bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined Laparoscopic and Perineal Approach to Omental Interposition Repair of Complex Rectovaginal Fistula
Authors: de Bruijn Hester , Maeda Yasuko , Murphy Jamie , Warusavitarne Janindra , Vaizey Carolynne J. 
Published: December 2017

INTRODUCTION:
Surgical repair of rectovaginal fistula remains a challenge. Complex and recurrent rectovaginal fistula repairs often fail because of scarring and devascularization of the surrounding tissue. Omental interposition may promote healing by introducing bulky vascularized tissue into the rectovaginal septum.

TECHNIQUE:
With the patient in the lithotomy position, the rectovaginal septum was dissected transperineally up to the fistula tract and the openings on both vaginal and rectal sides were closed using interrupted, absorbable sutures. The dissection was continued cranially to meet the laparoscopic dissection from above. The laparoscopic surgeon detached the omentum from the colon, then the anastomotic arterial branches between the Barlow’s arcade and the gastroepiploic arcade were divided and the greater omentum was mobilized, retaining blood supply from the left gastroepiploic artery. The rectum was then mobilized commencing on the right lateral side of the mesorectum and then proceeding anteriorly. The peritoneum between the rectum and the vagina was incised and the anterior mobilization was continued to connect with the perineal dissection. The mobilized omentum was pulled down between the rectum and the vagina.
The perineal operator secured the omentum around the rectal closure and at skin level with absorbable sutures. All of the patients had a defunctioning ileostomy or colostomy before omental repair.

RESULTS:
Patients underwent repair for complex or recurrent rectovaginal fistulas with this novel approach. Fistula healing was evaluated during examination under anaesthesia. All of the patients had completely healed at the latest follow-up (median = 15 mo; range, 8–41 mo). Postoperative complications included 1 superficial wound infection that was treated conservatively and 1 rectovaginal hematoma, which required CT-guided aspiration.

CONCLUSIONS:
Combined laparoscopic omental interposition with perineal rectovaginal fistula repair is a safe and effective treatment for complex rectovaginal fistulas.
Age-Related Changes in Tissue Value Properties in Children
Authors: Lee So Mi , Choi Young Hun , You Sun-Kyoung , Lee Won Kee , Kim Won Hwa , Kim Hye Jung , Lee Sang Yub , Cheon Hyejin 
Published: December 2017

Objectives
The properties of brain tissue undergo dynamic changes during maturation. T1 relaxation time (T1), T2 relaxation time (T2), and proton density (PD) are now simultaneously quantifiable within a clinically acceptable time, using a synthetic magnetic resonance imaging (MRI) sequence. This study aimed to provide age-specific reference values for T1, T2, and PD in children, using synthetic MRI.

Materials and Methods
We included 89 children (median age, 18 months; range, 34 weeks of gestational age to 17 years) who underwent quantitative MRI, using a multidynamic, multiecho sequence on 3 T MRI, between December 2015 and November 2016, and had no abnormal MRI/neurologic assessment findings. T1, T2, and PD were simultaneously measured in each of the 22 defined white matter and gray matter regions of interest. The measured values were plotted against age, and a curve fitting model that best explained the age dependence of tissue values was identified. Age-specific regional tissue values were calculated using a fit equation.

Results
The tissue values of all brain regions, except cortical PD, decreased with increasing age, and the robust negative association was best explained by modified biexponential model of the form Tissue values = T1 × exp (−C1 × age) + T2 × exp (−C2 × age). The quality of fit to the modified biexponential model was high in white matter and deep gray matter (white matter, R
2 = 97%–99% [T1], 88%–95% [T2], 88%–97% [PD]; deep gray matter, R
2 = 96%–97% [T1], 96% [T2], 49%–88% [PD]; cortex, 70%–83% [T1], 87%–90% [T2], 5%–27% [PD]). The white matter and deep gray matter changed the most dynamically within the first year of life.

Conclusions
Our study provides age-specific regional reference values, from the neonate to adolescent, of T1, T2, and PD, which could be objective tools for assessment of normal/abnormal brain development using synthetic MRI.
An Anatomic Morphological Study of Occipital Spurs in Human Skulls
Authors: Srivastava Monika , Asghar Adil , Srivastava Nitya Nand , Gupta Nandkishore , Jain Anuj , Verma Jayant 
Published: December 2017

Abstract
Occipital spurs are quite common; however, they are also the source of frequent discomfort to the patients. Their role has been implicated in causation of pain at the base of skull, which may extend to shoulder limiting the movement of the shoulder and neck. The present was carried out to find out the prevalence of occipital spur in human skull and to find out the anatomic morphological characteristics of occipital spur. A total of 30 cadaveric skulls were examined in the Department of Anatomy, Uttar Pradesh University of Medical Sciences, for the presence of occipital spur. These skulls were the part of boneset obtained as a part of undergraduate training in the department. All the measurements were taken using a digital Vernier Caliper after taking all necessary precaution to avoid any damage to these spurs. The prevalence of occipital spur in the present study was 10%. The mean width recorded in the present study was 13.40 mm (±6.7) and the mean length recorded was 13.45 mm (±1.05). Similarly, mean thickness noted was 2.43 mm (±0.43). Thus, the present study concludes that occipital spurs are the frequent source of discomfort to patients. The knowledge of this tubercle is of paramount importance to neurosurgeons, sports physicians, and radiologists for the diagnosis of such discomfort.
Latent tuberculosis infection in foreign-born communities: import vs. transmission in the Netherlands derived through mathematical modelling
Authors: Korthals Altes Hester , Kloet Serieke , Cobelens Frank , Bootsma Martin 
Published: December 2017

AbstractWhile tuberculosis represents a significant disease burden worldwide, low-incidence countries strive to reach the WHO target of elimination by 2025. Screening for TB in immigrants is an important component of the strategy to reduce the TB burden in low-incidence settings. An important option is the screening and preventive treatment of latent tuberculosis infection (LTBI). Whether this policy is worthwhile depends on the extent of transmission within the country, and introduction of new cases through import. Mathematical transmission models of tuberculosis have been used to identify key parameters in the epidemiology of TB and estimate transmission rates. An important application has also been to investigate the consequences of policy scenarios.Here, we formulate a mathematical model for TB transmission within the Netherlands to estimate the size of the pool of latent infections, and to determine the share of importation –either through immigration or travel- versus transmission within the Netherlands. We take into account importation of infections due to immigration, and travel to the country of origin, focusing on the three ethnicities most represented among TB cases, excluding those overrepresented in asylum seekers: Moroccans, Turkish and Indonesians. We fit a system of ordinary differential equations to the data from the Netherlands Tuberculosis Registry on (extra-)pulmonary TB cases from 1995-2013.We find that for all three foreign-born communities, immigration is the most important source of LTBI, but the extent of within-country transmission is much lower (about half) for the Turkish and Indonesian communities than for the Moroccan. This would imply that contact investigation would have a greater yield in the latter community than in the former. Travel remains a minor factor contributing LTBI, suggesting that targeting returning travelers might be less effective at preventing LTBI than immigrants upon entry in the country.
DARPP-32 and t-DARPP promote lung cancer growth through IKKα-dependent cell migration and Akt/Erk-mediated cell survival
Authors: Alam Sk. Kayum , Astone Matteo , Liu Ping , Hall Stephanie R. , Coyle Abbygail M. , Dankert Erin N. , Hoffman Dane K. , Zhang Wei , Kuang Rui , Roden Anja C. , Mansfield Aaron S. , Hoeppner Luke H. 
Published: December 2017

AbstractLung cancer is the leading cause of cancer-related death worldwide. In this study, we demonstrate that elevated expression of dopamine and cyclic adenosine monophosphate-regulated phosphoprotein, Mr 32000 (DARPP-32) and its truncated splice variant t-DARPP promotes lung tumor growth, while abrogation of DARPP-32 expression in human non-small cell lung cancer (NSCLC) cells reduces tumor growth in orthotopic mouse models. We observe a novel physical interaction between DARPP-32 and inhibitory kappa B kinase-α (IKKα) that promotes NSCLC cell migration through non-canonical nuclear factor kappa-light-chain-enhancer of activated B cells 2 (NF-κB2) signaling. Bioinformatics analysis of 513 lung adenocarcinoma patients reveals elevated t-DARPP isoform expression is associated with poor overall survival. Histopathological investigation of 62 human lung adenocarcinoma tissues also showed that t-DARPP expression is elevated with increasing tumor (T) stage. Our data suggest that DARPP-32 is a negative prognostic marker associated with increasing stages of NSCLC and may represent a novel therapeutic target.
TahcoRoll: An Efficient Approach for Signature Profiling in Genomic Data through Variable-Length k-mers
Authors: Ju Chelsea J.-T. , Jiang Jyun-Yu , Li Ruirui , Li Zeyu , Wang Wei 
Published: December 2017

Abstractk-mer profiling has been one of the trending approaches to analyze read data generated by high-throughput sequencing technologies. The tasks of k-mer profiling include, but are not limited to, counting the frequencies and determining the occurrences of short sequences in a dataset. The notion of k-mer has been extensively used to build de Bruijn graphs in genome or transcriptome assembly, which requires examining all possible k-mers presented in the dataset. Recently, an alternative way of profiling has been proposed, which constructs a set of representative k-mers as genomic markers and profiles their occurrences in the sequencing data. This technique has been applied in both transcript quantification through RNA-Seq and taxonomic classification of metagenomic reads. Most of these applications use a set of fixed-size k-mers since the majority of existing k-mer counters are inadequate to process genomic sequences with variable-length k-mers. However, choosing the appropriate k is challenging, as it varies for different applications. As a pioneer work to profile a set of variable-length k-mers, we propose TahcoRoll in order to enhance the Aho-Corasick algorithm. More specifically, we use one bit to represent each nucleotide, and integrate the rolling hash technique to construct an efficient in-memory data structure for this task. Using both synthetic and real datasets, results show that TahcoRoll outperforms existing approaches in either or both time and memory efficiency without using any disk space. In addition, compared to the most efficient state-of-the-art k-mer counters, such as KMC and MSBWT, TahcoRoll is the only approach that can process long read data from both PacBio and Oxford Nanopore on a commodity desktop computer. The source code of TahcoRoll is implemented in C++14, and available at https://github.com/chelseaju/TahcoRoll.git.
A CRISPR screening approach for identifying novel autophagy-related factors and cytoplasm-to-lysosome trafficking routes
Authors: Shoemaker Christopher J , Huang Tina Q , Weir Nicholas R , Polyakov Nicole , Denic Vladimir 
Published: December 2017

SummarySelective autophagy comprises cytoplasm-to-lysosome trafficking routes that transport cargos using double-membrane vesicles (autophagosomes). Cargos are detected by receptor proteins, which typically also bind to lipid-conjugated LC3 proteins on autophagosome membranes. We dissected lysosomal delivery of four SQSTM1-like receptors by genome-wide CRISPR screening looking for novel autophagy-related (ATG) factors and trafficking routes. We uncovered new mammalian ATG factors including TMEM41B, an endoplasmic reticulum membrane protein required for autophagosome membrane expansion and/or closure. Furthermore, we found that certain receptors remain robustly targeted to the lysosome even in the absence of ATG7 or other LC3 conjugation factors. Lastly, we identified a unique genetic fingerprint behind receptor flux in ATG7KO cells, which includes factors implicated in nucleating autophagosome formation and vesicle trafficking factors. Our work uncovers new ATG factors, reveals a malleable network of autophagy receptor genetic interactions, and provides a valuable resource (http://crispr.deniclab.com) for further mining of novel autophagy mechanisms.
Quantitative mass imaging of single molecules in solution
Authors: Young Gavin , Hundt Nikolas , Cole Daniel , Fineberg Adam , Andrecka Joanna , Tyler Andrew , Olerinyova Anna , Ansari Ayla , Marklund Erik G. , Collier Miranda P. , Chandler Shane A. , Tkachenko Olga , Allen Joel , Crispin Max , Billington Neil , Takagi Yasuharu , Sellers James R. , Eichmann Cedric , Selenko Philip , Frey Lukas , Riek Roland , Galpin Martin R. , Struwe Weston B. , Benesch Justin L.P. , Kukura Philipp 
Published: December 2017

AbstractThe cellular processes underpinning life are orchestrated by proteins and their interactions. Structural and dynamic heterogeneity, despite being key to protein and drug function, continues to pose a fundamental challenge to existing analytical and structural methodologies used to study these associations. Here, we use interferometric scattering microscopy to mass-image single biomolecules in solution with <2% mass error, up to 19-kDa resolution and 1-kDa precision. Thereby, we resolve oligomeric distributions at high dynamic range, detect small-molecule binding, and mass-image biomolecules composed not only of amino acids, but also heterogeneous species, such as lipo- and glycoproteins. These capabilities enable us to characterize the molecular mechanisms of processes as diverse as oligomeric selfassembly, glycoprotein cross-linking, amyloidogenic protein aggregation, and actin polymerization. Interferometric scattering mass spectrometry (iSCAMS) provides spatially resolved access to the dynamics of biomolecular interactions ranging from those involving small molecules to mesoscopic assemblies, one molecule at a time.
A simple mung bean infection model for studying the virulence of Pseudomonas aeruginosa
Authors: Garge Sneha , Azimi Sheyda , Diggle Stephen P. 
Published: December 2017

AbstractHere we highlight the development of a simple and high throughput mung bean model to study virulence in the opportunistic pathogen Pseudomonas aeruginosa. The model is easy to setup and infection and virulence can be monitored for up to 10 days. In a first test of the model, we found that mung bean seedlings infected with PAO1 showed poor development of roots and high mortality rates compared to un-infected controls. We also found that a quorum sensing (QS) mutant was significantly less virulent when compared with the PAO1 wild type. Our work introduces a new tool for studying virulence in P. aeruginosa, that will allow for high throughput virulence studies of mutants, and for testing the in vivo efficacy of new therapies at a time when new antimicrobial drugs are desperately needed.
Testing hypotheses about the microbiome using the linear decomposition model (LDM)
Authors: Hu Yi-Juan , Satten Glen A. 
Published: December 2017

AbstractMotivationMethods for analyzing microbiome data generally fall into one of two groups: tests of the global hypothesis of any microbiome effect, which do not provide any information on the contribution of individual operational taxonomic units (OTUs); and tests for individual OTUs, which do not typically provide a global test of microbiome effect. Without a unified approach, the findings of a global test may be hard to resolve with the findings at the individual OTU level. Further, many tests of individual OTU effects do not preserve the false discovery rate (FDR).ResultsWe introduce the linear decomposition model (LDM), that provides a single analysis path that includes global tests of any effect of the microbiome, tests of the effects of individual OTUs while accounting for multiple testing by controlling the FDR, and a connection to distance-based ordination. The LDM accommodates both continuous and discrete variables (e.g., clinical outcomes, environmental factors) as well as interaction terms to be tested either singly or in combination, allows for adjustment of confounding covariates, and uses permutation-based p-values that can control for correlation. The LDM can also be applied to transformed data, and an “omnibus” test can easily combine results from analyses conducted on different transformation scales. We also provide a new implementation of PERMANOVA based on our approach. For global testing, our simulations indicate the LDM provided correct type I error and can have comparable power to existing distance-based methods. For testing individual OTUs, our simulations indicate the LDM controlled the FDR well. In contrast, DESeq2 often had inflated FDR; MetagenomeSeq generally had the lowest sensitivity. The flexibility of the LDM for a variety of microbiome studies is illustrated by the analysis of data from two microbiome studies. We also show that our implementation of PERMANOVA can outperform existing implementations.
The Activation of MEK1 by Enhanced Homodimerization Drives Tumorigenesis
Authors: Yuan Jimin , Ng Wan Hwa , Tian Zizi , Yap Jiajun , Baccarini Manuela , Chen Zhongzhou , Hu Jiancheng 
Published: December 2017

SummaryHyperactive RAS/RAF/MEK/ERK signaling has a well-defined role in cancer biology. Aberrant pathway activation occurs mostly upstream of MEK; however, MEK mutations are prevalent in some cancer subsets. Here we show that cancer-related MEK mutants can be classified as those activated by relieving the inhibitory role of helix A, and those with in-frame deletions of β3-αC loop, which exhibit differential resistance to MEK inhibitors in vitro and in vivo. The β3-αC loop deletions activate MEK1 through enhancing homodimerization that can drive intradimer cross-phosphorylation of activation loop. Further, we demonstrate that MEK1 dimerization is required both for its activation by RAF and for its catalytic activity towards ERK. Our study identifies a novel group of MEK mutants, illustrates some key steps in RAF/MEK/ERK activation, and has important implications for the design of therapies targeting hyperactive RAS/RAF/MEK/ERK signaling in cancers.
Quantitative morphological variation in the developing Drosophila wing
Authors: Matamoro-Vidal Alexis , Huang Yunxian , Salazar-Ciudad Isaac , Shimmi Osamu , Houle David 
Published: December 2017

AbstractQuantitative variation in morphology is pervasive in all species and is the basis for the evolution of differences among species. The developmental causes of such variation are a relatively neglected research topic. Quantitative comparisons of variation arising at different developmental stages with the variation in the final structure enable us to determine when variation arises, and to generate hypotheses about the causes of that variation. We measured shape and size variation in the wing of Drosophila melanogaster at three developmental stages: late third instar, post-pupariation and in the adult fly. Flies of a wild-type and two mutants (shf and ds) with effects on the adult wing shape and size were studied. Despite experimental noise related to the difficulty of comparing developing structures, we found consistent differences in wing shape and size at each developmental stage between genotypes. In addition we provide linear rules allowing to link late disc morphology with early wings. Our approach provides a framework to analyze quantitative morphological variation in the developing fly wing. This framework should help to characterize the natural variation of the larval and pupal wing shape, and to measure the contribution of the processes occurring during these developmental stages to the natural variation in adult wing morphology.
Transfer RNA genes experience exceptionally elevated mutation rates
Authors: Thornlow Bryan P. , Hough Josh , Roger Jacquelyn M. , Gong Henry , Lowe Todd M. , Corbett-Detig Russell B. 
Published: December 2017

AbstractTransfer RNAs (tRNAs) are a central component for the biological synthesis of proteins, and they are among the most highly conserved and frequently transcribed genes in all living things. Despite their clear significance for fundamental cellular processes, the forces governing tRNA evolution are poorly understood. We present evidence that transcription-associated mutagenesis and strong purifying selection are key determinants of patterns of sequence variation within and surrounding tRNA genes in humans and diverse model organisms. Remarkably, the mutation rate at broadly expressed cytosolic tRNA loci is likely between seven and ten times greater than the nuclear genome average. Furthermore, evolutionary analyses provide strong evidence that tRNA genes, but not their flanking sequences, experience strong purifying selection, acting against this elevated mutation rate. We also find a strong correlation between tRNA expression levels and the mutation rates in their immediate flanking regions, suggesting a simple new method for estimating individual tRNA gene activity. Collectively, this study illuminates the extreme competing forces in tRNA gene evolution, and implies that mutations at tRNA loci contribute disproportionately to mutational load and have unexplored fitness consequences in human populations.Significance StatementWhile transcription-associated mutagenesis (TAM) has been demonstrated for protein coding genes, its implications in shaping genome structure at transfer RNA (tRNA) loci in metazoans have not been fully appreciated. We show that cytosolic tRNAs are a striking example of TAM because of their variable rates of transcription, well-defined boundaries and internal promoter sequences. tRNA loci have a mutation rate approximately seven-to tenfold greater than the genome-wide average, and these mutations are consistent with signatures of TAM. These observations indicate that tRNA loci are disproportionately large contributors to mutational load in the human genome. Furthermore, the correlations between tRNA locus variation and transcription implicate that prediction of tRNA gene expression based on sequence variation data is possible.