bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organ donation in trauma victims: A systematic review and meta-analysis
Authors: Cameron Adam , Erdogan Mete , Lanteigne Sara , Hetherington Alexandra , Green Robert S. 
Published: March 2018

BACKGROUND
Although trauma patients represent a large pool of potential organ donors (PODs), the donor conversion rates (DCRs) in this population are unclear. Our primary objective was to synthesize published evidence on DCRs in trauma patients. As a secondary objective, we investigated factors that affect organ donation (OD) in the trauma population.

METHODS
We searched four electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) and gray literature for articles on OD in trauma patients (PROSPERO 2017: CRD42017070388). Articles were excluded if it was not possible to calculate the DCR (actual organ donors divided by PODs). We pooled DCRs and performed subgroups analysis by trauma subpopulation, patients’ age, and study publication date.

RESULTS
We identified 27 articles with a total of 123,142 participants. Cohorts ranged in size from 28 to 120,512 patients (median, 132), with most studies performed in the United States. Conversion rates among individual studies ranged from 14.0% to 75.2% (median, 49.3%). All 27 studies were included in the meta-analysis. We found a pooled DCR of 48.1% using the random effects model. There was a high level of heterogeneity between studies (I
2 = 97.4%). Upon subgroup analysis, we found DCRs were higher in head trauma patients compared with traumatic cardiac arrest patients (45.3% vs 20.9%, p < 0.001), in pediatric patients compared with adults (61.0% vs 38.0%, p = 0.018), and in studies published after 2007 compared with those published before (50.8% vs 43.9%, p < 0.001). Few studies assessed for factors associated with OD in trauma patients.

CONCLUSIONS
We found variation in DCRs among trauma patients (range, 14.0–75.2%) and estimated a pooled DCR of 48.1%. Our results are limited by heterogeneity across studies, which may be attributable to differences in study design and population, definitions of a POD, and in the institutional criteria and processes regarding OD.

LEVEL OF EVIDENCE
Systematic reviews and meta-analyses level III.
Minimally invasive surgery techniques for the management of urgent or emergent small bowel pathology: A 2018 EAST Master Class Video Presentation
Authors: Martin Matthew J. , Pakula Andrea M. 
Published: March 2018

ABSTRACT
Although minimally invasive surgery techniques have been rapidly and widely adopted among nearly all fields of elective surgery, their use by trauma and acute care surgeons for urgent or emergent pathology has somewhat lagged behind. Trauma surgeons are frequently called upon to manage traumatic or emergent surgical small bowel pathology, and many of these may be ideally suited for increased incorporation of minimally invasive surgery techniques. This surgical technique video and associated article provide a technical guide and “how-to” instructions for laparoscopic and other minimally invasive approaches that can be utilized in the management of traumatic small bowel injuries, small bowel obstructions, or other emergent small bowel pathology.
Minimally invasive approach to incarcerated or strangulated groin hernias: A 2018 EAST Master Class Video Presentation
Authors: Martin Matthew J. , Pakula Andrea M. 
Published: March 2018

ABSTRACT
Groin hernia repair is one of the most common general surgical procedures performed worldwide. Although only a small percentage will become incarcerated or strangulated, this is an indication for repair. Minimally invasive surgery is becoming the standard of care for most procedures, and we believe this to be a safe and feasible approach for incarcerated or strangulated groin hernias. We present a description of our recommended approach with technical details and accompanying video clips to highlight these techniques.
Trauma surgeon performance of appendectomy in 5-year- to 10-year-old children is safe and decreases length of hospital stay
Authors: Wall Derek B. , Ortega Carlos 
Published: March 2018

BACKGROUND
Even in metropolitan areas, on-call pediatric surgeons may not always be immediately available for surgical care of appendicitis, potentially leading to delays in care. In 2012, the in-house trauma group at a suburban Level 1 trauma center (none with formal pediatric fellowship training) assumed surgical care of 5-year- to 10-year-old children with appendicitis, who had previously been cared for by pediatric surgeons. We propose to compare the outcomes of the trauma and pediatric surgery groups.

METHODS
Retrospective chart review of 5-year- to 10-year-olds undergoing emergency appendectomy at a suburban Level 1 trauma center between January 2007 and December 2016 was performed. Patients were classified as having surgery performed by the trauma surgery group or the pediatric surgery group. Patient characteristics, clinical course, and outcomes were compared.

RESULTS
A total of 220 patients were identified for study, 138 in the trauma group and 82 in the pediatric surgery group. Patients cared for by the trauma group were more likely to be female (47% vs. 32%; p = 0.03), were less likely to be diagnosed without imaging (2% vs. 26%; p < 0.0001), had a shorter time from diagnosis to surgery (214 vs. 318 minutes; p = 0.01), were more likely to have laparoscopic surgery (70% vs. 55%; p = 0.04), had a shorter operative time (40 vs. 49 minutes; p < 0.0001), and had a shorter length of stay (32 vs. 41 hours; p < 0.0001), despite more of them needing to be transferred from outside hospitals (60% vs. 37%; p < 0.001). There were no significant differences in patient age, rate of perforated appendicitis, 30-day readmissions, surgical site infections, or unanticipated procedures.

CONCLUSIONS
Trauma surgeon performance of emergency appendectomy in 5-year- to 10-year-old children decreased length of hospitalization with similar complication rates as compared with pediatric surgeons.

LEVEL OF EVIDENCE
Therapeutic study, level IV.
Prehospital low-titer cold-stored whole blood: Philosophy for ubiquitous utilization of O-positive product for emergency use in hemorrhage due to injury
Authors: McGinity Ashley C. , Zhu Caroline S. , Greebon Leslie , Xenakis Elly , Waltman Elizabeth , Epley Eric , Cobb Danielle , Jonas Rachelle , Nicholson Susannah E. , Eastridge Brian J. , Stewart Ronald M. , Jenkins Donald H. 
Published: March 2018

ABSTRACT
The mortality from hemorrhage in trauma patients remains high. Early balanced resuscitation improves survival. These truths, balanced with the availability of local resources and our goals for positive regional impact, were the foundation for the development of our prehospital whole blood initiative—using low-titer cold-stored O RhD-positive whole blood. The main concern with use of RhD-positive blood is the potential development of isoimmunization in RhD-negative patients. We used our retrospective massive transfusion protocol (MTP) data to analyze the anticipated risk of this change in practice. In 30 months, of 124 total MTP patients, only one female of childbearing age that received an MTP was RhD-negative. With the risk of isoimmunization very low and the benefit of increased resources for the early administration of balanced resuscitation high, we determined that the utilization of low-titer cold-stored O RhD-positive whole blood would be safe and best serve our community.
Direct to operating room trauma resuscitation decreases mortality among severely injured children
Authors: Wieck Minna M. , Cunningham Aaron J. , Behrens Brandon , Ohm Erika T. , Maxwell Bryan G. , Hamilton Nicholas A. , Adams M. Christopher , Cole Frederick J. , Jafri Mubeen A. 
Published: March 2018

BACKGROUND
Expediting evaluation and intervention for severely injured patients has remained a mainstay of advanced trauma care. One technique, direct to operating room (DOR) resuscitation, for selective adult patients has demonstrated decreased mortality. We sought to investigate the application of this protocol in children.

METHODS
All DOR pediatric patients from 2009 to 2016 at a pediatric Level I trauma center were identified. Direct to OR criteria included penetrating injury, chest injuries, amputations, significant blood loss, cardiopulmonary resuscitation, and surgeon discretion. Demographics, injury patterns, interventions, and outcomes were analyzed. Observed mortality was compared with expected mortality, calculated using Trauma Injury Severity Score methodology, with two-tailed t tests, and a p value less than 0.5 was considered significant.

RESULTS
Of 2,956 total pediatric trauma activations, 82 (2.8%) patients (age range, 1 month to 17 years) received DOR resuscitation during the study period. The most common indications for DOR were penetrating injuries (62%) and chest injuries (32%). Forty-four percent had Injury Severity Score (ISS) greater than 15, 33% had Glasgow Coma Scale (GCS) score of 8 or less, and 9% were hypotensive. The most commonly injured body regions were external (66%), head (34%), chest (30%), and abdomen (27%). Sixty-seven (82%) patients required emergent procedural intervention, most commonly wound exploration/repair (35%), central venous access (22%), tube thoracostomy (19%), and laparotomy (18%). Predictors of intervention were ISS greater than 15 (odds ratio, 14; p = 0.013) and GCS < 9 (odds ratio = 8.5, p = 0.044). The survival rate to discharge for DOR patients was 84% compared with an expected survival of 79% (Trauma Injury Severity Score) (p = 0.4). The greatest improvement relative to expected mortality was seen in the subgroup with penetrating trauma (84.5% vs 74.4%; p = 0.002).

CONCLUSION
A selective policy of resuscitating the most severely injured children in the OR can decrease mortality. Patients suffering penetrating trauma with the highest ISS, and diminished GCS scores have the greatest benefit. Trauma centers with appropriate resources should evaluate implementing similar policies.

LEVEL OF EVIDENCE
Diagnostic tests or criteria, level II.
Evaluation of Vision-Related Quality of Life in Chinese Patients With Leber Hereditary Optic Neuropathy and the G11778A Mutation
Authors: Cui Shilei , Jiang Hanqiu , Peng Jingting , Wang Jiawei , Zhang Xiaojun 
Published: March 2018

Objective:
To assess quality of life (QoL) measures in Chinese Leber hereditary optic neuropathy (LHON) patients with the G11778A mutation.

Methods:
Chinese LHON patients with the G11778A mutation were prospectively evaluated using the Visual Function Index (VF-14) at 6 months, 1 year, and 3 years after the involvement of the second eye. Patients who completed the VF-14 at all 3 follow-up time designations were included in the analysis.

Results:
Fifty-five patients met the inclusion criteria. The median age of patients when their vision was bilaterally affected was 16.3 years old (interquartile range: 13.9–18.3 years). In our patient cohort, 89.1% (n = 49) were male, and the ratio of males to females was 8.2:1. The median logMAR visual acuity was 2.0 (interquartile range: 1.0–2.6). The mean VF-14 scores of patients with LHON at 6-month, 1-year, and 3-year follow-ups were 18.0 ± 19.2 (range 0–85.4), 19.9 ± 20.0 (range 0–85.4), and 20.7 ± 20.2 (range 0–85.4), and the differences were statistically significant (P < 0.001). VF-14 score at 6 months was significantly correlated with visual acuity of the better eye (P < 0.001) but not with age of onset (P = 0.43). Overall, the QoL improvement was significantly correlated with age of onset (P = 0.006) but not with visual acuity of the better eye (P = 0.134). Several abilities were significantly improved at the 1-year follow-up compared with the 6-month follow-up, including seeing steps, curbs, or stairs (P < 0.01), doing handiwork (P < 0.05), playing sports (P < 0.05), cooking (P < 0.01), and watching television (P < 0.05). When these scores were further compared between 1- and 3-year follow-ups, only scores for cooking (P < 0.05) and watching television (P < 0.05) were higher at the 3-year follow-up than that at the 1-year follow-up. No changes were found during the follow-up for reading small print, reading a newspaper or book, or reading signs.

Conclusions:
Our results indicate that although most of our Chinese LHON patients with the G11778A mutation had permanent central visual loss, visual-related quality of life improved over time, especially in younger patients.
Visual Outcomes and Clinical Manifestations of Pediatric Optic Neuritis in Indian Population: An Institutional Study
Authors: Ambika Selvakumar , Padmalakshmi Krishnakumar , Venkatraman Viswanathan , Noronha Olma V. 
Published: March 2018

Background:
Optic neuritis in children is an uncommon disorder which usually occurs after a viral illness or vaccination and, less frequently, occurs as a manifestation of a demyelinating disorder. Pediatric optic neuritis usually is bilateral and presents with optic disc edema, recovers rapidly with steroid therapy, and generally has low conversion rate to multiple sclerosis or neuromyelitis optica spectrum disorder. We report the clinical features and treatment outcomes of pediatric optic neuritis in Indian population, for which little data are available.

Methods:
We reviewed the medical case records of patients with optic neuritis who were younger than 18 years, from 1999 to 2016. All patients were assessed and managed in the Neuro-Ophthalmology Department of Sankara Nethralaya, a unit of Medical Research Foundation and Pediatric Neurology Department of Kanchi Kamakoti—Childs Trust Hospital, Chennai, India.

Results:
One hundred seventeen eyes of 78 children with mean age of 11.84 (±4.58) years were identified. Forty-two (53.8%) were females and 36 (46.2%) were males. Thirty-nine patients (50%) had bilateral involvement and a similar number had unilateral involvement. Fifty-nine eyes (50.4%) had optic disc edema, 20 eyes (17.1%) had disc pallor, and 38 eyes (32.4%) had normal discs. Of 63 patients who had neuroimaging, 36 had MRI, and 27 underwent computed tomography. Eighty-four eyes (of 59 patients) received steroid therapy according to the protocol of the Optic Neuritis Treatment Trial (ONTT). Thirty-three eyes that were treated with other steroid protocols were excluded from the final visual outcome analyses. Sixty of the 84 eyes (72.3%) recovered visual acuity of 20/40 or better. Visual acuity improvement was statistically significant between initial and final visual acuity (logMAR) in our patients treated with the ONTT protocol (P ≤ 0.001).

Conclusions:
Our Indian pediatric population had good visual recovery after steroid treatment for optic neuritis. Profound loss of visual acuity on presentation and bilateral involvement were significantly associated with poor visual outcome.
HIF1-alpha expressing cells induce a hypoxic-like response in neighbouring cancer cells
Authors: Harrison Hannah , Pegg Henry J , Thompson Jamie , Bates Christian , Shore Paul 
Published: March 2018

AbstractHypoxia stimulates metastasis in cancer and is linked to poor patient prognosis. In tumours, oxygen levels vary and hypoxic regions exist within a generally well-oxygenated tumour. However, whilst the heterogeneous environment is known to contribute to metastatic progression, little is known about the mechanism by which heterogeneic hypoxia contributes to cancer progression. This is largely because existing experimental models do not recapitulate the heterogeneous nature of hypoxia. The primary effector of the hypoxic response is the transcription factor Hypoxia inducible factor 1-alpha (HIF1-alpha). HIF1-alpha is stabilised in response to low oxygen levels in the cellular environment and its expression is seen in hypoxic regions throughout the tumour.We have developed a model system in which HIF1-alpha can be induced within a sub-population of cancer cells, thus enabling us to mimic the effects of heterogeneic HIF1-alpha expression.We show that induction of HIF1-alpha not only recapitulates elements of the hypoxic response in the induced cells but also results in significant changes in proliferation, gene expression and mammosphere formation within the HIF1-alpha negative population.These findings suggest that the HIF1-alpha expressing cells found within hypoxic regions are likely to contribute to the subsequent progression of a tumour by modifying the behaviour of cells in the non-hypoxic regions of the local micro-environment.
Structure of WT1 zinc fingers bound to its cognate DNA: Implications of the KTS insert
Authors: Yengo Raymond K. , Nurmemmedov Elmar , Thunnissen Marjolein M.G.M. 
Published: March 2018

ABSTRACTWT1 is a transcription factor with a DNA binding N-terminal domain containing four C2H2-type zinc fingers. In order to perform its role as a transcription factor, WT1 needs to specifically recognize and properly bind to its target DNA. How this is done is still not completely clear. Two of WT1’s major isoforms are distinguished by the presence or absence of a 3 amino acid insert, Lysine-Threonine-Serine (KTS) in the linker between zinc-fingers 3 and 4. This KTS insert is conserved throughout all life forms expressing WT1. The –KTS isoform, which acts as a transcription factor, binds DNA with higher affinity than the +KTS isoform, which is thought to participate in RNA splicing and interaction with partner proteins. This study was aims at elucidating the effect of the KTS insert on DNA binding. Here we present the crystal structure of WT1 zinc fingers 2-4, with and without the KTS insert, bound to the WT1 9-base pair cognate DNA sequence, refined to 1.9 Å and 2.5 Å respectively. The structures show that the +KTS isoform of WT1 recognizes DNA with the same specificity as the –KTS isoform. The only differences in the DNA bound conformation of the two isoforms are found within the linker containing the KTS, and these mainly involve the loss of the C-capping interactions thought to stabilize the complex. These structures provide the molecular detail necessary for the interpretation of the WT1 transcriptional DNA recognition and validation of its transcriptional targets.
Mean-Variance QTL Mapping Identifies Novel QTL for Circadian Activity and Exploratory Behavior in Mice
Authors: Corty Robert W. , Kumar Vivek , Tarantino Lisa M. , Takahashi Joseph S. , Valdar William 
Published: March 2018

ABSTRACTWe illustrate, through two case studies, that “mean-variance QTL mapping” can discover QTL that traditional interval mapping cannot. Mean-variance QTL mapping is based on the double generalized linear model, which elaborates on the standard linear model by incorporating not only a linear model for the data itself, but also a linear model for the residual variance. Its potential for use in QTL mapping has been described previously, but it remains underutilized, with certain key advantages undemonstrated until now. In the first case study, we use mean-variance QTL mapping to reanalyze a reduced complexity intercross of C57BL/6J and C57BL/6N mice examining circadian behavior and find a mean-controlling QTL for circadian wheel running activity that was not detected by traditional interval mapping. Mean-variance QTL mapping was more powerful than traditional interval mapping at the QTL because it accounted for the fact that mice homozygous for the C57BL/6N allele had less residual variance than the other mice. In the second case study, we reanalyze an intercross between C57BL/6J and C58/J mice examining anxiety-like behaviors, and identify a variance-controlling QTL for rearing behavior. This QTL was not identified in the original analysis because traditional interval mapping does not target variance QTL.
Eye-movement intervention enhances extinction via amygdala deactivation
Authors: de Voogd Lycia D. , Kanen Jonathan W. , Neville David A. , Roelofs Karin , Fernández Guillén , Hermans Erno J. 
Published: March 2018

AbstractImproving extinction learning is essential to optimize psychotherapy for persistent fear-related disorders. In two independent studies (both n=24), we found that goal-directed eye movements activate a dorsal fronto-parietal network and transiently deactivate the amygdala. Connectivity analyses revealed this down-regulation engages a ventromedial prefrontal pathway known to be involved in cognitive regulation of emotion. Critically, when eye movements followed memory reactivation during extinction learning, this reduced spontaneous fear recovery 24 hours later. Stronger amygdala deactivation furthermore predicted a stronger reduction in subsequent fear recovery after reinstatement. In conclusion, we show that extinction learning can be improved with a non-invasive eye-movement intervention that triggers a transient suppression of the amygdala. Our finding that another task which taxes working memory leads to a similar amygdala suppression furthermore indicates that this effect is likely not specific to eye movements, which is in line with a large body of behavioral studies. This study contributes to the understanding of a widely used treatment for traumatic symptoms by providing a parsimonious account for how working memory tasks and goal-directed eye movements can enhance extinction-based psychotherapy, namely through neural circuits similar to those that support cognitive control of emotion.Significant statementFear-related disorders represent a significant burden on individual sufferers and society. There is a high need to optimize treatment, in particular via non-invasive means. One potentially effective intervention is execution of eye movements following trauma recall. However, a neurobiological understanding of how eye movements can reduce traumatic symptoms is lacking. We demonstrate that goal-directed eye-movements, like working memory tasks, deactivate the amygdala, the core neural substrate of fear learning. Effective connectivity analyses revealed amygdala deactivation engaged dorsolateral and ventromedial prefrontal pathways. When applied during safety learning, this deactivation predicts a reduction in later fear recovery. These findings provide a parsimonious and mechanistic account of how behavioral manipulations taxing working memory and suppress amygdala activity can alter retention of emotional memories.
Scaffolding of RhoA contractile signaling by anillin: a regulatory analogue of kinetic proofreading
Authors: Budnar Srikanth , Husain Kabir B. , Gomez Guillermo A. , Naghibosidat Maedeh , Verma Suzie , Hamilton Nicholas A. , Morris Richard G. , Yap Alpha S. 
Published: March 2018

AbstractScaffolding is a fundamental principle of cell signaling commonly thought to involve multi-domain proteins that tether different components of a pathway together into a complex 1,2. We now report an alternative mechanism for scaffolding that is necessary for RhoA-mediated contractile signaling. We find that anillin binding stabilizes active, GTP-RhoA, and promotes contractility at both the epithelial zonula adherens (ZA) and the cytokinetic furrow. However, anillin does not conform to the classical picture of a multi-domain tether, since its RhoA-binding AH domain alone was sufficient to promote contractile signaling. Moreover, anillin competes with contractile effectors for a common site on RhoA, presenting the conundrum of how an inhibitory interaction can otherwise promote signaling. To explain this, we propose that inactivation of RhoA is non-Poissonian, having a rate that increases with time, unless the process is reset via transient binding to anillin. Repeated cycles of binding and un-binding therefore increase cortical residence times of non-sequestered GTP-RhoA and hence the probability of engaging contractile effectors. We identify the modification of the local lipid environment as a potential mechanism underlying such non-Poisson statistics, and demonstrate agreement with a minimal cellular system. Finally, we show that Myosin II anchors anillin at the cortex to form a feedback pathway that enhances RhoA signaling. This new paradigm of scaffolding is a regulatory analogue of kinetic proofreading and may be employed by other binding proteins that do not fit the classical picture.