bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative administration of the 5-HT4 receptor agonist prucalopride reduces intestinal inflammation and shortens postoperative ileus via cholinergic enteric neurons
Authors: Stakenborg Nathalie , Labeeuw Evelien , Gomez-Pinilla Pedro J , De Schepper Sebastiaan , Aerts Raymond , Goverse Gera , Farro Giovanna , Appeltans Iris , Meroni Elisa , Stakenborg Michelle , Viola Maria Francesca , Gonzalez-Dominguez Erika , Bosmans Goele , Alpizar Yeranddy A , Wolthuis Albert , D’Hoore Andre , Van Beek Kim , Verheijden Simon , Verhaegen Marleen , Derua Rita , Waelkens Etienne , Moretti Milena , Gotti Cecilia , Augustijns Patrick , Talavera Karel , Vanden Berghe Pieter , Matteoli Gianluca , Boeckxstaens Guy E 
Published: November 2018

ObjectivesVagus nerve stimulation (VNS), most likely via enteric neurons, prevents postoperative ileus (POI) by reducing activation of alpha7 nicotinic receptor (α7nAChR) positivemuscularismacrophages (mMφ) and dampening surgery-induced intestinal inflammation. Here, we evaluated if 5-HT4 receptor (5-HT4R) agonist prucalopride can mimic this effect in mice and human.DesignUsing Ca2+imaging, the effect of electrical field stimulation (EFS) and prucalopride was evaluated in situ on mMφ activation evoked by ATP in jejunalmuscularistissue. Next, preoperative and postoperative administration of prucalopride (1–5 mg/kg) was compared with that of preoperative VNS in a model of POI in wild-type and α7nAChR knockout mice. Finally, in a pilot study, patients undergoing a Whipple procedure were preoperatively treated with prucalopride (n=10), abdominal VNS (n=10) or sham/placebo (n=10) to evaluate the effect on intestinal inflammation and clinical recovery of POI.ResultsEFS reduced the ATP-induced Ca2+response of mMφ, an effect that was dampened by neurotoxins tetrodotoxin and ω-conotoxin and mimicked by prucalopride. In vivo, prucalopride administered before, but not after abdominal surgery reduced intestinal inflammation and prevented POI in wild-type, but not in α7nAChR knockout mice. In humans, preoperative administration of prucalopride, but not of VNS, decreasedIl6andIl8expression in themuscularis externaand improved clinical recovery.ConclusionEnteric neurons dampen mMφ activation, an effect mimicked by prucalopride. Preoperative, but not postoperative treatment with prucalopride prevents intestinal inflammation and shortens POI in both mice and human, indicating that preoperative administration of 5-HT4R agonists should be further evaluated as a treatment of POI.Trial registration numberNCT02425774.
Optimal duration and predictors of diagnostic utility of patient-activated ambulatory ECG monitoring
Authors: Tan Eugene S J , Seow Swee-Chong , Kojodjojo Pipin , Singh Devinder , Yeo Wee Tiong , Lim Toon Wei 
Published: November 2018

ObjectiveWe studied the optimal duration of ambulatory event monitors for symptomatic patients and the predictors of detected events.MethodsPatients with palpitations or dizziness received a patient-activated handheld event monitor which records 30 s single-lead ECG strips. Patients were monitored in an ambulatory setting for a range of 1–4 weeks and ECG strips interpreted by five independent electrophysiologists. Event pick-up rates and clinical covariates were analysed.ResultsOf 335 consecutive adults (age 50±16 years, 58% female) with palpitations (94%) and dizziness (25%) monitored, 286 patients (85%) reported events, and clinically significant events were detected in 86 (26%) patients. Of these 86 patients, 26% had ≥2 significant events, and 73% had events detected in the first 3 days. No significant events were detected after 12 days. The most common ECG abnormalities detected were premature ventricular ectopy (38%), premature atrial ectopy (37%) and atrial fibrillation (AF)/atrial flutter (34%). A history of AF (adjusted OR (AOR) 4.2, 95% CI 1.1 to 15.8), previous arrhythmia (AOR 2.8, 95% CI 2.3 to 5.9) and previous abnormal ambulatory monitoring (AOR 3.4, 95% CI 1.0 to 9.4) were associated with detection of clinically significant events. Patients older than 50 years were 82% more likely to have a clinically significant event (OR 1.8, 95% CI 1.3 to 3.6).ConclusionPatient-activated ambulatory event monitoring for 7 days may be sufficient in the diagnosis of symptomatic patients as significant events first detected beyond 10 days were rare. Patients with a history of AF, arrhythmia or previous abnormal ambulatory monitoring may require even shorter monitoring periods.
Motorcycle taxi programme increases safe riding behaviours among its drivers in Kampala, Uganda
Authors: Muni Kennedy , Kobusingye Olive , Mock Charles , Hughes James P , Hurvitz Philip M , Guthrie Brandon 
Published: November 2018

BackgroundSafeBodais a motorcycle taxi company that provides road safety training and helmets to its drivers in Kampala, Uganda. We sought to determine whetherSafeBodadrivers are more likely to engage in safe riding behaviours than regular drivers (motorcycle taxi drivers not part ofSafeBoda).Methods We measured riding behaviours inSafeBodaand regular drivers through: (1) computer-assisted personal interview (CAPI), where 400 drivers were asked about their riding behaviours (eg, helmet and mobile phone use) and (2) roadside observation, where riding behaviours were observed in 3000 boda-boda drivers and their passengers along major roads in Kampala.ResultsAcross the two cross-sectional studies, a higher proportion ofSafeBodadrivers than regular drivers engaged in safe riding behaviours. For instance, helmet use amongSafeBodacompared with regular drivers was 21% points higher (95% CI 0.15 to 0.27; p<0.001) based on the CAPI and 45% points higher (95% CI 0.43 to 0.47; p<0.001) based on roadside observation. Furthermore, compared with regular drivers,SafeBodadrivers were more likely to report having a driver’s license (66.3% vs 33.5 %; p<0.001) and a reflective jacket (99.5% vs 50.5 %; p<0.001) and were less likely to report driving towards oncoming traffic (4% vs 45.7 %; p<0.001) in the past 30 days.ConclusionTheSafeBodaprogramme is associated with increased safe riding behaviours among motorcycle taxi drivers in Kampala. Therefore, the promotion and expansion of such programmes may lead to a reduction in morbidity and mortality due to road injuries.
Screening of BRCA1/2 deep intronic regions by targeted gene sequencing identifies the first germline BRCA1 variant causing pseudoexon activation in a patient with breast/ovarian cancer
Authors: Montalban Gemma , Bonache Sandra , Moles-Fernández Alejandro , Gisbert-Beamud Alexandra , Tenés Anna , Bach Vanessa , Carrasco Estela , López-Fernández Adrià , Stjepanovic Neda , Balmaña Judith , Diez Orland , Gutiérrez-Enríquez Sara 
Published: November 2018

BackgroundGenetic analysis of BRCA1 and BRCA2 for the diagnosis of hereditary breast and ovarian cancer (HBOC) is commonly restricted to coding regions and exon-intron boundaries. Although germline pathogenic variants in these regions explain about ~20% of HBOC cases, there is still an important fraction that remains undiagnosed. We have screened BRCA1/2 deep intronic regions to identify potential spliceogenic variants that could explain part of the missing HBOC susceptibility.MethodsWe analysed BRCA1/2 deep intronic regions by targeted gene sequencing in 192 high-risk HBOC families testing negative for BRCA1/2 during conventional analysis. Rare variants (MAF <0.005) predicted to create/activate splice sites were selected for further characterisation in patient RNA. The splicing outcome was analysed by RT-PCR and Sanger sequencing, and allelic imbalance was also determined when heterozygous exonic loci were present.ResultsA novel transcript was detected in BRCA1 c.4185+4105C>T variant carrier. This variant promotes the inclusion of a pseudoexon in mature mRNA, generating an aberrant transcript predicted to encode for a non-functional protein. Quantitative and allele-specific assays determined haploinsufficiency in the variant carrier, supporting a pathogenic effect for this variant. Genotyping of 1030 HBOC cases and 327 controls did not identify additional carriers in Spanish population.ConclusionScreening of BRCA1/2 intronic regions has identified the first BRCA1 deep intronic variant associated with HBOC by pseudoexon activation. Although the frequency of deleterious variants in these regions appears to be low, our study highlights the importance of studying non-coding regions and performing comprehensive RNA assays to complement genetic diagnosis.
Medina embolization device for the treatment of intracranial aneurysms: 18 months’ angiographic results
Authors: Haffaf Idriss , Clarençon Frédéric , Shotar Eimad , Rolla-Bigliani Claudia , Vande Perre Saskia , Mathon Bertrand , Drir Mehdi , Sourour Nader-Antoine 
Published: November 2018

Background and purposeThe Medina embolization device (MED) is a new flow disruption device combining the design of a detachable coil with an intrasaccular flow disrupter. Safety and short-term angiographic effectiveness of this device have recently been reported. However, long-term angiographic results are lacking. We report herein the 18 months’ angiographic outcome in patients treated for a wide-neck intracranial aneurysm with the MED.Materials and methodsNineteen patients (17 female, mean age 50 years) with 20 wide-neck intracranial aneurysms (six ruptured; 14 unruptured) were treated by the MED between January 2015 and June 2016. Procedure-related complications were systematically recorded; discharge and 6–9 months' follow-up modified Rankin Scale scores were assessed. Angiographic mid-term and long-term follow-up were performed with a mean delay of 6.4±1.5 months (n=16 aneurysms) and 17.7±4.2 months (n=15 aneurysms), respectively. Occlusion rates were evaluated after the procedure and at the mid-term and long-term follow-up using the Roy-Raymond scale.ResultsEmbolization with the MED was feasible in all except two cases (2/20, 10%). One per-procedural perforation was recorded (1/20, 5%) and one MED deployment failed because of the aneurysm’s shape (1/20, 5%). Three cases of thromboembolic complications were observed (3/20, 15%). Only one thromboembolic complication was responsible for clinical sequelae. Grade A occlusion rate was 61% (11/18) after the procedure, 75% at 6 months' follow-up (12/16), and 80% (12/15) at long-term follow-up. Two cases (2/18, 11%) of recanalization at mid-term were documented angiographically. No recanalization occurred between the mid-term and long-term follow-up.ConclusionMED is a hybrid embolization device, combining properties of a conventional coil with those of an intrasaccular flow disrupter. Our series focusing on long-term angiographic follow-up shows a satisfactory long-term occlusion rate. Larger series with longer angiographic follow-up times are warranted to confirm these preliminary results.
Equal performance of aspiration and stent retriever thrombectomy in daily stroke treatment
Authors: Bernsen Marie Louise Elisabeth , Goldhoorn Robert-Jan Berend , van Oostenbrugge Robert J , van Zwam Wim H , Uyttenboogaart Maarten , Roos Yvo B W E M , Hofmeijer Jeannette , Martens Jasper M 
Published: November 2018

BackgroundMechanical thrombectomy with stent retrievers has proved to be safe and effective in endovascular treatment of acute ischemic stroke. Direct aspiration has shown revascularization rates comparable to those of stent retrievers in the recent ASTER and COMPASS trials. However, the efficacy of aspiration in routine clinical practice has not yet been shown.ObjectiveTo show that aspiration has clinical and technical outcomes equal to those of stent retriever thrombectomy in daily clinical practice.MethodsWe analysed data of patients with a large vessel occlusion of the anterior circulation registered in the Dutch MR CLEAN Registry between March 2014 and June 2016. Primary outcome was functional outcome measured with the modified Rankin Scale (mRS) score. Secondary outcomes were reperfusion grade, periprocedural complication rate, and procedure duration. Association of treatment technique with functional outcome was estimated with univariable and multivariable ordinal logistic regression analysis and expressed as a common OR (cOR) for a shift towards better outcome on the mRS.ResultsAs first-line treatment, 207 of 1175 patients (17.6%) were treated with direct aspiration, and 968 (82.4%) by a stent retriever. We observed no differences in functional outcome (adjusted cOR=1.020 (95% CI 0.68 to 1.52)) and periprocedural complications. Successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2b) was similar. Duration of the procedure was shorter with aspiration (57 min (IQR 35–73) vs 70 min (IQR 47–95), p<0.0001).ConclusionDirect aspiration shows clinical outcomes equal to those of stent retriever thrombectomy in our large multicenter real-life cohort. We found no difference in complication rates and shorter procedure times for aspiration.
Dual suction Headway27 microcatheter thrombectomy for the treatment of distal intracranial arterial occlusion strokes: initial experience with the micro-ADAPT technique
Authors: Crockett Matthew Thomas , Phillips Timothy John , Chiu Albert Ho Yuen 
Published: November 2018

BackgroundRecent studies suggest that the proven benefits of endovascular thrombectomy (EVT) for the treatment of large vessel occlusion (LVO) strokes are transferable to more peripheral distal vessel occlusion (DVO) strokes under certain circumstances. Safely accessing and extracting these thrombi however remains challenging, particularly in more tortuous peripheral arteries. For such cases we have utilized the dual suction Headway27 microcatheter thrombectomy, or micro-ADAPT, technique with the aim of reducing potential trauma associated with negotiating stent retrievers or large bore aspiration catheters into the peripheral intracranial vasculature. We present our experience utilizing the micro-ADAPT in the treatment of DVO strokes. We describe our technique as well as present angiographic and clinical outcomes.MethodsA retrospective review of our institution’s prospectively collected EVT registry for the 12 months spanning July 2017 to June 2018 was undertaken. Data on all cases of micro-ADAPT EVT were collected and analyzed.ResultsMicro-ADAPT EVT was performed 14 times over the study period, with a recanalization rate of 79%. DVO strokes in multiple locations were treated, including the A3, M3, P3, and superior cerebellar artery. In cases where an LVO stroke was also present, the mean duration between primary LVO recanalization and secondary DVO micro-ADAPT recanalization was 15.5 min. No complications relating to the micro-ADAPT technique were recorded. No infarcts were present in the territory of the recanalized DVO stroke on day 1 CT in successful micro-ADAPT casesConclusionsIn the setting of challenging peripheral DVO strokes, the micro-ADAPT technique appears to be a fast and effective technique with a low complication rate.
Agatston score of the descending aorta is independently associated with coronary events in a low-risk population
Authors: Dudink Elton A M P , Peeters Frederique E C M , Altintas Sibel , Heckman Luuk I B , Haest Rutger J , Kragten Hans , Kietselaer Bas L J H , Wildberger Joachim , Luermans Justin G L M , Weijs Bob , Crijns Harry J G M 
Published: November 2018

ObjectivesA standard coronary artery calcium scan includes part of the aorta. This additional information is often not included in routine analyses. We aimed to determine the feasibility of assessing the Agatston score of the descending aorta calcification (DAC) on standard coronary calcium scans and the association of this score with coronary events in a low-risk study population.MethodsBetween January 2008 and March 2011, 390 consecutive patients who were referred for cardiac CT as part of work-up for pulmonary vein isolation (n=115) or assessment of presence of coronary artery disease (n=275) were included. At baseline, all patients were free of a history of cardiovascular disease. Two independent observers determined the Agatston score of the ascending aorta and descending aorta.ResultsA total of 16 patients (4.1%) developed coronary events (acute coronary syndrome (n=6) and symptomatic significant coronary artery disease requiring treatment (n=10)) during a follow-up of 67±12 months, with more events in patients with calcifications in the descending aorta than in those without (8.4% vs 3.7 %; p=0.08). Multivariable Cox regression, corrected for Framingham Risk Score (FRS) and coronary Agatston score (CAC), revealed that DAC was independently associated with coronary events (per 100 units; HR: 1.06, 95% CI 1.02 to 1.09; p=0.001). DAC furthermore increased the identification of patients that will experience a coronary event (area under the curve: 0.68 for FRS only, 0.75 for FRS+CAC and 0.78 for FRS+CAC+DAC).ConclusionsThe Agatston score of the descending aorta could be included in the standard analysis of cardiac CT scans of low-risk patients since it holds valuable information for the prediction of coronary events.
Shuffles and Circuits (On Lower Bounds for Modern Parallel Computation)
Authors: Roughgarden Tim , Vassilvitskii Sergei , Wang Joshua R. 
Published: November 2018

The goal of this article is to identify fundamental limitations on how efficiently algorithms implemented on platforms such as MapReduce and Hadoop can compute the central problems in motivating application domains, such as graph connectivity problems. We introduce an abstract model of massively parallel computation, where essentially the only restrictions are that the “fan-in” of each machine is limited to
s
bits, where
s
is smaller than the input size
n
, and that computation proceeds in synchronized rounds, with no communication between different machines within a round. Lower bounds on the round complexity of a problem in this model apply to every computing platform that shares the most basic design principles of MapReduce-type systems. We prove that computations in our model that use few rounds can be represented as low-degree polynomials over the reals. This connection allows us to translate a lower bound on the (approximate) polynomial degree of a Boolean function to a lower bound on the round complexity of every (randomized) massively parallel computation of that function. These lower bounds apply even in the “unbounded width” version of our model, where the number of machines can be arbitrarily large. As one example of our general results, computing any nontrivial monotone graph property—such as connectivity—requires a super-constant number of rounds when every machine receives only a subpolynomial (in
n
) number of input bits
s
. Finally, we prove that, in two senses, our lower bounds are the best one could hope for. For the unbounded-width model, we prove a matching upper bound. Restricting to a polynomial number of machines, we show that asymptotically better lower bounds would separate
P
from
NC
1
.
Myeloablative Haploidentical Transplantation Is Superior to Chemotherapy for Patients with Intermediate-risk Acute Myelogenous Leukemia in First Complete Remission
Authors: Lv Meng , Wang Yu , Chang Ying-Jun , Zhang Xiao-Hui , Xu Lan-Ping , Jiang Qian , Jiang Hao , Lu Jin , Chen Huan , Han Wei , Wang Feng-Rong , Wang Jing-Zhi , Chen Yao , Yan Chen-Hua , Zhang Yuan-Yuan , Sun Yu-Qian , Mo Xiao-Dong , Zhu Hong-Hu , Jia Jin-Song , Zhao Ting , Wang Jing , Liu Kai-Yan , Huang Xiao-Jun 
Published: November 2018

Abstract

Purpose:
Although myeloablative HLA haploidentical hematopoietic stem cell transplantation (haplo-HSCT) following pretransplant anti-thymocyte globulin (ATG) and granulocyte colony-stimulating factor (G-CSF) stimulated grafts (ATG+G-CSF) has been confirmed as an alternative to HSCT from HLA-matched sibling donors (MSD), the effect of haplo-HSCT on postremission treatment of patients with acute myeloid leukemia (AML) with intermediate risk (int-risk AML) who achieved first complete remission (CR1) has not been defined.

Patients and Methods:
In this prospective trial, among 443 consecutive patients ages 16–60 years with newly diagnosed de novo AML with int-risk cytogenetics, 147 patients with molecular int-risk AML who achieved CR1 within two courses of induction and remained in CR1 at 4 months postremission either received chemotherapy (n = 69) or underwent haplo-HSCT (n = 78).

Results:
The 3-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher in the haplo-HSCT group than in the chemotherapy group (74.3% vs. 47.3%; P = 0.0004 and 80.8% vs. 53.5%; P = 0.0001, respectively). In the multivariate analysis with propensity score adjustment, postremission treatment (haplo-HSCT vs. chemotherapy) was an independent risk factor affecting the LFS [HR 0.360; 95% confidence interval (CI), 0.163–0.793; P = 0.011], OS (HR 0.361; 95% CI, 0.156–0.832; P = 0.017), and cumulative incidence of relapse (HR 0.161; 95% CI, 0.057–0.459; P = 0.001) either in entire cohort or stratified by minimal residual disease after the second consolidation.

Conclusions:
Myeloablative haplo-HSCT with ATG+G-CSF is superior to chemotherapy as a postremission treatment in patients with int-risk AML during CR1. Haplo-HSCT might be a first-line postremission therapy for int-risk AML in the absence of HLA-MSDs. Haplo-HSCT might be superior to chemotherapy as a first-line postremission treatment of intermediate-risk AML in CR1.
3D Growth of Cancer Cells Elicits Sensitivity to Kinase Inhibitors but Not Lipid Metabolism Modifiers
Authors: Jones Dylan T. , Valli Alessandro , Haider Syed , Zhang Qifeng , Smethurst Elizabeth A. , Schug Zachary T. , Peck Barrie , Aboagye Eric O. , Critchlow Susan E. , Schulze Almut , Gottlieb Eyal , Wakelam Michael J.O. , Harris Adrian L. 
Published: November 2018

Abstract
Tumor cells exhibit altered lipid metabolism compared with normal cells. Cell signaling kinases are important for regulating lipid synthesis and energy storage. How upstream kinases regulate lipid content, versus direct targeting of lipid-metabolizing enzymes, is currently unexplored. We evaluated intracellular lipid concentrations in prostate and breast tumor spheroids, treated with drugs directly inhibiting metabolic enzymes fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), diacylglyceride acyltransferase (DGAT), and pyruvate dehydrogenase kinase (PDHK), or cell signaling kinase enzymes PI3K, AKT, and mTOR with lipidomic analysis. We assessed whether baseline lipid profiles corresponded to inhibitors' effectiveness in modulating lipid profiles in three-dimensional (3D) growth and their relationship to therapeutic activity. Inhibitors against PI3K, AKT, and mTOR significantly inhibited MDA-MB-468 and PC3 cell growth in two-dimensional (2D) and 3D spheroid growth, while moderately altering lipid content. Conversely, metabolism inhibitors against FASN and DGAT altered lipid content most effectively, while only moderately inhibiting growth compared with kinase inhibitors. The FASN and ACC inhibitors' effectiveness in MDA-MB-468, versus PC3, suggested the former depended more on synthesis, whereas the latter may salvage lipids. Although baseline lipid profiles did not predict growth effects, lipid changes on therapy matched the growth effects of FASN and DGAT inhibitors. Several phospholipids, including phosphatidylcholine, were also upregulated following treatment, possibly via the Kennedy pathway. As this promotes tumor growth, combination studies should include drugs targeting it. Two-dimensional drug screening may miss important metabolism inhibitors or underestimate their potency. Clinical studies should consider serial measurements of tumor lipids to prove target modulation. Pretherapy tumor classification by de novo lipid synthesis versus uptake may help demonstrate efficacy.