bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global leaf nitrogen and phosphorus stoichiometry and their scaling exponent
Authors: Tian Di , Yan Zhengbing , Niklas Karl J , Han Wenxuan , Kattge Jens , Reich Peter B , Luo Yongkai , Chen Yahan , Tang Zhiyao , Hu Huifeng , Wright Ian J , Schmid Bernhard , Fang Jingyun 
Published: December 2017

Abstract
Leaf nitrogen (N) and phosphorus (P) concentrations constrain photosynthetic and metabolic processes, growth and the productivity of plants. Their stoichiometry and scaling relationships regulate the allocation of N and P from subcellular to organism, and even ecosystem levels, and are crucial to the modelling of plant growth and nutrient cycles in terrestrial ecosystems. Prior work has revealed a general biogeographic pattern of leaf N and P stoichiometric relationships and shown that leaf N scales roughly as two-thirds the power of P. However, determining whether and how leaf N and P stoichiometries, especially their scaling exponents, change with functional groups and environmental conditions requires further verification. In this study, we compiled a global data set and documented the global leaf N and P concentrations and the N:P ratios by functional group, climate zone and continent. The global overall mean leaf N and P concentrations were 18.9 mg g−1 and 1.2 mg g−1, respectively, with significantly higher concentrations in herbaceous than woody plants (21.72 mg g−1 vs. 18.22 mg g−1 for N; and 1.64 mg g−1 vs. 1.10 mg g−1 for P). Both leaf N and P showed higher concentrations at high latitudes than low latitudes. Among six continents, Europe had the highest N and P concentrations (20.79 and 1.54 mg g−1) and Oceania had the smallest values (10.01 and 0.46 mg g−1). These numerical values may be used as a basis for the comparison of other individual studies. Further, we found that the scaling exponent varied significantly across different functional groups, latitudinal zones, ecoregions and sites. The exponents of herbaceous and woody plants were 0.659 and 0.705, respectively, with significant latitudinal patterns decreasing from tropical to temperate to boreal zones. At sites with a sample size ≥10, the values fluctuated from 0.366 to 1.928, with an average of 0.841. Several factors including the intrinsic attributes of different life forms, P-related growth rates and relative nutrient availability of soils likely account for the inconstant exponents of leaf N vs. P scaling relationships.
Pharmacodynamics and Pharmacokinetics of Lidocaine in a Rodent Model of Diabetic Neuropathy
Authors: ten Hoope Werner , Hollmann Markus W. , de Bruin Kora , Verberne Hein J. , Verkerk Arie O. , Tan Hanno L. , Verhamme Camiel , Horn Janneke , Rigaud Marcel , Picardi Susanne , Lirk Philipp 
Published: December 2017

Abstract

Background
Clinical and experimental data show that peripheral nerve blocks last longer in the presence of diabetic neuropathy. This may occur because diabetic nerve fibers are more sensitive to local anesthetics or because the local anesthetic concentration decreases more slowly in the diabetic nerve. The aim of this study was to investigate both hypotheses in a rodent model of neuropathy secondary to type 2 diabetes.

Methods
We performed a series of sciatic nerve block experiments in 25 Zucker Diabetic Fatty rats aged 20 weeks with a neuropathy component confirmed by neurophysiology and control rats. We determined in vivo the minimum local anesthetic dose of lidocaine for sciatic nerve block. To investigate the pharmacokinetic hypothesis, we determined concentrations of radiolabeled (14C) lidocaine up to 90 min after administration. Last, dorsal root ganglia were excised for patch clamp measurements of sodium channel activity.

Results
First, in vivo minimum local anesthetic dose of lidocaine for sciatic nerve motor block was significantly lower in diabetic (0.9%) as compared to control rats (1.4%). Second, at 60 min after nerve block, intraneural lidocaine was higher in the diabetic animals. Third, single cell measurements showed a lower inhibitory concentration of lidocaine for blocking sodium currents in neuropathic as compared to control neurons.

Conclusions
We demonstrate increased sensitivity of the diabetic neuropathic nerve toward local anesthetics, and prolonged residence time of local anesthetics in the diabetic neuropathic nerve. In this rodent model of neuropathy, both pharmacodynamic and pharmacokinetic mechanisms contribute to prolonged nerve block duration.
Effect of Boarding on Mortality in ICUs
Authors: Stretch Robert , Della Penna Nicolás , Celi Leo Anthony , Landon Bruce E. 
Published: December 2017

Objectives:
Hospitals use a variety of strategies to maximize the availability of limited ICU beds. Boarding, which involves assigning patients to an open bed in a different subspecialty ICU, is one such practice employed when ICU occupancy levels are high, and beds in a particular unit are unavailable. Boarding disrupts the normal geographic colocation of patients and care teams, exposing patients to nursing staff with different training and expertise to those caring for nonboarders. We analyzed whether medical ICU patients boarding in alternative specialty ICUs are at increased risk of mortality.

Design:
Retrospective cohort study using an instrumental variable analysis to control for unmeasured confounding. A semiparametric bivariate probit estimation strategy was employed for the instrumental model. Propensity score matching and standard logistic regression (generalized linear modeling) were used as robustness checks.

Setting:
The medical ICU of a tertiary care nonprofit hospital in the United States between 2002 and 2012.

Patients:
All medical ICU admissions during the specified time period.

Interventions:
None.

Measurements and Main Results:
The study population consisted of 8,429 patients of whom 1,871 were boarders. The instrumental variable model demonstrated a relative risk of 1.18 (95% CI, 1.01–1.38) for ICU stay mortality for boarders. The relative risk of in-hospital mortality among boarders was 1.22 (95% CI, 1.00–1.49). GLM and propensity score matching without use of the instrument yielded similar estimates. Instrumental variable estimates are for marginal patients, whereas generalized linear modeling and propensity score matching yield population average effects.

Conclusions:
Mortality increased with boarding of critically ill patients. Further research is needed to identify safer practices for managing patients during periods of high ICU occupancy.
Comparison of Hyaluronic Acid Gel With (HARDL) and Without Lidocaine (HAJUP) in the Treatment of Moderate-To-Severe Nasolabial Folds: A Randomized, Evaluator-Blinded Study
Authors: Baumann Leslie , Weiss Robert A. , Grekin Steven , Narins Rhoda , Gold Michael , Donofrio Lisa , Nogueira Alessandra , Shawcross Heather , Brown Sarah , Mashburn Jay H. 
Published: December 2017

BACKGROUND
Injectable fillers, such as those containing hyaluronic acid (HA), are increasingly used to smooth age-related facial creases and wrinkles.

OBJECTIVE
To compare efficacy and safety of a HA gel with lidocaine formulated by XpresHAn Technology (HARDL) with a HA gel without lidocaine produced by Hylacross technology (HAJUP) in the treatment of moderate-to-severe nasolabial folds.

MATERIALS AND METHODS
Subjects (n = 162) received initial and touch-up injections with HARDL and HAJUP on either side of the face. Investigator- and subject-assessed wrinkle severity was measured up to 48 weeks after final injection.

RESULTS
Mean (SD) Wrinkle Severity Rating Scale was improved by 1.1 (0.75) and 1.1 (0.68) with HARDL and HAJUP, respectively, at 24 weeks; improvements were sustained up to Week 48 with both treatments. Noninferiority of HARDL was demonstrated (mean difference −0.09 [95% confidence interval: −0.18 to −0.01], p = .032) at 24 weeks. Adverse events were reported in 43% subjects, 12% were treatment related, with a similar distribution for both treatments.

CONCLUSION
Effectiveness and safety profiles of HARDL and HAJUP were comparable.
Mesenchymal stem cell-derived extracellular vesicles attenuate pulmonary vascular permeability and lung injury induced by hemorrhagic shock and trauma
Authors: Potter Daniel R. , Miyazawa Byron Y. , Gibb Stuart L. , Deng Xutao , Togaratti Padma P. , Croze Roxanne H. , Srivastava Amit K. , Trivedi Alpa , Matthay Michael , Holcomb John B. , Schreiber Martin A. , Pati Shibani 
Published: December 2017

BACKGROUND
Mesenchymal stem cells (MSCs) have been shown to mitigate vascular permeability in hemorrhagic shock (HS) and trauma-induced brain and lung injury. Mechanistically, paracrine factors secreted from MSCs have been identified that can recapitulate many of the potent biologic effects of MSCs in animal models of disease. Interestingly, MSC-derived extracellular vesicles (EVs), contain many of these key soluble factors, and have therapeutic potential independent of the parent cells. In this study we sought to determine whether MSC-derived EVs (MSC EVs) could recapitulate the beneficial therapeutic effects of MSCs on lung vascular permeability induced by HS in mice.

METHODS
Mesenchymal stem cell EVs were isolated from human bone marrow-derived MSCs by ultracentrifugation. A mouse model of fixed pressure HS was used to study the effects of shock, shock + MSCs and shock + MSC EVs on lung vascular endothelial permeability. Mice were administered MSCs, MSC EVs, or saline IV. Lung tissue was harvested and assayed for permeability, RhoA/Rac1 activation, and for differential phosphoprotein expression. In vitro, human lung microvascular cells junctional integrity was evaluated by immunocytochemistry and endothelial cell impedance assays.

RESULTS
Hemorrhagic shock-induced lung vascular permeability was significantly decreased by both MSC and MSC EV infusion. Phosphoprotein profiling of lung tissue revealed differential activation of proteins and pathways related to cytoskeletal rearrangement and regulation of vascular permeability by MSCs and MSC EVs. Lung tissue from treatment groups demonstrated decreased activation of the cytoskeletal GTPase RhoA. In vitro, human lung microvascular cells, MSC CM but not MSC-EVs prevented thrombin-induced endothelial cell permeability as measured by electrical cell-substrate impedance sensing system and immunocytochemistry of VE-cadherin and actin.

CONCLUSION
Mesenchymal stem cells and MSC EVs modulate cytoskeletal signaling and attenuate lung vascular permeability after HS. Mesenchymal stem cell EVs may potentially be used as a novel “stem cell free” therapeutic to treat HS-induced lung injury.
Beta blockers in critically ill patients with traumatic brain injury: Results from a multicenter, prospective, observational American Association for the Surgery of Trauma study
Authors: Ley Eric J. , Leonard Samuel D. , Barmparas Galinos , Dhillon Navpreet K. , Inaba Kenji , Salim Ali , O'Bosky Karen R. , Tatum Danielle , Azmi Hooman , Ball Chad G. , Engels Paul T. , Dunn Julie A. , Carrick Matthew M. , Meizoso Jonathan P. , Lombardo Sarah , Cotton Bryan A. , Schroeppel Thomas J. , Rizoli Sandro , Chang David S. J. , de León Luis Alejandro , Rezende-Neto Joao , Jacome Tomas , Xiao Jimmy , Mallory Gina , Rao Krishnamurti , Widdel Lars , Godin Samuel , Coates Angela , Benedict Leo Andrew , Nirula Raminder , Kaul Sanjeev , Li Tong 
Published: December 2017

BACKGROUND
Beta blockers, a class of medications that inhibit endogenous catecholamines interaction with beta adrenergic receptors, are often administered to patients hospitalized after traumatic brain injury (TBI). We tested the hypothesis that beta blocker use after TBI is associated with lower mortality, and secondarily compared propranolol to other beta blockers.

METHODS
The American Association for the Surgery of Trauma Clinical Trial Group conducted a multi-institutional, prospective, observational trial in which adult TBI patients who required intensive care unit admission were compared based on beta blocker administration.

RESULTS
From January 2015 to January 2017, 2,252 patients were analyzed from 15 trauma centers in the United States and Canada with 49.7% receiving beta blockers. Most patients (56.3%) received the first beta blocker dose by hospital day 1. Those patients who received beta blockers were older (56.7 years vs. 48.6 years, p < 0.001) and had higher head Abbreviated Injury Scale scores (3.6 vs. 3.4, p < 0.001). Similarities were noted when comparing sex, admission hypotension, mean Injury Severity Score, and mean Glasgow Coma Scale. Unadjusted mortality was lower for patients receiving beta blockers (13.8% vs. 17.7%, p = 0.013). Multivariable regression determined that beta blockers were associated with lower mortality (adjusted odds ratio, 0.35; p < 0.001), and propranolol was superior to other beta blockers (adjusted odds ratio, 0.51, p = 0.010). A Cox-regression model using a time-dependent variable demonstrated a survival benefit for patients receiving beta blockers (adjusted hazard ratio, 0.42, p < 0.001) and propranolol was superior to other beta blockers (adjusted hazard ratio, 0.50, p = 0.003).

CONCLUSION
Administration of beta blockers after TBI was associated with improved survival, before and after adjusting for the more severe injuries observed in the treatment cohort. This study provides a robust evaluation of the effects of beta blockers on TBI outcomes that supports the initiation of a multi-institutional randomized control trial.

LEVEL OF EVIDENCE
Therapeutic/care management, level III.
Benchmarking clinical outcomes and the immunocatabolic phenotype of chronic critical illness after sepsis in surgical intensive care unit patients
Authors: Stortz Julie A. , Mira Juan C. , Raymond Steven L. , Loftus Tyler J. , Ozrazgat-Baslanti Tezcan , Wang Zhongkai , Ghita Gabriela L. , Leeuwenburgh Christiaan , Segal Mark S. , Bihorac Azra , Brumback Babette A. , Mohr Alicia M. , Efron Philip A. , Moldawer Lyle L. , Moore Frederick A. , Brakenridge Scott C. 
Published: December 2017

BACKGROUND
A growing number of patients survive sepsis but remain chronically critically ill. We sought to define clinical outcomes and incidence of chronic critical illness (CCI) after sepsis and to determine whether selected biomarkers of inflammation, immunosuppression, and catabolism differ between these patients and those that rapidly recover (RAP).

METHODS
This 3-year prospective observational cohort study (NCT02276417) evaluated 145 surgical intensive care unit patients with sepsis for the development of CCI (≥14 days of intensive care unit resource utilization with persistent organ dysfunction). Patient clinical demographics, outcomes, and serial serum/urine samples were collected for plasma protein and urinary metabolite analyses.

RESULTS
Of 145 sepsis patients enrolled, 19 (13%) died during their hospitalization and 71 (49%) developed CCI. The CCI patients were significantly older (mean, 63 ± 15 vs. 58 ± 13 years, p = 0.006) and more likely to be discharged to long-term acute care facilities (32% vs. 3%, p < 0.0001), whereas those with RAP were more often discharged to home or a rehabilitation facility. Six-month mortality was significantly higher in CCI as compared with RAP cohort (37% vs. 2%; p < 0.01). Multivariate logistic regression modeling revealed delayed onset sepsis (>48 hours after admission; odds ratio [OR], 10.93; 95% confidence interval [CI], 4.15–28.82]), interfacility transfer (OR, 3.58; 95% CI, 1.43–8.96), vasopressor-dependent septic shock (OR, 3.75; 95% CI, 1.47–9.54), and Sequential Organ Failure Assessment score of 5 or greater at 72 hours (OR, 5.03; 95% CI, 2.00–12.62) as independent risk factors for the development of CCI. The CCI patients also demonstrated greater elevations in inflammatory cytokines (IL-6, IL-8, IL-10), and biomarker profiles are consistent with persistent immunosuppression (absolute lymphocyte count and soluble programmed death ligand 1) and catabolism (plasma insulin-like growth factor binding protein 3 and urinary 3-methylhistidine excretion).

CONCLUSION
The development of CCI has become the predominant clinical trajectory in critically ill surgical patients with sepsis. These patients exhibit biomarker profiles consistent with an immunocatabolic phenotype of persistent inflammation, immunosuppression, and catabolism.

LEVEL OF EVIDENCE
Prognostic, level II.
Microparticles formed during storage of red blood cell units support thrombin generation
Authors: Bouchard Beth A. , Orfeo Thomas , Keith Hollis N. , Lavoie Elizabeth M. , Gissel Matthew , Fung Mark , Mann Kenneth G. 
Published: December 2017

BACKGROUNDIntact red blood cells (RBCs) appear to support thrombin generation in in vitro models of blood coagulation. During storage of RBC units, biochemical, structural, and physiological changes occur including alterations to RBC membranes and release of microparticles, which are collectively known as storage lesion. The clinical consequences of microparticle formation in RBC units are unclear. This study was performed to assess thrombin generation via the prothrombinase complex by washed RBCs and RBC-derived microparticles as a function of RBC unit age.METHODSWell-characterized kinetic and flow cytometric assays were used to quantify and characterize microparticles isolated from leukocyte-reduced RBC units during storage for 42 days under standard blood banking conditions.RESULTSStored RBCs exhibited known features of storage lesion including decreasing pH, cell lysis, and release of microparticles demonstrated by scanning electron microscopy. The rate of thrombin formation by RBC units linearly increased during storage, with the microparticle fraction accounting for approximately 70% of the prothrombinase activity after 35 days. High-resolution flow cytometric analyses of microparticle isolates identified phosphatidylserine-positive RBC-derived microparticles; however, their numbers over time did not correlate with thrombin formation in that fraction.CONCLUSIONRed blood cell-derived microparticles capable of supporting prothrombinase function accumulate during storage, suggesting an increased potential of transfused units as they age to interact in unplanned ways with ongoing hemostatic processes in injured individuals, especially given the standard blood bank practice of using the oldest units available.
A retrospective analysis of the respiratory adjusted shock index to determine the presence of occult shock in trauma patients
Authors: Caputo Nicholas , Reilly James , Kanter Marc , West Jason 
Published: December 2017

BACKGROUND
The shock index (SI), calculated as hear rate/systolic blood pressure, is a simple hemodynamic marker that may be used to assess for the presence of occult shock in trauma patients. The normal range for a healthy adult patient is 0.5 to 0.7. Recently, studies have demonstrated that tachypnea is the most important predictor of cardiac arrest in hospital wards and is an important indicator of derangements across multiple organ systems. As such, we have sought to determine whether the inclusion of the patient’s respiratory rate (RR) to the already existing SI (called the Respiratory Adjusted Shock Index [RASI]), calculated as hear rate/systolic blood pressure*(RR/10), will improve the overall diagnostic accuracy of detecting patients in early occult shock.

METHODS
A retrospective chart review over a 4-year period (2012–2016) at an urban, Level I trauma center was performed. All patients admitted to hospital for trauma were included in the study. Exclusion criteria were patients in traumatic arrest or in overt shock. Charts were reviewed for triage vital signs and point of care lactate drawn within 30 minutes of presentation. A lactate greater than 2 mmol/L was used to determine presence of hypoperfusion. The upper limit of normal for the RASI was calculated by multiplying the upper limit of the SI by 1.9 (RR of 19 divided by 10) and validated internally.

RESULTS
A total of 3,093 patients were included in this study. There was no difference in SI for patients discharged versus patients admitted, 0.6 (95% CI, 0.5–0.7) versus 0.7 (95% CI, 0.5–0.8) and a significant difference between the same groups of patients (discharged vs. admitted) for the RASI, 1.1 (95% CI, 1.04–1.18) versus 1.46 (95% CI, 1.35–1.55), respectively. Area under the curve for SI was 0.58 and for the RASI score was 0.94.

CONCLUSION
The RASI score improves diagnostic accuracy for detecting early occult shock in trauma patients when compared to the SI.

LEVEL OF EVIDENCE
Diagnostic, level II.
Transcriptomic changes following valproic acid treatment promote neurogenesis and minimize secondary brain injury
Authors: Nikolian Vahagn C. , Dennahy Isabel S. , Higgins Gerald A. , Williams Aaron M. , Weykamp Michael , Georgoff Patrick E. , Eidy Hassan , Ghandour Mohamed H. , Chang Panpan , Alam Hasan B. 
Published: December 2017

BACKGROUND
Early treatment with valproic acid (VPA) has demonstrated benefit in preclinical models of traumatic brain injury, including smaller brain lesion size, decreased edema, reduced neurologic disability, and faster recovery. Mechanisms underlying these favorable outcomes are not fully understood. We hypothesized that VPA treatment would upregulate genes involved in cell survival and proliferation and downregulate those associated with cell death and the inflammatory response.

METHODS
Ten female swine were subjected to a protocol of traumatic brain injury and hemorrhagic shock. They were assigned to two groups (n = 5): normal saline (NS; 3× volume of shed blood), or NS + VPA (150 mg/kg). Following 6 hours of observation, brain tissue was harvested to evaluate lesion size and edema. Brain tissue was processed for RNA sequencing. Gene set enrichment and pathway analysis was performed to determine the differential gene expression patterns following injury.

RESULTS
Animals treated with VPA were noted to have a 46% reduction in brain lesion size and a 57% reduction in ipsilateral brain edema. Valproic acid significantly upregulated genes involved in morphology of the nervous system, neuronal development and neuron quantity. The VPA treatment downregulated pathways related to apoptosis, glial cell proliferation, and neuroepithelial cell differentiation. Ingenuity Pathway Analysis identified VPA as the top upstream regulator of activated transcription, supporting it as a direct cause of these transcriptional changes. Master transcriptional regulator NEUROD1 was also significantly upregulated, suggesting that VPA may induce additional transcription factors.

CONCLUSION
Administration of VPA attenuated brain lesion size, reduced brain edema, and induced significant changes in the transcriptome of injured brain within 6 hours. Patterns of differential expression were consistent with the proposed neurogenic and prosurvival effects of VPA treatment.