bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Inflammation in Traumatic Brain Injury and Polytrauma Patients Using Network Analysis
Authors: Rowland Bradley , Savarraj Jude P.J. , Karri Jay , Zhang Xu , Cardenas Jessica , Choi H. Alex , Holcomb John B. , Wade Charles E. 
Published: April 2019

ABSTRACT

Introduction:
Traumatic brain injury (TBI) is associated with secondary injury to the central nervous system (CNS) via inflammatory mechanisms. The combination of polytrauma and TBI further exacerbates the inflammatory response to injury; however, combined injury phenomena have not been thoroughly studied. In this study, we examined the inflammatory differences between patients with TBI versus patients with polytrauma, but no TBI (polytrauma). We hypothesize that patients with TBI have a heightened early inflammatory response compared with polytrauma.

Methods:
We conducted a single-center retrospective study of a cohort of patients with polytrauma, who were enrolled in the PROPPR study. These patients had blood samples prospectively collected at eight time points in the first 3 days of admission. Using radiological data to determine TBI, our polytrauma cohort was dichotomized into TBI (n = 30) or polytrauma (n = 54). Inflammatory biomarkers were measured using ELISA. Data across time were compared for TBI versus polytrauma groups using Wilcoxon rank-sum test. Network analysis techniques were used to systematically characterize the inflammatory responses at admission.

Results:
Patients with TBI (51.6%) had a higher 30-day mortality compared with polytrauma (16.9%) (P <0.001). Expression levels of IL6, IL8, and CCL2 were elevated from the 2-h through 24-h time points, becoming significant at the 6-h time point (IL6, IL8, and CCL2; P <0.05) (Fig. 2). CSF3 showed a similar pattern, but did not attain significance. TBI and polytrauma networks underwent diverging trends from admission to the 6-h time point.

Conclusion:
Patients with TBI demonstrated upregulations in proinflammatory cytokines IL6, IL8, and CCL2. Utilizing informatics methods, we were able to identify temporal differences in network trends, as well as uncharacterized cytokines and chemokines in TBI. These data suggest TBI induces a distinct inflammatory response and pathologically heightened inflammatory response in the presence of polytrauma and may propagate worsened patient outcomes including mortality.
Comparison of male and female victims of intimate partner homicide and bidirectionality—an analysis of the national violent death reporting system
Authors: Velopulos Catherine G. , Carmichael Heather , Zakrison Tanya L. , Crandall Marie 
Published: April 2019

BACKGROUND
Intimate partner violence (IPV) is a public health crisis, affecting at least 1:4 women and 1:9 men. A recent multicenter trial on universal screening in trauma patients showed similar rates of positive screens between men and women. Few studies have explored the bidirectional violence in opposite-sex or same-sex relationships. Our goal was to estimate prevalence and risk factors for the most severe manifestation of IPV: intimate partner homicide.

METHODS
This is a 2003–2015 retrospective review of the National Violent Death Reporting System, a Centers for Disease Control and Prevention database of surveillance data. Deaths were coded IPV if the primary relationship between the suspect and victim fell into the categories of current partner or ex-partner. Bivariable and multivariable analysis examined differences between groups for factors and circumstances.

RESULTS
A total of 6,131 persons in opposite-sex relationships and 181 in same-sex relationships were murdered as a result of IPV. Women and Black men were disproportionately affected, and alcohol and preceding arguments were a factor in a higher proportion of male victims. Abuse preceded homicide in many women with almost half of male suspects attempting or committing suicide at the time of intimate partner homicide. Women were more likely than men to use a stabbing instrument, although firearms were still the most common means for each group. In 46.5% of homicides of women, the male suspect attempted suicide (p < 0.001). Bidirectionality was highest in male victims of female perpetrators and in same-sex pairings regardless of sex of the victim.

CONCLUSION
Homicide caused by IPV is a significant public health crisis for both men and women, with women and Black men at particular risk. Firearms are the most commonly used weapon for homicide in both sexes, and mental illness is not a common risk factor. A staggering proportion of these homicides involve suicide of the suspect, suggesting that each potential incident has two victims to target for prevention and intervention. Interventional programs to prevent such bidirectional mortality are urgently needed.

LEVEL OF EVIDENCE
Retrospective secondary data analysis, level III.
Noninvasive diagnostics for extremity compartment syndrome following traumatic injury: A state-of-the-art review
Authors: Walters Thomas J. , Kottke Melissa A. , Hargens Alan R. , Ryan Kathy L. 
Published: April 2019

ABSTRACT
Acute compartment syndrome (ACS) is a serious medical condition that can occur following traumatic injury to an extremity. If left undiagnosed, ACS can eventuate in amputation of the limb or even death. Because of this, fasciotomy to release the pressure within the muscle and restore tissue perfusion is often performed upon suspicion of ACS, as the sequelae to fasciotomy are less severe than those associated with not performing the fasciotomy. Currently, the “gold standard” of diagnosis is based on clinical assessment of such symptoms as pain out of proportion to the injury, obvious high pressure and swelling, pain on passive stretch of the muscles in the affected compartment, and deficits in sensory and/ormotor functions. Diagnosis is often confirmed using invasive measurements of intramuscular pressure (IMP); however, controversy exists as to how direct IMP measurement should be accomplished and threshold pressures for accurate diagnosis. Because of this and the attendant issues with invasive measurements, investigators have been searching over the last 25 years for a noninvasive means to quantitatively measure IMP or perfusion to the limb. The purpose of this review is to summarize the current state of the art of noninvasive devices that could potentially be used to diagnose ACS accurately and objectively. To do this, we divide the discussion into those medical devices that primarily measure mechanical surrogates of IMP (e.g., tissue hardness or myofascial displacement) and those that primarily measure indices of tissue perfusion (e.g., tissue oxygen saturation via near-infraredspectroscopy). While near-infrared spectroscopy-basedtechnologies have shown the most promise, whether such technologies will be of diagnostic benefit await the completion of ongoing clinical trials.

LEVEL OF EVIDENCE
Systematic Review, level II.
Effect of damage control laparotomy on major abdominal complications and lengths of stay: A propensity score matching and Bayesian analysis
Authors: Harvin John A. , Sharpe John P. , Croce Martin A. , Goodman Michael D. , Pritts Timothy A. , Dauer Elizabeth D. , Moran Benjamin J. , Rodriguez Rachel D. , Zarzaur Ben L. , Kreiner Laura A. , Claridge Jeffrey A. , Holcomb John B. 
Published: April 2019

BACKGROUND
In patients for whom surgical equipoise exists for damage control laparotomy (DCL) and definitive laparotomy (DEF), the effect of DCL and its associated resource utilization are unknown. We hypothesized that DEF would be associated with fewer abdominal complications and less resource utilization.

METHODS
In 2016, six US Level I trauma centers performed a yearlong, prospective, quality improvement project with the primary aim to safely decrease the use of DCL. From this cohort of patients undergoing emergent trauma laparotomy, those who underwent DCL but were judged by majority faculty vote at each center to have been candidates for potential DEF (pDEF) were prospectively identified. These pDEF patients were matched 1:1 using propensity scoring to the DEF patients. The primary outcome was the incidence of major abdominal complications (MAC). Deaths within 5 days were excluded. Outcomes were assessed using both Bayesian generalized linear modeling and negative binomial regression.

RESULTS
Eight hundred seventy-two total patients were enrolled, 639 (73%) DEF and 209 (24%) DCL. Of the 209 DCLs, 44 survived 5 days and were judged to be patients who could have safely been closed at the primary laparotomy. Thirty-nine pDEF patients were matched to 39 DEF patients. There were no differences in demographics, mechanism of injury, Injury Severity Score, prehospital/emergency department/operating room vital signs, laboratory values, resuscitation, or procedures performed during laparotomy. There was no difference in MAC between the two groups (31% DEF vs. 21% pDEF, relative risk 0.99, 95% credible interval 0.60–1.54, posterior probability 56%). Definitive laparotomy was associated with a 72%, 77%, and 72% posterior probability of more hospital-free, intensive care unit-free, and ventilator-free days, respectively.

CONCLUSION
In patients for whom surgeons have equipoise for DCL versus definitive surgery, definitive abdominal closure was associated with a similar probability of MAC, but a high probability of fewer hospital-free, intensive care unit-free, and ventilator-free days.

LEVEL OF EVIDENCE
Therapeutic/care management, level III.
Development of clinical tracheostomy score to identify cervical spinal cord injury patients requiring prolonged ventilator support
Authors: Scantling Dane , Granche Janeway , Williamson John , Gracely Edward , Thosani Darshak , McCracken Brendan 
Published: April 2019

BACKGROUND
Cervical spinal cord injuries often necessitate ventilator support (VS). Prolonged endotracheal tube use has conveyed substantial morbidity in prospective study. Tracheostomy is recommended if VS is anticipated to be 7 days or longer, which defines prolonged ventilation (PV). Identifying these patients on arrival and before tracheostomy need is readily evident could prevent morbidity while lowering hospital costs. We aimed to create a tracheostomy score (trach score) to identify patients requiring PV and who could benefit from immediate tracheostomy.

METHODS
A review of patients with cervical spine fractures and cervical spinal cord injuries from 2005 to 2017 from the Pennsylvania Trauma Outcome Study database was performed. Patients were excluded for missing data, no use of VS or death in less than 7 days. Patients were selected for a training set or validation set by state identification number. We used automated forward stepwise selection to select a logistic model. Significant continuous variables were dichotomized to create a simplified screening score (trach score) and this was applied to the validation set.

RESULTS
Needing ventilation for 7 or more days was positively associated with higher Injury Severity Scores having a complete or anterior injury, and having a motor cord injury from C1 to C4. Application of the logistic model to the validation data produced a receiver operating characteristic curve with area under the curve of 0.7712, with 95% confidence limit (CL) of 0.6943 to 0.8481. The validation receiver operating characteristic curve was statistically better than chance using a contrast test with χ2 with p value less than 0.01. In the validation set, a trach score of 0 correlated to 33% needing PV, a score of 1 with 67% needing PV, 2 with 85%, and 3 with 98%.

CONCLUSION
Use of the trach score identified the majority of patients requiring prolonged VS in our study. An early tracheostomy protocol using predictive modeling could aid in reduction of intensive care unit length of stay and improving ventilator weaning in these patients. External verification of this predictive tool and of an early tracheostomy protocol is needed.

LEVEL OF EVIDENCE
This work is a retrospective prognostic cohort study and meets evidence Level III criteria.
Escalation of mortality and resource utilization in emergency general surgery transfer patients
Authors: Keeven David D. , Davenport Daniel L. , Bernard Andrew C. 
Published: April 2019

BACKGROUND
Emergency general surgery (EGS) patients require greater resources and have increased rates of morbidity and mortality. Previous work has shown mortality differences in colectomy patients between direct admissions and transfers patients based on source, including emergency department, inpatient, and nursing home transfers. We hypothesize that patient transfer status negatively effects morbidity, mortality, and resource utilization in a mixed population of EGS patients.

METHODS
Data were obtained for patients undergoing EGS using public files from the American College of Surgeons National Surgery Quality Improvement Program for the years 2014 through 2016. We analyzed risk factors and 30-day outcomes by transfer status on frequently performed procedures using χ2 analysis and multivariable logistic regression. Significance was set at p < 0.001 for the bivariate analyses and p < 0.05 for the multivariable analyses.

RESULTS
A total of 167,636 procedures were identified. Transferred patients had increased clinical risk, operative complexity, and poorer outcomes. Fewer transfers were initiated for less technically sophisticated cases such as laparoscopic appendectomy and cholecystectomy, whereas more complex acute open cases were more often transferred. Transfer patients required longer operations and more transfusions and experienced more complications likely to require an intensive care unit stay. Transfer patients returned to the operating room more often, had higher rates of readmission, and greater 30-day mortality. These effects remained after adjusting for procedure group, secondary procedures, age, sex, and American Society of Anesthesiologists class.

CONCLUSION
Our study demonstrates significant increases in mortality, morbidity, and resource utilization in EGS transfer patients who were not attributable to case mix, demographics, and comorbid status alone. These data point to potential financial and quality assessment challenges for tertiary referral centers.

LEVEL OF EVIDENCE
Prognostic, level III; therapeutic, level IV.
Sex Differences in Head-fixed Running Behavior
Authors: Warner Emily J. , Padmanabhan Krishnan 
Published: April 2019

ABSTRACTSex differences in running behaviors between male and female mice occur naturally in the wild. Recent experiments using head restrained mice on a running wheel have exploited locomotion to provide insight in the neural underpinnings of a number of behaviors ranging from spatial navigation to decision making. However, it is largely unknown how males and females behave differently in this experimental paradigm. We found that in head-fixed mice that were initially exposed to a running wheel, all female mice ran forward naturally within the first two days, while almost all male mice scurried backward for up to 4 days. With daily exposure, male mice progressively learned to naturally run forward, with this transition occurring over the course of a 7-day period. Taken together, we have identified a sexually divergent behavior in head-fixed running that should be considered in experiments that use this experimental design. Furthermore, this sex-specific difference could serve as a new way to interrogate the neural underpinnings of a number of behaviors such as anxiety or fear.
Pre-Settlement Forests around Puget Sound: Eyewitness Evidence
Authors: Schroeder Tom 
Published: April 2019

AbstractWitness trees from GLO surveys covering 6,300 square miles around Puget Sound (western Washington State) reveal, for the first time, the character and local diversity in the region’s mid-19th-century forest cover, before it was severely logged during the settlement period. Although only a few coniferous and hardwood species occurred overall, discrete geographical areas supported distinctive species compositions. Geo-climatic and developmental factors are explored to explain these local differences. Profiles of tree diameters reveal that most trees were small to medium in size, even though most areas also exhibited a minority of larger legacy trees. Approximate stand ages and stages of ecological succession are inferred from local tree sizes and site qualities. Despite current inclusion within the Western Hemlock Zone, major portions of the Puget lowlands (below 1000 feet) displayed extremely few western hemlock, the putative climax species, even stands of decidedly advanced age; in extreme cases “pioneer old growth” prevailed. Conversely, hemlock was strongly predominant in the region’s framing foothills (above 1000 feet), even when stand age there was relatively low. These problematic successional conditions question whether many early forests around Puget Sound deserve a categorical recognition separate from the Western Hemlock Zone.
Stress-induced neuronal hypertrophy decreases the intrinsic excitability in stress habituation
Authors: Matovic Sara , Ichiyama Aoi , Igarashi Hiroyuki , Salter Eric W , Wang Xie-Fan , Henry Mathilde , Vernoux Nathalie , Tremblay Marie-Eve , Inoue Wataru 
Published: April 2019

AbstractA rapid activation of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark stress response to an imminent threat, but its chronic activation can be detrimental. Thus, the long-term survival of animals requires experience-dependent fine-tuning of the stress response. However, the cellular mechanisms underlying the ability to decrease the stress responsiveness of the HPA axis remain largely unsolved. Using a stress habituation model in male mice and slice patch-clamp electrophysiology, we studied hypothalamic corticotropin-releasing hormone neurons that form the apex of the HPA axis. We found that the intrinsic excitability of these neurons substantially decreased after daily repeated restraint stress in a time course that coincided with their loss of stress responsiveness in vivo. This plasticity of intrinsic excitability co-developed with an expansion of surface membrane area, resulting in an increase in input conductance with minimal changes in conductance density. Moreover, multi-photon and electron microcopy data found that repeated stress augmented ruffling of the plasma membrane, suggesting an ultrastructural plasticity that efficiently accommodates membrane area expansion with proportionally less expansion of gross cell volume. Overall, we report a novel structure-function relationship for intrinsic excitability plasticity that correlates with habituation of the neuroendocrine stress response.Significance statementThe long-term survival of animals requires experience-dependent fine-tuning of stress response. Using a mouse model of repeated stress that develops habituation of the hypothalamic-pituitary-adrenal (HPA) axis, our study demonstrates a robust decrease in the intrinsic excitability of the output neuroendocrine neurons of the HPA axis. Mechanistically, we show that repeated stress increases the cell size of these neurons (i.e. surface membrane area). This cell-size change increases input conductance, and hence decreases excitability. Our findings challenge a conventional view that plasticity of intrinsic excitability relies on changes on membrane excitability resulting from up- and down-regulation of various voltage-gated ion channels. Our study reports a novel structure-function relationship for intrinsic excitability plasticity that correlates with habituation of the neuroendocrine stress response.
BEN-solo factors partition active chromatin to ensure proper gene activation inDrosophila
Authors: Ueberschär Malin , Wang Huazhen , Zhang Chun , Kondo Shu , Aoki Tsutomu , Schedl Paul , Lai Eric C. , Wen Jiayu , Dai Qi 
Published: April 2019

AbstractTheDrosophilagenome encodes three BEN-solo proteins including Insensitive (Insv), Elba1 and Elba2 that possess activities in both transcriptional repression and chromatin insulation. These proteins all have a DNA binding BEN domain. A fourth protein Elba3 bridges Elba1 and Elba2 to form a heterotrimeric complex ELBA. Here we report comprehensive investigation on thein vivofunctions of these proteins inDrosophilaembryos. We generate ChIP-seq data of all these factors from all cognate and non-cognate mutants to assess common and distinct binding locations of Insv and ELBA, and genetic interdependencies. Notably, while most Elba1 and Elba2 binding requires the full ELBA complex, the adapter protein Elba3 can associate with chromatin and repress gene expression independently of Elba1 and Elba2. We also employ high-resolution ChIP-nexus mapping to show that Insv binds to DNA in a symmetric configuration while the ELBA complex binds asymmetricallyin vivo. We observe that motifs of known insulator proteins are enriched in ELBA and Insv ChIP peaks and demonstrate that ELBA collaborates with other insulator factors to regulate developmental patterning in embryos. To differentiate the insulator function of ELBA and Insv from their repressor activity, we determined real-time transcription change in mutant embryos using precision nuclear run-on sequencing. ELBA factor mutants dampen expression differences between pairs of ELBA-bound neighboring genes. Finally, transgenic reporters confirm insulation activity of ELBA- and Insv-bound sites. Altogether, these findings define ELBA and Insv as general insulator proteins inDrosophilaand demonstrate the functional importance of insulators in partitioning transcription units.
Two molecules of Has1 RNA helicase function simultaneously in the biogenesis of small and large ribosomal subunits
Authors: Gnanasundram Sivakumar Vadivel , Kos-Braun Isabelle C. , Koš Martin 
Published: April 2019

ABSTRACTThe RNA helicase Has1 is involved in the biogenesis of both small and large ribosomal subunits. How it performs these separate roles is not fully understood. Here we provide evidence that two molecules of Has1 are recruited and temporarily present in the same time in 90S pre-ribosomes. We identified multiple Has1 binding sites in the 18S, 5.8S and 25S rRNAs. We show that while the Has1 catalytic activity is not required for binding to 5.8S/25S region in pre-rRNA, it is essential for binding to 18S sites. After the cleavage of pre-rRNA at the site A2 Has1 remains associated not only with pre-60S but unexpectedly also with the pre-40S ribosomes. The recruitment to 90S/pre-40S and pre-60S ribosomes is mutually independent. Our data reconcile some seemingly contradictory observations about Has1 function in ribosome biogenesis.