bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recalibration and External Validation of the Risk Analysis Index
Authors: Arya Shipra , Varley Patrick , Youk Ada , Borrebach Jeffrey D. , Perez Sebastian , Massarweh Nader N. , Johanning Jason M. , Hall Daniel E. 
Published: March 2019

Objective and Background:
The Risk Analysis Index (RAI) predicts 30-, 180-, and 365-day mortality based on variables constitutive of frailty. Initially validated, in a single-center Veteran hospital, we sought to improve model performance by recalibrating the RAI in a large, veteran surgical registry, and to externally validate it in both a national surgical registry and a cohort of surgical patients for whom RAI was measured prospectively before surgery.

Methods:
The RAI was recalibrated among development and confirmation samples within the Veterans Affairs Surgical Quality Improvement Program (VASQIP; 2010–2014; N = 480,731) including major, elective noncardiac surgery patients to create the revised RAI (RAI-rev), comparing discrimination and calibration. The model was tested externally in the American College of Surgeons National Surgical Quality Improvement Program dataset (NSQIP; 2005–2014; N = 1,391,785), and in a prospectively collected cohort from the Nebraska Western Iowa Health Care System VA (NWIHCS; N = 6,856).

Results:
Recalibrating the RAI significantly improved discrimination for 30-day [c = 0.84–0.86], 180-day [c = 0.81–0.84], and 365-day mortality [c = 0.78–0.82] (P < 0.001 for all) in VASQIP. The RAI-rev also had markedly better calibration (median absolute difference between observed and predicted 180-day mortality: decreased from 8.45% to 1.23%). RAI-rev was highly predictive of 30-day mortality (c = 0.87) in external validation with excellent calibration (median absolute difference between observed and predicted 30-day mortality: 0.6%). The discrimination was highly robust in men (c = 0.85) and women (c = 0.89). Discrimination also improved in the prospectively measured cohort from NWIHCS for 180-day mortality [c = 0.77 to 0.80] (P < 0.001).

Conclusions:
The RAI-rev has improved discrimination and calibration as a frailty-screening tool in surgical patients. It has robust external validity in men and women across a wide range of surgical settings and available for immediate implementation for risk assessment and counseling in preoperative patients.
Medicare Reimbursement for General Surgery Procedures
Authors: Haglin Jack M. , Eltorai Adam E. M. , Richter Kent R. , Jogerst Kristen , Daniels Alan H. 
Published: March 2019

Objective:
The purpose of this study is to evaluate monetary trends from 2000 to 2018 in Medicare reimbursement rates for the most common general surgery procedures.

Summary Background Data:
A complete understanding of financial trends in general surgery in the United States is lacking. As such, an evaluation of trends in reimbursement rates in general surgery is important for defining the specialty's current and future financial health.

Methods:
The Physician Fee Schedule Look-Up Tool from the Centers for Medicare and Medicaid Services was queried for each of the 20 top codes top in general surgery. The total raw percent change in Medicare reimbursement rate for each procedure from 2000 to 2018 was calculated and averaged. All data was corrected for inflation. Both average annual and total percentage change were calculated based on these adjusted trends. Compound annual growth rate was calculated using the adjusted data.

Results:
After adjusting all data for inflation, the reimbursement rate for all included procedures decreased by an average of 24.4% throughout the study period. During this time, the adjusted reimbursement rate decreased by an average of 1.4% each year with an average compound annual growth rate of −1.6%.

Conclusion:
After adjusting for inflation, Medicare reimbursement rates in general surgery have steadily decreased from 2000 to 2018. It is important that these trends are understood and considered by surgeons, healthcare administrators, and policy-makers in order to develop and implement agreeable models of reimbursement while ensuring access to quality general surgery care in the United States.
Characteristic sounds facilitate object search in real-life scenes
Authors: Kvasova Daria , Garcia-Vernet Laia , Soto-Faraco Salvador 
Published: March 2019

AbstractReal-world multisensory events do not only provide temporally and spatially correlated information, but also semantic correspondences about object identity. Semantically consistent sounds can enhance visual detection, identification and search performance, but these effects are always demonstrated in simple and stereotyped displays that lack ecological validity. In order to address identity-based crossmodal relationships in real world scenarios, we designed a visual search task using complex, dynamic scenes. Participants searched objects in video clips from real life scenes with background sounds. Auditory cues embedded in the background sounds could be target-consistent, distracter-consistent, neutral and no sound (just background noise). We found that characteristic sounds enhance visual search of relevant objects in natural scenes but fail to increase the salience of irrelevant distracters. Our findings generalize previous results on object-based crossmodal interactions with simple stimuli and shed light upon how audio-visual semantically congruent relationships play out in real life contexts.
Optimizing root measurements in rhizotrons
Authors: Ytting NK , Kirkegaard JA , Thorup-Kristensen K 
Published: March 2019

AbstractBackground and AimsThe line intersect method is widely used in rhizotron and minirhizotron studies to quantify roots and study cultivar and treatment differences in root growth. We investigated ways to optimize the line intersect method and root depth measurements with respect to data variability and the time spent on counting roots.MethodsRoot intensity was measured with three different grid patterns and different lengths of counting line on 2 m long transparent tube rhizotrons. Rooting depth was recorded by measuring the depth of the deepest root and by measuring the depth below which 5, 10 and 25 roots were observed.ResultsFor root intensity the coefficient of variation (CV) was reduced 10-50 percentage points for grids that distributed counting lines equally across the measured area compared to using a restricted centralized area. In addition, the CV approached an asymptote of around 40 % when more than 50 root intersections per grid were observed. Further we show that recordings of the deepest root gave the most variance and least difference between means with a p-value of 0.65 for difference between cultivars. In contrast, a significant difference between cultivar rooting depths (p = 0.01) was found when using the depth below which 25 roots were observed.ConclusionWe propose the use of grid designs adapted to different root densities to decrease time spent on counting roots at high root intensities, and minimize data variability at low root intensities. Further on rooting depth measurements including more roots may be a more useful parameter statistically to reveal variety or treatment differences in rooting depth.
CD16-158-Valine Chimeric Receptor T Cells Overcome the Resistance of KRAS-mutated Colorectal Carcinoma Cells to Cetuximab
Authors: Arriga Roberto , Caratelli Sara , Lanzilli Giulia , Ottaviani Alessio , Cenciarelli Carlo , Sconocchia Tommaso , Spagnoli Giulio Cesare , Iezzi Giandomenica , Roselli Mario , Lauro Davide , Dotti Gianpietro , Ferrone Soldano , Sconocchia Giuseppe 
Published: March 2019

ABSTRACTKRAS mutation hinders the therapeutic efficacy of epidermal-growth-factor-receptor (EGFR) mAb (cetuximab and panitumumab)-based immunotherapy of EGFR+ cancers. Although, cetuximab controls KRAS-mutated cancer cell growthin vitroutilizing a NK cell-mediated antibody-dependent-cellular-cytotoxicity-(ADCC) mechanism, KRAS-mutated colorectal carcinoma (CRC) cells can still escape NK cell immunosurveillance. To overcome this limitation, we used cetuximab and panitumumab to redirect Fcγ chimeric receptor (CR) T cells against KRAS-mutated HCT116 CRC cells. We compared 4 polymorphic Fcγ-CR constructs including CD16158F-CR, CD16158V-CR, CD32131H-CR, and CD32131R-CR which were transduced into T cells utilizing retroviral transduction. Percentages of transduced T cells expressing CD32131H-CR (83.5±9.5) and CD32131R–CR (77.7.±13.2) were significantly higher than those expressing with CD16158F-CR (30.3±10.2) and CD16158V-CR (51.7±13.7) (p<0.003). CD32131R-CR T cells specifically bound soluble cetuximab and panitumumab. However, only CD16158V-CR T cells released significantly higher levels of interferon gamma (IFNγ=1145.5 pg/ml ±16.5 pg/ml, p<0.001) and tumor necrosis factor alpha (TNFα=614 pg/ml ± 21 pg/ml, p<0.001) than non-transduced T cells when incubated with KRAS-mutated HCT116 cells opsonized with cetuximab. Only CD16158V-CR T cells combined with cetuximab controlled the growth of HCT116 cells subcutaneously engrafted in CB17-SCID mice. These results suggest that CD16158V-CR T cells combined with cetuximab represent useful reagents to develop an effective immunotherapy of EGFR+KRAS-mutated cancer.
Depletion of resident muscle stem cells inhibits muscle fiber hypertrophy induced by lifelong physical activity
Authors: Englund Davis A. , Murach Kevin A. , Dungan Cory M. , Figueiredo Vandré C. , Vechetti Ivan J. , Dupont-Versteegden Esther E. , McCarthy John J. , Peterson Charlotte A. 
Published: March 2019

AbstractBackgroundA reduction in skeletal muscle stem cell (satellite cell) content with advancing age is thought to directly contribute to the progressive loss of skeletal muscle mass and function with aging (sarcopenia). However, we reported that the depletion of satellite cells throughout adulthood did not affect the onset or degree of sarcopenia observed in sedentary old mice. The current study was designed to determine if lifelong physical activity would alter the requirements for satellite cells during aging.MethodsWe administered vehicle or tamoxifen to adult (5 months old) female Pax7-DTA mice for 5 consecutive days to effectively deplete satellite cells. Following a 2-month washout period, mice were assigned to physically active (free access to a running wheel) or sedentary (locked running wheel) conditions. Thirteen months later, at a mean age of 20 months, mice were sacrificed for subsequent analysis.ResultsSatellite cell depletion throughout adulthood negatively impacted physical function and limited muscle fiber hypertrophy in response to lifelong physical activity. To further interrogate these findings, we performed transcriptome-wide analyses on the hind limb muscles that experienced hypertrophic growth (plantaris and soleus) in response to lifelong physical activity. Our findings demonstrate that satellite cell function is muscle type-specific; fusion with fibers is apparent in oxidative muscles, while initiation of Gαi2 signaling appears to require satellite cells in glycolytic muscles to induce muscle growth..ConclusionsThese findings suggest that satellite cells, or their secretory products, are viable therapeutic targets to preserve physical function with aging and promote muscle growth in older adults who regularly engage in physical activity.
Time-resolved NMR monitoring of tRNA maturation
Authors: Barraud Pierre , Gato Alexandre , Heiss Matthias , Catala Marjorie , Kellner Stefanie , Tisné Carine 
Published: March 2019

ABSTRACTAlthough the biological importance of post-transcriptional RNA modifications in gene expression is widely appreciated, methods to directly detect the introduction of these modifications during RNA biosynthesis are rare and do not easily provide information on the temporal nature of events. Here we introduce the application of NMR spectroscopy to observe the maturation of tRNAs in cell extracts. By following the maturation of yeast tRNAPhewith time-resolved NMR measurements, we found that modifications are introduced in a defined sequential order, and that the chronology is controlled by cross-talk between modification events. In particular, we uncovered a strong hierarchy in the introduction of the T54, Ψ55 and m1A58 modifications in the T-arm, and demonstrate that the modification circuits identified in yeast extract with NMR also impact the tRNA modification process in living cells. The NMR-based methodology presented here could be adapted to investigate different aspects of tRNA maturation and RNA modifications in general.
Development and Application of a Tri-allelic PCR Assay for ScreeningVgsc-L1014FKdrMutations Associated with Pyrethroid and Organochlorine Resistance in the MosquitoCulex quinquefasciatus
Authors: Silva Martins Walter Fabricio , Silva Pereira Bárbara Natieli , Vieira Alves Ana Thayse , Murphy Annabel , Silva Martins Paulo Geovani , Weetman David , Wilding Craig Stephen , Donnelly Martin James 
Published: March 2019

AbstractBackgroundCulex quinquefasciatus,has a widespread distribution across tropical and sub-tropical regions, and plays an important role in the transmission of vector-borne diseases of public health importance, including lymphatic filariasis (LF) and multiple arboviruses. Increased resistance to insecticides threatens the efficacy and sustainability of insecticide-based anti-vector interventions which mitigate the burden of mosquito transmitted diseases in endemic regions. InC. quinquefasciatustwo non-synonymous voltage gated sodium channel (Vgsc) variants, both resulting in a leucine to phenylalanine change at codon 1014, are associated with resistance to pyrethroids and DDT. This tri-allelic variation has compromised the ability to perform high-throughput single-assay screening. To facilitate the detection and monitoring of theVgsc-1014 locus in field-caught mosquitoes, an Engineered-Tail Allele-Specific-PCR (ETAS-PCR) diagnostic assay was developed and applied to wild mosquitoes from Brazil, Tanzania and Uganda.ResultsThis new cost-effective, single-tube assay was compared to two, well-established, genotyping approaches – pyrosequencing and TaqMan. The ETAS-PCR assay showed high specificity for discriminating the three alleles atVgsc-L1014F, with genotyping results strongly correlated with 98.64% and 100% against pyrosequencing and TaqMan, respectively.ConclusionsOur results support the utility of the ETAS-PCR/Vgsc-1014 diagnostic assay, which stands as an effective alternative for genotyping tri-allelic variants.
Splicing conservation signals in plant long non-coding RNAs
Authors: Corona-Gomez Jose Antonio , Garcia-Lopez Irving Jair , Stadler Peter F. , Fernandez-Valverde Selene L. 
Published: March 2019

AbstractLong non-coding RNAs (lncRNAs) have recently emerged as prominent regulators of gene expression in eukaryotes. LncRNAs often drive the modification and maintenance of gene activation or gene silencing states via chromatin conformation rearrangements. In plants, lncRNAs have been shown to participate in gene regulation, and are essential to processes such as vernalization and photomorphogenesis. Despite their prominent functions only over a dozen lncRNAs have been experimentally and functionally characterized.Similar to its animal counterparts, the rates of sequence divergence are much higher in plant lncRNAs than in protein coding mRNAs, making it difficult to identify lncRNA conservation using traditional sequence comparison methods. Beyond this, little is known about the evolutionary patterns of lncRNAs in plants. Here, we characterized the splicing conservation of lncRNAs in Brassicaceae. We generated a whole-genome alignment of 16 Brassica species and used it to identify synthenic lncRNA orthologues. Using a scoring system trained on transcriptomes from A. thaliana and B. oleracea, we identified splice sites across the whole alignment and measured their conservation. Our analysis revealed that 17.9% (112/627) of all intergenic lncRNAs display splicing conservation in at least one exon, an estimate that is substantially higher to previous estimates of lncRNA conservation in this group. Our findings agree with similar studies in vertebrates, demonstrating that splicing conservation can be evidence of stabilizing selection. We provide conclusive evidence for the existence of evolutionary deeply conserved lncRNAs in plants and describe a generally applicable computational workflow to identify functional lncRNAs in plants.
Familiar neighbours, but not relatives, enhance fitness in a territorial mammal
Authors: Siracusa Erin R. , Boutin Stan , Dantzer Ben , Lane Jeffrey E. , Coltman David W. , McAdam Andrew G. 
Published: March 2019

SummaryOne of the outstanding questions in evolutionary biology is the extent to which mutually beneficial interactions and kin-selection can facilitate the evolution of cooperation by mitigating conflict between interacting organisms. The indirect fitness benefits gained from associating with kin are an important pathway to conflict resolution [1], but conflict can also be resolved if individuals gain direct benefits from cooperating with one another (e.g. mutualism or reciprocity) [2]. Owing to the kin-structured nature of many animal societies, it has been difficult for previous research to assess the relative importance of these mechanisms [3–5]. However, one area that might allow for the relative roles of kin-selection and mutualistic benefits to be disentangled is in the resolution of conflict over territorial space [6]. While much research has focused on group-living species, the question of how cooperation can first be favoured in solitary, territorial species remains a key question. Using 22 years of data from a population of North American red squirrels, we assessed how kinship and familiarity with neighbours affected fitness in a territorial mammal. While living near kin did not enhance fitness, familiarity with neighbours increased survival and annual reproductive success. These fitness benefits were strong enough to compensate for the effects of aging later in life, with potential consequences for the evolution of senescence. We suggest that such substantial fitness benefits provide the opportunity for the evolution of cooperation between adversarial neighbours, offering insight into the role that mutually beneficial behaviours might play in facilitating and stabilizing social systems.Graphical Abstract
Transcriptomic analysis of insecticide resistance in the lymphatic filariasis vectorCulex quinquefasciatus
Authors: Martins Walter Fabricio Silva , Wilding Craig Stephen , Isaacs Alison Taylor , Rippon Emily Joy , Megy Karine , Donnelly Martin James 
Published: March 2019

ABSTRACTCulex quinquefasciatusplays an important role in transmission of vector-borne diseases of public health importance, including lymphatic filariasis (LF), as well as many arboviral diseases. Currently, efforts to tackleC. quinquefasciatusvectored diseases are based on either mass drug administration (MDA) for LF, or insecticide-based interventions. Widespread and intensive insecticide usage has resulted in increased resistance in mosquito vectors, includingC. quinquefasciatus. Herein, the transcriptome profile of Ugandan bendiocarb-resistantC. quinquefasciatuswas explored to identify candidate genes associated with insecticide resistance. Resistance to bendiocarb in exposed mosquitoes was marked, with 2.04% mortality following 1h exposure and 58.02% after 4h. Genotyping of the G119SAce-1target site mutation detected a highly significant association (p<0.0001; OR=25) between resistance andAce1-119S. However, synergist assays using the P450 inhibitor PBO or the esterase inhibitor TPP resulted in markedly increased mortality (to ≈80%), suggesting a role of metabolic resistance in the resistance phenotype. Using a novel, custom 60K whole-transcriptome microarray 16 genes significantly overexpressed in resistant mosquitoes were detected, with the P450Cyp6z18showing the highest differential gene expression (>8-fold increase vs unexposed controls). These results provide evidence that bendiocarb-resistance in UgandanC. quinquefasciatusis mediated by both target-site mechanisms and over-expression of detoxification enzymes.
Epigenomic Landscape ofArabidopsis thalianaMetabolism Reveals Bivalent Chromatin on Specialized Metabolic Genes
Authors: Zhao Kangmei , Rhee Seung Y. 
Published: March 2019

AbstractMetabolism underpins development and physiology, but little is known about how metabolic genes and pathways are regulated, especially in multicellular organisms. Here, we identified regulatory patterns of 16 epigenetic modifications across metabolism inArabidopsis thaliana. Surprisingly, specialized metabolic genes, often involved in defense, were predominantly regulated by two modifications that have opposite effects on gene expression, H3K27me3 (repression) and H3K18ac (activation). Using camalexin biosynthesis genes as an example, we confirmed that these two modifications were co-localized to form bivalent chromatin. Mutants defective in H3K27m3 and H3K18ac modifications showed that both modifications are required to determine the normal transcriptional kinetics of these genes upon stress stimuli. Our study suggests that this type of bivalent chromatin, which we name a kairostat, controls the precise timing of gene expression upon stimuli.One Sentence SummaryThis study identified a novel regulatory mechanism controlling specialized metabolism inArabidopsis thaliana.
Discovery of ongoing selective sweeps withinAnophelesmosquito populations using deep learning
Authors: Xue Alexander T. , Schrider Daniel R. , Kern Andrew D. ,   Ag1000G Consortium
Published: March 2019

AbstractIdentification of partial sweeps, which include both hard and soft sweeps that have not currently reached fixation, provides crucial information about ongoing evolutionary responses. To this end, we introducepartialS/HIC, a deep learning method to discover selective sweeps from population genomic data.partialS/HICuses a convolutional neural network for image processing, which is trained with a large suite of summary statistics derived from coalescent simulations incorporating population-specific history, to distinguish between completed versus partial sweeps, hard versus soft sweeps, and regions directly affected by selection versus those merely linked to nearby selective sweeps. We perform several simulation experiments under various demographic scenarios to demonstratepartialS/HIC’s performance, which exhibits excellent resolution for detecting partial sweeps. We also apply our classifier to whole genomes from eight mosquito populations sampled across sub-Saharan Africa by theAnopheles gambiae1000 Genomes Consortium, elucidating both continent-wide patterns as well as sweeps unique to specific geographic regions. These populations have experienced intense insecticide exposure over the past two decades, and we observe a strong overrepresentation of sweeps at insecticide resistance loci. Our analysis thus provides a list of candidate adaptive loci that may be relevant to mosquito control efforts. More broadly, our supervised machine learning approach introduces a method to distinguish between completed and partial sweeps, as well as between hard and soft sweeps, under a variety of demographic scenarios. As whole-genome data rapidly accumulate for a greater diversity of organisms,partialS/HICaddresses an increasing demand for useful selection scan tools that can track in-progress evolutionary dynamics.