bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistic machine learning: how data assimilation leverages physiologic knowledge using Bayesian inference to forecast the future, infer the present, and phenotype
Authors: Albers David J , Levine Matthew E , Stuart Andrew , Mamykina Lena , Gluckman Bruce , Hripcsak George 
Published: August 2018

AbstractWe introduce data assimilation as a computational method that uses machine learning to combine data with human knowledge in the form of mechanistic models in order to forecast future states, to impute missing data from the past by smoothing, and to infer measurable and unmeasurable quantities that represent clinically and scientifically important phenotypes. We demonstrate the advantages it affords in the context of type 2 diabetes by showing how data assimilation can be used to forecast future glucose values, to impute previously missing glucose values, and to infer type 2 diabetes phenotypes. At the heart of data assimilation is the mechanistic model, here an endocrine model. Such models can vary in complexity, contain testable hypotheses about important mechanics that govern the system (eg, nutrition’s effect on glucose), and, as such, constrain the model space, allowing for accurate estimation using very little data.
The impact of p53 function on the metabolic activation of the carcinogenic air pollutant 3-nitrobenzanthrone and its metabolites 3-aminobenzanthrone and N-hydroxy-3-aminobenzanthrone in human cells
Authors: Wohak Laura E , Baranski Ann-Christin , Krais Annette M , Schmeiser Heinz H , Phillips David H , Arlt Volker M 
Published: August 2018

Abstract
The tumour suppressor p53, encoded by TP53, is a key player in a wide network of signalling pathways. We investigated its role in the bioactivation of the environmental carcinogen 3-nitrobenzanthrone (3-NBA)found in diesel exhaust and its metabolites 3-aminobenzanthrone (3-ABA) and N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) in a panel of isogenic human colorectal HCT116 cells differing only with respect to their TP53 status [i.e. TP53(+/+), TP53(+/−), TP53(−/−), TP53(R248W/+) or TP53(R248W/−)]. As a measure of metabolic competence, DNA adduct formation was determined using 32P-postlabelling. Wild-type (WT) p53 did not affect the bioactivation of 3-NBA; no difference in DNA adduct formation was observed in TP53(+/+), TP53(+/−) and TP53(−/−) cells. Bioactivation of both metabolites 3-ABA and N-OH-3-ABA on the other hand was WT-TP53 dependent. Lower 3-ABA- and N-OH-3-ABA-DNA adduct levels were found in TP53(+/−) and TP53(−/−) cells compared to TP53(+/+) cells, and p53’s impact was attributed to differences in cytochrome P450 (CYP) 1A1 expression for 3-ABA whereas for N-OH-3-ABA, an impact of this tumour suppressor on sulphotransferase (SULT) 1A1/3 expression was detected. Mutant R248W-p53 protein function was similar to or exceeded the ability of WT-p53 in activating 3-NBA and its metabolites, measured as DNA adducts. However, identification of the xenobiotic-metabolising enzyme(s) (XMEs), through which mutant-p53 regulates these responses, proved difficult to decipher. For example, although both mutant cell lines exhibited higher CYP1A1 induction after 3-NBA treatment compared to TP53(+/+) cells, 3-NBA-derived DNA adduct levels were only higher in TP53(R248W/−) cells but not in TP53(R248W/+) cells. Our results show that p53’s influence on carcinogen activation depends on the agent studied and thereby on the XMEs that mediate the bioactivation of that particular compound. The phenomenon of p53 regulating CYP1A1 expression in human cells is consistent with other recent findings; however, this is the first study highlighting the impact of p53 on sulphotransferase-mediated (i.e. SULT1A1) carcinogen metabolism in human cells.
Computer-Assisted Navigation for Real Time Planning of Pedicle Subtraction Osteotomy in Cervico-Thoracic Deformity Correction
Authors: Shin John H , Yanamadala Vijay , Cha Thomas D 
Published: August 2018

Abstract

BACKGROUND
Pedicle subtraction osteotomy (PSO) at the cervicothoracic junction (CTJ) is a powerful technique to correct severe kyphosis and sagittal malalignment. Reported techniques have demonstrated the safety and efficacy of the PSO, however limited visualization of surrounding tissues increases the potential for complications with this advanced technique.

OBJECTIVE
To describe the application of computed tomographic (CT)-based image guidance to the planning and execution of PSO at the CTJ.

METHODS
Intraoperative registration and verification of anatomic landmarks are performed with the intraoperative O-arm CT across the CTJ. With the navigation probe, the targeted pedicle is identified and the intended trajectories are rehearsed and saved on the navigational computer. As the PSO is performed, the navigation probe is used to check the depth, accuracy, and trajectory through each side. The extent of soft tissue dissection around the lateral aspect of the vertebral body through which the PSO is performed is also verified in real time. This technique was performed in 12 consecutive patients from 2013-2016. An IRB approved, retrospective analysis was performed from a prospective spinal deformity outcomes database. Patient consent is not required for publication as this report does not describe a specific case but rather a surgical technique used in practice.

RESULTS
There were no vascular, esophageal, or soft tissue injuries in 12 consecutive patients. There were no cases of paralysis. Two patients developed hand weakness days after surgery. Intraoperative O-arm CT performed after closure of the osteotomy confirmed the accuracy of the osteotomy planning with no breach of the anterior cortical wall of the osteotomized vertebral body.

CONCLUSION
CT-guided navigation allows for 3-dimensional visualization of the CTJ and minimizes complications associated with inadequate surgical visualization of vascular and deep organ structures.
The Effects of a Life Stress Emotional Awareness and Expression Interview for Women with Chronic Urogenital Pain: A Randomized Controlled Trial
Authors: Carty Jennifer N , Ziadni Maisa S , Holmes Hannah J , Tomakowsky Janice , Peters Kenneth , Schubiner Howard , Lumley Mark A 
Published: August 2018

Abstract

Objective
Women with chronic urogenital pain (CUP) conditions have elevated rates of lifetime trauma, relational stress, and emotional conflicts, but directly assessing and treating psychological stress is rarely done in women’s health care settings. We developed and tested the effects on patients’ somatic and psychological symptoms of a life stress interview that encourages disclosure about stressors and uses experiential techniques to increase awareness of links between stress, emotions, and symptoms.

Methods
In this randomized trial, women with CUP recruited at a multidisciplinary women’s urology center received either a single 90-minute life stress interview (N = 37) or no interview (treatment-as-usual control; N = 25). Self-report measures of pain severity (primary outcome), pain interference, pelvic floor symptoms, and psychological symptoms (anxiety and depression) were completed at baseline and six-week follow-up.

Results
Differences between the life stress interview and control conditions at follow-up were tested with analyses of covariance, controlling for baseline level of the outcome and baseline depression. Compared with the control condition, the interview resulted in significantly lower pain severity and pelvic floor symptoms, but the interview had no effect on pain interference or psychological symptoms.

Conclusions
An intensive life stress emotional awareness expression interview improved physical but not psychological symptoms among women with CUP seen in a tertiary care clinic. This study suggests that targeting stress and avoided emotions and linking them to symptoms may be beneficial for this complex group of patients.
Added Value of Whole-Exome and Transcriptome Sequencing for Clinical Molecular Screenings of Advanced Cancer Patients With Solid Tumors
Authors: Koeppel Florence , Bobard Alexandre , Lefebvre Céline , Pedrero Marion , Deloger Marc , Boursin Yannick , Richon Catherine , Chen-Min-Tao Romy , Robert Guillaume , Meurice Guillaume , Rouleau Etienne , Michiels Stefan , Massard Christophe , Scoazec Jean-Yves , Solary Eric , Soria Jean-Charles , André Fabrice , Lacroix Ludovic 
Published: August 2018

Abstract
Comprehensive genomic profiling using high-throughput sequencing brings a wealth of information, and its place in the clinical setting has been increasingly prominent. This review emphasizes the utility of whole-exome sequencing (WES) and transcriptome sequencing (RNAseq) in patient care and clinical research, based on published reports as well as our experience with the MOSCATO-01 (MOlecular Screening for CAncer Treatment Optimization) molecular triage trial at Gustave Roussy Cancer Center. In this trial, all contributive samples of patients with advanced solid tumors were analyzed prospectively with targeted gene sequencing (TGS) and comparative genomic hybridization. In addition, 92 consecutive metastatic patients with contributive biopsies were sequenced for WES and RNAseq and compared with TGS and comparative genomic hybridization. Whole-exome sequencing allowed the reporting of additional variants in relevant genes in 38% of patients. Mutation detection sensitivity of WES was 95% compared with TGS. Additional information derived from WES and RNAseq could influence clinical decision, including fusion transcripts, expression levels, allele-specific expression, alternate transcripts, RNA-based pathogen diagnostic, tumor mutation load, mutational signatures, expression signatures, HLA genotyping, and neoepitope prediction. The current challenge is to be able to process the large-scale data from these comprehensive genome-wide technologies in an efficient way.
A Reassessment of the Taxonomic Position of Mesosaurs Based on Two Data Matrices
Authors: Laurin Michel , Piñeiro Graciela 
Published: August 2018

1AbstractThe Early Permian mesosaurs are the oldest known primarily aquatic amniotes. Despite the interest that they have generated over time, their affinities remain controversial. Recently, two hypotheses have been supported, in which mesosaurs are either the sister-group of all other sauropsids, or the sister-group of other parareptiles. We recently upheld the former hypothesis, but in the latest study on mesosaur affinities, MacDougall et al. published a study highly critical of our work, while upholding the hypothesis that mesosaurs are basal parareptiles. We expect that the debate about mesosaur affinities will continue in the foreseeable future, but we wish to respond to the two central comments published by MacDougall et al. in 2018, who argue that variability in the temporal fenestration of early sauropsids, combined with the omission of several recently-described parareptile taxa, explain the differences in topologies between their study and ours. Reanalyzing our data matrix and theirs without characters linked with temporal fenestration, and removing from their matrix the parareptile taxa that they added (and that we omitted) does not alter the resulting topologies. Thus, their main conclusions are false; the differences in taxonomic position of mesosaurs must result from character choice and scoring differences.
Bradycardic mice undergo effective heart rate improvement after specific homing to the sino-atrial node and differentiation of adult muscle derived stem cells
Authors: Mesirca Pietro , Mamaeva Daria , Bidaud Isabelle , Baudot Matthias , Davaze Romain , DiFrancesco Mattia L. , Mitutsova Violeta , Torrente Angelo G. , Arsic Nikola , Nargeot Joël , Striessnig Jörg , Lee Amy , Lamb Ned J. , Mangoni Matteo E. , Fernandez Anne 
Published: August 2018

AbstractCurrent treatments for heart automaticity disorders still lack a safe and efficient source of stem cells to restore normal biological pacemaking. Since adult Muscle-Derived Stem Cells (MDSC) show multi-lineage differentiation in vitro including into spontaneously beating cardiomyocytes, we questioned whether they could effectively differentiate into cardiac pacemakers, a specific population of cardiomyocytes producing electrical impulses in the sino-atrial node (SAN) of adult heart. We show here that beating cardiomyocytes, differentiated from MDSC in vitro, exhibit typical characteristics of cardiac pacemakers: expression of markers of the SAN lineage Hcn4, Tbx3 and Islet1, as well as spontaneous calcium transients and hyperpolarization-activated “funny” current and L-type Cav1.3 channels. Pacemaker-like myocytes differentiated in vitro from Cav1.3-deficient mouse stem cells produced slower rate of spontaneous Ca2+ transients, consistent with the reduced activity of native pacemakers in mutant mice. In vivo, undifferentiated wild type MDSC migrated and homed with increased engraftment to the SAN of bradycardic mutant Cav1.3-/- within 2-3 days after systemic I.P. injection. The increased homing of MDSCs corresponded to increased levels of the chemokine SDF1 and its receptor CXCR4 in mutant SAN tissue and was ensued by differentiation of MDSCs into Cav1.3-expressing pacemaker-like myocytes within 10 days and a significant improvement of the heart rate maintained for up to 40 days. Optical mapping and immunofluorescence analyses performed after 40 days on SAN tissue from transplanted wild type and mutant mice showed MDSCs integrated as pacemaking cells both electrically and functionally within recipient mouse SAN. These findings identify MDSCs as directly transplantable stem cells that efficiently home, differentiate and improve heart rhythm in mouse models of congenital bradycardia.
Morphogenesis of neurons and glia within an epithelium
Authors: Low Isabel I. C. , Williams Claire R. , Chong Megan K. , McLachlan Ian G. , Wierbowski Bradley M. , Kolotuev Irina , Heiman Maxwell G. 
Published: August 2018

ABSTRACTTo sense the outside world, some neurons protrude across epithelia, the cellular barriers that line every surface of our bodies. To study the morphogenesis of such neurons, we examined theC. elegansamphid, in which dendrites protrude through a glial channel at the nose. During development, amphid dendrites extend by attaching to the nose via DYF-7, a type of protein typically found in epithelial apical ECM. Here, we show that amphid neurons and glia exhibit epithelial properties, including tight junctions and apical-basal polarity, and develop in a manner resembling other epithelia. We find that DYF-7 is a fibril-forming apical ECM component that prevents rupture of the tube-shaped glial channel, reminiscent of roles for apical ECM in other narrow epithelial tubes. We also identify a role for FRM-2, a homolog of EPBL15/moe/Yurt which promote epithelial integrity in other systems. Finally, we show that other environmentally-exposed neurons share a requirement for DYF-7. Together, our results suggest that these neurons and glia can be viewed as part of an epithelium continuous with the skin, and are shaped by mechanisms shared with other epithelia.
Ultra-fast and accurate motif finding in large ChIP-seq datasets reveals transcription factor binding patterns
Authors: Li Yang , Ni Pengyu , Zhang Shaoqiang , Li Guojun , Su Zhengchang 
Published: August 2018

ABSTRACTThe availability of a large volume of chromatin immunoprecipitation followed by sequencing (ChIP-seq) datasets for various transcription factors (TF) has provided an unprecedented opportunity to identify all functional TF binding motifs clustered in the enhancers in genomes. However, the progress has been largely hindered by the lack of a highly efficient and accurate tool that is fast enough to find not only the target motifs, but also cooperative motifs contained in very large ChIP-seq datasets with a binding peak length of typical enhancers (∼ 1,000 bp). To circumvent this hurdle, we herein present an ultra-fast and highly accurate motif-finding algorithm, ProSampler, with automatic motif length detection. ProSampler first identifies significant k-mers in the dataset and combines highly similar significant k-mers to form preliminary motifs. ProSampler then merges preliminary motifs with subtle similarity using a novel graph-based Gibbs sampler to find core motifs. Finally, ProSampler extends the core motifs by applying a two-proportion z-test to the flanking positions to identify motifs longer than k. As the number of preliminary motifs is much smaller than that of k-mers in a dataset, we greatly reduce the search space of the Gibbs sampler compared with conventional ones. By storing flanking sequences in a hash table, we avoid extensive IO and the necessity of examining all lengths of motifs in an interval. When evaluated on both synthetic and real ChIP-seq datasets, ProSampler runs orders of magnitude faster than the fastest existing tools while more accurately discovering primary motifs as well as cooperative motifs than do the best existing tools. Using ProSampler, we revealed previously unknown complex motif occurrence patterns in large ChIP-seq datasets, thereby providing insights into the mechanisms of cooperative TF binding for gene transcriptional regulation. Therefore, by allowing fast and accurate mining of the entire ChIP-seq datasets, ProSampler can greatly facilitate the efforts to identify the entire cis-regulatory code in genomes.
Transcriptomic responses of the marine cyanobacteriumProchlorococcusto viral lysis products
Authors: Fang Xiaoting , Liu Yaxin , Zhao Yao , Chen Yue , Liu Riyue , Qin Qi-Long , Li Gang , Zhang Yu-Zhong , Chan Wan , Hess Wolfgang R. , Zeng Qinglu 
Published: August 2018

AbstractMarine phytoplankton contributes to about one half of global primary production, and a significant proportion of their photosynthetically fixed organic carbon is released after viral infection as dissolved organic matter (DOM). This DOM pool is known to be consumed by heterotrophic microorganisms; however, its impact on the uninfected co-occurring phytoplankton remains largely unknown. Here, we conducted transcriptomic analyses to study the effects of viral lysis products on the unicellular cyanobacteriumProchlorococcus, which is the most abundant photosynthetic organism on Earth. WhileProchlorococcusgrowth was not affected by viral lysis products, many tRNAs increased in abundance, which was also seen after amino acid addition, suggesting that amino acids are one of the compounds in viral lysis products that affected the expression of tRNA genes. The decreased transcript abundances of N metabolism genes also suggested thatProchlorococcusresponded to organic N compounds, consistent with abundant amino acids in viral lysis products. The addition of viral lysis products toProchlorococcusreduced the maximum photochemical efficiency of photosystem II and CO2fixation while increased its respiration rate, consistent with differentially expressed genes related to photosynthesis and respiration. One of the highest positive fold-changes was observed for the 6S RNA, a non-coding RNA functioning as a global transcriptional regulator in bacteria. The high level of 6S RNA might be responsible for some of the observed transcriptional responses. Taken together, our results revealed the transcriptional regulation ofProchlorococcusin response to viral lysis products and suggested its metabolic potential to utilize organic N compounds.ImportancePhotosynthetic microorganisms called phytoplankton are abundant in the oceans and contribute to about one half of global CO2fixation. Phytoplankton are frequently infected by viruses and after infection their organic carbon is released into the ocean as dissolved organic matter (DOM). Marine DOM is important for the marine food web because it supports the growth of heterotrophic microorganisms. However, the impact of viral DOM on the uninfected phytoplankton is largely unknown. In this study, we conducted transcriptomic analyses and identified many differentially expressed genes when viral DOM was added to the marine cyanobacteriumProchlorococcus. One effect of viral DOM is that the carbon fixation ofProchlorococcuswas reduced by ~16%, which might affect carbon cycling in the world’s oceans sinceProchlorococcusis the most abundant photosynthetic organism on Earth.
Quorums enable optimal pooling of independent judgements
Authors: Marshall James , Kurvers Ralf H.J.M. , Krause Jens , Wolf Max 
Published: August 2018

Majority-voting and the Condorcet Jury Theorem pervade thinking about collective decision-making. Thus, it is typically assumed that majority-voting is the best possible decision mechanism, and that scenarios exist where individually-weak decision-makers should not pool information. Condorcet and its applications implicitly assume that only one kind of error can be made, yet signal detection theory shows two kinds of errors exist, ‘false positives’ and ‘false negatives’. We apply signal detection theory to collective decision-making to show that majority voting is frequently sub-optimal, and can be optimally replaced by quorum decision-making. While quorums have been proposed to resolve within-group conflicts, or manage speed-accuracy trade-offs, our analysis applies to groups with aligned interests undertaking single-shot decisions. Our results help explain the ubiquity of quorum decision-making in nature, relate the use of sub- and super-majority quorums to decision ecology, and may inform the design of artificial decision-making systems.Impact StatementTheory typically assumes that majority voting is optimal; this is incorrect – majority voting is typically sub-optimal, and should be replaced by sub-majority or super-majority quorum voting. This helps explain the prevalence of quorum-sensing in even the simplest collective systems, such as bacterial communities.
Soil bacterial biomass and diversity are affected by different furrow-ridge mulched management systems during potato continuous cropping
Authors: Zhang Weina , Qin Shuhao , Xu Xuexue , Zhang Junlian , Liu Yuhui 
Published: August 2018

AbstractThe soil bacterial composition is vital for sustainable agriculture due to its importance in biogeochemical processes in the soil environment. Multiple management systems, such as different furrow-ridge mulched cropping systems, have been established to reduce the damage caused by continuous cropping of potato (Solanum tuberosumL.). However, little is known about the responses of soil bacterial biomass and diversity to these systems. In this study, six different ridge-furrow film planting patterns were tested in a 2-year continuous cropping potato field: flat plot without mulch (CK), flat plot with mulch (T1), on-ridge planting with full mulch (T2), on-furrow planting with full mulch (T3), on-ridge planting with half mulch (T4), and on-furrow planting with half mulch (T5). The soil physicochemical properties and bacterial composition were significantly affected by the planting pattern. Mulched soils, especially T2, maintained better soil physicochemical properties than controls. Fully mulched soil maintained higher bacterial biomass and diversity. Among the dominant genera, the abundances ofNitrosomonadaceaein T2 and T4 were higher than those in the other treatments. Consequently, compared with the other treatments, on-ridge with mulching patterns resulted in better soil physicochemical properties and high bacterial biomass and diversity, which could reduce the economic losses due to potato production by continuous cropping.