bluuebunny/crossref_metadata_2025_split huggingface dataset:
A map of direct TF–DNA interactions in the human genome
Authors: Gheorghe Marius , Sandve Geir Kjetil , Khan Aziz , Chèneby Jeanne , Ballester Benoit , Mathelier Anthony 
Published: November 2018

Abstract
Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is the most popular assay to identify genomic regions, called ChIP-seq peaks, that are bound in vivo by transcription factors (TFs). These regions are derived from direct TF–DNA interactions, indirect binding of the TF to the DNA (through a co-binding partner), nonspecific binding to the DNA, and noise/bias/artifacts. Delineating the bona fide direct TF–DNA interactions within the ChIP-seq peaks remains challenging. We developed a dedicated software, ChIP-eat, that combines computational TF binding models and ChIP-seq peaks to automatically predict direct TF–DNA interactions. Our work culminated with predicted interactions covering >2% of the human genome, obtained by uniformly processing 1983 ChIP-seq peak data sets from the ReMap database for 232 unique TFs. The predictions were a posteriori assessed using protein binding microarray and ChIP-exo data, and were predominantly found in high quality ChIP-seq peaks. The set of predicted direct TF–DNA interactions suggested that high-occupancy target regions are likely not derived from direct binding of the TFs to the DNA. Our predictions derived co-binding TFs supported by protein-protein interaction data and defined cis-regulatory modules enriched for disease- and trait-associated SNPs. We provide this collection of direct TF–DNA interactions and cis-regulatory modules through the UniBind web-interface (http://unibind.uio.no).
Therapeutic Ultrasound for Pain Management in Chronic Low Back Pain and Chronic Neck Pain: A Systematic Review
Authors: Noori Selaiman A , Rasheed Abdullah , Aiyer Rohit , Jung Boyoun , Bansal Nitin , Chang Ke-Vin , Ottestad Einar , Gulati Amitabh 
Published: November 2018

Background
Low back pain (LBP) and neck pain are major causes of pain and disability that are experienced across all ages. The primary goals of treatment are to improve patient function and facilitate a return to the patient’s desired level of daily activity. Therapeutic ultrasound is a noninvasive modality widely utilized in the management of musculoskeletal disorders, but there continues to be controversy regarding its use due to insufficient evidence of effectiveness. The objective of this systematic review was to evaluate the effectiveness of therapeutic ultrasound in the management of patients with chronic LBP and neck pain.

Methods
Using PRISMA guidelines, a search of the PubMed and CENTRAL (The Cochrane Library) databases was performed to retrieve randomized controlled trials (RCTs) that evaluated therapeutic ultrasound in patients with chronic LBP or neck pain.

Results
The search strategy identified 10 trials that met the criteria for inclusion. Three studies in LBP reported that both therapeutic and sham (placebo) ultrasound provided significant improvement in pain intensity. In each of these studies, ultrasound was found to be more effective than placebo when using only one of several validated instruments to measure pain. Three of the four studies on neck pain demonstrated significant pain relief with ultrasound in combination with other treatment modalities. However, only one of these studies demonstrated that the use of ultrasound was the cause of the statistically significant improvement in pain intensity.

Conclusions
Therapeutic ultrasound is frequently used in the treatment of LBP and neck pain and is often combined with other physiotherapeutic modalities. However, given the paucity of trials and conflicting results, we cannot recommend the use of monotherapeutic ultrasound for chronic LBP or neck pain. It does seem that ultrasound may be considered as part of a physical modality treatment plan that may be potentially helpful for short-term pain relief; however, it is undetermined which modality may be superior. In both pain syndromes, further trials are needed to define the true effect of low-intensity ultrasound therapy for axial back pain. No conclusive recommendations may be made for optimal settings or session duration.
Feasibility of App-Based Postsurgical Assessment of Pain, Pain Impact, and Regional Anesthesia Effects: A Pilot Randomized Controlled Trial
Authors: Highland Krista B , Tran Julie , Edwards Hisani , Bedocs Peter , Suen Joshua , Buckenmaier Chester C 
Published: November 2018

Abstract

Objective
Postsurgical follow-up calls enable nurses to assess a patient’s condition, provide tailored education, and improve the patient’s experience. Despite the benefits, barriers to phone-based assessments may include patient nonresponse and lack of time due to demanding clinical schedules. The purpose of this trial was to examine the feasibility and utility of a smartphone app, mCare, for assessing pain, pain impact, and peripheral nerve block effects in patients.

Design
Pilot randomized control trial.

Setting and Patients
Eligible patients at a military treatment facility undergoing same-day surgery were randomized to the mCare group (N = 24) or the standard-of-care telephone (N = 26) group.

Results
Outcomes included initial response (assessment completion) rates and participant and nurse satisfaction. There were no differences in the response rates upon initial contact attempt, and patients in both groups reported similar levels of satisfaction and convenience. Nurses reported greater satisfaction with the app compared with standard-of-care telephone calls.

Conclusions
Before wider implementation, further considerations of app-based assessment need to be fully explored.
Evaluating Improvements to Exposure Estimates from Fate and Transport Models by Incorporating Environmental Sampling Effort and Landscape-level Contaminant Use
Authors: Rumschlag Samantha L. , Bessler Scott M. , Rohr Jason R. 
Published: November 2018

ABSTRACTThe Pesticide in Water Calculator (PWC) is a fate and transport model used by the Environmental Protection Agency and Health Canada to estimate pesticide exposures in lentic freshwater ecosystems and make pesticide registration decisions. We leverage over 600,000 field measurements of 31 common insecticides and herbicides to test whether incorporating environmental sampling effort (number of times a pesticide is sampled) and landscape-level contaminant use (national application amount) can improve PWC validation and prediction, respectively. We found that maximum measured concentrations of 38% of herbicides and 42% of insecticides exceeded maximum estimated environmental concentrations (EECs) generated by the PWC, suggesting that EECs often do not represent worst-case exposure. For lentic systems, variance in pesticide field measurements explained by EECs increased by 50% when sampling effort was included. For lotic systems, variance explained increased by only 4%, most likely because lotic systems are sampled over 4.9 times as much as lentic systems. Including landscape-level use more than doubled the ability of the PWC to predict maximum pesticides concentrations in lentic systems. Exposure characterization in risk assessment can be improved by including sampling effort in model validation and landscape-level use in predictions, thus providing more defensible environmental standards and regulations.
A spatial map in the somatosensory cortex
Authors: Long Xiaoyang , Zhang Sheng-Jia 
Published: November 2018

AbstractSpatially selective firing in the forms of place cells, grid cells, boundary vector/border cells and head direction cells are the basic building blocks of a canonical spatial navigation system centered on the hippocampal-entorhinal complex. While head direction cells can be found throughout the brain, spatial tuning outside the hippocampal formation are often non-specific or conjunctive to other representations such as a reward. Although the precise mechanism of spatially selective activities is not understood, various studies show sensory inputs (particularly vision) heavily modulate spatial representation in the hippocampal-entorhinal circuit. To better understand the contribution from other sensory inputs in shaping spatial representation in the brain, we recorded from the primary somatosensory cortex in foraging rats. To our surprise, we were able to identify the full complement of spatial activity patterns reported in the hippocampal-entorhinal network, namely, place cells, head direction cells, boundary vector/border cells, grid cells and conjunctive cells. These newly identified somatosensory spatial cell types form a spatial map outside the hippocampal formation and support the hypothesis that location information is necessary for body representation in the somatosensory cortex, and may be analogous to spatially tuned representations in the motor cortex relating to the movement of body parts. Our findings are transformative in our understanding of how spatial information is used and utilized in the brain, as well as functional operations of the somatosensory cortex in the context of rehabilitation with brain-machine interfaces.
Efforful verb recollection drives beta suppression in mesial frontal regions involved in action initiation
Authors: Pavlova Anna A. , Butorina Anna V. , Nikolaeva Anastasia Y. , Prokofyev Andrey O. , Ulanov Maxim A. , Bondarev Denis P. , Stroganova Tatiana A. 
Published: November 2018

AbstractWhether the motor cortex activation accompanying concrete verbs comprehension is necessary for verbs conceptual processing is still a hotly debated topic in the literature. Answering this question, we examined to what extent the more difficult access to verb semantics requires an additional engagement of cortical motor system in verb generation task. Using power suppression of MEG beta oscillations (15-30 Hz) as an index of sensorimotor activation, we presented to our participants the noun cues which either were strongly associated with a single verb and prompted the fast and effortless verb retrieval, or were weakly associated with multiple verbs and were more difficult to respond to. A whole-brain analysis of beta suppression revealed that the only cortical regions sensitive to the difficulty of semantic access were the higher order motor areas on the medial and lateral surfaces of the frontal lobe. This differential activation of cortical motor system accompanied effortful verb retrieval and preceded the preparation of vocal response for more than 500 milliseconds. Since the mid-frontal frontal brain areas are involved in maintaining abstract representations of actions during their initiating and planning, we argue that our finding supports the view that motor associations contribute to retrieval of verb semantics.
Prospective real-time metagenomic sequencing during norovirus outbreak reveals discrete transmission clusters
Authors: Casto Amanda M. , Adler Amanda L. , Makhsous Negar , Crawford Kristen , Qin Xuan , Kuypers Jane M. , Huang Meei-Li , Zerr Danielle M. , Greninger Alexander L. 
Published: November 2018

AbstractBackgroundNorovirus outbreaks in hospital settings are a common challenge for infection prevention teams. Given the high burden of norovirus in most communities, it can be difficult to distinguish between on-going in-hospital transmission of virus and new introductions from the community and challenging to understand the long-term impacts of outbreak-associated viruses within medical systems using traditional epidemiological approaches alone.MethodsReal-time metagenomic sequencing during an on-going norovirus outbreak associated with a retrospective cohort study.ResultsWe describe a hospital-associated norovirus outbreak that affected 13 patients over a 27-day period in a large tertiary pediatric hospital and was chronologically associated with a spike in self-reported gastrointestinal symptoms among staff. Real-time metagenomic next-generation sequencing (mNGS) of norovirus genomes demonstrated that 10 chronologically overlapping hospital-acquired norovirus cases were partitioned into three discrete transmission clusters. Sequencing data also revealed close genetic relationships between some hospital-acquired and some community-acquired cases. Finally, this data was used to demonstrate chronic viral shedding by an immunocompromised hospital-acquired case patient. Analysis of serial samples from this patient provided novel insights into the evolution of norovirus within an immunocompromised host.ConclusionsThis study documents one of the first applications of real-time mNGS during a hospital-associated viral outbreak. Given its demonstrated ability to detect transmission patterns within outbreaks and elucidate the long-term impacts of outbreak-associated viral strains on patients and medical systems, mNGS constitutes a powerful resource to help infection control teams understand, prevent, and respond to viral outbreaks.Summary StatementReal-time metagenomic sequencing performed during a hospital-associated norovirus outbreak identified genetically-distinct, chronologically-overlapping case clusters. After the epidemiologically-defined outbreak had ceased, on-going transmission and shedding of outbreak-associated virus was also detected. These findings illustrate the value of genomics as a tool for infection control.
Rewiring of Th-memory-associated gene co-expression networks underlie immunotherapy-induced changes in symptom expression in mite-sensitised atopics
Authors: Jones Anya C. , Anderson Denise , Troy Niamh M. , Mallon Dominic , Hartmann Rochelle , Serralha Michael , Holt Barbara , Bosco Anthony , Holt Patrick G. 
Published: November 2018

ABSTRACTBackgroundMultiple regulatory mechanisms have been identified employing conventional hypothesis-driven approaches as contributing to allergen-specific immunotherapy outcomes, but understanding of how these integrate to maintain immunological homeostasis is incomplete.ObjectiveTo explore the potential for unbiased systems-level gene co-expression network analysis to advance understanding of immunotherapy mechanisms.MethodsWe profiled genome-wide allergen-specific Th-memory responses prospectively across 24mths of subcutaneous immunotherapy (SCIT) in 25 rhinitics, documenting changes in immunoinflammatory pathways and associated co-expression networks and their relationships to symptom scores to 36mths.ResultsPrior to immunotherapy, mite-specific Th-memory response networks involved multiple discrete co-expression modules including those related to Th2-, Type1-IFN-, Inflammation-, and FOXP3/IL2-associated signalling. A signature comprising 109 genes correlated with symptom scores, and these mapped to cytokine signalling/T-cell activation-associated pathways, with upstream drivers including hallmark Th1/Th2-and inflammation-associated genes. Reanalysis after 3.5mths SCIT updosing detected minimal changes to pathway/upstream regulator profiles despite 32.5% reduction in symptoms, however network analysis revealed underlying merging of FOXP3/IL2-with Inflammation-and Th2-associated modules. By 12mths on SCIT, symptoms had reduced by 41% without further significant changes to pathway/upstream regulator or network profiles. Continuing SCIT to 24mths stabilised symptoms at 47% of baseline, accompanied by upregulation of the Type1-IFN-associated network module and its merging into the Th2/FOXP3/IL2/Inflammation module.ConclusionsSCIT stimulates progressive integration of Th-memory-associated Th2-,FOXP3/IL2-, Inflammation-, and Type1-IFN-signalling subnetworks, forming a single highly integrated co-expression network module, maximising potential for stable homeostatic control of allergen-specific Th2 responses via cross-regulation. Th2-anatogonistic Type1-IFN signalling may play a key role in stabilising clinical effects of SCIT.Clinical ImplicationStabilisation of the clinical effectiveness of SCIT involves recruitment of Th2-antagonistic Type 1 IFN-dependent signalling into the overall gene co-expression network underlying the allergen-specific Th-memory response, and this does not occur until the 2ndyear of treatment.Capsule summarySCIT-induced rewiring of the gene network governing allergen-specific Th2-memory, as opposed to selective upregulation of genes associated with regulatory functions, underlies the clinical effectiveness of immunotherapy.
Multiplexed pooled library screening with Cpf1
Authors: Liu Jintan , Srinivasan Sanjana , Li Chieh-Yuan , Ho I-Lin , Wang Gang , Yao Wantong , Deem Angela Kay , Bristow Chris , Hart Traver , Draetta Giulio 
Published: November 2018

AbstractRNA interference and CRISPR/Cas9-based pooled library screens have revolutionized the field of functional genomics. However, currently available pooled library screens face a trade-off between library effectiveness and library complexity. We developed a multiplexed, high-throughput screening strategy based on an optimized AsCpf1 nuclease that minimizes library size without sacrificing gene targeting efficiency. Our AsCpf1-based multiplexed library performed similarly well compared to currently available CRISPR/Cas9 libraries, but with a single polycistronic crRNA clone targeting each gene. With this strategy, we constructed the smallest whole-genome knock-out library available, “Mini-human” for the human genome, which is one-fourth the size of the smallest CRISPR library currently available.
Trypanosoma bruceiPex13.2 is an accessory peroxin that functions in the import of PTS2 proteins and localizes to subdomains of the glycosome
Authors: Crowe Logan P. , Nicholson Kathleen R. , Wilkinson Christina L. , Morris Meredith T. 
Published: November 2018

ABSTRACTKinetoplastid parasites includingTrypanosoma brucei, Trypanosoma cruziandLeishmaniaharbor unique organelles known as glycosomes, which are evolutionarily related to peroxisomes. Glycosome/peroxisome biogenesis is mediated by proteins called peroxins that facilitate organelle formation, proliferation and degradation, and import of proteins housed therein. Import of matrix proteins occurs via one of two pathways that are dictated by their peroxisome targeting sequence (PTS). In PTS1 import, a C-terminal tripeptide sequence, most commonly SKL, is recognized by the soluble receptor Pex5. In PTS2 import, a less conserved N-terminal sequence is recognized by Pex7. The soluble receptors deliver their cargo to the import channel consisting minimally of Pex13 and Pex14. While much of the import process is conserved, kinetoplastids are the only organisms to have two Pex13s,TbPex13.1 andTbPex13.2. In previous studies, GFP-taggedTbPex13.1 localized to glycosomes and silencing either protein in the stage of the parasite that lives in the mammalian bloodstream impaired glycosome protein import and slowed parasite growth. While these findings suggest Pex13s are involved in protein import, the mechanisms by which they function are unknown and it is unclear why kinetoplastids would require two Pex13s. In this work, we demonstrate thatTbPex13.2 is associated with the glycosome membrane with its N-terminus facing the cytoplasm. Super-resolution microscopy reveals thatTbPex13.2 localizes to a few (1-3) foci per glycosome and import of PTS2 proteins was disrupted inTbPex13.2-deficient cells suggesting it may be an accessory factor for PTS2 import.
Decomposition of cohort, age and time effects in Iranian households’ cigarette consumption
Authors: Keshavarz Haddad GholamReza , Habibi Nader , Rafiee Sajad 
Published: November 2018

PurposeThe purpose of this paper is to examine cigarette consumption behavior of younger cohorts in the urban and rural areas of Iran. The authors use Iran’s annual Household Income and Expenditures Surveys (HIES) database over 2007–2013 for the statistical analysis. In order to control for a large number of households with zero expenditure on cigarette consumption, the authors have used the double-hurdle modeling approach for counting the outcomes of interest. The authors have also limited the sample to cases in which the head of household is between the ages of 21 and 45 and all children are younger than 18.Design/methodology/approachIn this study, the authors have conducted a multivariate econometric analysis to identify the impact of age and birth year cohort on the demand for cigarettes among Iranian households. The authors have used the HIES data for multiple years in the analysis. The ideal data set for the analysis is a panel data that include information on cigarette consumption of various age cohorts over a long period of time. Since no suitable panel data are available, the authors have constructed a multi-year cohort data by extracting cohort data from the annual HIES data set. Due to the unique properties of cigarette consumption, the authors have used the double-hurdle econometric model with appropriate diagnostics.FindingsAfter controlling for price and demographic factors, which affect the demand for cigarettes, the authors find that the younger cohorts in rural areas, who smoke, tend to consume fewer cigarettes than the older ones; however, the opposite is true among urban households. The probability of being a non-smoker is larger for younger cohorts in both rural and urban areas. Among smokers, the authors observe an inverse U-shape relation between age and quantity of cigarettes consumed per day. The trend is positive up to age 45, but diminishes for older smokers because of health concerns.Originality/valueIn comparison to previous studies of tobacco consumption in Iran, the authors have used a more comprehensive household income and expenditure survey data set with a large number of observations. Furthermore, the authors have applied an econometric method (the double-hurdle model), which is suitable for the analysis of the determinants of demand for cigarettes when a subset of households report no cigarette consumption.
Assessing ecological and physiological costs of melanism in North American Papilio glaucus females: two decades of dark morph frequency declines
Authors: Scriber J. Mark 
Published: November 2018

AbstractPolymorphisms for melanic form of insects may provide various selective advantages. However, melanic alleles may have significant/subtle pleiotrophic “costs.” Several potential pleiotrophic effects of the W (=Y)‐linked melanism gene in Papilio glaucus L. (Lepidoptera) showed no costs for melanic versus yellow in adult size, oviposition preferences, fecundity, egg viability, larval survival/growth rates, cold stress tolerance, or postdiapause emergence times. Sexual selection (males choosing yellow rather than mimetic dark females) had been suggested to provide a balanced polymorphism in P. glaucus, but spermatophore counts in wild females and direct field tethering studies of size‐matched pairs of virgin females (dark and yellow), show that male preferences are random or frequency‐dependent from Florida to Michigan, providing no yellow counter‐advantages. Recent frequency declines of dark (melanic/mimetic) females in P. glaucus populations are shown in several major populations from Florida (27.3°N latitude) to Ohio (38.5° N). Summer temperatures have increased significantly at all these locations during this time (1999–2018), but whether dark morphs may be more vulnerable (in any stage) to such climate warming remains to be determined. Additional potential reasons for the frequency declines in mimetic females are discussed: (i) genetic introgression of Z‐linked melanism suppressor genes from P. canadensis (R & J) and the hybrid species, P. appalachiensis (Pavulaan & Wright), (ii) differential developmental incompatibilities, or Haldane effects, known to occur in hybrids, (iii) selection against intermediately melanic (“dusty”) females (with the W‐linked melanic gene, b+) which higher temperatures can cause.