bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Vitamin A and Carotenoids on the Risk of Tuberculosis Progression
Authors: Aibana Omowunmi , Franke Molly F. , Huang Chuan-Chin , Galea Jerome T. , Calderon Roger , Zhang Zibiao , Becerra Mercedes C. , Smith Emily R. , Ronnenberg Alayne G. , Contreras Carmen , Yataco Rosa , Lecca Leonid , Murray Megan B.
Published: January 2017

Background

Low and deficient levels of vitamin A are common in low and middle income countries where tuberculosis burden is high. We assessed the impact of baseline levels of vitamins A and carotenoids on TB disease risk.

Methods and Findings

We conducted a case-control study nested within a longitudinal cohort of household contacts of pulmonary TB cases in Lima, Peru. We screened all contacts for TB disease at 2, 6, and 12 months after enrollment. We defined cases as HIV-negative household contacts with blood samples who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected 4 controls from among contacts who did not develop TB disease, matching on gender and year of age. We used conditional logistic regression to estimate odds ratios (ORs) for incident TB disease by vitamin A and carotenoids levels, controlling for other nutritional and socioeconomic factors.

Among 6751 HIV-negative household contacts with baseline blood samples, 192 developed secondary TB disease during follow-up. We analyzed 180 cases with viable samples and 709 matched controls. After controlling for possible confounders, we found that baseline vitamin A deficiency was associated with a 10-fold increase in risk of TB disease among household contacts (aOR 10.42; 95% CI 4.01–27.05; p < 0.001). This association was dose-dependent with stepwise increases in TB disease risk with each decreasing quartile of vitamin A level. Carotenoid levels were also inversely associated with TB risk among adolescents.

Our study is limited by the one year duration of follow up and by the relatively few blood samples available from household contacts under ten years of age.

Conclusions

Vitamin A deficiency strongly predicted risk of incident TB disease among household contacts of TB patients. Vitamin A supplementation among individuals at high risk of TB may provide an effective means of preventing TB disease.
The evolution of p53 network behavior
Authors: Sivakumar Hari , Hespanha João P. , Roh Kyoungmin , Proulx Stephen R.
Published: January 2017

We study the evolution of thep53 core regulation network across the taxonomic span of humans to protozoans and nematodes. We introduce a new model for the core regulation network in mammalian cells, and conduct a formal analysis of the different network configurations that emerge in the evolutionary path to complexity. Solving the high dimensional equations associated with this model is typically challenging, and we develop a novel algorithm to overcome this problem. A key technical tool used is the representation of the distinct pathways in the core regulation networks as “modules”, such that the behavior of the composite of two or more modules can be inferred from the characteristics of each of the individual modules. Apart from simplifying the complexity of the algorithm, this modular representation also allows us to qualitatively compare the distinct types of switching behaviors each network can exhibit. This then allows us to demonstrate how our model for the core regulation network in mammalian cells matches experimentally observed phenomena, and contrast this with the plausible behaviors admitted by the network configurations in putative primordial organisms. We show that the complexity of thep53 core regulation network in vertebrates permits a range of behaviors that can bring about distinct cell fate decisions not possible in the putative primordial organisms.

Significance Statement

Thep53 protein has been protecting organisms from tumors for a billion years. We study the link between the evolution of thep53 network structure and its corresponding tumor suppression strategies. We compare the dynamical behaviors in putative primordial organisms with simple networks with the vertebrate network that contains multiple feedback loops. We show that the vertebrate network, but not the ancestral network, can both repair moderate damage and induce apoptosis if too much damage accumulates, balancing the risk of cancer with the cost of too much cell death. Moreover, the complexity of the vertebrate network allows for adaptation, for example to increasep53 network sensitivity, which is consistent with recent research on large mammals.
Measuring physiological responses to stressors using a novelHmox1reporter mouse
Authors: McMahon Michael , Ding Shaohong , Acosta-Jimenez Lourdes P , Frangova Tania G. , Henderson Colin J. , Wolf C. Roland
Published: January 2017

Hmox1 protein holds great promise as a biomarker of organismal health as it is highly expressed in stressed or damaged cells. However, documenting Hmox1 expression patterns has thus far only been feasible in simple model organisms with limited relevance to humans. We now report a new Hmox1 reporter line that makes it possible to access this information in mice, the premiere model system for studying human disease and toxicology. Using a state-of-the-art strategy, we express multiple complementary reporter molecules from the murineHmox1locus, including firefly luciferase to allow long-term, non-invasive imaging of Hmox1 expression, and β-galactosidase for high-resolution mapping of expression patternspost-mortem. We validate the model by confirming the absence of haplo-insufficiency effects, the fidelity of reporter expression, and its responsiveness to oxidative and inflammatory stimuli. In addition to providing blueprints for Hmox1 expression in mice that provide novel biological insights for follow-up, this work paves the way for the broad application of this model to regulatory toxicology studies and, also, pre-clinical investigations into human degenerative diseases.
Crystal structure of 7,15-bis(4-tert-butylphenyl)-1,9-dimethylheptazethrene
Authors: Kamata Sho , Sato Sota , Wu Jishan , Isobe Hiroyuki
Published: January 2017

The title compound, C50H44,1, was synthesized as a derivative of heptazethrene bearing two methyl and twotert-butylphenyl substituents, respectively, at the 1,9- and 7,15-positions. The asymmetric unit consists of one half of the molecule, which lies about an inversion centre. Albeit remotely located, the substituents contort the heptazethrene plane. Thetert-butylphenyl substituents stand approximately perpendicular to the core plane, with a dihedral angle of 79.09 (5)° between the phenalene ring system and the substituted benzene ring, and prevent direct intermolecular contacts of the heptazethrene cores.
Crystal structures of two nickel compounds comprising neutral NiIIhydrazone complexes and dicarboxylic acids
Authors: Nakanishi Takumi , Sato Osamu
Published: January 2017

Two isostructural NiIIcompounds, bis{N-[1-(pyridin-2-yl-κN)ethylidene]pyridine-4-carbohydrazonato-κ2N′,O}nickel(II)–2,5-dichloroterephthalic acid (1/1), [Ni(C13H11N4O)2](C8H4Cl2O4), and bis{N-[1-(pyridin-2-yl-κN)ethylidene]pyridine-4-carbohydrazonato-κ2N′,O}nickel(II)–2,5-dibromoterephthalic acid (1/1), [Ni(C13H11N4O)2](C8H4Br2O4), were synthesized and their crystal structures determined. The pair ofN,N′,O-tridentateN-[1-(pyridin-2-yl-κN)ethyl]pyridine-4-carbohydrazonateLligands result in acis-NiO2N4octahedral coordination sphere for the metal ions. The asymmetric units consist of two half-molecules of the dicarboxylic acids, which are completed by crystallographic inversion symmetry. In the respective crystals, the 2,5-dichloroterephthalic acid (H2Cl2TPA,1-Cl) molecules form zigzag hydrogen-bonded chains with the [Ni(L)2] molecules, with the hydrogen-bond distances in1-Brslightly longer than those in1-Cl. The packing is consolidated by aromatic π–π stacking between the dicarboxylic acid molecules and terminal pyridine rings in [Ni(L)2] and short halogen–halogen interactions are also observed. The qualitative prediction of the H-atom position from the C—N—C angles of the terminal pyridine rings inLand the C—O distances in the carboxyl groups show that1-Cland1-Brare co-crystals rather than salts.
Crystal structure of (E)-2-{[(4-anilinophenyl)imino]methyl}-4-nitrophenol
Authors: Faizi Md. Serajul Haque , Haque Ashanul , Kalibabchuk Valentina A.
Published: January 2017

In the title compound, C19H15N3O3, which crystallizes as the phenol–imine tautomer, the dihedral angle between the aromatic rings bridged by the NH unit is 47.16 (16)°. The dihedral angle between the rings bridged by the imine unit is 6.24 (15)°; this near coplanarity is reinforced by an intramolecular O—H...N hydrogen bond, which generates anS(6) ring. In the crystal, N—H...O hydrogen bonds generate [201]C(13) chains. The chains are reinforced and cross-linked by C—H...O interactions to generate (001) sheets.
1-Ethyl-4-phenyl-1,5-benzodiazepine-2-thione
Authors: El Ghayati Lhoussaine , Hamou Ahabchane Noureddine , Lamine Doumbia Mohamadou , Sebbar Nada Kheira , Essassi El Mokhtar , Mague Joel T.
Published: January 2017

In the title compound, C17H16N2S, the seven-membered ring adopts a boat conformation. The two aromatic rings are inclined at an angle of 34.7 (1)° to one another. The molecules pack in helical chains running along the c-axis direction through C—H...S hydrogen bonds. These are further linked into layers parallel to (100) by weak C—H...π(ring) interactions. The structure was refined as a two-component inversion twin.
3-(4-Amino-3-ethyl-5-sulfanylidene-4,5-dihydro-1H-1,2,4-triazol-1-yl)-1,3-diphenylpropan-1-one
Authors: Xu Jianchao , Wang Hewen
Published: January 2017

In the title compound, C19H20N4OS, the 1,2,4-triazole ring forms dihedral angles of 58.64 (9) and 87.68 (9)° with the phenyl rings, which are inclined to one another by 43.30 (6)°. In the crystal, molecules are linked by N—H...O, N—H...S and C—H...S hydrogen bonds, forming chains propagating along the c-axis direction. Neighbouring chains are linked by three C—H...π interactions, forming layers parallel to the bc plane. Finally, the layers are linked by a fourth C—H...π interaction, forming a three-dimensional network.
5-(2,3-Dichlorophenyl)-3-(4-methoxyphenyl)-1-phenyl-4,5-dihydro-1H-pyrazole
Authors: Lokeshwari D. M. , Naveen S. , Prabhudeva M. G. , Raghavendra K. R. , Dileep Kumar A. , Lokanath N. K. , Ajay Kumar K.
Published: January 2017

In the racemic title compound, C22H18Cl2N2O, the dihedral angles between the central dihydropyrazole ring (r.m.s. deviation = 0.018 Å) and the pendant methoxyphenyl, phenyl and dichlorophenyl rings are 3.96 (9), 15.90 (9) and 66.65 (9)° respectively. Weak aromatic π–π stacking [shortest centroid–centroid separation = 3.8476 (11) Å] occurs in the crystal.
(E)-1-(1,3-Benzodioxol-5-yl)-3-[4-(dimethylamino)phenyl]prop-2-en-1-one
Authors: Kumara Karthik , Naveen S. , Dileep Kumar A. , Ajay Kumar K. , Lokanath N. K. , Warad Ismail
Published: January 2017

In the title compound, C18H17NO3, the olefinic double bond adopts an E conformation. The molecule is nearly planar as indicated by the dihedral angle of 3.11 (6)° between the benzodioxole and benzene rings. The carbonyl group lies in the plane of the olefinic double bond and the benzodioxole ring. The trans conformation of the C=C double bond in the central enone group is confirmed by the C=C—C—C torsion angle of −177.82 (14)°.
4-Iodo-N-(o-tolylsulfonyl)benzamide
Authors: Naveen S. , Suresha E. , Sudha A. G. , Lokanath N. K. , Suchetan P. A. , Abdoh M.
Published: January 2017

The title compound, C14H12INO3S, crystallizes with two independent molecules (A and B) in the asymmetric unit. The dihedral angle between the two aryl rings is 83.1 (4)° in molecule A and 79.8 (4)° in molecule B. In the crystal, the two molecules are linked by a pair of N—H...O hydrogen bonds, forming an A–B dimer with an R
2
2(8) ring motif. The dimer is further strengthened by a pair of C—H...O hydrogen bonds with an R
2
2(14) motif. Another pair of C—H...O interactions assembles these dimers along the diagonal of the bc plane, forming ribbons. Adjacent ribbons are connected by C—H...πaryl interactions between the A molecules, and thus the overall supramolecular architecture is one-dimensional.
Managerial tenure and earnings management
Authors: Hu Nan , Hao Qian , Liu Ling , Yao (1958-2012) Lee J.
Published: January 2017

Purpose

– The purpose of this paper is to understand the impact of tenure on earnings management.

Design/methodology/approach

– Analytical model; multivariate regression analysis.

Findings

– The paper predicts that managers are conservative in managing earnings when they first start to take top managerial positions, and then become aggressive in the next few years. Once they reach the maximum level of earnings management, they will become conservative again and report earnings less aggressively. This inverted U-shaped relationship between tenure and earnings management is confirmed by the data from the Chinese stock market.

Research limitations/implications

– It is based on China stock market data. Generalization of the research results to other countries is limited.

Practical implications

– With the knowledge of when earnings management is more likely to occur, regulators can set up policies targeting firms and managers with certain characteristics, instead of requiring observances from all firms and managers. This limited scope can greatly reduce the costs of preventing and identifying earnings management, while effectively maintaining the quality of earnings in the meantime.

Social implications

– This paper examines the earnings management behavior related to CEO tenure. It is hoped that the research results can improve the overall understanding of earnings management, then social wealth spent on preventing and identifying it could be reduced.

Originality/value

– It is an original work.
Does crime depend on the “state” of economic misery?
Authors: Lorde Troy , Jackman Mahalia , Naitram Simon , Lowe Shane
Published: January 2017

Purpose

It is generally understood that during periods of economic hardship, some persons turn to crime to compensate for income deficiencies. The paper investigates the impact of economic misery on crime. The purpose of this paper is to provide insight into the relationship between economic conditions and economic misery.

Design/methodology/approach

An index of misery is employed that takes into account not only the rate of unemployment, but also the rate of inflation. The non-linearity of the relationship between economic misery and crime is modelled using Markov-switching (MS) models and the synchronization of their cycles is measured via the concordance index.

Findings

The paper looked at the relationship between economic misery and five types of crime: property crime, theft from motor, theft of motor, fraud and robbery. No evidence of a contemporaneous relationship between economic misery and crime was uncovered. Property and theft of motor crime respond to the state of misery with a lag of one period, supporting the criminal motivation effect. Economic misery is in the same regime as property crime 50 per cent of the time and with theft from motor crime almost 60 per cent of the time.

Originality/value

Most of the theoretical and empirical work is based on larger economies. The paper provides some insight into the relationship between economic conditions and economic misery in developing microstates, a niche which has been largely ignored in the literature. The use of MS models in the paper deviates from the tradition of examining linear relationships on the basis that the variables under investigation are inherently cyclical and linear analysis is likely to provide a weak fit under these circumstances.
Revising satisfaction and dissatisfaction indexes of the Kano model by reclassifying indifference requirements
Authors: Shahin Arash , Mohammadi Somaye , Harsij Hossein , Rahbar Qazi Mahmoud Reza
Published: January 2017

Purpose

The purpose of this paper is to revise the Kano evaluation table and separating indifference attributes in order to develop satisfaction and dissatisfaction indexes.

Design/methodology/approach

The indifference requirements have been separated and reclassified, and after revising Kano satisfaction and dissatisfaction indexes based on the new evaluation table, the developed Kano model has been examined in the city of Isfahan regarding attributes of candidates in the presidential election of 2013.

Findings

According to the new classification, the indifference attributes can be separated into seven types. The results of the case study also show that among 20 priorities of the presidential candidates, payment of subsidy, offering loan and financial facilities are must-be attributes; protecting investment and national production, export incentives and increasing national unity are attractive attributes; and the remaining are one-dimensional attributes.

Practical implications

The case study implies that the findings are dependent on the cultural and social context of the respondents. On the other hand, the findings of Kano model analysis are limited to short-time periods.

Originality/value

This research is typically unique in separating indifference attributes and in revising the satisfaction and dissatisfaction indexes of the Kano model. Practically, the application of the Kano model in the presidential election is also a new subject.
The selective serotonin reuptake inhibitor dapoxetine inhibits voltage‐dependent K+ channels in rabbit coronary arterial smooth muscle cells
Authors: Kim Han Sol , Li Hongliang , Kim Hye Won , Shin Sung Eun , Jung Won‐Kyo , Ha Kwon‐Soo , Han Eun‐Taek , Hong Seok‐Ho , Firth Amy L , Choi Il‐Whan , Park Won Sun
Published: January 2017

We investigated the inhibitory effect of dapoxetine, a selective serotonin reuptake inhibitor (SSRI), on voltage‐dependent K+ (Kv) channels using native smooth muscle cells from rabbit coronary arteries. Dapoxetine inhibited Kv channel currents in a concentration‐dependent manner, with an IC50 value of 2.68±0.94 μmol/L and a slope value (Hill coefficient) of 0.63±0.11. Application of 10 μmol/L dapoxetine accelerated the rate of inactivation of Kv currents. Although dapoxetine did not modify current activation kinetics, it caused a significant negative shift in the inactivation curves. Application of train step (1 or 2 Hz) progressively increased the inhibitory effect of dapoxetine on Kv channels. In addition, the recovery time constant was extended in its presence, suggesting that the longer recovery time constant from inactivation underlies a use‐dependent inhibition of the channel. From these results, we conclude that dapoxetine inhibits Kv channels in a dose‐, time‐, use‐, and state (open)‐dependent manner, independent of serotonin reuptake inhibition.
Bromocriptine treatment at the end of lactation prevents hyperphagia, higher visceral fat and liver triglycerides in early‐weaned rats at adulthood
Authors: Peixoto‐Silva Nayara , Moura Egberto G , Carvalho Janaine C , Nobre Jéssica L , Quitete Fernanda T , Pinheiro Cintia R , Santos‐Silva Ana Paula , de Oliveira Elaine , Lisboa Patricia C
Published: January 2017

Non‐pharmacological early weaning (NPEW) leads offspring to obesity, higher liver oxidative stress and microsteatosis in adulthood. Pharmacological EW (PEW) by maternal treatment with bromocriptine (BRO) causes obesity in the adult progeny but precludes hepatic injury. To test the hypothesis that BRO prevents the deleterious changes of NPEW, we injected BRO into the pups from the NPEW model in late lactation. Lactating rats were divided into two groups: dams with an adhesive bandage around the body to prevent breastfeeding on the last 3 days of lactation and dams whose pups had free suckling (C). Offspring from both groups were subdivided into two groups: pups treated with BRO (intraperitoneal (i.p.) 4 mg/kg per day) on the last 3 days of lactation (NPEW/BRO and C/BRO) or pups treated with the vehicle (NPEW and C). At PN120, offspring were challenged with a high fat diet (HFD), and food intake was recorded after 30 minutes and 12 hours. Rats were killed at PN120 and PN200. At PN120, adipocyte size was greater in the NPEW group but was normal in the NPEW/BRO group. At PN200, the NPEW group presented hyperphagia, higher adiposity, adipocyte hypertrophy, hyperleptinaemia, glucose intolerance and increased hepatic triglycerides. These parameters were normalized in the NPEW/BRO group. In the feeding test, BRO groups showed lower HFD intake at 30 minutes than did their controls; however, at 12 hours, the NPEW group ate more HFD. The treatment with BRO can preclude some deleterious effects of the NPEW model, which prevented the development of overweight and its comorbidities.
Information Asymmetries in the Hiring Process and the Risk of New Leader Dismissal: Insights from English Premier League Soccer Organizations
Authors: Desai Malay N. , Lockett Andy , Paton David
Published: January 2017

Why are some new leaders dismissed more quickly than others? Adopting agency theory logic, the authors examine how different succession contexts shape boards’ information asymmetries about a potential candidate's competencies in the hiring process, which influences the propensity of making poor hiring decisions and hence the risk of new leader dismissal. Employing duration analysis on a sample of 164 newly appointed leaders in the English premier league (1996–2014), the authors find that the risk of new leader dismissal is: (i) greater when the predecessor leader's exit was initiated by them rather than by the board; (ii) greater when following a longer‐tenured predecessor; and (iii) lower for outside successions compared with inside successions.
Prediction of effective RNA interference targets and pathway‐related genes in lepidopteran insects by RNA sequencing analysis
Authors: Guan Ruo‐Bing , Li Hai‐Chao , Miao Xue‐Xia
Published: January 2017

When using RNA interference (RNAi) to study gene functions in Lepidoptera insects, we discovered that some genes could not be suppressed; instead, their expression levels could be up‐regulated by double‐stranded RNA (dsRNA). To predict which genes could be easily silenced, we treated the Asian corn borer (Ostrinia furnacalis) with dsGFP (green fluorescent protein) and dsMLP (muscle lim protein). A transcriptome sequence analysis was conducted using the cDNAs 6 h after treatment with dsRNA. The results indicated that 160 genes were up‐regulated and 44 genes were down‐regulated by the two dsRNAs. Then, 50 co‐up‐regulated, 25 co‐down‐regulated and 43 unaffected genes were selected to determine their RNAi responses. All the 25 down‐regulated genes were knocked down by their corresponding dsRNA. However, several of the up‐regulated and unaffected genes were up‐regulated when treated with their corresponding dsRNAs instead of being knocked down. The genes up‐regulated by the dsGFP treatment may be involved in insect immune responses or the RNAi pathway. When the immune‐related genes were excluded, only seven genes were induced by dsGFP, including ago‐2 and dicer‐2. These results not only provide a reference for efficient RNAi target predications, but also provide some potential RNAi pathway‐related genes for further study.
Allergen immunotherapy for IgE‐mediated food allergy: a systematic review and meta‐analysis
Authors: Nurmatov U. , Dhami S. , Arasi S. , Pajno G. B. , Fernandez‐Rivas M. , Muraro A. , Roberts G. , Akdis C. , Alvaro‐Lozano M. , Beyer K. , Bindslev‐Jensen C. , Burks W. , du Toit G. , Ebisawa M. , Eigenmann P. , Knol E. , Makela M. , Nadeau K. C. , O'Mahony L. , Papadopoulos N. , Poulsen L. K. , Sackesen C. , Sampson H. , Santos A. F. , van Ree R. , Timmermans F. , Sheikh A.
Published: January 2017

Background

The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE‐mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost‐effectiveness of AIT in the management of food allergy.

Methods

We undertook a systematic review and meta‐analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT‐NRS tool for quasi‐RCTs. Random‐effects meta‐analyses were undertaken, with planned subgroup and sensitivity analyses.

Results

We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty‐five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty‐seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta‐analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease‐specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta‐analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses.

Conclusions

AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE‐mediated food allergy whilst receiving (i.e. desensitization) and post‐discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost‐effectiveness of AIT.
The Presentation of Self in Philanthropic Life: The Political Negotiations of the Foundation Program Officer
Authors: Kohl‐Arenas Erica
Published: January 2017

This paper explores the negotiations of foundation program officers who aim to challenge structural inequality across regional geographies of poverty. Beyond the limits to confronting capitalist relationships of production as discussed in critical philanthropy literature, this paper shows how the professional “grantor–grantee” relationship reproduces institutional structures of power. Through the lens of Erving Goffman's “presentation of self” and data from archival and ethnographic research on immigrant and farmworker funding in California's Central Valley and recent interviews with program staff at large foundations in New York City, the paper suggests that Goffman's concepts of performance, idealization, negative idealization, and disruption expand upon a Gramscian theorization of hegemony by highlighting a micro‐sociology of power. Building consensus among greatly unequal actors and managing idealized stories about poverty and philanthropy, the foundation program officer brokers political opportunity for grassroots organizations and yet more commonly generates consent.
Classification of European beech forests: a Gordian Knot?
Authors: Willner Wolfgang , Jiménez‐Alfaro Borja , Agrillo Emiliano , Biurrun Idoia , Campos Juan Antonio , Čarni Andraž , Casella Laura , Csiky János , Ćušterevska Renata , Didukh Yakiv P. , Ewald Jörg , Jandt Ute , Jansen Florian , Kącki Zygmunt , Kavgacı Ali , Lenoir Jonathan , Marinšek Aleksander , Onyshchenko Viktor , Rodwell John S. , Schaminée Joop H.J. , Šibík Jozef , Škvorc Željko , Svenning Jens‐Christian , Tsiripidis Ioannis , Turtureanu Pavel Dan , Tzonev Rossen , Vassilev Kiril , Venanzoni Roberto , Wohlgemuth Thomas , Chytrý Milan
Published: January 2017

Questions

What are the main floristic patterns in European beech forests? Which classification at the alliance and suballiance level is the most convincing?

Location

Europe and Asia Minor.

Methods

We applied a TWINSPAN classification to a data set of 24 605 relevés covering the whole range of Fagus sylvatica forests and the western part of Fagus orientalis forests. We identified 24 ‘operational phytosociological units’ (OPUs), which were used for further analysis. The position of each OPU along the soil pH and temperature gradient was evaluated using Ellenberg Indicator Values. Fidelity of species to OPUs was calculated using the phi coefficient and constancy ratio. We compared alternative alliance concepts, corresponding to groups of OPUs, in terms of number and frequency of diagnostic species. We also established formal definitions for the various alliance concepts based on comparison of the total cover of the diagnostic species groups, and evaluated alternative geographical subdivisions of beech forests.

Results

The first and second division levels of TWINSPAN followed the temperature and soil pH gradients, while lower divisions were mainly geographical. We grouped the 22 OPUs of Fagus sylvatica forests into acidophytic, meso‐basiphytic and thermo‐basiphytic beech forests, and separated two OPUs of F. orientalis forests. However, a solution with only two ecologically defined alliances of F. sylvatica forests (acidophytic vs basiphytic) was clearly superior with regard to number and frequency of diagnostic species. In contrast, when comparing groupings with three to six geographical alliances of basiphytic beech forests, respectively, we did not find a strongly superior solution.

Conclusions

We propose to classify F. sylvatica forests into 15 suballiances – three acidophytic and 12 basiphytic ones. Separating these two groups at alliance or order level was clearly supported by our results. Concerning the grouping of the 12 basiphytic suballiances into ecological or geographical alliances, as advocated by many authors, we failed to find an optimal solution. Therefore, we propose a multi‐dimensional classification of basiphytic beech forests, including both ecological and geographical groups as equally valid concepts which may be used alternatively depending on the purpose and context of the classification.
DNA Damage Potential of Engine Emissions Measured In Vitro by Micronucleus Test in Human Bronchial Epithelial Cells
Authors: Cervena Tereza , Rossnerova Andrea , Sikorova Jitka , Beranek Vit , Vojtisek‐Lom Michal , Ciganek Miroslav , Topinka Jan , Rossner Pavel
Published: January 2017

Internal combustion engine emissions belong among the major anthropogenic sources of air pollution in urban areas. According to the International Agency for Research on Cancer, there is sufficient evidence of the carcinogenicity of diesel exhaust in human beings. Although alternative fuels, mainly biodiesel, have recently become popular, little is still known about the genotoxicity of emissions from these fuels. We analysed DNA damage expressed as the frequency of micronuclei (MN) in human bronchial epithelial cells (BEAS‐2B), induced by extractable organic matter (EOM; tested concentrations: 1, 10 and 25 μg/ml) obtained from particle emissions from various blends of biodiesel with diesel fuels (including neat diesel fuel (B0), a blend of 70% B0 and 30% biodiesel (B30) and neat biodiesel (B100)). We also tested the effect of selected diesel exhaust organic/genotoxic components [benzo[a]pyrene (B[a]P) concentrations: 25, 100 and 200 μM; 1‐nitropyrene (1‐NP) concentrations: 1, 5 and 10 μM; 3‐nitrobenzanthrone (3‐NBA) concentrations: 1, 5 and 50 μM]. The cells were treated with the compounds for 28 and 48 hr. Our results showed that most of the tested compounds (except for the 25 μM B[a]P, 28‐hr treatment) significantly increased MN frequency. The genotoxicity of EOMs from the engine emissions of diesel and biodiesel engines was comparable. Both nitro‐PAH compounds demonstrated higher genotoxic potential in comparison with B[a]P. Considering our results and due to increasing popularity of alternative fuels, it is prudent that the potential genotoxic effects of various fuels are investigated across engine technologies and operating conditions in a relevant model system.
A molecular roadmap of definitive erythropoiesis from human induced pluripotent stem cells
Authors: Razaq Muhammad A. , Taylor Stephen , Roberts David J. , Carpenter Lee
Published: January 2017

Human induced pluripotent stem cells (hiPSCs) are being considered for use in understanding haematopoietic disorders and as a potential source of in vitro manufactured red cells. Here, we show that hiPSCs are able to recapitulate various stages of developmental erythropoiesis. We show that primitive erythroblasts arise first, express CD31+ with CD235a+, embryonic globins and red cell markers, but fail to express the hallmark red cell transcripts of adult erythropoiesis. When hiPSC‐derived CD45+ CD235a− haematopoietic progenitors are isolated on day 12 and further differentiated on OP9 stroma, they selectively express CD36+ and CD235a+, adult erythroid transcripts for transcription factors (e.g., BCL11A, KLF1) and fetal/adult globins (HBG1/2, HBB). Importantly, hiPSC‐ and cord‐derived CD36+ CD235a+ erythroblasts show a striking homology by transcriptome array profiling (only 306 transcripts with a 2Log fold change >1·5‐ or 2·8‐fold). Phenotypic and transcriptome profiling of CD45+CD117+CD235a+ pro‐erythroblasts and terminally differentiated erythroblasts is also provided, including evidence of a HbF (fetal) to HbA (adult) haemoglobin switch and enucleation, that mirrors their definitive erythroblast cord‐derived counterparts. These findings provide a molecular roadmap of developmental erythropoiesis from hiPSC sources at several critical stages, but also helps to inform on their use for clinical applications and modelling human haematopoietic disease.
Cannabinoids for treating neurogenic lower urinary tract dysfunction in patients with multiple sclerosis: a systematic review and meta‐analysis
Authors: Abo Youssef Nadim , Schneider Marc P. , Mordasini Livio , Ineichen Benjamin V. , Bachmann Lucas M. , Chartier‐Kastler Emmanuel , Panicker Jalesh N. , Kessler Thomas M.
Published: January 2017

Objectives

To review systematically all the available evidence on efficacy and safety of cannabinoids for treating neurogenic lower urinary tract dysfunction (NLUTD) in patients with multiple sclerosis (MS).

Patients and Methods

The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement. Studies were identified by electronic search of the Cochrane register, Embase, Medline, Scopus (last search on 11 November 2016).

Results

After screening 8 469 articles, we included two randomized controlled trials and one open‐label study, in which a total of 426 patients were enrolled. Cannabinoids relevantly decreased the number of incontinence episodes in all three studies. Pooling data showed the mean difference in incontinence episodes per 24 h to be −0.35 (95% confidence interval −0.46 to −0.24). Mild adverse events were frequent (38–100%), but only two patients (0.7%) reported a serious adverse event.

Conclusions

Preliminary data imply that cannabinoids might be an effective and safe treatment option for NLUTD in patients with MS; however, the evidence base is poor and more high‐quality, well‐designed and adequately powered and sampled studies are urgently needed to reach definitive conclusions.
Prostate Health Index density improves detection of clinically significant prostate cancer
Authors: Tosoian Jeffrey J. , Druskin Sasha C. , Andreas Darian , Mullane Patrick , Chappidi Meera , Joo Sarah , Ghabili Kamyar , Mamawala Mufaddal , Agostino Joseph , Carter Herbert B. , Partin Alan W. , Sokoll Lori J. , Ross Ashley E.
Published: January 2017

Objectives

To explore the utility of Prostate Health Index (PHI) density for the detection of clinically significant prostate cancer (PCa) in a contemporary cohort of men presenting for diagnostic evaluation of PCa.

Patients and Methods

The study cohort included patients with elevated prostate‐specific antigen (PSA; >2 ng/mL) and negative digital rectal examination who underwent PHI testing and prostate biopsy at our institution in 2015. Serum markers were prospectively measured per standard clinical pathway. PHI was calculated as ([{−2}proPSA/free PSA] × [PSA]½), and density calculations were performed using prostate volume as determined by transrectal ultrasonography. Logistic regression was used to assess the ability of serum markers to predict clinically significant PCa, defined as any Gleason score ≥7 cancer or Gleason score 6 cancer in >2 cores or >50% of any positive core.

Results

Of 118 men with PHI testing who underwent biopsy, 47 (39.8%) were found to have clinically significant PCa on biopsy. The median (interquartile range [IQR]) PHI density was 0.70 (0.43–1.21), and was 0.53 (0.36–0.75) in men with negative biopsy or clinically insignificant PCa and 1.21 (0.74–1.88) in men with clinically significant PCa (P < 0.001). Clinically significant PCa was detected in 3.6% of men in the first quartile of PHI density (<0.43), 36.7% of men in the IQR of PHI density (0.43–1.21), and 80.0% of men with PHI density >1.21 (P < 0.001). Using a threshold of 0.43, PHI density was 97.9% sensitive and 38.0% specific for clinically significant PCa, and 100% sensitive for Gleason score ≥7 disease. Compared with PSA (area under the curve [AUC] 0.52), PSA density (AUC 0.70), %free PSA (AUC 0.75), the product of %free PSA and prostate volume (AUC 0.79), and PHI (AUC 0.76), PHI density had the highest discriminative ability for clinically significant PCa (AUC 0.84).

Conclusions

Based on the present prospective single‐centre experience, PHI density could be used to avoid 38% of unnecessary biopsies, while failing to detect only 2% of clinically significant cancers.
Surgical histopathology for suspected oncocytoma on renal mass biopsy: a systematic review and meta‐analysis
Authors: Patel Hiten D. , Druskin Sasha C. , Rowe Steven P. , Pierorazio Phillip M. , Gorin Michael A. , Allaf Mohamad E.
Published: January 2017

To estimate the proportion of oncocytic renal neoplasms diagnosed on renal mass biopsy (RMB) confirmed on surgical pathology, a systematic review of MEDLINE, Embase, and the Cochrane databases (1997 to 1 July 2016) was conducted quantifying all cases of reported oncocytic renal neoplasms on RMB suggestive of an oncocytoma. In addition, institutional data was assessed to identify additional cases. Concordance with surgical histopathology (positive predictive value [PPV]) was evaluated for patients undergoing surgery by performing a meta‐analysis. In all, 10 RMB series, including institutional data, were included in the meta‐analysis with 205 RMBs identifying oncocytic renal neoplasms and 46 (22.4%) proceeding to surgery. One additional study identified two neoplasms not captured by the primary RMB series for a total of 48 unique lesions included in the analysis. Surgical pathology showed oncocytoma (64.6%), chromophobe renal cell carcinoma (RCC; 12.5%), other RCC (12.5%), hybrid oncocytic/chromophobe tumour (6.3%), and other benign lesions (4.2%). PPV of oncocytoma on RMB was 67% (95% confidence interval 34–94%) with significant heterogeneity between studies (I2 = 71.8%, P < 0.01). Risk of bias was judged to be low for four of the 10 series. Confidently diagnosing a localised renal mass as a benign lesion, such as an oncocytoma, has implications for the ultimate management strategy a patient will undergo. RMB was found to be unreliable in confidently diagnosing a localised renal mass as an oncocytoma, with one in four found to be RCC on surgical pathology. Patients and physicians should be aware of the uncertainty in diagnosis when considering management strategies.
Effect of hypercholesterolaemia on myocardial function, ischaemia–reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning
Authors: Andreadou Ioanna , Iliodromitis Efstathios K , Lazou Antigone , Görbe Anikó , Giricz Zoltán , Schulz Rainer , Ferdinandy Péter
Published: January 2017

Hypercholesterolaemia is considered to be a principle risk factor for cardiovascular disease, having direct negative effects on the myocardium itself, in addition to the development of atherosclerosis. Since hypercholesterolaemia affects the global cardiac gene expression profile, among many other factors, it results in increased myocardial oxidative stress, mitochondrial dysfunction and inflammation triggered apoptosis, all of which may account for myocardial dysfunction and increased susceptibility of the myocardium to infarction. In addition, numerous experimental and clinical studies have revealed that hyperlcholesterolaemia may interfere with the cardioprotective potential of conditioning mechanisms. Although not fully elucidated, the underlying mechanisms for the lost cardioprotection in hypercholesterolaemic animals have been reported to involve dysregulation of the endothelial NOS‐cGMP, reperfusion injury salvage kinase, peroxynitrite‐MMP2 signalling pathways, modulation of ATP‐sensitive potassium channels and apoptotic pathways. In this review article, we summarize the current knowledge on the effect of hypercholesterolaemia on the non‐ischaemic and ischaemic heart as well as on the cardioprotection induced by drugs or ischaemic preconditioning, postconditioning and remote conditioning. Future perspectives concerning the mechanisms and the design of preclinical and clinical trials are highlighted.

Linked Articles

This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc
Acral and digital angioleiomyomata: 14‐year experience at the Cleveland Clinic and review of the literature
Authors: Hammond Margaret I. , Miner Andrew G. , Piliang Melissa P.
Published: January 2017

Background

Angioleiomyoma is a benign neoplasm thought to derive from the tunica media of small venous vessels. Angioleiomyomata most frequently occur in the lower extremities with less common occurrences on the trunk, head and upper extremities. Few cases of acral and digital angioleiomyoma have been described in the literature.

Methods

We add a series of 21 patients with acral angioleiomyoma including 6 cases of digital angioleiomyoma to the body of clinical and histological findings along with a review of the literature of digital angioleiomyomata.

Results

Digital angioleiomyoma are equally distributed between male and female patients and are more often painful than the angioleiomyoma of all body sites. Acral angioleiomyomata favor the feet over hands at a ratio of 2.5:1, while digital angioleiomyoma favor the fingers over toes at a ratio of 4.3:1.

Conclusions

We suggest that vascular leiomyoma be included in the differential diagnosis of smooth muscle tumors with particular regard to the digits of both the hands and the feet. Digital angioleiomyomata differ from acral angioleiomyomata in their equal gender distribution, increased tendency to cause pain and preponderance for the fingers over the toes.
Relationship of glycated haemoglobin and reported hypoglycaemia to cardiovascular outcomes in patients with type 2 diabetes and recent acute coronary syndrome events: The EXAMINE trial
Authors: Heller Simon R. , Bergenstal Richard M. , White William B. , Kupfer Stuart , Bakris George L. , Cushman William C. , Mehta Cyrus R. , Nissen Steven E. , Wilson Craig A. , Zannad Faiez , Liu Yuyin , Gourlie Noah M. , Cannon Christopher P. ,   for the EXAMINE Investigators
Published: January 2017

Aims

To investigate relationships between glycated haemoglobin (HbA1c) and reported hypoglycaemia and risk of major adverse cardiovascular events (MACE).

Methods

The EXAMINE trial randomized 5380 patients with type 2 diabetes (T2DM) and a recent acute coronary syndrome (ACS) event, in 49 countries, to double‐blind treatment with alogliptin or placebo in addition to standard of care. We used Cox proportional hazards models to analyse relationships among MACE, HbA1c levels and hypoglycaemic events.

Results

Patients randomized to alogliptin achieved lower HbA1c levels than the placebo group in all baseline HbA1c categories without differences in hypoglycaemia rates. No systematic change was found in MACE rates according to baseline HbA1c (Pinteraction = 0.971) or HbA1c category at 1 month. Patients in the combined treatment groups (n = 5380) who experienced serious hypoglycaemia (n = 34) had higher MACE rates than those who did not (35.3% vs 11.4%, adjusted hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.27–4.60; P = .007), although the association was less strong when analysing only events after the hypoglycaemic event (adjusted HR 1.60, 95% CI 0.80, 3.20).

Conclusions

There were no relationships between baseline HbA1c levels or HbA1c levels after 1 month of treatment and the risk of MACE. Alogliptin improved glycaemic control without increasing hypoglycaemia. Reported events of hypoglycaemia and serious hypoglycaemia were associated with MACE. These data underscore the safety of alogliptin in improving glycaemic control in T2DM post‐ACS. Further study of hypoglycaemia as an independent risk factor for MACE in patients with T2DM and coronary disease is needed.
Upper and/or lower gastrointestinal adverse events with glucagon‐like peptide‐1 receptor agonists: Incidence and consequences
Authors: Horowitz Michael , Aroda Vanita R. , Han Jenny , Hardy Elise , Rayner Chris K.
Published: January 2017

Aims

To characterize gastrointestinal adverse events (AEs) with different glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs).

Methods

Two retrospective intention‐to‐treat analyses of 6‐month patient‐level data were conducted. Data from three studies comparing exenatide once weekly (n = 617) with exenatide twice daily (n = 606) were pooled, and one (DURATION‐6) comparing exenatide once weekly (n = 461) with liraglutide (n = 450) was analysed separately. Patient‐reported gastrointestinal AEs were classified as upper or lower, AE incidences and timing were determined, subgroups were analysed, and associations of gastrointestinal AEs with efficacy were examined.

Results

Nausea was the most common gastrointestinal AE for all treatments. Fewer exenatide once‐weekly‐treated vs exenatide twice‐daily‐ or liraglutide‐treated patients reported gastrointestinal AEs (34% vs 45% and 25% vs 41%, respectively; both
P
 < .0001). Fewer exenatide once‐weekly‐treated patients reported upper plus lower events than liraglutide‐treated patients (
P
 < .001); the difference between exenatide once weekly and twice daily was not significant. Within each group, more women than men reported gastrointestinal AEs. Events occurrred early and were predominantly mild. Glycated haemoglobin reductions were similar for patients with or without gastrointestinal AEs. Weight loss was greater for patients with gastrointestinal AEs with exenatide once weekly and exenatide twice daily (
P
 < .05); no difference was observed in DURATION‐6.

Conclusions

Gastrointestinal AEs were less frequent with exenatide once weekly vs exenatide twice daily or liraglutide, and combined upper and lower events occurred less often. Gastrointestinal AEs were typically mild and occurred early. Gastrointestinal AEs did not affect glycaemic control but may be associated with greater weight loss.