bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reverse turnover pedicled latissimus dorsi muscle flap for lower back reconstruction
Authors: Kang Soo Hwan , Kim Yoo Chang , Sur Yoo Joon 
Published: December 2018

Abstract

Rationale:
Large soft tissue defects on the lower back represent a treatment challenge. Among a variety of reconstructive procedures, the latissimus dorsi (LD) muscle or musculocutaneous flap is one of most frequently used pedicled flaps. However, the pedicled LD flap carries a bulky pivot point and a short arc of rotation. If a pedicled LD muscle flap is transferred using a reverse turnover pattern, theses drawbacks can be avoided.

Patient concerns:
The first patient was a 56-year-old man with hepatocellular carcinoma and multiple bone metastases involving D11-L4 vertebral bodies. A chronic ulcer was developed on his lower back area after palliative radiation therapy for bone metastases. The second patient was a 41-year-old man with a soft tissue mass on his lower back, which was diagnosed as dermatofibrosarcoma protuberans via previous incisional biopsy. A large soft tissue defect was developed on his lower back as a result of a wide resection.

Diagnosis:
Both patients were referred to our department for the treatment of a large soft tissue defect on lower back.

Interventions:
They underwent the reverse turnover pedicled LD muscle flap and split-thickness skin graft.

Outcomes:
At postoperative 6-month follow-up, both patients remained free of wound problem.

Lessons:
The reverse turnover pedicled LD muscle flap is quite straightforward. Even if a soft tissue defect in the lower back is large or complicated by infection or radiation therapy, perfusion of LD by posterior intercostal arteries is likely to be preserved. We recommend the reverse turnover pedicled LD muscle flap as an effective alternative for reconstruction of soft tissue defects involving the lower back.
Disease-specific Hospitalizations Among 5-Year Survivors of Hepatoblastoma: A Nordic Population-based Cohort Study
Authors: Bonnesen Trine G. , Asdahl Peter H. , de Fine Licht Sofie , Gudmundsdottir Thorgerdur , Holmqvist Anna S. , Madanat-Harjuoja Laura-Maria , Tryggvadottir Laufey , Winther Jeanette F. , Hasle and Henrik 
Published: December 2018

Introduction:
The long-term risk of somatic disease in hepatoblastoma survivors has not been thoroughly evaluated in previous studies. In this population-based study of 86 five-year HB survivors, we used inpatient registers to evaluate the risk for a range of somatic diseases.

Methods:
In total, 86 five-year survivors of hepatoblastoma were identified in the Nordic cancer registries from 1964 to 2008 and 152,231 population comparisons were selected. Study subjects were followed in national hospital registries for somatic disease classified into 12 main diagnostic groups. Standardized hospitalization rate ratios (RRs) and absolute excess risks were calculated.

Results:
After a median follow-up of 11 years, 35 of the 86 five-year hepatoblastoma survivors had been hospitalized with a total of 69 hospitalizations, resulting in an RR of 2.7 (95% confidence interval [CI], 2.2-3.5) and an overall absolute excess risk of 4.2 per 100 person-years. Highest risk was seen for benign neoplasms (RR=16) with 6 hospitalizations for benign neoplasms in the colon and one in rectum.

Conclusions:
The pattern of hospitalizations found in this first comprehensive follow-up of hepatoblastoma survivors seems reassuring. Less than 50% of the 5-year survivors had been hospitalized and often for diseases that were not severe or life-threatening.
Effective Connectivity in Subjects With Mild Cognitive Impairment as Assessed Using Functional Near-Infrared Spectroscopy
Authors: Bu Lingguo , Huo Congcong , Qin Yuexia , Xu Gongcheng , Wang Yonghui , Li Zengyong 
Published: December 2018

Objective
This study aimed to reveal the physiological mechanism in subjects with mild cognitive impairment based on effective connectivity method.

Methods
Effective connectivity was assessed by dynamic Bayesian inference of the oxygenated hemoglobin concentration signals measured through functional near-infrared spectroscopy. The oxygenated hemoglobin concentration signals were recorded from the left prefrontal cortex, right prefrontal cortex, left motor cortex, right motor cortex, left occipital lobe, and right occipital lobe of 26 subjects with mild cognitive impairment (mild cognitive impairment group) and 28 healthy elderly subjects (control group) at resting state.

Results
The coupling strength of right prefrontal cortex to left prefrontal cortex (F = 7.964, P = 0.007) and left prefrontal cortex to right occipital lobe (F = 4.278, P = 0.044) in interval III as well as left prefrontal cortex to left occipital lobe (F = 5.637, P = 0.021), right occipital lobe to left prefrontal cortex (F = 4.762, P = 0.034), and right prefrontal cortex to left occipital lobe (F = 4.06, P = 0.049) in interval IV in the mild cognitive impairment group were significantly lower than those in the control group.

Conclusions
The decreased effective connectivity levels among brain regions may be a marker of impaired cognitive function in the mild cognitive impairment group. The constructed effective connectivity network based on functional near-infrared spectroscopy provide a noninvasive method to assess mild cognitive impairment.
Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5
Authors: Johnston Keira J.A. , Adams Mark J. , Nicholl Barbara I. , Ward Joey , Strawbridge Rona J , McIntosh Andrew , Smith Daniel J. , Bailey Mark E.S. 
Published: December 2018

AbstractChronic pain is highly prevalent worldwide, with a significant socioeconomic burden, and also contributes to excess mortality. Chronic pain is a complex trait that is moderately heritable and genetically, as well as phenotypically, correlated with major depressive disorder (MDD). Use of the Conditional False Discovery Rate (cFDR) approach, which leverages pleiotropy identified from existing GWAS outputs, has been successful in discovering novel associated variants in related phenotypes. Here, genome-wide association study outputs for both von Korff chronic pain grade as a quasi-quantitative trait and for MDD were used to identify variants meeting a cFDR threshold for each outcome phenotype separately, as well as a conjunctional cFDR (ccFDR) threshold for both phenotypes together. Using a moderately conservative threshold, we identified a total of 11 novel single nucleotide polymorphisms (SNPs), six of which were associated with chronic pain grade and nine of which were associated with MDD. Four SNPs on chromosome 14 were associated with both chronic pain grade and MDD. SNPs associated only with chronic pain grade were located within SLC16A7 on chromosome 12. SNPs associated only with MDD were located either in a gene-dense region on chromosome 1 harbouring LINC01360, LRRIQ3, FPGT and FPGT-TNNI3K, or within/close to LRFN5 on chromosome 14. The SNPs associated with both outcomes were also located within LRFN5. Several of the SNPs on chromosomes 1 and 14 were identified as being associated with expression levels of nearby genes in the brain and central nervous system. Overall, using the cFDR approach, we identified several novel genetic loci associated with chronic pain and we describe likely pleiotropic effects of a recently identified MDD locus on chronic pain.Author SummaryGenetic variants explaining variation in complex traits can often be associated with more than one trait at once (‘pleiotropy’). Taking account of this pleiotropy in genetic studies can increase power to find sites in the genome harbouring trait-associated variants. In this study we used the suspected underlying pleiotropy between chronic pain and major depressive disorder to discover novel variants associated with chronic pain, and to investigate genetic variation that may be shared between the two disorders.
Performance - Based Clustering Enables the Study of Physiological Features Supporting Sustained Attention Capacities
Authors: Marques-Carneiro José Eduardo , Staub Bérengère , Bonnefond Anne 
Published: December 2018

AbstractIn the present study, we investigated different sustained attention performance profiles in the general adult population and if age is a determinant factor among these profiles. We also reported some specificities in terms of brain oscillations. The sustained attention to response task was applied combined with electrophysiological recordings in 59 adults, aged from 19 to 86 years. We used a hierarchical cluster analysis to group individuals based on similarity of levels and patterns of performance across variables of interest. We focused on the most common attentional–related variables, which allowed us to identify four distinct clusters showing specific sustained attention profiles. Furthermore, our analysis clearly revealed that age was not the determinant factor of these profiles. Finally, we highlighted specificities in terms of brain oscillations. Subjects from cluster 1– the “high-performers” – demonstrated a globally increased theta-gamma coupling maintained over time and an increase of theta activity at the FC6 and F8 electrodes. Subjects from cluster 2, who adopted a more cautious response strategy, presented a higher level of modulation exerted by the electrode FT7 over Oz and a higher theta-gamma coupling at the Oz. This result suggests that cluster-based method to useful in understanding specific mechanisms underlying sustained attention features.
A Benchmark of Computational CRISPR-Cas9 Guide Design Methods
Authors: Bradford Jacob , Perrin Dimitri 
Published: December 2018

AbstractThe popularity of CRISPR-based gene editing has resulted in an abundance of tools to design CRISPR-Cas9 guides. This is also driven by the fact that designing highly specific and efficient guides is a crucial, but not trivial, task in using CRISPR for gene editing. Here, we thoroughly analyse the performance of 17 design tools. They are evaluated based on runtime performance, compute requirements, and guides generated. To achieve this, we implemented a method for auditing system resources while a given tool executes, and tested each tool on datasets of increasing size, derived from the mouse genome. We found that only five tools had a computational performance that would allow them to analyse an entire genome in a reasonable time, and without exhausting computing resources. There was wide variation in the guides identified, with some tools reporting every possible guide while others filtered for predicted efficiency. Some tools also failed to exclude guides that would target multiple positions in the genome. We also considered a collection of over a thousand guides for which experimental data is available. For the tools that attempt to filter based on efficiency, 65% to 85% of the guides they reported were experimentally found to be efficient, but with limited overlap in the sets produced by different tools. Our results show that CRISPR-Cas9 guide design tools need further work in order to achieve rapid whole-genome analysis and that improvements in guide design will likely require combining multiple approaches.
Selective neuronal vulnerability in Alzheimer’s disease: a network-based analysis
Authors: Roussarie Jean-Pierre , Yao Victoria , Plautz Zakary , Kasturia Shirin , Albornoz Christian , Schmidt Eric F , Brichta Lars , Barnea-Cramer Alona , Heintz Nathaniel , Hof Patrick , Heiman Myriam , Flajolet Marc , Troyanskaya Olga , Greengard Paul 
Published: December 2018

AbstractA major obstacle to treating Alzheimer’s disease (AD) is our lack of understanding of the molecular mechanisms underlying selective neuronal vulnerability, which is a key characteristic of the disease. Here we present a framework to integrate high-quality neuron-type specific molecular profiles across the lifetime of the healthy mouse, which we generated using bacTRAP, withpostmortemhuman functional genomics and quantitative genetics data. We demonstrate human-mouse conservation of cellular taxonomy at the molecular level for AD vulnerable and resistant neurons, identify specific genes and pathways associated with AD pathology, and pinpoint a specific functional gene module underlying selective vulnerability, enriched in processes associated with axonal remodeling, and affected by both amyloid accumulation and aging. Overall, our study provides a molecular framework for understanding the complex interplay between Aβ, aging, and neurodegeneration within the most vulnerable neurons in AD.
Substrate inhibition imposes fitness penalty at high protein stability
Authors: Adkar Bharat V. , Bhattacharyya Sanchari , Gilson Amy I. , Zhang Wenli , Shakhnovich Eugene I. 
Published: December 2018

AbstractProteins are only moderately stable. It has long been debated whether this narrow range of stabilities is solely a result of neutral drift towards lower stability or purifying selection against excess stability is also at work — for which no experimental evidence was found so far. Here we show that mutations outside the active site in the essentialE. colienzyme adenylate kinase result in stability-dependent increase in substrate inhibition by AMP, thereby impairing overall enzyme activity at high stability. Such inhibition caused substantial fitness defects not only in the presence of excess substrate but also under physiological conditions. In the latter case, substrate inhibition caused differential accumulation of AMP in the stationary phase for the inhibition prone mutants. Further, we show that changes in flux through Adk could accurately describe the variation in fitness effects. Taken together, these data suggest that selection against substrate inhibition and hence excess stability may have resulted in a narrow range of optimal stability observed for modern proteins.
Evidence for natural selection and barrier leakage in candidate loci underlying speciation in wood ants
Authors: Kulmuni J , Nouhaud P , Pluckrose L , Satokangas I , Dhaygude K , Butlin RK 
Published: December 2018

AbstractWhile speciation underlies novel biodiversity, it is poorly understood how natural selection shapes genomes during speciation. Selection is assumed to act against gene flow at barrier loci, promoting reproductive isolation and speciation. However, evidence for gene flow and selection is often indirect. Here we utilize haplodiploidy to identify candidate barrier loci in hybrids between two wood ant species and integrate survival analysis to directly measure if natural selection is acting at candidate barrier loci. We find multiple candidate barrier loci but surprisingly, proportion of them show leakage between samples collected ten years apart, natural selection favoring leakage in the latest sample. Barrier leakage and natural selection for introgressed alleles could be due to environment-dependent selection, emphasizing the need to consider temporal variation in natural selection in future speciation work. Integrating data on survival allows us to move beyond genome scans, demonstrating natural selection acting on hybrid genomes in real-time.
Domains of the TF protein important in regulating its own palmitoylation
Authors: Ramsey Jolene , Chavez Marbella , Mukhopadhyay Suchetana 
Published: December 2018

ABSTRACTSindbis virus particles contain the viral proteins capsid, E1 and E2, and low levels of a small membrane protein called TF. TF is produced during a (-1) programmed ribosomal frameshifting event during the translation of the structural polyprotein. TF from Sindbis virus-infected cells is present in two palmitoylated states, basal and maximal; unpalmitoylated TF is not detectable. Mutagenesis studies demonstrated that without palmitoylation, TF is not incorporated into released virions, suggesting palmitoylation of TF is a regulated step in virus assembly. In this work, we identified Domains within the TF protein that regulate its palmitoylation state. Mutations and insertions in Domain III, a region proposed to be in the cytoplasmic loop of TF, increase levels of unpalmitoylated TF found during an infection and even allow incorporation of unpalmitoylated TF into virions. Mutations in Domain IV, the TF unique region, are likely to impact the balance between basal and maximal palmitoylation.
Synaptic combinatorial molecular mechanisms generate repertoires of innate and learned behavior
Authors: Komiyama Noboru H. , van de Lagemaat Louie N. , Stanford Lianne E. , Pettit Charles M. , Strathdee Douglas J. , Strathdee Karen E. , Fricker David G. , Tuck Eleanor J. , Elsegood Kathryn A. , Ryan Tomás J. , Nithianantharajah Jess , Skene Nathan G. , Croning Mike D. R. , Grant Seth G. N. 
Published: December 2018

AbstractAlthough molecular mechanisms underpinning specific behaviors have been described, whether there are mechanisms that orchestrate a behavioral repertoire is unknown. To test if the postsynaptic proteome of excitatory synapses could impart such a mechanism we conducted the largest genetic study of mammalian synapses yet undertaken. A repertoire of sixteen innate and learned behaviors was assessed from 290,850 measures in 55 lines of mutant mice carrying targeted mutations in the principal classes of postsynaptic proteins. Each innate and learned behavior used a different combination of proteins. These combinations were comprised of proteins that amplified or attenuated the magnitude of each behavioral response. All behaviors required proteins found in PSD95 supercomplexes. We show the vertebrate increase in proteome complexity drove an expansion in behavioral repertoires and generated susceptibility to a wide range of diseases. Our results reveal a molecular mechanism that generates a versatile and complex behavioral repertoire that is central to human behavioral disorders.
A combinatorial postsynaptic molecular mechanism converts patterns of nerve impulses into the behavioral repertoire
Authors: Kopanitsa Maksym V. , van de Lagemaat Louie N. , Afinowi Nurudeen O. , Strathdee Douglas J. , Strathdee Karen E. , Fricker David G. , Tuck Eleanor J. , Elsegood Kathryn A. , Croning Mike D. R. , Komiyama Noboru H. , Grant Seth G. N. 
Published: December 2018

AbstractHow is the information encoded within patterns of nerve impulses converted into diverse behavioral responses? To address this question, we conducted the largest genetic study to date of the electrophysiological and behavioral properties of synapses. Postsynaptic responses to elementary patterns of activity in the hippocampal CA1 region were measured in 58 lines of mice carrying mutations in the principal classes of excitatory postsynaptic proteins. A combinatorial molecular mechanism was identified in which distinct subsets of proteins amplified or attenuated responses across timescales from milliseconds to an hour. The same mechanism controlled the diversity and magnitude of innate and learned behavioral responses. PSD95 supercomplex proteins were central components of this synaptic machinery. The capacity of vertebrate synapses to compute activity patterns increased with genome evolution and is impaired by disease-relevant mutations. We propose that this species-conserved molecular mechanism converts the temporally encoded information in nerve impulses into the repertoire of innate and learned behavior.
Fitness of reciprocal F1hybrids betweenRhinanthus minorandRhinanthus majorunder controlled conditions and in the field
Authors: Wesselingh Renate A. , Hořčicová Šárka , Mirzaei Khaled 
Published: December 2018

AbstractThe performance of first-generation hybrids determines to a large extent the long-term outcome of hybridization in natural populations. F1hybrids can facilitate further gene flow between the two parental species, especially in animal-pollinated flowering plants. We studied the performance of reciprocal F1hybrids betweenRhinanthus minorandR. major, two hemiparasitic, annual, self-compatible plant species, from seed germination to seed production under controlled conditions and in the field. We sowed seeds with known ancestry outdoors before winter and followed the complete life cycle until plant death in July the following season. While germination under laboratory conditions was much lower for the F1hybrid formed onR. majorcompared to the reciprocal hybrid formed onR. minor, this difference disappeared under field conditions, pointing at an artefact caused by the experimental conditions during germination in the lab rather than at an intrinsic genetic incompatibility. Both F1hybrids performed as well as or sometimes better thanR. minor, which had a higher fitness thanR. majorin one of the two years in the greenhouse and in the field transplant experiment. The results confirm findings from naturally mixed populations, where F1hybrids appear as soon as the two species meet and which leads to extensive advanced-hybrid formation and introgression in subsequent generations.
Cheating emergences in the arbuscular mycorrhizal mutualism: a network and phylogenetic analysis
Authors: Perez-Lamarque Benoît , Selosse Marc-André , Öpik Maarja , Morlon Hélène , Martos Florent 
Published: December 2018

AbstractWhile mutualisms are widespread and essential in ecosystem functioning, the emergence of uncooperative cheaters threatens their stability, unless there are functional or evolutionary mechanisms limiting cheaters interactions.Here, we evaluated the constraints upon mycoheterotrophic (MH) cheating plants in the mutualistic interaction network of autotrophic (AT) plants and arbuscular mycorrhizal fungi. For this purpose, we assembled a world-scale network of >25,000 interactions in order to investigate(i)the specialization and(ii)the phylogenetic distribution of MH or AT plants and their respective fungal partners.We show that MH cheating repeatedly evolved in the vascular flora, suggesting low phylogenetic constraint for plants. However, MH cheaters are significantly more specialized than AT plants, and their fungi also appear more specialized and more closely related than fungi of AT plants, which suggest that cheaters are specifically isolated into modules by functional constraintsThis unprecedented comparison of MH vs. AT plants thus reveals that MH cheating is most likely constrained by the specialization of phylogenetically conserved cheating-susceptible fungi, which suggests mechanisms for avoidance of these fungi. Beyond the mycorrhizal symbiosis, our approach highlights an empirical multiple-partners mutualistic system illustrating that the overall persistence of mutualism can be linked to functional constraints upon cheating emergences.
Motivation and Cognitive Control in Depression
Authors: Grahek Ivan , Shenhav Amitai , Musslick Sebastian , Krebs Ruth M. , Koster Ernst H.W. 
Published: December 2018

AbstractDepression is linked to deficits in cognitive control and a host of other cognitive impairments arise as a consequence of these deficits. Despite of their important role in depression, there are no mechanistic models of cognitive control deficits in depression. In this paper we propose how these deficits can emerge from the interaction between motivational and cognitive processes. We review depression-related impairments in key components of motivation along with new cognitive neuroscience models that focus on the role of motivation in the decision-making about cognitive control allocation. Based on this review we propose a unifying framework which connects motivational and cognitive control deficits in depression. This framework is rooted in computational models of cognitive control and offers a mechanistic understanding of cognitive control deficits in depression.