bluuebunny/crossref_metadata_2025_split huggingface dataset:
Editing aberrant splice sites efficiently restores β-globin expression in β-thalassemia
Authors: Xu Shuqian , Luk Kevin , Yao Qiuming , Shen Anne H. , Zeng Jing , Wu Yuxuan , Luo Hong-Yuan , Brendel Christian , Pinello Luca , Chui David H. K. , Wolfe Scot A. , Bauer Daniel E. 
Published: January 2019

Abstract
The thalassemias are compelling targets for therapeutic genome editing in part because monoallelic correction of a subset of hematopoietic stem cells (HSCs) would be sufficient for enduring disease amelioration. A primary challenge is the development of efficient repair strategies that are effective in HSCs. Here, we demonstrate that allelic disruption of aberrant splice sites, one of the major classes of thalassemia mutations, is a robust approach to restore gene function. We target the IVS1-110G&gt;A mutation using Cas9 ribonucleoprotein (RNP) and the IVS2-654C&gt;T mutation by Cas12a/Cpf1 RNP in primary CD34+ hematopoietic stem and progenitor cells (HSPCs) from β-thalassemia patients. Each of these nuclease complexes achieves high efficiency and penetrance of therapeutic edits. Erythroid progeny of edited patient HSPCs show reversal of aberrant splicing and restoration of β-globin expression. This strategy could enable correction of a substantial fraction of transfusion-dependent β-thalassemia genotypes with currently available gene-editing technology.
Comprehensive Paired Tumor/Germline Testing for Lynch Syndrome: Bringing Resolution to the Diagnostic Process
Authors: Salvador Monalyn U. , Truelson Melissa R.F. , Mason Carla , Souders Beth , LaDuca Holly , Dougall Brittany , Black Mary Helen , Fulk Kelly , Profato Jessica , Gutierrez Stephanie , Jasperson Kory , Tippin-Davis Brigette , Lu Hsiao-Mei , Gray Phillip , Shah Swati , Chao Elizabeth C. , Ghahramani Negar , Landsverk Megan , Gau Chia-Ling , Chen Daniel , Pronold Melissa 
Published: January 2019

PURPOSE The current diagnostic testing algorithm for Lynch syndrome (LS) is complex and often involves multiple follow-up germline and somatic tests. We aimed to describe the results of paired tumor/germline testing performed on a large cohort of patients with colorectal cancer (CRC) and endometrial cancer (EC) to better determine the utility of this novel testing methodology. MATERIALS AND METHODS We retrospectively reviewed a consecutive series of patients with CRC and EC undergoing paired tumor/germline analysis of the LS genes at a clinical diagnostic laboratory (N = 702). Microsatellite instability, MLH1 promoter hypermethylation, and germline testing of additional genes were performed if ordered. Patients were assigned to one of five groups on the basis of prior tumor screening and germline testing outcomes. Results for each group are described. RESULTS Overall results were informative regarding an LS diagnosis for 76.1% and 60.8% of patients with mismatch-repair–deficient (MMRd) CRC and EC without and with prior germline testing, respectively. LS germline mutations were identified in 24.8% of patients in the group without prior germline testing, and interestingly, in 9.5% of patients with previous germline testing; four of these were discordant with prior tumor screening. Upon excluding patients with MLH1 promoter hypermethylation and germline mutations, biallelic somatic inactivation was seen in approximately 50% of patients with MMRd tumors across groups. CONCLUSION Paired testing identified a cause for MMRd tumors in 76% and 61% of patients without and with prior LS germline testing, respectively. Findings support inclusion of tumor sequencing as well as comprehensive LS germline testing in the LS testing algorithm. Paired testing offers a complete, convenient evaluation for LS with high diagnostic resolution.
Indeterminate Pulmonary Nodules at Diagnosis in Rhabdomyosarcoma: Are They Clinically Significant? A Report From the European Paediatric Soft Tissue Sarcoma Study Group
Authors: Vaarwerk Bas , Bisogno Gianni , McHugh Kieran , Brisse Hervé J. , Morosi Carlo , Corradini Nadège , Jenney Meriel , Orbach Daniel , Chisholm Julia C. , Ferrari Andrea , Zanetti Ilaria , De Salvo Gian Luca , van Rijn Rick R. , Merks Johannes H.M. ,   on behalf of the EpSSG Radiology Group
Published: January 2019

Purpose To evaluate the clinical significance of indeterminate pulmonary nodules at diagnosis (defined as ≤ 4 pulmonary nodules < 5 mm or 1 nodule measuring ≥ 5 and < 10 mm) in patients with pediatric rhabdomyosarcoma (RMS). Patients and Methods We selected patients with supposed nonmetastatic RMS treated in large pediatric oncology centers in the United Kingdom, France, Italy, and the Netherlands, who were enrolled in the European Soft Tissue Sarcoma Study Group (E pSSG) RMS 2005 study. Patients included in the current study received a diagnosis between September 2005 and December 2013, and had chest computed tomography scans available for review that were done at time of diagnosis. Local radiologists were asked to review the chest computed tomography scans for the presence of pulmonary nodules and to record their findings on a standardized case report form. In the E pSSG RMS 2005 Study, patients with indeterminate pulmonary nodules were treated identically to patients without pulmonary nodules, enabling us to compare event-free survival and overall survival between groups by log-rank test. Results In total, 316 patients were included; 67 patients (21.2%) had indeterminate pulmonary nodules on imaging and 249 patients (78.8%) had no pulmonary nodules evident at diagnosis. Median follow-up for survivors (n = 258) was 75.1 months; respective 5-year event-free survival and overall survival rates (95% CI) were 77.0% (64.8% to 85.5%) and 82.0% (69.7% to 89.6%) for patients with indeterminate nodules and 73.2% (67.1% to 78.3%) and 80.8% (75.1% to 85.3%) for patients without nodules at diagnosis ( P = .68 and .76, respectively). Conclusion Our study demonstrated that indeterminate pulmonary nodules at diagnosis do not affect outcome in patients with otherwise localized RMS. There is no need to biopsy or upstage patients with RMS who have indeterminate pulmonary nodules at diagnosis.
The OsJAZ1 degron modulates jasmonate signaling sensitivity during rice development
Authors: Tian Jiaqi , Cao Lichun , Chen Xiaofei , Chen Mingjiao , Zhang Peng , Cao Liming , Persson Staffan , Zhang Dabing , Yuan Zheng 
Published: January 2019

ABSTRACT
Jasmonates (JAs) are crucial to the coordination of plant stress responses and development. JA signaling depends on JASMONATE-ZIM DOMAIN (JAZ) proteins that are destroyed by the SCFCOI1-mediated 26S proteasome when the JAZ co-receptor COI1 binds active JA or the JA-mimicking phytotoxin coronatine (COR). JAZ degradation releases JAZ-interacting transcription factors that can execute stress and growth responses. The JAZ proteins typically contain Jas motifs that undergo conformational changes during JA signal transduction and that are important for the JAZ-COI1 interaction and JAZ protein degradation. However, how alterations in the Jas motif and, in particular, the JAZ degron part of the motif, influence protein stability and plant development have not been well explored. To clarify this issue, we performed bioassays and genetic experiments to uncover the function of the OsJAZ1 degron in rice JA signaling. We found that substitution or deletion of core segments of the degron altered the OsJAZ1-OsCOI1b interaction in a COR-dependent manner. We show that these altered interactions function as a regulator for JA signaling during flower and root development. Our study therefore expands our understanding of how the JAZ degron functions, and provides the means to change the sensitivity and specificity of JA signaling in rice.
Faecal incontinence: investigation and treatment
Authors: Nazarko Linda 
Published: January 2019

Up to 10% of adults can experience faecal incontinence in their lives, which can be caused by many factors. Linda Nazarko investigates the causes of incontinence as well as treatment and management pathways that nurses can consider for their patients Faecal incontinence (FI) is a hidden problem that is under diagnosed, under investigated and under treated. Up to 10% of adults can experience an episode of FI. The prevalence of FI in the adult population has been estimated at 0.8–6.2%, a recent North American research indicated a prevalence of 8.3% in adults living in the community ( Ditah et al, 2014 ). This article explores the reasons why adults can develop FI, the importance of assessment, what treatments are available and how intractable FI can best be managed.
An evaluation of an innovative workforce development strategy
Authors: Akpenyi Onyinye , Sayer Melissa , Nicholson Ellen , Clarke Mary 
Published: January 2019

Practice nurses are strategically placed to provide high-quality care to their patients; however, a shortage in the nursing population and increasing demands on general practice have left nurses in need of new development schemes to meet these workforce challenges Background: A training scheme was devised to address a deficit in recruiting practice nurses. It was a competency-based programme tailored to the role and population needs. Aims: This study aimed to evaluate the effectiveness of the training scheme, assess whether or not objectives were met, and identify areas in need of improvement. Methods: An online survey was created and sent to nurses. Satisfaction questionnaires were given to patients seen by the nurses towards the end of their training scheme. Findings: Responses were received from 6 nurses and 16 patients. Nurses rated the scheme highly and reported confidence in handling the role, but had notable variation in perception of competency in different programme domains. Patients consistently rated the nurses as ‘outstanding’ and were ‘very likely’ to recommend them. There was a correlation between patients' and nurses' perception of competency. Conclusion: A successful pilot of the training scheme which will ideally pave the way for further research.
Lumbar fusion involving the sacrum increases dislocation risk in primary total hip arthroplasty
Authors: Salib C. G. , Reina N. , Perry K. I. , Taunton M. J. , Berry D. J. , Abdel M. P. 
Published: January 2019

Aims Concurrent hip and spine pathologies can alter the biomechanics of spinopelvic mobility in primary total hip arthroplasty (THA). This study examines how differences in pelvic orientation of patients with spine fusions can increase the risk of dislocation risk after THA. Patients and Methods We identified 84 patients (97 THAs) between 1998 and 2015 who had undergone spinal fusion prior to primary THA. Patients were stratified into three groups depending on the length of lumbar fusion and whether or not the sacrum was involved. Mean age was 71 years (40 to 87) and 54 patients (56%) were female. The mean body mass index (BMI) was 30 kg/m2 (19 to 45). Mean follow-up was six years (2 to 17). Patients were 1:2 matched to patients with primary THAs without spine fusion. Hazard ratios (HR) were calculated. Results Dislocation in the fusion group was 5.2% at one year versus 1.7% in controls but this did not reach statistical significance (HR 1.9; p = 0.33). Compared with controls, there was no significant difference in rate of dislocation in patients without a sacral fusion. When the sacrum was involved, the rate of dislocation was significantly higher than in controls (HR 4.5; p = 0.03), with a trend to more dislocations in longer lumbosacral fusions. Patient demographics and surgical characteristics of THA (i.e. surgical approach and femoral head diameter) did not significantly impact risk of dislocation (p > 0.05). Significant radiological differences were measured in mean anterior pelvic tilt between the one-level lumbar fusion group (22°), the multiple-level fusion group (27°), and the sacral fusion group (32°; p < 0.01). Ten-year survival was 93% in the fusion group and 95% in controls (HR 1.2; p = 0.8). Conclusion Lumbosacral spinal fusions prior to THA increase the risk of dislocation within the first six months. Fusions involving the sacrum with multiple levels of lumbar involvement notably increased the risk of postoperative dislocation compared with a control group and other lumbar fusions. Surgeons should take care with component positioning and may consider higher stability implants in this high-risk cohort.
Common NOD2 Risk Variants as Major Susceptibility Factors for Bacterial Infections in Compensated Cirrhosis
Authors: Reichert Matthias Christian , Ripoll Cristina , Casper Markus , Greinert Robin , Vandieken Edith , Grünhage Frank , Appenrodt Beate , Zipprich Alexander , Lammert Frank 
Published: January 2019

OBJECTIVES:
Common nucleotide-binding oligomerization domain containing 2 (NOD2) gene variants have been associated with bacterial infections (BIs) in cirrhosis, in particular, spontaneous bacterial peritonitis, and mortality. Our aim was to evaluate the independent association of NOD2 variants with BI according to the decompensation stage.

METHODS:
Consecutive patients with cirrhosis in 2 academic medical centers were included and genotyped for the NOD2 variants p.R702W, p.G908R, and c.3020insC. Electronic medical records were screened for BI (requiring antibiotic therapy) and past and present decompensation (as defined by variceal bleeding, encephalopathy, ascites, and/or jaundice). Clinically significant portal hypertension (CSPH) was assessed with liver stiffness and/or hepatic venous pressure gradient measurements.

RESULTS:
Overall, 735 patients were recruited (men 65%; interquartile age range 53–68 years). Alcoholic cirrhosis was the predominant etiology (n = 406, 55%), and most patients were in the decompensated stage (n = 531, 72%). In total, 158 patients (21%) carried at least one NOD2 variant. BIs were detected in 263 patients (36%), and NOD2 variants were associated with BI (odds ratio = 1.58; 95% confidence interval 1.11–2.27; P = 0.02). In compensated patients, the combination of NOD2 variants and presence of CSPH was the best independent predictors of BI, whereas other factors, such as spleen size and hemoglobin, and decompensations including hepatic encephalopathy or jaundice, gained relevance in decompensated patients.

CONCLUSIONS:

NOD2 risk variants are associated with BI in cirrhosis. The genetic effect on BI is strongest in compensated patients, whereas in decompensated patients their presence is less relevant. In this situation, CSPH becomes an independent factor associated with BI.
Whole Genome Messenger RNA Profiling Identifies a Novel Signature to Predict Gastric Cancer Survival
Authors: Dai Jin , Li Zhe-Xuan , Zhang Yang , Ma Jun-Ling , Zhou Tong , You Wei-Cheng , Li Wen-Qing , Pan Kai-Feng 
Published: January 2019

OBJECTIVES:
Molecular prognostic biomarkers for gastric cancer (GC) are still limited. We aimed to identify potential messenger RNAs (mRNAs) associated with GC prognosis and further establish an mRNA signature to predict the survival of GC based on the publicly accessible databases.

METHODS:
Discovery of potential mRNAs associated with GC survival was undertaken for 441 patients with GC based on the Cancer Genome Atlas (TCGA), with information on clinical characteristics and vital status. Gene ontology functional enrichment analysis and pathway enrichment analysis were conducted to interrogate the possible biological functions. We narrowed down the list of mRNAs for validation study based on a significance level of 1.00 × 10−4, also integrating the information from the methylation analysis and constructing the protein–protein interaction network for elucidating biological processes. A total of 54 mRNAs were further studied in the validation stage, using the Gene Expression Omnibus (GEO) database (GSE84437, n = 433). The validated mRNAs were used to construct a risk score model predicting the prognosis of GC.

RESULTS:
A total of 13 mRNAs were significantly associated with survival of GC, after the validation stage, including DCLK1, FLRT2, MCC, PRICKLE1, RIMS1, SLC25A15, SLCO2A1, CDO1, GHR, CD109, SELP, UPK1B, and CD36. Except CD36, DCLK1, and SLCO2A1, other mRNAs are newly reported to be associated with GC survival. The 13 mRNA-based risk score had good performance on distinguishing GC prognosis, with a higher score indicating worse survival in both TCGA and GEO datasets.

CONCLUSIONS:
We established a 13-mRNA signature to potentially predict the prognosis of patients with GC, which might be useful in clinical practice for informing patient stratification.
Fenomenologia i performatyka gestu w tańcu współczesnym
Authors: Fazan Teresa 
Published: January 2019

The paper covers the problem of gestural expression and the role of the body in the aesthetic experience analysed in the Maurice Merleau-Ponty’s phenomenology of art and Erika Fischer-Lichte’s theory of performance. The author compiles these theorists’ conclusions and contextualizes them in the field of modern and postmodern dance. The ultimate goal is to analyse the artists’ statements in the context of formulated conclusions and syntheses. In summary, the author draws attention to current aesthetic research on dance and pinpoints the benefits of philosophical phenomenological) interest in the modern and postmodern dance.
Effects of task goal orientation on learner engagement in task performance
Authors: Dao Phung 
Published: January 2019

Abstract
The study investigated the potential impact of task goal orientation on cognitive, social and emotional aspects of task performance through the lens of learner engagement. Sixteen EFL learner dyads completed a convergent decision-making task and a divergent opinion-exchange task. Their audio-recorded interactions were transcribed and coded for evidence of engagement, including idea units and language-related-episodes (cognitive engagement), instances of explicit task enjoyment, reported emotions (emotional engagement), and responsiveness (social engagement). To determine the effects of task goal orientation on learner engagement, scores for engagement types were compared between two tasks. To understand learners’ perception about their engagement, posttask exit questionnaire responses were analyzed using content-analysis approach. Findings showed that learners showed greater cognitive and social engagement in the convergent than divergent tasks. No differences were observed in learners’ emotional engagement. Results are discussed in terms of the role of task goal orientation in promoting learners’ cognitive and social engagement.
Is there anybody out there: what do senior surgeons expect of their youngsters?
Authors: Vallböhmer Daniel , Fuchs Hans , Dittmar Ronny , Krones Carsten J. 
Published: January 2019

AbstractSurgery is indeed one of the most fascinating medical professions. However, it is also a stressful field of work with a high workload, and often leaves little time for personal and family needs. Within the last decade, a noticeable decline occurred in the willingness of medical students to enter a surgical residency. In fact, Generation Y is highly interested in a medical career with a respectful working atmosphere and balanced work and private life, as published in several recent papers. Therefore, surgery must evolve with the times to retain its attractiveness as a career choice for medical students and to compete for the best talents from Generation Y. However, little is known about what senior surgeons really expect from young surgical residents. On the basis of a recent survey by the Professional Association of German Surgeons, this paper tries to give some insights in this very relevant topic and a perspective on how to increase the attractiveness of our fascinating specialty. In fact, in this survey, senior surgeons defined a very clear requirement profile for surgical residency applicants. While the colleagues defined accurate applicant documents, a previous internship, self-motivation, and impressions from the job interview as the most important factors for a successful application for a surgical residency, a standard period of study or a dissertation was deemed of lower importance.
Thyroid function in patients with Prader-Willi syndrome: an Italian multicenter study of 339 patients
Authors: Iughetti Lorenzo , Vivi Giulia , Balsamo Antonio , Corrias Andrea , Crinò Antonino , Delvecchio Maurizio , Gargantini Luigi , Greggio Nella Augusta , Grugni Graziano , Hladnik Uros , Pilotta Alba , Ragusa Letizia , Salvatoni Alessandro , Wasniewska Malgorzata , Weber Giovanna , Predieri Barbara 
Published: January 2019

AbstractBackgroundPrader-Willi syndrome (PWS) is a genetic disorder due to loss of expression of paternally transcribed genes of the imprinted region of chromosome 15q11-13. PWS is characterized by peculiar signs and symptoms and many endocrine abnormalities have been described (growth hormone deficiency, hypogonadotropic hypogonadism). The abnormalities of thyroid function are discussed in literature and published data are discordant. The aim of our study was to report the thyroid function in patients with PWS to identify the prevalence of thyroid dysfunction.MethodsThyroid function tests were carried out in 339 patients with PWS, aged from 0.2 to 50 years. A database was created to collect personal data, anthropometric data, thyroid function data and possible replacement therapy with L-thyroxine. Subjects were classified according to thyroid function as: euthyroidism (EuT), congenital hypothyroidism (C-HT), hypothyroidism (HT – high thyroid-stimulating hormone [TSH] and low free thyroxine [fT4]), central hypothyroidism (CE-H – low/normal TSH and low fT4), subclinical hypothyroidism (SH – high TSH and normal fT4), and hyperthyroidism (HyperT – low TSH and high fT4).ResultsTwo hundred and forty-three out of 339 PWS patients were younger than 18 years (71.7%). The prevalence of thyroid dysfunction was 13.6%. Specifically, C-HT was found in four children (1.18%), HT in six patients (1.77%), CE-H in 23 patients (6.78%), SH in 13 patients (3.83%), and HyperT in none. All other subjects were in EuT (86.4%).ConclusionsHypothyroidism is a frequent feature in subjects with PWS. Thyroid function should be regularly investigated in all PWS patients both at the diagnosis and annually during follow-up.
Multi-term fractional differential equations with nonlocal boundary conditions
Authors: Ahmad Bashir , Alghamdi Najla , Alsaedi Ahmed , Ntouyas Sotiris K. 
Published: January 2019

AbstractWe introduce and study a new kind of nonlocal boundary value problems of multi-term fractional differential equations. The existence and uniqueness results for the given problem are obtained by applying standard fixed point theorems. We also construct some examples for demonstrating the application of the main results.
Crystal structure of chlorido-(6,6′-((1,2-phenylenebis(azanylylidene))bis(methanylylidene))bis(3-methoxyphenolato)-κ4
O,N,N′,O′)iron(III), C22H18ClN2FeO4
Authors: Cuihong Zhang , Yuan Ge , Xiaoping Huo , Liguo Yang , Xin Li , Zongcheng Miao 
Published: January 2019

Abstract
C22H18ClN2FeO4, monoclinic, P21/n (no. 14), a = 7.0779(6) Å, b = 19.0203(16) Å, c = 14.7233(12) Å, β = 103.1570(10)°, V = 1930.1(3) Å3, Z = 4, R
gt(F) = 0.0278, wR
ref(F
2) = 0.1037, T = 296(2) K.