bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Return to Functional Baseline After Mechanical Ventilation in the ICU*
Authors: Wilson Michael E. , Barwise Amelia , Heise Katherine J. , Loftsgard Theodore O. , Dziadzko Mikhail , Cheville Andrea , Majzoub Abdul , Novotny Paul J. , Gajic Ognjen , Biehl Michelle 
Published: December 2017

Objective:
Predictors of long-term functional impairment in acute respiratory failure of all causes are poorly understood. Our objective was to assess the frequency and predictors of long-term functional impairment or death after invasive mechanical ventilation for acute respiratory failure of all causes.

Design:
Population-based, observational cohort study.

Setting:
Eight adult ICUs of a single center.

Patients:
All adult patients from Olmsted County, Minnesota, without baseline functional impairment who received mechanical ventilation in ICUs for acute respiratory failure of all causes from 2005 through 2009.

Interventions:
None.

Measurements and Main Results:
In total, 743 patients without baseline functional impairment received mechanical ventilation in the ICU. At 1- and 5-year follow-up, the rates of survival with return to baseline functional ability were 61% (366/597) and 53% (356/669). Among 71 patients with new functional impairment at 1 year, 55% (39/71) had recovered and were alive without functional impairment at 5 years. Factors predictive of new functional impairment or death at 1 year were age, comorbidities, discharge to other than home, mechanical ventilation of 7 days or longer, and stroke. Of factors known at the time of intubation, the following are predictive of new functional impairment or death: age, comorbidities, nonsurgical condition, Acute Physiology and Chronic Health Evaluation III score, stroke, and sepsis. Post hoc sensitivity analyses revealed no significant change in predictor variables in patient populations when stroke was excluded or who received more than 48 hours of mechanical ventilation.

Conclusions:
At 1- and 5-year follow-up, many patients who received mechanical ventilation for acute respiratory failure from all causes are no longer alive or have new moderate-to-severe functional impairment. Functional recovery between year 1 and year 5 is possible and common. Sepsis, stroke, illness severity, age, and comorbidities predict long-term functional outcome at intubation.
Intra-articular Triamcinolone Versus Hyaluronate Injections for Low Back Pain With Symptoms Suggestive of Lumbar Zygapophyseal Joint Arthropathy
Authors: Annaswamy Thiru M. , Armstead Corey , Carlson Luke , Elkins Nicholas J. , Kocak Denizen , Bierner Samuel M. 
Published: December 2017

Objective
The aim of the study was to compare hyaluronate with triamcinolone injections in treating chronic low back pain suggestive of lumbar zygopophyseal joint arthropathy.

Design
This was a prospective, double-blind, randomized controlled trial. Thirty subjects were randomly assigned to receive bilateral L3-S1 lumbar zygopophyseal joint injections with triamcinolone (KA) or Synvisc-One (HA). Pain (visual analog scale) and Pain Disability Questionnaire scores at 1, 3, and 6 mos were evaluated.

Results
No significant intergroup differences (P > 0.05) in outcomes were noted in the 30 recruited subjects. For KA/HA (baseline; 1 mo; 3 mos; 6 mos), visual analog scale scores were the following: 70 (15)/74 (10); 58 (29)/45 (25); 58 (29)/56 (25); and 59 (28)/63 (24), respectively. Pain Disability Questionnaire scores were the following: 100 (23)/102 (28); 77 (30)/74 (34); 87 (26)/74 (36); and 96 (25)/79 (25). Overall percent improvement at 6 mos for KA was 51 (35) and for HA was 42 (33) (P = 0.51). Synvisc-One group visual analog scale scores improved significantly (70 [20]–45 [25] at 1 mo, P = 0.008). Pain Disability Questionnaire scores improved at 1 mo (100 [23]–77 [30], P = 0.009) in the KA group and at all time points in the HA group (102 [28]–74 [34] at 1 mo, P = 0.002; 74 [36] at 3 mos, P = 0.037; 79 at 6 mos [median = 52–99.5], P < 0.001). Medians and quartiles were used in statistical analysis when data did not pass normality.

Conclusions
Patients with chronic low back pain suggestive of lumbar lumbar zygopophyseal joint arthropathy responded similarly to triamcinolone or hyaluronate injections. Synvisc-One group showed significant short- and long-term functional improvement and short-term pain improvement; KA group showed only significant short-term functional benefit and no significant short- or long-term pain improvement.
Diabetic Retinopathy and Dementia in Type 1 Diabetes
Authors: Rodill Liora G. , Exalto Lieza G. , Gilsanz Paola , Biessels Geert Jan , Quesenberry Charles P. , Whitmer Rachel A. 
Published: December 2017

Objective:
Retinopathy impacts over one-third of those with diabetes mellitus and is associated with impaired cognitive performance and cerebrovascular lesions in middle-aged adults with type 1 diabetes. However, the association between diabetic retinopathy (DR) and risk of dementia in type 1 diabetes is unknown. We investigated the association between DR and incident dementia in a large, elderly population with type 1 diabetes.

Methods:
A cohort of 3742 patients with type 1 diabetes aged 50 years and above was followed from January 1, 1996 to September 30, 2015 for incident dementia. DR diagnoses were identified from electronic medical records. Age as timescale Cox proportional hazard models evaluated associations between time-updated DR and dementia risk. Models were adjusted for demographics, severe glycemic events, glycosylated hemoglobin, and vascular comorbidities.

Results:
Among 3742 patients with type 1 diabetes (47% female, 21% nonwhite), 182 (5%) were diagnosed with dementia during a mean follow-up of 6.2 years. No significant association was found between DR and incident dementia in the main analyses [adjusted Hazard Ratio=1.12; 95% confidence interval, 0.82-1.54), nor among subgroup restricted to those aged 60 years and above or 70 years and above.

Conclusions:
DR was not associated with risk of dementia, suggesting that pathophysiological processes underlying dementia may be different in type 1 versus type 2 diabetes.
Effect of polyamide 6 on the morphology and electrical conductivity of carbon black-filled polypropylene composites
Authors: Zhang Xuewei , Liu Jiang , Wang Yi , Wu Wei 
Published: December 2017

Carbon black (CB)-filled polypropylene (PP) with surface resistivity between 10
6
and 10
9
Ω sq
−1
is the ideal antistatic plastic material in the electronics and electric industry. However, a large amount of CB may have an adverse effect on the mechanical properties and processing performance of the material, thus an improved ternary system is developed. Blends of CB-filled PP and polyamide 6 (PA6) have been prepared by melt blending in order to obtain electrically conductive polymer composites with a low electrical percolation threshold based on the concept of double percolation. The morphological developments of these composites were studied by scanning electron microscopy. The results showed that CB particles were selectively dispersed in PA6 phases due to the good interaction and interfacial adhesion between CB and PA6. At the same CB loadings, the surface resistivity of PP/PA6/CB composite was smaller than that of PP/CB composite system, which indicated the better conductivity in the former composite. The increasing amount of PA6 in the composites changed the morphology from a typical sea–island morphology to a co-continuous morphology. What is more, with 8 wt% of CB and PP/PA6 phase ratio of 70/30 in which the PP and PA6 phases formed a co-continuous structure, the electrical conductivity of the composite peaked at 2.01 × 10
5
Ω sq
−1
.
Spontaneous dormancy protects Trypanosoma cruzi during extended drug exposure
Authors: Sánchez-Valdéz Fernando J. , Padilla Angel , Wang Wei , Orr Dylan , Tarleton Rick 
Published: December 2017

AbstractThe ability of the Chagas disease agent Trypanosoma cruzi to resist extended in vivo exposure to highly effective trypanocidal compounds prompted us to explore the potential for dormancy and its contribution to failed drug treatments in this infection. We document the development of non-proliferating intracellular amastigotes in vivo and in vitro in the absence of drug treatment. Non-proliferative amastigotes ultimately converted to trypomastigotes and established infections in new host cells. Most significantly, dormant amastigotes were uniquely resistant to extended drug treatment in vivo and in vitro and could re-establish a flourishing infection after as many as 30 days of drug exposure. These results demonstrate a dormancy pathway in T. cruzi that accounts for the failure of highly cytotoxic compounds to completely resolve the infection. The ability of T. cruzi to establish dormancy throws into question current methods for identifying curative drugs but also suggests alternative therapeutic approaches.
Without quality presence-absence data, discrimination metrics such as TSS can be misleading measures of model performance
Authors: Leroy Boris , Delsol Robin , Hugueny Bernard , Meynard Christine N. , Barhoumi Chéïma , Barbet-Massin Morgane , Bellard Céline 
Published: December 2017

ABSTRACTThe discriminating capacity (i.e., ability to correctly classify presences and absences) of species distribution models (SDMs) is commonly evaluated with metrics such as the Area Under the Receiving Operating Characteristic Curve, the Kappa statistic and the True Skill Statistic (TSS). AUC and Kappa have been repeatedly criticised, but the TSS has fared relatively well since its introduction, mainly because it has been considered as independent of prevalence. In addition, discrimination metrics have been contested because they should be calculated on presence-absence data, but are often used on presence-only or presence-background data. Here, we investigate the TSS and an alternative set of metrics −similarity indices, also known as F-measures. We first show that even in ideal conditions (i.e., perfectly random presence-absence sampling), TSS can be misleading because of its dependence on prevalence, whereas similarity/F-measures provide adequate estimations of model discrimination capacity. Second, we show that in real-world situations where sample prevalence is different from true species prevalence (i.e., biased sampling or presence-pseudoabsence), no discrimination capacity metric provide adequate estimations of model discrimination capacity, including metrics specifically designed for presence-pseudoabsence. Our conclusions are twofold. First, they unequivocally appeal SDM users to understand the potential shortcomings of discrimination metrics when quality presence-absence data are lacking, and we provide recommendations to obtain such data. Second, in the specific case of virtual species, which are increasingly used to develop and test SDM methodologies, we strongly recommend the use of similarity/F-measures, which were not biased by prevalence, contrary to TSS.
Host adaptation mediated by intergenic evolution in a bacterial pathogen
Authors: Hossein Khademi S. M. , Jelsbak Lars 
Published: December 2017

AbstractBacterial pathogens evolve during the course of infection as they adapt to the selective pressures that confront them inside the host. Identification of adaptive mutations and their contributions to pathogen fitness remain a central challenge. Although mutations can either target intergenic or coding regions in the pathogen genome, studies of host adaptation have focused predominantly on molecular evolution within coding regions, whereas the role of intergenic mutations remains unclear. Here, we address this issue and investigate the extent to which intergenic mutations contribute to the evolutionary response of pathogens to host environments, and whether intergenic mutations have distinct roles in host adaptation. We characterize intergenic evolution in 44 lineages of a clinically important bacterial pathogen, Pseudomonas aeruginosa, as they adapt to their hosts. We identify 88 intergenic regions in which parallel evolution occurs. At the genetic level, we find that mutations in these regions under selection are located primarily within regulatory elements upstream of transcriptional start sites. At the functional level, we show that these mutations both create or destroy regulatory interactions in connection to transcriptional processes and are directly responsible for evolution of important pathogenic phenotypes including antibiotic sensitivity. Importantly, we find that intergenic mutations are more likely to be selected than coding region mutations and that intergenic mutations enable essential genes to become targets of evolution. In summary, our results highlight the evolutionary significance of intergenic mutations in creating host-adapted variants and that intergenic and coding regions have different qualitative and quantitative contributions to this process.SignificancePathogens adapt to their host during infection, but the contribution and function of non-coding intergenic sequences to adaptation is poorly understood. Here, genome-wide identification of adaptive mutations within intergenic regions demonstrates that these sequences constitute an important part of the genetic basis for host adaptation. We find that intergenic mutations are abundant relative to adaptive mutations within coding sequences, and can contribute directly to evolution of pathogen-relevant traits. Importantly, we find that intergenic mutations modify expression of essential genes and thus make contributions that are functionally distinct from coding mutations. These results improve our understanding of the evolutionary processes in vivo and can potentially assist in refining predictions of pathogen evolution, disease outcome and antibiotic resistance development.
Social interactions impact on the dopaminergic system and drive individuality
Authors: Torquet N. , Marti F. , Campart C. , Tolu S. , Nguyen C. , Oberto V. , Naudé J. , Didienne S. , Jezequel S. , Le Gouestre L. , Debray N. , Mourot A. , Mariani J. , Faure P. 
Published: December 2017

SummaryIndividuality is a ubiquitous and well-conserved feature among animal species. The behavioral patterns of individual animals affect their respective role in the ecosystem and their prospects for survival. Even though some of the factors shaping individuality have been identified, the mechanisms underlying individuation are poorly understood and are generally considered to be genetics-based. Here we devised a large environment where mice live continuously, and observed that individuality, measured by both social and individual traits, emerged and settled within the group. Midbrain dopamine neurons underwent neurophysiological adaptations that mirrored this phenotypic divergence in individual behaviors. Strikingly, modifying the social environment resulted in a fast re-adaptation of both the animal’s personality and its dopaminergic signature. These results indicate that individuality can rapidly evolve upon social challenges, and does not just depend on the genetic or epigenetic initial status of the animal.
Foxd1 is required for terminal differentiation of anterior hypothalamic neuronal subtypes
Authors: Newman Elizabeth A. , Wan Jun , Wang Jie , Qian Jiang , Blackshaw Seth 
Published: December 2017

AbstractAlthough the hypothalamus functions as a master homeostat for many behaviors, little is known about the transcriptional networks that control its development. To investigate this question, we analyzed mice deficient for the Forkhead domain transcription factor Foxd1. Foxd1 is selectively expressed in neuroepithelial cells of the prethalamus and hypothalamus prior to the onset of neurogenesis, and is later restricted to neural progenitors of the prethalamus and anterior hypothalamus. During early stages of neurogenesis, we observed that Foxd1-deficient mice showed reduced expression of Six3 and Vax1 in anterior hypothalamus, but overall patterning of the prethalamus and hypothalamus is unaffected. After neurogenesis is complete, however, a progressive reduction and eventual loss of expression of molecular markers of the suprachiasmatic, paraventricular and periventricular hypothalamic is observed. These findings demonstrate that Foxd1 acts in hypothalamic progenitors to allow sustained expression of a subset of genes selectively expressed in mature neurons of the anterior hypothalamus.HighlightsFoxd1 is broadly expressed in neuroepithelial cells of the hypothalamus and prethalamus.Foxd1 mutants show severe defects in anterior hypothalamic development, although prethalamic development is only modestly affected.Loss of Foxd1 results does not affect initial patterning of the hypothalamus, but leads to a progressive loss of expression of markers specific to neurons of the suprachiasmatic, paraventricular and periventricular nuclei.Foxd1 regulates expression of multiple transcription factors expressed in developing anterior hypothalamus.
The primary transcriptome, small RNAs, and regulation of antimicrobial resistance inAcinetobacter baumannii
Authors: Kröger Carsten , MacKenzie Keith D. , Al-Shabib Ebtihal Y. , Kirzinger Morgan W. B. , Suchan Danae M. , Chao Tzu-Chiao , Akulova Valentyna , Miranda-CasoLuengo Alesksandra A. , Monzon Vivian A. , Conway Tyrrell , Sivasankaran Sathesh K. , Hinton Jay C. D. , Hokamp Karsten , Cameron Andrew D. S. 
Published: December 2017

ABSTRACTWe present the first high-resolution determination of transcriptome architecture in the priority pathogenAcinetobacter baumannii. Pooled RNA from 16 laboratory conditions was used for differential RNA-seq (dRNA-seq) to identify 3731 transcriptional start sites (TSS) and 110 small RNAs, including the first identification inA. baumanniiof sRNAs encoded at the 3’ end of coding genes. Most sRNAs were conserved among sequencedA. baumanniigenomes, but were only weakly conserved or absent in otherAcinetobacterspecies. Single nucleotide mapping of TSS enabled prediction of −10 and −35 RNA polymerase binding sites and revealed an unprecedented base preference at position +2 that hints at an unrecognized transcriptional regulatory mechanism. To apply functional genomics to the problem of antimicrobial resistance, we dissected the transcriptional regulation of the drug efflux pump responsible for chloramphenicol resistance,craA. The twocraApromoters were both down-regulated >1000-fold when cells were shifted to nutrient limited medium. This conditional down-regulation ofcraAexpression renders cells sensitive to chloramphenicol, a highly effective antibiotic for the treatment of multidrug resistant infections. An online interface that facilitates open data access and visualization is provided as “AcinetoCom” (http://bioinf.gen.tcd.ie/acinetocom/).
ProteomeGenerator: A framework for comprehensive proteomics based on de novo transcriptome assembly and high-accuracy peptide mass spectral matching
Authors: Cifani Paolo , Dhabaria Avantika , Yoshimi Akihide , Abdel-Wahab Omar , Poirier John T. , Kentsis Alex 
Published: December 2017

SUMMARYModern mass spectrometry now permits genome-scale and quantitative measurements of biological proteomes. However, analyses of specific specimens are currently hindered by the incomplete representation of biological variability of protein sequences in canonical reference proteomes, and the technical demands for their construction. Here, we report ProteomeGenerator, a framework for de novo and reference-assisted proteogenomic database construction and analysis based on sample-specific transcriptome sequencing and high-resolution and high-accuracy mass spectrometry proteomics. This enables assembly of proteomes encoded by actively transcribed genes, including sample-specific protein isoforms resulting from non-canonical mRNA transcription, splicing, or editing. To improve the accuracy of protein isoform identification in non-canonical proteomes, ProteomeGenerator relies on statistical target-decoy database matching augmented with spectral-match calibrated sample-specific controls. We applied this method for the proteogenomic discovery of splicing factor SRSF2-mutant leukemia cells, demonstrating high-confidence identification of non-canonical protein isoforms arising from alternative transcriptional start sites, intron retention, and cryptic exon splicing, as well as improved accuracy of genome-scale proteome discovery. Additionally, we report proteogenomic performance metrics for the current state-of-the-art implementations of SEQUEST HT, Proteome Discoverer, MaxQuant, Byonic, and PEAKS mass spectral analysis algorithms. Finally, ProteomeGenerator is implemented as a Snakemake workflow, enabling open, scalable, and facile discovery of sample-specific, non-canonical and neomorphic biological proteomes (https://github.com/jtpoirier/proteomegenerator).
Synthetic hormone-responsive transcription factors can monitor and reprogram plant development
Authors: Khakhar Arjun , Leydon Alexander R. , Lemmex Andrew C. , Klavins Eric , Nemhauser Jennifer L. 
Published: December 2017

AbstractDevelopmental programs continuously sculpt plant morphology to meet environmental challenges, and these same programs have been manipulated to increase agricultural productivity1,2. Small molecule phytohormones act as signals within these programs creating chemical circuitry3 that, in many cases, has been represented in mathematical models4,5. To date, model validation and forward engineering of plant morphology has been largely restricted to adding or subtracting genes, as more nuanced tools to modulate key control parameters identified by such models in vivo are severely limited6,7. Here, we use Arabidopsis thaliana to validate a novel set of synthetic and modular hormone activated Cas9-based repressors (HACRs) that respond to three phytohormones: auxin, gibberellins and jasmonates. We demonstrate that HACRs can regulate genes in response to both exogenous hormone treatments, as well as in response to local differences in endogenous hormone levels associated with developmental events. We further show that HACRs can be used to reprogram the agriculturally relevant traits of shoot branching and phyllotaxy by tuning canalization strength, a critical control parameter predicted by mathematical models. By deploying a HACR to re-parameterize the threshold for induction of the auxin transporter PIN-FORMED1 (PIN1), we observed a decrease in shoot branching and phyllotactic noise as predicted by existing models4,5. The approach described here provides a framework for improved mapping of developmental circuitry, as well as a means to better leverage model predictions to engineer development.