bluuebunny/crossref_metadata_2025 huggingface dataset:
A Randomized Switch From Nevirapine-Based Antiretroviral Therapy to Single Tablet Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in Virologically Suppressed Human Immunodeficiency Virus-1-Infected Rwandans
Authors: Collins Sean E. , Grant Philip M. , Uwinkindi Francois , Talbot Annie , Seruyange Eric , Slamowitz Deborah , Mugeni Adeline , Remera Eric , Niyonsenga Simon Pierre , Nyirimigabo Josbert , Uwizihiwe Jean Paul , Dongier Pierre , Muhayimpundu Ribakare , Mazarati Jean-Baptiste , Zolopa Andrew , Nsanzimana Sabin
Published: July 2016

Background.  Many human immunodeficiency virus (HIV)-infected patients remain on nevirapine-based antiretroviral therapy (ART) despite safety and efficacy concerns. Switching to a rilpivirine-based regimen is an alternative, but there is little experience with rilpivirine in sub-Saharan Africa where induction of rilpivirine metabolism by nevirapine, HIV subtype, and dietary differences could potentially impact efficacy.

Methods.  We conducted an open-label noninferiority study of virologically suppressed (HIV-1 ribonucleic acid [RNA] < 50 copies/mL) HIV-1-infected Rwandan adults taking nevirapine plus 2 nucleos(t)ide reverse-transcriptase inhibitors. One hundred fifty participants were randomized 2:1 to switch to coformulated rilpivirine-emtricitabine-tenofovir disoproxil fumarate (referenced as the Switch Arm) or continue current therapy. The primary efficacy endpoint was HIV-1 RNA < 200 copies/mL at week 24 assessed by the US Food and Drug Administration Snapshot algorithm with a noninferiority margin of 12%.

Results.  Between April and September 2014, 184 patients were screened, and 150 patients were enrolled; 99 patients switched to rilpivirine-emtricitabine-tenofovir, and 51 patients continued their nevirapine-based ART. The mean age was 42 years and 43% of participants were women. At week 24, virologic suppression (HIV-1 RNA level <200 copies/mL) was maintained in 93% and 92% in the Switch Arm versus the continuation arm, respectively. The Switch Arm was noninferior to continued nevirapine-based ART (efficacy difference 0.8%; 95% confidence interval, −7.5% to +12.0%). Both regimens were generally safe and well tolerated, although 2 deaths, neither attributed to study medications, occurred in participants in the Switch Arm.

Conclusions.  A switch from nevirapine-based ART to rilpivirine-emtricitabine-tenofovir disoproxil fumarate had similar virologic efficacy to continued nevirapine-based ART after 24 weeks with few adverse events.
Cross-species genome-wide identification of evolutionary conserved microProteins
Authors: Straub Daniel , Wenkel Stephan
Published: July 2016

MicroProteins are small single domain proteins that act by engaging their targets into non-productive protein complexes. In order to identify novel microProteins in any sequenced genome of interest, we have developed miPFinder, a program that identifies and classifies potential microProteins. In the past years, several microProteins have been discovered in plants where they are mainly involved in the regulation of development. The miPFinder algorithm identifies all up to date known plant microProteins and extends the microProtein concept to other protein families. Here, we reveal potential microProtein candidates in several plant and animal reference genomes. A large number of these microProteins are species-specific while others evolved early and are evolutionary highly conserved. Most known microProtein genes originated from large ancestral genes by gene duplication, mutation and subsequent degradation. Gene ontology analysis shows that putative microProtein ancestors are often located in the nucleus, and involved in DNA binding and formation of protein complexes. Additionally, microProtein candidates act in plant transcriptional regulation, signal transduction and anatomical structure development. MiPFinder is freely available to find microProteins in any genome and will aid in the identification of novel microProteins in plants and animals
Shifts in outcrossing rates and changes to floral traits are associated with the evolution of herbicide resistance in the common morning glory
Authors: Kuester Adam , Fall Eva , Chang Shu-Mei , Baucom Regina S.
Published: July 2016

Human-mediated selection can strongly influence the evolutionary response of natural organisms within ecological timescales. But what traits allow for, or even facilitate, adaptation to the strong selection humans impose on natural systems? Using a combination of lab and greenhouse studies of 32 natural populations of the common agricultural weed,Ipomoea purpurea, we show that herbicide resistant populations self-fertilize more than susceptible populations. We likewise show that anther-stigma distance, a floral trait associated with self-fertilization in this species, exhibits a non-linear relationship with resistance such that the most and least resistant populations exhibit lower anther-stigma separation compared to populations with moderate levels of resistance. Overall, our results extend the general finding that plant mating can be impacted by human-mediated agents of selection to that of the extreme selection of the agricultural system. This work highlights the influence of human-mediated selection on rapid responses of natural populations that can lead to unexpected long-term evolutionary consequences.

Statement of authorship

AK collected seeds, performed experiments, analyzed data and wrote the paper; EF collected data; SMC collected data and contributed to the manuscript; RSB designed the study, performed the analyses, and wrote the paper. All authors discussed the results and commented on the manuscript.

Data accessibility

Primary data used in these analyses will be made available in the public github repositoryhttps://github.com/rsbaucom/MatingSystem2015, which can be anonymously accessed. Upon acceptance, data will be made available through the Dryad public repository.
Tempus et Locus: a tool for extracting precisely dated viral sequences from GenBank, and its application to the phylogenetics of primate erythroparvovirus 1 (B19V)
Authors: Carter Alice R. , Gatherer Derek
Published: July 2016

The presence of data in the “collection_date” field of a GenBank sequence record is of great assistance in the use of that sequence for Bayesian phylogenetics using “tip-dating”. We presentTempus et Locus(TeL), a tool for extracting such sequences from a GenBank-formatted sequence database. TeL shows that 60% of viral sequences in GenBank have collection date fields, but that this varies considerably between species. Primate erythroparvovirus 1 (human parvovirus B19 or B19V) has only 40% of its sequences dated, of which only 112 are of more than 4 kb. 100 of these are from B19V sub-genotype 1a and were collected from a mere 6 studies conducted in 5 countries between 2002 and 2013. Nevertheless, Bayesian phylogenetic analysis of this limited set gives a date for the common ancestor of sub-genotype 1a in 1990 (95% HPD 1981-1996) which is in reasonable agreement with estimates of previous studies where collection dates have been assembled by more laborious methods of literature search and direct enquiries to sequence submitters. We conclude that although collection dates should become standard for all future GenBank submissions of virus sequences, accurate dating of ancestors is possible with even a small number of sequences if sampling information is high quality.
Simultaneous measurement of chromatin accessibility, DNA methylation, and nucleosome phasing in single cells
Authors: Pott Sebastian
Published: July 2016

Gaining insights into the regulatory mechanisms that underlie the transcriptional variation observed between individual cells necessitates the development of methods that measure chromatin organization in single cells. Here I adapted Nucleosome Occupancy and Methylome-sequencing (NOMe-seq) to measure chromatin accessibility and endogenous DNA methylation in single cells (scNOMe-seq). scNOMe-seq recovered characteristic accessibility and DNA methylation patterns at DNase hypersensitive sites (DHSs). An advantage of scNOMe-seq is that sequencing reads are sampled independently of the accessibility measurement. scNOMe-seq therefore controlled for fragment loss, which enabled direct estimation of the fraction of accessible DHSs within individual cells. In addition, scNOMe-seq provided high resolution of chromatin accessibility within individual loci which was exploited to detect footprints of CTCF binding events and to estimate the average nucleosome phasing distances in single cells. scNOMe-seq is therefore well-suited to characterize the chromatin organization of single cells in heterogeneous cellular mixtures.
Adaptation of the Arizona Cognitive Task Battery for use with the Ts65Dn Mouse Model (Mus musculus) of Down syndrome
Authors: Hunsaker Michael R. , Smith Genevieve K. , Kesner Raymond P.
Published: July 2016

We propose and validate a clear strategy to efficiently and comprehensively characterize neurobehavioral deficits in the Ts65Dn mouse model of Down syndrome. This novel approach uses neurocognitive theory to design and select behavioral tasks that test specific hypotheses concerning the results of Down syndrome. In this manuscript we model in Ts65Dn mice the Arizona Cognitive Task Battery used to study human populations with Down syndrome. We observed specific deficits for spatial memory, impaired long-term memory for visual objects, acquisition and reversal of motor responses, reduced motor dexterity, and impaired adaptive function as measured by nesting and anxiety tasks. The Ts65Dn mice showed intact temporal ordering, novelty detection, and visual object recognition with short delays. These results phenocopy the performance of participants with Down syndrome on the Arizona Cognitive Task Battery. This approach extends the utility of mouse models of Down syndrome by integrating the expertise of clinical neurology and cognitive neuroscience into the mouse behavioral laboratory. Further, by directly emphasizing the reciprocal translation of research between human disease states and the associated mouse models, we demonstrate that it is possible for both groups to mutually inform each others’ research to more efficiently generate hypotheses and elucidate treatment strategies.
Dysregulation of Long Non-coding RNA (lncRNA) Genes and Predicted lncRNA-Protein Interactions during Zika Virus Infection
Authors: Ramaiah Arunachalam , Contreras Deisy , Gangalapudi Vineela , Sameer Padhye Masumi , Tang Jie , Arumugaswami Vaithilingaraja
Published: July 2016

Zika Virus (ZIKV) is a causative agent for poor pregnancy outcome and fetal developmental abnormalities, including microcephaly and eye defects. As a result, ZIKV is now a confirmed teratogen. Understanding host-pathogen interactions, specifically cellular perturbations caused by ZIKV, can provide novel therapeutic targets. In order to complete viral replication, viral pathogens control the host cellular machineries and regulate various factors, including long noncoding RNA (lncRNA) genes, at transcriptional levels. The role of lncRNA genes in the pathogenesis of ZIKV-mediated microcephaly and eye defects is currently unknown. To gain additional insights, we focused on profiling the differentially expressed lncRNA genes during ZIKV infection in mammalian cells. For this study, we employed a contemporary clinical Zika viral isolate, PRVABC59, of Asian genotype. We utilized an unbiased RNA sequencing approach to profile the lncRNA transcriptome in ZIKV infected Vero cells. We identified a total of 121 lncRNA genes that are differentially regulated at 48 hours post-infection. The majority of these genes are independently validated by reverse-transcription qPCR. A notable observation was that the lncRNAs, MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) and NEAT1 (Nuclear Paraspeckle Assembly Transcript 1), are down-regulated upon Zika viral infection. MALAT1 and NEAT1 are known as nuclear localized RNAs that regulate gene expression and cell proliferation. Protein-lncRNA interaction maps revealed that MALAT1 and NEAT1 share common interacting partners and form a larger network comprising of 71 cellular factors. ZIKV-mediated dysregulation of these two regulatory lncRNAs can alter the expression of respective target genes and associated biological functions, an important one being cell division. In conclusion, this investigation is the first to provide insight into the biological connection of lncRNAs and ZIKV which can be further explored for developing antiviral therapy and understanding fetal developmental processes.
An examination of the potential efficacy of high‐intensity fires for reversing woody encroachment in savannas
Authors: Smit Izak P. J. , Asner Gregory P. , Govender Navashni , Vaughn Nicholas R. , van Wilgen Brian W.
Published: July 2016

Frequent fires are often proposed as a way of preventing woody encroachment in savannas, yet few studies have examined whether high‐intensity fires can effectively reverse woody encroachment.

We applied successive fire treatments to examine the effect of fire intensity on woody vegetation structure. The treatments included early dry season, low‐intensity fires; late dry season, higher‐intensity fires; and an unburnt control. We used pre‐ and post‐fire airborne LiDAR to compare vegetation structural changes brought about by fires of different intensity.

Early dry season fires were of lower intensity (1400–2100 kW m−1) than late dry season fires (2500–4300 kW m−1). The two treatments also differed in terms of fuel consumed, scorch heights and char heights, indicating that clear differences in fire intensity and severity were achieved.

After 4 years and two fire applications, relative woody cover increased by between 20 and 110% in different height categories following low‐intensity and control treatments and declined by between 3 and 70% following high‐intensity fire treatments. Declines were markedly higher following two repeated high‐intensity fires than following a high and then a moderate‐intensity fire. Because woody shrubs in lower height classes can recover rapidly, repeated high‐intensity fires would be needed to maintain lower cover.

Tall trees are often assumed to be unaffected by fires. However, we found that the rate of tree loss was directly related to fire intensity, where 36% of trees were lost following repeated high‐intensity fires, compared to 22% after a high‐ and then a moderate‐intensity fire and 6% after two low‐intensity fires (3% without fire).

Synthesis and applications. Using LiDAR data we show that high‐intensity fires can, at least in the short term, significantly reduce woody cover in South African savannas. The use of repeated high‐intensity fires simultaneously causes both a positive (reduction in cover of short shrubs) and a negative (loss of tall trees) outcome, and managers need to make trade‐offs when contemplating the use of fire intensity to achieve specific goals. One potential solution may be to repeatedly apply high‐intensity treatments to some areas, and not to others. This could generate a heterogeneous landscape where grasses become dominant and tall trees become scarce in some places, but in others, tall trees persist (or at least decline at slower rates), and shorter woody shrubs increase in dominance. Whether this would be acceptable, or practical, remains to be tested.
Avian pest control in vineyards is driven by interactions between bird functional diversity and landscape heterogeneity
Authors: Barbaro Luc , Rusch Adrien , Muiruri Evalyne W. , Gravellier Bastien , Thiery Denis , Castagneyrol Bastien
Published: July 2016

Insectivorous birds are increasingly recognized for the crucial pest control services they provide to agroecosystems. While both the foraging activity and functional diversity of birds are enhanced by multiscale habitat heterogeneity, little is known about how these relationships may influence avian top‐down control of insects. Specifically, interactive effects of bird community structure and habitat heterogeneity on pest control across spatial scales have rarely been explored.

We sampled bird communities and measured avian predation on plasticine model prey, as a proxy for lepidopteran pest control, in 20 vineyards of south‐western France. Vineyards differed both in sward heterogeneity at the local scale and amount of surrounding semi‐natural habitats at the landscape scale. Functional diversity metrics and community‐weighted mean traits were computed for bird communities based on a species–trait table including diet, foraging method, nesting site, migration strategy, laying date, home range size, clutch size and body mass. We used mixed models to test for the interacting effects of habitat heterogeneity and bird functional diversity on avian predation rates of plasticine prey.

Contrary to expectations, bird functional diversity decreased with landscape‐scale heterogeneity, but was higher in vineyards managed with heterogeneous sward structures. In contrast, foliage‐gleaning insectivores were more abundant in landscapes supporting more semi‐natural habitats, suggesting an increase in their contribution to pest control along the landscape heterogeneity gradient. Accordingly, we found that avian predation on plasticine prey increased with bird functional evenness both in more heterogeneous vineyards at the local scale and in landscape mosaics supporting more semi‐natural habitats.

Synthesis and applications. Our study demonstrates that habitat heterogeneity at both local and landscape scales influenced avian insectivory in vineyard agroecosystems by interacting with bird community structure. It provides important insights for ecological intensification in vineyards, pointing out that management options need to be adapted to both the functional composition of local bird communities and landscape context. We suggest that both on‐field and off‐field management can be used to enhance natural pest control services provided by birds in vineyards, especially by favouring sward heterogeneity and patches of semi‐natural habitats within large vineyard stands at the landscape scale.
Landscape structure influences urban vegetation vertical structure
Authors: Mitchell Matthew G. E. , Wu Dan , Johansen Kasper , Maron Martine , McAlpine Clive , Rhodes Jonathan R.
Published: July 2016

Vegetation vertical structure is important for biodiversity and ecosystem service provision. In cities, however, while variation in the spatial extent and distribution of vegetation has been widely investigated, vertical vegetation structure and its potential drivers have not. Understanding how vegetation vertical structure varies across cities and identifying the potential drivers of this variation will improve the management of urban vegetation for biodiversity and ecosystem services.

We used light detection and ranging (LiDAR) data to quantify the vertical structure of vegetation across Brisbane, Australia, at 1‐km2 and 1‐ha spatial scales and investigated how this structure varied in response to biophysical, socioeconomic, urban form and landscape structure variables.

Using model selection techniques, we found that landscape structure variables related to tree cover (tree cover extent and spatial configuration) best explained the vegetation vertical structure at both spatial scales. Biophysical and urban form variables were also important, but only in combination with landscape structure.

Mean vegetation vertical complexity, foliage projective cover and canopy height at a site all decreased as the treed proportion of the surrounding urban landscape decreased. In general, these vertical structure variables also increased where patches of vegetation were clustered together spatially.

Synthesis and applications. Using light detection and ranging (LiDAR) data and model selection techniques, we show that the extent and vertical structure of urban vegetation are not independent and that reduced extent and increased fragmentation of urban vegetation are associated with simplification of its vertical structure. If common, this relationship means that managing urban vegetation for biodiversity and ecosystem services should not focus solely on the amount of tree cover or green space present across cities, but also on identifying where interventions to improve vegetation vertical complexity are required. Our study provides important insights into where these locations may be in cities.
Comparison of insulin lispro mix 25 with insulin lispro mix 50 as insulin starter in Chinese patients with type 2 diabetes mellitus (CLASSIFY study): Subgroup analysis of a Phase 4 open‐label randomized trial
Authors: Su Qing , Liu Chao , Zheng Hongting , Zhu Jun , Li Peng Fei , Qian Lei , Yang Wen Ying
Published: July 2016

Background

Premixed insulins are recommended starter insulins in Chinese patients after oral antihyperglycemic medication (OAM) failure. In the present study, we compared the efficacy and safety of insulin lispro mix 25 (LM25) twice daily (b.i.d.) and insulin lispro mix 50 (LM50) b.i.d. as a starter insulin regimen in Chinese patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with OAMs.

Methods

The primary efficacy outcome in the present open‐label parallel randomized clinical trial was change in HbA1c from baseline to 26 weeks. Patients were randomized in a ratio of 1:  1 to LM25 (n = 80) or LM50 (n = 76). A mixed‐effects model with repeated measures was used to analyze continuous variables. The Cochran–Mantel–Haenszel test with stratification factor was used to analyze categorical variables.

Results

At the end of the study, LM50 was more efficacious than LM25 in reducing mean HbA1c levels (least‐squares [LS] mean difference 0.48; 95 % confidence interval [CI] 0.22, 0.74; P < 0.001). More subjects in the LM50 than LM25 group achieved HbA1c targets of <7.0 % (72.4 % vs 45.0 %; P = 0.001) or ≤6.5 % (52.6 % vs 20.0 %; P < 0.001). Furthermore, LM50 was more effective than LM25 at reducing HbA1c in patients with baseline HbA1c, blood glucose excursion, and postprandial glucose greater than or equal to median levels (P ≤ 0.001). The rate and incidence of hypoglycemic episodes and increase in weight at the end of the study were similar between treatment groups.

Conclusions

In Chinese patients with T2DM, LM50 was more efficacious than LM25 as a starter insulin.
Investment Financing of Organizational Capital
Authors: Jiang Daniel X. , Luo Miao , Cai Jun
Published: July 2016

We identify that the cost of external capital and the frontier technology (FT) shock level are two important factors affecting external capital supply. We explore how they interact to affect the investment financing of organizational capital (OC). We show that the FT shock level has experienced a dramatic change from being counter‐cyclical before 1991 to pro‐cyclical after 1991. This structural break alters the OC investment sensitivities during the two sub‐periods. We find that the OC investment‐cash flow sensitivity is low and the OC investment‐q sensitivity is high only when the cost of external capital is low and the FT shock level is simultaneously high. These patterns are mainly driven by financially constrained firms. In addition, our empirical findings suggest that OC investments made during recessions when the FT shock level is also low generate higher productivity than in other conditions.
Information Content and Intra‐industry Effects of Cash Refund Capital Reduction Announcements in Taiwan
Authors: Chang Chu‐hsuan , Lu Te‐kang
Published: July 2016

Capital reduction through returning cash to shareholders is one mechanism by which firms distribute their surpluses. While distribution of excess funds can lower agency costs, it may also signal a decline in the firm's future investment opportunities. In this paper, we examine the information content and information transfer effects of the announcement of capital reduction and cash distribution in Taiwan during the period 2002–2010. We find that there is a significantly positive market reaction when Taiwanese firms announce a reduction in their capital and return cash to shareowners. We also document contagion intra‐industry effects by showing that portfolios of rival firms in the same industry experience a significant and contemporaneous positive stock price performance. Consistently, our results support the free cash flow hypothesis of contagion intra‐industry effects in the long‐run stock return and operating performance of firms following cash refund capital reduction announcements. Moreover, multivariate analysis indicates that these contagion effects are influenced by competitors' features, which are negatively correlated with competitors' size and growth opportunity, and positively influenced by their dividend policy and ownership structure.
Derivation of Corporate Debt Pricing Model and Its Empirical Implications
Authors: Kang Won , Shin Jungsoon
Published: July 2016

One of the reasons the empirical capital asset pricing model (CAPM) fails to confirm the theory is because historical returns on stocks are used. On the other hand, the bond returns observed at the time of issuance are expected returns. We combine the empirical CAPM with the Modigliani‐Miller propositions adjusted for risky debts, and propose a corporate debt pricing model (CDPM) which is the flipside of the empirical CAPM. The model shows that the systematic risk of defaultable corporate debt can be measured by the covariance between the returns on debt and equity market index. Using individual firm data, we test three versions of CDPM. All validate the positive relationship between individual deltas and returns with full or partial samples. Since CDPM is directly derived from CAPM, the results prove that CAPM can be validated even with individual firm data if proper expected returns are used in the test.
Enrichment and in vitro features of the putative gonocytes from cryopreserved testicular tissue of neonatal bulls
Authors: Cai H. , Tang B. , Wu J. Y. , Zhao X. X. , Wang Z. Z. , An X. L. , Lai L. X. , Li Z. Y. , Zhang X. M.
Published: July 2016

Enrichment and propagation of gonocytes or spermatogonial stem cells (SSCs) from cryopreserved testicular tissue is essential to applySSCs‐related techniques in large domestic animals. We previously reported the cryopreservation of adult bovine testicular tissue. Here, we conducted the enrichment and culture of putative gonocytes from cryopreserved testicular tissues of post‐natal 1‐day‐old bulls. The testicular structure was well maintained after freezing and thawing. HighermRNAlevels of gonocyte/SSCs markers (PLZF,GFRα1, andUCHL‐1) than those of pluripotency genes (Oct4,Sox2, andNanog) were detected in the frozen–thawed sex cords.GFRα1 was specifically detected in the membrane and cytoplasm of gonocytes by immunostaining. Differential plating provided 40–50% enrichment of putative gonocytes. They were single, paired‐, aligned‐cells, or grape cluster‐like colonies in minimum essential medium (MEM) containing 2.5%FBS + 2 mM glutamine + 100 IU/mLpenicillin‐streptomycin + 40 μg/mLgentamycin + 15 mM HEPES + 10 mM β‐mercaptoethanol + 0.1 mM non‐essential amino acids + 1 mM sodium pyruvate. On day 3, gonocyte progeny increased and the contaminated somatic cells spread and concurrently divided slowly. On day 5, gonocyte progeny proliferated continuously and typical intercellular bridges formed by incomplete cytokinesis in paired‐cells or aligned‐cysts were observed. Immunochemically, they were stillGFRα1 andPLZFpositive. These cells expressed significantly higher gonocyte/SSCs markermRNAs than pluripotency genemRNAs, concomitant with a higher level of differentiated spermatogonia markerc‐kit. With time, gonocyte progeny colonies appeared in varied sizes and expanded dramatically on day 7. After cultured for 9–10 days, however, large colonies collapsed and dispersed as some single cells and small syncytial cysts. Together,MEMcontaining 10% dimethyl sulfoxide + 2.5% newborn calf serum provides efficient cryoprotection for the testicular tissue from 1‐day‐old neonatal bulls. Putative gonocytes enriched from these nascent tissues present robust proliferation capacity, conserved gonocyte/SSCs markers, andSSCs‐like in vitro features.
Cofilin is correlated with sperm quality and influences sperm fertilizing capacity in humans
Authors: Chen S. M. , Chen X. M. , Lu Y. L. , Liu B. , Jiang M. , Ma Y. X.
Published: July 2016

Spermatozoa should undergo a series of biochemical modifications in female reproduction tract, which is collectively called sperm capacitation. The capacitated spermatozoa can bind to the egg zona pellucida, resulting in the occurrence of acrosome reaction which enabled spermatozoa penetrate into the egg. The formation of actin plays an important role in these processes. Actin polymerized during sperm capacitation, but the polymers dispersed before acrosome reaction. In this study, we take our focus on actin‐binding protein, cofilin. Our results showed that the % and intensity of sperm expressing cofilin in normal sperm were significantly higher than in abnormal sperm, and the sperm expressing cofilin was correlated with sperm quality. Furthermore, treatment with anti‐cofilin antibody increased the percentage of sperm capacitation and inhibited progesterone‐ or A23187‐ induced acrosome reaction in a dose‐dependent manner. The presence of 100 ng/mL anti‐cofilin antibodies markedly blocked the sperm penetration of zona‐free hamster eggs. Besides, immunofluorescence results revealed that cofilin was colocalized with F‐actin in the midpiece of spermatozoa; however, phospho‐cofilin was expressed in the tail rather than in the midpiece of spermatozoa, which was not colocalized with F‐actin in spermatozoa. Moreover, western blot revealed that phospho‐cofilin increased in sperm capacitation, and the total cofilin and cofilin in insoluble fraction increased in acrosome reaction; immunofluorescence results showed that the amount of cofilin in acrosome increased in sperm capacitation. In conclusion, our study revealed that cofilin expression in human sperm is correlated with sperm quality and the alterations of cofilin and phospho‐cofilin in fertilization affects sperm capacitation, acrosome reaction, and spermatozoa–oocyte fusion.
Peak systolic velocity thresholds of cavernosal penile arteries in patients with and without risk factors for arterial erectile deficiency
Authors: Cavallini G. , Scroppo F. I. , Zucchi A.
Published: July 2016

To simultaneously assess the peak systolic velocity (PSV) and the end‐diastolic velocity (EDV) at dynamic duplex examination of the cavernosal penile arteries, and penile rigidity in subjects with satisfactory erectile function with and without risk factors for arterial erectile deficiency (ED). This multicenter prospective study examined two populations having satisfactory sexual function with dynamic duplex examination of the cavernosal arteries; one population had risk factors for arterial ED (65 patients, Group 1) and the other (60 patients, Group 2) had no risk factors. Penile rigidity was assessed using the Schramek grading system score (SGSS). The PSV, the EDV, and the SGSS values of Group 1 and of Group 2 were measured and compared using analysis of variance. The EDV and PSV data presented in this abstract are the arithmetical means of the data of the left and right cavernosal arteries. The Group 1 patients showed a mean ± standard deviation PSV of 26.4 ± 13.2 cm/sec and the Group 2 patients showed a PSV of 44.7 ± 9.6 cm/sec (p = 0.002). The EDV of Group 1 was −15.6 ± 16.1 cm/sec and the EDV of Group 2 was −14.9 ± 13.7 cm/sec (p = 0.329). The SGSS in Group 1 was 3.2 ± 0.3 and the SGSS in Group 2 was 4.8 ± 0.2 (p = 0.008). Intra‐ and inter‐operator variability were not statistically significant. The PSVs and the SGSSs of patients with risk factors for ED and satisfactory erectile function were subnormal and significantly lower than the PSVs and the SGSSs of patients without risk factors. It has been hypothesized that compensatory mechanisms, probably of psychological origin, might allow satisfactory erectile response, even in the presence of a subnormal PSV.
How to Restore Fairness After Doping Infringement?
Authors: Hämäläinen Mika
Published: July 2016

This article addresses the question how to restore the biggest possible amount of fairness after a discovery of doping infringement. I will analyse eight actions that could be taken: (1) disqualification and re‐ranking, (2) change in official result, (3) medal stripping and medal re‐awarding, (4) ban, (5) rematch, (6) legal action, (7) apology and (8) forgiveness. I conclude that the best way to restore the biggest possible amount of fairness seems to be a selected combination of actions. I also propose that re‐ranking and medal re‐awarding should be accompanied by a ceremony in which the new winners are celebrated because they typically did not have the possibility of enjoying their success in front of the original audience.
It's immoral, but I'd do it! Psychopathy traits affect decision‐making in sacrificial dilemmas and in everyday moral situations
Authors: Pletti Carolina , Lotto Lorella , Buodo Giulia , Sarlo Michela
Published: July 2016

This research investigated whether emotional hyporeactivity affects moral judgements and choices of action in sacrificial moral dilemmas and in everyday moral conflict situations in which harm to other's welfare is differentially involved. Twenty‐six participants with high trait psychopathy (HP) and 25 with low trait psychopathy (LP) were selected based on the primary psychopathy scale of the Levenson Self‐Report Psychopathy Scale. HP participants were more likely to sacrifice one person to save others in sacrificial dilemmas and to pursue a personal advantage in everyday moral situations entailing harm to another's good. While deciding in these situations, HP participants experienced lower unpleasantness as compared to LP participants. Conversely, no group differences emerged in choice of action and unpleasantness ratings for everyday moral situations that did not entail harm to others. Importantly, moral judgements did not differ in the two groups. These results suggest that high psychopathy trait affects choices of action in sacrificial dilemmas because of reduced emotional reactivity to harmful acts. The dissociation between choice of action and moral judgement suggests that the former is more closely related to emotional experience. Also, emotion seems to play a critical role in discriminating harmful from harmless acts and in driving decisions accordingly.
Extralevator with vs nonextralevator abdominoperineal excision for rectal cancer: the RELAPe randomized controlled trial
Authors: Bianco F. , Romano G. , Tsarkov P. , Stanojevic G. , Shroyer K. , Giuratrabocchetta S. , Bergamaschi R. ,   for the International Rectal Cancer Study Group
Published: July 2016

Aim

A randomized controlled trial was conducted to test the null hypothesis that there is no difference in circumferential resection margin (CRM) between extralevator abdominoperineal excision (ELAPE) and non‐ELAPE for rectal cancer.

Method

This was a multicentre, randomized controlled trial registered as NCT01702116. Patients with rectal cancer involving the external anal sphincter were randomized to ELAPE or non‐ELAPE following neoadjuvant chemoradiation. Randomization was performed according to Consolidated Standards of Reporting Trials (CONSORT) guidelines. The primary end‐point was CRM (in mm), defined as the shortest distance between the tumour and the cut edge of the specimen. Pathologists and centralized pathology were blinded to the patients’ study arm. Interrater reliability (IRR) was assessed using Kendall's coefficient. Intra‐operative perforation (IOP) was any rectal defect determined at pathology. Complications were classified using the Clavien–Dindo classification. Participating surgeons were retrained and credentialed. A sample size calculation showed that 34 subjects would provide sufficient power to reject the null hypothesis.

Results

Thirty‐four patients underwent the allocated intervention. Seventeen patients treated with ELAPE were comparable with 17 patients treated with non‐ELAPE regarding age, gender, body mass index (BMI), American Society of Anesthesiology (ASA) class and pre‐existing comorbidities. CRM depth (7.14 ± 5.76 mm vs 2.98 ± 3.28 mm, P = 0.016) and involvement rates (5.8% vs 41.0%, P = 0.04) were significantly increased in patients treated with ELAPE. The IRR for CRM was 0.78. There were no significant differences in IOP (5.8% vs 11.7%, P = 0.77) and complication rates (29% vs 29%, P = 0.97).

Conclusions

ELAPE was associated with statistically improved CRM with no difference in IOP and complication rates compared with non‐ELAPE for rectal cancer involving the external anal sphincter.
Fine needle aspiration cytology of a nodal low‐grade serous neoplasm: a case report of low‐grade serous carcinoma arising from a serous borderline tumour with cyto‐histological correlation
Authors: Razack R. , Van der Merwe H. , Schubert P.
Published: July 2016

This case report describes a rare case of nodal low grade serous pelvic neoplasia. Together with histological correlation, it illustrates previously undocumented cytomorphological features and also discusses important differential diagnosis and potential pitfalls for misdiagnosis.
Alcohol‐Focused Behavioral Couple Therapy
Authors: McCrady Barbara S. , Wilson Adam D. , Muñoz Rosa E. , Fink Brandi C. , Fokas Kathryn , Borders Adrienne
Published: July 2016

Alcohol Behavioral Couple Therapy (ABCT) has emerged over the last 30 years as a highly efficacious treatment for those with alcohol use disorders. This review highlights the historical and conceptual underpinnings of ABCT, as well as the specific treatment elements and structure. Proposed active ingredients, moderators, and mediators of treatment outcome are discussed. Efficacy is evaluated for reductions in identified patient drinking, improved relationship functioning, and reductions in intimate partner violence. Adaptations of ABCT for substances other than alcohol are described. Other adaptations, including brief interventions, interventions addressing PTSD and TBI along with alcohol use, and interventions deliverable via technology platforms are described. Additional cost‐benefit and cost‐effectiveness findings supporting the economic value of ABCT are noted. Future directions for research in this area include possible adaptations for female identified patients, nontraditional couples, LGBT partners and dyads involving nonintimate partner relationships. The development of more flexible models and enhanced dissemination strategies may improve clinical uptake and utility as well as increasing the feasibility of this treatment for integrated healthcare settings.
Heat resistance throughout ontogeny: body size constrains thermal tolerance
Authors: Klockmann Michael , Günter Franziska , Fischer Klaus
Published: July 2016

Heat tolerance is a trait of paramount ecological importance and may determine a species' ability to cope with ongoing climate change. Although critical thermal limits have consequently received substantial attention in recent years, their potential variation throughout ontogeny remained largely neglected. We investigate whether such neglect may bias conclusions regarding a species' sensitivity to climate change. Using a tropical butterfly, we found that developmental stages clearly differed in heat tolerance. It was highest in pupae followed by larvae, adults and finally eggs and hatchlings. Strikingly, most of the variation found in thermal tolerance was explained by differences in body mass, which may thus impose a severe constraint on adaptive variation in stress tolerance. Furthermore, temperature acclimation was beneficial by increasing heat knock‐down time and therefore immediate survival under heat stress, but it affected reproduction negatively. Extreme temperatures strongly reduced survival and subsequent reproductive success even in our highly plastic model organism, exemplifying the potentially dramatic impact of extreme weather events on biodiversity. We argue that predictions regarding a species' fate under changing environmental conditions should consider variation in thermal tolerance throughout ontogeny, variation in body mass and acclimation responses as important predictors of stress tolerance.
Increased autumn rainfall disrupts predator–prey interactions in fragmented boreal forests
Authors: Terraube Julien , Villers Alexandre , Poudré Léo , Varjonen Rauno , Korpimäki Erkki
Published: July 2016

There is a pressing need to understand how changing climate interacts with land‐use change to affect predator–prey interactions in fragmented landscapes. This is particularly true in boreal ecosystems facing fast climate change and intensification in forestry practices. Here, we investigated the relative influence of autumn climate and habitat quality on the food‐storing behaviour of a generalist predator, the pygmy owl, using a unique data set of 15 850 prey items recorded in western Finland over 12 years. Our results highlighted strong effects of autumn climate (number of days with rainfall and with temperature <0 °C) on food‐store composition. Increasing frequency of days with precipitation in autumn triggered a decrease in (i) total prey biomass stored, (ii) the number of bank voles (main prey) stored, and (iii) the scaled mass index of pygmy owls. Increasing proportions of old spruce forests strengthened the functional response of owls to variations in vole abundance and were more prone to switch from main prey to alternative prey (passerine birds) depending on local climate conditions. High‐quality habitat may allow pygmy owls to buffer negative effects of inclement weather and cyclic variation in vole abundance. Additionally, our results evidenced sex‐specific trends in body condition, as the scaled mass index of smaller males increased while the scaled mass index of larger females decreased over the study period, probably due to sex‐specific foraging strategies and energy requirements. Long‐term temporal stability in local vole abundance refutes the hypothesis of climate‐driven change in vole abundance and suggests that rainier autumns could reduce the vulnerability of small mammals to predation by pygmy owls. As small rodents are key prey species for many predators in northern ecosystems, our findings raise concern about the impact of global change on boreal food webs through changes in main prey vulnerability.
Increased MicroRNA‐1266 levels as a biomarker for disease activity in psoriasis vulgaris
Authors: Seifeldin Neveen Salah , El Sayed Shereen Bendary , Asaad Marwa Kamal
Published: July 2016

Background

Increasing evidence has shown that serum microRNA (miR) levels are useful biomarkers for the diagnosis, prognosis, and therapeutic value in various diseases. Psoriasis is characterized by a specific miR expression profile, with a characteristic miR signature, distinct from that of healthy skin.

Objectives

To understand the role of miR‐1266 in the pathogenesis of psoriasis and to explore if it has the potential as a blood biomarker. We assessed serum miR‐1266 levels in patients with psoriasis before and after treatment and compared it with controls. In addition, we evaluated the relationship between miR‐1266 and clinical severity in psoriasis before and after treatment.

Methods

miR‐1266 was measured using real‐time polymerase chain reaction in 35 patients with chronic plaque psoriasis and 35 healthy controls before and after treatment. Moreover, the correlation between miR‐1266 levels and psoriasis area and severity index score was determined.

Results

Serum miR‐1266 levels were considerably higher in patients with psoriasis than in healthy control subjects. Furthermore, miR‐1266 levels showed a strong positive correlation with psoriasis area and severity index score before and after treatment, having a marked decline with therapy.

Conclusion

miR‐1266 may have an important role in the pathogenesis of psoriasis vulgaris. This may presumably have possible future implications on the treatment of this chronic disease.
The use of patch tests in the diagnosis of delayed hypersensitivity drug eruptions
Authors: Hassoun‐Kheir Nasreen , Bergman Reuven , Weltfriend Sara
Published: July 2016

Background

Adverse drug reactions (ADRs) are common. In the absence of a sufficiently sensitive and specific laboratory test, identification of the culprit drug remains a diagnostic challenge. Patch tests have recently been advocated as a means of detecting drug sensitivity.

Objective

To further elucidate the usefulness of patch tests in revealing the causative drugs of cutaneousADRs (CADRs).

Materials and methods

We conducted a non‐blinded, prospective, controlled clinical trial. Twenty‐five patients with a history ofCADRs were patch tested, and 25 healthy subjects who had never experiencedCADRs served as controls.

Results

A morbilliform eruption was the most frequent skin reaction. Patch tests were positive in eight of the 25 patients withCADR(32%). Specifically, five of the 13 patients with morbilliform drug eruption (38.4%) tested positive, as did one of the four patients with erythema multiforme/Stevens–Johnson syndrome (25%), and one of the two patients with the drug reaction with eosinophilia and systemic symptoms syndrome. Antibiotics and anticonvulsants resulted in positive patch tests most often. Patch test sensitivity was 32%, specificity was 92%, and negative and positive predictive values were 57.5% and 80%, respectively. Significant correlation was found between the patch test result and the clinical probability of aCADRaccording to the imputability score of the drug.

Conclusions

Patch testing for drugs causingADRs shows high specificity rates even though the sensitivity is low. Such tests may therefore be useful in supporting the diagnosis of delayed‐typeCADRs, particularly when antibiotics or anticonvulsants are involved and the cutaneous reaction is a morbilliform rash.
Long‐term follow‐up and management of small and medium‐sized CD4+ T cell lymphoma and CD8+ lymphoid proliferations of acral sites: a multicenter experience
Authors: Virmani Pooja , Jawed Sarah , Myskowski Patricia L. , Horwitz Steven , Skripnik Lucas Anna , Moskowitz Alison , Pulitzer Melissa , Zain Jasmine , Rosen Steven T. , Querfeld Christiane
Published: July 2016

Background

Primary cutaneous CD4+ small–medium pleomorphic T cell lymphoma (SMPTCL) is a low‐grade cutaneous T cell lymphoma. Its clinical and histopathologic features are comparable with those of CD8+ lymphoid proliferations (LPs) of the ear and acral sites.

Objectives

We performed a retrospective analysis of patients with CD4+ SMPTCL or CD8+ LP to elucidate the clinical course, prognosis, and outcomes.

Methods

Demographic, clinical, and treatment data were reviewed. Histopathologic data based on architectural, cytomorphologic, and immunohistochemical features were assessed. Immunohistochemical staining for T and B cell markers was evaluated.

Results

A total of 25 patients including 22 with CD4+ SMPTCL and three with CD8+ LP were identified. All patients presented with a single lesion, predominantly on the head, neck, or upper trunk (84%). No patients showed extracutaneous disease at any evaluation. The most common histopathologic changes showed a dense nodular infiltrate of small cells with hyperchromatic nuclei without significant follicular or adnexal involvement. Patients were treated with excision (48%), local radiation (28%), or topical or intralesional steroids (24%). All patients achieved complete resolution of disease. Five patients demonstrated cutaneous relapse at new sites.

Conclusions

The CD4+ SMPTCL/CD8+ LP subgroup usually presents with solitary lesions and demonstrates an indolent clinical course. Typical presentation, classic histopathology, widespread expression of follicular T helper cell markers, and loss of a T cell antigen are diagnostic features of CD4+ SMPTCL, whereas monomorphous CD8+ infiltrate without follicular T helper cell markers is consistent with CD8+ LP. Local skin‐directed therapy is appropriate in these patients.