bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study
Authors: Corcoran John P. , Psallidas Ioannis , Gerry Stephen , Piccolo Francesco , Koegelenberg Coenraad F. , Saba Tarek , Daneshvar Cyrus , Fairbairn Ian , Heinink Richard , West Alex , Stanton Andrew E. , Holme Jayne , Kastelik Jack A. , Steer Henry , Downer Nicola J. , Haris Mohammed , Baker Emma H. , Everett Caroline F. , Pepperell Justin , Bewick Thomas , Yarmus Lonny , Maldonado Fabien , Khan Burhan , Hart-Thomas Alan , Hands Georgina , Warwick Geoffrey , De Fonseka Duneesha , Hassan Maged , Munavvar Mohammed , Guhan Anur , Shahidi Mitra , Pogson Zara , Dowson Lee , Popowicz Natalia D. , Saba Judith , Ward Neil R. , Hallifax Rob J. , Dobson Melissa , Shaw Rachel , Hedley Emma L. , Sabia Assunta , Robinson Barbara , Collins Gary S. , Davies Helen E. , Yu Ly-Mee , Miller Robert F. , Maskell Nick A. , Rahman Najib M. 
Published: July 2020

BackgroundOver 30% of adult patients with pleural infection either die and/or require surgery. There is no robust means of predicting at baseline presentation which patients will suffer a poor clinical outcome. A validated risk prediction score would allow early identification of high-risk patients, potentially directing more aggressive treatment thereafter.ObjectivesTo prospectively assess a previously described risk score (the RAPID (Renal (urea), Age, fluid Purulence, Infection source, Dietary (albumin)) score) in adults with pleural infection.MethodsProspective observational cohort study that recruited patients undergoing treatment for pleural infection. RAPID score and risk category were calculated at baseline presentation. The primary outcome was mortality at 3 months; secondary outcomes were mortality at 12 months, length of hospital stay, need for thoracic surgery, failure of medical treatment and lung function at 3 months.ResultsMortality data were available in 542 out of 546 patients recruited (99.3%). Overall mortality was 10% at 3 months (54 out of 542) and 19% at 12 months (102 out of 542). The RAPID risk category predicted mortality at 3 months. Low-risk mortality (RAPID score 0–2): five out of 222 (2.3%, 95% CI 0.9 to 5.7%); medium-risk mortality (RAPID score 3–4): 21 out of 228 (9.2%, 95% CI 6.0 to 13.7%); and high-risk mortality (RAPID score 5–7): 27 out of 92 (29.3%, 95% CI 21.0 to 39.2%). C-statistics for the scores at 3 months and 12 months were 0.78 (95% CI 0.71–0.83) and 0.77 (95% CI 0.72–0.82), respectively.ConclusionsThe RAPID score stratifies adults with pleural infection according to increasing risk of mortality and should inform future research directed at improving outcomes in this patient population.
Gene expression andin situprotein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue
Authors: Aguiar Jennifer A. , Tremblay Benjamin J-M. , Mansfield Michael J. , Woody Owen , Lobb Briallen , Banerjee Arinjay , Chandiramohan Abiram , Tiessen Nicholas , Cao Quynh , Dvorkin-Gheva Anna , Revill Spencer , Miller Matthew S. , Carlsten Christopher , Organ Louise , Joseph Chitra , John Alison , Hanson Paul , Austin Richard C. , McManus Bruce M. , Jenkins Gisli , Mossman Karen , Ask Kjetil , Doxey Andrew C. , Hirota Jeremy A. 
Published: July 2020

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilises angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) host molecules for viral entry. ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection. Additional host molecules including ADAM17, cathepsin L, CD147 and GRP78 may also function as receptors for SARS-CoV-2.To determine the expression andin situlocalisation of candidate SARS-CoV-2 receptors in the respiratory mucosa, we analysed gene expression datasets from airway epithelial cells of 515 healthy subjects, gene promoter activity analysis using the FANTOM5 dataset containing 120 distinct sample types, single cell RNA sequencing (scRNAseq) of 10 healthy subjects, proteomic datasets, immunoblots on multiple airway epithelial cell types, and immunohistochemistry on 98 human lung samples.We demonstrate absent to lowACE2promoter activity in a variety of lung epithelial cell samples and lowACE2gene expression in both microarray and scRNAseq datasets of epithelial cell populations. Consistent with gene expression, rare ACE2 protein expression was observed in the airway epithelium and alveoli of human lung, confirmed with proteomics. We present confirmatory evidence for the presence of TMPRSS2, CD147 and GRP78 proteinin vitroin airway epithelial cells and confirm broadin situprotein expression of CD147 and GRP78 in the respiratory mucosa.Collectively, our data suggest the presence of a mechanism dynamically regulating ACE2 expression in human lung, perhaps in periods of SARS-CoV-2 infection, and also suggest that alternative receptors for SARS-CoV-2 exist to facilitate initial host cell infection.
The undiagnosed disease burden associated with alpha-1 antitrypsin deficiency genotypes
Authors: Nakanishi Tomoko , Forgetta Vincenzo , Handa Tomohiro , Hirai Toyohiro , Mooser Vincent , Lathrop G. Mark , Cookson William O.C.M. , Richards J. Brent 
Published: July 2020

Alpha-1 antitrypsin deficiency (AATD), mainly due to the PI*ZZ genotype inSERPINA1, is one of the most common inherited diseases. Since it is associated with a high disease burden and partially prevented by smoking cessation, identification of PI*ZZ individuals through genotyping could improve health outcomes.We examined the frequency of the PI*ZZ genotype in individuals with and without diagnosed AATD from UK Biobank, and assessed the associations of the genotypes with clinical outcomes and mortality. A phenome-wide association study (PheWAS) was conducted to reveal disease associations with genotypes. A polygenic risk score (PRS) for forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio was used to evaluate variable penetrance of PI*ZZ.Among 458 164 European-ancestry participants in UK Biobank, 140 had the PI*ZZ genotype and only nine (6.4%, 95% CI 3.4–11.7%) of them were diagnosed with AATD. Those with PI*ZZ had a substantially higher odds of COPD (OR 8.8, 95% CI 5.8–13.3), asthma (OR 2.0, 95% CI 1.4–3.0), bronchiectasis (OR 7.3, 95%CI 3.2–16.8), pneumonia (OR 2.7, 95% CI 1.5–4.9) and cirrhosis (OR 7.8, 95% CI 2.5–24.6) diagnoses and a higher hazard of mortality (2.4, 95% CI 1.2–4.6), compared to PI*MM (wildtype) (n=398 424). These associations were stronger among smokers. PheWAS demonstrated associations with increased odds of empyema, pneumothorax, cachexia, polycythaemia, aneurysm and pancreatitis. Polygenic risk score and PI*ZZ were independently associated with FEV1/FVC <0.7 (OR 1.4 per 1-sdchange, 95% CI 1.4–1.5 and OR 4.5, 95% CI 3.0–6.9, respectively).The important underdiagnosis of AATD, whose outcomes are partially preventable through smoking cession, could be improved through genotype-guided diagnosis.
COVID-19: guidance on palliative care from a European Respiratory Society international task force
Authors: Janssen Daisy J.A. , Ekström Magnus , Currow David C. , Johnson Miriam J. , Maddocks Matthew , Simonds Anita K. , Tonia Thomy , Marsaa Kristoffer 
Published: July 2020

BackgroundMany people are dying from coronavirus disease 2019 (COVID-19), but consensus guidance on palliative care in COVID-19 is lacking. This new life-threatening disease has put healthcare systems under pressure, with the increased need of palliative care provided to many patients by clinicians who have limited prior experience in this field. Therefore, we aimed to make consensus recommendations for palliative care for patients with COVID-19 using the Convergence of Opinion on Recommendations and Evidence (CORE) process.MethodsWe invited 90 international experts to complete an online survey including stating their agreement, or not, with 14 potential recommendations. At least 70% agreement on directionality was needed to provide consensus recommendations. If consensus was not achieved on the first round, a second round was conducted.Results68 (75.6%) experts responded in the first round. Most participants were experts in palliative care, respiratory medicine or critical care medicine. In the first round, consensus was achieved on 13 recommendations based upon indirect evidence and clinical experience. In the second round, 58 (85.3%) out of 68 of the first-round experts responded, resulting in consensus for the 14th recommendation.ConclusionThis multi-national task force provides consensus recommendations for palliative care for patients with COVID-19 concerning: advance care planning; (pharmacological) palliative treatment of breathlessness; clinician–patient communication; remote clinician–family communication; palliative care involvement in patients with serious COVID-19; spiritual care; psychosocial care; and bereavement care. Future studies are needed to generate empirical evidence for these recommendations.
Genome-wide characterization of copy number variations in the host genome in genetic resistance to Marek’s disease using next generation sequencing
Authors: Bai Hao , He Yanghua , Ding Yi , Chu Qin , Lian Ling , Heifetz Eliyahu M. , Yang Ning , Cheng Hans H. , Zhang Huanmin , Chen Jilan , Song Jiuzhou 
Published: July 2020

AbstractBackgroundMarek’s disease (MD) is a highly neoplastic disease primarily affecting chickens, and remains as a chronic infectious disease that threatens the poultry industry. Copy number variation (CNV) has been examined in many species and is recognized as a major source of genetic variation that directly contributes to phenotypic variation such as resistance to infectious diseases. Two highly inbred chicken lines, 63(MD-resistant) and 72(MD-susceptible), as well as their F1generation and six recombinant congenic strains (RCSs) with varied susceptibility to MD, are considered as ideal models to identify the complex mechanisms of genetic and molecular resistance to MD.ResultsIn the present study, to unravel the potential genetic mechanisms underlying resistance to MD, we performed a genome-wide CNV detection using next generation sequencing on the inbred chicken lines with the assistance of CNVnator. As a result, a total of 1649 CNV regions (CNVRs) were successfully identified after merging all the nine datasets, of which 90 CNVRs were overlapped across all the chicken lines. Within these shared regions, 1360 harbored genes were identified. In addition, 55 and 44 CNVRs with 62 and 57 harbored genes were specifically identified in line 63and 72, respectively. Bioinformatics analysis showed that the nearby genes were significantly enriched in 36 GO terms and 6 KEGG pathways including JAK/STAT signaling pathway. Ten CNVRs (nine deletions and one duplication) involved in 10 disease-related genes were selected for validation by using quantitative real-time PCR (qPCR), all of which were successfully confirmed. Finally, qPCR was also used to validate two deletion events in line 72that were definitely normal in line 63. One high-confidence gene,IRF2was identified as the most promising candidate gene underlying resistance and susceptibility to MD in view of its function and overlaps with data from previous study.ConclusionsOur findings provide valuable insights for understanding the genetic mechanism of resistance to MD and the identified gene and pathway could be considered as the subject of further functional characterization.
Transcriptomic and proteomic analyses of ovarian follicles reveal the role of VLDLR in chicken follicle selection
Authors: Chen Qiuyue , Wang Yiya , Liu Zemin , Guo Xiaoli , Sun Yi , Kang Li , Jiang Yunliang 
Published: July 2020

Abstract
Background
Follicle selection in chickens refers to the process of selecting one follicle from a group of small yellow follicles (SY, 6–8 mm in diameter) for development into 12–15 mm hierarchical follicles (usually F6 follicles), which is an important process affecting laying performance in the poultry industry. Although transcriptomic analysis of chicken ovarian follicles has been reported, integrated analysis of chicken follicles for selection by using both transcriptomic and proteomic approaches is still rarely performed. In this study, we compared the proteomes and transcriptomes of SY and F6 follicles in laying hens and identified several genes involved in chicken follicle selection.

Results
Transcriptomic analysis revealed 855 differentially expressed genes (DEGs) between SY follicles and F6 follicles in laying hens, among which 202 were upregulated and 653 were downregulated. Proteomic analysis revealed 259 differentially expressed proteins (DEPs), including 175 upregulated and 84 downregulated proteins. Among the identified DEGs and DEPs, changes in the expression of seven genes, including VLDLR1, WIF1, NGFR, AMH, BMP15, GDF6 and MMP13, and nine proteins, including VLDLR, VTG1, VTG3, PSCA, APOB, APOV1, F10, ZP2 and ZP3L2, were validated. Further analysis indicated that the mRNA level of chicken VLDLR was higher in F6 follicles than in SY follicles and was also higher in granulosa cells (GCs) than in thecal cells (TCs), and it was stimulated by FSH in GCs.

Conclusions
By comparing the proteomes and transcriptomes of SY and F6 follicles in laying hens, we identified several differentially expressed proteins/genes that might play certain roles in chicken follicle selection. These data may contribute to the identification of functional genes and proteins involved in chicken follicle selection.
Care of older people with Cognitive Impairment or Dementia Hospitalized in Traumatology Units (CARExDEM): a quasi-experiment
Authors: Casafont Claudia , Risco Ester , Piazuelo Mercè , Ancín-Pagoto Marta , Cobo-Sánchez José Luis , Solís-Muñoz Montserrat , Zabalegui Adelaida 
Published: July 2020

Abstract
Background
In our context, as in other European countries, care of patients with cognitive disorders or dementia still represents a major challenge in hospital settings. Thus, there is a need to ensure quality and continuity of care, avoiding preventable readmissions, which involve an increase in public expenses. Healthcare professionals need to acquire the necessary knowledge and skills to care for hospitalized patients with cognitive disorders and dementia.

Methods
A quasi-experimental design with repeated observations, taken at baseline, post-intervention, and at one and three months post-intervention, in people hospitalized with cognitive disorders or dementia. The study will be carried out in four general hospitals in Spain and will include 430 PwD and their caregivers. The intervention was previously developed using the Balance of Care methodology where nurses, physicians, social workers and informal caregivers identified the best practices for this specific care situation. We aim to personalize the intervention, as recommended in the literature. The study has an innovative approach that includes new technologies and previous scientific evidence. Valid, reliable instruments will be used to measure the intervention outcomes. Quality of care and comorbidity will be analyzed based on the use of restraints and psychotropic medication, pain control, falls, functional capacity and days of hospitalization. Continuity of care will be measured based on post-discharge emergency hospital visits, visits to specialists, cost, and inter-sectorial communication among healthcare professionals and informal caregivers. Statistical analysis will be performed to analyze the effect of the intervention on quality of care, comorbidity and continuity of care for patients with dementia.

Discussion
Our aim is to helping healthcare professionals to improve the management of cognitive disorders or dementia care during hospitalization and the quality of care, comorbidity and continuity of care in patients with dementia and their informal caregivers. Moving towards dementia-friendly environments is vital to achieving the optimum care outcomes.

Trial registration
Registered in Clinical Trials. ClinicalTrials.gov Identifier: NCT04048980 retrospectively registered on the 6th August 2019. https://clinicaltrials.gov/
Protocol Record HCB/2017/0499.
Sponsor: Hospital Clinic Barcelona.
Pegylated interferon may be considered in chronic viral hepatitis E resistant to ribavirin in kidney transplant recipients
Authors: Ollivier-Hourmand I. , Lebedel L. , Lecouf A. , Allaire M. , Nguyen T. T. N. , Lier C. , Dao T. 
Published: July 2020

Abstract
Background
Hepatitis E virus (HEV) may be resistant to immunosuppression reduction and ribavirin treatment in kidney transplant recipients because of mutant strains and severe side effects of ribavirin which conduct to dose reduction. Sofosbuvir efficacy is controversial. Peg-interferon 2 alpha (PEG-IFN) is currently contraindicated due to a high risk of acute humoral and cellular rejection. The present study assessed, for the first time, the effect of PEG-IFN in a kidney transplant recipient infected with HEV.

Case presentation
The patient had chronic active HEV that was resistant to immunosuppression reduction and optimal ribavirin treatment. He developed significant liver fibrosis. PEG-IFN was administered for 10 months, and it was well tolerated and did not induce rejection. A sustained virological response was obtained.

Conclusions
We conclude that prolonged treatment with PEG-IFN in kidney transplant recipients infected with HEV could be considered as a salvage option.
Intracellular expression of arginine deiminase activates the mitochondrial apoptosis pathway by inhibiting cytosolic ferritin and inducing chromatin autophagy
Authors: Feng Qingyuan , Bian Xuzhao , Liu Xuan , Wang Ying , Zhou Huiting , Ma Xiaojing , Quan Chunju , Yao Yi , Zheng Zhongliang 
Published: July 2020

Abstract
Background
Based on its low toxicity, arginine starvation therapy has the potential to cure malignant tumors that cannot be treated surgically. The Arginine deiminase (ADI) gene has been identified to be an ideal cancer-suppressor gene. ADI expressed in the cytosol displays higher oncolytic efficiency than ADI-PEG20 (Pegylated Arginine Deiminase by PEG 20,000). However, it is still unknown whether cytosolic ADI has the same mechanism of action as ADI-PEG20 or other underlying cellular mechanisms.

Methods
The interactions of ADI with other protein factors were screened by yeast hybrids, and verified by co-immunoprecipitation and immunofluorescent staining. The effect of ADI inhibiting the ferritin light-chain domain (FTL) in mitochondrial damage was evaluated by site-directed mutation and flow cytometry. Control of the mitochondrial apoptosis pathway was analyzed by Western Blotting and real-time PCR experiments. The effect of p53 expression on cancer cells death was assessed by siTP53 transfection. Chromatin autophagy was explored by immunofluorescent staining and Western Blotting.

Results
ADI expressed in the cytosol inhibited the activity of cytosolic ferritin by interacting with FTL. The inactive mutant of ADI still induced apoptosis in certain cell lines of ASS- through mitochondrial damage. Arginine starvation also generated an increase in the expression of p53 and p53AIP1, which aggravated the cellular mitochondrial damage. Chromatin autophagy appeared at a later stage of arginine starvation. DNA damage occurred along with the entire arginine starvation process. Histone 3 (H3) was found in autophagosomes, which implies that cancer cells attempted to utilize the arginine present in histones to survive during arginine starvation.

Conclusions
Mitochondrial damage is the major mechanism of cell death induced by cytosolic ADI. The process of chromatophagy does not only stimulate cancer cells to utilize histone arginine but also speeds up cancer cell death at a later stage of arginine starvation.
Comparison of adenocarcinoma and adenosquamous carcinoma prognoses in Chinese patients with FIGO stage IB-IIA cervical cancer following radical surgery
Authors: Zhang Xiaojing , Lv Zunfu , Xu Xiaoxian , Yin Zhuomin , Lou Hanmei 
Published: July 2020

Abstract
Background
To compare adenocarcinoma (AC) and adenosquamous carcinoma (ASC) prognoses in patients with FIGO stage IB–IIA cervical cancer who underwent radical hysterectomy.

Methods
We performed a retrospective analysis of 240 patients with AC and 130 patients with ASC. Kaplan–Meier curves, Cox regression models, and log-rank tests were used for statistical analysis.

Results
Patients with ASC had higher frequencies of lymphovascular space invasion (LVSI) and serum squamous cell carcinoma antigen (SCC-Ag) > 5 ng/ml (p = 0.049 and p = 0.013, respectively); moreover, they were much older (P = 0.029) than patients with AC. There were no clinically significant differences in overall survival (OS) between the groups. When stratified into three risk groups based on clinicopathological features, survival outcomes did not differ between patients with AC and those with ASC in any risk group. Multivariate analysis showed that lymph node metastasis (LNM) was an independent risk factor for recurrence-free survival (RFS) and OS in patients with AC and in patients with ASC. Carcinoembryonic antigen (CEA) > 5 ng/ml and SCC-Ag > 5 ng/ml were independent predictors of RFS and OS in patients with AC. In addition, among those stratified as intermediate-risk, patients with ASC who received concurrent chemoradiotherapy (CCRT) had significantly better RFS and OS (P = 0.036 and P = 0.047, respectively).

Conclusions
We did not find evidence to suggest that AC and ASC subtypes of cervical cancer were associated with different survival outcomes. CCRT is beneficial for survival in intermediate-risk patients with ASC, but not in those with AC. Serum tumour markers can assist in evaluating prognosis and in providing additional information for patient-tailored therapy for cervical AC.
Clinicopathological significance and prognosis of long noncoding RNA SNHG16 expression in human cancers: a meta-analysis
Authors: Jiao Ruonan , Jiang Wei , Wei Xin , Zhang Mengpei , Zhao Si , Huang Guangming 
Published: July 2020

Abstract
Background
Recent studies have highlighted the important role of long non-coding RNA SNHG16 in various human cancers. Here, we conducted a meta-analysis to investigate the effect of SNHG16 expression on clinicopathological features and prognosis in patients with different kinds of human cancers.

Methods
We performed a systematic search in electronic databases including PubMed, EMBASE, Cochrane Library and Web of Science, to investigate the potential association between SNHG16 expression and prognostic significance and clinical features in cancer patients. Odds ratios (ORs) or hazards ratios (HRs) with corresponding 95% confidence intervals (95% CIs) were pooled to estimate the prognosis value of SNHG16 by StataSE 15.0 software.

Results
A total of 16 eligible studies with 1299 patients were enrolled in our meta-analysis. The results revealed that increased expression level of SNHG16 was significantly associated with larger tumor size (OR: 3.357; 95% CI: 2.173–5.185; P < 0.001), advanced TNM stage (OR: 2.930; 95% CI: 1.522–5.640; P = 0.001) and poor histological grade (OR: 3.943; 95% CI: 1.955–7.952; P < 0.001), but not correlated with smoking status (P = 0.489), sex (P = 0.932), distant metastasis (P = 0.052), or lymph node metastasis (P = 0.155). Moreover, the pooled HR showed that elevated expression SNHG16 was associated with a significantly poorer overall survival (OS) (HR = 1.866, 95% CI: 1.571–2.216, P < 0.001). For the set of cancer types, high expression of SNHG16 was significantly associated with shorter OS in patients with cancers of the urinary system (HR: 2.523, 95% CI:1.540–4.133; P <0.001), digestive system (HR: 2.406, 95% CI:1.556–3.721; P <0.001), and other cancers (including glioma and non-small cell lung cancer) (HR: 1.786, 95% CI:1.406–2.267; P <0.001).

Conclusions
LncRNA SNHG16 overexpression might serve as an unfavorable prognostic factor, which provides a basis for medical workers to evaluate the prognosis of patients and to help the decision-making process.