bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two paralogous znf143 genes in zebrafish encode transcriptional activator proteins with similar functions but expressed at different levels during early development
Authors: Huning Laura , Kunkel Gary R. 
Published: January 2020

Abstract
Background
ZNF143 is an important transcriptional regulator protein conserved in metazoans and estimated to bind over 2000 promoter regions of both messenger RNA and small nuclear RNA genes. The use of zebrafish is a useful model system to study vertebrate gene expression and development. Here we characterize znf143a, a novel paralog of znf143b, previously known simply as znf143 in zebrafish. This study reveals a comparison of quantitative and spatial expression patterns, transcriptional activity, and a knockdown analysis of both ZNF143 proteins.

Results
ZNF143a and ZNF143b have a fairly strong conservation with 65% amino acid sequence identity, and both are potent activators in transient transfection experiments. In situ hybridization analyses of both znf143 mRNAs show that these genes are expressed strongly in regions of the brain at 24 h post fertilization in zebrafish development. A transient knockdown analysis of znf143 expression from either gene using CRISPR interference revealed similar morphological defects in brain development, and caused brain abnormalities in up to 50% of injected embryos. Although present in the same tissues, znf143a is expressed at a higher level in early development which might confer an evolutionary benefit for the maintenance of two paralogs in zebrafish.

Conclusions
znf143a encodes a strong activator protein with high expression in neural tissues during early embryogenesis in zebrafish. Similar to its paralogous gene, znf143b, both znf143 genes are required for normal development in zebrafish.
Zn/Cd status-dependent accumulation of Zn and Cd in root parts in tobacco is accompanied by specific expression of ZIP genes
Authors: Palusińska Małgorzata , Barabasz Anna , Kozak Katarzyna , Papierniak Anna , Maślińska Karolina , Antosiewicz Danuta Maria 
Published: January 2020

Abstract
Background
Root-to-shoot translocation of zinc (Zn) and cadmium (Cd) depends on the concentrations of both metals in the medium. A previous study on tobacco (Nicotiana tabacum) pointed to the contribution of NtZIP1, NtZIP2, NtZIP4 and NtIRT1-like in the regulation of this phenomenon. To learn more, Zn and Cd accumulation, root/shoot distribution and the expression of ZIP genes were investigated in the apical, middle and basal root parts.

Results
We show that Zn/Cd status-dependent root-shoot distribution of both metals was related to distinct metal accumulation in root parts. At low Zn and Cd in the medium, the apical part contained the highest metal level; at higher concentrations, the middle and basal parts were the major sink for excess metal. The above were accompanied by root part-specific expression pattern modifications of ZIPs (NtZIP1-like, NtZIP2, NtZIP4A/B, NtZIP5A/B, NtZIP5-like, NtZIP8, NtZIP11, NtIRT1, and NtIRT1-like) that fell into four categories with respect to the root part. Furthermore, for lower Zn/Cd concentrations changes were noted for NtZIP5A/B and NtZIP5-like only, but at higher Zn and Cd levels for NtZIP1-like, NtZIP5-like, NtZIP8, NtZIP11, NtIRT1, and NtIRT1-like. NtZIP1, here renamed to NtZIP5B, was cloned and characterized. We found that it was a zinc deficiency-inducible transporter involved in zinc and cadmium uptake from the soil solution primarily by the middle root part.

Conclusions
We conclude that regulation of the longitudinal distribution of Zn and Cd is highly specific, and that the apical, middle and basal root parts play distinct roles in Zn/Cd status-dependent control of metal translocation efficiency to shoots, including the stimulation of Zn translocation to shoots in the presence of Cd. These results provide new insight into the root part-specific unique role of NtZIP5B and other ZIP genes in the longitudinal distribution of zinc and cadmium and their contribution to the regulation of root-to-shoot translocation.
Gaps between current clinical practice and evidence-based guidelines for treatment and care of older patients with Community Acquired Pneumonia: a descriptive cross-sectional study
Authors: Eekholm Signe , Ahlström Gerd , Kristensson Jimmie , Lindhardt Tove 
Published: January 2020

AbstractBackgroundCommunity acquired pneumonia (CAP) remains a significant cause of morbidity and in-hospital mortality, and readmission rates are rising for older persons (> 65 years). Optimized treatment and nursing care will benefit patients and the health economy. Hence, there is a need to describe gaps between current clinical practice and recommendations in evidence-based guidelines for diagnostic procedures, medical treatment and nursing interventions for older patients with CAP.MethodsStructured observations, individual ad hoc interviews and audits of patient records were carried out in an emergency department and three medical units. Data were analysed by manifest content analysis and descriptive statistics.ResultsThirty patients (median age 74 years) admitted with CAP and 86 physicians, nurses, physiotherapists were included. The median length of stay (LOS) was 6.5 days, in-hospital mortality was10 and 40.7% were readmitted within one month. The severity assessment tool (CURB-65) was used in 16.7% of the patients, correct antibiotic treatment prescribed for 13.3% and chest radiography (≤6 weeks post-discharge) prescribed for 22.2%. Fluid therapy, nutrition support and mobilisation plans were found to be developed sporadically, and interventions to be performed unsystematically and sparingly. Positive Expiratory Pressure therapy and oral care were the nursing interventions with lowest adherence, ranging from 18.2 to 55.6%.ConclusionsAdherence to recommendations was low for several central treatment and nursing care interventions for patients with CAP with possible consequences for patients and the use of resources. Thus, there is an urgent need to identify and remove barriers to adherence to recommendations in the neglected areas in view of the potential to improve patient outcomes.
Electroacupuncture versus solifenacin for women with urgency-predominant mixed urinary incontinence: a protocol for a three-armed non-inferiority randomized controlled trial
Authors: Sun Yuanjie , Liu Yan , Su Tongsheng , Sun Jianhua , Wu Ying , Liu Zhishun 
Published: January 2020

Abstract
Background
Among women suffering from urinary incontinence (UI), about one-third are diagnosed with mixed urinary incontinence (MUI), among which urgency-predominant MUI causes more shame and inconvenience to patients. The treatments for urgency-predominant MUI have limited guidelines and previous studies have indicated that electroacupuncture (EA) might be a safe and effective option. The present study aims to evaluate the effect of EA on women with urgency-predominant MUI.

Methods
The study is a multicentered, three-armed, non-inferiority randomized clinical trial. A total of 282 female patients with urgency-predominant MUI will be randomly divided into three groups, namely the EA group, sham electroacupuncture (SA) group, and solifenacin treatment group at a ratio of 1:1:1. Thirty-six sessions of acupuncture treatment over 12 weeks and solifenacin treatment over 36 weeks will be provided. The primary outcome will be the decrease of urgency urinary incontinence (UUI) episodes after 12-week treatment. Secondary outcomes will include changes in incontinence episodes, urinary frequency, urgency, severity of symptoms, and influence on quality of life, assessed using the International Consultation on Incontinence Questionnaire Short Form (ICIQ SF) and Overactive Bladder Questionnaire Short Form (OAB-q SF). All patients will be continuously followed up until week 36 and their allocations will be statistically analyzed.

Discussion
Though placebo of solifenacin is rather difficult to access and all patients in the trial cannot be fully blinded, the present study will serve as an introduction of three-armed, randomized, non-inferiority, and sham acupuncture-controlled clinical trials to the acupuncture field, in an attempt to compare the effects of EA and solifenacin for treating women with urgency-predominant MUI.

Trial registration
ClinicalTrials.gov: NCT03787654. Registered on 25 December, 2018.
An integrated analysis of public genomic data unveils a possible functional mechanism of psoriasis risk via a long-range ERRFI1 enhancer
Authors: Kubota Naoto , Suyama Mikita 
Published: January 2020

Abstract
Background
Psoriasis is a chronic inflammatory skin disease, for which genome-wide association studies (GWAS) have identified many genetic variants as risk markers. However, the details of underlying molecular mechanisms, especially which variants are functional, are poorly understood.

Methods
We utilized a computational approach to survey psoriasis-associated functional variants that might affect protein functions or gene expression levels. We developed a pipeline by integrating publicly available datasets provided by GWAS Catalog, FANTOM5, GTEx, SNP2TFBS, and DeepBlue. To identify functional variants on exons or splice sites, we used a web-based annotation tool in the Ensembl database. To search for noncoding functional variants within promoters or enhancers, we used eQTL data calculated by GTEx. The data of variants lying on transcription factor binding sites provided by SNP2TFBS were used to predict detailed functions of the variants.

Results
We discovered 22 functional variant candidates, of which 8 were in noncoding regions. We focused on the enhancer variant rs72635708 (T > C) in the 1p36.23 region; this variant is within the enhancer region of the ERRFI1 gene, which regulates lipid metabolism in the liver and skin morphogenesis via EGF signaling. Further analysis showed that the ERRFI1 promoter spatially contacts with the enhancer, despite the 170 kb distance between them. We found that this variant lies on the AP-1 complex binding motif and may modulate binding levels.

Conclusions
The minor allele rs72635708 (rs72635708-C) might affect the ERRFI1 promoter activity, which results in unstable expression of ERRFI1, enhancing the risk of psoriasis via disruption of lipid metabolism and skin cell proliferation. Our study represents a successful example of predicting molecular pathogenesis by integration and reanalysis of public data.
The importance of power, context and agency in improving patient experience through a patient and family centred care approach
Authors: Ocloo Josephine , Goodrich Joanna , Tanaka Hiro , Birchall-Searle Julia , Dawson Derek , Farr Michelle 
Published: January 2020

AbstractBackgroundResearch shows that the way that healthcare staff experience their job impacts on their individual performance, patient experience and outcomes as well as on the performance of organisations. This article builds on this literature by investigating, with multi-disciplinary clinical teams as well as patients and relatives, what factors help or hinder changes designed to improve patient experience.MethodsQualitative research looking at patient- and family-centred care (PFCC) on two care pathways (stroke and hip fracture) was conducted in England and Wales. A realist approach combined with participatory action research was used to account for the complexity of organisational context and power relations. Multiple methods were used, including documentary analysis, participatory steering groups with staff and patient representatives, observations of the care pathways (n = 7), staff and patient and relative focus groups (n = 8), and hospital staff, patient and PFCC staff interviews (n = 47).ResultsFindings highlight multiple factors that support and hinder good patient experiences. Within individual care, paternalistic values and a lack of shared decision-making and patient-centred care still exist. Supportive interdisciplinary teamwork is needed to address issues of hierarchy, power and authority amongst staff and managers. At the organisational level, key issues of waiting times, patient flow, organisational resources and timely discharge affect staff’s time and capacity to deliver care. In addition, macro contextual factors, such as finance, policy, targets and measures, set particular limits for improvement projects.ConclusionsGiven this context, improving patient experience needs to go well beyond small-scale projects at the micro and meso level to incorporate a more critical understanding of systems, the wider organisational context and how power operates at multiple levels to enable and constrain action. In order to more meaningfully understand and address the factors that can help or hinder activities to improve patient experiences, PFCC frameworks and methods need to account for how power inequities operate and require the adoption of more participatory co-produced and empowering approaches to involve patients, relatives, carers and staff in improving complex healthcare environments.
Ambulances are for emergencies: shifting behaviour through a research-informed behaviour change campaign
Authors: Borg Kim , Dumas David , Andrew Emily , Smith Karen , Walker Tony , Haworth Matthew , Bragge Peter 
Published: January 2020

Abstract
Background
A major review of Victoria’s ambulance services identified the need to improve public awareness of the role of ambulances as an emergency service. A communications campaign was developed to address this challenge. This research paper expands on an initial evaluation of the campaign by focusing on the long-term behavioural outcomes.

Methods
The behavioural evaluation involved two types of data collection – administrative data (routine collection from various health services) and survey data (cross-sectional community-wide surveys to measure behavioural intentions).

Results
Behavioural intentions for accessing two of the targeted non-emergency services increased after the second phase of the campaign commenced. There was also a significant change in the slope of call trends for emergency ambulances. This decrease is also likely attributed to the second phase of the campaign as significant level effects were identified 3 and 9 months after it commenced.

Conclusions
A long-term campaign developed through evidence review, stakeholder consultation and behavioural theory was successful in reducing the number of daily calls requesting an emergency ambulance in Victoria and in increasing intentions to use alternative services. This research highlights the importance of collaborative intervention design along with the importance of implementing a robust monitoring and evaluation framework.
Contrast-enhanced, conebeam CT-based, fractionated radiotherapy and follow-up monitoring of orthotopic mouse glioblastoma: a proof-of-concept study
Authors: Stegen Benjamin , Nieto Alexander , Albrecht Valerie , Maas Jessica , Orth Michael , Neumaier Klement , Reinhardt Sabine , Weick-Kleemann Moritz , Goetz Wilfried , Reinhart Merle , Parodi Katia , Belka Claus , Niyazi Maximilian , Lauber Kirsten 
Published: January 2020

Abstract
Background
Despite aggressive treatment regimens comprising surgery and radiochemotherapy, glioblastoma (GBM) remains a cancer entity with very poor prognosis. The development of novel, combined modality approaches necessitates adequate preclinical model systems and therapy regimens that closely reflect the clinical situation. So far, image-guided, fractionated radiotherapy of orthotopic GBM models represents a major limitation in this regard.

Methods
GL261 mouse GBM cells were inoculated into the right hemispheres of C57BL/6 mice. Tumor growth was monitored by contrast-enhanced conebeam CT (CBCT) scans. When reaching an average volume of approximately 7 mm3, GBM tumors were irradiated with daily fractions of 2 Gy up to a cumulative dose of 20 Gy in different beam collimation settings. For treatment planning and tumor volume follow-up, contrast-enhanced CBCT scans were performed twice per week. Daily repositioning of animals was achieved by alignment of bony structures in native CBCT scans. When showing neurological symptoms, mice were sacrificed by cardiac perfusion. Brains, livers, and kidneys were processed into histologic sections. Potential toxic effects of contrast agent administration were assessed by measurement of liver enzyme and creatinine serum levels and by histologic examination.

Results
Tumors were successfully visualized by contrast-enhanced CBCT scans with a detection limit of approximately 2 mm3, and treatment planning could be performed. For daily repositioning of the animals, alignment of bony structures in native CT scans was well feasible. Fractionated irradiation caused a significant delay in tumor growth translating into significantly prolonged survival in clear dependence of the beam collimation setting and margin size. Brain sections revealed tumors of similar appearance and volume on the day of euthanasia. Importantly, the repeated contrast agent injections were well tolerated, as liver enzyme and creatinine serum levels were only subclinically elevated, and liver and kidney sections displayed normal histomorphology.

Conclusions
Contrast-enhanced, CT-based, fractionated radiation of orthotopic mouse GBM represents a versatile preclinical technique for the development and evaluation of multimodal radiotherapeutic approaches in combination with novel therapeutic agents in order to accelerate translation into clinical testing.
Etiologic spectrum of interstitial lung diseases in Chinese children older than 2 years of age
Authors: Tang Xiaolei , Li Huimin , Liu Hui , Xu Hui , Yang Haiming , Liu Jinrong , Zhao Shunying 
Published: January 2020

Abstract
Background
Childhood interstitial lung diseases (ILD) (chILD) refer to a rare heterogeneous group of disorders. Global collaborations have been working on the etiologies and classification scheme of chILD. With the development of medical technologies, some new diseases were identified to be associated with chILD and its etiologic spectrum is expanding. The aim of this study is to describe the etiologic spectrum of chILD in children older than 2 years of age and summarize the approaches to diagnosis of chILD.

Methods
We made a retrospective analysis of children older than 2 years of age with chILD who referred to Beijing Children’s Hospital from 21 provinces all over China from 2013 to 2018. After excluding pulmonary infection, congenital heart disease, bronchopulmonary dysplasia, bronchiolitis obliterans and bronchiectasis, 133 patients were included and categorized by etiology. Clinical manifestations, high-resolution computed tomography, laboratory data, genetic data and pathologic findings were all collected and reviewed.

Results
Systemic disease associated ILD were the most common causes, accounting for 49.6% of the patients, followed by alveolar structure disorder-associated ILD (27%), exposure related ILD (13.5%), and disorders masquerading as ILD (3.8%). In systemic disease associated ILD, in addition to common etiologies such as vasculitis (10.5%) and connective tissue diseases (9.0%), primary immunodeficiency diseases (PID) associated ILD (9.8%), interstitial pneumonia with autoimmune features (6.8%), and metabolic diseases (6.8%) were not rarely found. Some newly reported etiologies such as STING–associated vasculopathy with onset in infancy, COPA syndrome and STAT3 mutation were included in PID associated ILD. Genetic tests contributed to 15% of the diagnoses which mainly distributed in PID associated ILD, metabolic diseases and surfactant dysfunction disorders, and contributed to the final diagnoses more than lung biopsies (13.5%) and biopsies of rashes or other tissues (12%).

Conclusions
This study first demonstrated an etiologic spectrum of chILD in Chinese children older than 2 years of age and summarized the approaches to diagnosis. The etiologic spectrum of chILD is expanding with more genetic etiologies being recognized.
Brain metabolism and neurological symptoms in combined malonic and methylmalonic aciduria
Authors: Tucci Sara 
Published: January 2020

AbstractCombined malonic and methylmalonic aciduria (CMAMMA) is an inborn error of metabolism which has been proposed being a benign condition. However, older patients may present with neurological manifestations such as seizures, memory problems, psychiatric problems and/ or cognitive decline. In fibroblasts from CMAMMA patients we have recently demonstrated a dysregulation of energy metabolism with increased dependency on β-oxidation for energy production. Because of the inability of the brain to rely efficiently on this pathway to retrieve the required energy to a great extent, we hypothesize an alternative disease-causing mechanism that does not only include the accumulation of the metabolites malonic and methylmalonic acids. Here, we suggest a novel hypothesis on the possible pathophysiological mechanism responsible for the development of neurological symptoms in the long-run.
Perinatal features of Prader-Willi syndrome: a Chinese cohort of 134 patients
Authors: Yang Lili , Zhou Qiong , Ma Bo , Mao Shujiong , Dai Yanli , Zhu Mingqiang , Zou Chaochun 
Published: January 2020

Abstract
Background
Prader-Willi syndrome (PWS) is a rare and complex genetic disorder caused by lacking expression of imprinted genes on the paternally derived chromosome 15q11-q13 region. This study aimed to characterize the perinatal features of 134 Chinese individuals with PWS.

Methods
This study included the patients of a PWS registry in China. Anonymous data of 134 patients were abstracted. Perinatal and neonatal presentations were analyzed, and compared between the two PWS genetic subtypes. We also compared the perinatal features of PWS patients with the general population and other previous reported large cohorts from France, UK and USA.

Results
This study included 134 patients with PWS (115 patients with 15q11-q13 deletion and 19 with maternal uniparental disomy). Higher mean maternal age was found in this cohort (30.5 vs. 26.7), particularly in the maternal uniparental disomy (UPD) group (36.0 vs. 26.7) comparing with the general population. 88.6% of mothers reported a decrease of fetal movements. 42.5 and 18.7% of mothers had polyhydramnios and oligohydramnios during pregnancy, respectively. 82.8% of the patients were born by caesarean section. 32.1% of neonates had birth asphyxia, 98.5% had hypotonia and 97.8% had weak cry or even no cry at neonatal period. Feeding difficulty existed in 99.3% of the infants, 94.8% of whom had failure to thrive. 69.4% of the infants ever used feeding tube during hospitalization, however, 97.8% of them discontinued tube feeding after discharge. Maternal age and pre-pregnancy weight were significantly higher in the UPD group (both P < 0.05).

Conclusions
Differential diagnosis of PWS should be highlighted if infants having following perinatal factors including polyhydramnios, decreased intrauterine fetal movements, caesarean section, low birth weight, feeding difficulty, hypotonia and failure to thrive. Higher maternal age may be a risk factor of PWS, especially for UPD. Further studies are needed for elucidating the mechanism of PWS.