bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fundoscopy-directed genetic testing to re-evaluate negative whole exome sequencing results
Authors: Cho Ahra , Lima de Carvalho Jose Ronaldo , Tanaka Akemi J. , Jauregui Ruben , Levi Sarah R. , Bassuk Alexander G. , Mahajan Vinit B. , Tsang Stephen H. 
Published: January 2020

Abstract
Background
Whole exome sequencing (WES) allows for an unbiased search of the genetic cause of a disease. Employing it as a first-tier genetic testing can be favored due to the associated lower incremental cost per diagnosis compared to when using it later in the diagnostic pathway. However, there are technical limitations of WES that can lead to inaccurate negative variant callings. Our study presents these limitations through a re-evaluation of negative WES results using subsequent tests primarily driven by fundoscopic findings. These tests included targeted gene testing, inherited retinal gene panels, whole genome sequencing (WGS), and array comparative genomic hybridization.

Results
Subsequent genetic testing guided by fundoscopy findings identified the following variant types causing retinitis pigmentosa that were not detected by WES: frameshift deletion and nonsense variants in the RPGR gene, 353-bp Alu repeat insertions in the MAK gene, and large exonic deletion variants in the EYS and PRPF31 genes. Deep intronic variants in the ABCA4 gene causing Stargardt disease and the GUCY2D gene causing Leber congenital amaurosis were also identified.

Conclusions
Negative WES analyses inconsistent with the phenotype should raise clinical suspicion. Subsequent genetic testing may detect genetic variants missed by WES and can make patients eligible for gene replacement therapy and upcoming clinical trials. When phenotypic findings support a genetic etiology, negative WES results should be followed by targeted gene sequencing, array based approach or whole genome sequencing.
HPV-mediated down-regulation of NOD1 inhibits apoptosis in cervical cancer
Authors: Liu Xubin , Ma Hanyu , Fei Lingyan , Jiang Mengjie , Xia Meng , Bai Lihong , Pi Xufang , Chen Shangwu , Yu Li 
Published: January 2020

AbstractCervical cancer is the fourth most common malignant tumor in women worldwide. The persistent infection of high-risk Human Papillomavirus (hrHPV) is considered to be the primary cause of this disease. As an innate immune receptor, the nucleotide-binding oligomerization domain protein-1 (NOD1) recognizes the pathogen-associated molecular pattern (PAMP), subsequently initiating immune responses. NOD1 is also involved in the apoptotic signaling pathway and mutates in many cancer cells. In the study, we revealed that NOD1 expression decreased during the progression of cervical intraepithelial neoplasia to cervical cancer and that HPV16 E6/E7 oncoproteins induced down-regulation of NOD1. Moreover, the activation of NOD1 promoted the apoptosis of HPV16-positive cervical cancer cells. The data indicated that the dysregulation of NOD1-mediated inflammation and apoptosis may contribute to cervical intraepithelial neoplasia progression and cervical cancer.
Acute myeloid leukemia with inv(16)(p13.1q22) and deletion of the 5’MYH11/3’CBFB gene fusion: a report of two cases and literature review
Authors: Lv Lili , Yu Jingwei , Qi Zhongxia 
Published: January 2020

Abstract
Background
Abnormalities of chromosome 16 are found in about 5–8% of acute myeloid leukemia (AML). The AML with inv(16)(p13.1q22) or t (16;16)(p13.1;q22) is associated with a high rate of complete remission (CR) and favorable overall survival (OS) when treated with high-dose Cytarabine. At the inversion breakpoints, deletion of 3’CBFB has been reported, but most of them were studied by chromosome and fluorescence in situ hybridization (FISH) analyses. The genomic characteristics of such deletions remain largely undefined, hindering further understanding of the clinical significance of the deletions.

Case presentation
We report here two AML cases with inv(16) and deletion of the 5’MYH11/3’CBFB gene fusion, which were characterized by chromosome, FISH, and single nucleotide polymorphism (SNP) microarray analyses. Both cases have achieved CR for more than three years.

Conclusions
Deletion of 3’CBFB in AML with inv(16) is also accompanied with deletion of 5’MYH11 in all the cases studied by SNP microarray, suggesting that 3’CBFB and 5’MYH11 were most likely deleted together as a fusion product of inv(16) instead of occurring separately. In concert with the findings of other published studies of similar patients, our study suggests that deletion of 5’MYH11/3’CBFB in AML with inv(16) may not have negative impact on the prognosis of the disease.
Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) – Study protocol from a randomized controlled trial
Authors:   the BRONCHIOLE investigators, Sundh Josefin , Magnuson Anders , Montgomery Scott , Andell Pontus , Rindler Gustaf , Fröbert Ole 
Published: January 2020

Abstract
Background
Observational studies indicate that beta-blockers are associated with a reduced risk of exacerbation and mortality in patients with chronic obstructive pulmonary disease (COPD) even without overt cardiovascular disease, but data from randomized controlled trials (RCT) are lacking. The aim of this RCT is to investigate whether beta-blocker therapy in patients with COPD without diagnosed cardiovascular disease is associated with a decreased 1-year risk of the composite endpoint of death, exacerbations, or cardiovascular events.

Methods
The Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) study is an open-label, multicentre, prospective RCT. A total of 1700 patients with COPD will be randomly assigned to either standard COPD care and metoprolol at a target dose of 100 mg per day or to standard COPD care only. The primary endpoint is a composite of death, COPD exacerbations, and cardiovascular events. Major exclusion criteria are ischemic heart disease, left-sided heart failure, cerebrovascular disease, critical limb ischemia, and atrial fibrillation/flutter. Study visits are an inclusion visit, a metoprolol titration visit at 1 month, follow-up by telephone at 6 months, and a final study visit after 1 year. Outcome data are obtained from medical history and record review during study visits, as well as from national registries.

Discussion
BRONCHIOLE is a pragmatic randomized trial addressing the potential of beta-blockers in patients with COPD. The trial is expected to provide relevant clinical data on the efficacy of this treatment on patient-related outcomes in patients with COPD.

Trial registration
ClinicalTrials.gov, ID: NCT03566667. Registered on 25 June 2018.
Randomised, double-blind, placebo controlled multi-centre study to assess the efficacy, tolerability and safety of Enterosgel® in the treatment of irritable bowel syndrome with diarrhoea (IBS-D) in adults
Authors: Kemppinen Anu , Howell Carol , Allgar Victoria , Dodd Matthew , Gregson John , Knowles Charles , McLaughlin John , Pandya Preeti , Whorwell Peter , Markaryan Elena , Yiannakou Yan 
Published: January 2020

Abstract
Background
Irritable bowel syndrome (IBS) with diarrhoea (IBS-D) is a common and chronic condition that can significantly impair quality of life. The emergence of new drugs for IBS-D has been slow and there is a need for new treatments, including drug-free treatments, which are easy to use and suitable for different patient groups. Currently available drug-free treatments include Enterosgel®, an intestinal adsorbent approved for use in IBS-D and acute diarrhoea and available over-the-counter in the UK and 30 countries worldwide. The aim of this randomised, double-blind, placebo-controlled, multi-centre study is to test the efficacy and safety of Enterosgel® compared to placebo in symptomatic treatment in IBS-D.

Methods/design
We will recruit 430 participants with IBS-D from approximately 30 primary and secondary care sites in England. Participants meeting the required abdominal pain and stool consistency criteria over a 2-week screening period will be randomly allocated to receive blinded treatment (Enterosgel® or placebo) for 8 weeks. This will be followed by an 8-week open-label treatment phase with Enterosgel®. Participants will be allowed to adjust their daily dosage during both phases based on their symptoms. Participants will then return to standard care and those who responded to treatment will receive a follow-up call 8 weeks later. Co-medication with loperamide will be permitted and use recorded. The primary outcome measure is the percentage of participants defined as responders for abdominal pain and stool consistency during at least 4 weeks in the 8-week blinded phase. Secondary outcome measures include stool frequency, stool consistency, abdominal pain, bloating, urgency, adequate relief, questionnaire scores and rescue medication use. Exploratory outcomes will be assessed in subsets of participants including qualitative and quantitative data on faecal microorganisms and biomarkers and gut-related measurements from magnetic resonance imaging data.

Discussion
This is the first large scale randomised controlled trial investigating Enterosgel® in IBS-D. A study design with blinded phase followed by an open-label phase was chosen to encourage participation and study completion. Demonstrating that Enterosgel® is effective and safe in IBS-D could encourage adoption by patients and healthcare professionals and foster future clinical trials assessing its use in related conditions.

Trial registration
ISRCTN17149988. Prospectively registered on 14 November 2017.
Exploring why sodium lignosulfonate influenced enzymatic hydrolysis efficiency of cellulose from the perspective of substrate–enzyme adsorption
Authors: Zheng Wenqiu , Lan Tianqing , Li Hui , Yue Guojun , Zhou Haifeng 
Published: January 2020

Abstract
Background
Cellulase adsorbed on cellulose is productive and helpful to produce reducing sugars in enzymatic hydrolysis of lignocellulose; however, cellulase adsorbed on lignin is non-productive. Increasing productive adsorption of cellulase on cellulose would be beneficial in improving enzymatic hydrolysis. Adding lignin that was more hydrophilic in hydrolysis system could increase productive adsorption and promote hydrolysis. However, the effect mechanism is still worth exploring further. In this study, lignosulfonate (LS), a type of hydrophilic lignin, was used to study its effect on cellulosic hydrolysis.

Results
The effect of LS on the enzymatic hydrolysis of pure cellulose (Avicel) and lignocellulose [dilute acid (DA) treated sugarcane bagasse (SCB)] was investigated by analyzing enzymatic hydrolysis efficiency, productive and non-productive cellulase adsorptions, zeta potential and particle size distribution of substrates. The result showed that after adding LS, the productive cellulase adsorption on Avicel reduced. Adding LS to Avicel suspension could form the Avicel–LS complexes. The particles were charged more negatively and the average particle size was smaller than Avicel before adding LS. In addition, adding LS to cellulase solution formed the LS–cellulase complexes. For DA-SCB, adding LS decreased the non-productive cellulase adsorption on DA-SCB from 3.92 to 2.99 mg/g lignin and increased the productive adsorption of cellulase on DA-SCB from 2.00 to 3.44 mg/g cellulose. Besides, the addition of LS promoted the formation of LS–lignin complexes and LS–cellulase complexes, and the complexes had more negative charges and smaller average sizes than DA-SCB lignin and cellulase particles before adding LS.

Conclusions
In this study, LS inhibited Avicel’s hydrolysis, but enhanced DA-SCB’s hydrolysis. This stemmed from the fact that LS could bind cellulase and Avicel, and occupied the binding sites of cellulase and Avicel. Thus, a decreased productive adsorption of cellulase on Avicel arose. Regarding DA-SCB, adding LS, which enhanced hydrolysis efficiency of DA-SCB, increased the electrostatic repulsion between DA-SCB lignin and cellulase, and therefore, decreased non-productive adsorption of cellulase on DA-SCB lignin and enhanced productive adsorption of cellulase on DA-SCB cellulose.

Graphical abstract
Maternal survival in a low-resource setting, Mpilo Central Hospital, Bulawayo, Zimbabwe
Authors: Ngwenya Solwayo , Nleya Faith , Mwembe Desmond 
Published: January 2020

Abstract
Objectives
Maternal mortality is an important global subject. This dataset was generated from a retrospective cross-sectional study carried out at Mpilo Central Hospital, covering the period January 1, 2015 to December 31, 2018. The aim of the study was to compare how frequently the exposure to a risk factor was related to maternal death. Maternal deaths that were recorded during the study period were considered as cases. Controls were selected randomly from women of child-bearing age who survived during the study period. Low-resourced countries contribute significantly to global maternal deaths. Understanding risk factors could help reduce maternal mortality.

Data description
The dataset contains data of 387 pregnant women who were included in the study. Data were collected as secondary data using a data collection sheet, as recorded by the hospital staff that gave all necessary demographic details in birth and mortality registers. The data collected included socio-demographic and clinical data. The independent variables were maternal age, gravidity, parity, antenatal visits, booking status, marital status, educational status, days spent in hospital, mode of delivery, fetal outcomes, and maternal complications. The dependent variable was maternal mortality. The data can be used to determine the relationship between the independent variables and maternal death.
Inside the system-wide cultural district: a new relational and organisational taxonomy of cultural districts based on the sector policies by Italian Regions (2000–2015)
Authors: Colavitti Anna Maria , Usai Alessia 
Published: January 2020

AbstractA considerable environmental turbulence pushes cultural and creative firms to cluster and to adopt new forms of cross-integration. An issue common also to wider entrepreneurial ecosystems (EEs) of SMEs. This evolutionary trend has given birth to a new generation of cultural districts defined as system-wide cultural districts (SWCDs) in which culture acts like a lever for all production sectors and not merely the cultural one, as in the past. The paper investigates the internal nested geographies of SWCDs through a comparative analysis of the district policies implemented by Italian Regions from 2000 to 2015 providing a new classification of cultural districts that updates the existing ones and reflecting on the links between SWCDs, urban policies and landscape planning.
Everything in moderation: ICT and reading performance of Dutch 15-year-olds
Authors: Gubbels Joyce , Swart Nicole M. , Groen Margriet A. 
Published: January 2020

AbstractPrevious research on the relationship between students’ home and school Information and Communication Technology (ICT) resources and academic performance has shown ambiguous results. The availability of ICT resources at school has been found to be unrelated or negatively related to academic performance, whereas the availability of ICT resources at home has been found to be both positively and negatively related to academic performance. In addition, the frequency of use of ICT is related to students’ academic achievement. This relationship has been found to be negative for ICT use at school, however, for ICT use at home the literature on the relationship with academic performance is again ambiguous. In addition to ICT availability and ICT use, students’ attitudes towards ICT have also been found to play a role in student performance. In the present study, we examine how availability of ICT resources, students’ use of those resources (at school, outside school for schoolwork, outside school for leisure), and students’ attitudes toward ICT (interest in ICT, perceived ICT competence, perceived ICT autonomy) relate to individual differences in performance on a digital assessment of reading in one comprehensive model using the Dutch PISA 2015 sample of 5183 15-year-olds (49.2% male). Student gender and students’ economic, social, and cultural status accounted for a substantial part of the variation in digitally assessed reading performance. Controlling for these relationships, results indicated that students with moderate access to ICT resources, moderate use of ICT at school or outside school for schoolwork, and moderate interest in ICT had the highest digitally assessed reading performance. In contrast, students who reported moderate competence in ICT had the lowest digitally assessed reading performance. In addition, frequent use of ICT outside school for leisure was negatively related to digitally assessed reading performance, whereas perceived autonomy was positively related. Taken together, the findings suggest that excessive access to ICT resources, excessive use of ICT, and excessive interest in ICT is associated with lower digitally assessed reading performance.
Determination of the increased risk of developing atrial fibrillation in fibromyalgia syndrome
Authors: Akkaya Hasan , Güntürk Ertuğrul Emre , Kaydok Ercan , Özdemir Betül 
Published: January 2020

Abstract
Introduction
Atrial fibrillation (AF) is the leading cause of ischemic stroke and is one of the most common arrhythmias. Previous studies have shown that impaired diastolic functions, P wave dispersion (Pd), and prolonged atrial conduction times (ACT) are associated with increased incidence of atrial fibrillation (AF). The aim of this study was to evaluate diastolic functions, Pd, and ACT in fibromyalgia syndrome (FMS) patients to determine whether there is an increase in the risk of developing AF.

Methods
The study included a total of 140 female patients (70 FMS group, 70 healthy control group). Pd was evaluated using 12 lead electrocardiography (ECG), and diastolic functions and ACT with echocardiography. The ECG and echocardiographic evaluations were performed by different cardiologists blinded to the clinical information of the subjects.

Results
There was no difference between the two groups in laboratory and clinical parameters. Patients with FMS had significantly higher echocardiographic parameters of ACT known as left-sided intra-atrial (13.9 ± 5.9 vs. 8.1 ± 1.8, p < 0.001), right-sided intra-atrial (21.9 ± 8.2 vs. 10.4 ± 3.5, p < 0.001) and interatrial [40 (25–64) ms vs. 23 (14–27) ms p < 0.001] electromechanical interval (EMI) compared with the control group. Pd was significantly greater in the FMS group compared with the control group [46 (29–62) ms vs. 32 (25–37) ms, p < 0.001]. In the FMS group, there was no significant relationship of the echocardiographic parameters of ACT, Pmax and Pd with age, E/A ratio and deceleration time (DT); while all these five parameters were significantly correlated with left atrial dimension, isovolumetric relaxation time (IVRT), fibromyalgia impact questionnaire (FIQ) and visual analogue scale (VAS). There was a strong correlation between FIQ and VAS and echocardiographic parameters of ACT, Pmax and Pd.

Conclusions
Impaired diastolic functions, an increase in Pd, and prolongation of ACT were observed in FMS. Current disorders are thought to be associated with an increased risk of AF in FMS. The risk of developing AF increases with the severity of FMS and clinical progression.
Neutrophil/lymphocyte and platelet/lymphocyte ratios as potential markers of disease activity in patients with Ankylosing spondylitis: a case-control study
Authors: Al-Osami Mohammed Hadi , Awadh Nabaa Ihsan , Khalid Khalid Burhan , Awadh Ammar Ihsan 
Published: January 2020

Abstract
Background
The neutrophil/ lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) have the potential to be inflammatory markers that reflect the activity of many inflammatory diseases. The aim of this study was to evaluate the NLR and PLR as potential markers of disease activity in patients with ankylosing spondylitis.

Methods
The study involved 132 patients with ankylosing spondylitis and 81 healthy controls matched in terms of age and gender. Their sociodemographic data, disease activity scores using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), erythrocyte sedimentation rate (ESR), and white blood cell, neutrophil, lymphocyte and platelet counts were recorded. The patients with ankylosing spondylitis were further divided according to their BASDAI scores into patients with inactive disease (BASDAI < 4) and patients with active disease (BASDAI ≥4). The correlations between the NLR, PLR and disease activity were analysed.

Results
There was a statistically significant difference in the NLR and PLR between the active and inactive ankylosing spondylitis patients (2.31 ± 1.23 vs. 1.77 ± 0.73, p = 0.002), (142.04 ± 70.98 vs. 119.24 ± 32.49, p <  0.001, respectively). However, there was no significant difference in both the NLR and PLR between the healthy control group and ankylosing spondylitis patients (p > 0.05). In addition, the PLR was significantly higher in both the active and inactive groups compared to those in the healthy control group (142.04 ± 70.98 vs. 99.32 ± 33.97, p = 0.014), (119.24 ± 32.49 vs. 99.32 ± 33.97, p = 0.019). The BASDAI scores were positively correlated with the PLR (r = 0.219, p = 0.012) and the NLR, but they were not statistically significant with the later (r = 0.170, p = 0.051). Based on the ROC curve, the best NLR cut-off value for predicting severe disease activity in ankylosing spondylitis patients was 1.66, with a sensitivity of 61.8% and a specificity of 50.6%, whereas the best PLR cut-off value was 95.9, with a sensitivity of 70.9% and a specificity of 55.5%.

Conclusion
The PLR may be used as a useful marker in the assessment and monitoring of disease activity in AS together with acute phase reactants such as the ESR.