bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common errors in temporary hemodialysis catheter insertion
Authors: Samaha Daniel , Clark Edward G. 
Published: April 2019

AbstractNon‐tunneled hemodialysis catheter (NTHC) insertion is an essential skill for nephrology practice and remains a requirement of training. However, improper insertion technique can increase the risk of potentially fatal infectious and mechanical complications. Evidence‐based strategies can reduce the rates of such complications and should be integrated into practice and training. Ultrasound (US) guidance should routinely be used for NTHC insertion at the femoral and internal jugular sites (with avoidance of the subclavian site). Nephrologists should receive proper training in the use of US for line insertion. With respect to other aspects of the procedure, proper insertion technique readily prevents guidewire‐induced arrhythmias. In addition, adherence to infection‐control guidelines results in a sustainable reduction in bloodstream infections. All these aspects of NTHC insertion may be best taught and evaluated through a program that includes simulation‐based mastery learning (SBML) training. As a separate issue, nephrologists (and intensivists) should be aware that a dysfunctional catheter should be replaced at a new site rather than being changed over a guidewire. This review of common errors related to NTHC insertion seeks to highlight evidence‐based approaches to practice and training.
Reduction in sympathetic tone in patients with obstructive sleep apnoea: is fixed CPAP more effective than APAP? A randomised, parallel trial protocol
Authors: Treptow Erika , Pepin Jean Louis , Bailly Sebastien , Levy Patrick , Bosc Cecile , Destors Marie , Woehrle Holger , Tamisier Renaud 
Published: April 2019

IntroductionObstructive sleep apnoea (OSA) is a prevalent disease associated with cardiovascular events. Hypertension is one of the major intermediary mechanisms leading to long-term cardiovascular adverse events. Intermittent hypoxia and hypercapnia associated with nocturnal respiratory events stimulate chemoreflexes, resulting in sympathetic overactivity and blood pressure (BP) elevation. Continuous positive airway pressure (CPAP) is the primary treatment for OSA and induces a small but significant reduction in BP. The use of auto-adjusting positive airway pressure (APAP) has increased in the last years and studies showed different ranges of BP reduction when comparing both modalities. However, the pathophysiological mechanisms implicated are not fully elucidated. Variations in pressure through the night inherent to APAP may induce persistent respiratory efforts and sleep fragmentation that might impair sympathovagal balance during sleep and result in smaller decreases in BP. Therefore, this double-blind randomised controlled trial aims to compare muscle sympathetic nerve activity (MSNA) assessed by microneurography (reference method for measuring sympathetic activity) after 1 month of APAP versus fixed CPAP in treatment-naive OSA patients. This present manuscript describes the design of our study, no results are presented herein. and is registered under the below reference number.Methods and analysisAdult subjects with newly diagnosed OSA (Apnoea–Hypopnoea Index >20/hour) will be randomised for treatment with APAP or fixed CPAP. Measurements of sympathetic activity by MSNA, heart rate variability and catecholamines will be obtained at baseline and after 30 days. The primary composite outcome will be the change in sympathetic tone measured by MSNA in bursts/min and bursts/100 heartbeats. Sample size calculation was performed with bilateral assumption. We will use the Student’s t-test to compare changes in sympathetic tone between groups.Ethics and disseminationThe protocol was approved by The French Regional Ethics Committee. The study started in March 2018 with primary completion expected to March 2019. Dissemination plans of the results include presentations at conferences and publication in peer-reviewed journals.Trial registration numberNCT03428516; Pre-results.
Efficacy of low-dose and/or adjuvant methadone in palliative medicine
Authors: Chalker Cameron , O'Neill Hannah , Cranfield Faith 
Published: April 2019

ObjectivesTo summarise the current body of published evidence on the use of low-dose and/or adjuvant methadone in the palliative care setting.MethodsThe authors searched multiple databases (PubMED, SCORPUS, EMBASE and the Cochrane library) for relevant articles using the terms ‘methadone’, ‘palliative’, ‘low dose’ and ‘adjuvant’. The review was restricted to articles published between 2003 and 2018. Paediatric and single-case studies were also excluded. Evidence quality was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method.ResultsOur search yielded 171 results, of which seven met the inclusion criteria. Four were retrospective chart reviews, one was a retrospective cohort study, one was a case series and one was a double-blind randomised control trial. The overall quality was found to be very low. Of the seven articles, all seven reported some improvement in pain with the addition of low-dose or adjuvant methadone. This improvement was statistically significant in four out of seven articles; statistical significance was not commented on in the remaining three articles.ConclusionWhile case series and chart reviews offer promising results about the utility of adjuvant and/or low-dose methadone in the management of complex pain, the very low evidence quality, relative dearth of studies and near absence of randomised controlled trials make it impossible to draw firm conclusions. Thus, while very preliminary evidence suggests methadone is a potentially effective and valuable agent, further research must be performed before such findings can be implemented into clinical practice.
Detection of Seoul virus in wild brown rats (Rattus norvegicus) from pig farms in Northern England
Authors: Murphy Ellen G , Williams Nicola J , Bennett Malcolm , Jennings Daisy , Chantrey Julian , McElhinney Lorraine M 
Published: April 2019

IntroductionHantaviruses are maintained by mammalian hosts, such as rodents, and are shed in their excretions. Clinical disease can occur in humans from spillover infection. Brown rats (Rattus norvegicus) are the globally distributed reservoir host of Seoul virus (SEOV). Human cases of SEOV‐associated haemorrhagic fever with renal syndrome (SEOV‐HFRS)have been reported in Great Britain (GB) since 1977.MethodsBrown rats (n=68) were trapped from a variety of peridomestic locations, with a focus on pig farms. Kidney and lung tissues were tested for viral RNA using a pan‐hantavirus RT‐PCR assay followed by Sanger sequencing and analysis.ResultsSEOV RNA was detected in 19 per cent (13/68, 95% CI 11 to 30) of rats and all sequences fell within SEOV lineage 9. Twelve sequences were highly similar to each other and to the previously reported GB Humber strain of SEOV (98 per cent). One rat SEOV sequence was more distant. The SEOV prevalence in rats from pig farms was significantly greater (p=0.047) than other sites sampled. No significant sex or age differences were observed among positive and negative rats.DiscussionThe results from this study suggest that SEOV could be widespread in wild rats in GB and therefore pose a potential risk to public health.
A New Approach for Semi-Automatic Building and Extending a Multilingual Terminology Thesaurus
Authors: Horák Aleš , Baisa Vít , Rambousek Adam , Suchomel Vít 
Published: April 2019

This paper describes a new system for semi-automatically building, extending and managing a terminological thesaurus — a multilingual terminology dictionary enriched with relationships between the terms themselves to form a thesaurus. The system allows to radically enhance the workow of current terminology expert groups, where most of the editing decisions still come from introspection. The presented system supplements the lexicographic process with natural language processing techniques, which are seamlessly integrated to the thesaurus editing environment. The system’s methodology and the resulting thesaurus are closely connected to new domain corpora in the six languages involved. They are used for term usage examples as well as for the automatic extraction of new candidate terms. The terminological thesaurus is now accessible via a web-based application, which (a) presents rich detailed information on each term, (b) visualizes term relations, and (c) displays real-life usage examples of the term in the domain-related documents and in the context-based similar terms. Furthermore, the specialized corpora are used to detect candidate translations of terms from the central language (Czech) to the other languages (English, French, German, Russian and Slovak) as well as to detect broader Czech terms, which help to place new terms in the actual thesaurus hierarchy. This project has been realized as a terminological thesaurus of land surveying, but the presented tools and methodology are reusable for other terminology domains.
Wnt/PCP Signaling Contribution to Carcinoma Collective Cell Migration and Metastasis
Authors: VanderVorst Kacey , Dreyer Courtney A. , Konopelski Sara E. , Lee Hyun , Ho Hsin-Yi Henry , Carraway Kermit L. 
Published: April 2019

Abstract
Our understanding of the cellular mechanisms governing carcinoma invasiveness and metastasis has evolved dramatically over the last several years. The previous emphasis on the epithelial–mesenchymal transition as a driver of the migratory properties of single cells has expanded with the observation that carcinoma cells often invade and migrate collectively as adherent groups. Moreover, recent analyses suggest that circulating tumor cells within the vasculature often exist as multicellular clusters and that clusters more efficiently seed metastatic lesions than single circulating tumor cells. While these observations point to a key role for collective cell migration in carcinoma metastasis, the molecular mechanisms driving collective tumor cell migration remain to be discerned. Wnt/PCP (planar cell polarity) signaling, one of the noncanonical Wnt signaling pathways, mediates collective migratory events such as convergent extension during developmental processes. Wnt/PCP signaling components are frequently dysregulated in solid tumors, and aberrant pathway activation contributes to tumor cell migratory properties. Here we summarize key studies that address the mechanisms by which Wnt/PCP signaling mediate collective cell migration in developmental and tumor contexts. We emphasize Wnt/PCP component localization within migrating cells and discuss how component asymmetry may govern the spatiotemporal control of downstream cytoskeletal effectors to promote collective cell motility.
Activation of MAPK Signaling by CXCR7 Leads to Enzalutamide Resistance in Prostate Cancer
Authors: Li Shangze , Fong Ka-wing , Gritsina Galina , Zhang Ali , Zhao Jonathan C. , Kim Jung , Sharp Adam , Yuan Wei , Aversa Caterina , Yang Ximing J. , Nelson Peter S. , Feng Felix Y. , Chinnaiyan Arul M. , de Bono Johann S. , Morrissey Colm , Rettig Matthew B. , Yu Jindan 
Published: April 2019

Abstract

Castration-resistant prostate cancer (CRPC) that has developed resistance to the new-generation androgen receptor (AR) antagonist enzalutamide is a lethal disease. Transcriptome analysis of multiple prostate cancer models identified CXCR7, an atypical chemokine receptor, as one of the most upregulated genes in enzalutamide-resistant cells. AR directly repressed CXCR7 by binding to an enhancer 110 kb downstream of the gene and expression was restored upon androgen deprivation. We demonstrate that CXCR7 is a critical regulator of prostate cancer sensitivity to enzalutamide and is required for CRPC growth in vitro and in vivo. Elevated CXCR7 activated MAPK/ERK signaling through ligand-independent, but β-arrestin 2-dependent mechanisms. Examination of patient specimens showed that CXCR7 and pERK levels increased significantly from localized prostate cancer to CRPC and further upon enzalutamide resistance. Preclinical studies revealed remarkable efficacies of MAPK/ERK inhibitors in suppressing enzalutamide-resistant prostate cancer. Overall, these results indicate that CXCR7 may serve as a biomarker of resistant disease in patients with prostate cancer and that disruption of CXCR7 signaling may be an effective strategy to overcome resistance.

Significance:
These findings identify CXCR7-mediated MAPK activation as a mechanism of resistance to second-generation antiandrogen therapy, highlighting the therapeutic potential of MAPK/ERK inhibitors in CRPC.
A Phase I/II Trial of Carfilzomib, Pegylated Liposomal Doxorubicin, and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma
Authors: Schroeder Mark A. , Fiala Mark A. , Huselton Eric , Cardone Michael H. , Jaeger Savina , Jean Sae Rin , Shea Kathryn , Ghobadi Armin , Wildes Tanya , Stockerl-Goldstein Keith E. , Vij Ravi 
Published: April 2019

Abstract

Purpose:
Pegylated liposomal doxorubicin (PLD) combined with bortezomib is an effective salvage regimen for relapsed refractory multiple myeloma (RRMM). Carfilzomib, a second-generation proteasome inhibitor, has clinical efficacy even among bortezomib-refractory patients.

Patients and Methods:
We performed a phase I/II trial of carfilzomib, PLD, and dexamethasone (KDD) with the primary endpoints being safety and efficacy (NCT01246063). Twenty-three patients were enrolled in the phase I portion and the MTD of carfilzomib was determined to be 56 mg/m2 (days 1, 2, 8, 9, 15, and 16) when combined with PLD (30 mg/m2 on day 8) and dexamethasone (20 mg on days 1, 2, 8, 9, 15, and 16). Seventeen additional patients were enrolled in the phase II portion.

Results:
KDD was determined to be well tolerated with the only common grade 3/4 nonhematologic adverse events of infection. Grade 3/4 hematologic toxicity included lymphopenia (63%), thrombocytopenia (40%), anemia (40%), and neutropenia (28%). In the cohort of patients treated at the MTD, where median prior therapies were 2% and 42% were refractory to bortezomib, the overall response rate was 83% (20/24) with 54% (13/24) having a very good partial response or better. The median progression-free survival was 13.7 months (95% CI, 5.0–21.7).

Conclusions:
This trial is the first to report outcomes using a triplet regimen of high-dose carfilzomib. KDD was well tolerated and appears efficacious in RRMM. Additional study is needed to more precisely determine patient outcomes with this regimen and its utility compared with other carfilzomib containing salvage regimens.
Clinical and Genome-wide Analysis of Cisplatin-induced Tinnitus Implicates Novel Ototoxic Mechanisms
Authors: El Charif Omar , Mapes Brandon , Trendowski Matthew R. , Wheeler Heather E. , Wing Claudia , Dinh Paul C. , Frisina Robert D. , Feldman Darren R. , Hamilton Robert J. , Vaughn David J. , Fung Chunkit , Kollmannsberger Christian , Mushiroda Taisei , Kubo Michiaki , Gamazon Eric R. , Cox Nancy J. , Huddart Robert , Ardeshir-Rouhani-Fard Shirin , Monahan Patrick , Fossa Sophie D. , Einhorn Lawrence H. , Travis Lois B. , Dolan M. Eileen 
Published: April 2019

Abstract

Purpose:
Cisplatin, a commonly used chemotherapeutic, results in tinnitus, the phantom perception of sound. Our purpose was to identify the clinical and genetic determinants of tinnitus among testicular cancer survivors (TCS) following cisplatin-based chemotherapy.

Experimental Design:
TCS (n = 762) were dichotomized to cases (moderate/severe tinnitus; n = 154) and controls (none; n = 608). Logistic regression was used to evaluate associations with comorbidities and SNP dosages in genome-wide association study (GWAS) following quality control and imputation (covariates: age, noise exposure, cisplatin dose, genetic principal components). Pathway over-representation tests and functional studies in mouse auditory cells were performed.

Results:
Cisplatin-induced tinnitus (CisIT) significantly associated with age at diagnosis (P = 0.007) and cumulative cisplatin dose (P = 0.007). CisIT prevalence was not significantly greater in 400 mg/m2-treated TCS compared with 300 (P = 0.41), but doses &gt;400 mg/m2 (median 580, range 402–828) increased risk by 2.61-fold (P &lt; 0.0001). CisIT cases had worse hearing at each frequency (0.25–12 kHz, P &lt; 0.0001), and reported more vertigo (OR = 6.47; P &lt; 0.0001) and problems hearing in a crowd (OR = 8.22; P &lt; 0.0001) than controls. Cases reported poorer health (P &lt; 0.0001) and greater psychotropic medication use (OR = 2.4; P = 0.003). GWAS suggested a variant near OTOS (rs7606353, P = 2 × 10−6) and OTOS eQTLs were significantly enriched independently of that SNP (P = 0.018). OTOS overexpression in HEI-OC1, a mouse auditory cell line, resulted in resistance to cisplatin-induced cytotoxicity. Pathway analysis implicated potassium ion transport (q = 0.007).

Conclusions:
CisIT associated with several neuro-otological symptoms, increased use of psychotropic medication, and poorer health. OTOS, expressed in the cochlear lateral wall, was implicated as protective. Future studies should investigate otoprotective targets in supporting cochlear cells.
Molecular Characterization of Neuroendocrine-like Bladder Cancer
Authors: Batista da Costa José , Gibb Ewan A. , Bivalacqua Trinity J. , Liu Yang , Oo Htoo Zarni , Miyamoto David T. , Alshalalfa Mohammed , Davicioni Elai , Wright Jonathan , Dall’Era Marc A. , Douglas James , Boormans Joost L. , Van der Heijden Michiel S. , Wu Chin-Lee , van Rhijn Bas W.G. , Gupta Shilpa , Grivas Petros , Mouw Kent W. , Murugan Paari , Fazli Ladan , Ra Seong , Konety Badrinath R. , Seiler Roland , Daneshmand Siamak , Mian Omar Y. , Efstathiou Jason A. , Lotan Yair , Black Peter C. 
Published: April 2019

AbstractPurpose:Neuroendocrine (NE) bladder carcinoma is a rare and aggressive variant. Molecular subtyping studies have found that 5% to 15% of muscle-invasive bladder cancer (MIBC) have transcriptomic patterns consistent with NE bladder cancer in the absence of NE histology. The clinical implications of this NE-like subtype have not been explored in depth.Experimental Design:Transcriptome-wide expression profiles were generated for MIBC collected from 7 institutions and clinical-use of Decipher Bladder. Using unsupervised clustering, we generated a clustering solution on a prospective training cohort (PTC; n = 175), developed single-sample classifiers to predict NE tumors, and evaluated the resultant models on a testing radical cystectomy (RC) cohort (n = 225). A random forest model was finalized and applied to 5 validation cohorts (n = 1302). Uni- and multivariable survival analyses were used to characterize clinical outcomes.Results:In the training cohort (PTC), hierarchical clustering using an 84-gene panel showed a cluster of 8 patients (4.6%) with highly heterogeneous expression of NE markers in the absence of basal or luminal marker expression. NE-like tumors were identified in 1% to 6.6% of cases in validation cohorts. Patients with NE-like tumors had significantly worse 1-year progression-free survival (65% NE-like vs. 82% overall; P = 0.046) and, after adjusting for clinical and pathologic factors, had a 6.4-fold increased risk of all-cause mortality (P = 0.001). IHC confirmed the neuronal character of these tumors.Conclusions:A single-patient classifier was developed that identifies patients with histologic urothelial cancer harboring a NE transcriptomic profile. These tumors represent a high-risk subgroup of MIBC, which may require different treatment.
Therapeutic Targeting of Non-oncogene Dependencies in High-risk Neuroblastoma
Authors: Huang Chen-Tsung , Hsieh Chiao-Hui , Lee Wen-Chi , Liu Yen-Lin , Yang Tsai-Shan , Hsu Wen-Ming , Oyang Yen-Jen , Huang Hsuan-Cheng , Juan Hsueh-Fen 
Published: April 2019

Abstract

Purpose:
Neuroblastoma is a pediatric malignancy of the sympathetic nervous system with diverse clinical behaviors. Genomic amplification of MYCN oncogene has been shown to drive neuroblastoma pathogenesis and correlate with aggressive disease, but the survival rates for those high-risk tumors carrying no MYCN amplification remain equally dismal. The paucity of mutations and molecular heterogeneity has hindered the development of targeted therapies for most advanced neuroblastomas. We use an alternative method to identify potential drugs that target nononcogene dependencies in high-risk neuroblastoma.

Experimental Design:
By using a gene expression–based integrative approach, we identified prognostic signatures and potentially effective single agents and drug combinations for high-risk neuroblastoma.

Results:
Among these predictions, we validated in vitro efficacies of some investigational and marketed drugs, of which niclosamide, an anthelmintic drug approved by the FDA, was further investigated in vivo. We also quantified the proteomic changes during niclosamide treatment to pinpoint nucleoside diphosphate kinase 3 (NME3) downregulation as a potential mechanism for its antitumor activity.

Conclusions:
Our results establish a gene expression–based strategy to interrogate cancer biology and inform drug discovery and repositioning for high-risk neuroblastoma.
About Face: Molecular Aberrations in Head and Neck Mucosal Melanomas
Authors: Shoushtari Alexander N. 
Published: April 2019

Abstract
Detailed molecular characterization of a large cohort of mucosal melanomas, most arising from head and neck primaries, suggests that chromosomal translocations and other complex rearrangements have prognostic importance. CDK4 amplification is a frequent event in these rare tumors, and CDK4/6 inhibition may represent a rational clinical trial strategy.
See related article by Zhou et al., p. 3548
Heterochely and laterality in Kingsleya castrensis Pedraza, Martinelli-Filho & Magalhães, 2015 (Decapoda, Pseudothelphusidae)
Authors: Martinelli Filho José E. , Dos Santos Thuareag M. Trindade , Petracco Marcelo , De Lima-Gomes Renata C. , Magalhães Célio U. 
Published: April 2019

Abstract
Crabs of the family Pseudothelphusidae are restricted to the Neotropical region and new species are described every year. They are threatened by habitat loss and knowledge of this family is almost limited to taxonomy and faunal surveys. Here, we investigate the presence of heterochely and laterality in Kingsleya castrensis, as a tool to infer ecological and behavioural aspects. Since most Pseudothelphusidae were described from a few individuals only, some aspects of morphological variation, sexual dimorphism, heterochely and laterality are confirmed herein for the first time for a species of Kingsleya. The sizes of dactylus and propodus of males, as well as the allometric growth of both sides of the chelipeds, were significantly larger and higher, respectively, when compared to females. The right side was significantly longer than the left and both sexes displayed right-handedness. These results are similar to those from other freshwater crab families, and provide a clue to a possible aggressive, display, and territorial behaviour in K. castrensis.