bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptation, modification, and psychometric assessment of a Norwegian version of the Basel extent of rationing of nursing care for nursing homes instrument (BERNCA-NH)
Authors: Norman Rebecka Maria , Sjetne Ingeborg Strømseng 
Published: December 2019

AbstractBackgroundTo our knowledge, no instrument has been developed and tested for measuring unfinished care in Norwegian nursing home settings. The Basel Extent of Rationing of Nursing Care for Nursing Homes instrument (BERNCA-NH) was developed and validated in Switzerland to measure the extent of implicit rationing of nursing care in nursing homes. The BERNCA-NH comprises a list of nursing care activities in which a care worker reports the frequency to which activities were left unfinished over the last 7 working days as a result of lack of time. The aim of this study was to adapt and modify a Norwegian version of the BERNCA-NH intended for all care workers, and assess the instruments’ psychometric properties in a Norwegian nursing home setting.MethodsThe BERNCA-NH was translated into Norwegian and modified to fit the Norwegian setting with inputs from individual cognitive interviews with informants from the target population. The instrument was then tested in a web-based survey with a final sample of 931 care workers in 162 nursing home units in different parts of Norway. The psychometric evaluation included score distribution, response completeness and confirmatory factor analysis (CFA) of a hypothesised factor structure and evaluation of internal consistency. Hypothesised relation to other variables was assessed through correlations between the subscale scores and three global ratings.ResultsThe Norwegian version of BERNCA-NH comprised four subscales labelled: routine care, ‘when required’ care, documentation and psychosocial care. All subscales demonstrated good internal consistency. The CFA supported the four-factor structure with fit statistics indicating a robust model. There were moderate to strong bivariate associations between the BERNCA-NH subscales and the three global ratings. Three items which were not relevant for all care workers were not included in the subscales and treated as single items.ConclusionsThis study found good psychometric properties of the Norwegian version BERNCA-NH, assessed in a sample of care workers in Norwegian nursing homes. The results indicate that the instrument can be used to measure unfinished care in similar settings.
Protocol of a longitudinal study on the specific needs of Syrian refugee families in Switzerland
Authors: El Ghaziri Nahema , Blaser Jérémie , Darwiche Joëlle , Suris Joan-Carles , Sanchis Zozaya Javier , Marion-Veyron Régis , Spini Dario , Bodenmann Patrick 
Published: December 2019

Abstract
Background
The ongoing Syrian civil war has led to massive population displacements, leading to the reorganization of the asylum policies of several countries. Accordingly, like other European countries, the Swiss government has recently chosen to implement a specific resettlement program. This program is characterized by the fact that the whole nuclear family is granted a work and residence permit upon arrival, and benefits from enhanced integration services. The aim of the present project is to evaluate the effects of the Swiss resettlement program, with a special focus on mental health, while adopting a family perspective.

Methods
The outcomes of 15 Syrian families taking part in this program will be compared to those of 15 Syrian families that came to Switzerland through other means (i.e., following the usual asylum procedure, which is much more stressful and time consuming). Each family member above 8 years old will be invited to participate to a 3-wave longitudinal survey concerning the resettlement process: upon arrival in the collective shelters, six and 12 months later. Questionnaires will be used for the evaluation of participants’ mental health, risk behaviors, general health, romantic relationship, parent-child relationship, family functioning, parentification, social support, and social identities related to group belongingness.

Discussion
The findings of the present project will provide longitudinal information on Syrian refugees. A comprehensive approach will be adopted by screening potential difficulties that the sample may be faced with and potential strengths that participants may rely on. Accordingly, physical and mental health, as well as the quality of family functioning, the feeling of support and of belongingness to different groups will be evaluated.
We will also compare the results of families who had the chance to immigrate through the Swiss resettlement program, to the results of families that did not. This comparison will allow the elaboration of hypotheses regarding adjusted asylum policies. Furthermore, it will enhance our knowledge regarding the impact of displacement on the family system. Indeed, although the role of the family for the well-being of adults and children has been established, surprisingly few studies have adopted this focus in the asylum field.
Crossing fitness valleys via double substitutions within codons
Authors: Belinky Frida , Sela Itamar , Rogozin Igor B. , Koonin Eugene V. 
Published: December 2019

Abstract
Background
Single nucleotide substitutions in protein-coding genes can be divided into synonymous (S), with little fitness effect, and non-synonymous (N) ones that alter amino acids and thus generally have a greater effect. Most of the N substitutions are affected by purifying selection that eliminates them from evolving populations. However, additional mutations of nearby bases potentially could alleviate the deleterious effect of single substitutions, making them subject to positive selection. To elucidate the effects of selection on double substitutions in all codons, it is critical to differentiate selection from mutational biases.

Results
We addressed the evolutionary regimes of within-codon double substitutions in 37 groups of closely related prokaryotic genomes from diverse phyla by comparing the fractions of double substitutions within codons to those of the equivalent double S substitutions in adjacent codons. Under the assumption that substitutions occur one at a time, all within-codon double substitutions can be represented as “ancestral-intermediate-final” sequences (where “intermediate” refers to the first single substitution and “final” refers to the second substitution) and can be partitioned into four classes: (1) SS, S intermediate–S final; (2) SN, S intermediate–N final; (3) NS, N intermediate–S final; and (4) NN, N intermediate–N final. We found that the selective pressure on the second substitution markedly differs among these classes of double substitutions. Analogous to single S (synonymous) substitutions, SS double substitutions evolve neutrally, whereas analogous to single N (non-synonymous) substitutions, SN double substitutions are subject to purifying selection. In contrast, NS show positive selection on the second step because the original amino acid is recovered. The NN double substitutions are heterogeneous and can be subject to either purifying or positive selection, or evolve neutrally, depending on the amino acid similarity between the final or intermediate and the ancestral states.

Conclusions
The results of the present, comprehensive analysis of the evolutionary landscape of within-codon double substitutions reaffirm the largely conservative regime of protein evolution. However, the second step of a double substitution can be subject to positive selection when the first step is deleterious. Such positive selection can result in frequent crossing of valleys on the fitness landscape.
Calibration: the Achilles heel of predictive analytics
Authors:   On behalf of Topic Group ‘Evaluating diagnostic tests and prediction models’ of the STRATOS initiative, Van Calster Ben , McLernon David J. , van Smeden Maarten , Wynants Laure , Steyerberg Ewout W. 
Published: December 2019

Abstract
Background
The assessment of calibration performance of risk prediction models based on regression or more flexible machine learning algorithms receives little attention.

Main text
Herein, we argue that this needs to change immediately because poorly calibrated algorithms can be misleading and potentially harmful for clinical decision-making. We summarize how to avoid poor calibration at algorithm development and how to assess calibration at algorithm validation, emphasizing balance between model complexity and the available sample size. At external validation, calibration curves require sufficiently large samples. Algorithm updating should be considered for appropriate support of clinical practice.

Conclusion
Efforts are required to avoid poor calibration when developing prediction models, to evaluate calibration when validating models, and to update models when indicated. The ultimate aim is to optimize the utility of predictive analytics for shared decision-making and patient counseling.
RNA disruption indicates CHOP therapy efficacy in canine lymphoma
Authors: Parissenti Amadeo M. , Pritzker Laura B. , Guo Baoqing , Narendrula Rashmi , Wang Shirly Xiaohui , Lin Lin Laura , Pei Jingchun , Skowronski Karolina , Bienzle Dorothee , Woods J. Paul , Pritzker Kenneth P. H. , Coomber Brenda L. 
Published: December 2019

Abstract
Background
Assessment of the efficacy of a multi-agent chemotherapy protocol in which cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) are administered in canine lymphoma is generally performed by physical measurement of lymph node diameter. However, no consistent correlation has been made with prognostic indicators and the length or absence of clinical remission based on lymph node size. RNA disruption measured mid-therapy has been correlated with increased disease-free survival in recent studies of human cancer and was assessed in this study of canine lymphoma patients. Fine needle aspirate samples were taken before treatment and at weeks 3, 6, and 11 of CHOP therapy. RNA was isolated from these samples and assessed using an Agilent Bioanalyzer. RNA disruption assay (RDA) analysis was performed on the data from the resulting electropherograms.

Results
An increased RNA disruption index (RDI) score was significantly associated with improved progression-free survival.

Conclusions
Predicting the risk of early relapse during chemotherapy could benefit veterinary patients by reducing ineffective treatment and could allow veterinary oncologists to switch earlier to a more effective drug regimen.
Low BRAF V600 mutation prevalence in primary skin nodular melanoma in Indonesia: a real-time PCR detection among Javanese patients
Authors: Rinonce Hanggoro Tri , Aji Rovi Panji Mustiko , Hayati Ni’mah , Pudjohartono Maria Fransiska , Kameswari Bidari , Irianiwati  
Published: December 2019

AbstractBackgroundCutaneous melanoma is a rare, aggressive skin malignancy with a high mortality rate. Although only contributing 7.6% of the cases worldwide, Asia is responsible for 18.6% of deaths from cutaneous melanoma. BRAF V600 mutation presents a potential prognostic predictor in melanoma. Unfortunately, studies on that mutation in melanoma, particularly nodular subtype, in Indonesia are still scarce. This research aimed to investigate the prevalence of BRAF V600 mutation in primary skin nodular melanoma in Yogyakarta and Central Java, Indonesia. Its association with clinicopathological parameters was also analyzed.MethodsForty paraffin-embedded tissue samples from primary skin nodular melanoma cases in 2011–2018 were collected from the two biggest referral hospitals in Yogyakarta and Central Java, Indonesia. The BRAF V600 mutation status was assessed using qualitative real-time PCR and its associations with age, sex, anatomic location, lymph node metastasis, tumor thickness, ulceration, mitotic index, necrosis, lymphovascular invasion, and tumor-infiltrating lymphocytes were analyzed.ResultsBRAF V600 mutations were found in 4 (10%) samples. These mutations were significantly associated with the central (non-extremity) region (p = 0.013) and presence of lymphovascular invasion (p = 0.005). However, it was not associated with any other variables analyzed in this study.ConclusionThe prevalence of BRAF V600 mutation in Indonesian primary skin nodular melanoma cases is low and significantly associated with anatomic location and lymphovascular invasion. It is lower than prevalences in other Asian populations as well as in Caucasian populations and suggests that melanoma cases in Javanese people may have distinct clinicopathological characteristics from other Asian ethnicities.
The effect of 5α-oleandrin on keloid fibroblast activities
Authors: Dachlan Ishandono , Wirohadidjojo Yohanes Widodo , Wahyuningsih Mae Sri Hartati , Aryandono Teguh , Soebono Hardyanto , Afandy Dwiki 
Published: December 2019

Abstract
Background
Keloids develop due to hyperactivity of keloid fibroblast (KF) in proliferation, migration, and collagen deposition along with low rates of collagen degradation. These are a result of the Wnt/β catenin signaling pathways under stimulation of TGF-β. 5α-oleandrin can suppress Wnt-targeted genes of osteosarcoma cells. We aimed to evaluate the anti-fibrotic effects of 5α-oleandrin on KF activities.

Methods
We collected the core of keloid materials from six patients who underwent keloid debulking surgery. Passage 4 of KF cells were then treated with mitomycin-C, 5α-oleandrin, and dilution medium as the negative control. To determine the effective dose of 5α-oleandrin, we diluted 5α-oleandrin into various concentrations. The incubation periods were 24 h, 48 h, and 72 h. The anti-proliferation and anti-fibrotic properties were measured using standard assay.

Results
Both the mitomycin-C and 5α-oleandrin treated groups indicated decrease in proliferation index (86.16 ± 4.20% and 73.76 ± 4.94%, respectively), collagen deposition index (90.26 ± 1.72% and 71.35 ± 4.26%, respectively), and migration capacity (33.51 ± 1.50% and 28.57 ± 1.58%, respectively). These were significant changes (p ≤ 0.05) compared to the non-treated group. Antifibrotic activities of 5α-oleandrin in cellular proliferation and collagen deposition were better than mitomycin-C.

Conclusions
The 5α-oleandrin has good antifibrotic effect in keloid fibroblast activities.
Use of air stacking to improve pulmonary function in Indonesian Duchenne muscular dystrophy patients: bridging the standard of care gap in low middle income country setting
Authors: Iskandar Kristy , Sunartini  , Nugrahanto Andika Priamas , Ilma Nissya , Kalim Alvin Santoso , Adistyawan Guritno , Siswanto  , Naning Roni 
Published: December 2019

Abstract
Background
Duchenne Muscular Dystrophy (DMD) is a fatal X-linked recessive neuromuscular disease, characterized by progressive loss of muscle strength. Respiratory failure is the main cause of morbidity and mortality in DMD patients. Respiratory devices have been reported to increase the effectiveness of cough and pulmonary function, thus prolong the survival rate. However, there is scarcity of studies about DMD patients’ respiratory profiles and usage of respiratory devices in Indonesia.

Methods
We recruited 8 Indonesian DMD patients in Dr. Sardjito Hospital and UGM Academic Hospital, Yogyakarta. Baseline pulmonary function was measured using spirometry. Peak Cough Flow was measured at baseline, with chest compression, after air stacking with manual ventilation bag, and with the combined techniques. Data recorded was presented as mean ± SD and analysed using ANOVA.

Results
Here we show the respiratory profiles from 8 non-ambulatory DMD patients (mean age: 13.25 ± 3.96 years old) confirmed by genetic testing. None of them had access to respiratory devices. Spirometry measurements showed 7 of 8 patients had severe restrictive pulmonary function with mean FEV1/FVC 22.40 ± 10.30% of predictive values (normal ratio > 70%). In addition, all patients showed poor cough performances measured by peak cough flowmeter (160 ± 44.58 L/min (normal value > 270 L/min)) that were improved by air stacking using a manual ventilation bag (167.4 ± 46.72 L/min). Three patients who had nocturnal hypoventilation did not have daytime hypercapnia. Manual ventilation bag or mechanical in−/ex-sufflation was indicated in 75% of patients while nocturnal assisted ventilation was indicated in 50% of patients. Neither daytime assisted ventilation nor tracheostomy was indicated in these patients.

Conclusion
Use of manual exsufflation in combination with the manual ventilation bag for air stacking to improve cough performance is recommended as the first step of respiratory management in DMD patients. Provision of manual ventilation bag serve as an affordable and effective device for respiratory support in the early stage of respiratory involvement in those non-ambulatory patients with DMD.
Heparanase upregulation from adipocyte associates with inflammation and endothelial injury in diabetic condition
Authors: Arfian Nur , Setyaningsih Wiwit Ananda Wahyu , Romi Muhammad Mansyur , Sari Dwi Cahyani Ratna 
Published: December 2019

Abstract
Background
Diabetes Mellitus (DM) is one of the metabolic diseases which leads to fatty tissue injury, and consequently inducing lipotoxicity and cellular senescence. This condition contributes to endothelial dysfunction with chronic inflammation and organ damage. Heparanase which has a role in disrupting endothelial surface layer (glycocalyx) may promote endothelial Nitric oxide synthase (eNOS) reduction and inflammation. However, its relationship with DM and organ injury has not been fully elucidated yet. This study aimed to determine how heparanase from fatty tissue may contribute to endothelial dysfunction and inflammation in patients with hyperglycemia and in a hyperglycemia model in rats.

Methods
This population study with a cross-sectional design was conducted with 28 subjects without diagnosis and medication of DM. Fasting blood glucose levels, lipid profile, heparanase protein, MCP-1 protein and HbA1c were quantified. In vivo study was performed with a diabetic model in Wistar rats induced with streptozotocin 60 mg/kg body weight by single intraperitoneal injection. Rats were euthanized after 1 month (DM1 group, n = 6), 2 months (DM2 group, n = 6) and 4 months (DM4 group, n = 6). White Adipose Tissue (WAT) was harvested from visceral fat. Real Time and Reverse Transcriptase-PCR (RT-PCR) was done to quantify expressions of heparanase, MCP-1, eNOS, IL-6 and p-16 (senescence). Immunostaining was performed to localize MCP-1 and macrophage (CD68). Western blot tests were used to examine eNOS, MCP-1 and heparanase protein expression.

Results
This study revealed associations between blood glucose levels with higher HbA1c, LDL, cholesterol, heparanase and MCP-1. The in vivo study also revealed lipid levels as the source of Heparanase and MCP-1 mRNA and protein expressions. This finding was associated with inflammation, cellular senescence and macrophage infiltration in fat tissue based on immunostaining and qRT-PCR analysis. RT-PCR revealed significantly lower expression of eNOS and higher expression of IL-6 in DM groups compared to the control group.

Conclusion
Heparanase upregulation in fat tissue was associated with endothelial injury and inflammation in hyperglycemia conditions.
Genepanel.iobio - an easy to use web tool for generating disease- and phenotype-associated gene lists
Authors: Ekawade Aditya , Velinder Matt , Ward Alistair , DiSera Tonya , Miller Chase , Qiao Yi , Marth Gabor 
Published: December 2019

AbstractWhen ordering genetic testing or triaging candidate variants in exome and genome sequencing studies, it is critical to generate and test a comprehensive list of candidate genes that succinctly describe the complete and objective phenotypic features of disease. Significant efforts have been made to curate gene:disease associations both in academic research and commercial genetic testing laboratory settings. However, many of these valuable resources exist as islands and must be used independently, generating static, single-resource gene:disease association lists. Here we describe genepanel.iobio (https://genepanel.iobio.io) an easy to use, free and open-source web tool for generating disease- and phenotype-associated gene lists from multiple gene:disease association resources, including the NCBI Genetic Testing Registry (GTR), Phenolyzer, and the Human Phenotype Ontology (HPO). We demonstrate the utility of genepanel.iobio by applying it to complex, rare and undiagnosed disease cases that had reached a diagnostic conclusion. We find that genepanel.iobio is able to correctly prioritize the gene containing the diagnostic variant in roughly half of these challenging cases. Importantly, each component resource contributed diagnostic value, showing the benefits of this aggregate approach. We expect genepanel.iobio will improve the ease and diagnostic value of generating gene:disease association lists for genetic test ordering and whole genome or exome sequencing variant prioritization.
Competitive endogenous RNA (ceRNA) regulation network of lncRNAs, miRNAs, and mRNAs in Wilms tumour
Authors: Tang Fucai , Lu Zechao , Wang Jiamin , Li Zhibiao , Wu Weijia , Duan Haifeng , He Zhaohui 
Published: December 2019

Abstract
Background
Competitive endogenous RNAs (ceRNAs) have revealed a new mechanism of interaction between RNAs. However, an understanding of the ceRNA regulatory network in Wilms tumour (WT) remains limited.

Methods
The expression profiles of mRNAs, miRNAs and lncRNAs in Wilms tumour samples and normal samples were obtained from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database. The EdgeR package was employed to identify differentially expressed lncRNAs, miRNAs and mRNAs. Functional enrichment analyses via the ClusterProfile R package were performed, and the lncRNA–miRNA–mRNA interaction ceRNA network was established in Cytoscape. Subsequently, the correlation between the ceRNA network and overall survival was analysed.

Results
A total of 2037 lncRNAs, 154 miRNAs and 3609 mRNAs were identified as differentially expressed RNAs in Wilms tumour. Of those, 205 lncRNAs, 26 miRNAs and 143 mRNAs were included in the ceRNA regulatory network. The results of Gene Ontology (GO) analysis revealed that the differentially expressed genes (DEGs) were mainly enriched in terms related to response to mechanical stimuli, transcription factor complexes, and transcription factor activity (related to RNA polymerase II proximal promoter sequence-specific DNA binding). The results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the DEGs were mainly enriched in pathways related to the cell cycle. The survival analysis results showed that 16 out of the 205 lncRNAs, 1 out of 26 miRNAs and 5 out of 143 mRNAs were associated with overall survival in Wilms tumour patients (P < 0.05).

Conclusions
CeRNA networks play an important role in Wilms tumour. This finding might provide effective, novel insights for further understanding the mechanisms underlying Wilms tumour.