bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Association of Abdominal Striae With Pelvic Organ Prolapse
Authors: Miranne Jeannine M. , Kramer MaryJo E. , Mete Mihriye , Iglesia Cheryl B. 
Published: March 2018

Objective
Our objective was to estimate the prevalence of abdominal wall striae among women with and without pelvic organ prolapse (POP) in a population with pelvic floor disorders.

Methods
This cross-sectional study included nonpregnant women with urinary incontinence and POP presenting to a tertiary urogynecology practice between December 2012 and August 2013. Participants completed a nonvalidated questionnaire about striae, and the degree of abdominal wall striae was quantified on physical examination. Baseline demographics, clinical characteristics, and Pelvic Organ Prolapse Quantification (POP-Q) measurements were recorded.

Results
One hundred thirty-two women were approached for participation, of which 110 (83%) completed study questionnaires. Of these 110, 59 had POP defined at POP-Q stages 2–4, whereas 51 had normal pelvic support, POP-Q stages 0–1. The mean (SD) age was 55.5 (12) years, and most (78/110) were sexually active. Women with POP were more parous than women without POP (median 2 vs 1, respectively; P = 0.03). However, there was no difference in medical comorbidities, smoking status, or steroid use between groups (P > 0.05). More women with POP reported striae (42/59 [71%] vs 23/51 [45%], P = 0.006) and had quantifiable abdominal wall striae compared with women with normal support (39/59 [66%] vs 22/51 [44%], P = 0.02). On multivariate logistic regression, women with POP were 2.5 times more likely to have striae compared with women without POP after adjusting for skin type and smoking status (odds ratio, 2.5; 95% confidence interval, 1.03–6.06; P = 0.04).

Conclusion
Women with POP are more likely to have striae compared with women without POP.
Successful Treatment of Paradoxical Puborectalis Contraction and Intractable Anorectal Pain With Sacral Neuromodulation
Authors: Roth Ted M. 
Published: March 2018

Background
Paradoxical puborectalis contraction (PPC) is a syndrome of obstructed defecation associated with a cluster of complaints including rectal pain, incomplete evacuatory sensation, prolonged repetitive straining with bowel movements, and the need for digital manipulation. Traditional treatment has yielded mixed results.

Case
We present a case of PPC successfully treated with staged sacral neuromodulation and review her diagnostic features, medical regimen, and prior unsuccessful interventions tried. Symptoms were analyzed using a visual analog scale pain score (0–10). Criteria to progress to implantation of the pulse generator included a pain score less than 3 during test stimulation and/or greater than 50% decrease in the pain score compared to baseline.
Our patient had a pain score of 0 (baseline 8) with stage 1 sacral neuromodulation. In addition, she had dramatic relief in her straining with bowel movements and need for digital manipulation. Her pulse generator was implanted after a 2-week trial, and she has experienced a lasting improvement at her follow-up of 2 years.

Conclusions
Sacral neuromodulation is an established therapy for overactive bladder syndrome, urinary retention, and fecal incontinence. In urology, the use of sacral neuromodulation has been described to benefit some patients with pelvic floor pain. Sacral neuromodulation can be a successful treatment for PPC and functional anorectal pain with resulting improvement in quality of life without the sequelae of an invasive and irreversible surgery.
Single-molecule optical mapping enables accurate molecular diagnosis of facioscapulohumeral muscular dystrophy (FSHD)
Authors: Dai Yi , Li Pidong , Wang Zhiqiang , Liang Fan , Yang Fan , Fang Li , Huang Yu , Huang Shangzhi , Zhou Jiapeng , Wang Depeng , Cui Liying , Wang Kai 
Published: March 2018

ABSTRACTFacioscapulohumeral Muscular Dystrophy (FSHD) is a common adult muscular dystrophy in which the muscles of the face, shoulder blades and upper arms are among the most affected. FSHD is the only disease in which “junk” DNA is reactivated to cause disease, and the only known repeat array-related disease where fewer repeats cause disease. More than 95% of FSHD cases are associated with copy number loss of a 3.3kb tandem repeat (D4Z4 repeat) at the subtelomeric chromosomal region 4q35, of which the pathogenic allele contains less than 10 repeats and has a specific genomic configuration called 4qA. Currently, genetic diagnosis of FSHD requires pulsed-field gel electrophoresis followed by Southern blot, which is labor-intensive, semi-quantitative and requires long turnaround time. Here, we developed a novel approach for genetic diagnosis of FSHD, by leveraging Bionano Saphyr single-molecule optical mapping platform. Using a bioinformatics pipeline developed for this assay, we found that the method gives direct quantitative measurement of repeat numbers, can differentiate 4q35 and the highly paralogous 10q26 regions, can determine the 4qA/4qB allelic configuration, and can quantitate levels of post-zygotic mosaicism. We evaluated this approach on 5 patients (including two with post-zygotic mosaicism) and 2 patients (including one with post-zygotic mosaicism) from two separate cohorts, and had complete concordance with Southern blots, but with improved quantification of repeat numbers resolved between haplotypes. We concluded that single-molecule optical mapping is a viable approach for molecular diagnosis of FSHD and may be applied in clinical diagnostic settings once more validations are performed.
Conservation and divergence in modules of the transcriptional programs of the human and mouse immune systems
Authors: Shay Tal , Jojic Vladimir , Zuk Or , Benoist Christophe , Koller Daphne , Regev Aviv ,   ImmGen consortium
Published: March 2018

AbstractStudies in mouse have shed important light on human hematopoietic differentiation and disease. However, substantial differences between the two species often limit the translation of findings from mouse to human.Here, we compare previously defined modules of co-expressed genes in human and mouse immune cells based on compendia of genome-wide profiles. We show that the overall modular organization of the transcriptional program is conserved. We highlight modules of co-expressed genes in one species that dissolve or split in the other species. Many of the associated regulatory mechanisms – as reflected by computationally inferred trans regulators, or enriched cis-regulatory elements – are conserved between the species. Nevertheless, the degree of conservation in regulatory mechanism is lower than that of expression, suggesting that distinct regulation may underlie some of the conserved transcriptional responses.
Purge Haplotigs: Synteny Reduction for Third-gen Diploid Genome Assemblies
Authors: Roach Michael J , Schmidt Simon , Borneman Anthony R 
Published: March 2018

AbstractRecent developments in third-gen long read sequencing and diploid-aware assemblers have resulted in the rapid release of numerous reference-quality assemblies for diploid genomes. However, assembling highly heterozygous genomes is still facing a major problem where the two haplotypes for a region are highly polymorphic and the synteny is not recognised during assembly. This causes issues with downstream analysis, for example variant discovery using the haploid assembly, or haplotype reconstruction using the diploid assembly. A new pipeline—Purge Haplotigs—was developed specifically for third-gen assemblies to identify and reassign the duplicate contigs. The pipeline takes a draft haplotype-fused assembly or a diploid assembly, and read alignments to produce an improved assembly. The pipeline was tested on a simulated dataset and on four recent diploid (phased) de novo assemblies from third-generation long-read sequencing. All assemblies after processing with Purge Haplotigs were less duplicated with minimal impact on genome completeness. The software is available at https://bitbucket.org/mroachawri/purge_haplotigs under a permissive MIT licence.
Topological linkage disequilibrium calculated from coalescent genealogies
Authors: Wirtz Johannes , Rauscher Martina , Wiehe Thomas 
Published: March 2018

AbstractWe revisit the classical concept of two-locus linkage disequilibrium (LD) and introduce a novel way of looking at haplotypes. In contrast to defining haplotypes as allele combinations at two marker loci, we concentrate on the clustering of sampled chromosomes induced by their coalescent genealogy. The root of a binary coalescent trees defines two clusters of chromosomes. At two different loci this assignment may be different as a result of recombination. We show that the amount of shared chromosomes among clusters at two different loci, measured by the squared correlation, constitutes a natural measure ofLD. We call thistopological LD(tLD) since it is induced by the topology of the coalescent tree. We find that its rate of decay decreases more slowly with distance between loci than that of conventionalLD. Furthermore,tLDhas a smaller coefficient of variation, which should render it more accurate for any kind of mapping purposes than conventionalLD. We conclude with a practical application to the LCT region in human populations.
Microtubule end tethering of a processive Kinesin-8 motor Kif18b is required for spindle positioning
Authors: McHugh Toni , Gluszek-Kustusz Agata , Welburn Julie P.I. 
Published: March 2018

AbstractMitotic spindle positioning specifies the plane of cell division during anaphase. Spindle orientation and positioning is therefore critical to ensure symmetric division in mitosis and asymmetric division during development. The control of astral microtubule length plays an essential role in positioning the spindle. Here we show using gene knockout that the Kinesin-8 Kif18b controls microtubule length to center the mitotic spindle at metaphase. Using an integrated approach, we reveal that Kif18b is a highly processive plus end-directed motor that uses a C-terminal non-motor microtubule-binding region to accumulate at growing microtubule plus ends. This region is regulated by phosphorylation to spatially control Kif18b accumulation at plus ends and is essential for Kif18b-dependent spindle positioning and regulation of microtubule length. Finally, we demonstrate that Kif18b shortens microtubules by increasing the catastrophe rate of dynamic microtubules. Overall, our work reveals that Kif18b utilizes its motile properties to reach microtubule ends where it regulates astral microtubule length to ensure spindle centering.
Distinct control of PERIOD2 degradation and circadian rhythms by the oncoprotein MDM2
Authors: Liu JingJing , Zou Xianlin , Gotoh Tetsuya , Brown Anne M. , Jiang Liang , Kim Jae Kyoung , Finkielstein Carla V. 
Published: March 2018

ABSTRACTThe circadian clock relies on post-translational modifications to set the timing for degradation of core regulatory components and, thus, sets clock progression. Ubiquitin-modifying enzymes targeting clock components for degradation are known to mostly recognize phosphorylated substrates. A case in point is the circadian factorPERIOD2(PER2) whose phospho-specific turnover involves its recognition by β-transducin repeat containing proteins (β-TrCPs). Yet, the existence of this unique mode of regulation of PER2’s stability falls short of explaining persistent oscillatory phenotypes reported in biological systems lacking functional elements of the phospho-dependent PER2 degradation machinery.In this study, we challenge the phosphorylation-centric view that PER2 degradation enhances circadian rhythm robustness byi) identifying the PER2:MDM2 endogenous complex,ii) establishing PER2 as a previously uncharacterized substrate for MDM2,iii) revealing an alternative phosphorylation-independent mechanism for PER2 ubiquitin-mediated degradation,iv) pinpointing residues for ubiquitin modification, andv) establishing the importance of MDM2-mediated PER2 turnover for defining the circadian period length. Our results not only expand MDM2’s suite of specific substrates beyond the cell cycle to include circadian components but also uncover novel regulatory players that likely impact our view of how other mechanisms crosstalk and modulate the clock itself.
Temperature explains broad patterns of Ross River virus transmission across Australia
Authors: Shocket Marta S. , Ryan Sadie J. , Mordecai Erin A. 
Published: March 2018

ABSTRACTTemperature impacts the physiology of ectotherms, including vectors that transmit disease. While thermal biology predicts nonlinear effects of temperature on vector and pathogen traits that drive disease transmission, the empirical relationship between temperature and transmission remains unknown for most vector-borne pathogens. We built a mechanistic model to estimate the thermal response of Ross River virus, an important mosquito-borne pathogen of humans in Australia, the Pacific Islands, and potentially emerging worldwide. Transmission peaks at moderate temperatures (26.4°C) and declines to zero at low (17.0°C) and high (31.5°C) temperatures. The model predicted broad patterns of disease across Australia. First, transmission is year-round endemic in the tropics and sub-tropics but seasonal in temperate zones. Second, nationwide human cases peak seasonally as predicted from population-weighted seasonal temperatures. These results illustrate the importance of nonlinear, mechanistic models for inferring the role of temperature in disease dynamics and predicting responses to climate change.
The Claustrum Coordinates Cortical Slow-Wave Activity
Authors: Narikiyo Kimiya , Mizuguchi Rumiko , Ajima Ayako , Mitsui Sachiko , Shiozaki Momoko , Hamanaka Hiroki , Johansen Joshua P. , Mori Kensaku , Yoshihara Yoshihiro 
Published: March 2018

AbstractDuring sleep and awake rest, the neocortex generates large-scale slow-wave activity. Here we report that the claustrum, a poorly understood subcortical neural structure, coordinates neocortical slow-wave generation. We established a transgenic mouse line allowing genetic and electrophysiological interrogation of a subpopulation of claustral glutamatergic neurons. These claustral excitatory neurons received inputs from glutamatergic neurons in a large neocortical network. Optogenetic activation of claustral neurons in vitro induced excitatory post-synaptic responses in most neocortical neurons, but elicited action potentials primarily in inhibitory interneurons. Optogenetic activation of claustral neurons in vivo induced a Down-state featuring a prolonged silencing of neural acticity in all layers of many cortical areas, followed by a globally synchronized Down-to-Up state transition. These results demonstrate a crucial role of the claustrum in synchronizing inhibitory interneurons across the neocortex for spatiotemporal coordination of brain state. Thus, the claustrum is a major subcortical hub for the synchronization of neocortical slow-wave activity.
In vivo pulse-labeling of isochronic cohorts of cells in the central nervous system using FlashTag
Authors: Govindan Subashika , Oberst Polina , Jabaudon Denis 
Published: March 2018

AbstractThis protocol describes a fluorescence birthdating technique to label, track and isolate isochronic cohorts of newborn cells in the central nervous system in vivo. Injection of carboxyfluorescein esters into the cerebral ventricle allows pulse-labeling of M-phase progenitors in touch with the ventricle and their progeny across the central nervous system, a procedure we termed FlashTag. Labeled cells can be imaged ex vivo or in fixed tissue, targeted for electrophysiological experiments, or isolated using Fluorescence-Activated Cell Sorting (FACS) for cell culture or (single-cell) RNA-sequencing. The dye is retained for several weeks, allowing labeled cells to be identified postnatally. This protocol describes the labeling procedure using in utero injection, the isolation of live cells using FACS, as well as the processing of labeled tissue using immunohistochemistry.
Disrupted neural adaptation in autism spectrum disorder
Authors: Millin Rachel , Kolodny Tamar , Flevaris Anastasia V. , Kale Alex M. , Schallmo Michael-Paul , Gerdts Jennifer , Bernier Raphael A. , Murray Scott O. 
Published: March 2018

AbstractThere has been long-standing speculation that autism spectrum disorder (ASD) involves an increase in excitation relative to inhibition. However, there is little direct evidence of increased neural excitation in humans with ASD. Here we provide a potential explanation for this discrepancy: we show that increased neural excitation emerges only after repeated stimulation, manifesting as a deficit in neural adaptation. We measured fMRI responses induced by repeated audio-visual stimulation and button presses in early sensory-motor cortical areas. Across all cortical areas we show reduced adaptation in individuals with ASD compared to neurotypical individuals. The degree of adaptation is correlated between cortical areas and with button-press reaction times across subjects. These findings suggest that increased neural excitation in ASD, manifesting as dysregulated neural adaptation, is domain-general and behaviorally-relevant.
Iteratively improving Hi-C experiments one step at a time
Authors: Golloshi Rosela , Sanders Jacob , McCord Rachel Patton 
Published: March 2018

AbstractThe 3D organization of eukaryotic chromosomes affects key processes such as gene expression, DNA replication, cell division, and response to DNA damage. The genome-wide chromosome conformation capture (Hi-C) approach can characterize the landscape of 3D genome organization by measuring interaction frequencies between all genomic regions. Hi-C protocol improvements and rapid advances in DNA sequencing power have made Hi-C useful to diverse biological systems, not only to elucidate the role of 3D genome structure in proper cellular function, but also to characterize genomic rearrangements, assemble new genomes, and consider chromatin interactions as potential biomarkers for diseases. Yet, the Hi-C protocol is still complex and subject to variations at numerous steps that can affect the resulting data. Thus, there is still a need for better understanding and control of factors that contribute to Hi-C experiment success and data quality. Here, we evaluate recently proposed Hi-C protocol modifications as well as often overlooked variables in sample preparation and examine their effects on Hi-C data quality. We examine artifacts that can occur during Hi-C library preparation, including microhomology-based artificial template copying and chimera formation that can add noise to the downstream data. Exploring the mechanisms underlying Hi-C artifacts pinpoints steps that should be further optimized in the future. To improve the utility of Hi-C in characterizing the 3D genome of specialized populations of cells or small samples of primary tissue, we identify steps prone to DNA loss which should be optimized to adapt Hi-C to lower cell numbers.Highlights3 to 5 bullet points (maximum 85 characters, including spaces, per bullet point)Variability in Hi-C libraries can arise from early steps of cell preparationHi-C 2.0 changes to interaction capture steps also benefit 6-cutter librariesArtificial molecule fusions can arise during end repair and PCR, increasing noiseCommon causes of Hi-C DNA loss identified for future optimization
China’s urban-rural relationship: evolution and prospects
Authors: Zhang Zhenghe , Lu Yawen 
Published: March 2018

Purpose
In the 69 years since the founding of the People’s Republic of China, especially the 40 years since the reform and opening-up, the relationship between urban and rural areas has undergone profound change. When the deepening reform of the urban-rural relationship is entering a critical period, it is necessary to reassess the evolution of the urban-rural relationship in China and draw a picture for that relationship in the future. The paper aims to discuss these issues.

Design/methodology/approach
This paper combs the policies on the urban and rural development since the founding of the People’s Republic of China, and analyzes macro data on the industries, population, personal income, and other aspects.

Findings
The study found that this urbanism affects individuals’ lives and the choices of society through the will of the state, and then provides feedback at the whole level of social values.

Originality/value
This paper divides the evolution of China’s urban-rural relationship into two major stages – nurturing cities with rural areas and leading rural areas with cities, which are then subdivided into five periods. The features of the relationship between the urban and rural areas in different periods are analyzed, and the future development of urban-rural relations is also considered.
Returns to public agricultural and rural investments in China
Authors: Fan Shenggen , Cho Emily EunYoung , Rue Christopher 
Published: March 2018

Purpose
The purpose of this paper is to review China’s past returns in a period over the last 40 years to public agricultural and rural investments to highlight the importance for future strategic investments in China’s agri-food system and in rural areas.

Design/methodology/approach
The paper synthesizes research findings from previous studies and reviews more recent trends. Based on the main findings, the authors provide forward-looking guidance for China’s investments agriculture and rural areas in the context of emerging global and domestic trends in agriculture, food security, and nutrition.

Findings
Public investments in the agricultural research and development (R&D), rural education, and rural infrastructure have been shown to have significant positive returns to agricultural growth as well as to reductions in poverty and regional inequality. Returns to overall agricultural GDP were highest for agricultural R&D, followed by education, roads, and telephones. Investment in education had the greatest returns to poverty reduction, as well as to nonfarm GDP and overall rural GDP. Investment in agricultural R&D had the second greatest returns in term of poverty reduction, and was also a close second in returns to nonfarm GDP and overall rural GDP following education. The rural infrastructure spending also saw significant returns to poverty reduction, largely through growth in agricultural and nonagricultural sectors. Investments in agriculture and rural areas will continue to be important, as China and the world face emerging challenges amidst a changing global landscape, particularly regarding climate change, rapid urbanization, nutritional imbalances, and food safety concerns. In addressing these emerging challenges, continued support for agricultural R&D and innovations can play a key role.

Originality/value
The paper highlights research findings on key investment areas that will be increasingly important for China’s agri-food system, and provides guidance in the context of emerging trends impacting food security and nutrition.