bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prehospital trauma experience of the Israel defense forces on the Syrian border 2013–2017
Authors: Benov Avi , Shkolnik Irena , Glassberg Elon , Nadler Roy , Gendler Sami , Antebi Ben , Chen Jacob , Fink Noam , Bader Tarif 
Published: February 2019

BACKGROUND
The Israeli Defense Force Medical Corps (IDF-MC) is routinely collecting prehospital data to establish a prehospital registry. Since February 2013, Israel has been providing medical care to Syrian refugees. This unique humanitarian aid begins in prehospital settings and typically culminates in Israeli civilian hospitals. This report describes the accumulated experience of the IDF-MC to provide Syrian refugees with prehospital treatment.

METHODS
Care provided by IDF-MC medical teams, including prehospital casualty care, is regularly documented and after-action reports are conducted. Records of casualties arriving at the Israeli-Syrian border from February 16, 2013, to December 31, 2017, were prospectively extracted from the IDF Trauma Registry. Patients who did not have a casualty card were excluded. The database included demographic information, injury signature and treatment given.

RESULTS
During the study period, 2,785 Syrian casualties were treated, of whom 2,339 were trauma victims. The most common mechanism of injury was penetrating (60.4%). Prehospital lifesaving interventions included 127 endotracheal intubations, 30 cricothyroidotomies, 55 chest decompressions, and 58 tourniquets for extremity hemorrhage control. Remote Damage Control Resuscitation included reconstituted freeze-dried plasma (n = 75) and tranexamic acid (n = 222 casualties) with no adverse effects.

CONCLUSION
The experience of the IDF-MC teams in caring for civilian casualties along a hostile international border is unique. In this capacity, the IDF-MC has demonstrated effectiveness in providing lifesaving and resuscitative interventions including tranexamic acid and freeze-dried plasma. In this experience, tourniquets have been effective in controlling hemorrhage when applied early and endotracheal intubation and cricothyroidotomy have provided effective airway options in select patients. Prehospital combat casualty care presents a significant challenge both in terms of providing adequate care and in terms of data collection and analysis. The experience described in this article is one example of effective, ongoing prehospital data gathering process. Efforts to provide medical relief to victims of the Syrian civil war continue to this day. While we hope for a better future, as long as these lessons continue to accumulate, it is our obligation to use them to support improvement of trauma care and hopefully save more lives.

LEVEL OF EVIDENCE
Therapeutic, level III.
The promising future of drones in prehospital medical care and its application to battlefield medicine
Authors: Braun Jonathan , Gertz S. David , Furer Ariel , Bader Tarif , Frenkel Hagay , Chen Jacob , Glassberg Elon , Nachman Dean 
Published: February 2019

ABSTRACT
Unmanned aerial vehicles, commonly referred to as drones, have been made widely available in recent years leading to an exponential growth in their roles and applications. The rapidly developing field of medical drones is on the verge of revolutionizing prehospital medicine enabling advanced health care delivery to once-inaccessible patients. The aim of this review is to clarify the basic technical properties of currently available medical drones and review recent advances and their usefulness in military and civilian health care missions. A thorough search was conducted using conventional medical literature databases and nonmedical popular search engines. The results indicate increasingly rapid incorporation of unmanned aerial vehicles into search and rescue missions, telemedicine assignments, medical supply routes, public health surveillance, and disaster management. Medical drones appear to be of great benefit for improving survivability of deployed forces on and off the battlefield. The emerging aerial medical delivery systems appear to provide particularly promising solutions for bridging some of the many serious gaps between third world health care systems and their western counterparts and between major metropolitan centers and distant rural communities. The global nature of drone-based health care delivery needs points to a need for an international effort between collaborating civilian and military medical forces to harness the currently available resources and novel emerging technologies for broader lifesaving capabilities.

LEVEL OF EVIDENCE
Level V.
Psychiatric outcome at least 20 years after trauma: A survey on the status of subjective general health and psychiatric symptoms with a focus on posttraumatic stress disorder
Authors: Halvachizadeh Sascha , Teuber Henrik , Allemann Florin , Luidl Anna Theresa , von Känel Roland , Zelle Boris , Tiziani Simon , Rauen Katrin , Pape Hans-Christoph , Pfeifer Roman 
Published: February 2019

BACKGROUND
Information on long-term psychiatric sequelae after severe trauma is sparse. We therefore performed a survey addressing several symptoms related to posttraumatic stress disorder (PTSD) in patients who sustained multiple injuries more than 20 years after trauma.

METHODS
Patients injured between January 1, 1973, and December 31, 1990, were contacted at least 20 years later. We included multiply injured patients aged between 3 and 60 years from a single level 1 trauma center. A questionnaire based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnostic criteria for PTSD, including individual symptoms related to intrusion, avoidance, and hyperarousal was sent to all patients.

RESULTS
A total of 359 patients (56.35%) received a questionnaire. Of these, 337 patients (93.87%) returned the questionnaire and were included in the study (223 males [66.17%] and 114 females [33.82%]). Mean ± SD follow-up was 29.5 ± 8.5 years. Nearly half the study population (47.18%) experienced lasting psychiatric sequelae, such as intrusive recollection (n = 65, 19.28%), avoidance (n = 92, 27.29%), or hyperarousal (n = 95, 28.18%) at least monthly. Ten patients (2.96%) fulfilled all Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnostic criteria for PTSD. A total of 131 patients (38.87%) reported fair or poor general health status. There was no difference in injury severity in patients with or without PTSD (injury severity score, 8.33 vs. 20.36, respectively; p = 0.52) or PTSD-related symptoms including intrusion (19.88 vs. 20.32, p = 0.74), avoidance (19.99 vs. 20.3, p = 0.79), and hyperarousal (19.36 vs. 20.68, p = 0.26).

CONCLUSION
At least 20 years after injury, no correlation was found between the development of psychiatric complications and the severity of injury. While the rate of full-blown PTSD was low, nearly half the study population regularly suffered from at least one psychiatric symptom attributable to the initial trauma. Awareness for the development of psychiatric complications and early initiation of psychiatric counseling are advisable.

LEVEL OF EVIDENCE
Prognostic and epidemiologic, level II.
Glass Slippers and Glass Cliffs: Fitting In and Falling Off
Authors: Krishnan Nithya , Biggerstaff Deborah , Szczepura Ala , Dolton Monica , Livingston Sondra , Hattersley John , Eris Josette , Ascher Nancy , Higgins Robert , Braun Hillary , Wood Kathryn , Raymond Neil 
Published: February 2019

Background.
A glass ceiling effect exists for women in male-dominated professions. Recent studies also show a glass-cliff effect where senior women can more easily fall from positions of leadership. Transplantation remains a male-dominated specialty. This study investigated gender and the perception of adverse clinical incidents in transplantation.

Methods.
Prospective randomised web-based survey involving five clinical scenarios presenting two versions of episodes with errors or mistakes, with either a male or female as a randomly named protagonist (Set1 and Set2). To address unconscious bias, the study was described as examining actions following clinical adverse incidents in transplantation. Each scenario was followed by 2 closed questions: (1) clinical performance rating and (2) selection of action required. Reasoning was invited (open-text comments). Responses were analyzed using quantitative and qualitative methods.

Results.
One hundred ninety-one invitees responded; 134 completed questionnaires. There were no statistically significant differences (P > 0.05) in responses between sets for performance ratings or recommended actions. However, for “first solo laparoscopic surgery” scenario, there was some indication that “No Action” was more likely if surgeon was male (P = 0.056). Male responses rated female performance as significantly worse (P = 0.035) for the laboratory-based scenario. One hundred two participants provided open-text comments. Thematic analysis identified 7 themes. Acceptable levels of risk theme demonstrated engendered leadership beliefs, that is, when clinical judgment proved incorrect, males described as forceful but females as needing support. In cases where things went wrong, respondents were more likely to comment females should not have decided to proceed.

Conclusions.
While gender may no longer be an overt issue in perceived performance of senior staff in transplantation, respondents’ use of language and their choice of words display elements of unconscious (covert) engendered views.
Inhibition of Cyclin-dependent Kinase 2 Signaling Prevents Liver Ischemia and Reperfusion Injury
Authors: Xu Jin , Xue Zhengze , Zhang Cheng , Liu Yuan , Busuttil Ronald W. , Zhang Jiamin , Kupiec-Weglinski Jerzy W. , Ji Haofeng 
Published: February 2019

Background.
Liver ischemia and reperfusion injury (IRI) is a major complication of liver transplant, hepatectomy, and hemorrhagic shock. The cyclin-dependent kinase 2 (CDK2) acts as a pivotal regulator of cell cycle and proliferation.

Methods.
This study evaluated the modulation and therapeutic potential of CDK2 inhibition in a mouse model of partial liver warm IRI.

Results.
Liver IR-triggered intrinsic CDK2 expression, peaking by 0.5 hour of reperfusion and maintaining a high-level throughout 1 to 24 hours. Roscovitine, a specific CDK2 inhibitor, prevented liver IR-mediated damage with abolished serum alanine aminotransferase levels and reserved liver pathology. CDK2 inhibition-mediated liver protection was accompanied by decreased macrophage/neutrophil infiltration, diminished hepatocyte apoptosis, abolished toll like receptor 4 signaling and downstream gene inductions (C-X-C motif ligand-10, Tumor necrosis factor-α, interleukin-1β, and interleukin-6), yet augmented interleukin-10 expression. In vitro, CDK2 inhibition by Roscovitine suppressed macrophage TLR4 activation and further depressed downstream inflammatory signaling (myeloid differentiation factor 88, interferon regulatory transcription factor 3, p38, c-Jun N-terminal kinase, and extracellular-regulated kinase).

Conclusions.
Our novel findings revealed the critical role of CDK2 in hepatic cytoprotection and homeostasis against liver IRI. As CDK2 inhibition regulated local immune response and prevented hepatocyte death, this study provided the evidence for new treatment approaches to combat IRI in liver transplant.
Genetic Variants Associated With Immunosuppressant Pharmacokinetics and Adverse Effects in the DeKAF Genomics Genome-wide Association Studies
Authors: Oetting William S. , Wu Baolin , Schladt David P. , Guan Weihua , van Setten Jessica , Keating Brendan J. , Iklé David , Remmel Rory P. , Dorr Casey R. , Mannon Roslyn B. , Matas Arthur J. , Israni Ajay K. , Jacobson Pamala A. 
Published: February 2019

Background.
The immunosuppressants tacrolimus and mycophenolate are important components to the success of organ transplantation, but are also associated with adverse effects, such as nephrotoxicity, anemia, leukopenia, and new-onset diabetes after transplantation. In this report, we attempted to identify genetic variants which are associated with these adverse outcomes.

Methods.
We performed a genome-wide association study, using a genotyping array tailored specifically for transplantation outcomes containing 722 147 single nucleotide polymorphisms, and 2 cohorts of kidney allograft recipients—a discovery cohort and a confirmation cohort—to identify and then confirm genetic variants associated with immunosuppressant pharmacokinetics and adverse outcomes.

Results.
Several genetic variants were found to be associated with tacrolimus trough concentrations. We did not confirm variants associated with the other phenotypes tested although several suggestive variants were identified.

Conclusions.
These results show that adverse effects associated with tacrolimus and mycophenolate are complex, and recipient risk is not determined by a few genetic variants with large effects with but most likely are due to many variants, each with small effect sizes, and clinical factors.
Analysis of 75 Candidate SNPs Associated With Acute Rejection in Kidney Transplant Recipients: Validation of rs2910164 in MicroRNA MIR146A
Authors: Oetting William S. , Schladt David P. , Dorr Casey R. , Wu Baolin , Guan Weihua , Remmel Rory P. , Iklé David , Mannon Roslyn B. , Matas Arthur J. , Israni Ajay K. , Jacobson Pamala A. 
Published: February 2019

Background.Identifying kidney allograft recipients who are predisposed to acute rejection (AR) could allow for optimization of clinical treatment to avoid rejection and prolong graft survival. It has been hypothesized that a part of this predisposition is caused by the inheritance of specific genetic variants. There are many publications reporting a statistically significant association between a genetic variant, usually in the form of a single-nucleotide polymorphism (SNP), and AR. However, there are additional publications reporting a lack of this association when a different cohort of recipients is analyzed for the same single-nucleotide polymorphism.Methods.In this report, we attempted to validate 75 common genetic variants, which have been previously reported to be associated with AR, using a large kidney allograft recipient cohort of 2390 European Americans and 482 African Americans.Results.Of those variants tested, only 1 variant, rs2910164, which alters the expression of the microRNAMIR146A, was found to exhibit a significant association within the African American cohort. Suggestive variants were found in the genesCTLAandTLR4.Conclusions.Our results show that most variants previously reported to be associated with AR were not validated in our cohort. This shows the importance of validation when reporting the associations with complex clinical outcomes such as AR. Additional work will need to be done to understand the role of MIR146A in the risk of AR in kidney allograft recipients.
The Proportional Relationship Between Pretransplant WT1 mRNA Levels and Risk of Mortality After Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Not in Remission
Authors: Ido Kentaro , Nakamae Mika , Koh Hideo , Okamura Hiroshi , Nanno Satoru , Nishimoto Mitsutaka , Takeoka Yasunobu , Hirose Asao , Nakashima Yasuhiro , Hashimoto Yoshinori , Nakane Takahiko , Hino Masayuki , Nakamae Hirohisa 
Published: February 2019

Background.
The relationship between the expression levels of Wilms’ tumor-1 gene (WT1) mRNA in peripheral blood before allogeneic hematopoietic cell transplantation (allo-HCT) and risk of mortality in acute myeloid leukemia (AML) patients in noncomplete remission (non-CR) remains quite elusive.

Methods.
We retrospectively assessed the impact of the pretransplant WT1 mRNA level on survival after allo-HCT in non-CR AML patients.

Results.
A total of 125 AML patients, including 46 non-CR patients (36.8%), were analyzed. On multivariate analysis of non-CR AML patients, WT1 mRNA ≥5000 copies/μg RNA was significantly related to increased risk of mortality (hazard ratio, 2.7; 95% confidence interval, 1.3-5.5; P = 0.008). Furthermore, in the entire cohort, log10-transformed WT1 mRNA before allo-HCT was found to be significantly associated with the increased risk of mortality irrespective of whether the disease status was CR or non-CR, using Akaike’s information criterion. As the pretransplant WT1 mRNA level elevated, the hazard ratio of mortality monotonically increased in a nonlinear manner regardless of remission status, suggesting that WT1 mRNA level in peripheral blood might reflect tumor burden.

Conclusions.
This study demonstrated that the pretransplant WT1 mRNA level was a powerful prognostic factor in allo-HCT even for non-CR AML patients, and there may be a WT1 mRNA threshold in non-CR patients for benefiting from allo-HCT.
Greater Susceptibility for Metabolic Syndrome in Pediatric Solid Organ and Stem Cell Transplant Recipients
Authors: Blöte Ricarda , Memaran Nima , Borchert-Mörlins Bianca , Thurn-Valsassina Daniela , Goldschmidt Imeke , Beier Rita , Sauer Martin , Müller Carsten , Sarganas Giselle , Oh Jun , Büscher Rainer , Kemper Markus J. , Sugianto Rizky I. , Epping Jelena , Schmidt Bernhard M.W. , Melk Anette 
Published: February 2019

Background.
Cardiovascular comorbidity is of increasing importance after transplantation. Metabolic syndrome (MS) contributes to the risk for cardiovascular sequelae. Our aim was to assess the risk for MS in pediatric solid organ and stem cell transplant recipients by comparing them with matched untransplanted peers in a multicenter study.

Methods.
We prospectively assessed MS in 295 pediatric transplant recipients and compared them with 1475 age- and sex-matched controls.

Results.
Posttransplant metabolic syndrome (PTMS) was most frequent in lung (43%) and kidney (39%), followed by liver (16%) and stem cell (13%) recipients, compared with nontransplanted peers (4%; P < 0.01). The risk of displaying PTMS was almost 22-fold higher after lung (95% confidence interval, CI, 8.2-57.4), 16-fold higher after kidney (95% CI, 9.1-28.9), 5-fold higher after liver (95% CI, 2.1-10.1), and 4-fold higher after stem cell (95% CI, 1.4-9.5) transplantation. The contribution of individual components leading to MS differed depending on transplant type. In the combined analysis of all transplant groups, older age, less physical activity, calcineurin or mammalian target of rapamycin inhibitor-based immunosuppression, and hypovitaminosis D were associated with PTMS.

Conclusions.
By investigating a large group of patients, our study not only shows a high prevalence of PTMS but also identifies kidney and lung transplant patients as being at a particularly high risk. Moreover, knowledge on the factors associated with PTMS allows for individualized treatment approaches as well as potential preventive measures.
Single cell ATAC-seq identifies broad changes in neuronal abundance and chromatin accessibility in Down Syndrome
Authors: Spektor Roman , Yang Jee Won , Lee Seoyeon , Soloway Paul D. 
Published: February 2019

AbstractDown Syndrome (DS) is caused by triplication of chr21 and is associated with cognitive impairment, Alzheimer’s Disease, and other developmental alterations. The Ts65Dn mouse model for DS has triplication of sequences syntenic with human chr21, and traits resembling those seen in humans with DS. We performed single-cell combinatorial indexing assay for transposase accessible chromatin using sequencing (sci-ATAC-seq) on cortices of adult Ts65Dn mice and control littermates. Analyses of 13,766 cells revealed 26 classes of cells. The most abundant class of excitatory neurons was reduced by 17% in Ts65Dn mice, and three of the four most common classes of interneurons were increased by 50%. Ts65Dn mice display changes in accessibility at binding motifs for transcription factors that are determinants of neuronal lineage, and others encoded within triplicated regions. These studies define previously uncharacterized cellular and molecular features of DS, and potential mechanisms underlying the condition.
The great tit HapMap project: a continental-scale analysis of genomic variation in a songbird
Authors: Spurgin Lewis G. , Bosse Mirte , Adriaensen Frank , Albayrak Tamer , Barboutis Christos , Belda Eduardo , Bushuev Andrey , Cecere Jacopo G. , Charmantier Anne , Cichon Mariusz , Dingemanse Niels J. , Doligez Blandine , Eeva Tapio , Erikstad Kjell Einar , Fedorov Vyacheslav , Griggio Matteo , Heylen Dieter , Hille Sabine , Hinde Camilla A. , Ivankina Elena , Kempenaers Bart , Kerimov Anvar , Krist Milos , Kvist Laura , Laine Veronika N. , Mänd Raivo , Matthysen Erik , Nager Ruedi , Nikolov Boris P. , Norte A. Claudia , Orell Markku , Ouyang Jenny , Petrova-Dinkova Gergana , Richner Heinz , Rubolini Diego , Slagsvold Tore , Tilgar Vallo , Török János , Tschirren Barbara , Vágási Csongor I. , Yuta Teru , Groenen Martien A.M. , Visser Marcel E. , van Oers Kees , Sheldon Ben C. , Slate Jon 
Published: February 2019

AbstractA major aim of evolutionary biology is to understand why patterns of genomic diversity vary among populations and species. Large-scale genomic studies of widespread species are useful for studying how the environment and demographic history shape patterns of genomic divergence, and with the continually decreasing cost of sequencing and genotyping, such studies are now becoming feasible. Here, we carry out one of the most geographically comprehensive surveys of genomic variation in a wild vertebrate to date; the great tit (Parus major) HapMap project. We screenedca500,000 SNP markers across 647 individuals from 29 populations, spanning almost the entire geographic range of the European great tit subspecies. We found that genome-wide variation was consistent with a recent colonisation across Europe from a single refugium in South-East Europe, with bottlenecks and reduced genetic diversity in island populations. Differentiation across the genome was highly heterogeneous, with clear “islands of differentiation” even among populations with very low levels of genome-wide differentiation. Low local recombination rate in the genome was a strong predictor of high local genomic differentiation (FST), especially in island and peripheral mainland populations, suggesting that the interplay between genetic drift and recombination is a key driver of highly heterogeneous differentiation landscapes. We also detected genomic outlier regions that were confined to one or more peripheral great tit populations, most likely as a result of recent directional selection at the range edges of this species. Haplotype-based measures of selection were also related to recombination rate, albeit less strongly, and highlighted population-specific sweeps that likely resulted from positive selection. These regions under positive selection contained candidate genes associated with morphology, thermal adaptation and colouration, providing promising avenues for future investigation. Our study highlights how comprehensive screens of genomic variation in wild organisms can provide unique insights into evolution.