bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of general anaesthesia and non-general anaesthesia approach in transfemoral transcatheter aortic valve implantation
Authors: Eskandari Mehdi , Aldalati Omar , Dworakowski Rafal , Byrne Jonathan A , Alcock Emma , Wendler Olaf , MacCarthy Philip A , Ludman Peter F , Hildick-Smith David J R , Monaghan Mark J 
Published: March 2018

ObjectivePerforming transfemoral transcatheter aortic valve implantation (TAVI) without general anaesthesia (GA) has been increasingly adopted. We sought to study the impact of GA and non-GA approaches on procedural outcome and 30-day and 1-year mortality in transfemoral TAVI.MethodsThe UK TAVI registry holds information for every TAVI procedure in the UK. We analysed the data for patients implanted during 2013–2014 using either an Edwards Sapien or a Medtronic CoreValve prosthesis. Propensity score-matching analysis was performed to adjust for confounding factors.Results2243 patients were studied (aged 81.4±7.5 years, 1195 males). 1816 (81%) underwent TAVI with GA and 427 (19%) without GA. Transoesophageal echocardiography (TOE) was used in 92.3% of GA and 12.4% of non-GA cases (p<0.001). There was no significant difference in the rate of successful valve deployment (GA 97.2% vs non-GA 95.7%, p=0.104) and in the incidence of more than mild aortic regurgitation (AR) at the end of the procedure (GA 5.6% vs non-GA 7.0%, p=0.295). However, procedure time was longer (131±60 vs 121±60mins, p=0.002) and length of stay was greater (8.0±13.5 vs 5.7±5.5 days, p<0.001) for GA cases. 30-day and 1-year mortality rates did not differ between the GA and non-GA cases. After propensity matching, these results remained unchanged. A second propensity analysis (adjusted for mode of anaesthesia) did not show an association between use of TOE and rate of successful valve deployment or frequency of significant AR. Neither was TOE associated with a longer procedural time or greater length of stay.ConclusionProcedure outcome, and 30-day and 1-year mortality are not influenced by mode of anaesthesia. However, GA is associated with longer procedure duration and greater length of stay.
Correlation of non-vitamin K antagonist oral anticoagulant exposure and cerebral microbleeds in Chinese patients with atrial fibrillation
Authors: Soo Yannie , Abrigo Jill , Leung Kam Tat , Liu Wenyan , Lam Bonnie , Tsang Suk Fung , Ip Vincent , Ma Karen , Ip Bonaventure , Ma Sze Ho , Fan Florence , Chu Winnie , Wong Lawrence , Mok Vincent , Leung Thomas W 
Published: March 2018

Background and purposeCerebral microbleeds (CMBs) are radiological markers which predict future intracerebral haemorrhage. Researchers are exploring how CMBs can guide anticoagulation decisions in atrial fibrillation (AF). The purpose of this study is to evaluate the correlation of non-vitamin K antagonist oral anticoagulants (NOAC) exposure and prevalence of CMBs in Chinese patients with AF.MethodsWe prospectively recruited Chinese patients with AF on NOAC therapy of ≥30 days for 3T MRI brain for evaluation of CMBs and white matter hyperintensities. Patients with AF without prior exposure to oral anticoagulation were recruited as control group.ResultsA total of 282 patients were recruited, including 124 patients in NOAC group and 158 patients in control group. Mean duration of NOAC exposure was 723.8±500.3 days. CMBs were observed in 103 (36.5%) patients. No significant correlation was observed between duration of NOAC exposure and quantity of CMBs. After adjusting for confounding factors (ie, age, hypertension, labile hypertension, stroke history and white matter scores), previous intracerebral haemorrhage was predictive of CMBs (OR 15.28, 95% CI 1.81 to 129.16), particularly lobar CMBs (OR 5.37, 95% CI 1.27 to 22.6). While white matter score was predictive of mixed lobar CMBs (OR 1.65, 95% CI 1.1 to 2.5), both exposure and duration of NOAC use were not predictive of presence of CMBs.ConclusionsIn Chinese patients with AF, duration of NOAC exposure did not correlate with prevalence and burden of CMBs. Further studies with follow-up MRI are needed to determine if long-term NOAC therapy can lead to development of new CMBs.
Optimal ventilator strategies for trauma-related ARDS
Authors: Goatly Giles , Guidozzi N , Khan M 
Published: March 2018

BackgroundAcute respiratory distress syndrome (ARDS) was first described in the 1960s and has become a major area of research due to the mortality and morbidity associated with it. ARDS is currently defined using the Berlin Consensus; however, this is not wholly applicable for trauma-related ARDS.MethodsA systematic review of the literature was undertaken using the Preferred Reporting for Systematic Reviews and Meta Analyses methodology. The Ovid Medline, Web of Science and PubMed online databases were interrogated for papers published between 1 January 1995 and 31 December 2017.ResultsThe literature search yielded a total of 64 papers that fulfilled the search criteria.ConclusionsDespite decades of dedicated research into different treatment modalities, ARDS continues to carry a high burden of mortality. The ARDS definitions laid out in the Berlin consensus are not entirely suited to trauma. While trauma-related ARDS represents a small portion of the available research, the evidence continues to favour low tidal volume ventilation as the benchmark for current practice. Positive end expiratory ventilation and airway pressure release ventilation in trauma cohorts may be beneficial; however, the evidence to date does not show this.
Three-dimensional graphene as gas diffusion layer for micro direct methanol fuel cell
Authors: Zhu Yingli , Zhang Xiaojian , Li Jianyu , Qi Gary 
Published: March 2018

The gas diffusion layer (GDL), as an important structure of the membrane electrode assembly (MEA) of the direct methanol fuel cell (DMFC), provides a support layer for the catalyst and the fuel and the product channel. Traditionally, the material of GDL is generally carbon paper (CP). In this paper, a new material, namely three-dimensional graphene (3DG) is used as GDL for micro DMFC. The experimental results reveal that the performance of the DMFC has been improved significantly by application of 3DG. The peak powers increase from 25 mW to 31.2 mW and 32 mW by using 3DG as the anode and cathode GDL instead of CP, respectively. The reason may be the decrease of charge and mass transfer resistance of the cell. This means that the unique 3D porous architecture of the 3DG can provide lower contact resistance and sufficient fuel diffusion paths. The output performance of the cell will be further improved when porous metal current collectors is used.
Evidence of cosmic strings by the observation of the alignment of quasar polarization axes on Mpc scale
Authors: Slagter Reinoud Jan 
Published: March 2018

The recently found alignment of the polarization axes (PA) of quasars in large quasar groups (LQGs) on Mpc scales can be explained by general relativistic cosmic string networks. By considering the cosmic string as a result of spontaneous symmetry breaking of the gauged U(1) abelian Higgs model with topological charge [Formula: see text], many stability features of [Formula: see text]-vortex solutions of superconductivity can be taken over. Decay of the high multiplicity ([Formula: see text]) super-conducting vortex into a lattice of [Formula: see text] vortices of unit magnetic flux is energetically favorable. The temporarily broken axial symmetry will leave an imprint of a preferred azimuthal-angle on the lattice. The stability of the lattice depends critically on the parameters of the model, especially when gravity comes into play. In order to handle the strong nonlinear behavior of the time-dependent coupled field equations of gravity and the scalar-gauge field, we will use a high-frequency approximation scheme to second order on a warped 5D axially symmetric spacetime with the scalar-gauge field residing on the brane. We consider different winding numbers for the subsequent orders of perturbations of the scalar field. A profound contribution to the energy–momentum tensor comes from the bulk spacetime and can be understood as “dark”-energy. The cosmic string becomes super-massive by the contribution of the 5D Weyl tensor on the brane and the stored azimuthal preferences will not fade away. During the recovery to axial symmetry, gravitational and electro-magnetic radiation will be released. The perturbative appearance of a nonzero energy–momentum component [Formula: see text] can be compared with the phenomenon of bifurcation along the Maclaurin–Jacobi sequence of equilibrium ellipsoids of self-gravitating compact objects, signaling the onset of secular instabilities. There is a kind of similarity with the Goldstone-boson modes of spontaneously broken symmetries of continuous groups. The recovery of the SO(2) symmetry from the equatorial eccentricity takes place on a time-scale comparable with the emission of gravitational waves. The emergent azimuthal-angle dependency in our model can be used to explain the aligned PA in LQGs on Mpc scales. Spin axis direction perpendicular to the major axes of LQGs when the richness decreases can be explained as a second-order effect in our approximation scheme by the higher multiplicity terms. The preferred directions are modulo [Formula: see text], with [Formula: see text] being an integer dependent on the [Formula: see text]th order of approximation. When more data of quasars of high redshift becomes available, one could prove that the alignment emerged after the symmetry breaking scale and must have a cosmological origin. The effect of the warp factor on the second-order perturbations could also be an indication of the existence of extra large dimensions.
Mechanisms for the increased fatigability of the lower limb in people with type 2 diabetes
Authors: Senefeld Jonathon , Magill Steven B. , Harkins April , Harmer Alison R. , Hunter Sandra K. 
Published: March 2018

Fatiguing exercise is the basis of exercise training and a cornerstone of management of type 2 diabetes mellitus (T2D); however, little is known about the fatigability of limb muscles and the involved mechanisms in people with T2D. The purpose of this study was to compare fatigability of knee extensor muscles between people with T2D and controls without diabetes and determine the neural and muscular mechanisms for a dynamic fatiguing task. Seventeen people with T2D [ten men and seven women: 59.6 (9.0) yr] and twenty-one age-, body mass index-, and physical activity-matched controls [eleven men and ten women: 59.5 (9.6) yr] performed one hundred twenty high-velocity concentric contractions (one contraction/3 s) with a load equivalent to 20% maximal voluntary isometric contraction (MVIC) torque with the knee extensors. Transcranial magnetic stimulation (TMS) and electrical stimulation of the quadriceps were used to assess voluntary activation and contractile properties. People with T2D had larger reductions than controls in power during the fatiguing task [42.8 (24.2) vs. 26.4 (15.0)%; P < 0.001] and MVIC torque after the fatiguing task [37.6 (18.2) vs. 26.4 (12.1)%; P = 0.04]. People with T2D had greater reductions than controls in the electrically evoked twitch amplitude after the fatiguing task [44.0 (20.4) vs. 35.4 (12.1)%, respectively; P = 0.01]. However, the decrease in voluntary activation was similar between groups when assessed with electrical stimulation [12.1 (2.6) vs. 12.4 (4.4)% decrease; P = 0.84] and TMS ( P = 0.995). A greater decline in MVIC torque was associated with larger reductions of twitch amplitude ( r2 = 0.364, P = 0.002). Although neural mechanisms contributed to fatigability, contractile mechanisms were responsible for the greater knee extensor fatigability in men and women with T2D compared with healthy controls. NEW & NOTEWORTHY Transcranial magnetic stimulation and percutaneous muscle stimulation were used to determine the contributions of neural and contractile mechanisms of fatigability of the knee extensor muscles after a dynamic fatiguing task in men and women with type 2 diabetes (T2D) and healthy age-, body mass index-, and physical activity-matched controls. Although neural and contractile mechanisms contributed to greater fatigability of people with T2D, fatigability was primarily associated with impaired contractile mechanisms and glycemic control.
Functional Precision Medicine Identifies Novel Druggable Targets and Therapeutic Options in Head and Neck Cancer
Authors: Xu Chang , Nikolova Olga , Basom Ryan S. , Mitchell Ryan M. , Shaw Reid , Moser Russell D. , Park Heuijoon , Gurley Kay E. , Kao Michael C. , Green Carlos L. , Schaub Franz X. , Diaz Robert L. , Swan Hallie A. , Jang In S. , Guinney Justin , Gadi Vijayakrishna K. , Margolin Adam A. , Grandori Carla , Kemp Christopher J. , Méndez Eduardo 
Published: March 2018

AbstractPurpose: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with high mortality and a lack of targeted therapies. To identify and prioritize druggable targets, we performed genome analysis together with genome-scale siRNA and oncology drug profiling using low-passage tumor cells derived from a patient with treatment-resistant HPV-negative HNSCC.Experimental Design: A tumor cell culture was established and subjected to whole-exome sequencing, RNA sequencing, comparative genome hybridization, and high-throughput phenotyping with a siRNA library covering the druggable genome and an oncology drug library. Secondary screens of candidate target genes were performed on the primary tumor cells and two nontumorigenic keratinocyte cell cultures for validation and to assess cancer specificity. siRNA screens of the kinome on two isogenic pairs of p53-mutated HNSCC cell lines were used to determine generalizability. Clinical utility was addressed by performing drug screens on two additional HNSCC cell cultures derived from patients enrolled in a clinical trial.Results: Many of the identified copy number aberrations and somatic mutations in the primary tumor were typical of HPV(−) HNSCC, but none pointed to obvious therapeutic choices. In contrast, siRNA profiling identified 391 candidate target genes, 35 of which were preferentially lethal to cancer cells, most of which were not genomically altered. Chemotherapies and targeted agents with strong tumor-specific activities corroborated the siRNA profiling results and included drugs that targeted the mitotic spindle, the proteasome, and G2–M kinases WEE1 and CHK1. We also show the feasibility of ex vivo drug profiling for patients enrolled in a clinical trial.Conclusions: High-throughput phenotyping with siRNA and drug libraries using patient-derived tumor cells prioritizes mutated driver genes and identifies novel drug targets not revealed by genomic profiling. Functional profiling is a promising adjunct to DNA sequencing for precision oncology. Clin Cancer Res; 24(12); 2828–43. ©2018 AACR.
The Primitive Palmomental Reflex in Amyotrophic Lateral Sclerosis
Authors: Taiello Alfonsa Claudia , Spataro Rossella , La Bella Vincenzo 
Published: March 2018

<b><i>Background and Purpose:</i></b> The palmomental reflex (PMR) is a primitive reflex that might be released due to inhibition in adulthood. It has been associated with several neurodegenerative conditions. The aim of the present study was to evaluate the frequency of PMR in amyotrophic lateral sclerosis (ALS). <b><i>Patients and Methods:</i></b> Non-demented ALS patients (<i>n</i> = 179) were recruited. Two groups of disease controls were enrolled: (a) non-demented patients with other neurological disorders (NC;<i> n</i> = 86, mean age 60 ± 14 years); (b) healthy subjects, healthy controls (HC; <i>n</i> = 175, mean age 61 ± 12 years). PMR was elicited by a brisk stroke along the thenar eminence of the right hand with a key or a pen. <b><i>Results:</i></b> The PMR could be elicited in 46% of the ALS patients, compared to 29% of NC and 16% of HC (<i>p</i> &#x3c; 0.001). A multivariate analysis showed that bulbar-onset and female gender are associated with an increased risk of PMR. <b><i>Conclusion:</i></b> We demonstrate a higher frequency of the PMR in ALS patients compared to NC or HC. Its expression increases with age, being higher in bulbar-onset patients. Given that the reflex circuit is located in the brain stem, its release due to inhibition might be associated to the presence of a cortico-bulbar tract dysfunction in ALS.
Vitamin B12 Deficiency and the Role of Gender: A Cross-Sectional Study of a Large Cohort
Authors: Margalit Ili , Cohen Eytan , Goldberg Elad , Krause Ilan 
Published: March 2018

<b><i>Background:</i></b> Vitamin B12 deficiency is associated with hematological, neurological, and cardiovascular consequences. Epidemiologic data on these related illnesses indicate gender differences. <b><i>Methods:</i></b> A cross-sectional study was designed to examine gender differences in vitamin B12 deficiency among a healthy population. Data from healthy individuals aged 18–65, who were provided with a routine medical evaluation during 2000–2014, were retrieved from the medical charts. Individuals with background illnesses and those who had used medications or nutritional supplements were excluded. Vitamin B12 deficiency was defined by 2 cutoff values (206 and 140 pmol/L). The multivariate analysis was adjusted for age, body mass index, estimated glomerular filtration rate, hyperhomocysteinemia, folate deficiency, albumin, and transferrin saturation. Sensitivity analyses were implemented by excluding individuals with anemia, hyperhomocysteinemia, or folate deficiency and by age stratification. <b><i>Results:</i></b> In all, 7,963 individuals met the inclusion criteria. Serum vitamin B12 mean levels were 312.36 and 284.31 pmol/L for women and men respectively (<i>p</i> &#x3c; 0.001). Deficiency prevalence was greater for men (25.5%) in comparison with women (18.9%; <i>p</i> &#x3c; 0.001). Men were strongly associated with severe deficiency (adjusted OR 2.26; 95% CI 1.43–3.56). <b><i>Conclusions:</i></b> Among the healthy population, men are susceptible to vitamin B12 deficiency. This can be explained by neither diet habits nor estrogen effects. Genetic variations are therefore hypothesized to play a role.
PAR2 (Protease-Activated Receptor 2) Deficiency Attenuates Atherosclerosis in Mice
Authors: Jones Shannon M. , Mann Adrien , Conrad Kelsey , Saum Keith , Hall David E. , McKinney Lisa M. , Robbins Nathan , Thompson Joel , Peairs Abigail D. , Camerer Eric , Rayner Katey J. , Tranter Michael , Mackman Nigel , Owens A. Phillip 
Published: March 2018

Objective—
PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammation and has been implicated in the pathogenesis of several autoimmune conditions. The objective of this study was to determine the effect of PAR2 deficiency on the development of atherosclerosis.

Approach and Results—

PAR2 mRNA and protein expression is increased in human carotid artery and mouse aortic arch atheroma versus control carotid and aortic arch arteries, respectively. To determine the effect of PAR2 deficiency on atherosclerosis, male and female low-density lipoprotein receptor–deficient (
Ldlr
−/−
) mice (8–12 weeks old) that were
Par2
+/+
or
Par2
−/−
were fed a fat- and cholesterol-enriched diet for 12 or 24 weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma cholesterol concentrations or lipoprotein distributions. Bone marrow transplantation showed that PAR2 on nonhematopoietic cells contributed to atherosclerosis. PAR2 deficiency significantly attenuated levels of the chemokines
Ccl2
and
Cxcl1
in the circulation and macrophage content in atherosclerotic lesions. Mechanistic studies using isolated primary vascular smooth muscle cells showed that PAR2 deficiency is associated with reduced
Ccl2
and
Cxcl1
mRNA expression and protein release into the supernatant resulting in less monocyte migration.

Conclusions—

Our results indicate that PAR2 deficiency is associated with attenuation of atherosclerosis and may reduce lesion progression by blunting
Ccl2
- and
Cxcl1
-induced monocyte infiltration.
Deficiency of Dab2 (Disabled Homolog 2) in Myeloid Cells Exacerbates Inflammation in Liver and Atherosclerotic Plaques in LDLR (Low-Density Lipoprotein Receptor)-Null Mice—Brief Report
Authors: Adamson Samantha E. , Polanowska-Grabowska Renata , Marqueen Kathryn , Griffiths Rachael , Angdisen Jerry , Breevoort Sarah R. , Schulman Ira G. , Leitinger Norbert 
Published: March 2018

Objective—
Inflammatory macrophages promote the development of atherosclerosis. We have identified the adaptor protein Dab2 (disabled homolog 2) as a regulator of phenotypic polarization in macrophages. The absence of Dab2 in myeloid cells promotes an inflammatory phenotype, but the impact of myeloid Dab2 deficiency on atherosclerosis has not been shown.

Approach and Results—

To determine the role of myeloid Dab2 in atherosclerosis, Ldlr
−/−
mice were reconstituted with either Dab2-positive or Dab2-deficient bone marrow and fed a western diet. Consistent with our previous finding that Dab2 inhibits NFκB (nuclear factor κ-light-chain-enhancer of activated B cells) signaling in macrophages, Ldlr
−/−
mice reconstituted with Dab2-deficient bone marrow had increased systemic inflammation as evidenced by increased serum IL-6 (interleukin-6) levels and increased inflammatory cytokine expression levels in liver. Serum lipid levels were significantly lower in Ldlr
−/−
mice reconstituted with Dab2-deficient bone marrow, and further examination of livers from these mice revealed drastically increased inflammatory tissue damage and massive infiltration of immune cells. Surprisingly, the atherosclerotic lesion burden in Ldlr
−/−
mice reconstituted with Dab2-deficient bone marrow was decreased compared with Ldlr
−/−
mice reconstituted with wild-type bone marrow. Further analysis of aortic root sections revealed increased macrophage content and evidence of increased apoptosis in lesions from Ldlr
−/−
mice reconstituted with Dab2-deficient bone marrow but no difference in collagen or α-smooth muscle actin content.

Conclusions—
Dab2 deficiency in myeloid cells promotes inflammation in livers and atherosclerotic plaques in a mouse model of atherosclerosis. Nevertheless, decreased serum lipids as a result of massive inflammatory liver damage may preclude an appreciable increase in atherosclerotic lesion burden in mice reconstituted with Dab2-deficient bone marrow.