bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and Implementation Guidelines for a Modular Spectral-Domain Optical Coherence Tomography Scanner
Authors: Atry Farid , De La Rosa Israel Jacob , Rarick Kevin R. , Pashaie Ramin
Published: February 2018

In the past decades, spectral-domain optical coherence tomography (SD-OCT) has transformed into a widely popular imaging technology which is used in many research and clinical applications. Despite such fast growth in the field, the technology has not been readily accessible to many research laboratories either due to the cost or inflexibility of the commercially available systems or due to the lack of essential knowledge in the field of optics to develop custom-made scanners that suit specific applications. This paper aims to provide a detailed discussion on the design and development process of a typical SD-OCT scanner. The effects of multiple design parameters, for the main optical and optomechanical components, on the overall performance of the imaging system are analyzed and discussions are provided to serve as a guideline for the development of a custom SD-OCT system. While this article can be generalized for different applications, we will demonstrate the design of a SD-OCT system and representative results for in vivo brain imaging. We explain procedures to measure the axial and transversal resolutions and field of view of the system and to understand the discrepancies between the experimental and theoretical values. The specific aim of this piece is to facilitate the process of constructing custom-made SD-OCT scanners for research groups with minimum understanding of concepts in optical design and medical imaging.
Physiological and Pathological Function of Serine/Arginine-Rich Splicing Factor 4 and Related Diseases
Authors: Tan Wanyan , Wang Wei , Ma Qingfeng
Published: February 2018

Serine/arginine-rich splicing factors (SRSFs) have one or two RNA recognition motifs in the N terminal and a serine/arginine-enriched domain in the C terminal. SRSFs are essential components of spliceosomes and are involved in alternative splicing, spliceosome assembly, mRNA export, and nonsense-mediated mRNA decay. The maintenance of cellular and tissue homeostasis relies on accurate alternative splicing, and various patterns of abnormal alternative splicing can cause different diseases. SRSF4 is associated with many physiological and pathological processes and has applications in the diagnosis and prognosis of specific diseases. In this review, we discuss knowledge of SRSF4 in physiological and pathological processes and highlight the applications of SRSF4 in the regulation of gene expression and associated diseases.
Irradiated Human Umbilical Vein Endothelial Cells Undergo Endothelial-Mesenchymal Transition via the Snail/miR-199a-5p Axis to Promote the Differentiation of Fibroblasts into Myofibroblasts
Authors: Yi Minxiao , Liu Bo , Tang Yang , Li Fang , Qin Wan , Yuan Xianglin
Published: February 2018

Radiation induced pulmonary fibrosis (RIPF) is one of the major side effects of radiotherapy for lung cancer. Previous studies have shown that endothelial cells and activated myofibroblasts play a key role in RIPF. However, the interaction between irradiated endothelial cells and activation of myofibroblasts has not been reported. The aim of the present study was to examine whether irradiated endothelial cells would affect the differentiation of fibroblasts into myofibroblasts in the process of RIPF. In the current study, we used a coculture system that allowed direct contact between human fetal lung fibroblasts (MRC-5) and irradiated human umbilical vein endothelial cells (HUVECs). After 24 or 48 h, cells were sorted by flow cytometry. Radiation induced endothelial-mesenchymal transition (EndMT) by significantly increasing the expression of Snail and vimentin and reducing the expression of CD31 in HUVECs. In addition, irradiation of HUVECs induced the expression of collagen type I and α-smooth muscle actin (α-SMA) in MRC-5 cells. Further investigation indicated that irradiation of HUVECs induced the differentiation of fibroblasts into myofibroblasts through the Snail/miR-199a-5p axis. We conclude that irradiated endothelial cells undergo EndMT to promote differentiation of fibroblasts into myofibroblasts via the Snail/miR-199a-5p axis.
Effective Immunotherapy in Bone Marrow Metastatic Melanoma Presenting with Disseminated Intravascular Coagulopathy
Authors: Gbadamosi Bolanle , Ezekwudo Daniel , Nayak Bhadresh , Yu Zhou , Gjorgova-Gjeorgjievski Sandra , Xie Ming , Robert Colvin , Jaiyesimi Ishmael , Huben Marianne
Published: February 2018

Malignant melanoma is responsible for the majority of skin cancer deaths and is increasing in prevalence. Bone marrow (BM) involvement by melanoma is rare in the absence of widespread visceral disease. Here, we report the case of a 30-year-old female who presented to the hospital with back pain, low-grade fever, and easy bruising. She was found to be bicytopenic and in disseminated intravascular coagulopathy (DIC). Surprisingly, BM biopsy showed extensive involvement by metastatic malignant melanoma in the absence of visceral or brain metastasis. The unique presentation of this case and the challenge of management of a potentially treatable cancer in a critically ill patient are discussed, alongside a review of published cases of metastatic melanoma in the BM and an exploration of currently available treatment options. The excellent response of our patient to combined immune checkpoint inhibitors has yet to be paralleled in the available literature.
Soil-Transmitted Helminths in Top Soils Used for Horticultural Purposes in Cape Coast, Ghana
Authors: Yawson David Oscar , Kudu Isaac Benjamin Yao , Adu Michael Osei
Published: February 2018

This paper investigated the concentrations of eggs of three helminths (roundworm, hookworm, and whipworm) in the so-called black soils used for domestic and urban landscaping, home gardening and as growth medium for potted plants and pot experiments. The black soils are largely collected from active or abandoned waste dumpsites and fallowed or vegetated idle sites in the urban fringe or rural areas. Users buy black soils from dealers. Samples of black soils used for various purposes and at different places were collected for analysis of helminth eggs. The Modified EPA Method, which combines flotation and sedimentation, was used to isolate the eggs. The results show that these black soils have substantial loads of helminth eggs, with roundworm being dominant, followed by hookworm. Mean concentrations of helminth eggs were 2.45 (roundworm), 1.38 (hookworm), and 0.25 (whipworm) g−1 soil, respectively. The helminth egg loads also declined with duration of use of the black soils. It is concluded that black soils used for horticultural purposes in Ghana can be a potential source of helminth infestation. Therefore, treatment of black soils, regulation of black soil market and use, and development of growth media industry should be important components of helminth control strategy.
Earable RCC: Development of an Earphone-Type Reliable Chewing-Count Measurement Device
Authors: Taniguchi Kazuhiro , Kondo Hisashi , Tanaka Toshiya , Nishikawa Atsushi
Published: February 2018

Gastric cancer patients having undergone gastrectomy are at a high risk of becoming malnourished owing to decreased gastric function. To prevent malnutrition, patients need to thoroughly chew a mouthful of food at least 30 times. For these gastrectomy patients requiring dietary support, we developed a chewing-count measurement device named earable RCC using an earphone-type sensor. Experiments to evaluate the performance of this device were conducted on six healthy volunteers who participated in “gum-chewing tests” and “almond-eating tests.” The precision calculated based on the results was ≥0.958, indicating that the earphone-type chewing-count measurement device could experimentally distinguish chewing from other actions. In addition, the recall calculated from the test results was ≥0.937, showing that the device does not miss chewing actions and can accurately count the number of chews with high probability at the timing of chewing. The experimental results also imply that earphone-type sensors may be used to measure swallowing, occlusal force, and tongue motion. Our future plans include clinical testing of the earphone-type chewing-count measurement device to determine its utility in patients who have undergone gastrectomy. We also intend to expand the application of this device for use in other patients to aid in dementia prevention and dietary support.
Quantifying Liver Stagnation Spleen Deficiency Pattern for Diarrhea Predominate Irritable Bowel Syndromes Using Multidimensional Analysis Methods
Authors: Huang Zhongyu , Hou Zhengkun , Liu Xianhua , Liu Fengbin , Wu Yuefeng
Published: February 2018

Objective. This study aims to offer a new approach for quantifying severity of traditional Chinese medicine pattern with multidimensional analysis methods. Methods. A scale and theoretical models were constructed based on the definition of liver stagnation spleen deficiency pattern. Clinical data of 344 IBS‐D patients from a cross‐sectional study was used for feature validation of the model. Confirmatory factor analysis was used for evaluating the models. Also, multidimensional item response model was used for assessing multidimensional psychometric properties of the scale. Results. Detecting two latent traits, the Cronbach’s alpha of the 9‐item scale was 0.745. Multidimensional model was evaluated with significant goodness of fit indices while the unidimensional model was rejected. The multidimensional item response model showed all the items had adequate discrimination. Parameters presented adequate explanation regarding mental syndromes having high factor loading on the liver stagnation factor and abdominal discomfort syndromes highly related to the spleen deficiency factor. Test information function showed that scale demonstrated the highest discrimination power among patients with moderate to high level of severity. Conclusions. The application of the multidimensional analysis methods on the basis of theoretical model construction provides a useful and rational approach for quantifying the severity of traditional Chinese medicine patterns.
A Network Pharmacology Approach to Uncover the Multiple Mechanisms of Hedyotis diffusa Willd. on Colorectal Cancer
Authors: Liu Xinkui , Wu Jiarui , Zhang Dan , Wang Kaihuan , Duan Xiaojiao , Zhang Xiaomeng
Published: February 2018

Background. As one of the most frequently diagnosed cancer diseases globally, colorectal cancer (CRC) remains an important cause of cancer‐related death. Although the traditional Chinese herb Hedyotis diffusa Willd. (HDW) has been proven to be effective for treating CRC in clinical practice, its definite mechanisms have not been completely deciphered. Objective. The aim of our research is to systematically explore the multiple mechanisms of HDW on CRC. Methods. This study adopted the network pharmacology approach, which was mainly composed of active component gathering, target prediction, CRC gene collection, network analysis, and gene enrichment analysis. Results. The network analysis showed that 10 targets might be the therapeutic targets of HDW on CRC, namely, HRAS, PIK3CA, KRAS, TP53, APC, BRAF, GSK3B, CDK2, AKT1, and RAF1. The gene enrichment analysis implied that HDW probably benefits patients with CRC by modulating pathways related to cancers, infectious diseases, endocrine system, immune system, nervous system, signal transduction, cellular community, and cell motility. Conclusions. This study partially verified and predicted the pharmacological and molecular mechanism of HDW against CRC from a holistic perspective, which will also lay a foundation for the further experimental research and clinical rational application of HDW.
Arsenic Mobility in As-Containing Soils from Geogenic Origin: Fractionation and Leachability
Authors: Martiñá-Prieto Diego , Cancelo-González Javier , Barral María Teresa
Published: February 2018

The lithogenic arsenic in soils of the Anllóns River basin (Spain) was quantified, its chemical fractions were determined, and its leachability characteristics were compared under various experimental conditions. Fifty soil samples of C horizons, sampling an area of 50 km2along the river course, were submitted to an exploratory analysis. Pseudo-total arsenic ranged between 2 and 489 mg kg−1. Arsenic leachability using the standard methods DIN 38414-S4 and TCLP was less than 0.25% of pseudo-total As. Then the effect of pH (3, 6, and 9), solid : liquid (S : L) ratio (1 : 10 and 1 : 50), phosphate (10 mM), and contact time (24 and 240 h) on arsenic mobilization was studied in nine soils with the highest As concentration. Arsenic mobilization increased at alkaline pH and lower S : L ratio; the most decisive factor was the addition of phosphate, increasing arsenic leachability up to 1,000 times, and this increased even 2.3 times when the contact time was extended from 24 hours to 240 hours. The results suggest that the mobilization of arsenic may be underestimated in short-term water leaching tests and that the environmental conditions favouring arsenic mobilization should be taken into account for a sound evaluation of the transfer risk of arsenic towards aquatic ecosystems.
High‐Fat Diet Increases HMGB1 Expression and Promotes Lung Inflammation in Mice Subjected to Mechanical Ventilation
Authors: de Souza Ana Beatriz Farias , Chírico Máira Tereza Talma , Cartelle Christiane Teixeira , de Paula Costa Guilherme , Talvani André , Cangussú Sílvia Dantas , de Menezes Rodrigo Cunha Alvim , Bezerra Frank Silva
Published: February 2018

This study aims to evaluate the effects of a high‐fat diet and mechanical ventilation on the pulmonary and systemic inflammatory response in C57BL/6 mice. Male C57BL/6 mice were divided into two groups: one received a standard diet, and the other received a high‐fat diet. After 10 weeks, the groups were further divided into two groups each: control group (CG), mechanical ventilation group (MVG), diet group (DG), and diet mechanical ventilation group (DMVG). MVG and DMVG underwent mechanical ventilation for 60 minutes. All animals were euthanized for subsequent analysis. Animals receiving a high‐fat diet presented higher body mass, adipose index, and greater adipocyte area. In the lung, the expression of HMGB1 was greater in DG and DMVG than in CG and MVG. CCL2 and IL‐22 levels in MVG and DMVG were increased compared to those in CG and DG, whereas IL‐10 and IL‐17 were decreased. Superoxide dismutase activity was higher in MVG and DMVG than in CG. Catalase activity was lower in DG than in CG, and in MV groups, it was lower than that in CG and DG. MV and obesity promote inflammation and pulmonary oxidative stress in adult C57BL/6 mice.
Position Tolerance Design Method for Array Antenna in Internet of Things
Authors: Wang Congsi , Yuan Shuai , Yang Xiaodong , Gao Wei , Zhu Cheng , Wang Zhihai , Wang Shaoxi , Peng Xuelin
Published: February 2018

The position error of array antenna significantly deteriorates the gain and sidelobe of the array, which seriously hinders the realization of high performance of communication antenna for Internet of Things (IoT). Based on the sensitivity analysis theory, the sensitivity of the array radiation field with respect to the position of the antenna element is derived. Besides, a novel design method of position tolerance for array antenna is proposed and applied to a 20 × 20 planar array. Compared with the array designed by traditional method, the gain loss is basically the same (being 0.5 dB), while the peak sidelobe level is lowered by 1.937 dB (φ = 0°)/1.586 dB (φ = 90°). Besides, the uncertainty analysis results show that the newly designed array has a much higher chance to achieve the desired performance, which fully demonstrates the innovation and effectiveness of the new method.
Analytical and Numerical Study of Soret and Dufour Effects on Double Diffusive Convection in a Shallow Horizontal Binary Fluid Layer Submitted to Uniform Fluxes of Heat and Mass
Authors: Lagra A. , Bourich M. , Hasnaoui M. , Amahmid A. , Er-Raki M.
Published: February 2018

Combined Soret and Dufour effects on thermosolutal convection induced in a horizontal layer filled with a binary fluid and subject to constant heat and mass fluxes are investigated analytically and numerically. The thresholds marking the onset of supercritical and subcritical convection are predicted analytically and explicitly versus the governing parameters. The present investigation shows that different regions exist in the N-Du plane corresponding to different parallel flow regimes. The number, the extent, and the locations of these regions depend on whether SrDu>-(1+Le2)/2Le2=f(Le) or SrDu<-(1+Le2)/2Le2. Conjugate effects of cross-phenomena on thresholds of fluid flow and heat and mass transfer characteristics are illustrated and discussed.
Acute Lymphoblastic Leukemia following Lenalidomide Maintenance for Multiple Myeloma: Two Cases with Unexpected Presentation and Good Prognostic Features
Authors: Khan Abdullah M. , Muzaffar Jameel , Murthy Hermant , Wingard John R. , Moreb Jan S.
Published: February 2018

Lenalidomide maintenance following autologous stem cell transplant (ASCT) is considered the standard of care for eligible patients with multiple myeloma (MM). A recent meta-analysis has provided additional evidence that lenalidomide maintenance is associated with a higher incidence of second primary malignancies, including both hematologic and solid malignancies. Acute lymphoblastic leukemia (ALL) as a second primary malignancy is rarely described in the literature. Herein, we describe two patients with MM treated with induction therapy, ASCT, and lenalidomide maintenance that experienced cytopenias while on maintenance. ALL was unexpectedly diagnosed on bone marrow biopsy. One patient was diagnosed on routine biopsy performed as part of requirements of the clinical trial. Both patients had B-cell ALL, without known poor risk cytogenetics, and were managed with standard induction therapies resulting in complete remission. We also reviewed the literature for similar cases of secondary ALL (sALL) in MM patients exposed to immunomodulatory drugs (IMiDs). In conclusion, persistent cytopenias in responding MM patients receiving IMiDs maintenance should be an indication for bone marrow biopsy. Patients develop sALL after median of 32.5 months (range, 20–84) from being on lenalidomide or thalidomide maintenance, often presenting with cytopenias, display low tolerance to chemotherapy, but remission can often be achieved.
Estimation of a Moving Heat Source due to a Micromilling Process Using the Modified TFBGF Technique
Authors: Ribeiro Sidney , Fernandes Ana Paula , Cunha Daniel Fernandes da , Silva Marcio Bacci da , Shan Jerry , Guimaraes Gilmar
Published: February 2018

Moving heat sources are present in numerous engineering problems as welding and machining processes, heat treatment, or biological heating. In all these cases, the heat input identification represents an important factor in the optimization of the process. The aim of this study is to investigate the heat flux delivered to a workpiece during a micromilling process. The temperature measurements were obtained using a thermocouple at an accessible region of the workpiece surface while micromilling a small channel. The analytical solution is calculated from a 3D transient heat conduction model with a moving heat source, called direct problem. The estimation of the moving heat source uses the Transfer Function Based on Green’s Function Method. This method is based on Green’s function and the equivalence between thermal and dynamic systems. The technique is simple without iterative processes and extremely fast. From the temperature on accessible regions it is possible to estimate the heat flux by an inverse procedure of the Fast Fourier Transform. A test of micromilling of 6365 aluminium alloy was made and the heat delivered to the workpiece was estimated. The estimation of the heat without use of optimization technique is the great advantage of the technique proposed.
Bilateral Conjunctival Infiltration as an Extramedullary Relapse of AML
Authors: Mozaheb Zahra , Khooei Alireza
Published: February 2018

Acute myelogenous leukemia (AML) accounts for 1.2% of all cancer deaths. Relapse is the major cause of treatment failure in acute myeloid leukemia (AML) patients. AML rarely presents as ocular manifestation in relapse or at presentation. The M4 subtype of AML is most commonly presented with extramedullary involvement. In this report, we presented a young female with AML who was diagnosed and treated for AML about 40 months ago. She did not transplant because she did not have a full-match donor. About 4 months ago, she visited with a red eye and conjunctival infiltration. She was referred to an ophthalmologist for a biopsy, and the pathology report showed the relapse of AML which was treated with systemic chemotherapy. Red eyes with subconjunctival nodules in patients with a history of previous AML should raise the suspicion for recurrent disease that warrants urgent biopsy and systemic treatment. Eye involvement with leukemia is usually responsive to systemic chemotherapy.
A Model Linking Sickle Cell Hemoglobinopathies and SMARCB1 Loss in Renal Medullary Carcinoma
Authors: Msaouel Pavlos , Tannir Nizar M. , Walker Cheryl Lyn
Published: February 2018

Renal medullary carcinoma (RMC) is a highly aggressive malignancy that predominantly afflicts young adults and adolescents with sickle hemoglobinopathies. It is characterized by complete loss of expression of the chromatin remodeler and tumor suppressor SMARCB1. Despite therapy, the outcomes of patients with RMC remain very poor, highlighting the need to understand the etiology of this cancer, and develop new diagnostic, preventive, and therapeutic strategies. A key knowledge gap in RMC biology is why sickle hemoglobinopathies predispose to the development of this cancer. We propose a model wherein the extreme conditions of hypoxia and hypertonicity of the renal medulla, combined with regional ischemia induced by red blood cell sickling, activate DNA repair mechanisms to drive deletions and translocations in SMARCB1, which is localized in a fragile region of chromosome 22. This mechanism would explain the linkage between RMC and sickle hemoglobinopathies, as well as the age dependence and predilection of RMC toward the right kidney.

Significance: This perspective proposes an integrated and testable model of renal medullary carcinoma pathogenesis. Insights provided by this model can additionally inform other malignancies arising from the renal medulla and/or associated with loss of the SMARCB1 tumor suppressor gene. Clin Cancer Res; 24(9); 2044–9. ©2018 AACR.
A Human Genome-Wide RNAi Screen Reveals Diverse Modulators that Mediate IRE1α–XBP1 Activation
Authors: Yang Zhifen , Zhang Jing , Jiang Dadi , Khatri Purvesh , Solow-Cordero David E. , Toesca Diego A.S. , Koumenis Constantinos , Denko Nicholas C. , Giaccia Amato J. , Le Quynh-Thu , Koong Albert C.
Published: February 2018

Activation of the unfolded protein response (UPR) signaling pathways is linked to multiple human diseases, including cancer. The inositol-requiring kinase 1α (IRE1α)–X-box binding protein 1 (XBP1) pathway is the most evolutionarily conserved of the three major signaling branches of the UPR. Here, we performed a genome-wide siRNA screen to obtain a systematic assessment of genes integrated in the IRE1α–XBP1 axis. We monitored the expression of an XBP1-luciferase chimeric protein in which luciferase was fused in-frame with the spliced (active) form of XBP1. Using cells expressing this reporter construct, we identified 162 genes for which siRNA inhibition resulted in alteration in XBP1 splicing. These genes express diverse types of proteins modulating a wide range of cellular processes. Pathway analysis identified a set of genes implicated in the pathogenesis of breast cancer. Several genes, including BCL10, GCLM, and IGF1R, correlated with worse relapse-free survival (RFS) in an analysis of patients with triple-negative breast cancer (TNBC). However, in this cohort of 1,908 patients, only high GCLM expression correlated with worse RFS in both TNBC and non-TNBC patients. Altogether, our study revealed unidentified roles of novel pathways regulating the UPR, and these findings may serve as a paradigm for exploring novel therapeutic opportunities based on modulating the UPR.

Implications: Genome-wide RNAi screen identifies novel genes/pathways that modulate IRE1α–XBP1 signaling in human tumor cells and leads to the development of improved therapeutic approaches targeting the UPR.

Visual Overview: http://mcr.aacrjournals.org/content/molcanres/16/5/745/F1.large.jpg. Mol Cancer Res; 16(5); 745–53. ©2018 AACR.
Tongue-Palate Contact Timing during /s/ and /z/ in English
Authors: Liker Marko , Gibbon Fiona E.
Published: February 2018

Although numerous studies have investigated supraglottal strategies for signalling voicing in fricatives, there is still no agreement about the precise characteristics of tongue-to-palate contact timing during voiced as opposed to voiceless fricatives. In this study we use electropalatography (EPG) to investigate articulatory and coarticulatory characteristics of tongue-to-palate contact timing during /s/ and /z/ in English. Five typically speaking participants, speakers of Southern British English, produced 500 trochaic words containing the intervocalic alveolar fricatives /s/ or /z/. The time between the start of the frication and the maximum contact at the place of articulation was expressed as a percentage of each fricative's total duration (time to target, TT).This measure was used to analyse articulatory and coarticulatory timing during /s/ and /z/. Data for absolute timing were also presented. The results showed that the time between the start of the frication and the maximum contact point was longer for /s/ than for /z/. This difference was consistent across speakers but was not significant for all of them. The results of the coarticulatory effects showed that the influence of vowel context on TT values for /s/ and /z/ did not differ significantly, but there was a tendency for /z/ to be more resistant to coarticulation effects than /s/.
Transvenous Lead Extraction in Adults With Congenital Heart Disease
Authors: Gourraud Jean-Baptiste , Chaix Marie-A , Shohoudi Azadeh , Pagé Pierre , Dubuc Marc , Thibault Bernard , Poirier Nancy C. , Dore Annie , Marcotte François , Mongeon François-Pierre , Asgar Anita W. , Ibrahim Réda , Khairy Paul , Mondésert Blandine
Published: February 2018

Background:

Safety and feasibility data on transvenous lead extraction (TLE) in the challenging population of adults with congenital heart disease (A-CHD) are limited. Herein, we report the results of TLE in A-CHD during a 20-year period.

Methods and Results:

All consecutive TLE procedures in A-CHD were included in a monocentric prospective registry from 1996. A total of 121 leads were extracted in 49 A-CHD (median age, 38 years; 51% men) during 71 TLE procedures. Twenty-four (49%) patients had transposition of the great arteries. Main indications for extraction were infection in 34 (48%) and lead failure in 22 (31%). A laser sheath was required for 56 (46%) leads and a femoral approach for 10 (8%). Complete TLE was achieved for 111 leads (92%). In multivariable analysis, lead duration (odds ratio, 1.02; 95% confidence interval, 1.00–1.04;
P
<0.01) and number of previous cardiac surgeries (odds ratio, 2.65; 95% confidence interval, 1.52–4.67;
P
<0.01) were predictive of TLE failure. No perioperative death or pericardial effusion was observed. Subpulmonary atrioventricular valve regurgitation increased in 8 patients (5 with transposition of the great arteries) and was independently associated with an implantable cardioverter defibrillator lead (odds ratio, 9.69; 95% confidence interval, 1.31–71.64;
P
=0.03) and valvular vegetation (odds ratio, 7.29; 95% confidence interval, 1.32–40.51;
P
=0.02). After a median of 54 (19–134) months of follow-up after the first TLE, 3 deaths occurred independently from lead management.

Conclusions:

Despite complex anatomic issues, TLE can be achieved successfully in most A-CHD using advanced extraction techniques. Subpulmonary atrioventricular valve regurgitation is a prevalent complication, particularly in patients with transposition of the great arteries.
Characteristics of Single-Loop Macroreentrant Biatrial Tachycardia Diagnosed by Ultrahigh-Resolution Mapping System
Authors: Kitamura Takeshi , Martin Ruairidh , Denis Arnaud , Takigawa Masateru , Duparc Alexandre , Rollin Anne , Frontera Antonio , Thompson Nathaniel , Massoullié Gregoire , Cheniti Ghassen , Wolf Michael , Vlachos Konstantinos , Martin Claire A. , Al Jefairi Nora , Duchateau Josselin , Klotz Nicolas , Pambrun Thomas , Sacher Frédéric , Cochet Hubert , Hocini Meleze , Haïssaguerre Michel , Maury Philippe , Jaïs Pierre , Derval Nicolas
Published: February 2018

Background:

Biatrial tachycardia (BiAT) is a rare form of atrial macroreentrant tachycardia, in which both atria form a critical part of the circuit. We aimed to identify the characteristics and precise circuits of single-loop macroreentrant BiATs.

Methods and Results:

We identified 8 patients (median age, 59.5 years old) with 9 BiATs in a cohort of 336 consecutive patients from 2 institutions who had undergone AT catheter ablation using an automatic ultrahigh-resolution mapping system. Seven of the 8 patients had a history of persistent AF ablation, including septal or anterior left atrium ablation before developing BiAT. One of the 8 patients had a history of an atrial septal patch closure with a massively enlarged right atrium. Nine ATs (median cycle length, 334 ms; median 12 561 points in the left atrium; 8814 points in the right atrium) were diagnosed as single-loop macroreentrant BiATs. We observed 3 types of BiAT (1) BiAT with a perimitral and peritricuspid reentrant circuit (n=3), (2) BiAT using the right atrium septum and a perimitral circuit (n=3), and (3) BiAT using only the left atrium and right atrium septum (n=3). Catheter ablation successfully terminated 8 of the 9 BiATs.

Conclusions:

All patients who developed BiAT had an electric obstacle on the anteroseptal left atrium, primarily from prior ablation lesions. In this situation, mapping of both atria should be considered during AT. Because 3 types of single-loop BiAT were observed, ablation strategies should be adjusted to the type of BiAT circuit.
MicroRNAs Associated With Reverse Left Ventricular Remodeling in Humans Identify Pathways of Heart Failure Progression
Authors: Shah Ravi , Ziegler Olivia , Yeri Ashish , Liu Xiaojun , Murthy Venkatesh , Rabideau Dustin , Xiao Chun Yang , Hanspers Kristina , Belcher Arianna , Tackett Michael , Rosenzweig Anthony , Pico Alexander R. , Januzzi James L. , Das Saumya
Published: February 2018

Background:

Plasma extracellular RNAs have recently garnered interest as biomarkers in heart failure (HF). Most studies in HF focus on single extracellular RNAs related to phenotypes and outcomes, and few describe their functional roles. We hypothesized that clusters of plasma microRNAs (miRNAs) associated with left ventricular (LV) remodeling in human HF would identify novel subsets of genes involved in HF in animal models.

Methods and Results:

We prospectively measured circulating miRNAs in 64 patients with systolic HF (mean age, 64.8 years; 91% men; median LV ejection fraction, 26%) with serial echocardiography (10 months apart) during medical therapy. We defined LV reverse remodeling as a 15% reduction in LV end-systolic volume index. Using principal components analysis, we identified a component associated with LV reverse remodeling (odds ratio=3.99;
P
=0.01) that provided risk discrimination for LV reverse remodeling superior to a clinical model (C statistic, 0.58 for a clinical model versus 0.71 for RNA-based model). Using network bioinformatics, we uncovered genes not previously widely described in HF regulated simultaneously by >2 miRNAs. We observed increased myocardial expression of these miRNAs during HF development in animals, with downregulation of target gene expression, suggesting coordinate miRNA–mRNA regulation. Target mRNAs were involved in autophagy, metabolism, and inflammation.

Conclusions:

Plasma miRNAs associated with LV reverse remodeling in humans are dysregulated in animal HF and target clusters of genes involved in mechanisms implicated in HF. A translational approach integrating human HF, bioinformatics, and model systems may uncover novel pathways involved in HF.

CLINICAL TRIAL REGISTRATION:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00351390
Risk of Dementia in Adults With Congenital Heart Disease
Authors: Bagge Carina N. , Henderson Victor W. , Laursen Henning B. , Adelborg Kasper , Olsen Morten , Madsen Nicolas L.
Published: February 2018

Background:

More children with congenital heart disease (CHD) are surviving to adulthood, and CHD is associated with risk factors for dementia. We compared the risk of dementia in CHD adults to that of the general population.

Methods:

In this cohort study, we used medical registries and a medical record review covering all Danish hospitals to identify adults with CHD diagnosed between 1963 and 2012. These individuals with CHD were followed from January 1, 1981, 30 years of age, or date of first CHD registration (index date for matched members of the general population cohort) until hospital diagnosis of dementia, death, emigration, or end of study (December 31, 2012). For each individual with CHD, we identified 10 members of the general population utilizing the Danish Civil Registration System matched on sex and birth year. We computed cumulative incidences and hazard ratios (HRs) of dementia, adjusting for sex and birth year.

Results:

The cumulative incidence of dementia was 4% by 80 years of age in 10 632 adults with CHD (46% male). The overall HR comparing adults with CHD with the general population cohort was 1.6 (95% confidence interval [CI], 1.3−2.0). The HR among individuals with CHD without extracardiac defects was 1.4 (95% CI, 1.1−1.8). Adults with mild-to-moderate CHD had an HR of 1.5 (95% CI, 1.1−2.0), whereas the HR was 2.0 (95% CI, 1.2−3.3) for severe CHD, including univentricular hearts. The HR for early onset dementia (<65 years of age) was 2.6 (95% CI, 1.8−3.8), whereas the late-onset HR was 1.3 (95% CI, 1.0−1.8).

Conclusions:

CHD was associated with an increased risk of dementia compared with the general population, in particular for early onset dementia. Further understanding of dementia risk in the population with CHD is a potential target for future investigation.
Downregulated Serum 14, 15-Epoxyeicosatrienoic Acid Is Associated With Abdominal Aortic Calcification in Patients With Primary Aldosteronism
Authors: Liu Pinming , Zhang Shaoling , Gao Jingwei , Lin Ying , Shi Guangzi , He Wanbing , Touyz Rhian M. , Yan Li , Huang Hui
Published: February 2018

Patients with primary aldosteronism (PA) have increased risk of target-organ damage, among which vascular calcification is an important indicator of cardiovascular mortality. 14, 15-Epoxyeicosatrienoic acid (14, 15-EET) has been shown to have beneficial effects in vascular remodeling. However, whether 14, 15-EET associates with vascular calcification in PA is unknown. Thus, we aimed to investigate the association between 14, 15-EET and abdominal aortic calcification (AAC) in patients with PA. Sixty-nine patients with PA and 69 controls with essential hypertension, matched for age, sex, and blood pressure, were studied. 14, 15-Dihydroxyeicosatrienoic acid (14, 15-DHET), the inactive metabolite from 14, 15-EET, was estimated to reflect serum 14, 15-EET levels. AAC was assessed by computed tomographic scanning. Compared with matched controls, the AAC prevalence was almost 1-fold higher in patients with PA (27 [39.1%] versus 14 [20.3%];
P
=0.023), accompanied by significantly higher serum 14, 15-DHET levels (7.18±4.98 versus 3.50±2.07 ng/mL;
P
<0.001). Plasma aldosterone concentration was positively associated with 14, 15-DHET (β=0.444;
P
<0.001). Multivariable logistic analysis revealed that lower 14, 15-DHET was an independent risk factor for AAC in PA (odds ratio, 1.371; 95% confidence interval, 1.145–1.640;
P
<0.001), especially in young patients with mild hypertension and normal body mass index. In conclusion, PA patients exibited more severe AAC, accompanied by higher serum 14, 15-DHET levels. On the contrary, decreased 14, 15-EET was significantly associated with AAC prevalence in PA patients, especially in those at low cardiovascular risk.
Effect and Safety of Morphine Use in Acute Anterior ST‐Segment Elevation Myocardial Infarction
Authors: Bonin Mickael , Mewton Nathan , Roubille Francois , Morel Olivier , Cayla Guillaume , Angoulvant Denis , Elbaz Meyer , Claeys Marc J. , Garcia‐Dorado David , Giraud Céline , Rioufol Gilles , Jossan Claire , Ovize Michel , Guerin Patrice , Bonnefoy‐Cudraz Eric , Delarche Nicolas , Coste Pierre , Vanzetto Gerald , Metge Marc , Aupetit Jean‐François , Jouve Bernard , Motreff Pascal , Tron Christophe , Labeque Jean‐Noel , Steg Philippe Gabriel , Cottin Yves , Range Grégoire , Clerc Jérome , Coussement Patrick , Prunier Fabrice , Moulin Frédéric , Roth Olivier , Belle Loïc , Dubois Philippe , Barragan Paul , Gilard Martine , Piot Christophe , Colin Patrice , De Poli Fabien , Morice Marie‐Claude , Ider Omar , Dubois‐Randé Jean‐Luc , Unterseeh Thierry , Le Breton Hervé , Béard Thierry , Blanchard Didier , Grollier Gilles , Malquarti Vincent , Staat Patrick , Sudre Arnaud , Elmer Eskil , Hansson Magnus J. , Bergerot Cyrille , Boussaha Inesse , Derumeaux Geneviève
Published: February 2018

Background

Morphine is commonly used to treat chest pain during myocardial infarction, but its effect on cardiovascular outcome has never been directly evaluated. The aim of this study was to examine the effect and safety of morphine in patients with acute anterior
ST
‐segment elevation myocardial infarction followed up for 1 year.

Methods and Results

We used the database of the CIRCUS (Does Cyclosporine Improve Outcome in ST Elevation Myocardial Infarction Patients) trial, which included 969 patients with anterior
ST
‐segment elevation myocardial infarction, admitted for primary percutaneous coronary intervention. Two groups were defined according to use of morphine preceding coronary angiography. The composite primary outcome was the combined incidence of major adverse cardiovascular events, including cardiovascular death, heart failure, cardiogenic shock, myocardial infarction, unstable angina, and stroke during 1 year. A total of 554 (57.1%) patients received morphine at first medical contact. Both groups, with and without morphine treatment, were comparable with respect to demographic and periprocedural characteristics. There was no significant difference in major adverse cardiovascular events between patients who received morphine compared with those who did not (26.2% versus 22.0%, respectively;
P
=0.15). The all‐cause mortality was 5.3% in the morphine group versus 5.8% in the no‐morphine group (
P
=0.89). There was no difference between groups in infarct size as assessed by the creatine kinase peak after primary percutaneous coronary intervention (4023±118 versus 3903±149 IU/L;
P
=0.52).

Conclusions

In anterior
ST
‐segment elevation myocardial infarction patients treated by primary percutaneous coronary intervention, morphine was used in half of patients during initial management and was not associated with a significant increase in major adverse cardiovascular events at 1 year.
Relationship Between the Ambulatory Arterial Stiffness Index and the Lower Limit of Cerebral Autoregulation During Cardiac Surgery
Authors: Obata Yurie , Barodka Viachaslau , Berkowitz Dan E. , Gottschalk Allan , Hogue Charles W. , Steppan Jochen
Published: February 2018

Background

Pulse pressure, the ambulatory arterial stiffness index (
AASI
), and the symmetric
AASI
are established predictors of adverse cardiovascular outcomes. However, little is known about their relationship to cerebral autoregulation. This study evaluated whether these markers of vascular properties relate to the lower limit of cerebral autoregulation (
LLA
).

Methods and Results

The
LLA
was determined during cardiac surgery with transcranial Doppler ultrasonography in 181 patients. All other variables were calculated from continuous intraoperative readings obtained before cardiopulmonary bypass. The
LLA
varied directly with the
AASI
(β=3.12 per 0.1 change in
AASI
,
P
<0.001) and to a lesser extent the symmetric
AASI
(β=2.02 per 0.1 change in symmetric
AASI
,
P
≤0.022), while peripheral pulse pressure was not significantly related (β=0.0,
P
>0.99). Logistic regression revealed that the likelihood of
LLA
being >65 mm Hg increased by 50% (95% confidence interval, 11%–102%,
P
=0.008) for every 0.1 increase in the
AASI
. The
AASI
was able to predict a
LLA
above certain thresholds (area under the curve receiver operating characteristic for
AASI
predicting an
LLA
>65 mm Hg: 0.60; 95% confidence interval, 0.51%–0.68%,
P
=0.043). Incorporating additional variables improved the model's predictive ability (area under the curve for
AASI
predicting a
LLA
>65 mm Hg: 0.75; 95% confidence interval, 0.68–0.82,
P
=0.036).

Conclusions

These data indicate that the
LLA
is related to the mechanical properties of the vasculature as represented by the
AASI
. The
AASI
can be used to predict
LLA
threshold levels during cardiac surgery. It is now possible to link elevations in the
LLA
with an increased
AASI
as determined from readily accessible intraoperative variables.
Conventional and Ambulatory Blood Pressure as Predictors of Diastolic Left Ventricular Function in a Flemish Population
Authors: Wei Fang‐Fei , Yang Wen‐Yi , Thijs Lutgarde , Zhang Zhen‐Yu , Cauwenberghs Nicholas , Van Keer Jan , Huang Qi‐Fang , Mujaj Blerim , Kuznetsova Tatiana , Allegaert Karel , Verhamme Peter , Staessen Jan A.
Published: February 2018

Background

No longitudinal study compared associations of echocardiographic indexes of diastolic left ventricular function studies with conventional (
CBP
) and daytime ambulatory (
ABP
) blood pressure in the general population.

Methods and Results

In 780 Flemish (mean age, 50.2 years; 51.7% women), we measured left atrial volume index (
LAVI
), peak velocities of the transmitral blood flow (E) and mitral annular movement (e′) in early diastole and E/e′ 9.6 years (median) after
CBP
and
ABP
. In adjusted models including
CBP
and
ABP
, we expressed associations per 10/5‐mm Hg systolic/diastolic blood pressure increments.
LAVI
and E/e′ were 0.65/0.40 mL/m
2
and 0.17/0.09 greater with higher systolic/diastolic
ABP
(
P
≤0.028), but not with higher baseline
CBP
(
P
≥0.086). e′ was lower (
P
≤0.032) with higher diastolic
CBP
(−0.09 cm/s) and
ABP
(−0.19 cm/s). When we substituted baseline
CBP
by
CBP
recorded concurrently with echocardiography,
LAVI
and E/e′ remained 0.45/0.38 mL/m
2
and 0.15/0.08 greater with baseline
ABP
(
P
≤0.036), while
LAVI
(+0.53 mL/m
2
) and E/e′ (+0.19) were also greater (
P
<0.001) in relation to concurrent systolic
CBP
. In categorized analyses of baseline data, sustained hypertension or masked hypertension compared with normotension or white‐coat hypertension was associated with greater
LAVI
(24.0 versus 22.6 mL/m
2
) and E/e′ (7.35 versus 6.91) and lower e′ (10.7 versus 11.6 cm/s;
P
≤0.006 for all) with no differences (
P
≥0.092) between normotension and white‐coat hypertension or between masked hypertension and sustained hypertension.

Conclusions

ABP
is a long‐term predictor of diastolic left ventricular function, statistically outperforming distant but not concurrent
CBP
. Masked hypertension and sustained hypertension carry equal risk for deterioration of diastolic left ventricular function.
Antiplatelet Therapy Changes for Patients With Myocardial Infarction With Recurrent Ischemic Events: Insights Into Contemporary Practice From the TRANSLATE‐ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) Study
Authors: Fanaroff Alexander C. , Kaltenbach Lisa A. , Peterson Eric D. , Akhter Mohammed W. , Effron Mark B. , Henry Timothy D. , Wang Tracy Y.
Published: February 2018

Background

Guidelines recommend P2Y
12
inhibitor therapy for 1 year after myocardial infarction (
MI
), yet little guidance is provided on antiplatelet management for patients with recurrent ischemic events during that year. We describe changes in P2Y
12
inhibitor type among patients with recurrent ischemic events in the first year after
MI
.

Methods and Results

The
TRANSLATE
‐
ACS
(Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study enrolled 12 365 patients with MI treated with percutaneous coronary intervention. We examined whether P2Y
12
inhibitor choice changed among patients with recurrent
MI
, stent thrombosis, and/or unplanned revascularization during the first year after
MI
, and modeled factors associated with P2Y
12
inhibitor intensification (changing clopidogrel to prasugrel or ticagrelor). In the first year after
MI
, 1414 patients (11%) had a total of 1740 recurrent ischemic events (771 recurrent
MI
s, 969 unplanned revascularizations, and 165 stent thromboses). Median time to the first recurrent ischemic event was 154 days (25th–75th percentiles, 55–287 days). Of those with recurrent ischemic events, 101 of 1092 (9.3%) occurring in clopidogrel‐treated patients led to P2Y
12
inhibitor intensification. Recurrent events involving stent thrombosis or
MI
were the strongest factors associated with P2Y
12
inhibitor intensification, yet only 40% of patients with stent thrombosis and 14% of patients with recurrent
MI
had P2Y
12
inhibitor intensification. Increasing age and longer time from the index
MI
were associated with lower likelihood for intensification.

Conclusions

Few patients after
MI
with a recurrent ischemic event who were taking clopidogrel switched to a more potent P2Y
12
inhibitor, even after stent thrombosis events. Specific guidance is needed for patients who have recurrent ischemic events, particularly when closely spaced.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier:
NCT
01088503.
Characteristics of Randomized Trials Focusing on Stroke due to Intracerebral Hemorrhage
Authors: Tamborska Arina , Poon Michael T.C. , Al-Shahi Salman Rustam
Published: February 2018

Background and Purpose—

The absence of treatments for intracerebral hemorrhage with significant consistent benefit in randomized controlled trials (RCTs) could be because of lack of treatment efficacy or the design of RCTs.

Methods—

We searched the Cochrane Stroke Group Trials Register in December 2015 for completed and published RCTs reporting clinical outcome in adults with intracerebral hemorrhage. We collected data on publication year and language, study characteristics, and effect size. We regarded RCTs to be at lower risk of bias if they performed ≥2 of describing randomization, using blinding, or specifying the primary outcome. We registered this systematic review (PROSPERO, international prospective register of systematic reviews CRD42016051103).

Results—

We found 136 eligible RCTs: 57% were phase II, 76% were single center, 98% studied acute treatments, 49% involved drug interventions, 24% were placebo-controlled, the primary outcome was death or disability in 30%, and median sample size was 77 (interquartile range, 47–160). Forty-six percent explained randomization, 24% blinded treatment allocation, and 24% specified the primary outcome such that 38 (28%) were at lower risk of bias. RCTs at lower risk of bias were more likely to use multicenter recruitment (adjusted odds ratio, 6.95; 95% confidence interval, 2.2–21.5) and be published in English (adjusted odds ratio, 12.9, 95% confidence interval, 2.7–62.5). RCTs with larger sample sizes were independently more likely to be phase III/IV (
P
<0.01) and use multicenter recruitment (
P
<0.01). RCTs at lower risk of bias had smaller pooled treatment effects on death/disability (
P
=0.02).

Conclusions—

Intracerebral hemorrhage RCTs have often been at high risk of bias, and these RCTs have been characterized by small sample sizes and larger effect sizes.