bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of Peyronie's Disease with Collagenase Clostridium histolyticum and Vacuum Therapy: A Randomized, Open-Label Pilot Study
Authors: Ralph David J. , Abdel Raheem Amr , Liu Genzhou 
Published: September 2017

Abstract

Background
Collagenase Clostridium histolyticum (CCH) is indicated for the treatment of penile curvature in adult men with Peyronie's disease (PD) with palpable plaque and curvature deformity of at least 30° at the start of therapy.

Aim
To evaluate the efficacy and safety of CCH plus vacuum-pump therapy with and without penile modeling for the management of PD.

Methods
Adult men with PD and penile curvature of at least 30° were randomly assigned to receive CCH 0.58 mg plus vacuum therapy alone (n = 15) or with penile plaque modeling (n = 15). Patients received no more than four treatment cycles (cycle = ∼6-week duration), each consisting of two intralesional injections of CCH administered 24 to 72 hours apart. Vacuum therapy was applied twice daily from 14 days after the second injection of each cycle until the following cycle. Modeling was performed 24 to 72 hours after the second injection of each cycle.

Outcomes
The primary end point was change in penile curvature from baseline to week 36; additional end points included changes in Peyronie's Disease Questionnaire (PDQ) domain scores, composite response (≥20% decrease in penile curvature and decrease in PDQ bother score ≥ 1 point), and global response (small but important, moderate, or much improvement in the Global Assessment of PD).

Results
At week 36, improvement in penile curvature from baseline was similar in the two groups (mean change from baseline = −23.7° [SD = 10.9] for CCH + vacuum + modeling and −23.3° [SD = 7.2] for CCH + vacuum; between-group difference = −0.3°, 95% CI = −7.3 to 6.6). Improvements in most PDQ domains, including bother, were observed from baseline to week 36 in the two groups. Most patients were composite (66.7% and 84.6% with CCH + vacuum + modeling and CCH + vacuum, respectively) and global (86.7% and 92.3%, respectively) responders. The most common adverse events were penile contusion, penile swelling, and penile pain.

Clinical Implications
Vacuum-pump therapy administered alone or in combination with modeling after CCH treatment could improve PD symptoms.

Strengths and Limitations
This was a pilot study with a small sample and limited follow-up duration.

Conclusion
CCH and vacuum-pump therapy (alone or combined with modeling) could be an appropriate consideration for men with PD and warrants further investigation.
Characteristics of Subgroups in the Adult Baby/Diaper Lover Community
Authors: Zamboni Brian D. 
Published: September 2017

Abstract

Background
There is a lack of research on adult baby/diaper lover (ABDL) behavior, particularly from community samples. Prior studies have not examined differences between the AB and DL subgroups in the ABDL community.

Aim
To explore whether endorsements of AB role-play enjoyment and ratings of sexual enjoyment during ABDL activity were related to parenting and attachment variables, negative mood states, and reported problems with ABDL and to explore differences by relationship status and by sexual orientation.

Method
Data from a larger survey of an online ABDL community were analyzed. The final sample included 1,795 men and 139 women.

Outcomes
Participants completed questions about their ABDL interests, the short form of the Experiences in Close Relationships Scale, the Maternal and Paternal Relationship Scales designed for this study, the shortened version of the Profile of Mood States, and questions about problems with ABDL.

Results
Greater enjoyment of role playing was associated with being raised by a single female caregiver, a more negative paternal relationship, higher attachment anxiety, and more negative mood states. Differences based on relationship status and sexual orientation were minimal. Participants who most liked no sexual activity reported higher enjoyment of role playing and lower enjoyment of sexual activity in ABDL behavior compared with other groups. Regardless of sexual orientation, men rated sexual enjoyment in ABDL higher than role-play enjoyment. Ratings of sexual interest in diapers were generally not different from ratings of sexual interest in adults.

Clinical Implications
ABDL clients who enjoy role playing and want to understand their behaviors might wish to explore family-of-origin experiences more than clients who find diapers erotic. Clients who find diapers erotic are likely to have other sexual interests. ABDL subgroups are generally comfortable with their practices and might not have a need for therapy.

Strengths and Limitations
Despite the lack of a comparison group, this study has a large, non-psychiatric sample of a marginalized sexual subculture and affirms that such individuals should not be readily pathologized.

Conclusion
In contrast to persons who find diapers erotic, AB role playing is more likely to be an interpersonal, non-sexual behavior helping some individuals decrease attachment anxiety and negative mood states. Atypical behaviors are not troubling for some individuals, regardless of the origins and motivations of the behavior.
A nomogram predicting re‐operation due to secondary hemorrhage after monopolar transurethral resection of prostate
Authors: Guo Run‐Qi , Yu Wei , Meng Yi‐Sen , Zhang Kai , Xu Ben , Xiao Yun‐Xiang , Wu Shi‐Liang , Pan Bai‐Nian 
Published: September 2017

AbstractWe aim to develop a nomogram to predict re‐operation due to secondary hemorrhage after Monopolar transurethral resection of the prostate (M‐TURP). We identified patients undergoing M‐TURP at Peking University First Hospital from 2000 to 2013. Univariate and multivariate logistic regression models were developed to predict the occurrence re‐operation due to secondary hemorrhage. The discriminatory ability of the nomogram was tested using the area under the receiver operating characteristic curve (ROC), and internal validation was performed via bootstrap resampling. Of the 1901 patients who underwent M‐TURP during the study period, 9.1% (173 patients) experienced hemorrhage after M‐TURP, and they had a 22.0% re‐operation rate (38 patients). Benign prostatic hyperplasia (BPH)‐related complications (odds ratio, 0.386; 95% CI, 0.177–0.841), percent of resected prostate (OR, 0.156; 95% CI, 0.023–1.060) and suprapubic cystostomy (OR, 0.298; 95% CI, 0.101–0.881) were independently associated with re‐operation. The nomogram accurately predicted re‐operation (area under the ROC curve 0.718). The negative predictive value was 88.0%, while the positive predictive value was 47.9%. Re‐operation due to secondary hemorrhage after M‐TURP was associated with no BPH‐related complications, lower percent of resected prostate and no suprapubic cystostomy and was accurately predicted with using the nomogram.
Central sensitization associated with low fetal hemoglobin levels in adults with sickle cell anemia
Authors: Darbari Deepika S. , Vaughan Kathleen J. , Roskom Katherine , Seamon Cassie , Diaw Lena , Quinn Meghan , Conrey Anna , Schechter Alan N. , Haythornthwaite Jennifer A. , Waclawiw Myron A. , Wallen Gwenyth R. , Belfer Inna , Taylor VI James G. 
Published: September 2017

Abstract
Pain is the hallmark of sickle cell anemia (SCA), presenting as recurrent acute events or chronic pain. Central sensitization, or enhanced excitability of the central nervous system, alters pain processing and contributes to the maintenance of chronic pain. Individuals with SCA demonstrate enhanced sensitivity to painful stimuli however central mechanisms of pain have not been fully explored. We hypothesized that adults with SCA would show evidence of central sensitization as observed in other diseases of chronic pain.

Methods
We conducted a prospective study of static and dynamic quantitative sensory tests in 30 adults with SCA and 30 matched controls.

Results
Static thermal testing using cold stimuli showed lower pain thresholds (p = 0.04) and tolerance (p = 0.04) in sickle cell subjects, but not for heat. However, SCA subjects reported higher pain ratings with random heat pulses (p < 0.0001) and change in scores with temporal summation at the heat pain threshold (p = 0.002). Similarly, with the use of pressure pain stimuli, sickle cell subjects reported higher pain ratings (p = 0.04), but not higher pressure pain tolerance/thresholds or allodynia to light tactile stimuli. Temporal summation pain score changes using 2 pinprick probes (256 and 512 mN) were significantly greater (p = 0.004 and p = 0.008) with sickle cell, and delayed recovery was associated with lower fetal hemoglobin (p = 0.002 and 0.003).

Conclusions
Exaggerated temporal summation responses provide evidence of central sensitization in SCA.

Implications
The association with fetal hemoglobin suggests this known SCA modifier may have a therapeutic role in modulating central sensitization.
Design of a single‐mode photonic crystal fibre with ultra‐low material loss and large effective mode area in THz regime
Authors: Ahmed Kawsar , Paul Bikash Kumar , Chowdhury Sawrab , Sen Shuvo , Islam Md. Ibadul , Islam Md. Shadidul , Hasan Md. Rabiul , Asaduzzaman Sayed 
Published: September 2017

A novel low‐loss photonic crystal fibre (PCF) has been suggested for THz spectral applications. The proposed PCF contains five layers cladding with three layers core. The cladding and core region of the fibre are arranged in the octagonal and porous manner, respectively, where both the core and cladding vicinity are constituted by circular air cavities. The optical properties of the PCF are investigated by utilising the full vectorial finite‐element method along with the perfect match layers boundary condition. All numerical outcomes show the ultra‐low effective material loss of 0.049 cm−1 and large effective area of 3 × 10−7 m2 at 1 THz operating frequency. The power fraction is also considered as another significant parameter to design a low loss fibre. The almost more than half of the useful power (about 53.78% at f  = 1 THz) goes through the core over the wider operating frequency. In addition this, the proposed single‐mode PCF can be fabricated using the sol–gel method and is useful not only for high data traffic transmission applications but also for THz waveguide applications.
Development of expertise in elite and sub‐elite British rugby league players: A comparison of practice experiences
Authors: Rothwell Martyn , Stone Joseph A. , Davids Keith , Wright Craig 
Published: September 2017

AbstractPrevious studies have investigated how individuals reach an expert level by counting the number of hours engaged in specific practice types. Here we sought to understand and compare the microstructure (e.g. practice tasks undertaken) of these practice hours experienced by elite and sub‐elite British rugby league players. Semi‐structured interviews explored the practice experiences of eight international and eight domestic level players. A two‐staged thematic analysis was used to interpret the data. The analysis revealed that both player groups experienced a rich and narrow landscape of affordances and were exposed to early diversification of sports experiences during childhood. Differences were identified in domestic level players’ experiences of amateur and professional sports, where episodes of negative developmental environments were reported. International players’ practice experiences revealed differences in their professional careers, where exposure to scenario‐based practice and dynamic learning environments were reported. The findings suggest that insights from ecological dynamics provide a suitable theoretical framework to guide coaches in the design of practice environments that should consider the physical, psychological, emotional and social dimensions of expertise acquisition.
OncomiR: an online resource for exploring pan-cancer microRNA dysregulation
Authors: Wong Nathan W , Chen Yuhao , Chen Shuai , Wang Xiaowei 
Published: September 2017

Abstract

Summary
Dysregulation of microRNAs (miRNAs) is extensively associated with cancer development and progression. miRNAs have been shown to be biomarkers for predicting tumor formation and outcome. However, identification of the relationships between miRNA expression and tumor characteristics can be difficult and time-consuming without appropriate bioinformatics expertise. To address this issue, we present OncomiR, an online resource for exploring miRNA dysregulation in cancer. Using combined miRNA-seq, RNA-seq and clinical data from The Cancer Genome Atlas, we systematically performed statistical analyses to identify dysregulated miRNAs that are associated with tumor development and progression in most major cancer types. Additional analyses further identified potential miRNA-gene target interactions in tumors. These results are stored in a backend database and presented through a web server interface. Moreover, through a backend bioinformatics pipeline, OncomiR can also perform dynamic analysis with custom miRNA selections for in-depth characterization of miRNAs in cancer.

Availability and implementation
The OncomiR website is freely accessible at www.oncomir.org.

Supplementary information
Supplementary data are available at Bioinformatics online.
Reconstructing the Molecular Life History of Gliomas
Authors: Barthel Floris P. , Wesseling Pieter , Verhaak Roel G.W. 
Published: September 2017

ABSTRACTAt the time of clinical presentation, the very heterogeneous group of pediatric and adult gliomas carry a wide range of diverse somatic genomic alterations. These include chromosome-sized gains and losses, focal amplification and deletions, rearrangements resulting in transcript fusions, small insertions/deletions, and point mutations. Tumor cells pay a penalty for maintaining these abnormalities which therefore must provide cells with a competitive advantage to become engrained into the glioma genome. Here, we propose a model for gliomagenesis consisting of five consecutive phases that glioma cells have traversed prior to diagnosis. Tumor growth is repressed by activated DNA damage response pathways and dysfunctional telomeres in physiological conditions. Disruption of the p16-RB-p53 pathway and the acquisition of a telomere maintenance mechanism can bypass these bottlenecks. We relate somatic alterations to each of these steps, in order to reconstruct the life history of glioma. Understanding the story that each glioma tells at presentation may facilitate the design of novel, more effective therapeutic approaches.Key ConceptsGlioma initiating event: The first event that initiates the clonal expansion of cellsOncogene-induced senescence: Durable growth arrest triggered by continued oncogene exposureReplicative senescence: Durable growth arrest triggered via telomere dysfunction and activated DNA damage pathwaysCrisis: Widespread cell death triggered via telomere dysfunctionSenescence bypass event: Any molecular alteration that bypasses or suppresses oncogene-induced senescenceSenescence-associated secretory phenotype (SASP): Senescent cells secrete various immunogenic cytokines, growth factors and proteases into the microenvironmentFunctional redundancy: Used to describe two or more genomic changes that provide overlapping functional effectNeutral evolution:changes due to stochastic allelic variation that do not affect fitnessSelective sweep:The elimination of genetic variation following strong positive selection effectively reducing the tumor to a single cloneClonal event: Somatic mutation or copy number event that is conserved across all tumor cellsSubclonal event: Somatic mutation or copy number event that is only present in a subset (subclone) of tumor cellsChromothripsis: A punctuated shattering of genomic DNAKataegis: Clustered regions of hypermutationPolyploidization: The multiplication of chromosome content in a cellBreakage fusion bridge (BFB) cycle: Cyclic fusion of uncapped telomeres, bridge formation during anaphase and subsequent breakage leading to unequal inheritance of DNADicentric chromosome: Two fused chromosomes span across the mitotic spindle in anaphase, called dicentric because it has two centromeresDouble minute (DM) chromosome: Extra-chromosomal circular DNA segment lacking centromere(s) and telomeresImmortalization event: The last straw in the immortalization process that directly leads to telomere stabilization
BldC delays entry into development to produce a sustained period of vegetative growth inStreptomyces venezuelae
Authors: Bush Matthew J. , Chandra Govind , Al-Bassam Mahmoud M. , Findlay Kim C. , Buttner Mark J. 
Published: September 2017

ABSTRACTStreptomycetes are filamentous bacteria that differentiate by producing spore-bearing reproductive structures called aerial hyphae. The transition from vegetative to reproductive growth is controlled by thebld(bald) loci, and mutations inbldgenes prevent the formation of aerial hyphae, either by blocking entry into development (typically mutations in activators) or by inducing precocious sporulation in the vegetative mycelium (typically mutations in repressors). One of thebldgenes,bldC, encodes a 68-residue DNA-binding protein related to the DNA-binding domain of MerR-family transcription factors. Recent work has shown that BldC binds DNA by a novel mechanism, but there is less insight into its impact onStreptomycesdevelopment. Here we used ChIP-seq coupled with RNA-seq to define the BldC regulon in the model speciesStreptomyces venezuelae, showing that BldC can function both as a repressor and as an activator of transcription. Using electron microscopy and time-lapse imaging, we show thatbldCmutants are bald because they initiate development prematurely, bypassing the formation of aerial hyphae. This is consistent with the premature expression of BldC target genes encoding proteins with key roles in development (e.g.whiD,whiI,sigF), chromosome condensation and segregation (e.g.smeA-sffA,hupS), and sporulation-specific cell division (e.g.dynAB), suggesting that BldC-mediated repression is critical to maintain a sustained period of vegetative growth prior to sporulation. We discuss the possible significance of BldC as an evolutionary link between MerR family transcription factors and DNA architectural proteins.IMPORTANCEUnderstanding the mechanisms that drive bacterial morphogenesis depends on the dissection of the regulatory networks that underpin the cell biological processes involved. Recently,Streptomyces venezuelaehas emerged as an attractive new model system for the study of morphological differentiation inStreptomyces. This has led to significant progress in identifying the genes controlled by the transcription factors that regulate aerial mycelium formation (Bld regulators) and sporulation (Whi regulators). Taking advantage ofS. venezuelae, we used ChIP-seq coupled with RNA-seq to identify the genes directly under the control of BldC. BecauseS. venezuelaesporulates in liquid culture, the complete spore-to-spore life cycle can be examined using time-lapse microscopy, and we applied this technique to thebldCmutant. These combined approaches reveal BldC to be a member of an emerging class of Bld regulators that function principally to repress key sporulation genes, thereby extending vegetative growth and blocking the onset of morphological differentiation.
A multi-locus association analysis method integrating phenotype and expression data reveals multiple novel associations to flowering time variation in wild-collectedArabidopsis thaliana
Authors: Zan Yanjun , Carlborg Örjan 
Published: September 2017

AbstractWhen a species adapts to a new habitat, selection for the fitness traits often result in a confounding between genome-wide genotype and adaptive alleles. It is a major statistical challenge to detect such adaptive polymorphisms if the confounding is strong, or the effects of the adaptive alleles are weak. Here, we describe a novel approach to dissect polygenic traits in natural populations. First, candidate adaptive loci are identified by screening for loci that are directly associated to the trait or control the expression of genes known to affect it. Then, the multi-locus genetic architecture is inferred using a backward elimination association analysis across all the candidate loci using an adaptive false-discovery rate based threshold. Effects of population stratification are controlled by corrections for population structure in the pre-screening step and by simultaneously testing all candidate loci in the multi-locus model. We illustrate the method by exploring the polygenic basis of an important adaptive trait, flowering time inArabidopsis thaliana, using public data from the 1,001 genomes project. Our method revealed associations between 33 (29) loci and flowering time at 10 (16)°C in this collection of natural accessions, where standard genome wide association analysis methods detected 5 (3) loci. The 33 (29) loci explained approximately 55 (48)% of the total phenotypic variance of the respective traits. Our work illustrates how the genetic basis of highly polygenic adaptive traits in natural populations can be explored in much greater detail by using new multi-locus mapping approaches taking advantage of prior biological information as well as genome and transcriptome data.
Induction and Relief of Curiosity Elicit Parietal and Frontal Activity
Authors: van Lieshout Lieke L. F. , Vandenbroucke Annelinde R. E. , Müller Nils C. J. , Cools Roshan , de Lange Floris P. 
Published: September 2017

AbstractCuriosity is a basic biological drive, but little is known about its behavioral and neural mechanisms. We can be curious about several types of information. On the one hand, curiosity is a function of the expected value of information, serving primarily to help us maximize reward. On the other hand, curiosity can be a function of the uncertainty of information, helping us to update what we know. In the current studies, we aimed to disentangle the contribution of information uncertainty and expected value of rewards to curiosity in humans of either sex. To this end, we designed a lottery task in which uncertainty and expected value of trial outcomes were manipulated independently, and examined how neural activity and behavioral measures of curiosity were modulated by these factors. Curiosity increased linearly with increased outcome uncertainty, both when curiosity was explicitly probed as well as when it was implicitly tested by people’s willingness to wait. Increased expected value, however, did not strongly relate to these curiosity measures. Neuroimaging results showed greater BOLD response with increasing outcome uncertainty in parietal cortex at the time of curiosity induction. Outcome updating when curiosity was relieved resulted in an increased signal in the insula, orbitofrontal cortex and parietal cortex. Furthermore, the insula showed a linear increase corresponding to the size of the information update. These results suggest that curiosity is monotonically related to the uncertainty about one’s current world model, the induction and relief of which are associated with activity in parietal and insular cortices respectively.Significance statementHumans are curious by nature. When you hear your phone beep, you probably feel the urge to check the message right away, even though the message itself likely doesn’t give you a direct reward. In this study, we demonstrated that curiosity can be driven by outcome uncertainty, irrespective of reward. The induction of curiosity was accompanied by increased activity in the parietal cortex, whereas the information update at the time of curiosity relief was associated with activity in insular cortex. These findings advance our understanding of the behavioral and neural underpinnings of curiosity, which lies at the core of human information-seeking and serves to optimize the individual’s current world-model.