bluuebunny/crossref_metadata_2025 huggingface dataset:
SMAC mimetics as potential cancer therapeutics in myeloid malignancies
Authors: Boddu Prajwal , Carter Bing Z. , Verstovsek Srdan , Pemmaraju Naveen
Published: March 2019

Evasion of apoptosis has been identified as one of the essential hallmarks of cancer. Inhibitor of apoptosis proteins (IAPs) are implicated in a host of myeloid malignancies, providing the rationale for strategies aimed at neutralizing IAPs to lower the cancer cell apoptosis threshold. Modes of IAP antagonism may include down‐regulating IAP expression, up‐regulating endogenous pro‐apoptotic proteins, such as tumour necrosis factor‐α or Fas ligand, or directly antagonizing IAP activity against caspases. Direct targeting of IAPs using mimetics of the second mitochondria‐derived activator of caspase (SMAC) protein has shown therapeutic promise by sensitizing the effect of chemotherapy on malignant cells. In pre‐clinical studies, SMAC mimetics have demonstrated broad synergistic activity with a wide range of therapeutics, including cytotoxic chemotherapy, receptor tyrosine kinase inhibitors, agents targeting death receptors and alternative mechanisms of cell death, such as necroptosis or autophagy and immune check point blockade. SMAC mimetics represent a novel approach for further investigation in patients with high‐risk, chemo‐refractory blood cancers, as single agents or in thoughtfully selected combinations. In this review, we discuss the development and therapeutic rationale of small molecule SMAC mimetics, with an emphasis on agents in clinical development for myeloid malignancies.
Silencing of DLEU2 suppresses pancreatic cancer cell proliferation and invasion by upregulating microRNA‐455
Authors: Xu Baoli , Gong Xufei , Zi Li , Li Guang , Dong Shuxiao , Chen Xinrui , Li Yutao
Published: March 2019

Long noncoding RNA (lncRNA) DLEU2 has been shown to be dysregulated in several type of tumor. However, the potential biological roles and molecular mechanisms of DLEU2 in pancreatic cancer (PC) progression are poorly understood. In this study, we found that the DLEU2 level was substantially upregulated in PC tissues and PC cell lines, and significantly associated with poor clinical outcomes in PC patients. Overexpression of DLEU2 significantly induced PC cell proliferation and invasion, whereas knockdown of DLEU2 impaired cell proliferation and invasion in vitro. Furthermore, bioinformatics analysis, luciferase reporter assay, and RNA immunoprecipitation assay revealed that DLEU2 directly bond to microRNA‐455 (miR‐455) and functioned as an endogenous sponge for miR‐455, which could remarkably suppress cell growth and invasion. We also determined that SMAD2 was a direct target of miR‐455, and the restoration of SMAD2 rescued cell growth and invasion that were reduced by DLEU2 knockdown or miR‐455 overexpression. In addition, low miR‐455 expression and high SMAD2 expression was correlated with poor patient survival. These results indicate that DLEU2 is an important promoter of PC development, and targeting the DLEU2/miR‐455/SMAD2 pathway could be a promising therapeutic approach in the treatment of PC.
Cinobufagin suppresses colorectal cancer angiogenesis by disrupting the endothelial mammalian target of rapamycin/hypoxia‐inducible factor 1α axis
Authors: Li Xiaowu , Chen Chunhui , Dai Yu , Huang Chengzhi , Han Qinrui , Jing Linlin , Ma Ye , Xu Yihua , Liu Yawei , Zhao Liang , Wang Junjiang , Sun Xuegang , Yao Xueqing
Published: March 2019

Inducing angiogenesis is a hallmark of cancers that sustains tumor growth and metastasis. Neovascularization is a surprisingly early event during the multistage progression of cancer. Cinobufagin, an important bufadienolide originating from Chan Su, has been clinically used to treat cancer in China since the Tang dynasty. Here, we show that cinobufagin suppresses colorectal cancer (CRC) growth in vivo by downregulating angiogenesis. The hierarchized neovasculature is significantly decreased and the vascular network formation is disrupted in HUVEC by cinobufagin in a dose‐dependent way. Endothelial apoptosis is observed by inducing reactive oxygen species (ROS) accumulation and mitochondrial dysfunction which can be neutralized by N‐acetyl‐l‐cysteine (NAC). Expression of hypoxia‐inducible factor 1α (HIF‐1α) is reduced and phosphorylation of mTOR at Ser2481 and Akt at Ser473 is downregulated in HUVEC. Endothelial apoptosis is triggered by cinobufagin by stimulation of Bax and cascade activation of caspase 9 and caspase 3. Increased endothelial apoptosis rate and alterations in the HIF‐1α/mTOR pathway are recapitulated in tumor‐bearing mice in vivo. Further, the anti‐angiogenesis function of cinobufagin is consolidated based on its pro‐apoptotic effects on an EOMA‐derived hemangioendothelioma model. In conclusion, cinobufagin suppresses tumor neovascularization by disrupting the endothelial mTOR/HIF‐1α pathway to trigger ROS‐mediated vascular endothelial cell apoptosis. Cinobufagin is a promising natural anti‐angiogenetic drug that has clinical translation potential and practical application value.
The Civic Side of Diversity: Ambivalence and Belonging at the Neighborhood Level
Authors: Hoekstra Erin , Gerteis Joseph
Published: March 2019

Although diversity has become a cherished ideal for Americans, a growing literature suggests that many are also ambivalent about lived experiences of diversity. Focusing on three historically homogeneous neighborhoods in Atlanta, Minneapolis, and Los Angeles, this paper explores the “civic talk” used to express this ambivalence through interrelated frames of social order and civic engagement. In all three neighborhoods, long–term residents and neighborhood association members speak fluently about race, class, and other forms of diversity in their neighborhoods. Yet when they assess who “belongs” in the neighborhoods, the discussion is coded in civic terms. This framing enables neighborhood association members to act as gatekeepers, wielding civic discourse in ways that reinforce traditional neighborhood boundaries and social hierarchies, while maintaining structural inequalities.
Feeling at Home in the Neighborhood: Belonging, the House and the Plaza in Helsinki and Madrid
Authors: Kuurne (Ketokivi) Kaisa , Gómez M. Victoria
Published: March 2019

Drawing on multisited ethnographic fieldwork in two historic, attractive, and socially mixed neighborhoods, Kumpula in Helsinki and Malasaña in Madrid, this paper examines what makes people feel at home (or not) in their neighborhood. Marrying the literatures on social belonging and materiality, we analyze the interactions through which local places, people, and materials become familiar and personal. We identify the house in Kumpula and the plaza in Madrid as “everyday totems” that weave local life and community together. In both neighborhoods, the testimonies of home are accompanied with an attachment to the local totem and related lifestyle, but the house and the plaza generate different everyday politics of belonging. House–based belonging in Kumpula requires resources and long–term engagement that over time contributes to a personal, but rather exclusive web of belonging. Plaza–based belonging in Malasaña is more inclusive and elastic, but joining the web of belonging requires time and sociability.
Cultural Archipelagos and Immigrants’ Experiences
Authors: Carrillo Héctor
Published: March 2019

In his essay in this issue of City & Community, Amin Ghaziani describes cultural archipelagos as providing a “conceptual framework” to explain “the unexpected emergence of new clusters for specific subgroups of queer people” in cities that are known for their distinguishable “gayborhoods.” This essay centers the experiences of transnational immigrants from countries in the so–called global South who relocate to cities in richer countries such as the United States. While transnational immigrants’ distinct experiences pre– and post–migration confirm the usefulness of the cultural archipelagos framework, those experiences also clarify that cultural archipelagos need not be conceived (as Ghaziani implies) as a subsequent stage of gay/queer culture that necessarily and always is preceded by the formation of strong and identifiable gayborhoods. I therefore argue that the experiences of transnational gay/queer immigrants invite us to take a step back and consider how those immigrants relate or not to the notion of gayborhoods in the first place.
Cultural Archipelagos: New Directions in the Study of Sexuality and Space
Authors: Ghaziani Amin
Published: March 2019

Research on sexuality and space makes assumptions about spatial singularity: Across the landscape of different neighborhoods in the city, there is one, and apparently only one, called the gayborhood. This assumption, rooted in an enclave epistemology and theoretical models that are based on immigrant migration patterns, creates blind spots in our knowledge about urban sexualities. I propose an alternative conceptual framework that emphasizes spatial plurality. Drawing on the location patterns of lesbians, transgender individuals, same–sex families with children, and people of color, I show that cities cultivate “cultural archipelagos” in response to the geo–sexual complexities that arise from within–group heterogeneity. Rather than inducing spatially singular or scholastic outcomes, as some scholarship predicts, subgroup variations produce diverse yet distinct types of queer spaces. The analytic frame of cultural archipelagos suggests more generally that we cannot categorize urban or social worlds using simple binaries such as “the gayborhood” versus all other undifferentiated straight spaces. Thinking in terms of plurality provides a more generative approach to advance the study of sexuality and space.
A fast algorithm for local feature selection in data classification
Authors: Hoseininejad Fereshteh Sadat , Forghani Yahya , Ehsani Omid
Published: March 2019

Typical feature selection methods select a global feature subset that is applied over all regions of the sample space. In localized feature selection (LFS), each region of the sample space is associated with its own optimized feature subset. This allows the feature subset to adapt to local variations in the sample space. Feature subsets are selected such that within a localized region, within‐class distances are minimized and between‐class distances are maximized. LFS outperforms global feature selection methods. LFS is solved using a randomized rounding approach when weights of regions are fixed. Randomized rounding is a too time‐consuming algorithm. In this paper, we show that LFS has a closed‐form solution when weights of regions are fixed. Using this closed‐form solution can decrease the runtime of solving LFS substantially. Experimental results on real datasets confirm that the classification error rate of our proposed method and the randomized rounding‐based method are the same; the runtime of our proposed method is much better than that of the randomized rounding‐based method; and the classification error rate of our proposed method and the randomized rounding‐based method outperforms the state‐of‐the‐art feature selection methods.
Trustee reputation in securitization: When does it matter?
Authors: Deku Solomon Y. , Kara Alper , Marques‐Ibanez David
Published: March 2019

We consider the role of trustees–who are nominated to protect the interests of investors–in securitization pricing and whether investors rely on them to mitigate risks. In particular, we examine the effect of trustee reputation on initial yield spreads of European mortgage‐backed security (MBS) issuances between 1999 and the first half of 2007. We find that engaging reputable trustees led to lower spreads during the credit boom period prior to the 2007–2009 financial crisis. Our findings suggest that trustees’ reputation was considered by investors to be more important when risk assessment became more challenging.
Economic volatility and financial markets: The case of mortgage‐backed securities
Authors: Antinolfi Gaetano , Brunetti Celso
Published: March 2019

The volatility of aggregate economic activity in the United States decreased markedly in the mid‐eighties. The decrease involved several components of GDP and has been linked to a more stable economic environment, identified by smaller shocks, more effective policy, and a diverse set of innovations in technology as well as financial markets. We study one such financial innovation, and document a negative relation between the rapid growth of mortgage‐backed securities and the volatility of GDP and some of its components from the mid‐1970s to the late 1990s. We also document that this relation changed sign, from negative to positive, in the early 2000s.
Can Loan Valuation Adjustment (LVA) approach immunize collateralized debt from defaults?
Authors: Wojakowski Rafal M. , Ebrahim M. Shahid , Jaafar Aziz , Osman Salleh Murizah
Published: March 2019

This study focuses on structuring tangible asset backed loans to inhibit their endemic option to default. We adapt the pragmatic approach of a margin loan in the configuring of collateralized debt to yield a quasi‐default‐free facility. We link our practical method to the current Basel III (2017) regulatory framework. Our new concept of the Loan Valuation Adjustment (LVA) and novel method to minimize the LVA converts the risky loan into a quasi risk‐free loan and achieves value maximization for the lending financial institution. As a result, entrepreneurial activities are promoted and economic growth invigorated. Information asymmetry, costly bailouts and resulting financial fragility are reduced while depositors are endowed with a safety net equivalent to deposit insurance but without the associated moral hazard between risk‐averse lenders and borrowers.
Annual report readability and stock liquidity
Authors: Boubaker Sabri , Gounopoulos Dimitrios , Rjiba Hatem
Published: March 2019

We examine the effect of annual report textual complexity on firms’ stock liquidity. Using techniques from computational linguistics, we predict and find that less readable filings are associated with lower stock liquidity. Our study provides evidence that difficult‐to‐read annual reports hinder investors’ ability to process and analyze information contained in corporate annual reports, reducing thereby their willingness to trade which decreases stock liquidity. Our findings are robust to a battery of sensitivity tests, including endogeneity, use of alternative estimation techniques, and use of alternative liquidity and readability proxies.
Morphological and biomechanical responses of floodplain willows to tidal flooding and salinity
Authors: Markus‐Michalczyk Heike , Zhu Zhenchang , Bouma Tjeerd J.
Published: March 2019

Willow floodplain plantations have been proposed as part of plans to create tidal wetlands for ecosystem‐based flooding defence of estuaries. Forests characterised by willows (genus Salix) are found in riparian floodplains in Europe up to the river mouth, e.g. up to tidal wetlands along the Scheldt and Elbe. However, sea level rise accompanied by accelerated tidal flooding and salt‐water intrusion may limit the effectiveness of willows for flooding defence of floodplains located at estuaries near their junction with the sea.

We studied juvenile floodplain willows (Salix alba and Salix viminalis) in a mesocosm experiment with a combined tidal flooding and salinity treatment in a climate chamber. Permanent and semi‐permanent flooding of roots and periodic flooding of shoots reduced shoot length, shoot biomass, bending capacity, and breaking resistance. However, partial submergence did not affect shoot morphology or biomechanical traits. In S. viminalis, shoot diameter was generally larger compared to S. alba and this larger diameter resulted in a higher maximum breaking force. However, S. alba showed more consistent results in diameter size with lower variation than S. viminalis. The applied salinity treatments of up to 2 parts per thousand did not have significant effects on willow shoot morphology or biomechanical traits.

We conclude that juveniles of both willow species are resilient to periodic tidal flooding and salinity values of up to 2 parts per thousand with respect to shoot traits. However, the reduction in shoot growth and biomechanical properties with permanent flooding suggests that juvenile willow establishment will be sensitive to sea level rise and increased flooding, and will result in changes in the vegetation of tidal freshwater wetlands. Salix alba and S. viminalis may serve in innovative capacities as supplementary features for estuarine flooding defence in tidal wetlands and tools for ecological restoration at appropriate sites. However, studies addressing whole ecosystems at a large scale are recommended before using S. alba and S. viminalis in floodplain plantations to protect river estuaries.
Paleoenvironmental proxies and what the Xiamaling Formation tells us about the mid‐Proterozoic ocean
Authors: Zhang Shuichang , Wang Xiaomei , Wang Huajian , Bjerrum Christian J. , Hammarlund Emma U. , Haxen Emma R. , Wen Hanjie , Ye Yuntao , Canfield Donald E.
Published: March 2019

The Mesoproterozoic Era (1,600–1,000 million years ago, Ma) geochemical record is sparse, but, nevertheless, critical in untangling relationships between the evolution of eukaryotic ecosystems and the evolution of Earth‐surface chemistry. The ca. 1,400 Ma Xiamaling Formation has experienced only very low‐grade thermal maturity and has emerged as a promising geochemical archive informing on the interplay between climate, ecosystem organization, and the chemistry of the atmosphere and oceans. Indeed, the geochemical record of portions of the Xiamaling Formation has been used to place minimum constraints on concentrations of atmospheric oxygen as well as possible influences of climate and climate change on water chemistry and sedimentation dynamics. A recent study has argued, however, that some portions of the Xiamaling Formation deposited in a highly restricted environment with only limited value as a geochemical archive. In this contribution, we fully explore these arguments as well as the underlying assumptions surrounding the use of many proxies used for paleo‐environmental reconstructions. In doing so, we pay particular attention to deep‐water oxygen‐minimum zone environments and show that these generate unique geochemical signals that have been underappreciated. These signals, however, are compatible with the geochemical record of those parts of the Xiamaling Formation interpreted as most restricted. Overall, we conclude that the Xiamaling Formation was most likely open to the global ocean throughout its depositional history. More broadly, we show that proper paleo‐environmental reconstructions require an understanding of the biogeochemical signals generated in all relevant modern analogue depositional environments. We also evaluate new data on the δ98Mo of Xiamaling Formation shales, revealing possible unknown pathways of molybdenum sequestration into sediments and concluding, finally, that seawater at that time likely had a δ98Mo value of about 1.1‰.
The Causal Effects of the Minimum Wage Introduction in Germany – An Overview
Authors: Caliendo Marco , Wittbrodt Linda , Schröder Carsten
Published: March 2019

In 2015, Germany introduced a statutory hourly minimum wage that was not only universally binding but also set at a relatively high level. We discuss the shortrun effects of this new minimum wage on a wide set of socioeconomic outcomes, such as employment and working hours, earnings and wage inequality, dependent and selfemployment, as well as reservation wages and satisfaction. We also discuss difficulties in the implementation of the minimum wage and the measurement of its effects related to non-compliance and suitability of data sources. Two years after the minimum wage introduction, the following conclusions can be drawn: while hourly wages increased for low-wage earners, some small negative employment effects are also identifiable. The effects on aspired goals, such as poverty and inequality reduction, have not materialised in the short run. Instead, a tendency to reduce working hours is found, which alleviates the desired positive impact on monthly income. Additionally, the level of noncompliance was substantial in the short run, thus drawing attention to problems when implementing such a wide reaching policy.
Building multiple nests is associated with reduced breeding performance in a south temperate population of Grass Wrens Cistothorus platensis platensis
Authors: Llambías Paulo Emilio , Jefferies María Milagros , Cáceres Apaza Daniel Pascual , Garrido Paula Sabrina , Zarco Agustín , Arrieta Ramiro Santiago , Bender José Benjamin
Published: March 2019

Grass Wrens Cistothorus platensis build two types of non‐breeding nest structures: platforms and dummy nests. Platforms are rudimentary accumulations of grasses concealed between vegetation. Dummy and breeding nests are dome‐shaped with a similar structural layer. We used a nest‐removal experiment and observational data to evaluate several hypotheses regarding the adaptive significance of building multiple nests in a south temperate population of Grass Wrens. Building non‐breeding nests was not a strategy of males to attract additional females, as most of these nests were built after pair formation and both sexes collaborated during building. Building non‐breeding nests was not a post‐pairing display as the presence of multiple nests did not increase female investment in the breeding attempt: clutch size and female provisioning to nestlings did not differ between experimental and control territories where no non‐breeding nests were removed. Similarly, in non‐manipulated territories, clutch size and female provisioning were not correlated with the number of non‐breeding nests or with males’ nest‐building effort. Contrary to this hypothesis, the number of non‐breeding nests was associated with delayed clutch initiation and reduced hatching success. The presence of non‐breeding nests did not reduce nest predation and brood parasitism, which did not differ between experimental and control territories. We did not detect differences in concealment between non‐breeding and breeding nests, suggesting that non‐breeding nests were not the result of abandonment before egg‐laying to reduce subsequent nest predation. Dummy nests did not provide shelter; they were not used frequently for roosting over the breeding season and were not maintained during the non‐breeding season. We suggest that building non‐breeding nests may be an attempt by males to manipulate the decision of females to breed with a mate they might otherwise reject or to start reproduction earlier than optimal for the females.
The roles of geography, climate and sexual selection in driving divergence among insect populations on mountaintops
Authors: Pato Joaquina , Illera Juan Carlos , Obeso José Ramón , Laiolo Paola
Published: March 2019

Aim

Analysing the drivers of intraspecific variation and how reproductive barriers arise is an essential step to infer the mechanisms of biogeographic differentiation. In populations of a specialized alpine species, we explore the role of geography and climate in the divergence of genetic, morphological and acoustic characters, and analyse the functional consequences of variation on mate choice.

Taxon

Chorthippus cazurroi (Orthoptera: Caelifera, Acrididae, Gomphocerinae).

Location

The entire distribution of the species (23 populations from six massifs of the Cantabrian Mountains, NW Spain).

Methods

First, we analysed the extent of intraspecific spatial divergence and the covariation among climatic niche, genetic (mtDNA), acoustic (song structure) and morphological (body size) traits. Then, we analysed the consequences of phenotypic variation by means of a crossing experiment among populations from different elevations. This served to test for differences in sexual selection among body size‐divergent populations and for the relationship between male traits, female preference and reproduction.

Results

Genetic, morphologic and acoustic divergence increased with geographic distance. Female morphology was also affected by climate variation, while male one tightly covaried with the song differentiation. Females more closely approached males investing more time in song activities, but weakly responded to the rest of acoustic features and morphological variation. They also distanced themselves slightly more from males from different populations, although this behaviour did not lead to clear differences in reproductive parameters.

Main conclusions

The process of colonization of mountain massifs has led to significant genetic and phenotypic changes in C. cazurroi. Phenotypic divergence does not constitute a strong intrinsic barrier to reproduction and is largely unpaired from female preference, overall suggesting that sexual selection is a minor actor in the process of differentiation as compared, for instance, to drift. This does not exclude that traits associated with individual condition are under strong selection and, therefore, do not vary so extensively. This study dismisses the idea that alpine specialists with narrow distributions lack genetic and phenotypic variability, and highlights the importance of synthesizing biogeographic and experimental approaches to obtain stronger and deeper inferences about the dynamics and mechanisms of biological differentiation.
Increased level of fibrinogen chains in the proteome of blood platelets in secondary progressive multiple sclerosis patients
Authors: Bijak Michal , Olejnik Alicja , Rokita Bozena , Morel Agnieszka , Dziedzic Angela , Miller Elzbieta , Saluk‐Bijak Joanna
Published: March 2019

Epidemiological studies indicate a high risk of stroke, heart failure and myocardial infarction in patients with multiple sclerosis, especially in its secondary progressive (SPMS) phase. Some ischaemic events are directly associated with abnormal platelet functions and their prothrombotic activity. Recent reports, including this study, confirm the increased activation of circulating platelets in SPMS, and also show increased platelet reactivity, among other responses, as well as strong aggregation. In this current study, we conducted a comparative analysis of the platelet proteome in SPMS patients and in healthy controls, to demonstrate the quantitative and qualitative differences likely to affect functional changes observed in SPMS. During densitometry evaluation of 2‐D fluorescence difference gel electrophoresis, we observed differences between the electrophoretic patterns of SPMS platelets and the control samples. To determine a detailed characterisation of the proteome changes in the SPMS patients’ blood platelets, in the next stage, we performed mass spectrometry of selected spots and indicated the increased presence of four proteins (fibrinogen, α‐2 macroglobulin, septin‐14 and tubulin β‐1 chain). The most important of these is the increased amount of prothrombotic protein, fibrinogen, which seems to confirm the accuracy of the imaging and potentially explains the increased risk of platelet‐origin thrombotic events. This study provides new knowledge of the potential existence of the molecular mechanisms responsible for the acceleration of the platelet pro‐coagulant function in SPMS. This can help to identify new targets for therapy, which can then be used not only in the second stage of the disease.
Efficacy of tildrakizumab for moderate‐to‐severe plaque psoriasis: pooled analysis of three randomized controlled trials at weeks 12 and 28
Authors: Papp K.A. , Reich K. , Blauvelt A. , Kimball A.B. , Gooderham M. , Tyring S.K. , Sinclair R. , Thaci D. , Li Q. , Cichanowitz N. , Green S. , La Rosa C.
Published: March 2019

Background

Efficacy of tildrakizumab for plaque psoriasis was demonstrated in randomized, placebo‐controlled trials.

Objective

To consolidate tildrakizumab efficacy results by pooling data.

Methods

Data (N = 2081) from tildrakizumab 100 mg, tildrakizumab 200 mg and placebo groups in three trials were pooled.

Results

Proportions of Psoriasis Area and Severity Index (PASI) 75 responders at week 12 were better with tildrakizumab 100 mg (62.3%) and tildrakizumab 200 mg (64.8%) vs. placebo (5.6%; P < 0.0001) and for PASI 90, PASI 100 and Physician's Global Assessment (PGA) ‘clear’ or ‘minimal’ vs. placebo (P < 0.0001). Responses increased from weeks 12 to 28. Week 12 PASI and PGA responses to tildrakizumab vs. placebo were numerically greater in patients with lower vs. higher bodyweight and were better with tildrakizumab 200 mg than tildrakizumab 100 mg for patients with higher bodyweight. Week 12 PASI 75 responses vs. placebo with tildrakizumab 100 mg were similar between patients with (55.0%) or without (56.7%) prior biologics. PASI 90, PASI 100 and PGA responses were generally higher in patients without prior biologics. Week 8 PASI 50 response predicted PASI 90 response.

Conclusion

Pooled data confirmed the efficacy of tildrakizumab for moderate‐to‐severe plaque psoriasis.
Finasteride for androgenetic alopecia is not associated with sexual dysfunction: a survey‐based, single‐centre, controlled study
Authors: Haber R.S. , Gupta A.K. , Epstein E. , Carviel J.L. , Foley K.A.
Published: March 2019

Background

The occurrence of sexual dysfunction side‐effects associated with finasteride use in men with androgenetic alopecia (AGA) is thought to be less prevalent than is publicized. There is a need to investigate sexual dysfunction among finasteride users with population‐based controls.

Objective

To evaluate the presence of sexual dysfunction in men using finasteride or not using finasteride.

Method

Adult men visiting a dermatologist's office for any reason were asked to complete a survey including a modified version of the Arizona Sexual Experience Scale (ASEX) to assess the presence of sexual dysfunction with and without finasteride use.

Results

Data from 762 men aged 18–82 were collected: 663 finasteride users and 99 non‐finasteride users. There were no significant differences between finasteride users and non‐user controls in reporting sexual dysfunction using the ASEX. Regression analysis indicated that self‐reporting libido loss and reduced sexual performance, not finasteride use, predict a higher ASEX score.

Conclusion

The use of finasteride does not result in sexual dysfunction in men with AGA. These data are consistent with other large survey‐based controlled studies.
Ethical considerations in fish research
Authors: Sloman Katherine A. , Bouyoucos Ian A. , Brooks Edward J. , Sneddon Lynne U.
Published: March 2019

Fishes are used in a wide range of scientific studies, from conservation research with potential benefits to the species used to biomedical research with potential human benefits. Fish research can take place in both laboratories and field environments and methods used represent a continuum from non‐invasive observations, handling, through to experimental manipulation. While some countries have legislation or guidance regarding the use of fish in research, many do not and there exists a diversity of scientific opinions on the sentience of fish and how we determine welfare. Nevertheless, there is a growing pressure on the scientific community to take more responsibility for the animals they work with through maximising the benefits of their research to humans or animals while minimising welfare or survival costs to their study animals. In this review, we focus primarily on the refinement of common methods used in fish research based on emerging knowledge with the aim of improving the welfare of fish used in scientific studies. We consider the use of anaesthetics and analgesics and how we mark individuals for identification purposes. We highlight the main ethical concerns facing researchers in both laboratory and field environments and identify areas that need urgent future research. We hope that this review will help inform those who wish to refine their ethical practices and stimulate thought among fish researchers for further avenues of refinement. Improved ethics and welfare of fishes will inevitably lead to increased scientific rigour and is in the best interests of both fishes and scientists.
Diffusion of polyphenols from alginate, alginate/chitosan, and alginate/inulin particles
Authors: Pravilović Radoslava N. , Balanč Bojana D. , Djordjević Verica B. , Bošković‐Vragolović Nevenka M. , Bugarski Branko M. , Pjanović Rada V.
Published: March 2019

Thymus serpyllum L (thyme) aqueous extract was encapsulated within three different types of particles. Thus, electrostatic extrusion was applied to obtain alginate, alginate/chitosan, and alginate/inulin particles with encapsulated extract which is known as a rich source of polyphenolic compounds. The effect of admixed chitosan and inulin was evaluated from the point of polyphenols release by using Franz diffusion cell. The alginate/chitosan particles exhibited the effective diffusion coefficient of 1.94·10−9 ·m2 s−1 which was about 2.7 times lower in comparison to that of alginate/inulin particles and about 6.3 times lower than the effective diffusion coefficient of plain alginate particles. Swelling studies also confirmed decreased permeability of composite particles compared to plain alginate particles. In addition, according to the Korsmeyer–Peppas model, the composite particles exhibited anomalous diffusion of polyphenols controlled by molecular diffusion and polymer relaxation.

Practical applications

The calcium alginate particles are meant for delivery of biologically active compounds in foods with added value. Coating of alginate particles using chitosan has been investigated to control release of encapsulated biologically active compounds, but also as an improver of the particles structure.
Medical Faculty Beliefs: Self‐Rated Importance and Confidence in Teaching Geriatrics Primary Care
Authors: Hyer Kathryn , Jester Dylan J. , Badana Adrian N. S. , D'Aoust Rita , Robinson Bruce E. , Guerra Lucy , Michael Melanie , Molinari Victor , Schwartz Amy , Schocken Dawn , Wills Todd , Wilson Cheryl , Andel Ross
Published: March 2019

OBJECTIVES

To evaluate and contrast 25 content areas essential to the primary care of older adults by medical faculty, thus identifying faculty beliefs and areas of possible improvement.

DESIGN

Using measures from the Healthcare Effectiveness Data and Information Set, the Consumer Assessment of Healthcare Providers and Systems, and Healthy People 2020, nine practicing clinical faculty identified 25 content areas essential to the primary care of older adults.

SETTING

A large academic health center in southeastern United States.

PARTICIPANTS

Eighty‐two university medical faculty.

MEASUREMENTS

Faculty rated importance, knowledge, and confidence in teaching the 25 content areas on a scale from 1 (low) to 10 (high). Gap scores reflecting the difference in ratings for importance and confidence in teaching were calculated and assessed. The survey had high internal consistency within each of the three domains—Cronbach's α > .94.

RESULTS

The most important content areas were being able to explain details about patient's condition and taking medication clearly, followed by taking age‐appropriate history. The three largest gaps were: “evaluating sensory impairment,” “identifying and counseling at‐risk drivers,” and “evaluating cognition.” The three smallest gaps were: “explaining prescribed medications,” “explaining health conditions in easy‐to‐understand language,” and “taking an age‐appropriate patient history and performing a physical assessment.”

CONCLUSION

Medical faculty were comfortable with topics reflecting primary care expertise but expressed less confidence with more specialized topics, such as sensory or cognitive impairment and driving. This may represent key areas for geriatrics training applicable to all those involved in education and training of future healthcare professionals. Integration of specialists (eg, neurologists, psychiatrists) may improve the geriatrics curricula. J Am Geriatr Soc 67:576–580, 2019.
Medicare Shared Savings ACOs and Hospice Care for Ischemic Stroke Patients
Authors: Kaufman Brystana G. , O'Brien Emily C. , Stearns Sally C. , Matsouaka Roland A. , Holmes G. Mark , Weinberger Morris , Schwamm Lee H. , Smith Eric E. , Fonarow Gregg C. , Xian Ying , Taylor Donald H.
Published: March 2019

OBJECTIVES

Palliative care services have the potential to improve the quality of end‐of‐life care and reduce cost. Services such as the Medicare hospice benefit, however, are often underutilized among stroke patients with a poor prognosis. We tested the hypothesis that the Medicare Shared Savings Program (MSSP) is associated with increased hospice enrollment and inpatient comfort measures only among incident ischemic stroke patients with a high mortality risk.

DESIGN

A difference‐in‐differences design was used to compare outcomes before and after hospital participation in the MSSP for patients discharged from MSSP hospitals (N = 273) vs non‐MSSP hospitals (N = 1490).

SETTING

Records from a national registry, Get with the Guidelines (GWTG)‐Stroke, were linked to Medicare hospice claims (2010‐2015).

PARTICIPANTS

Fee‐for‐service Medicare beneficiaries age 65 and older hospitalized for incident ischemic stroke at a GWTG‐Stroke hospital from January 2010 to December 2014 (N = 324 959).

INTERVENTION

Discharge from an MSSP hospital or beneficiary alignment with an MSSP Accountable Care Organization (ACO).

MEASUREMENTS

Hospice enrollment in the year following stroke.

RESULTS

Among patients with high mortality risk, ACO alignment was associated with a 16% increase in odds of hospice enrollment (adjusted odds ratio [OR] = 1.16; 95% confidence interval [CI] = 1.06‐1.26), increasing the probability of hospice enrollment from 20% to 22%. In the low mortality risk group, discharge from an MSSP vs non‐MSSP hospital was associated with a decrease in the predicted probability of inpatient comfort measures or discharge to hospice from 9% to 8% (OR = .82; CI = .74‐.91), and ACO alignment was associated with reduced odds of a short stay (<7 days) (OR = .86; CI = .77‐.96).

CONCLUSION

Among ischemic stroke patients with severe stroke or indicators of high mortality risk, MSSP was associated with increased hospice enrollment. MSSP contract incentives may motivate improved end‐of‐life care among the subgroups most likely to benefit.
Ultrahigh‐pressure and high‐P lawsonite eclogites in Muzhaerte, Chinese western Tianshan
Authors: Lü Zeng , Zhang Lifei , Yue Ji , Li Xiaoli
Published: March 2019

Lawsonite eclogites are crucial to decipher material recycling along a cold geotherm into the deep Earth and orogenic geodynamics at convergent margins. However, their tectono‐metamorphic role and record especially at ultrahigh‐pressure (UHP) conditions are poorly known due to rare exposure in orogenic belts. In a ~4 km long cross‐section in Muzhaerte, China, at the western termination of the HP‐UHP metamorphic belt of western Tianshan, metabasite blocks contain omphacite and lawsonite inclusions in porphyroblastic garnet, although matrix assemblages have been significantly affected by overprinting at shallower structural levels. Two types of lawsonite eclogites occur in different parts of the section and are distinguished based on inclusion assemblages in garnet: Type 1 (UHP) with the peak equilibrium assemblage garnet+omphacite±jadeite+lawsonite+rutile+coesite±chlorite±glaucophane and Type 2 (HP) with the assemblage garnet+omphacite±diopside+lawsonite+titanite+quartz±actinolite±chlorite+glaucophane. Pristine coesite and lawsonite and their pseudomorphs in Type 1 are present in the mantle domains of zoned garnet, indicative of a coesite‐lawsonite eclogite facies. Regardless of grain size and zoning profiles, garnet with Type 1 inclusions systematically shows higher Mg and lower Ca contents than Type 2 (prp4–25grs13–24 and prp1–8grs20–45 respectively). Phase equilibria modelling indicates that the low‐Ca garnet core and mantle of Type 1 formed at UHP conditions and that there was a major difference in peak pressures (i.e., maximum return depth) between the two types (2.8–3.2 GPa at 480–590°C and 1.3–1.85 GPa at 390–500°C respectively). Scattered exposures of Type 1 lawsonite eclogite is scatteredly exposed in the north of the Muzhaerte section with a structural thickness of ~1 km, whereas Type 2 occurs throughout the rest of the section. We conclude from this regular distribution that they were derived from two contrasting units that formed along two different geothermal systems (150–200°C/GPa for the northern UHP unit and 200–300°C/GPa for the southern HP unit), with subsequent stacking of UHP and HP slices at a kilometre scale.
Parental Education and College Students' Attitudes Toward Love: Survey Evidence From China
Authors: Hu Anning , Wu Xiaogang
Published: March 2019

Objective

This study examines the correlation between parental education and college students' attitudes toward love (ATL) as well as its formative mechanisms.

Background

Family formation in modern societies tightly involves people's ATL, but its correlation with family origin is still elusive.

Method

Panel data from the random probability sample of the Beijing College Students Panel Survey were used to analyze a gradational measure of ATL. In total, 2,473 respondents were followed for 4 consecutive years. The population of interest is the college students in Beijing, China. The random‐effect linear regression and mediation analyses were conducted.

Results

Students with better‐educated parents are more likely to embrace realistic rather than romantic ATL. The effect is stable across individuals of different genders and ages. Further analyses highlight the mediating effect of family income and objectified cultural capital.

Conclusion

Due to economic and cultural advantages, parental education gives rise to adult children' likelihood of holding realistic ATL.

Implications

The link between parental education and propensity of realistic ATL serves as a potential mechanism for establishing assortative mating by family socioeconomic status, maintaining intergenerational transmission of economic advantages.
Molecular mechanism of tuberoinfundibular peptide of 39 on glucocorticoid receptor mediated glutamate/GABA imbalance and cerebral abnormalities against cognitive deficit model
Authors: Venkatesh Gunasekaran , Sankar Veintramuthu , Ramanathan Muthiah
Published: March 2019

Objectives

This study is designed to evaluate the role of tuberoinfundibular peptide of 39 (TIP39) in connection with glucocorticoid receptor-mediated glutamate/GABA abnormalities in chronic unpredictable mild stress (CUMS) model.

Methods

Male Sprague–Dawley rats were treated with TIP39 (1 and 10 nmol, i.c.v) and diazepam 2 mg/kg throughout the stress period (28 days) in alternate days. Then, rats were subjected for different behavioural activity followed by biochemical, gene expression and histological examinations.

Key findings

Chronic unpredictable mild stress rats showed significant cognitive impairment in Morris water maze, Novel object recognition and Y maze test. This was reversed after TIP39 administration. Moreover, TIP39 significantly decreased the brain glutamate and acetyl cholinesterase levels in CUMS rats, whereas it increases the level of GABA after TIP39 treatment. These changes were evident with increased glutamic acid decarboxylase enzyme activity by TIP39. TIP39 significantly decreased the brain glucocorticoid and mineralocorticoid receptor expression ratio in comparison with CUMS rats. Moreover, histological abnormalities in prefrontal cortex and hippocampus were markedly improved after TIP39 administration in CUMS rats.

Conclusions

Tuberoinfundibular peptide of 39 can be a potent neuroendocrine modulator in treating cognitive impairment induced by CUMS rats by controlling glucocorticoid receptor-mediated glutamate/GABA abnormalities in brain.
Automated classification of near‐fault acceleration pulses using wavelet packets
Authors: Chang Zhiwang , De Luca Flavia , Goda Katsuichiro
Published: March 2019

This study proposes a new algorithm for automatically classifying two types of velocity‐pulses that are integral of a distinct acceleration pulse (acc‐pulse) or a succession of high‐frequency one‐sided acceleration spikes (non‐acc‐pulse). For achieving this, wavelet packet transform is used to filter the high‐frequency content and to extract the coherent velocity‐pulse. Then, the pulse period is unequivocally derived through the peak point method. Following the determination of the pulse‐starting (ts) and pulse‐ending (te) time instants in the velocity time‐history, a local acceleration time‐history truncated by ts and te is obtained. The maximum relative energy of the pulse between two adjacent zero crossings is then employed as indicator for distinguishing the two types of velocity‐pulses. The criteria for identifying acc‐pulses and non‐acc‐pulses are calibrated using a training data set of manually classified ground motions from the Next Generation Attenuation West 2 project. Finally, significance of such a classification between velocity‐pulses of different characteristics is assessed through the comparison of elastic acceleration response spectra of the two categories of pulse‐like records.
The Unity of Christ and the Anointing of the Spirit in Gregory of Nyssa’s Antirrheticus Adversus Apolinarium
Authors: Abecina Alexander L.
Published: March 2019

I investigate Gregory of Nyssa’s use of the Spirit’s anointing motif in the Antirrheticus adversus Apolinarium to ground the unity of the divine and human in Christ, against Apolinarius of Laodicea’s own Spirit‐based account of Christ’s unity. Gregory’s three explicit references to Christ’s anointing by the Spirit – eternal, post‐passion and at conception – are analysed with respect to the exegesis of Psalm 44 (45):6‐7, Acts 2:36, John 17:5 and Luke 1:35. The development of Gregory’s Christology between Contra Eunomium III and the Antirrheticus is sketched and some concluding comments are given on the enduring influence this developed Christology had in In Illud: Tunc et ispse and In Canticum canticorum.
Microbial diversity in the tick Argas japonicus (Acari: Argasidae) with a focus on Rickettsia pathogens
Authors: Yan P. , Qiu Z. , Zhang T. , Li Y. , Wang W. , Li M. , Yu Z. , Liu J.
Published: March 2019

The soft tick Argas japonicus mainly infests birds and can cause human dermatitis; however, no pathogen has been identified from this tick species in China. In the present study, the microbiota in A. japonicus collected from an epidemic community was explored, and some putative Rickettsia pathogens were further characterized. The results obtained indicated that bacteria in A. japonicus were mainly ascribed to the phyla Proteobacteria, Firmicutes and Actinobacteria. At the genus level, the male A. japonicus harboured more diverse bacteria than the females and nymphs. The bacteria Alcaligenes, Pseudomonas, Rickettsia and Staphylococcus were common in nymphs and adults. The abundance of bacteria belonging to the Rickettsia genus in females and males was 7.27% and 10.42%, respectively. Furthermore, the 16S rRNA gene of Rickettsia was amplified and sequenced, and phylogenetic analysis revealed that 13 sequences were clustered with the spotted fever group rickettsiae (Rickettsia heilongjiangensis and Rickettsia japonica) and three were clustered with Rickettsia limoniae, which suggested that the characterized Rickettsia in A. japonicus were novel putative pathogens and also that the residents were at considerable risk for infection by tick‐borne pathogens.