , Lei Zhengqing , Yang Pinghua , Si Anfeng , Xiang Daimin , Tang Xuewu , Guo Guangmeng , Zhou Jiahua , Hüser Norbert
Published: April 2019

Hepatocellular carcinoma (HCC) is a fatal disease with increasing morbidity and poor prognosis due to surgical recurrence and metastasis. Moreover, the molecular mechanism of HCC progression remains unclear. Although the role of p120‐catenin (p120ctn) in liver cancer is well studied, the effects of secreted p120ctn transported by exosomes are less understood. Here, we show that p120ctn in exosomes secreted from liver cancer cells suppresses HCC cell proliferation and metastasis and expansion of liver cancer stem cells (CSCs). Mechanically, exosome p120ctn inhibits HCC cell progression via the STAT3 pathway, and the STAT3 inhibitor S3I‐201 abolishes the observed effects on growth, metastasis, and self‐renewal ability between exosome p120ctn‐treated HCC cells and control cells. Taken together, we propose that p120ctn‐containing exosomes derived from cancer cells inhibit the progression of liver cancer and may offer a new therapeutic strategy.
Perceptions on Use of the Subjective Global Assessment Before and After It Became Part of Regular Practice
Authors: Laur Celia , Davidson Bridget , Keller Heather
Published: April 2019

Background

Subjective global assessment (SGA) is a standardized diagnostic tool for malnutrition and identifies those who would benefit from nutrition treatment. SGA has been validated in several patient populations; however, implementation in clinical practice is inconsistent. The objective of this study was to understand and contrast the perceptions on use of SGA before and after it became a regular practice for hospital dietitians.

Methods

The More‐2‐Eat implementation project provided the opportunity to undertake this qualitative study, as 5 hospitals adopted INPAC (Integrated Nutrition Pathway for Acute Care), which includes the use of SGA. Between 2015 and 2018, interviews were conducted with dietitians at baseline (n = 9), a year after implementation (n = 18), and a year after project completion (n = 6). Thematic analysis was conducted.

Results

Themes before SGA adoption included a desire for a malnutrition diagnosis and care planning; lacking comfort in use of SGA; and reflecting on SGA training needs. After a year of implementing INPAC and a year after project completion, themes described becoming a better clinician; allowing dietitians to see the right people, sooner; recognizing the variability in the treatment path for mildly/moderately malnourished (SGA B) patients; improving overall efficiency in delivery of care; and establishing policy and procedures to sustain and spread use of SGA.

Conclusion

Initially, dietitians were hesitant to use SGA. Adoption through a focused implementation study and experience with implementation of SGA changed these perceptions. Understanding these perceptions before and after use may support adoption of this useful diagnostic tool.
How does government funding affect nonprofits' program spending? Evidence from international development organizations
Authors: Lu Jiahuan , Zhao Jianzhi
Published: April 2019

Under the new governance models, the scope of government funding of nonprofit activities in service delivery and policy implementation is extensive. There is a long‐standing concern that government funding may compromise nonprofit operations and lead to unintended consequences. This research examines the concern by exploring the effect of government funding on nonprofits' spending on programs and services. Existing theories and empirical evidence propose competing arguments concerning the relationship between government funding and nonprofits' program spending. Using a 20‐year panel dataset of international development nonprofits registered with the United States Agency for International Development, we find that nonprofits receiving more government funding spend significantly higher proportions of their organizational resources on development programs. Government funding seems to increase nonprofits' program spending and to make them more focused on their mission‐related activities.
PTEN‐deficient prostate cancer is associated with an immunosuppressive tumor microenvironment mediated by increased expression of IDO1 and infiltrating FoxP3+ T regulatory cells
Authors: Vidotto Thiago , Saggioro Fabiano P. , Jamaspishvili Tamara , Chesca Deise L. , Picanço de Albuquerque Clarissa G. , Reis Rodolfo B. , Graham Charles H. , Berman David M. , Siemens D. Robert , Squire Jeremy A. , Koti Madhuri
Published: April 2019

Background

Accumulating evidence shows that tumor cell–specific genomic changes can influence the cross talk between cancer cells and the surrounding tumor microenvironment (TME). Loss of the PTEN tumor suppressor gene is observed in 20% to 30% of prostate cancers (PCa) when first detected and the rate increases with PCa progression and advanced disease. Recent findings implicate a role for PTEN in cellular type I interferon response and immunosuppression in PCa. However, the way that PTEN inactivation alters antitumor immune response in PCa is poorly understood.

Materials and Methods

To investigate the changes associated with PTEN loss and an immunosuppressive TME in PCa, we used CIBERSORT to estimate the relative abundance of 22 immune‐cell types from 741 primary and 96 metastatic tumors. Our in silico findings were then validated by immunohistochemical analysis of immune cells and IDO1 and PDL1 checkpoint proteins in a cohort of 94 radical prostatectomy specimens.

Results

FoxP3+ T regulatory cells (Tregs) were significantly increased in PTEN‐deficient PCa in all three public domain cohorts. Loss of PTEN in bone metastases was associated with lower CD8+ T‐cell abundance, but in liver metastasis, FoxP3+ Tregs were present at higher levels. PTEN‐deficient lymph node metastasis had a distinct profile, with high levels of CD8+ T cells. Moreover, we found that metastatic PCa presents higher abundance of FoxP3+ Treg when compared to primary lesions. Since PTEN‐deficient tumors are likely to be immunosuppressed as a consequence of increased FoxP3+ Tregs, we then evaluated the localization and expression of IDO1, PDL1 immune checkpoints, and the corresponding density of FoxP3+ Treg and CD8+ T cells using our validation cohort (n = 94). We found that IDO1 protein expression and FoxP3+ Treg density were higher in neoplastic glands compared with benign adjacent tissue. Moreover, higher densities of FoxP3+ Treg cells in both stromal (P = 0.04) and tumor (P = 0.006) compartments were observed in PTEN‐deficient tumors compared to tumors that retained PTEN activity. Similarly, IDO1 protein expression was significantly increased in the tumor glands of PTEN‐deficient PCa (P < 0.0001). Spearman correlation analysis showed that IDO1 expression was significantly associated with FoxP3+ Treg and CD8+ T‐cell density (P < 0.01).

Conclusions

Our findings imply that PTEN deficiency is linked to an immunosuppressive state in PCa with distinct changes in the frequency of immune cell types in tumors from different metastatic sites. Our data suggest that determining PTEN status may also help guide the selection of patients for future immunotherapy trials in localized and metastatic PCa.
Hyperglycemia and T Cell infiltration are associated with stromal and epithelial prostatic hyperplasia in the nonobese diabetic mouse
Authors: Aaron‐Brooks LaTayia M. , Sasaki Takeshi , Vickman Renee E. , Wei Lin , Franco Omar E. , Ji Yuan , Crawford Susan E. , Hayward Simon W.
Published: April 2019

Background

Prostatic inflammation and various proinflammatory systemic comorbidities, such as diabetes and obesity are associated with human benign prostatic hyperplasia (BPH). There is a paucity of in vivo models reflecting specific aspects of BPH pathogenesis. Our aim was to investigate the nonobese diabetic (NOD) mouse as a potential model for subsequent intervention studies.

Materials and Methods

We used the NOD mouse, a model of autoimmune inflammation leading to type 1 diabetes to examine the effects of systemic inflammation and diabetes on the prostate. We assessed changes in prostatic histology, infiltrating leukocytes, and gene expression associated with aging and diabetic status.

Results

Both stromal expansion and epithelial hyperplasia were observed in the prostates. Regardless of diabetic status, the degree of prostatic hyperplasia varied. Local inflammation was associated with a more severe prostatic phenotype in both diabetic and nondiabetic mice. Testicular atrophy was noted in diabetic mice, but prostate glands showed persistent focal cell proliferation. In addition, a prostatic intraepithelial neoplasia (PIN)‐like phenotype was seen in several diabetic animals with an associated increase in c‐Myc and MMP‐2 expression. To examine changes in gene and cytokine expression we performed microarray and cytokine array analysis comparing the prostates of diabetic and nondiabetic animals. Microarray analysis revealed several differentially expressed genes including CCL3, CCL12, and TNFS10. Cytokine array analysis revealed increased expression of cytokines and proteases such as LDLR, IL28 A/B, and MMP‐2 in diabetic mice.

Conclusion

Overall, NOD mice provide a model to examine the effects of hyperglycemia and chronic inflammation on the prostate, demonstrating relevance to some of the mechanisms present underlying BPH and potentially the initiation of prostate cancer.
Progress in the long battle against antimicrobial resistance
Authors: Chaplin Steve
Published: April 2019

The annual ESPAUR report provides a roundup of the achievements of the UK Five Year Antimicrobial Resistance Strategy 2013 to 2018 in terms of antimicrobial consumption, resistance, and stewardship in England. This article summarises the findings of the 2018 report.
Diagnosis and management of hypertension in primary care
Authors: Pucci Mark
Published: April 2019

Hypertension is a major modifiable risk factor for cardiovascular disease, but conflicting opinions remain about optimal blood pressure targets. This article discusses the various definitions of hypertension, provides guidance on management in primary care and advises when referral to secondary care is needed.
How social prescribing can benefit patients and prescribers
Authors: Dowden Angela
Published: April 2019

Social prescribing has the potential to address unmet patient needs and ease pressure on GPs and other healthcare professionals. This article investigates the evidence behind social prescribing, the benefits and drawbacks, and how it is gaining a higher profile in the NHS.
Managing severe asthma: back to the basic elements of care
Authors: Greener Mark
Published: April 2019

Severe asthma is potentially life threatening. Newer biological therapies may offer a beacon of hope for some patients. However, it is important to address the basics first, such as co‐morbidities that can contribute to poorly controlled asthma, and clear diagnostic guidelines and criteria for referral are still needed.
Mycobacterium shimoidei, a rare non‐tuberculous mycobacteria pathogen identified by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry
Authors: Nagano Hiroaki
Published: April 2019

Non‐tuberculous mycobacteria (NTM) cause several infectious diseases in humans. This study reports on Mycobacterium shimoidei infection in an immunosuppressed 61‐year‐old male with a background of emphysema. His chief complaint was haemoptysis. Chest computed tomography showed a large, thin‐walled cavitary lesion in the upper right lobe. Although NTM were identified in two separate expectorated sputum samples, DNA–DNA hybridization (DDH) failed to identify the species. M. shimoidei was finally identified using matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS). Following antimicrobial agent susceptibility tests, treatment with clarithromycin, levofloxacin, and ethambutol commenced. Six months post‐treatment, acid‐fast sputum culture was negative and repeat imaging demonstrated improvement of the radiographic abnormalities. This study aimed to assess the utility of MALDI‐TOF MS for successful identification of rare NTM species that are not identifiable by DDH. It is the first report of M. shimoidei from Okinawa, which is the only prefecture in Japan categorized as subtropical.
Role of Water and Defects in Photo‐Oxidative Degradation of Methylammonium Lead Iodide Perovskite
Authors: Ouyang Yixin , Shi Li , Li Qiang , Wang Jinlan
Published: April 2019

Great progress has been made in improving power conversion efficiency of perovskite solar cells (PSCs), and now the pressing issue is the poor stability of organic–inorganic halide perovskites under ambient conditions. Degradation of MAPbI3 induced by light and oxygen is a dominant factor limiting the lifetime of PSCs. Here, based on ab initio molecular dynamics simulations and first‐principles density functional theory calculations, the interactions between oxygen, water, and surface defects of MAPbI3 are investigated. It is found that the photo‐oxidation of MAPbI3 concentrates on the surface of the crystal, and this degradation can be accelerated by surface iodine vacancy and moisture. When oxygen coadsorbs with water molecules or oxygen adsorbs at the iodine vacancy on the MAPbI3 surface, the energy levels of adsorbed O2 are significantly lowered, facilitating the photoexcited electron transfer and the formation of reactive superoxide anions (O2−). The understanding of the role of water and defects in MAPbI3 photo‐oxidation from this study paves the way for further optimization of stable perovskite solar cells.
How heavy can neutralino dark matter be?
Authors: Fukuda Hajime , Luo Feng , Shirai Satoshi
Published: April 2019

Abstract

What is the upper limit of the mass of the neutralino dark matter whose thermal relic is consistent with the observation? If the neutralino dark matter and colored sparticles are extremely degenerated in mass, with a mass difference less than the QCD scale, the dark matter annihilation is significantly increased and enjoys the “second freeze-out” after the QCD phase transition. In this case, the neutralino dark matter with a mass much greater than 100 TeV can realize the correct dark matter abundance. We study the dark matter abundance and its detection in the case of such highly degenerated mass spectrum of the neutralino dark matter and colored supersymmetric particles.
Factorisation of soft gluons in multiparton scattering
Authors: Diehl Markus , Nagar Riccardo
Published: April 2019

Abstract

We show that soft gluons exchanged between the two colliding protons in multiparton scattering processes can be decoupled, such that their effects are described by the vacuum expectation values of Wilson lines. Our argument relies on nonabelian Ward identities and generalises the proof of factorisation for single Drell-Yan production given by Collins, Soper and Sterman.
Internet Gaming Disorder and Its Associated Personality Traits: A Systematic Review Using PRISMA Guidelines
Authors: Şalvarlı Şerife İnci , Griffiths Mark D.
Published: April 2019

For most individuals, videogame playing is a fun and enjoyable activity that brings many benefits. However, for a small minority, the activity can be problematic and has led to much research into “gaming disorder.” In explanations concerning the contributory factors to gaming disorder, personality traits have been increasingly studied. The present paper carried out a systematic review of available literature using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The inclusion criteria were (i) publication date between 2000 and 2018, (ii) being an empirical study, (iii) written in English and Turkish languages (the two languages spoken by the authors), (iv) published in a scholarly peer-reviewed journal, and (v) conducted an assessment of IGD and personality traits objectively. Studies were excluded from the review if they were (i) single-case studies, (ii) unpublished thesis and dissertation studies, and (iii) not published in a peer-reviewed journal. Following these procedures, 21 eligible empirical studies were included. Results demonstrated that 24 distinct personality traits had been examined in relation to IGD and that some of these traits were demonstrated as risk factors for gaming addiction (although not always in the same direction).
The Quest for Restructuring the Nigerian Nation: Myth or Reality? The Role of Libraries in Amplifying the Debate
Authors: Dapo-Asaju Harriet Seun , Bamgbose Oludayo John
Published: April 2019

The primary duty of library and information professionals is to render information services to their patrons. Although the information provided often shapes public opinion and could help in making informed decisions, librarians and other information professionals often steer clear of politics and the processes that lead to emergence of leaders, even though their activities could be greatly affected by the nature of those who emerge as political leaders. It is against this background that this research sought to take a look at the issue of political restructuring, which has been a burning issue within the Nigerian political space, and what roles Nigerian librarians could play in the realization of the demands of restructuring in Nigeria. This article is of the view that besides being perceived as relevant in the scheme of things in Nigeria, librarians’ engagement could further positively impact on the condition of service of librarians and their public perception.
From Enslavement to Emancipation: Naming Practices in the Danish West Indies
Authors: Abel Sarah , Tyson George F. , Palsson Gisli
Published: April 2019

In most contexts, personal names function as identifiers and as a locus for identity. Therefore, names can be used to trace patterns of kinship, ancestry, and belonging. The social power of naming, however, and its capacity to shape the life course of the person named, becomes most evident when it has the opposite intent: to sever connections and injure. Naming in slave society was primarily practical, an essential first step in commodifying human beings so they could be removed from their roots and social networks, bought, sold, mortgaged, and adjudicated. Such practices have long been integral to processes of colonization and enslavement. This paper discusses the implications of naming practices in the context of slavery, focusing on the names given to enslaved Africans and their descendants through baptism in the Lutheran and Moravian churches in the Danish West Indies. Drawing on historiographical accounts and a detailed analysis of plantation and parish records from the island of St. Croix, we outline and contextualize these patterns and practices of naming. We examine the extent to which the adoption of European and Christian names can be read as an effort toward resistance and self-determination on the part of the enslaved. Our account is illuminated by details from the lives of three former slaves from the Danish West Indies.
Increased Variability of Thailand's Chao Phraya River Peak Season Flow and Its Association With ENSO Variability: Evidence From Tree Ring δ18O
Authors: Xu Chenxi , Buckley Brendan M. , Promchote Parichart , Wang S.‐Y. Simon , Pumijumnong Nathsuda , An Wenling , Sano Masaki , Nakatsuka Takeshi , Guo Zhengtang
Published: April 2019

We present a statistically robust reconstruction of Thailand's Chao Phraya River peak season streamflow (CPRPF) that spans the 202 years from 1804 to 2005 CE. Our reconstruction is based on tree ring δ18O series derived from three Pinus merkusii sites from Laos and Thailand. The regional δ18O index accounts for 57% of the observed variance of CPRPF. Spatial correlation and 21‐year running correlation analyses reveal that CPRPF is greatly influenced by regional precipitation variations associated with the El Niño–Southern Oscillation (ENSO). Periods of enhanced and reduced ENSO activity are associated with strong and weak ENSO‐streamflow correlation, respectively. At the longer timescale, the Pacific Decadal Oscillation (PDO) appears to modulate the ENSO‐streamflow correlations, with the most extreme flood events along the Chao Phraya River occurring during periods of increased frequency of La Niña events that coincide with extended cold phases of the PDO. The CPRPF reconstruction could aid management planning for Thailand's water resources.
The Shadow Price of Irrigation Water in Major Groundwater‐Depleting Countries
Authors: Bierkens Marc F. P. , Reinhard Stijn , de Bruijn Jens A. , Veninga Willeke , Wada Yoshihide
Published: April 2019

In many semiarid regions with irrigation, the depletion rate of groundwater resources has increased substantially during the last decades. A possible reason for this is that the price that users pay for their water does not reflect its scarcity and value. An alternative way to assess the perceived value of water is calculating its shadow price, which is defined here as the marginal value produced, and relates to the efficiency gain from current reallocation. Here we determine the shadow price of water used for irrigation for the most important groundwater‐depleting countries and for four staple crops and one cash crop. To quantify the shadow price, the relation between the output and the water input is represented using production functions. We use globally available panel data on country‐specific crop yields and prices together with crop‐specific water consumption, calculated with the global hydrological model PCR‐GLOBWB, to parameterize the production function by country and crop with econometric analyses. Our results show that the variation of shadow prices for staple crops within several countries is high, indicating economically inefficient use of water resources, including nonrenewable groundwater. We also analyze the effects of reallocating irrigation water between crops, showing that changes in water allocation could lead to either an increase in the economic efficiency of water use or large reductions in irrigation water consumption. Our study thus provides a hydroeconomic basis to stimulate sustainable use of finite groundwater resources globally.
Mobility and Bioavailability of Sediment Phosphorus in Urban Stormwater Ponds
Authors: Frost Paul C. , Prater Clay , Scott Andrew B. , Song Keunyea , Xenopoulos Marguerite A.
Published: April 2019

Stormwater ponds can serve as retention hotspots for phosphorus (P) moving out of the urban environment. This retention may be reduced by P speciation that reduces the bioavailability of P to primary producers and alters its mobility in sediments. Here we examined the mobility and fate of dissolved P in urban stormwater ponds with a set of complementary field measurements and short‐term laboratory and field experiments. We measured the types and amount of P in water column and sediments of urban stormwater ponds. We further assessed the mobility of different P types in pond sediments in the field and rates of P release from sediment cores maintained under laboratory conditions. Finally, we assessed P uptake rates by pond algal communities using short‐term bioassay experiments. We found that dissolved organic P was highly prevalent in urban pond water and sediments and that this type of P was mobile within sediments and could be released under high or low O2 conditions. We also found highly variable P demand by algae among stormwater ponds and that algal growth responses to P was correlated to water column N:P ratios. Altogether, our results indicate an important role for organic phosphorus cycling in urban stormwater ponds, which likely constrains the overall retention efficiency in these aquatic ecosystems.