bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a Novel Cryoablation System: In vivo Testing in a Chronic Porcine Model
Authors: Weimar Timo , Lee Anson M. , Ray Shuddhadeb , Schuessler Richard B. , Damiano Ralph J. 
Published: January 2019

Objective Cryoablation is commonly used at present in the surgical treatment of atrial fibrillation (AF). However, there have been few studies examining the efficacy of the commonly used ablation devices. This report compares the efficacy of two cryoprobes in creating transmural endocardial lesions on the beating heart in a porcine model for chronic AF. Methods In six Hanford miniature swine, the right atrial appendage and the inferior vena cava were isolated using a bipolar radiofrequency clamp to create areas of known conduction block. A connecting ablation line was performed endocardially via a purse string with the novel malleable 10-cm Cryo1 probe for 2 minutes at −40°C. Additional ablation lines were created with the Cryo1 and the 3.5-cm 3011 Maze Linear probe on the right and the left atrial wall. Epicardial activation mapping was performed before and immediately after ablation as well as 14 days postoperatively. Histologic examination was performed 14 days postoperatively. Results Transmural lesions were confirmed in 83/84 cross-sections (99%) for the Cryo1 probe and in 40/41 cross-sections (98%) for the 3011 Maze Linear probe. There was no difference between the devices in lesion width (mean ± SD, Cryo1, 10.7 ± 3.5 mm; 3011, 10.0 ± 3.9mm; P = 0.31), lesion depth (Cryo1, 4.5 ± 1.7 mm; 3011, 4.6 ± 1.5 mm; P = 0.74), or atrial wall thickness (Cryo1, 4.5 ± 1.8 mm; 3011, 4.7 ± 1.7 mm; P = 0.74). There was a conduction delay across the right atrial ablation line (20 ± 2 milliseconds vs 51 ± 8 milliseconds, P < 0.001) that remained unchanged at 14 days (51 ± 8 milliseconds vs 52 ± 10 milliseconds, P = 0.88). Conclusions The Cryo1 probe created transmural lesions on the beating heart, resulting insustained conduction delay. Both probes had a similar performance in lesion geometry in this chronic animal model.
Thoracoscopic Epicardial Lead Implantation as an Alternative to Failed Endovascular Insertion for Cardiac Pacing and Resynchronization Therapy
Authors: Nesher Nahum , Ganiel Amir , Paz Yosef , Kramer Amir , Mohr Refael , Ben-Gal Yanai , Pevni Demitri 
Published: January 2019

Objective Numerous anomalies or postprocedural stricture of the venous system prevent optimal endovascular implantation of a pacing lead in more than 10% of patient indicated for permanent pacing or cardiac resynchronization therapy. The purpose of this report was to summarize our experience and immediate postoperative results of thoracoscopic lead implantation as a lesser invasive solution to an unsuccessful endovascular lead insertion. Methods From January 2008 to April 2013, 11 epicardial leads were introduced thoracoscopically at our center as a rescue treatment after failed endovascular attempts. Patients were ventilated using a double-lumen endotracheal tube. A 5-mm 30-degree lance thoracoscope was used with either 2 or 3 additional working ports. A screw-in pacing lead (Medtronic Model 5071 Pacing lead, Minneapolis, MN USA) was inserted into the left ventricular epicardium. After the lead placement and assessment for threshold less than 1 V, the lead was brought to the chest wall and tunneled to the pacemaker generator pocket. At the end of the procedure, a small, flexible 14F thoracic drain, was left inside the pleural cavity for the next 24 hours. Results There were no mortality or any major surgical complications among these patients. All patients responded to the epicardial lead implantation in terms of appropriate pacing and conductivity. No clinical failure was observed, and no patient required a repeat procedure. Conclusions Thoracoscopic lead insertion is safe and easy to perform. We believe it should be offered as the first choice after failed endovascular pacing lead implantation.
Disrupted filamin A/αIIbβ3 interaction induces macrothrombocytopenia by increasing RhoA activity
Authors: Donada Alessandro , Balayn Nathalie , Sliwa Dominika , Lordier Larissa , Ceglia Valentina , Baschieri Francesco , Goizet Cyril , Favier Rémi , Tosca Lucie , Tachdjian Gérard , Denis Cecile V. , Plo Isabelle , Vainchenker William , Debili Najet , Rosa Jean-Philippe , Bryckaert Marijke , Raslova Hana 
Published: January 2019

AbstractFilamin A (FLNa) links the cell membrane with the cytoskeleton and is central in several cellular processes. Heterozygous mutations in the X-linked FLNA gene are associated with a large spectrum of conditions, including macrothrombocytopenia, called filaminopathies. Using an isogenic pluripotent stem cell model derived from patients, we show that the absence of the FLNa protein in megakaryocytes (MKs) leads to their incomplete maturation, particularly the inability to produce proplatelets. Reduction in proplatelet formation potential is associated with a defect in actomyosin contractility, which results from inappropriate RhoA activation. This dysregulated RhoA activation was observed when MKs were plated on fibrinogen but not on other matrices (fibronectin, vitronectin, collagen 1, and von Willebrand factor), strongly suggesting a role for FLNa/αIIbβ3 interaction in the downregulation of RhoA activity. This was confirmed by experiments based on the overexpression of FLNa mutants deleted in the αIIbβ3-binding domain and the RhoA-interacting domain, respectively. Finally, pharmacological inhibition of the RhoA-associated kinase ROCK1/2 restored a normal phenotype and proplatelet formation. Overall, this work suggests a new etiology for macrothrombocytopenia, in which increased RhoA activity is associated with disrupted FLNa/αIIbβ3 interaction.
The use of targeted sequencing and flow cytometry to identify patients with a clinically significant monocytosis
Authors: Cargo Catherine , Cullen Matthew , Taylor Jan , Short Mike , Glover Paul , Van Hoppe Suzan , Smith Alex , Evans Paul , Crouch Simon 
Published: January 2019

Abstract
The diagnosis of chronic myelomonocytic leukemia (CMML) remains centered on morphology, meaning that the distinction from a reactive monocytosis is challenging. Mutational analysis and immunophenotyping have been proposed as potential tools for diagnosis; however, they have not been formally assessed in combination. We aimed to investigate the clinical utility of these technologies by performing targeted sequencing, in parallel with current gold standard techniques, on consecutive samples referred for investigation of monocytosis over a 2-year period (N = 283). Results were correlated with the morphological diagnosis and objective outcome measures, including overall survival (OS) and longitudinal blood counts. Somatic mutations were detected in 79% of patients, being invariably identified in those with a confirmed diagnosis (99%) but also in 57% of patients with nondiagnostic bone marrow features. The OS in nondiagnostic mutated patients was indistinguishable from those with CMML (P = .118) and significantly worse than in unmutated patients (P = .0002). On multivariate analysis, age, ASXL1, CBL, DNMT3A, NRAS, and RUNX1 mutations retained significance. Furthermore, the presence of a mutation was associated with a progressive decrease in hemoglobin/platelet levels and increasing monocyte counts compared with mutation-negative patients. Of note, the immunophenotypic features of nondiagnostic mutated patients were comparable to CMML patients, and the presence of aberrant CD56 was highly specific for detecting a mutation. Overall, somatic mutations are detected at high frequency in patients referred with a monocytosis, irrespective of diagnosis. In those without a World Health Organization–defined diagnosis, the mutation spectrum, immunophenotypic features, and OS are indistinguishable from CMML patients, and these patients should be managed as such.
Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis
Authors: Fenaux Pierre , Kiladjian Jean Jacques , Platzbecker Uwe 
Published: January 2019

AbstractAnemia of lower-risk myelodysplastic syndromes (MDSs) and primary myelofibrosis (PMF) generally becomes resistant to available treatments, leading to red blood cell (RBC) transfusions, iron overload, shortened survival, and poor quality of life. The transforming growth factor-β superfamily, including activins and growth differentiation factors (GDFs), is aberrantly expressed in lower-risk MDSs and PMF. Luspatercept (and sotatercept), ligand traps that particularly inhibit GDF11, lead to RBC transfusion independence in 10% to 50% of lower-risk MDSs resistant to available treatments, and have started to be used in PMF.
Low prevalence of substance use in people with 22q11.2 deletion syndrome
Authors: Vingerhoets Claudia , van Oudenaren Mathilde J.F. , Bloemen Oswald J.N. , Boot Erik , van Duin Esther D.A. , Evers Laurens J.M. , Fiksinski Ania M. , Breetvelt Elemi J. , Palmer Lisa D. , Vergaelen Elfi , Vogels Annick , Meijer Carin , Booij Jan ,   Genetic Risk and Outcome of Psychosis (GROUP) investigators, de Haan Liewe , Swillen Ann , Vorstman Jacob A.S. , Bassett Anne S. , van Amelsvoort Therese A.M.J. 
Published: January 2019

Background22q11.2 deletion syndrome (22q11DS), one of the most common recurrent copy number variant disorders, is associated with dopaminergic abnormalities and increased risk for psychotic disorders.AimsGiven the elevated prevalence of substance use and dopaminergic abnormalities in non-deleted patients with psychosis, we investigated the prevalence of substance use in 22q11DS, compared with that in non-deleted patients with psychosis and matched healthy controls.MethodThis cross-sectional study involved 434 patients with 22q11DS, 265 non-deleted patients with psychosis and 134 healthy controls. Psychiatric diagnosis, full-scale IQ and COMT Val158Met genotype were determined in the 22q11DS group. Substance use data were collected according to the Composite International Diagnostic Interview.ResultsThe prevalence of total substance use (36.9%) and substance use disorders (1.2%), and weekly amounts of alcohol and nicotine use, in patients with 22q11DS was significantly lower than in non-deleted patients with psychosis or controls. Compared with patients with 22q11DS, healthy controls were 20 times more likely to use substances in general (P < 0.001); results were also significant for alcohol and nicotine use separately. Within the 22q11DS group, there was no relationship between the prevalence of substance use and psychosis or COMT genotype. Male patients with 22q11DS were more likely to use substances than female patients with 22q11DS.ConclusionsThe results suggest that patients with 22q11DS are at decreased risk for substance use and substance use disorders despite the increased risk of psychotic disorders. Further research into neurobiological and environmental factors involved in substance use in 22q11DS is necessary to elucidate the mechanisms involved.Declaration of interestNone.
Essential experimental steps and estimates of renal carcinoma initiating cells.
Authors: Gedye Craig , Sirskyj Danylo , Lobo Nazleen Carol , Hyatt Ella , Evans Andrew , Finelli Antonio , Fleshner Neil Eric , Hamilton Robert James , Kulkarni Girish S. , Robinette Michael , Zlotta Alexandre , Jewett Michael A.S. , Ailles Laurie 
Published: January 2019

11127 Background: Rare cancer stem cells (CSC), proposed to be solely responsible for tumor propagation and re-initiation, are functionally identified as tumor-initiating cells (TIC) from ex vivo tumors using xenotransplantation and clonogenic limiting dilution assays (LDA). TIC have not previously been described from ex vivohuman clear cell renal cell carcinoma (ccRCC). Methods: Primary human ccRCC samples (n=120) from patients undergoing nephrectomy were processed and implanted as subcapsular fragments or cell suspension injection LDAs with Matrigel in NOD/SCID/IL2Rγ-/- (NSG) mice, and observed for at least 6 months. In vitro clonogenic LDAs assays were performed from primary cell suspensions and ccRCC cell lines. LDAs were supplemented with human stromal cells and proteins, and the Y-26732 ROCK inhibitor. Multiparametric flow cytometry and immunofluorescence were used to investigate tumor heterogeneity and cell viability. Results: ccRCC TIC appeared rare from injected suspensions, but xenografts engrafted frequently from tiny fragments, and clonogenic frequencies were 103-104greater than TIC frequencies, suggesting that LDAs underestimated ccRCC tumor cell potential. We systematically identified multiple methodological steps that distort quantitation and identification of ccRCC TIC. For example cell viability was highly variable prior to processing, disaggregation itself destroyed up to 99% of tumor cells, standard assays substantially overestimated tumor cell viability in suspensions, and supplementation with human extracellular cells or proteins, or inhibition of anoikis by Y-26732 increased clonogenic and TIC frequencies in cell lines and primary ccRCC suspensions. Annexin-V staining revealed that tumor cells were more apoptotic then normal stromal cells, and that tumor cells positive for CD44 (a putative CSC marker) were more viable than CD44- tumor cells. Conclusions: We describe multiple, unappreciated and largely unavoidable observational errors in essential methods used to study TIC in ccRCC. ccRCC TIC may be more common than appreciated. Re-examination of the CSC hypothesis in other solid tumors is warranted in view of these previously unexplored methodological biases.
“In Case I Die Where I Am Selected to Be Sent”: Coercion and the Tlaxcalan Resettlement of 1591
Authors: Jeffres Travis 
Published: January 2019

Abstract
The Tlaxcalans famously aided Hernando Cortés’s overthrow of the Aztec Empire and provided large numbers of allies in Spain’s subsequent American conquests. In 1591 nearly one thousand Tlaxcalans were resettled along New Spain’s war-torn frontier in an effort to pacify northern peoples known as Chichimecs. Historians have cast them as eager volunteers and interpreted the campaign as another example of Tlaxcala’s distinguished colonial service. However, records written by Tlaxcalans in their own language (Nahuatl) reveal that the mission met a furious resistance and that many of the settlers were coerced. The resettlement also attended a period of decline in the province and coincided with administrators’ efforts to undermine its privileges and subordinate its people alongside other indios in New Spain. Reconstructing the sociopolitical context and incorporating native texts, this article considers the resettlement from a Tlaxcalan perspective and sheds new light on the experiences of indigenous allies in the colonial Americas.
Putting VE-cadherin into JAIL for junction remodeling
Authors: Cao Jiahui , Schnittler Hans 
Published: January 2019

ABSTRACTJunction dynamics of endothelial cells are based on the integration of signal transduction, cytoskeletal remodeling and contraction, which are necessary for the formation and maintenance of monolayer integrity, but also enable repair and regeneration. The VE-cadherin–catenin complex forms the molecular basis of the adherence junctions and cooperates closely with actin filaments. Several groups have recently described small actin-driven protrusions at the cell junctions that are controlled by the Arp2/3 complex, contributing to cell junction regulation. We identified these protrusions as the driving force for VE-cadherin dynamics, as they directly induce new VE-cadherin-mediated adhesion sites, and have accordingly referred to these structures as junction-associated intermittent lamellipodia (JAIL). JAIL extend over only a few microns and thus provide the basis for a subcellular regulation of adhesion. The local (subcellular) VE-cadherin concentration and JAIL formation are directly interdependent, which enables autoregulation. Therefore, this mechanism can contribute a subcellularly regulated adaptation of cell contact dynamics, and is therefore of great importance for monolayer integrity and relative cell migration during wound healing and angiogenesis, as well as for inflammatory responses. In this Review, we discuss the mechanisms and functions underlying these actin-driven protrusions and consider their contribution to the dynamic regulation of endothelial cell junctions.
Nocebo as a source of bias in the assessment of treatment effect
Authors: Wartolowska Karolina 
Published: January 2019

The term nocebo refers to the worse outcomes or side effects experienced by patients as a result of their negative expectations regarding a treatment. It may distort estimates of treatment effectiveness and safety in both clinical trials and clinical practice; moreover, it may cause discontinuation of therapy or drop out from a trial. Nocebo effect is evoked by the information given to patients during a clinical consultation or during enrolment into a study, but information available from the media or the Internet may also play an important role. In research settings, a trial design may introduce bias from the nocebo effect. For example, if the non-treatment group is unblinded and aware that they are not receiving any treatment, their treatment expectations are not met, which results in worse outcomes, and subsequently, the problems that the trial was supposed to investigate may be enhanced in the non-treatment arm. Nocebo effect is common, and its magnitude may be large, but it receives less attention and research focus than the placebo effect. Unlike the placebo effect, which is usually taken into consideration while interpreting treatment results and controlled for in clinical trials, the nocebo effect is under-recognised by clinical researchers as well as clinicians. It is important to recognise and any potential nocebo effect must be considered while assessing the effect of treatment and should be minimised through careful choice and phrasing of treatment-related information given to the patients.
Cutaneous neonatal Langerhans cell histiocytosis: a systematic review of case reports
Authors: Venning Victoria , Yhao Evelyn , Huynh Elizabeth , Frew John W. 
Published: January 2019

Background:Cutaneous langerhans cell histiocytosis (LCH) is a rare disorder characterized by proliferation of cells with phenotypical characteristics of Langerhans cells. Although some cases spontaneously resolve, no consistent variables have been identified that predict which cases will manifest with systemic disease later in childhood.Methods:A systematic review (Pubmed, Embase, Cochrane database and all published abstracts from 1946-2018) was undertaken to collate all reported cases of cutaneous LCH in the international literature. This study was registered with PROSPERO (CRD42016051952). Descriptive statistics and correlation analyses were undertaken. Bias was analyzed according to GRADE criteria.Results:A total of 83 articles encompassing 128 cases of cutaneous LCH were identified. Multiple lesions were weakly associated with an increased length of survival (R=0.304 (p<0.05)), Worse prognosis was associated with internal organ involvement with a statistically significant chi squared statistic (χ2=14.96, 2DF p<0.001) and an elevated odds ratio ((OR)= 12.30 95% CI=2.67-56.74). Vesicular lesions (OR=10.8 95% CI=2.83-41.26), but not ulceration (OR=0.53 95% CI 0.12-2.05) were associated with greater risk of mortality.Conclusions:Congenital and neonatal LCH most commonly presents as multiple lesions in multiple anatomical sites at birth. Significant differences, including the associations of mortality with lesion morphology and number were seen in this neonatal cohort compared to overall pediatric LCH. These findings require validation in a large prospective cohort.
Brisk Attitude and Optimism: Top Workers’ Childhood Experiences Forming the Basis of Success at Work
Authors: Uusiautti Satu , Määttä Kaarina 
Published: December 2018

<p style="text-align:justify">This study focused on the phenomenon of success at work asking whether it would be possible to find factors from top workers’ children and school experiences that would explain their later success. This study was a part of a larger research in which Finnish top workers, employees of the year, who have been selected as successful professionals of their field in Finland were researched. This article focuses on the narrative data collected through qualitative interviews. In this article, their childhood and adolescence experiences were analyzed in order to find out whether successful development could be enhanced already in early phases of life. This study employed the narrative interview method through which top workers were asked to reminisce their childhood and adolescence experiences. What factors have supported their success and how have they coped with adversities in life? According to the results, the most important key to success at work adopted from home was caring upbringing as parents did not set any ambitious goals for success for their children but made the children think about their future and have an optimistic attitude to life. The role of careers counseling at school was also discussed. Analyzing these factors is important if aiming at helping people’s chances of finding an occupation they fit and in which they can use their talents. Experiences and events taking place in childhood and adolescence can be crucial, or at least, direct people in a right direction.</p>
A Sociolinguística Educacional na formação do professor: crenças e atitudes linguísticas de acadêmicos de Letras
Authors: Ribeiro Thiago Leonardo , Ramos Pinto Vera Maria 
Published: January 2019

Os documentos oficiais de ensino, como os Parâmetros Curriculares Nacionais (PCN/1998), orientam que o ensino de língua portuguesa nas salas de aula deve levar em consideração a abordagem da variação linguística juntamente com o ensino da gramática normativa. Desse modo, é necessário que os professores de Língua Portuguesa (LP) tenham consciência da diversidade da nossa língua e conheçam a realidade linguística dos seus alunos, para não possibilitar a eles apenas o conhecimento da norma padrão. Diante disso, com base em estudos teórico-metodológicos de Bortoni-Ricardo (2004, 2005), Cyranka (2007, 2014, 2015, 2016), Coelho et al (2010, 2015), Faraco (2008, 2015), Lambert e Lambert (1972), Gómez Molina (1987), Santos (1996), entre outros, neste artigo, apresentamos as crenças e atitudes linguísticas de acadêmicos que ingressam nos cursos de Letras sobre a visão do ensino de Língua Portuguesa, sobretudo, no que diz respeito à abordagem da variação linguística nas aulas de LP, com base na pesquisa de doutorado de Pinto (2018), cuja tese defendida é a de que, na formação inicial do docente de Letras, além do conhecimento teórico-científico e metodológico sobre e como lidar com a variação linguística no contexto escolar, é preciso que os professores sejam mediadores na construção da consciência linguística desses futuros docentes.
Hard facts, soft measures: Gender, quality and inequality debates in Danish film and television in the 2010s
Authors: Redvall Eva Novrup , Sørensen Inge Ejbye 
Published: January 2019

Abstract
This article investigates discussions about gender, quality and equality in Danish film and television in the 2010s. Contrary to Sweden, where gender diversity has been part of public debate and formal screen policy since the 2000s, there was little discussion of gender in the Danish screen industry until the Danish Film Institute (DFI) began focusing on diversity as a priority area before the Film Strategy for 2015–18. The article analyses how both DFI and industry players have continuously argued against gender quotas, instead opting for soft measures such as ‘gender declarations’ and initiatives to raise awareness. One of these initiatives was a manifesto, ManusFestet, that used humour to raise questions about gender representation on-screen. The article discusses how a balance between hard facts and soft measures seems to be experienced as a constructive way forward, as long as this combination does in fact facilitate the intended change.