bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significant Reduction of Pulmonary Embolism in Orthopaedic Trauma Patients
Authors: Starr Adam J. , Shirley Zachary , Sutphin Patrick D. , Sanders Drew , Eastman Alexander , Au Brigham , Sathy Ashoke , Hu Gene , Gebrelul Aaron , Minei Joseph , Cripps Michael W. 
Published: November 2018

Objectives:
To report results of a protocol to lessen incidence of pulmonary embolism (PE) among orthopaedic trauma patients.

Design:
Retrospective review.

Setting:
Level 1 trauma center.

Patient/Participants:
Orthopaedic trauma inpatients were included in the study.

Intervention:
On arrival, an orthopaedic trauma patient's PE risk is calculated using a previously developed tool. If possible, patients at high risk are given their first dose of enoxaparin before leaving the emergency room. If other injuries preclude enoxaparin, then chemoprophylaxis is held for 24 hours. Twenty-four hours after arrival, the patient's ability to receive enoxaparin is reassessed. If possible, enoxaparin is started, with dosing twice a day. If enoxaparin is still contraindicated, a removable inferior vena cava filter is placed. Adequacy of enoxaparin dosing is tested using anti-factor Xa assay, drawn 4 hours after the third dose of enoxaparin. If the anti-factor Xa result is less than 0.2 IU/mL, a removable inferior vena cava filter is placed. If the result is 0.2–0.5 IU/mL, enoxaparin dosing is continued. If greater than 0.5 IU/mL, the dose of enoxaparin is reduced.

Outcome Measure:
The main outcome measure was rate of PE.

Results:
From September 1, 2015 to December 31, 2015, our hospital admitted 420 orthopaedic trauma patients. Fifty-one patients were classed as high risk for PE. In September through December 2015, 9 sustained PE, 1 of which was fatal. From September 1, 2016 to December 31, 2016, our hospital admitted 368 orthopaedic trauma patients with comparable age and Injury Severity Score to 2015. Forty patients were at high risk for PE, 1 sustained a nonfatal PE. PE incidence from September to December 2016 was significantly lower than in 2015 (P = 0.02). Overall, 26 patients managed under the new protocol had IVCFs placed, 21 had their filters removed, and 3 died with filters in place. There were no complications during filter placement or removal. One patient had hemorrhage felt to be attributable to enoxaparin.

Conclusions:
Our protocol emphasizes more robust enoxaparin dosing, and more frequent use of IVCF, but only among those at high risk. We lessened the incidence of PE, with a low complication rate.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Role of immunotherapy in stage III nonsmall cell lung cancer
Authors: Wrona Anna 
Published: November 2018

Purpose of review
Despite aggressive treatment based on definitive chemoradiotherapy, 5-year overall survival in unresectable stage III nonsmall cell lung cancer remains poor (15–20%). The novel immunotherapy based on immune checkpoint inhibitors (ICIs) presents as the therapeutic ‘Holly Grail’ in lung cancer treatment.

Recent findings
Preclinical models provide evidence of immunotherapy–radiotherapy (IM-RT) synergy. The exposure to ionizing radiation turns tumor in an in-situ vaccine, primes the innate immune system, increases immunotherapy efficacy by overcoming the immunosuppressive microenvironment of immune-resistant tumors and promotes a systemic, out-of-field antitumor T-cell-mediated response called abscopal effect. The immunomodulatory and abscopal effects of radiotherapy can be further enhanced by combining with systemic immunotherapies. The phase III START trial proved that liposomal vaccine – tecemotide (L-BLP25) administered as maintenance therapy after concurrent chemoradiotherapy (CRT) in LA-NSCLC prolongs survival. In the phase III PACIFIC trial consolidation with durvalumab, an anti-PDL-1 antibody, was associated with survival benefit in patients diagnosed with LA-NSCLC who responded to concurrent chemoradiotherapy.

Summary
PACIFIC trial results are expected to definitely establish durvalumab as standard consolidation strategy in LA-NSCLC. Many clinical trials are ongoing in the field of immunoradiotherapy in LA-NSCLC to define the optimal conditions for this therapeutic combination.
Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper
Authors: Herpain Antoine , Bouchez Stefaan , Girardis Massimo , Guarracino Fabio , Knotzer Johann , Levy Bruno , Liebregts Tobias , Pollesello Piero , Ricksten Sven-Erik , Riha Hynek , Rudiger Alain , Sangalli Fabio 
Published: November 2018

Abstract:
Levosimendan is an inodilator that promotes cardiac contractility primarily through calcium sensitization of cardiac troponin C and vasodilatation via opening of adenosine triphosphate–sensitive potassium (KATP) channels in vascular smooth muscle cells; the drug also exerts organ-protective effects through a similar effect on mitochondrial KATP channels. This pharmacological profile identifies levosimendan as a drug that may have applications in a wide range of critical illness situations encountered in intensive care unit medicine: hemodynamic support in cardiogenic or septic shock; weaning from mechanical ventilation or from extracorporeal membrane oxygenation; and in the context of cardiorenal syndrome. This review, authored by experts from 9 European countries (Austria, Belgium, Czech republic, Finland, France, Germany, Italy, Sweden, and Switzerland), examines the clinical and experimental data for levosimendan in these situations and concludes that, in most instances, the evidence is encouraging, which is not the case with other cardioactive and vasoactive drugs routinely used in the intensive care unit. The size of the available studies is, however, limited and the data are in need of verification in larger controlled trials. Some proposals are offered for the aims and designs of these additional studies.
Effect of a 30-Month Health-Promoting Program on the Prevalence of Cardiovascular Risk Factors in Patients With First Episode Schizophrenia
Authors: Søgaard Hans J. , Højlund Mikkel , Elliott Anja , Viuff Anne G. , Vandborg Kirsten , Viuff Jakob , Munk-Jørgensen Povl , Hjorth Peter 
Published: November 2018

Background:
Lifestyle interventions aimed at reducing cardiovascular risk factors in patients with first-episode schizophrenia (FES) have shown modest efficacy, probably owing to a short observation period and the presumption of linear trajectories of cardiovascular risk factors.

Study Question:
How prevalent are abnormal cardiovascular values in patients with FES and how do cardiovascular risk factors develop during a 30-month program?

Study Design:
A 30-month naturalistic longitudinal study of 136 consecutively referred patients with FES from 2 outpatient clinics. The health-promoting program consisted of individual guidance, group sessions, and normal treatment and care.

Measures and Outcomes:
The prevalence of abnormal cardiovascular risk factors (body mass index, waist circumference (WC), body fat percentage, systolic and diastolic blood pressure, pulse, total cholesterol, high- and low-density lipoproteins, triglycerides, mean glucose, and visceral adiposity index) was estimated at index. The cardiovascular risk factor trajectories were analyzed with longitudinal mixed-effect models.

Results:
The patient with FES showed elevated cardiovascular risk factors at index. Thus, 56.8% of the patients were overweight in different grades and 50.4% had increased WC. A total of 81.8% had high level of body fat and hypertension prevalence with only 20% with normal blood pressure. Important changes during the intervention period were that the risk factors weight and WC were increasing the first 581 and 646 days, after which they decreased. Almost all cardiovascular risk factors worsened initially, improving after 1–2 years.

Conclusions:
Patients with FES show increases in cardiovascular risk factors at index. Short observation periods and the presumption of linear trajectories may indicate that the effect of health-promoting programs is ineffective, as the effects are curvilinear and improvements appear only after 1 year. The implication clinically is the importance of a long intervention period regarding lifestyle modifications to ascertain improvement among patients with FES.
Models of Care—There Is More Than One Way to Deliver
Authors: Sironi Giovanna , Barr Ronald D. , Ferrari Andrea 
Published: November 2018

Abstract
Adolescents and young adults (AYAs) with cancer constitute a particular group of patients with unique features, whose needs during and after treatment are poorly met. A standardized model of care for them has yet to be established, as neither the pediatric nor the adult oncology systems seamlessly fit their needs. Regardless of the setting in which they are treated, their health care providers should be aware of the impact that the disease and its treatments have on these especially vulnerable patients. Simple ways of improving the AYA experience should be considered: reducing isolation through connections with peers, adapting the staff's approach to the emotional and developmental needs of this age group, and modifying the hospital environment making it more age appropriate. Commitment of national governments is valuable; building and sharing international experience will accelerate advances in clinical care, education, and research. Further progress in the care of AYA cancer patients is still needed to improve their outcomes.
Intraoral Endoscopic Ligation of Maxillary Artery in the Infratemporal Fossa
Authors: Polev Georgiy A. , Carrau Ricardo L. , Golbin Denis A. , Avdeeva Klementina S. , Grachev Nickolai S. , Vorozhtsov Igor N. , Lasunin Nikolay V. , Cherekaev Vasily A. , Salas Galicia Juan Eugenio 
Published: November 2018

Abstract
Ligation of the sphenopalatine and posterior nasal arteries is indicated for posterior epistaxis as initial treatment or when conservative measures fail. In some patients, a transnasal approach or its alternative transantral approach are not possible due to tumor filling the nasal corridor, pterygopalatine fossa, or maxillary sinus. Aim of this study was to evaluate feasibility of endoscopically assisted transoral approach for the ligation of the maxillary artery (MA). Six fresh cadaver specimens (12 sides), previously prepared with intravascular injections of colored latex, were dissected. A combined transnasal and transoral approach exposed the MA from the deep belly of the temporalis muscle laterally to its terminal branches medially. Anatomical relationships of the MA with the deep belly of the temporalis muscle and the lower head of the lateral pterygoid muscle, and feasibility of access to the MA via a transoral approach were assessed. In all specimens, the MA was found at the point where horizontal fibers of the lower head of the lateral pterygoid muscle cross the vertical fibers of the deep belly of the temporalis muscle. In 5 specimens, the artery ran anteriorly and laterally to lower head of the lateral pterygoid muscle, and in 1 specimen, it ran posteriorly and medially to this muscle, diving between its fibers. The modified endoscopically assisted transoral approach is feasible to ligate the MA. It can be used for proximal vascular control in cases when transnasal and transantral approaches are not viable.
MR-TRYX: A Mendelian randomization framework that exploits horizontal pleiotropy to infer novel causal pathways
Authors: Cho Yoonsu , Haycock Philip C , Sanderson Eleanor , Gaunt Tom R , Zheng Jie , Morris Andrew P , Smith George Davey , Hemani Gibran 
Published: November 2018

AbstractIn Mendelian randomization (MR) analysis, variants that exert horizontal pleiotropy are typically treated as a nuisance. However, they could be valuable in identifying novel pathways to the traits under investigation. Here, we developed the MR-TRYX framework, following the advice of William Bateson to “TReasure Your eXceptions”. We begin by detecting outliers in a single exposure-outcome MR analysis, hypothesising they are due to horizontal pleiotropy. We search across thousands of complete GWAS summary datasets in the MR-Base database to systematically identify other (“candidate”) traits that associate with the outliers. We developed a multi-trait pleiotropy model of the heterogeneity in the exposure-outcome analysis due to pathways through candidate traits. Through detailed investigation of several causal relationships, many pleiotropic pathways were uncovered with already established causal effects, validating the approach, but also novel putative causal pathways. Adjustment for pleiotropic pathways reduced the heterogeneity across the analyses.
Object visibility, not energy expenditure, accounts for spatial biases in human grasp selection
Authors: Maiello Guido , Paulun Vivian C. , Klein Lina K. , Fleming Roland W. 
Published: November 2018

AbstractHumans exhibit spatial biases when grasping objects. These biases may be due to actors attempting to shorten their reaching movements and therefore minimize energy expenditures. An alternative explanation could be that they arise from actors attempting to minimize the portion of a grasped object occluded from view by the hand. We re-analyze data from a recent study, in which a key condition decouples these two competing hypotheses. The analysis reveals that object visibility, not energy expenditure, most likely accounts for spatial biases observed in human grasping.
Diffusion MRI Indices and their Relation to Cognitive Impairment in Brain Aging: The updated multi-protocol approach in ADNI3
Authors: Zavaliangos-Petropulu Artemis , Nir Talia M. , Thomopoulos Sophia I. , Reid Robert I. , Bernstein Matt A. , Borowski Bret , Jack Clifford R. , Weiner Michael W. , Jahanshad Neda , Thompson Paul M. ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: November 2018

AbstractBrain imaging with diffusion-weighted MRI (dMRI) is sensitive to microstructural white matter changes associated with brain aging and neurodegeneration. In its third phase, the Alzheimer’s Disease Neuroimaging Initiative (ADNI3) is collecting data across multiple sites and scanners using different dMRI acquisition protocols, to better understand disease effects. It is vital to understand when data can be pooled across scanners, and how the choice of dMRI protocol affects the sensitivity of extracted measures to differences in clinical impairment. Here, we analyzed ADNI3 data from 317 participants (mean age: 75.4±7.9 years; 143 men/174 women), who were each scanned at one of 47 sites with one of six dMRI protocols using scanners from three different manufacturers. We computed four standard diffusion tensor imaging (DTI) indices including fractional anisotropy (FADTI) and mean, radial, and axial diffusivity, and one FA index based on the tensor distribution function (FATDF), in 24 bilaterally averaged white matter regions of interest. We found that protocol differences significantly affected dMRI indices, in particular FADTI. We ranked the diffusion indices for their strength of association with four clinical assessments. In addition to diagnosis, we evaluated cognitive impairment as indexed by three commonly used screening tools for detecting dementia and Alzheimer’s disease: the Alzheimer’s Disease Assessment Scale (ADAS-cog), the Mini-Mental State Examination (MMSE), and the Clinical Dementia Rating scale sum-of-boxes (CDR-sob). Using a nested random-effects model to account for protocol and site, we found that across all dMRI indices and clinical measures, the hippocampal-cingulum and fornix (crus) / stria terminalis regions most consistently showed strong associations with clinical impairment. Overall, the greatest effect sizes were detected in the hippocampal-cingulum and uncinate fasciculus for associations between axial or mean diffusivity and CDR-sob. FATDF detected robust widespread associations with clinical measures, while FADTI was the weakest of the five indices for detecting associations. Ultimately, we were able to successfully pool dMRI data from multiple acquisition protocols from ADNI3 and detect consistent and robust associations with clinical impairment and age.
The Fate of Glutamine in Human Metabolism. The interplay with glucose in proliferating cells
Authors: Mazat Jean-Pierre , Ransac Stéphane 
Published: November 2018

AbstractGenome-scale models of metabolism (GEM) are used to study how metabolism varies in different physiological conditions. However, the great number of reactions involved in GEM makes it difficult to understand these variations. In order to have a more understandable tool, we developed a reduced metabolic model of central carbon and nitrogen metabolism, C2M2N with 77 reactions, 54 internal metabolites and 3 compartments, taking into account the actual stoichiometry of the reactions, including the stoichiometric role of the cofactors and the irreversibility of some reactions. In order to model OXPHOS functioning, the proton gradient through the inner mitochondrial membrane is represented by two pseudo-metabolites DPH (ΔpH) and DPSI (Δψ).To illustrate the interest of such a reduced and quantitative model of metabolism in mammalian cells, we used Flux Balance Analysis (FBA), to study all the possible fates of glutamine in metabolism. Our analysis shows that glutamine can supply carbon sources for cell energy production and can be used as carbon and nitrogen sources to synthesize essential metabolites. Finally, we studied the interplay between glucose and glutamine for the formation of cell biomass according to ammonia microenvironment. We then propose a quantitative analysis of the Warburg effect.
Systematic Allelic Analysis Defines the Interplay of Key Pathways in X Chromosome Inactivation
Authors: Nesterova Tatyana B , Wei Guifeng , Coker Heather , Pintacuda Greta , Bowness Joseph S , Zhang Tianyi , Almeida Mafalda , Bloechl Bianca , Moindrot Benoit , Carter Emma J , Rodrigo Ines Alvarez , Pan Qi , Bi Ying , Song Chun-Xiao , Brockdorff Neil 
Published: November 2018

AbstractXist RNA, the master regulator of X chromosome inactivation, acts in cis to induce chromosome silencing through the stepwise recruitment of factors that modify underlying chromatin structure. Whilst considerable progress has been made towards defining key silencing factors and the elements to which they bind, their relative contribution to silencing different genes, and their relationship with one another is poorly understood. Here we describe a systematic analysis of Xist-mediated allelic silencing in ES cell-based models. We show that Spen, recruited through the Xist A-repeat, plays a central role, being critical for silencing of all except a subset of weakly expressed genes. Polycomb, recruited through the Xist B/C-repeat, also plays a key role, favouring silencing of genes with pre-existing H3K27me3 chromatin. LBR and the Rbm15/ m6A-methyltransferase complex, previously proposed to have a central role, make at most a minor contribution to gene silencing. We integrate our findings in a comprehensive model for Xist-mediated chromosome silencing.
Growth disrupting mutations in epigenetic regulatory molecules are associated with abnormalities of epigenetic aging
Authors: Jeffries Aaron R , Maroofian Reza , Salter Claire G. , Chioza Barry A. , Cross Harold E. , Patton Michael A. , Temple I. Karen , Mackay Deborah , Rezwan Faisal I. , Aksglæde Lise , Baralle Diana , Dabir Tabib , Hunter Matthew Frank , Kamath Arveen , Kumar Ajith , Newbury-Ecob Ruth , Selicorni Angelo , Springer Amanda , Maldergem Lionel van , Varghese Vinod , Yachelevich Naomi , Tatton-Brown Katrina , Mill Jonathan , Crosby Andrew H. , Baple Emma 
Published: November 2018

AbstractGermline mutations in fundamental epigenetic regulatory molecules including DNA methyltransferase 3A (DNMT3A) are commonly associated with growth disorders, whereas somatic mutations are often associated with malignancy. We profiled genome-wide DNA methylation patterns inDNMT3Ac.2312G>A; p.(Arg771Gln) carriers in a large Amish sibship with Tatton-Brown-Rahman syndrome (TBRS), their mosaic father and 15 TBRS patients with distinct pathogenic de novoDNMT3Avariants. This defined widespread DNA hypomethylation at specific genomic sites enriched at locations annotated to genes involved in morphogenesis, development, differentiation, and malignancy predisposition pathways. TBRS patients also displayed highly accelerated DNA methylation aging. Notably, these findings were most striking in a carrier of the AML associated driver mutation p.Arg882Cys. Our studies additionally defined phenotype related accelerated and decelerated epigenetic aging in two histone methyltransferase disorders; NSD1 Sotos syndrome overgrowth disorder and KMT2D Kabuki syndrome growth impairment. Together, our findings provide fundamentally new insights into aberrant epigenetic mechanisms, the role of epigenetic machinery maintenance and determinants of biological aging in these growth disorders.
Worldwide phylogeography and history of wheat genetic diversity
Authors: Balfourier François , Bouchet Sophie , Robert Sandra , Oliveira Romain De , Rimbert Hélène , Kitt Jonathan , Choulet Frédéric ,   International Wheat Genome Sequencing Consortium,   BreedWheat Consortium, Paux Etienne 
Published: November 2018

AbstractSince its domestication in the Fertile Crescent ~8,000 to 10,000 years ago, wheat has undergone a complex history of spread, adaptation and selection. To get better insights into the wheat phylogeography and genetic diversity, we describe allele distribution through time using a set of 4,506 landraces and cultivars originating from 105 different countries genotyped with a high-density SNP array. Although the genetic structure of landraces is collinear to ancient human migration roads, we observe a reshuffling through time, related to breeding programs, with the apparition of new alleles enriched with structural variations that may be the signature of introgressions from wild relatives after 1960.One Sentence SummaryA phylogeographical study reveals the complex history of wheat genetic diversity through time and space.
Identification of slow-cycling germline stem cells and their regulation by PLZF
Authors: Sharma Manju , Srivastava Anuj , Fairfield Heather E. , Bergstrom David , Flynn William F. , Braun Robert E 
Published: November 2018

ABSTRACTLong-term maintenance of spermatogenesis in mammals is supported by GDNF, an essential growth factor required for spermatogonial stem cell (SSC) self-renewal. Exploiting a transgenic GDNF overexpression model, which expands and normalizes the pool of undifferentiated spermatogonia between Plzf+/+ and Plzflu/lu mice, we used RNAseq to identify a rare subpopulation of cells that express EOMES, a T-box transcription factor. Lineage tracing and busulfan challenge show that these are long-term SSCs that contribute to steady state spermatogenesis as well as regeneration following chemical injury. EOMES+ SSCs have a lower proliferation index than EOMES− GFRA1+ spermatogonia in wild-type but not in Plzflu/lu mice. This comparison demonstrates that PLZF regulates their proliferative activity and suggests that EOMES+ SSCs are lost through proliferative exhaustion in Plzflu/lu mice. Single cell RNA sequencing of EOMES+ cells from Plzf+/+ and Plzflu/lu mice support a hierarchical model of both slow- and rapid-cycling SSCs.