bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug-Associated Spontaneous Orgasm: A Case Report and Systematic Review of Literature
Authors: Chen Wei-Hsi , Chu Yuan-Hsiang , Chen Kuo-Yen 
Published: December 2017

Objectives
Spontaneous orgasm is characterized by a spontaneous onset of orgasm without any preceding sexual or nonsexual trigger. It sheds insight on the mechanisms underlying orgasms and the sexual response cycle in humans.

Methods
We report a male patient of repetitive spontaneous orgasm under trazodone treatment and systematically review the literature on drug-associated spontaneous orgasm (DASO).

Results
A total of 25 patients (18 women and 7 men), including our reported case, experienced 27 DASO events. Over half of them were under 50 years of age during the DASO event. Depression was the leading morbidity for these patients, and a limited list of antidepressants and antipsychotics were involved in 92.5% of all DASO events. Although offending drugs possess variable pharmacological properties, their common effect is an augmentation of serotonin-1A (5HT1A) neurotransmission. Offending drugs seemingly increase personal susceptibility to DASO. Over half of the patients, especially men, did not concurrently experience sexual arousal or desire during the DASO event. In the remaining patients, the orgasm was accompanied by or ensued with arousal or desire. A reduction of dose or discontinuation of the offending drug usually abolished DASO.

Conclusions
It appears that 5HT1A has a key role in generating orgasm. Orgasms may be activated through arousal-independent or arousal-dependent pathways, and both orgasms and sexual arousal are bidirectionally activated. This double-bidirectional model of sexual response cycle may promote the success of sexual procreation and recreation, and further research on this pathway could offer an innovative method to manage anorgasmia in the future.
Integrating Multiplex SiMPull and Computational Modeling to Evaluate Combinatorial Aspects of EGFR Signaling
Authors: Salazar-Cavazos Emanuel , Nitta Carolina Franco , Mitra Eshan D. , Wilson Bridget S. , Lidke Keith A , Hlavacek William S. , Lidke Diane S. 
Published: December 2017

AbstractThe Epidermal Growth Factor Receptor (EGFR/ErbB1/HER1) plays an important role in both physiological and cancer-related processes. To study the factors that influence receptor phosphorylation, we have coupled Single Molecule Pull-down (SiMPull) measurements with rule-based modeling of EGFR signaling. Using SiMPull, we quantified the phosphorylation state of thousands of individual receptors. These measurements enabled the first direct detection of multisite phosphorylation on full-length EGFR and revealed that the extent of phosphorylation varies by tyrosine site and is dependent on the relative abundance of signaling partners that limit access by tyrosine phosphatases. We also evaluated the impact of oncogenic mutations and ligands with varying affinity on phosphorylation kinetics. Simulations highlight the importance of dimer lifetimes on EGFR phosphorylation and signaling output.
Collateral sensitivity to β-lactam drugs in drug-resistant tuberculosis is driven by the transcriptional wiring of BlaI operon genes
Authors: Trigos AS , Goudey BW , Bedő J , Conway TC , Faux NG , Wyres KL 
Published: December 2017

AbstractBackground:The evolution and spread of antimicrobial resistance is a major global public health threat. In some cases the evolution of resistance to one antimicrobial seemingly results in enhanced sensitivity to another (known as ‘collateral sensitivity’). This largely underexplored phenomenon represents a fascinating evolutionary paradigm that opens new therapeutic possibilities for patients infected with pathogens unresponsive to classical treatments. Intrinsic resistance to β-lactams in Mycobacterium tuberculosis (Mtb, the causative agent of tuberculosis) has traditionally curtailed the use of these low-cost and easy-to-administer drugs for tuberculosis treatment. Recently, β-lactam sensitivity has been reported in strains resistant to classical tuberculosis drug therapy, leading to a resurgence of interest in using β-lactams in the clinic. Unfortunately though, there remains a limited understanding of the mechanisms driving β-lactam sensitivity.Methods:We used a novel combination of systems biology and computational approaches to characterize the molecular underpinnings of β-lactam sensitivity in Mtb. We performed differential gene expression and coexpression analyses of genes previously associated with β-lactam sensitivity and genes associated with resistance to classical tuberculosis drugs. Protein-protein interaction and gene regulatory network analyses were used to validate regulatory interactions between these genes, and random walks through the networks identified key mediators of these interactions. Further validation was obtained using functional in silico knockout of gene pairs.Results:Our results reveal up regulation of the key regulatory inhibitor of β-lactamase production, blal, following treatment with classical drugs. Co-expression and network analyses showed direct co-regulation between genes associated with β-lactam sensitivity and those associated with resistance to classical tuberculosis treatment. blal and its downstream genes (sigC and atpH) were found to be key mediators of these interactions.Conclusions:Our results support the hypothesis that Mtb β-lactam sensitivity is a collateral consequence of the evolution of resistance to classical tuberculosis drugs, mediated through changes to transcriptional regulation. These findings support continued exploration of β-lactams for the treatment of tuberculosis, particularly for patients infected with strains resistant to classical therapies that are otherwise difficult to treat. Importantly, this work also highlights the potential of systems-level and network biology approaches to improve our understanding of collateral drug sensitivity.
Shifts in plant functional strategies over the course of wheat domestication
Authors: Roucou Agathe , Violle Cyrille , Fort Florian , Roumet Pierre , Ecarnot Martin , Vile Denis 
Published: December 2017

Abstract

Human selection, changes in environmental conditions and management practices drove the phenotypic trajectory of crops during domestication. The characterization of the crop domestication syndrome lies mostly on reproductive characters. However, biophysical and ecophysiological constraints during vegetative growth are also at play and can strongly impact crop phenotypes. It has been argued that a broadened examination of crop phenotypes through a functional trait‐based lens should improve our understanding of the domestication syndrome.

We used a collection of 39 genotypes representative of key steps during tetraploid wheat domestication and grew them in a common garden experiment. We quantified the vegetative phenotype of each genotype through the measurements of 13 functional traits related to root, leaf and whole‐plant dimensions.

In modern cultivars, compared to ancestral forms, leaf longevity was shorter, while net photosynthetic rate, leaf production rate and nitrogen content were higher. Modern cultivars had a shallower root system and exhibited a larger proportion of fine roots, preferring to invest biomass above‐rather than below‐ground. We found ancestral forms to be integrated phenotypes characterized by coordination between above‐ and below‐ground functioning. Conversely, in modern forms, human selection appeared to have broken this coordination and to have generated a new type of network of trait covariations.

Synthesis and applications. The examination of leaf, root and whole‐plant traits of wheat accessions indicated a strong shift in plant functional strategies over the course of domestication. Elite genotypes tended to better optimize resource‐use acquisition strategies than ancestral ones. The characterization of the crop phenotype based on vegetative traits thus suggests a much more complete domestication syndrome. Our findings highlight the benefits of using a functional trait‐based characterization of crop phenotypes to document the extent of domestication syndrome and to further advance the agroecological management of cereals.
Great Expectations: The Job at the Top and the People who do it
Authors: Allen Nicholas 
Published: December 2017

AbstractAnthony King thought and wrote a great deal about British prime ministers and political leadership more generally. But in contrast to the way in which single papers embodied his contribution to our understanding of ‘government overload’, ‘executive‐legislative relations’ and ‘career politicians’, his contribution to our understanding of the prime ministership was defined by a body of work. This essay explores that body of work and identifies some of the themes that characterised it. It then relates King's work to claims about the ‘presidentialisation’ of the office, as well as the importance of the expectations surrounding contemporary prime ministers. As Britain grapples with the challenge of Brexit, we should all take note of his counsel against expecting too much in the way of ‘strong’ prime ministerial leadership.
Remembering Tony King
Authors: Wright Tony 
Published: December 2017

AbstractTony King combined scholarship with a real‐world grasp that few could match. This was evident both in his public activities and in his published work. His studies of legislatures and of career politicians changed the way in which issues were viewed and he was skilled at identifying emerging trends before anyone else. He analysed the failings of government, but always as a practical improver. He was a natural communicator in the Bagehot tradition, as evidenced in his writings on the constitution, and he wanted a less adversarial political culture. He showed political scientists that it was possible to combine good scholarship with an ability to communicate.
Friends of the Court? Why EU governments file observations before the Court of Justice
Authors: DEDERKE JULIAN , NAURIN DANIEL 
Published: December 2017

AbstractThe preliminary reference procedure under which the Court of Justice of the European Union (CJEU) responds to questions from national courts regarding the interpretation of EU law is a key mechanism in many accounts of the development of European integration and law. While the significance of the procedure has been broadly acknowledged, one aspect has been largely omitted: The opportunity for member state governments to submit their views (‘observations’) to the Court in ongoing cases. Previous research has shown that these observations matter for the Court's decisions, and thus that they are likely to have a significant impact on the course of European integration. Still, little is known about when and why member states decide to engage in the preliminary reference procedure by submitting observations. This article shows that there is significant variation, both between cases and between member states, in the number of observations filed. A theoretical argument is developed to explain this variation. Most importantly, a distinction is made between legal and political reasons for governments to get involved in the preliminary reference cases, and it is argued that both types of factors should be relevant. By matching empirical data from inter‐governmental negotiations on legislative acts in the Council of the EU with member states’ subsequent participation in the Court procedures, a research design is developed to test these arguments. It is found that the decision to submit observations can be tied both to concerns with the doctrinal development of EU law and to more immediate political preferences. The conclusion is that the legal (the CJEU) and political (the Council) arenas of the EU system are more interconnected than some of the previous literature would lead us to believe.
Concomitant Psychiatric and Nonalcohol‐Related Substance Use Disorders Among Hospitalized Patients with Alcoholic Liver Disease in the United States
Authors: Jinjuvadia Raxitkumar , Jinjuvadia Chetna , Puangsricharoen Pimpitcha , Chalasani Naga , Crabb David W. , Liangpunsakul Suthat ,   the Translational Research and Evolving Alcoholic Hepatitis Treatment Consortium
Published: December 2017

BackgroundDespite that the epidemiological studies on the comorbidity of alcohol misuse and psychiatric disorders have been studied, less is known about the magnitude of these disorders among patients with alcoholic liver disease (ALD). Our aim was to determine the prevalence of psychiatric and substance use disorders among hospitalized ALD patients in the United States.MethodsWe utilized a single‐level clinical classification software to identify patients with ALD and psychiatric/substance use disorders from the 2011 National Inpatient Sample data. The primary outcome was the prevalence of these disorders among hospitalized patients with ALD (n = 74,972) compared to those with chronic liver diseases not caused by alcohol (n = 350,140) and those without underlying liver diseases (n = 1,447,063).ResultsThe prevalence of adjustment disorder, anxiety disorder, posttraumatic stress disorder, and depression was significantly higher among hospitalized patients with ALD when compared to those with chronic liver diseases not caused by alcohol (all with p‐values <0.05). Younger age, female gender, and White race were the independent predictors of psychiatric/substance use disorders among hospitalized patients with ALD.ConclusionsHospitalized patients with ALD have significantly high prevalence of concomitant psychiatric and substance abuse disorders when compared to those with chronic liver diseases not caused by alcohol and those without underlying liver diseases. Screening and appropriate intervention should be implemented as part of routine clinical care for these patients.
Epidemiology and morphology of full‐thickness macular holes
Authors: Forsaa Vegard Asgeir , Lindtjørn Birger , Kvaløy Jan Terje , Frøystein Torbjørn , Krohn Jørgen 
Published: December 2017

AbstractPurposeTo investigate the incidence of full‐thickness macular holes (FTMHs) and their morphological features according to the International Vitreomacular Traction Study (IVTS) classification.MethodsThe clinical records of all new patients with FTMH, referred between 2008 and 2014, were reviewed for demographics, cause of the FTMH, age at diagnosis, symptom duration, laterality, visual acuity (VA), axial length and lens status. A detailed analysis of the patients’ spectral domain optical coherence tomography (SD‐OCT) images was performed, and the primary FTMHs were classified in clinical stages according to the IVTS classification. From the SD‐OCT, accurate macula drawings were made by means of a computer‐drawing software. By merging these drawings and displaying them as colour‐coded maps, the morphology and shape of the FTMH were visualized.ResultsThe study included 177 eyes (152 primary and 25 secondary FTMH) in 166 patients. In primary FTMH, the male‐to‐female ratio was 1:2.2. The age‐ and gender‐adjusted annual incidences of primary FTMH were 7.9 eyes and 7.4 individuals per 100 000 inhabitants. Mean primary FTMH minimum linear diameter (MLD) and basal diameter (BD) were 435 μm and 872 μm, respectively, and 13% were classified as small, 31% as medium and 55% as large. Vitreomacular traction (VMT) and epiretinal membrane (ERM) were present in 34% and 36% of the eyes, respectively.ConclusionThis study provides data on the incidence rates of FTMH adjusted to different standard populations. The morphological analysis and novel computational visualization technique offer new insight into the structural complexity of FTMH and how VMT and ERM significantly influence FTMH configuration.
Design, synthesis, and molecular docking studies of N‐(9,10‐anthraquinone‐2‐carbonyl)amino acid derivatives as xanthine oxidase inhibitors
Authors: Zhang Ting‐Jian , Li Song‐Ye , Yuan Wei‐Yan , Zhang Yi , Meng Fan‐Hao 
Published: December 2017

A series of N‐(9,10‐anthraquinone‐2‐carbonyl)amino acid derivatives (1a–j) was designed and synthesized as novel xanthine oxidase inhibitors. Among them, the L/D‐phenylalanine derivatives (1d and 1i) and the L/D‐tryptophan derivatives (1e and 1j) were effective with micromolar level potency. In particular, the L‐phenylalanine derivative 1d (IC50 = 3.0 μm) and the D‐phenylalanine derivative 1i (IC50 = 2.9 μm) presented the highest potency and were both more potent than the positive control allopurinol (IC50 = 8.1 μm). Preliminary SAR analysis pointed that an aromatic amino acid fragment, for example, phenylalanine or tryptophan, was essential for the inhibition; the D‐amino acid derivative presented equal or greater potency compared to its L‐enantiomer; and the 9,10‐anthraquinone moiety was welcome for the inhibition. Molecular simulations provided rational binding models for compounds 1d and 1i in the xanthine oxidase active pocket. As a result, compounds 1d and 1i could be promising lead compounds for further investigation.
The association between irisin and muscle metabolism in different thyroid disorders
Authors: Zybek‐Kocik Ariadna , Sawicka‐Gutaj Nadia , Szczepanek‐Parulska Ewelina , Andrusiewicz Mirosław , Waligórska‐Stachura Joanna , Białas Piotr , Krauze Tomasz , Guzik Przemysław , Skrobisz Jerzy , Ruchała Marek 
Published: December 2017

SummaryBackgroundIrisin is a new adipo‐myokine, encoded by the FNDC5 gene. Currently, there is a discussion regarding the relation between thyroid function and irisin concentration. This prospective study assesses the influence of thyrometabolic changes on serum irisin concentration in association with altered muscle metabolism. This is performed on a large cohort of patients affected by severe hypo‐ or hyperthyroidism, as well as by the expression of the FNDC5 gene in thyroid tissue affected by different pathologies.MethodsThe study group comprised 119 patients with newly diagnosed severe hyperthyroidism or hypothyroidism, and a control group of 45 healthy subjects. Body composition, serum irisin concentrations, and thyroid‐related hormones, creatine kinase, dystrophin and titin concentrations were evaluated. FNDC5 expression was also analysed in tissue samples from 80 patients with nontoxic multinodular goitre, toxic goitre, Graves’ disease and papillary thyroid cancer.ResultsIrisin concentration was lower in patients with prolonged hypothyroidism. There was a tendency towards lower dystrophin and titin concentrations in patients with hypothyroidism and hyperthyroidism. Restoration of euthyroidism in patients with hypothyroidism resulted in a decreased muscle mass with an increase in irisin concentrations, while the hyperthyroid group showed an increase in fat mass. Statistically significant overexpression of FNDC5 gene was found in patients with toxic goitre as compared to Graves’ disease, papillary thyroid cancer and controls.ConclusionsThe presented data support the theory that irisin concentration changes are associated with prolonged hypothyroidism and might primarily constitute the result of prolonged myopathy. These changes are most likely not related to the expression of the FNDC5 gene in the thyroid gland.
Sustainability and depth of outreach: Evidence from microfinance institutions in sub‐Saharan Africa
Authors: Awaworyi Churchill Sefa 
Published: December 2017

AbstractThe feasibility of microfinance institutions (MFIs) to expand outreach to the poorest while remaining financially sustainable has long been debated. Using data from 206 MFIs in 33 African countries, we adopt the three‐stage least square technique to assess whether a trade‐off exists between sustainability and outreach depth. Our results confirm the existence of a trade‐off. The evidence also supports ongoing subsidies for MFIs with the aim of encouraging outreach. In addition, we examine whether there is an inflection point beyond which higher interest rates reduce profitability for MFIs. We find no evidence of a threshold beyond which profitability is reduced.
What is the role of mitochondrial dysfunction in skin photoaging?
Authors: Naidoo Khimara , Hanna Rebecca , Birch‐Machin Mark A. 
Published: December 2017

AbstractSkin ageing is a complex process involving both internal and external factors, which leads to a progressive loss of cutaneous function and structure. Solar radiation is the primary environmental factor implicated in the development of skin ageing, and the term photoaging describes the distinct clinical, histological and structural features of chronically sun‐exposed skin. The changes that accompany photoaging are undesirable for aesthetic reasons and can compromise the skin and make it more susceptible to a number of dermatological disorders. As a result, skin ageing is a topic that is of growing interest and concern to the general population, illustrated by the increased demand for effective interventions that can prevent or ameliorate the clinical changes associated with aged skin. In this viewpoint essay, we explore the role that mitochondria play in the process of skin photoaging. There is continuing evidence supporting the proposal that mitochondrial dysfunction and oxidative stress are important contributing factors in the development of skin photoaging. Further skin‐directed mitochondrial research is warranted to fully understand the impact of mitochondrial status and function in skin health. A greater understanding of the ageing process and the regulatory mechanisms involved could lead to the development of novel preventative interventions for skin ageing.
Report card on ecosystem‐based fisheries management in tuna regional fisheries management organizations
Authors: Juan‐Jordá Maria José , Murua Hilario , Arrizabalaga Haritz , Dulvy Nicholas K , Restrepo Victor 
Published: December 2017

AbstractInternational instruments of fisheries governance have set the core principles for the management of highly migratory fishes. We evaluated the progress of tuna Regional Fisheries Management Organizations (tRFMOs) in implementing the ecological component of ecosystem‐based fisheries management (EBFM). We first developed a best case tRFMO for EBFM implementation. Second, we developed criteria to evaluate progress in applying EBFM against this best case tRFMO. We assessed progress of the following four ecological components: target species, bycatch species, ecosystem properties and trophic relationships, and habitats. We found that many of the elements necessary for an operational EBFM are already present, yet they have been implemented in an ad hoc way, without a long‐term vision and a formalized plan. Overall, tRFMOs have made considerable progress monitoring the impacts of fisheries on target species, moderate progress for bycatch species, and little progress for ecosystem properties and trophic relationships and habitats. The tRFMOs appear to be halfway towards implementing the ecological component of EBFM, yet it is clear that the “low‐hanging fruit” has been plucked and the more difficult, but surmountable, issues remain, notably the sustainable management of bycatch. All tRFMOs share the same challenge of developing a formal mechanism to better integrate ecosystem science and advice into management decisions. We hope to further discussion across the tRFMOs to inform the development of operational EBFM plans.