bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Intensity Variable Stepping Training in Patients With Motor Incomplete Spinal Cord Injury: A Case Series
Authors: Holleran Carey L. , Hennessey Patrick W. , Leddy Abigail L. , Mahtani Gordhan B. , Brazg Gabrielle , Schmit Brian D. , Hornby T. George 
Published: March 2018

Background and Purpose:
Previous data suggest that large amounts of high-intensity stepping training in variable contexts (tasks and environments) may improve locomotor function, aerobic capacity, and treadmill gait kinematics in individuals poststroke. Whether similar training strategies are tolerated and efficacious for patients with other acute-onset neurological diagnoses, such as motor incomplete spinal cord injury (iSCI), is unknown. Individuals with iSCI potentially have greater bilateral impairments. This case series evaluated the feasibility and preliminary short- and long-term efficacy of high-intensity variable stepping practice in ambulatory participants for more than 1 year post-iSCI.

Case Series Description:
Four participants with iSCI (neurological levels C5-T3) completed up to 40 one-hour sessions over 3 to 4 months. Stepping training in variable contexts was performed at up to 85% maximum predicted heart rate, with feasibility measures of patient tolerance, total steps/session, and intensity of training. Clinical measures of locomotor function, balance, peak metabolic capacity, and gait kinematics during graded treadmill assessments were performed at baseline and posttraining, with more than 1-year follow-up.

Outcomes:
Participants completed 24 to 40 sessions over 8 to 15 weeks, averaging 2222 ± 653 steps per session, with primary adverse events of fatigue and muscle soreness. Modest improvements in locomotor capacity where observed at posttraining, with variable changes in lower extremity kinematics during treadmill walking.

Discussion:
High-intensity, variable stepping training was feasible and tolerated by participants with iSCI although only modest gains in gait function or quality were observed. The utility of this intervention in patients with more profound impairments may be limited.

Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A200)
Retrospective Application of New Pediatric Ventilator-Associated Pneumonia Criteria Identifies a High-Risk Population*
Authors: Gionfriddo Ashley , Nonoyama Mika L. , Laussen Peter C. , Cox Peter N. , Clarke Megan , Floh Alejandro A. 
Published: March 2018

Objectives:
To promote standardization, the Centers for Disease Control and Prevention introduced a new ventilator-associated pneumonia classification, which was modified for pediatrics (pediatric ventilator-associated pneumonia according to proposed criteria [PVAP]). We evaluated the frequency of PVAP in a cohort of children diagnosed with ventilator-associated pneumonia according to traditional criteria and compared their strength of association with clinically relevant outcomes.

Design:
Retrospective cohort study.

Setting:
Tertiary care pediatric hospital.

Patients:
Critically ill children (0–18 yr) diagnosed with ventilator-associated pneumonia between January 2006 and December 2015 were identified from an infection control database. Patients were excluded if on high frequency ventilation, extracorporeal membrane oxygenation, or reintubated 24 hours following extubation.

Interventions:
None.

Measurements and Main Results:
Patients were assessed for PVAP diagnosis. Primary outcome was the proportion of subjects diagnosed with PVAP. Secondary outcomes included association with intervals of care. Two hundred seventy-seven children who had been diagnosed with ventilator-associated pneumonia were eligible for review; 46 were excluded for being ventilated under 48 hours (n = 16), on high frequency ventilation (n = 12), on extracorporeal membrane oxygenation (n = 8), ineligible bacteria isolated from culture (n = 8), and other causes (n = 4). ICU admission diagnoses included congenital heart disease (47%), neurological (16%), trauma (7%), respiratory (7%), posttransplant (4%), neuromuscular (3%), and cardiomyopathy (3%). Only 16% of subjects (n = 45) met the new PVAP definition, with 18% (n = 49) having any ventilator-associated condition. Failure to fulfill new definitions was based on inadequate increase in mean airway pressure in 90% or Fio
2 in 92%. PVAP was associated with prolonged ventilation (median [interquartile range], 29 d [13–51 d] vs 16 d [8–34.5 d]; p = 0.002), ICU (median [interquartile range], 40 d [20–100 d] vs 25 d [14–61 d]; p = 0.004) and hospital length of stay (median [interquartile range], 81 d [40–182 d] vs 54 d [31–108 d]; p = 0.04), and death (33% vs 16%; p = 0.008).

Conclusions:
Few children with ventilator-associated pneumonia diagnosis met the proposed PVAP criteria. PVAP was associated with increased morbidity and mortality. This work suggests that additional study is required before new definitions for ventilator-associated pneumonia are introduced for children.
Morphine Pharmacokinetics in Children With Down Syndrome Following Cardiac Surgery
Authors: Goot Benjamin H. , Kaufman Jon , Pan Zhaoxing , Bourne David W. A. , Hickey Francis , Twite Mark , Galinkin Jeffrey , Christians Uwe , Zuk Jeannie , da Cruz Eduardo M. 
Published: March 2018

Objectives:
To assess if morphine pharmacokinetics are different in children with Down syndrome when compared with children without Down syndrome.

Design:
Prospective single-center study including subjects with Down syndrome undergoing cardiac surgery (neonate to 18 yr old) matched by age and cardiac lesion with non-Down syndrome controls. Subjects were placed on a postoperative morphine infusion that was adjusted as clinically necessary, and blood was sampled to measure morphine and its metabolites concentrations. Morphine bolus dosing was used as needed, and total dose was tracked. Infusions were continued for 24 hours or until patients were extubated, whichever came first. Postinfusion, blood samples were continued for 24 hours for further evaluation of kinetics. If patients continued to require opioid, a nonmorphine alternative was used. Morphine concentrations were determined using a unique validated liquid chromatography tandem-mass spectrometry assay using dried blood spotting as opposed to large whole blood samples. Morphine concentration versus time data was modeled using population pharmacokinetics.

Setting:
A 16-bed cardiac ICU at an university-affiliated hospital.

Patients:
Forty-two patients (20 Down syndrome, 22 controls) were enrolled.

Interventions:
None.

Measurements and Main Results:
The pharmacokinetics of morphine in pediatric patients with and without Down syndrome following cardiac surgery were analyzed. No significant difference was found in the patient characteristics or variables assessed including morphine total dose or time on infusion. Time mechanically ventilated was longer in children with Down syndrome, and regarding morphine pharmacokinetics, the covariates analyzed were age, weight, presence of Down syndrome, and gender. Only age was found to be significant.

Conclusions:
This study did not detect a significant difference in morphine pharmacokinetics between Down syndrome and non-Down syndrome children with congenital heart disease.
Facilitating Weight Shifting During Treadmill Training Improves Walking Function in Humans With Spinal Cord Injury
Authors: Wu Ming , Kim Janis , Wei Feng 
Published: March 2018

Objective
The aim of the study was to determine whether the integration of dynamic weight shifting into treadmill training would improve the efficacy of treadmill training in humans with spinal cord injury.

Design
Sixteen humans with spinal cord injury were randomly assigned to receive robotic or treadmill-only training and underwent 6 wks of training. A force was applied to the pelvis for facilitating weight shifting and to the legs for assisting with leg swing for participants in the robotic group. No assistance force was applied for participants in the treadmill-only group. Outcome measures consisted of overground walking speed, 6-min walking distance, and other clinical measures and were assessed before, after 6 wks of training, and 8 wks after the end of training.

Results
A greater improvement in 6-min walking distance was observed after robotic training than that after treadmill-only training (P = 0.03), but there was not a significant difference between the two groups in improvements in walking speed. However, a greater improvement was observed for the participants who underwent robotic training than those who underwent treadmill-only training (i.e., 15% vs. 2%).

Conclusions
Applying a pelvis assistance force for facilitating weight shifting during treadmill training may improve locomotor function in humans with spinal cord injury.
Chronic postsurgical pain and cancer: the catch of surviving the unsurvivable
Authors: Humble Stephen R. , Varela Nicolas , Jayaweera Asantha , Bhaskar Arun 
Published: March 2018

Purpose of review
Chronic postsurgical pain (CPSP) is an important and well recognized cause of much long-term suffering, which in some cases may be preventable and affects many people living with cancer. Unfortunately, general consensus is lacking as to how best reduce the risk of developing CPSP.

Recent findings
Cancer is now not always a short-lived, fatal disease and is now moving towards a chronic illness. Poorly managed perioperative pain is the greatest risk factor for CPSP. Recent trials have examined preventive strategies for CPSP associated with breast surgery and thoracotomy, two operations used in cancer treatment. Standard antinociceptive drugs, 5% lidocaine patches and ketamine do not prevent CPSP. The evidence for gabapentinoids is conflicting. Intravenous lidocaine and, separately, regional anaesthesia appear beneficial.

Summary
Well-managed pain, irrespective of technique, reduces the risk of CPSP. The literature is inconclusive regarding an ‘optimal approach.’ Regional anaesthesia, intravenous lidocaine and the aggressive management of perioperative pain using multimodal analgesia including antineuropathic pain agents such as gabapentinoids and certain antidepressants are recommended. Clinicians should not rely on general anaesthesia, opioids, NSAIDs and ketamine to prevent CPSP. A blanket approach using gabapentinoids for all patients undergoing major surgery is not indicated. Instead, the presence of perioperative neuropathic pain should be checked for regularly.
Clinical and Electrographic Correlates of Bilateral Independent Periodic Discharges
Authors: Freund Brin , Gugger James J. , Reynolds Alexandra , Tatum William O. , Claassen Jan , Kaplan Peter W. 
Published: March 2018

Purpose:
Periodic discharges (PDs) are EEG patterns denoting brain dysfunction and ictal tendency. Their exact meaning regarding etiology and outcomes is not well known. In particular, bilateral independent PDs (BIPDs) are poorly described.

Methods:
We performed a retrospective, multicenter study evaluating neuroimaging, epileptic, clinical, and EEG correlates of BIPDs.

Results:
Twenty-five patients studied with a mean Glasgow Coma Scale 6.5 and modified Rankin scale 3.9 who underwent EEG monitoring, mean duration 287 hours (range 0.75–3,216). Most common causes of BIPDs were cardiac arrest, Central Nervous System infections, and acute/chronic ischemic/hemorrhagic stroke. Most had subcortical and cortical injuries on neuroimaging. Most of the PDs ranged from 0.5 to 2 Hz in frequency, were of multiple phase types, and localized to the frontal head regions. Eighteen of 25 patients had clinical or electrographic seizures. There was a trend toward seizures in those with BIPDs with a history of epilepsy (P = 0.08) and acute metabolic dysfunction (P = 0.08), particularly with coincident acute structural lesions (P = 0.05). Seizures were predicted by bilaterally symmetric frequencies (P = 0.02) and trended toward higher likelihood with PD frequency <2 Hz (P = 0.08). Two of 25 patients survived past discharge with modified Rankin scale <3. Cardiac arrest was associated with withdrawal of life-sustaining therapy (P < 0.001).

Conclusions:
BIPDs arise from acute and chronic neurologic injuries, often associated with metabolic dysfunction. Outcomes are poor in this population. Seizures are common, particularly in patients with PDs that are of a lower frequency or are symmetric in frequency. Further study is warranted to evaluate the association between BIPDs and seizures, as well as functional and longer term outcomes.
Uncovering novel pathways for enhancing hyaluronan synthesis in recombinantLactococcus lactis: Genome-scale metabolic modelling and experimental validation
Authors: Badri Abinaya , Raman Karthik , Jayaraman Guhan 
Published: March 2018

AbstractHyaluronan (HA) is a naturally occurring high-value polysaccharide with important medical applications. HA is commercially produced from pathogenic microbial sources. HA-producing recombinant cell factories that are being developed with GRAS organisms are comparatively less productive than the best natural producers. The metabolism of these recombinant systems needs to be more strategically engineered to achieve significant improvement. Here, we use a genome-scale metabolic network model to account for the entire metabolic network of the cell to predict strategies for improving HA production. We here analyze the metabolic network ofLactococcus lactisadapted to produce HA, and identify non-conventional overexpression and knock-out strategies to enhance HA flux.To experimentally validate our predictions, we identify an alternate route for enhancement of HA synthesis, originating from the nucleoside inosine, which has the capacity to function in parallel with the traditionally known route from glucose. Adopting this strategy resulted in a 2.8-fold increase in HA yield. The strategies identified and the experimental results show that the cell is capable of involving a larger subset of metabolic pathways in HA production. Apart from being the first report of the use of a nucleoside to improve HA production, our study shows how experimental results enable model refinement. Overall, we point out that well-constructed genome-scale metabolic models could be very potent tools to derive efficient strategies to improve biosynthesis of important high-value products.
Pollen Patterns Form from Modulated Phases
Authors: Radja Asja , Horsley Eric M. , Lavrentovich Maxim O. , Sweeney Alison M. 
Published: March 2018

AbstractPollen grains are known for their impressive variety of species-specific, microscale surface patterning. Despite having similar biological developmental steps, pollen grain surface features are remarkably geometrically varied. Previous work suggests that a physical process may drive this pattern formation and that the observed diversity of patterns can be explained by viewing pollen pattern development as a phase transition to a spatially modulated phase. Several studies have shown that the polysaccharide material of plant cell walls undergoes phase separation in the absence of cross-linking stabilizers of the mixed phase. Here we show experimental evidence that phase separation of the extracellular polysaccharide material (primexine) during pollen cell development leads to a spatially modulated phase. The spatial pattern of this phase-separated primexine is also mechanically coupled to the undulation of the pollen cell membrane. The resulting patterned pools of denser primexine form the negative template of the ultimate sites of sporopollenin deposition, leading to the final micropattern observed in the mature pollen. We then present a general physical model of pattern formation via modulated phases. Using analytical and numerical techniques, we find that most of the pollen micropatterns observed in biological evolution could result from a physical process of modulated phases. However, an analysis of the relative rates of transitions from states that are equilibrated to or from states that are not equilibrated suggests that while equilibrium states of this process have occurred throughout evolutionary history, there has been no particular evolutionary selection for symmetric, equilibrated states.
The complex architecture of plant transgene insertions
Authors: Jupe Florian , Michael Todd P. , Rivkin Angeline C. , Zander Mark , Timothy Motley S. , Sandoval Justin P. , Keith Slotkin R. , Chen Huaming , Castagnon Rosa , Nery Joseph R. , Ecker Joseph R. 
Published: March 2018

AbstractOver the last 35 years the soil bacterium Agrobacterium tumefaciens has been the workhorse tool for plant genome engineering. Replacement of native tumor-inducing (Ti) plasmid elements with customizable cassettes enabled insertion of a sequence of interest called Transfer DNA (T-DNA) into any plant genome. Although these T-DNA transfer mechanisms are well understood, detailed understanding of structure and epigenomic status of insertion events was limited by current technologies. To fill this gap, we analyzed transgenic Arabidopsis thaliana lines from three widely used collections (SALK, SAIL and WISC) with two single molecule technologies, optical genome mapping and nanopore sequencing. Optical maps for four randomly selected T-DNA lines revealed between one and seven insertions/rearrangements, and for the first time the actual length of individual transgene insertions from 27 to 236 kilobases. De novo nanopore sequencing-based genome assemblies for two segregating lines resolved T-DNA structures up to 36 kb into the insertions and revealed large-scale T-DNA associated translocations and exchange of chromosome arm ends. The multiple internally rearranged nature of T-DNA arrays made full assembly impossible, even with long nanopore reads. For the current TAIR10 reference genome, nanopore contigs corrected 83% of non-centromeric misassemblies. This unprecedented nucleotide-level definition of T-DNA insertions enabled the mapping of epigenome data. We identify variable small RNA transgene targeting and DNA methylation. SALK_059379 T-DNA insertions were enriched for 24nt siRNAs and contained dense cytosine DNA methylation. Transgene silencing via the RNA-directed DNA methylation pathway was confirmed by in planta assays. In contrast, SAIL_232 T-DNA insertions are predominantly targeted by 21/22nt siRNAs, with DNA methylation and silencing limited to a reporter, but not the resistance gene. With the emergence of genome editing technologies that rely on Agrobacterium for gene delivery, this study provides new insights into the structural impact of engineering plant genomes and demonstrates the utility of state-of-the-art long-range sequencing technologies to rapidly identify unanticipated genomic changes.
Continuous-trait probabilistic model for comparing multi-species functional genomic data
Authors: Yang Yang , Gu Quanquan , Zhang Yang , Sasaki Takayo , Crivello Julianna , O’Neill Rachel J. , Gilbert David M. , Ma Jian 
Published: March 2018

SummaryA large amount of multi-species functional genomic data from high-throughput assays are becoming available to help understand the molecular mechanisms for phenotypic diversity across species. However, continuous-trait probabilistic models, which are key to such comparative analysis, remain underexplored. Here we develop a new model, called phylogenetic hidden Markov Gaussian processes (Phylo-HMGP), to simultaneously infer heterogeneous evolutionary states of functional genomic features in a genome-wide manner. Both simulation studies and real data application demonstrate the effectiveness of Phylo-HMGP. Importantly, we applied Phylo-HMGP to analyze a new cross-species DNA replication timing (RT) dataset from the same cell type in five primate species (human, chimpanzee, orangutan, gibbon, and green monkey). We demonstrate that our Phylo-HMGP model enables discovery of genomic regions with distinct evolutionary patterns of RT. Our method provides a generic framework for comparative analysis of multi-species continuous functional genomic signals to help reveal regions with conserved or lineage-specific regulatory roles.
Meta-analysis challenges a textbook example of status signalling: evidence for publication bias
Authors: Sánchez-Tójar Alfredo , Nakagawa Shinichi , Sánchez-Fortún Moisès , Martin Dominic A. , Ramani Sukanya , Girndt Antje , Bókony Veronika , Kempenaers Bart , Liker András , Westneat David F. , Burke Terry , Schroeder Julia 
Published: March 2018

AbstractThe status signalling hypothesis aims to explain conspecific variation in ornamentation by suggesting that some ornaments signal dominance status. Here, we use multilevel meta-analytic models to challenge the textbook example of this hypothesis, the black bib of house sparrows (Passer domesticus). We conducted a systematic review, and obtained raw data from published and unpublished studies to test whether dominance rank is positively associated with bib size across studies. Contrary to previous studies, our meta-analysis did not support this prediction. Furthermore, we found several biases in the literature that further question the support available for the status signalling hypothesis. First, the overall effect size of unpublished studies was zero, compared to the medium effect size detected in published studies. Second, the effect sizes of published studies decreased over time, and recently published effects were, on average, no longer distinguishable from zero. We discuss several explanations including pleiotropic, population- and context-dependent effects. Our findings call for reconsidering this established textbook example in evolutionary and behavioural ecology, raise important concerns about the validity of the current scientific publishing culture, and should stimulate renewed interest in understanding within-species variation in ornamental traits.
In vivocloning of β 1-4 endoglucanase gene ofSerratia liquefaciensusing Muduction and itsin silicoanalysis
Authors: Sankar S. Gowri , Mary J. Asnet , Vennison S. John , Anand A. Alwin Prem 
Published: March 2018

AbstractCellulose is the major structural component in the plant cell wall. The bio-degradation of cellulose molecules is facilitated by cellulase. In the present study,in vivocloning of cellulase (β-1, 4 endoglucanase) gene from a cellulolytic bacteriumSerratia liquefaciensintoE. coliDH5α has been performed using mini-Mu phage transduction. The enzyme activity of cloned endoglucanase was 81.2U/mg at optimum temperature (40°C) and 80.2U/mg at optimum pH7, while the wildtype has 65.9U/mg and 64.9U/mg respectively. The conserved domain analysis shows thatS. liquefaciensendoglucanase belongs to GH8 family. The nucleotide sequence analysis of wildtype and cloned endoglucanase shows that mutations were found at residues 51(Lys - Asn), 203(Trp-Cys), 246(Thr-Iso), 260(Gly-Ala) and 288(Phe-Leu). The structural analysis shows the active site of wildtype endoglucanase is a narrow groove which lies parallel to the central axis, whereas cloned endoglucanase is broad and tilted to ∼70° from the central axis. The increased enzyme activity in the cloned endoglucanase is due to the structural modification conferred by changes in amino acid resulting in widening of the cleft in the active site.