bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Magnetic Resonance Imaging Detects Between-Group Differences in Neural Activation Among Men with Delayed Orgasm Compared with Normal Controls: Preliminary Report
Authors: Flannigan Ryan , Heier Linda , Voss Henning , Chazen J. Levi , Paduch Darius A. 
Published: July 2019

Abstract

Background
Mechanisms underlying delayed orgasm (DO) are poorly understood; however, known effects of psychotropic medications on sexual function provides a rationale for aberrant central nervous system signaling as a cause.

Aim
To compare brain activation between men with normal orgasm and those with lifelong DO during sexual stimulation using brain fMRI algorithms.

Methods
3 subjects with self-reported life-long DO and 6 normal controls were included in this study. The International Index of Erectile Function, Male Sexual Health Questionnaire, and self-reported time to orgasm were used to assess sexual function. Subjects underwent a 3-T fMRI study while viewing 3 video clips: a neutral control (NC), a positive emotional control (EC), and a sexual condition (SC). Each video sequence was repeated 5 times, with 50-second clips presented in a randomized fashion. fMRI data were analyzed in a block design manner to determine areas of differential brain activation between groups. The Allen Brain Atlas of gene expression in the human brain was used to identify signaling pathways in the areas of differential fMRI activation between the DO and control groups.

Outcomes
The primary outcome was differential activation of fMRI neural activation between groups.

Results
Analysis of differential activation in the SC compared with the NC and EC revealed increased activation in the right frontal operculum (P = .003), right prefrontal gyrus (P = .003), and inferior occipital gyrus (P = .003). Increased activation in the right fusiform gyrus of the occipital lobe and the right hippocampus (P = .0004) was seen in the DO group compared with controls. Using the Allen Atlas of Human Brain Expression, we identified corresponding neurotransmitter receptors to this region, including adenosine receptors, muscarinic and nicotinic cholinergic receptors, cannabinoid receptors, and dopamine receptors, among others.

Clinical Implications
Lifelong DO in men may be due to abnormal neurotransmitter signaling leading to poor progression of arousal due to aberrant processing of sexual cues. Identification of neurotransmitter pathways by fMRI will aid the development of pharmacotherapeutic agents.

Strengths & Limitations
Strengths of this study include the novel application of functional neuroimaging to investigate the pathogenesis of DO. Limitations include the small sample size, making this study exploratory in nature.

Conclusion
This study revealed differences in brain activation on visualization of sexual stimuli in men with a history of DO compared with controls. Identified regions are rich in numerous neurotransmitter receptor subtypes and may be amenable to pharmacologic targeting to identify novel therapies for these men.
Sexual Function in Patients Treated With Stereotactic Radiotherapy For Prostate Cancer: A Systematic Review of the Current Evidence
Authors: Loi Mauro , Wortel Ruud C. , Francolini Giulio , Incrocci Luca 
Published: July 2019

ABSTRACT

Introduction
Sexual function can be impaired by all prostate cancer treatment modalities, but studies specifically addressing the impact of stereotactic body radiotherapy (SBRT) on sexual function are scarce.

Aim
To systematically evaluate sexual outcomes in patients treated by SBRT for prostate cancer and determine clinical factors associated with erectile dysfunction (ED).

Methods
A systematic review of the available literature was performed on PubMed/Medline, Scopus, and Cochrane Library databases in June 2017 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Only articles providing data on baseline and post-treatment sexual function after SBRT (≥5 Gy/fraction) were included in this analysis (n = 12).

Main Outcome Measure
Sexual function deteriorates after SBRT of the prostate.

Results
Deterioration of sexual health was found, with Expanded Prostate Cancer Index Composite–26 sexual domain scores showing a median decrease of 9.2 at 12 months and a median decrease of the Sexual Health Inventory for Men subdomain score by 2.7 at 12 months (from baseline median value of 56.3 and 16, respectively). At 60 months, ED was reported by 26–55% of previously sexually functioning patients in 5 of the 12 studies.

Clinical Implications
ED affects ≤55% of previously sexually functioning patients at 5 years, as reported for other non-surgical treatment modalities.

Strengths & Limitations
This study enforced strict inclusion criteria of selected studies and exclusion of patients receiving concurrent androgen deprivation therapy. However, inconsistencies in the choice of assessment tool and definition of ED hamper a robust meta-analysis of pooled data.

Conclusion
Sexual function decline after SBRT for prostate cancer appears to be similar to other modalities and should be specifically addressed in future studies.
Testosterone Levels Are Not Associated With Magnitude of Deformity in Men With Peyronie’s Disease
Authors: Mulhall John P. , Matsushita Kazuhito , Nelson Christian J. 
Published: July 2019

Abstract

Introduction
There are some data suggesting that there is a relationship between the magnitude of Peyronie’s disease (PD)–associated penile curvature and low serum testosterone.

Aim
To evaluate the relationship between PD associated penile deformity and total testosterone (TT) and free testosterone (FT) levels.

Methods
We identified patients diagnosed with PD who had early morning TT measurements. Because laboratories have different reference values, we analyzed testosterone values 2 ways, as raw values and as standardized values (TT and FT values converted into z-scores for each laboratory). Deformity assessment was conducted during an intracavernosal injection–induced rigid erection. The association between T levels and magnitude of penile curvature was analyzed in a number of ways. First, an independent measure t-test tested differences in curvature degree by TT groups (low T: &lt;300 ng/dL; normal T: ≥300 ng/dL). Second, an association was sought between T levels based on quartiles of the normal range (&lt;300, 300–450, 450–600, and &gt;600 ng/dL). These analyses were conducted for both TT and FT levels and using both raw and standardized T values. Third, multivariable analysis using multiple linear regression was performed in an attempt to define predictors of the degree of penile curvature. Factors entered into the model included: TT level, FT level, patient age, race (white vs other), number of co-morbidities, body mass index, presence of erectile dysfunction, duration of PD, and prostatectomy (yes vs no).

Main Outcome Measures
The relationship between T levels and the magnitude of penile curvature.

Results
184 subjects met all study criteria. Average age was 54 ± 12 years. Mean TT level was 425 ± 176 ng/dL, and mean curvature magnitude was 35° ± 19°. The percent of subjects in the first through fourth TT quartiles was 26%, 34%, 24%, and 16%. As a continuous variable, there was no association between TT levels (r = −0.01, P = .95) or FT levels (r = −0.08, P = .30) and the curvature magnitude. When examining TT groups, there was no difference in mean curvature between the low TT group and the normal TT group (35.4° ± 17° vs 34° ± 20°, P = .70). When analyzing the TT and FT levels standardized into z-scores, there was no association between degree of curvature and TT z-scores (r = −0.003, P = .95) and FT z-scores (r = −0.08, P = .43). There was also no association between testosterone levels and degree of curvature in the multivariable model.

Conclusions
There does not appear to be any association between testosterone levels and the magnitude of PD-associated penile deformity.
Mainstreaming Foreign Law in the Asian Law School Curriculum
Authors: DE VISSER Maartje , HARDING Andrew 
Published: July 2019

AbstractExposure to foreign law is immensely valuable as it expands students’ argumentative and analytical terrain. More pragmatically, there has been a discernable shift towards rule-of-law thinking in furthering regional integration and a flurry of Free Trade Agreements (FTAs) involving Asian countries. Law schools ought to capitalize on this reality. The preferred educational strategy to adopt, we argue, entails systematically integrating foreign law across the traditional components that make up undergraduate curricula. Asian law schools should simultaneously offer general comparative courses that train students in comparative methodology and theory, enabling them to become discerning consumers of and sensible contributors to comparative research, including in the context of domestic law reform. In advocating such mainstreaming of foreign law, we further suggest a broad understanding of this notion as encompassing all rules that do not have their origins in the municipal legal order, including those produced by regional organizations like the Association of Southeast Asian Nations (ASEAN) and the South Asian Association for Regional Cooperation (SAARC). Unlike Europe's law schools, which have been laggards in adapting law school curricula to changes in their wider regional environment, Asia's law schools have the opportunity to anticipate the growing relevance of foreign law in practice and thereby ensure that they remain germane to the legal industry and society at large.
Do sound symbolism effects for written words relate to individual phonemes or to phoneme features?
Authors: MONAGHAN PADRAIC , FLETCHER MATTHEW 
Published: July 2019

abstractThe sound of words has been shown to relate to the meaning that the words denote, an effect that extends beyond morphological properties of the word. Studies of these sound-symbolic relations have described this iconicity in terms of individual phonemes, or alternatively due to acoustic properties (expressed in phonological features) relating to meaning. In this study, we investigated whether individual phonemes or phoneme features best accounted for iconicity effects. We tested 92 participants’ judgements about the appropriateness of 320 nonwords presented in written form, relating to 8 different semantic attributes. For all 8 attributes, individual phonemes fitted participants’ responses better than general phoneme features. These results challenge claims that sound-symbolic effects for visually presented words can access broad, cross-modal associations between sound and meaning, instead the results indicate the operation of individual phoneme to meaning relations. Whether similar effects are found for nonwords presented auditorially remains an open question.
JURISDICTION AND FREEZING INJUNCTIONS: A REASSESSMENT
Authors: Saranovic Filip 
Published: July 2019

AbstractThe existing international scope of English freezing injunctions in support of foreign proceedings is excessively claimant-friendly and inconsistent with the need for a level playing field in litigation. The English courts must reconsider the current boundaries of relief by taking into account an international systemic perspective of the purpose of private international law rules. This requires a multilateral and horizontal approach to the existence of jurisdiction rather than the unilateral and vertical approach that exists under the rules of jurisdiction of English national law. The traditional justifications for the availability of collateral freezing injunctions with respect to assets located abroad rest on a series of fundamental theoretical flaws. This article proposes a range of reforms with the aim of strengthening the equality of the parties and eliminating encroachment on the sovereignty of foreign States.
Synthesizing Nile crocodileCrocodylus niloticusattack data and historical context to inform mitigation efforts in South Africa and eSwatini (Swaziland)
Authors: Pooley Simon , Botha Hannes , Combrink Xander , Powell George 
Published: July 2019

AbstractConflicts with wildlife are a major challenge for conservation across Africa, and Nile crocodilesCrocodylus niloticusare allegedly responsible for more attacks on people than any other species; however, there is a lack of data regarding such attacks. We analysed reported attacks on people by Nile crocodiles in South Africa and eSwatini (Swaziland) during 1949–2016, identifying spatial and temporal patterns in attack incidence, as well as victim demographics. Through a literature review and archival searches we identified records of 214 attacks. Most attacks occurred in natural water bodies, with attacks in dams increasing since 2000. Most victims were attacked while swimming or bathing, others while fishing, doing domestic chores, and crossing waterways. There was a significant relationship between gender and activity when attacked. Children (< 16 years old) accounted for 51% of all attacks, with a higher fatality rate compared to adults. Most victims were male (65%), with teenage boys being the largest individual category. We make recommendations for conservation policy and management to mitigate attacks by Nile crocodiles.
Trunk-like Soft Actuator: Design, Modeling, and Experiments
Authors: Bao Guanjun , Chen Lingfeng , Zhang Yaqi , Cai Shibo , Xu Fang , Yang Qinghua , Zhang Libin 
Published: July 2019

SUMMARYIn recent years, soft robotics is widely considered as the most promising field for both research and application. First of all, the actuator is fundamental for designing, modeling, and controlling of soft robots. This paper presents a new type of pneumatic trunk-like soft actuator, which contains a chamber for stiffness adjustment in addition to three chambers for driving. Thus, the salient feature of the proposed actuator is the ability of stiffness self-regulation. The structure of the proposed actuator is described in detail. Then the theoretical models for elongation and bending motion of the actuator are established. The elongation as well as single-chamber and multi-chamber driving bending of the actuator were tested to verify the mathematical models. Finally, a dual-segment soft robot based on the proposed trunk-like soft actuator was developed and tested by experiments, which implies its potential application in practice.
Protection of wear resistance behaviour of enamel against electron beam irradiation
Authors: Hegde Mithra N. , Gatti Priya , Hegde Nidarsh D. 
Published: July 2019

Abstract
Introduction
Irradiation is known to cause oxidation process among the tissue-altering the properties of teeth leading to tissue necrosis and caries formation. Hence protection of the oral cavity is a major concern to deal with therapy side effects.

Aim
Evaluation of wear resistance property of Enamel against electron beam radiation and analysing the radio protective effects of natural organic compounds.

Materials and methods
Total of 36 healthy extracted human molar teeth were collected, four samples were used as control, and remaining 32 were divided into four groups (N = 8 each): radiation control group and three groups treated with organic compounds during radiation treatment. The enamel samples were tested for FTIR spectroscopy, XRD analysis, SEM and EDAX analysis before and after 70 Gy radiation treatment.

Results and discussion
The particle size of radiation control samples had increased showing decrease in its crystallinity index. Calcium to Phosphorous ratio had also decreased along with structural changes as observed by SEM analysis. But groups treated with organic compounds has maintained tooth integrity in comparable to control groups after radiation treatment.

Conclusion
Virgin coconut oil, vitamin E oil and curcumin has potential radioprotective action against radiation in protecting tissue properties. Hence, with further advanced research, these natural substances should emerge as a topical applicator during radiotherapy to oral cancer patients.
Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein
Authors: Zhou Haixia , Chen Yingzhu , Zhang Shuyuan , Niu Peihua , Qin Kun , Jia Wenxu , Huang Baoying , Zhang Senyan , Lan Jun , Zhang Linqi , Tan Wenjie , Wang Xinquan 
Published: July 2019

AbstractMost neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies.
Blockade of leukemia inhibitory factor as a therapeutic approach to KRAS driven pancreatic cancer
Authors: Wang Man-Tzu , Fer Nicole , Galeas Jacqueline , Collisson Eric A. , Kim Sung Eun , Sharib Jeremy , McCormick Frank 
Published: July 2019

AbstractKRAS mutations are present in over 90% of pancreatic ductal adenocarcinomas (PDAC), and drive their poor outcomes and failure to respond to targeted therapies. Here we show that Leukemia Inhibitory Factor (LIF) expression is induced specifically by oncogenic KRAS in PDAC and that LIF depletion by genetic means or by neutralizing antibodies prevents engraftment in pancreatic xenograft models. Moreover, LIF-neutralizing antibodies synergize with gemcitabine to eradicate established pancreatic tumors in a syngeneic, KrasG12D-driven, PDAC mouse model. The related cytokine IL-6 cannot substitute for LIF, suggesting that LIF mediates KRAS-driven malignancies through a non-STAT-signaling pathway. Unlike IL-6, LIF inhibits the activity of the Hippo-signaling pathway in PDACs. Depletion of YAP inhibits the function of LIF in human PDAC cells. Our data suggest a crucial role of LIF in KRAS-driven pancreatic cancer and that blockade of LIF by neutralizing antibodies represents an attractive approach to improving therapeutic outcomes.
Lamin A molecular compression and sliding as mechanisms behind nucleoskeleton elasticity
Authors: Makarov Alex A. , Zou Juan , Houston Douglas R. , Spanos Christos , Solovyova Alexandra S. , Cardenal-Peralta Cristina , Rappsilber Juri , Schirmer Eric C. 
Published: July 2019

AbstractLamin A is a nuclear intermediate filament protein critical for nuclear architecture and mechanics and mutated in a wide range of human diseases. Yet little is known about the molecular architecture of lamins and mechanisms of their assembly. Here we use SILAC cross-linking mass spectrometry to determine interactions within lamin dimers and between dimers in higher-order polymers. We find evidence for a compression mechanism where coiled coils in the lamin A rod can slide onto each other to contract rod length, likely driven by a wide range of electrostatic interactions with the flexible linkers between coiled coils. Similar interactions occur with unstructured regions flanking the rod domain during oligomeric assembly. Mutations linked to human disease block these interactions, suggesting that this spring-like contraction can explain in part the dynamic mechanical stretch and flexibility properties of the lamin polymer and other intermediate filament networks.
Eradication of unresectable liver metastasis through induction of tumour specific energy depletion
Authors: Huo Da , Zhu Jianfeng , Chen Guojun , Chen Qian , Zhang Chao , Luo Xingyu , Jiang Wei , Jiang Xiqun , Gu Zhen , Hu Yong 
Published: July 2019

AbstractTreatment of liver metastasis experiences slow progress owing to the severe side effects. In this study, we demonstrate a strategy capable of eliminating metastatic cancer cells in a selective manner. Nucleus-targeting W18O49 nanoparticles (WONPs) are conjugated to mitochondria-selective mesoporous silica nanoparticles (MSNs) containing photosensitizer (Ce6) through a Cathepsin B-cleavable peptide. In hepatocytes, upon the laser irradiation, the generated singlet oxygen species are consumed by WONPs, in turn leading to the loss of their photothermally heating capacity, thereby sparing hepatocyte from thermal damage induced by the laser illumination. By contrast, in cancer cells, the cleaved peptide linker allows WONPs and MSNs to respectively target nucleus and mitochondria, where the therapeutic powers could be unleashed, both photodynamically and photothermally. This ensures the energy production of cancer cells can be abolished. We further assess the underlying molecular mechanism at both gene and protein levels to better understand the therapeutic outcome.
Genomic diversity and novel genome-wide association with fruit morphology in Capsicum, from 746k polymorphic sites
Authors: Colonna Vincenza , D’Agostino Nunzio , Garrison Erik , Albrechtsen Anders , Meisner Jonas , Facchiano Angelo , Cardi Teodoro , Tripodi Pasquale 
Published: July 2019

AbstractCapsicum is one of the major vegetable crops grown worldwide. Current subdivision in clades and species is based on morphological traits and coarse sets of genetic markers. Broad variability of fruits has been driven by breeding programs and has been mainly studied by linkage analysis. We discovered 746k variable sites by sequencing 1.8% of the genome in a collection of 373 accessions belonging to 11 Capsicum species from 51 countries. We describe genomic variation at population-level, confirm major subdivision in clades and species, and show that the known major subdivision of C. annuum separates large and bulky fruits from small ones. In C. annuum, we identify four novel loci associated with phenotypes determining the fruit shape, including a non-synonymous mutation in the gene Longifolia 1-like (CA03g16080). Our collection covers all the economically important species of Capsicum widely used in breeding programs and represent the widest and largest study so far in terms of the number of species and number of genetic variants analyzed. We identified a large set of markers that can be used for population genetic studies and genetic association analyses. Our results provide a comprehensive and precise perspective on genomic variability in Capsicum at population-level and suggest that future fine genetic association studies will yield useful results for breeding.