bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early palliative care versus standard care in haematologic cancer patients at their last active treatment: study protocol of a feasibility trial
Authors: Tanzi Silvia , Luminari Stefano , Cavuto Silvio , Turola Elena , Ghirotto Luca , Costantini Massimo 
Published: April 2020

Abstract
Background
Patients with advanced haematological malignancies suffer from a very high symptom burden and psychological, spiritual, social and physical symptoms comparable with patients with metastatic non-haematological malignancy. Referral to palliative care services for these patients remains limited or often confined to the last days of life. We developed a palliative care intervention (PCI) integrated with standard haematological care. The aim of the study was focussed on exploring the feasibility of the intervention by patients, professionals and caregivers and on assessing its preliminary efficacy.
Methods/design.
This is a mixed-methods phase 2 trial.
The Specialist Palliative Care Team (SPCT) will follow each patient on a monthly basis in the outpatient clinic or will provide consultations during any hospital admission. SPCT and haematologists will discuss active patient issues to assure a team approach to the patient’s care.
This quantitative study is a monocentric parallel-group superiority trial with balanced randomisation comparing the experimental PCI plus haematological standard care versus haematological standard care alone.
The primary endpoint will calculate on adherence to the planned PCI, measured as the percentage of patients randomised to the experimental arm who attend all the planned palliative care visits in the 24 weeks after randomisation.
The qualitative study follows the methodological indications of concurrent nested design and was aimed at exploring the acceptability of the PCI from the point of view of patients, caregivers and physicians.

Discussion
In this trial, we will test the feasibility of an integrated palliative care approach starting when the haematologist decides to propose the last active treatment to the patient, according to his/her clinical judgement. We decided to test this criterion because it is able to intercept a wide range of patients’needs. The feasibility of this approach requires that we enrol at least 60 patients and that more than 50% of them be followed by the palliative care team for at least 24 weeks.
The trial will include integrated qualitative data analysis; to give essential information on feasibility and acceptability.

Trial registration
ClinicalTrials.gov: NCT03743480 (November 16, 2018).
Palliative Performance Scale: cross cultural adaptation and psychometric validation for Polish hospice setting
Authors: Dzierżanowski Tomasz , Gradalski Tomasz , Kozlowski Michael 
Published: April 2020

Abstract
Background
Measuring functional status in palliative care may help clinicians to assess a patient’s prognosis, recommend adequate therapy, avoid futile or aggressive medical care, consider hospice referral, and evaluate provided rehabilitation outcomes. An optimized, widely used, and validated tool is preferable. The Palliative Performance Scale Version 2 (PPSv2) is currently one of the most commonly used performance scales in palliative settings. The aim of this study is the psychometric validation process of a Polish translation of this tool (PPSv2-Polish).

Methods
Two hundred patients admitted to a free-standing hospice were evaluated twice, on the first and third day, for test-retest reliability. In the first evaluation, two different care providers independently evaluated the same patient to establish inter-rater reliability values. PPSv2-Polish was evaluated simultaneously with the Karnofsky Performance Score (KPS), Eastern Cooperative Oncology Group (ECOG) Performance Status (ECOG PS), and Barthel Activities of Daily Living (ADL) Index, to determine its construct validity.

Results
A high level of full agreement between test and retest was seen (63%), and a good intra-class correlation coefficient of 0.85 (P < 0.0001) was achieved. Excellent agreement between raters was observed when using PPSv2-Polish (Cohen’s kappa 0.91; P < 0.0001). Satisfactory correlations with the KPS and good correlations with ECOG PS and Barthel ADL were noticed. Persons who had shorter prognoses and were predominantly bedridden also had lower scores measured by the PPSv2-Polish, KPS and Barthel ADL. A strong correlation of 0.77 between PPSv2-Polish scores and survival time was noted (P < 0.0001). Moderate survival correlations were seen between KPS, ECOG PS, and Barthel ADL of 0.41; − 0.62; and 0.58, respectively (P < 0.0001).

Conclusion
PPSv2-Polish is a valid and reliable tool measuring performance status in a hospice population and can be used in daily clinical practice in palliative care and research.
Circaea mollis Siebold & Zucc. Alleviates postmenopausal osteoporosis in a mouse model via the BMP-2/4/Runx2 pathway
Authors: Park Ji Hye , Son Yang Ju , Lee Chang Ho , Nho Chu Won , Yoo Gyhye 
Published: April 2020

AbstractBackgroundCircaea mollisSieb. & Zucc. has been used as a traditional herbal medicine in Hani Ethnopharmacy and possesses anti-arthritic activities. This study aimed to investigate the effect ofCircaea mollisSiebold & Zucc on postmenopausal osteoporosis.MethodsFor in vitro study, MCF7 breast cancer cells and MC3T3-E1 pre-osteoblast cells were utilized to estimate estrogenic and osteogenic activity. Osteoblastic markers were measured by western blot and real-time PCR. For in vivo study, female mature C57BL/6 mice were ovariectomized and oral administrated with 10 mg/kg and 40 mg/kg of EECM respectively.ResultsEtOH extract ofCircaea mollisSiebold & Zucc. (EECM) increased alkaline phosphatase activity and osteoblast marker levels at day 7 during differentiation of mouse preosteoblasts. EECM reduced osteoclast differentiation and bone resorption in an osteoblast-osteoclast primary co-culture system. In ovariectomized mice, EECM prevented the decrease in bone mineral density and recovered OSX and Runx2 via BMP2/4, Smad1/5/9 and p38.ConclusionsThe results suggest that EECM may be effective in preventing bone loss, offering a promising alternative for the nutritional management of postmenopausal osteoporosis.
Contact characteristics and factors associated with the degree of urgency among older people in emergency primary health care: a cross-sectional study
Authors: Haraldseide Lisa Marie , Sortland Linn Solveig , Hunskaar Steinar , Morken Tone 
Published: April 2020

Abstract
Background
As the proportion of older people increases, so will the consumption of health services. The aim of this study was to describe the contact characteristics among older people and to identify factors associated with the degree of urgency at the Norwegian out-of-hours (OOH) emergency primary health care services.

Methods
Inhabitants aged ≥70 years who contacted the OOH service during 2014–2017 in seven OOH districts in Norway were included. We investigated the variables sex, age, time of contact, mode of contact, ICPC-2 based reason for encounter (RFE), priority degree and initial response. We also performed frequency analyses, rate calculations and a log-binomial regression.

Results
A total of 38,293 contacts were registered. The contact rate/1000 inhabitants/year was three times higher in the oldest age group (≥90 years) compared to the youngest age group (70–74 years). Direct attendance accounted for 8.4% of the contacts and 32.8% were telephone contacts from health professionals. The most frequent RFE chapter used was “A General and unspecified” (21.0%) which also showed an increasing rate with higher age. 6.0% of the contacts resulted in a home visit from a doctor. Variables significantly associated with urgent priority degree were RFEs regarding cardiovascular (Relative risk (RR) 1.85; CI 1.74–1.96), neurological (RR 1.55; CI 1.36–1.77), respiratory (RR 1.40; CI 1.30–1.51) and digestive (RR 1.22; CI 1.10–1.34) issues. In addition, telephone calls from health professionals (RR 1.21; CI 1.12–1.31), direct attendance (RR 1.13; CI 1.04–1.22), contacts on weekdays (RR 1.13; CI 1.06–1.20) and contacts from men (RR 1.13; CI 1.09–1.17) were significantly associated with urgent priority degree.

Conclusions
This study provides important information about the Norwegian older inhabitants’ contact with the OOH emergency primary health care services. There are a wide variety of RFEs, and the contact rate is high and increases with higher age. Telephone contact is most common. The OOH staff frequently identify older people as having “general and unspecified” reasons for encounters. OOH nursing staff would benefit from having screening tools and enhanced geriatric training to best support this vulnerable group when these individuals call the OOH service.
Inhibition of microRNA-451 is associated with increased expression of Macrophage Migration Inhibitory Factor and mitigation of the cardio-pulmonary phenotype in a murine model of Bronchopulmonary Dysplasia
Authors: Gilfillan Margaret , Das Pragnya , Shah Dilip , Alam Mohammad Afaque , Bhandari Vineet 
Published: April 2020

Abstract
Background
Macrophage migration inhibitory factor (MIF) has been implicated as a protective factor in the development of bronchopulmonary dysplasia (BPD) and is known to be regulated by MicroRNA-451 (miR-451). The aim of this study was to evaluate the role of miR-451 and the MIF signaling pathway in in vitro and in vivo models of BPD.

Methods
Studies were conducted in mouse lung endothelial cells (MLECs) exposed to hyperoxia and in a newborn mouse model of hyperoxia-induced BPD. Lung and cardiac morphometry as well as vascular markers were evaluated.

Results
Increased expression of miR-451 was noted in MLECs exposed to hyperoxia and in lungs of BPD mice. Administration of a miR-451 inhibitor to MLECs exposed to hyperoxia was associated with increased expression of MIF and decreased expression of angiopoietin (Ang) 2. Treatment with the miR-451 inhibitor was associated with improved lung morphometry indices, significant reduction in right ventricular hypertrophy, decreased mean arterial wall thickness and improvement in vascular density in BPD mice. Western blot analysis demonstrated preservation of MIF expression in BPD animals treated with a miR-451 inhibitor and increased expression of vascular endothelial growth factor-A (VEGF-A), Ang1, Ang2 and the Ang receptor, Tie2.

Conclusion
We demonstrated that inhibition of miR-451 is associated with mitigation of the cardio-pulmonary phenotype, preservation of MIF expression and increased expression of several vascular growth factors.
Validation of age, PaO2/FlO2 and plateau pressure score in Korean patients with acute respiratory distress syndrome: a retrospective cohort study
Authors: Hwang Hyeontaek , Choi Sun Mi , Lee Jinwoo , Park Young Sik , Lee Chang-Hoon , Yoo Chul-Gyu , Kim Young Whan , Han Sung Koo , Lee Sang-Min 
Published: April 2020

Abstract
Background
A predictive scoring system for acute respiratory distress syndrome (ARDS) patients, which incorporates age, PaO2/FlO2, and plateau pressure, APPS, was developed recently. It was validated externally in a Caucasian population but has not been studied in Asian populations. The aim of this study was to validate APPS in Korean ARDS patients.

Methods
We retrospectively reviewed the medical records of patients who were diagnosed with ARDS using the Berlin criteria and admitted to the medical ICU at Seoul National University Hospital from January 2015 to December 2016. The validation of the APPS was performed by evaluating its calibration and predictive accuracy. Its calibration was plotted and quantified using the Hosmer–Lemeshow test. Its predictive accuracy was assessed by calculating the area under the receiver operating characteristics (AUC–ROC) curve.

Results
A total of 116 patients were analyzed, 32 of whom survived. Of the 116 patients, 11 (9.5%) were classified as APPS grade 1 (score 3–4), 88 (75.9%) as grade 2 (score 5–7) and 17 (14.6%) as grade 3 (score 8–9). In-hospital mortality was 27.3% for grade 1, 73.9% for grade 2 and 94.1% for grade 3 (P for trend < 0.001). The APPS was well calibrated (Hosmer–Lemeshow test, P = 0.578) and its predictive accuracy was acceptable (AUC–ROC 0.704, 95% confidence interval 0.599–0.809).

Conclusions
The APPS predicted in-hospital mortality in Korean patients with ARDS with similar power to its application in a Western population and with acceptable predictive accuracy.

Trial registration
Retrospectively registered.
MyD88 regulates a prolonged adaptation response to environmental dust exposure-induced lung disease
Authors: Johnson Amber N. , Harkema Jack R. , Nelson Amy J. , Dickinson John D. , Kalil Julianna , Duryee Michael J. , Thiele Geoffrey M. , Kumar Balawant , Singh Amar B. , Gaurav Rohit , Glover Sarah C. , Tang Ying , Romberger Debra J. , Kielian Tammy , Poole Jill A. 
Published: April 2020

Abstract
Background
Environmental organic dust exposures enriched in Toll-like receptor (TLR) agonists can reduce allergic asthma development but are associated with occupational asthma and chronic bronchitis. The TLR adaptor protein myeloid differentiation factor88 (MyD88) is fundamental in regulating acute inflammatory responses to organic dust extract (ODE), yet its role in repetitive exposures is unknown and could inform future strategies.

Methods
Wild-type (WT) and MyD88 knockout (KO) mice were exposed intranasally to ODE or saline daily for 3 weeks (repetitive exposure). Repetitively exposed animals were also subsequently rested with no treatments for 4 weeks followed by single rechallenge with saline/ODE.

Results
Repetitive ODE exposure induced neutrophil influx and release of pro-inflammatory cytokines and chemokines were profoundly reduced in MyD88 KO mice. In comparison, ODE-induced cellular aggregates, B cells, mast cell infiltrates and serum IgE levels remained elevated in KO mice and mucous cell metaplasia was increased. Expression of ODE-induced tight junction protein(s) was also MyD88-dependent. Following recovery and then rechallenge with ODE, inflammatory mediators, but not neutrophil influx, was reduced in WT mice pretreated with ODE coincident with increased expression of IL-33 and IL-10, suggesting an adaptation response. Repetitively exposed MyD88 KO mice lacked inflammatory responsiveness upon ODE rechallenge.

Conclusions
MyD88 is essential in mediating the classic airway inflammatory response to repetitive ODE, but targeting MyD88 does not reduce mucous cell metaplasia, lymphocyte influx, or IgE responsiveness. TLR-enriched dust exposures induce a prolonged adaptation response that is largely MyD88-independent. These findings demonstrate the complex role of MyD88-dependent signaling during acute vs. chronic organic dust exposures.
The unsynchronized changes of CT image and nucleic acid detection in COVID-19: reports the two cases from Gansu, China
Authors: Gao Jing , Liu Jun-Qiang , Wen Heng-Jun , Liu Hua , Hu Wei-Dong , Han Xia , Li Chuan-Xing , Wang Xiao-Jun 
Published: April 2020

AbstractThe novel coronavirus disease (COVID-19) outbreak started in December 2019 in Wuhan, China, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The CT image is used to assess the disease progress, whereas the continued two times of negative results from SARS-CoV-2 nucleic acid detection had been considered as a criterion for ending antiviral treatment. We compared the two COVID-19 cases with similar backgrounds and CT image repeated intervals under treatment. Our report highlighted the unsynchronized expression in the changes of CT image and nucleic acid detection in COVID-19, and lasting positive nucleic acid test result in patients recovered from pneumonia. It may be contributed to recognize the disease and improve prevention.
Bioinformatics combined with quantitative proteomics analyses and identification of potential biomarkers in cholangiocarcinoma
Authors: Da Zijian , Gao Long , Su Gang , Yao Jia , Fu Wenkang , Zhang Jinduo , Zhang Xu , Pei Zhaoji , Yue Ping , Bai Bing , Lin Yanyan , Meng Wenbo , Li Xun 
Published: April 2020

AbstractBackgroundCholangiocarcinoma (CCA) is an invasive malignancy arising from biliary epithelial cells; it is the most common primary tumour of the bile tract and has a poor prognosis. The aim of this study was to screen prognostic biomarkers for CCA by integrated multiomics analysis.MethodsThe GSE32225 dataset was derived from the Gene Expression Omnibus (GEO) database and comprehensively analysed by using R software and The Cancer Genome Atlas (TCGA) database to obtain the differentially expressed RNAs (DERNAs) associated with CCA prognosis. Quantitative isobaric tags for relative and absolute quantification (iTRAQ) proteomics was used to screen differentially expressed proteins (DEPs) between CCA and nontumour tissues. Through integrated analysis of DERNA and DEP data, we obtained candidate proteins APOF, ITGAV and CASK, and immunohistochemistry was used to detect the expression of these proteins in CCA. The relationship between CASK expression and CCA prognosis was further analysed.ResultsThrough bioinformatics analysis, 875 DERNAs were identified, of which 10 were associated with the prognosis of the CCA patients. A total of 487 DEPs were obtained by using the iTRAQ technique. Comprehensive analysis of multiomics data showed that CASK, ITGAV and APOF expression at both the mRNA and protein levels were different in CCA compared with nontumour tissues. CASK was found to be expressed in the cytoplasm and nucleus of CCA cells in 38 (45%) of 84 patients with CCA. Our results suggested that patients with positive CASK expression had significantly better overall survival (OS) and recurrence-free survival (RFS) than those with negative CASK expression. Univariate and multivariate analyses demonstrated that negative expression of CASK was a significantly independent risk factor for OS and RFS in CCA patients.ConclusionsCASK may be a tumour suppressor; its low expression is an independent risk factor for a poor prognosis in CCA patients, and so it could be used as a clinically valuable prognostic marker.
Health related quality of life in adult primary Ciliary dyskinesia patients in Cyprus: development and validation of the Greek version of the QOL-PCD questionnaire
Authors: Ioannou Phivos , Kouis Panayiotis , Kakkoura Maria G. , Kaliva Margarita , Toliopoulou Aristoula , Andreou Kyriacos , Behan Laura , Lucas Jane S. , Papanikolaou Vicky , Charalambous George , Middleton Nicos , Yiallouros Panayiotis K. 
Published: April 2020

Abstract
Background
The QOL-PCD questionnaire is a recently developed Health Related Quality of Life (HRQoL) instrument for Primary Ciliary Dyskinesia. The aim of this study was to translate the adult QOL-PCD questionnaire into Greek language and to conduct psychometric validation to assess its performance.

Methods
Forward translations to Greek and backward translation to English were performed, followed by cognitive interviews in 12 adult PCD patients. The finalized translated version was administered to a consecutive sample of 31 adult, Greek speaking PCD patients in Cyprus for psychometric validation, which included assessment of internal consistency, test-retest reliability, construct and convergent validity. Internal consistency was assessed by Cronbach’s alpha test in terms of the overall and sub-scales. Test-retest reliability was assessed by repeat administration of the questionnaire within 2 weeks and calculation of the intra-class correlation (ICC). Construct validity was assessed by comparing different groups of patients based on a-priori hypotheses and convergent validity was evaluated by examining associations between the QOL-PCD and SF-36 questionnaires.

Results
Moderate to good internal consistency was observed (Cronbach’s α: 0.46–0.88 across sub-scales) and test-retest reliability assessment demonstrated good repeatability for most scales (ICC: 0.67–0.91 across subscales). Patients of female gender, older age and lower lung function exhibited lower QOL-PCD scores in general, while high correlations for most QOL-PCD scales with corresponding SF-36 scales were observed, in particular for physical functioning (r = 0.78, p < 0.05).

Conclusion
The adult version of QoL-PCD questionnaire has been translated according to international guidelines resulting to a cross-culturally validated Greek version which exhibited moderate to good metric properties in terms of internal consistency, stability, known-group and convergent validity.
Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant
Authors: Pachetti Maria , Marini Bruna , Benedetti Francesca , Giudici Fabiola , Mauro Elisabetta , Storici Paola , Masciovecchio Claudio , Angeletti Silvia , Ciccozzi Massimo , Gallo Robert C. , Zella Davide , Ippodrino Rudy 
Published: April 2020

Abstract
Background
SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance.

Methods
We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann–Whitney and Fisher-Exact tests were used to assess statistical significance.

Results
We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations [range: 2–5], otherwise they have a median of 1 mutation [range: 0–3] (p value < 0.001).

Conclusions
These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.