bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosis and management of carotid free-floating thrombus: A systematic literature review
Authors: Fridman Sebastian , Lownie Stephen P , Mandzia Jennifer 
Published: February 2019

Background There is no consensus regarding the management of carotid free-floating thrombi in patients with acute ischemic stroke and transient ischemic attack. Aims This systematic review aims to (1) describe the current imaging methods for diagnosis of carotid free-floating thrombi and its associated risk factors, (2) estimate the proportion of carotid free-floating thrombi diagnosed in stroke patients, (3) estimate the proportion of carotid free-floating thrombi patients treated medically and surgically, and (4) evaluate 30-day outcomes. Methods We searched MEDLINE, EMBASE, and manually for references reporting carotid free-floating thrombi from 1960 until June 2017. We estimated the frequency of carotid free-floating thrombi and evaluated 30-day outcomes using Cox regression. We defined the timing of surgical intervention as early (less than 72 h) and delayed (more or equal to 72 h). Summary of review We retrieved 525 carotid free-floating thrombi cases from 58 case series and 83 case reports. Carotid free-floating thrombi were present in 1.53% of stroke patients. Carotid free-floating thrombi diagnosis was made by digital subtraction angiography (38.1%), carotid duplex ultrasound (29.5%), and computed tomography angiography (29.5%). The 30-day risk of transient ischemic attack, silent brain ischemia, any stroke or death was 17.1%. In multivariate analyses, there were no differences in outcome for any anticoagulation regime or timing of revascularization procedure. Conclusions The diagnosis of carotid free-floating thrombi is more common due to the increased use of early noninvasive vascular imaging in transient ischemic attack and stroke. It poses a high short-term risk of stroke and death, but there is as yet no established treatment. The low quality of evidence in the carotid free-floating thrombi literature limits the interpretation of our results and warrants a large-scale prospective cohort study in carotid free-floating thrombi.
Dissecting CLL through high-dimensional single-cell technologies
Authors: Gohil Satyen H. , Wu Catherine J. 
Published: February 2019

Abstract
We now have the potential to undertake detailed analysis of the inner workings of thousands of cancer cells, one cell at a time, through the emergence of a range of techniques that probe the genome, transcriptome, and proteome combined with the development of bioinformatics pipelines that enable their interpretation. This provides an unprecedented opportunity to better understand the heterogeneity of chronic lymphocytic leukemia and how mutations, activation states, and protein expression at the single-cell level have an impact on disease course, response to treatment, and outcomes. Herein, we review the emerging application of these new techniques to chronic lymphocytic leukemia and examine the insights already attained through this transformative technology.
Single-cell approaches reveal novel cellular pathways for megakaryocyte and erythroid differentiation
Authors: Psaila Bethan , Mead Adam J. 
Published: February 2019

Abstract
The classical model of hematopoiesis proposes a hierarchy in which a small number of multipotent hematopoietic stem cells (HSCs) maintain all blood lineages by giving rise to progeny that pass through discrete progenitor stages. At each stage, lineage differentiation potential is restricted, coupled with the loss of ability to self-renew. Recently, single-cell approaches have been used to test certain assumptions made by this model, in particular relating to megakaryocyte (Mk) and erythroid (E) development. An alternative model has emerged in which substantial heterogeneity and lineage-priming exists within the HSC compartment, including the existence of multipotent but megakaryocyte/platelet-biased HSCs. Hematopoietic differentiation follows a hierarchical continuum, passing through cellular nodes and branch points. Megakaryocytes are produced via a shared pathway with the erythroid lineage, also shared in its early stages with mast cells, eosinophils, and basophils, but separate from other myeloid and lymphoid lineages. In addition, distinct pathways for direct differentiation of Mk from HSCs may coexist and could be important in situations of increased physiological requirements or in malignancies. Further work at single-cell resolution using multiomic approaches and examining Mk-E biased subsets within their physiological context will undoubtedly improve our understanding of normal hematopoiesis and ability to manipulate this in pathology.
Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR T-cell therapy
Authors: Hay Kevin A. , Gauthier Jordan , Hirayama Alexandre V. , Voutsinas Jenna M. , Wu Qian , Li Daniel , Gooley Ted A. , Cherian Sindhu , Chen Xueyan , Pender Barbara S. , Hawkins Reed M. , Vakil Aesha , Steinmetz Rachel N. , Schoch Gary , Chapuis Aude G. , Till Brian G. , Kiem Hans-Peter , Ramos Jorge D. , Shadman Mazyar , Cassaday Ryan D. , Acharya Utkarsh H. , Riddell Stanley R. , Maloney David G. , Turtle Cameron J. 
Published: February 2019

AbstractAutologous T cells engineered to express a CD19-specific chimeric antigen receptor (CAR) have produced impressive minimal residual disease–negative (MRD-negative) complete remission (CR) rates in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, the factors associated with durable remissions after CAR T-cell therapy have not been fully elucidated. We studied patients with relapsed/refractory B-ALL enrolled in a phase 1/2 clinical trial evaluating lymphodepletion chemotherapy followed by CD19 CAR T-cell therapy at our institution. Forty-five (85%) of 53 patients who received CD19 CAR T-cell therapy and were evaluable for response achieved MRD-negative CR by high-resolution flow cytometry. With a median follow-up of 30.9 months, event-free survival (EFS) and overall survival (OS) were significantly better in the patients who achieved MRD-negative CR compared with those who did not (median EFS, 7.6 vs 0.8 months; P &lt; .0001; median OS, 20.0 vs 5.0 months; P = .014). In patients who achieved MRD-negative CR by flow cytometry, absence of the index malignant clone by IGH deep sequencing was associated with better EFS (P = .034). Stepwise multivariable modeling in patients achieving MRD-negative CR showed that lower prelymphodepletion lactate dehydrogenase concentration (hazard ratio [HR], 1.38 per 100 U/L increment increase), higher prelymphodepletion platelet count (HR, 0.74 per 50 000/μL increment increase), incorporation of fludarabine into the lymphodepletion regimen (HR, 0.25), and allogeneic hematopoietic cell transplantation (HCT) after CAR T-cell therapy (HR, 0.39) were associated with better EFS. These data allow identification of patients at higher risk of relapse after CAR T-cell immunotherapy who might benefit from consolidation strategies such as allogeneic HCT. This trial was registered at www.clinicaltrials.gov as #NCT01865617.
Posttranscriptional modulation of TERC by PAPD5 inhibition rescues hematopoietic development in dyskeratosis congenita
Authors: Fok Wilson Chun , Shukla Siddharth , Vessoni Alexandre Teixeira , Brenner Kirsten Ann , Parker Roy , Sturgeon Christopher M. , Batista Luis Francisco Zirnberger 
Published: February 2019

Abstract
Reduced levels of TERC, the telomerase RNA component, cause dyskeratosis congenita (DC) in patients harboring mutations in TERC, PARN, NOP10, NHP2, NAF1, or DKC1. Inhibition of the noncanonical poly(A) polymerase PAPD5, or the exosome RNA degradation complex, partially restores TERC levels in immortalized DKC1 mutant cells, but it remains unknown if modulation of posttranscriptional processing of TERC could improve hematopoietic output in DC. We used human embryonic stem cells (hESCs) with a common dyskerin mutation (DKC1_A353V), which have defective telomere maintenance and reduced definitive hematopoietic potential, to understand the effects of reducing EXOSC3 activity, or silencing PAPD5-mediated oligoadenylation, on hematopoietic progenitor specification and function in DC. Reduction of EXOSC3 or PAPD5 levels in DKC1 mutant hESCs led to functional improvements in TERC levels and telomerase activity, with concomitant telomere elongation and reduced levels of DNA damage signaling. Interestingly, the silencing of PAPD5, but not EXOSC3, significantly restored definitive hematopoietic potential in DKC1 mutant cells. Mechanistically, we show that PAPD5 inhibition is sustained in differentiated CD34+ cells, with a concomitant increase in mature, functional, forms of TERC, indicating that regulation of PAPD5 is a potential strategy to reverse hematologic dysfunction in DC patients.
High probability of follow-up termination among AYA survivors after allogeneic hematopoietic cell transplantation
Authors: Miyamura Koichi , Yamashita Takuya , Atsuta Yoshiko , Ichinohe Tatsuo , Kato Koji , Uchida Naoyuki , Fukuda Takahiro , Ohashi Kazuteru , Ogawa Hiroyasu , Eto Tetsuya , Inoue Masami , Takahashi Satoshi , Mori Takehiko , Kanamori Heiwa , Yabe Hiromasa , Hama Asahito , Okamoto Shinichiro , Inamoto Yoshihiro 
Published: February 2019

Abstract
The need for long-term follow-up (LTFU) after allogeneic hematopoietic cell transplantation (HCT) has been increasingly recognized for managing late effects such as subsequent cancers and cardiovascular events. A substantial population, however, has already terminated LTFU at HCT centers. To better characterize follow-up termination, we analyzed the Japanese transplant registry database. The study cohort included 17 980 survivors beyond 2 years who underwent their first allogeneic HCT between 1974 and 2013. The median patient age at HCT was 34 years (range, 0-76 years). Follow-up at their HCT center was terminated in 4987 patients. The cumulative incidence of follow-up termination was 28% (95% confidence interval [CI], 27%-29%) at 10 years, increasing to 67% (95% CI, 65%-69%) at 25 years after HCT. Pediatric patients showed the lowest probability of follow-up termination for up to 16 years after HCT, whereas adolescent and young adult (AYA) patients showed the highest probability of follow-up termination throughout the period. Follow-up termination was most often made by physicians based on the patient’s good physical condition. Multivariate analysis identified 6 factors associated with follow-up termination: AYA patients, female patients, standard-risk malignancy or nonmalignant disease, unrelated bone marrow transplantation, HCT between 2000 and 2005, and absence of chronic graft-versus-host disease. These results suggest the need for education of both physicians and patients about the importance of LTFU, even in survivors with good physical condition. The decreased risk for follow-up termination after 2005 may suggest the increasing focus on LTFU in recent years.
RETRACTED ARTICLE: Data cleansing method of talent management data in wireless sensor network based on data mining technology
Authors: Bai Yanli 
Published: February 2019

AbstractData mining technology is a very common computer technology, which has been widely used in many fields because of its superior performance. The method of talent management data cleaning in wireless sensor networks is studied based on data mining technology. The research status of data mining technology is first introduced at home and abroad, and the specific application forms of wireless sensor networks are analyzed. Then, the structure characteristics of wireless sensor networks are introduced, and a data cleansing technology is proposed based on clustering model. A cluster-based replication record deletion algorithm is proposed, and finally, the accuracy of data cleansing methods is verified. The results show that the research method of this paper is correct and effective.
TES functions as a Mena‐dependent tumor suppressor in gastric cancer carcinogenesis and metastasis
Authors: Wang Dan‐dan , Chen Yi‐bing , Zhao Jing‐jing , Zhang Xiao‐fei , Zhu Guang‐chao , Weng De‐sheng , Pan Ke , Lv Lin , Pan Qiu‐zhong , Jiang Shan‐shan , Wang Lei‐lei , Xia Jian‐chuan 
Published: February 2019

AbstractBackgroundIn our previous study, we identified a candidate tumor suppressor gene, testin LIM domain protein (TES), in primary gastric cancer (GC). TES contains three LIM domains, which are specific interacting regions for the cell adhesion and cytoskeleton regulatory proteins. Mena is a known cytoskeleton regulator that regulates the assembly of actin filaments and modulates cell adhesion and motility by interacting with Lamellipodin (Lpd). Therefore, we hypothesized that TES plays a role as tumor suppressor in GC through interacting with Mena. This study aimed to investigate the tumor suppressive functions of TES in GC.MethodsWe explored the tumor suppressive effect of TES in GC by in vitro cell proliferation assay, colony formation assay, cell cycle analysis, Transwell assays, and in vivo tumorigenicity and metastasis assays. The interaction of TES and Mena was investigated through immunoprecipitation‐based mass spectrometry. We also analyzed the expression of TES and Mena in 172 GC specimens using immunohistochemistry and investigated the clinicopathological and prognostic significance of TES and Mena in GC.ResultsTES suppressed GC cell proliferation and colony formation, induced cell cycle arrest, and inhibited tumorigenicity in vitro. Additionally, it inhibited GC cell migration and invasion in vitro and suppressed metastasis in vivo. TES interacted with Mena, and inhibited the interaction of Mena with Lpd. Transwell assays suggested that TES suppressed migration and invasion of GC cells in a Mena‐dependent fashion. In GC patients with high Mena expression, the expression of TES was associated with tumor infiltration (P = 0.005), lymph node metastasis (P = 0.003), TNM stage (P = 0.003), and prognosis (P = 0.010). However, no significant association was observed in GC patients with low Mena expression.ConclusionsWe believe that TES functions as a Mena‐dependent tumor suppressor. TES represents a valuable prognostic marker and potential target for GC treatment.
Genes in immune pathways associated with abnormal white matter integrity in first-episode and treatment-naïve patients with schizophrenia
Authors: Xiang Bo , Wang Qiang , Lei Wei , Li Mingli , Li Yinfei , Zhao Liansheng , Ma Xiaohong , Wang Yingcheng , Yu Hua , Li Xiaojing , Meng Yajing , Guo Wanjun , Deng Wei , Ren Hongyan , Li Tao 
Published: February 2019

BackgroundPrevious studies have inferred a strong genetic component in schizophrenia. However, the genetic variants involved in the susceptibility to schizophrenia remain unclear.AimsTo detect potential gene pathways and networks associated with schizophrenia, and to explore the relationship between common and rare variants in these pathways and abnormal white matter integrity in schizophrenia.MethodThe analysis included 100 first-episode treatment-naïve patients with schizophrenia and 140 healthy controls. A network-based analysis was carried out on the data collected from the Psychiatric Genomics Consortium Phase I (PGC-I). Based on our genome-wide association study and whole-exome sequencing data-sets, we performed a gene-set analysis to detect associations between the combining effects of common and rare genetic variants and abnormal white matter integrity in schizophrenia.ResultsPatients had significantly reduced functional anisotropy in the left and right anterior cingulate cortex, left and right precuneus and extra-nuclear (t = 4.61–5.10, PFDR < 0.01), compared with controls. Generated from co-expression network analysis of the PGC-1 summary statistics of schizophrenia, a subnetwork of 207 genes associated with schizophrenia was identified (P < 0.01), and 176 genes were co-expressed in four gene modules. Functional enrichment analysis for genes in each module revealed that the yellow module was enriched with highly co-expressed, innate immune response genes. Furthermore, rare variants of enriched genes in the yellow module were associated with reduced functional anisotropy in the left anterior cingulate cortex (P = 0.006; Padjusted = 0.024) in patients only.ConclusionsThe pathogenesis of schizophrenia may be substantially influenced by genes involved in the immune system, via both pathway and network.Declaration of interestsNone.
Factors deterring and prompting the decision to attempt suicide on the railway networks: findings from 353 online surveys and 34 semi-structured interviews
Authors: Marzano Lisa , Mackenzie Jay-Marie , Kruger Ian , Borrill Jo , Fields Bob 
Published: February 2019

BackgroundThere is a suicide on the British railways every 36 hours. However, the reasons why people choose to die by train are not well understood.AimsTo explore factors influencing and discouraging the decision to attempt suicide on the railway networks.MethodWe conducted an online survey and qualitative interviews with individuals who had contemplated or attempted suicide by train.ResultsA total of 353 survey responders had considered and 23 had attempted suicide at rail locations (including railways and metro/underground); a third of these cases were impulsive. The most frequently reported motivations for contemplating or attempting suicide were perceptions of quick and certain lethality (54 and 37%, respectively) and easy access to rail settings (33 and 38%, respectively). The main factor discouraging people from rail suicide was its wider impact, especially on train drivers (19%). In qualitative interviews (N = 34) the desire to avoid intervention from others was also a common motivating factor for attempting suicide on the railway networks.ConclusionsPeople attempt suicide by train because railway settings are easy to access and because of an inaccurate perception of certain and quick lethality. Tackling exaggerated perceptions of lethality may help reduce suicides by train.Declaration of interestNone.
Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy
Authors: Nghiem Paul , Bhatia Shailender , Lipson Evan J. , Sharfman William H. , Kudchadkar Ragini R. , Brohl Andrew S. , Friedlander Phillip A. , Daud Adil , Kluger Harriet M. , Reddy Sunil A. , Boulmay Brian C. , Riker Adam I. , Burgess Melissa A. , Hanks Brent A. , Olencki Thomas , Margolin Kim , Lundgren Lisa M. , Soni Abha , Ramchurren Nirasha , Church Candice , Park Song Y. , Shinohara Michi M. , Salim Bob , Taube Janis M. , Bird Steven R. , Ibrahim Nageatte , Fling Steven P. , Homet Moreno Blanca , Sharon Elad , Cheever Martin A. , Topalian Suzanne L. 
Published: February 2019

PURPOSE Merkel cell carcinoma (MCC) is an aggressive skin cancer often caused by the Merkel cell polyomavirus. Clinical trials of programmed cell death-1 pathway inhibitors for advanced MCC (aMCC) demonstrate increased progression-free survival (PFS) compared with historical chemotherapy data. However, response durability and overall survival (OS) data are limited. PATIENTS AND METHODS In this multicenter phase II trial (Cancer Immunotherapy Trials Network-09/Keynote-017), 50 adults naïve to systemic therapy for aMCC received pembrolizumab (2 mg/kg every 3 weeks) for up to 2 years. Radiographic responses were assessed centrally per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. RESULTS Among 50 patients, the median age was 70.5 years, and 64% had Merkel cell polyomavirus–positive tumors. The objective response rate (ORR) to pembrolizumab was 56% (complete response [24%] plus partial response [32%]; 95% CI, 41.3% to 70.0%), with ORRs of 59% in virus-positive and 53% in virus-negative tumors. Median follow-up time was 14.9 months (range, 0.4 to 36.4+ months). Among 28 responders, median response duration was not reached (range, 5.9 to 34.5+ months). The 24-month PFS rate was 48.3%, and median PFS time was 16.8 months (95% CI, 4.6 months to not estimable). The 24-month OS rate was 68.7%, and median OS time was not reached. Although tumor viral status did not correlate with ORR, PFS, or OS, there was a trend toward improved PFS and OS in patients with programmed death ligand-1–positive tumors. Grade 3 or greater treatment-related adverse events occurred in 14 (28%) of 50 patients and led to treatment discontinuation in seven (14%) of 50 patients, including one treatment-related death. CONCLUSION Here, we present the longest observation to date of patients with aMCC receiving first-line anti–programmed cell death-1 therapy. Pembrolizumab demonstrated durable tumor control, a generally manageable safety profile, and favorable OS compared with historical data from patients treated with first-line chemotherapy.
Loyal Subjects at Empire's Edge: Hispanics in the Vision of a Belizean Colonial Nation, 1882–1898
Authors: Dutt Rajeshwari 
Published: February 2019

Abstract
This essay juxtaposes the trial of a prominent Hispanic, Manuel Jesús Castillo, in 1882 with the celebrations of the centenary of St. George's Caye in 1898 to gain a deeper understanding of the methods employed by officials in Belize to impose order on the complex post–Caste War society there in a way that was materially and politically advantageous to colonial rule at the nineteenth century's end. Colonial officials used the language and theme of loyalty to further imperial and class agendas in the context of political, social, and economic contestation. The idiom of loyalty served to simplify the complex reality of an often-discordant multiethnic society into a simple binary of loyalty versus disloyalty that determined the Britishness of the colony's subjects and provided beleaguered colonial officials with the vehicle for counteracting the dominance of the unofficial members of the colonial government.
Sex and Democracy: The Meanings of theDestapein Postdictatorial Argentina
Authors: Milanesio Natalia 
Published: February 2019

AbstractIn 1983, elections in Argentina ended one of the bloodiest dictatorships in Latin America (1976–83), and once the elected president Raúl Alfonsín took office, Argentines rejoiced in a democratic spring. The destape was the most explosive cultural trend in the return to democracy, emerging timidly in 1981 as the military grew weaker but remained in power and gaining momentum between 1983 and 1987. Destapar means to take the lid off, uncover, expose, and the destape was, in fact, an avalanche of sexual images and narratives. This article considers the censorship and repression of sexual content in the media during the dictatorship and examines the destape as a large-scale media phenomenon that amplified sexual explicitness to a historically unrivaled degree. The essay demonstrates that for most Argentines the destape was a metaphor for democracy, freedom, modernity, national adulthood, self-expression, and the exuberant enjoyment of life. While the article focuses mostly on celebratory meanings, it also briefly examines the positions of ultra-Catholics and of feminists, who, from very different perspectives, raised the most critical voices against the destape.