bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eliapixant (BAY 1817080), a P2X3 receptor antagonist, in refractory chronic cough: a randomised, placebo-controlled, crossover phase 2a study
Authors: Morice Alyn , Smith Jaclyn A. , McGarvey Lorcan , Birring Surinder S. , Parker Sean M. , Turner Alice , Hummel Thomas , Gashaw Isabella , Fels Lueder , Klein Stefan , Francke Klaus , Friedrich Christian 
Published: May 2021

BackgroundATP actingviaP2X3 receptors is an important mediator of refractory chronic cough (RCC). This phase 2a double-blinded crossover study assessed the safety, tolerability and efficacy of eliapixant (BAY 1817080), a selective P2X3 receptor antagonist, in adults with RCC attending specialist centres.MethodsIn period A, patients received placebo for 2 weeks then eliapixant 10 mg for 1 week. In period B, patients received eliapixant 50, 200 and 750 mg twice daily for 1 week per dose level. Patients were randomised 1:1 to period A–B (n=20) or B–A (n=20). The primary efficacy end-point was change in cough frequency assessed over 24 h. The primary safety end-point was frequency and severity of adverse events (AEs).Results37 patients completed randomised therapy. Mean cough frequency fell by 17.4%versusbaseline with placebo. Eliapixant reduced cough frequency at doses ≥50 mg (reductionversusplacebo at 750 mg: 25% (90% CI 11.5–36.5%); p=0.002). Doses ≥50 mg also significantly reduced cough severity. AEs, mostly mild or moderate, were reported in 65% of patients with placebo and 41–49% receiving eliapixant. Cumulative rates of taste-related AEs were 3% with placebo and 5–21% with eliapixant; all were mild.ConclusionsSelective P2X3 antagonism with eliapixant significantly reduced cough frequency and severity, confirming this as a viable therapeutic pathway for RCC. Taste-related side-effects were lower at therapeutic doses than with the less selective P2X3 antagonist gefapixant. Selective P2X3 antagonism appears to be a novel therapeutic approach for RCC.
Long-term air pollution and road traffic noise exposure and COPD: the Danish Nurse Cohort
Authors: Liu Shuo , Lim Youn-Hee , Pedersen Marie , Jørgensen Jeanette T. , Amini Heresh , Cole-Hunter Thomas , Mehta Amar J. , So Rina , Mortensen Laust H. , Westendorp Rudi G.J. , Loft Steffen , Bräuner Elvira V. , Ketzel Matthias , Hertel Ole , Brandt Jørgen , Jensen Steen S. , Christensen Jesper H. , Sigsgaard Torben , Geels Camilla , Frohn Lise M. , Brboric´ Maja , Radonic´ Jelena , Turk Sekulic Maja , Bønnelykke Klaus , Backalarz Claus , Simonsen Mette K. , Andersen Zorana J. 
Published: May 2021

BackgroundWhile air pollution has been linked to the development of chronic obstructive pulmonary disease (COPD), evidence on the role of environmental noise is just emerging. We examined the associations of long-term exposure to air pollution and road traffic noise with COPD incidence.MethodsWe defined COPD incidence for 24 538 female nurses from the Danish Nurse Cohort (age >44 years) as the first hospital contact between baseline (1993 or 1999) and 2015. We estimated residential annual mean concentrations of particulate matter with an aerodynamic diameter <2.5 µm (PM2.5) since 1990 and nitrogen dioxide (NO2) since 1970 using the Danish Eulerian Hemispheric Model/Urban Background Model/Air Geographic Information System modelling system, and road traffic noise (Lden) since 1970 using the Nord2000 model. Time-varying Cox regression models were applied to assess the associations of air pollution and road traffic noise with COPD incidence.Results977 nurses developed COPD during a mean of 18.6 years’ follow-up. We observed associations with COPD for all three exposures with HRs and 95% CIs of 1.19 (1.01–1.41) per 6.26 µg·m−3for PM2.5, 1.13 (1.05–1.20) per 8.19 µg·m−3for NO2and 1.15 (1.06–1.25) per 10 dB for Lden. Associations with NO2and Ldenattenuated slightly after mutual adjustment, but were robust to adjustment for PM2.5. Associations with PM2.5were attenuated to null after adjustment for either NO2or Lden. No potential interaction effect was observed between air pollutants and noise.ConclusionLong-term exposure to air pollution, especially traffic-related NO2, and to road traffic noise were independently associated with COPD.
Compatibility of a novel filter paper-based bio-safe sputum transport kit with line probe assay for diagnosing drug-resistant tuberculosis: a single-site evaluation study
Authors: Anthwal Divya , Gupta Rakesh Kumar , Singhal Ritu , Bhalla Manpreet , Verma Ajoy Kumar , Khayyam Khalid Umar , Myneedu Vithal Prasad , Sarin Rohit , Gupta Ashawant , Gupta Nalini Kant , Singh Manjula , Sivaswami Tyagi Jaya , Haldar Sagarika 
Published: May 2021

BackgroundNear-patient access to appropriate tests is a major obstacle for the efficient diagnosis of tuberculosis (TB) and associated drug resistance.MethodsWe recently developed the “TB Concentration & Transport” kit for bio-safe, ambient-temperature transportation of dried sputum onTrans-Filter, and the “TB DNA Extraction” kit for DNA extraction fromTrans-Filter for determining drug resistance by DNA sequencing. In the present study, we evaluated the compatibility of Kit-extracted DNA with Hain's line probe assays (LPAs), which are endorsed by National TB programmes for the detection of drug resistance in sputum collected from presumptive multidrug-resistant TB patients (n=207).ResultsTrans-Filter-extracted DNA was seamlessly integrated with the LPA protocol (Kit-LPA). The sensitivity of Kit-LPA for determining drug resistance was 83.3% for rifampicin (95% CI 52–98%), 77.7% for isoniazid (95% CI 52–94%), 85.7% for fluoroquinolones (95% CI 42–100%) and 66.6% for aminoglycosides (95% CI 9–99%), with a specificity range of 93.7% (95% CI 87–97) to 99.1% (95% CI 95–100) using phenotypic drug susceptibility testing (DST) as a reference standard. A high degree of concordance was noted between results obtained from Kit-LPA and LPA (99% to 100% (κ value: 0.83–1.0)).ConclusionsThis study demonstrates successful integration of our developed kits with LPA. The adoption of these kits across Designated Microscopy Centres in India can potentially overcome the existing challenge of transporting infectious sputum at controlled temperature to centralised testing laboratories and can provide rapid near-patient cost-effective “Universal DST” services to TB subjects residing in remote areas.
Quantitative18F-fluorodeoxyglucose positron emission tomography/computed tomography to assess pulmonary inflammation in COPD
Authors: Vass Laurence , Fisk Marie , Cheriyan Joseph , Mohan Divya , Forman Julia , Oseni Adelola , Devaraj Anand , Mäki-Petäjä Kaisa M. , McEniery Carmel M. , Fuld Jonathan , Hopkinson Nicholas S. , Lomas David A. , Cockcroft John R. , Tal-Singer Ruth , Polkey Michael I. , Wilkinson Ian B. 
Published: May 2021

RationaleCOPD and smoking are characterised by pulmonary inflammation.18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging may improve knowledge of pulmonary inflammation in COPD patients and aid early development of novel therapies as an imaging biomarker.ObjectivesTo evaluate pulmonary inflammation, assessed by FDG uptake, in whole and regional lung in “usual” (smoking-related) COPD patients, alpha-1 antitrypsin deficiency (α1ATD) COPD patients, smokers without COPD and never-smokers using FDG PET/CT. Secondly, to explore cross-sectional associations between FDG PET/CT and systemic inflammatory markers in COPD patients and repeatability of the technique in COPD patients.MethodsData from two imaging studies were evaluated. Pulmonary FDG uptake (normalised Ki; nKi) was measured by Patlak graphical analysis in four subject groups: 84 COPD patients, 11 α1ATD-COPD patients, 12 smokers and 10 never-smokers. Within the COPD group, associations between nKiand systemic markers of inflammation were assessed. Repeatability was evaluated in 32 COPD patients comparing nKivalues at baseline and at 4-month follow-up.ResultsCOPD patients, α1ATD-COPD patients and smokers had increased whole lung FDG uptake (nKi) compared with never-smokers (0.0037±0.001, 0.0040±0.001, 0.0040±0.001versus0.0028±0.001 mL·cm−3·min−1, respectively, p<0.05 for all). Similar results were observed in upper and middle lung regions. In COPD participants, plasma fibrinogen was associated with whole lung nKi(β=0.30, p=0.02) in multivariate analysis adjusted for current smoking, forced expiratory volume in 1 s % predicted, systemic neutrophils and C-reactive protein levels. Mean percentage difference in nKibetween the baseline and follow-up was 3.2%, and the within subject coefficient of variability was 7.7%.ConclusionsFDG PET/CT has potential as a noninvasive tool to enable whole lung and regional quantification of FDG uptake to assess smoking- and COPD-related pulmonary inflammation.
Alveolar macrophage transcriptomic profiling in COPD shows major lipid metabolism changes
Authors: Fujii Wataru , Kapellos Theodore S. , Baßler Kevin , Händler Kristian , Holsten Lisa , Knoll Rainer , Warnat-Herresthal Stefanie , Oestreich Marie , Hinkley Emily R. , Hasenauer Jan , Pizarro Carmen , Thiele Christoph , Aschenbrenner Anna C. , Ulas Thomas , Skowasch Dirk , Schultze Joachim L. 
Published: May 2021

BackgroundImmune cells play a major role in the pathogenesis of COPD. Changes in the distribution and cellular functions of major immune cells, such as alveolar macrophages (AMs) and neutrophils are well known; however, their transcriptional reprogramming and contribution to the pathophysiology of COPD are still not fully understood.MethodTo determine changes in transcriptional reprogramming and lipid metabolism in the major immune cell type within bronchoalveolar lavage fluid, we analysed whole transcriptomes and lipidomes of sorted CD45+Lin−HLA-DR+CD66b−AutofluorescencehiAMs from controls and COPD patients.ResultsWe observed global transcriptional reprogramming featuring a spectrum of activation states, including pro- and anti-inflammatory signatures. We further detected significant changes between COPD patients and controls in genes involved in lipid metabolism, such as fatty acid biosynthesis in GOLD2 patients. Based on these findings, assessment of a total of 202 lipid species in sorted AMs revealed changes of cholesteryl esters, monoacylglycerols and phospholipids in a disease grade-dependent manner.ConclusionsTranscriptome and lipidome profiling of COPD AMs revealed GOLD grade-dependent changes, such as in cholesterol metabolism and interferon-α and γ responses.
In Situ Fabrication of Activated Carbon from a Bio-Waste Desmostachya bipinnata for the Improved Supercapacitor Performance
Authors: Gupta Gopal Krishna , Sagar Pinky , Pandey Sumit Kumar , Srivastava Monika , Singh A. K. , Singh Jai , Srivastava Anchal , Srivastava S. K. , Srivastava Amit 
Published: May 2021

AbstractHerein, we demonstrate the fabrication of highly capacitive activated carbon (AC) using a bio-waste Kusha grass (Desmostachya bipinnata), by employing a chemical process followed by activation through KOH. The as-synthesized few-layered activated carbon has been confirmed through X-ray powder diffraction, transmission electron microscopy, and Raman spectroscopy techniques. The chemical environment of the as-prepared sample has been accessed through FTIR and UV–visible spectroscopy. The surface area and porosity of the as-synthesized material have been accessed through the Brunauer–Emmett–Teller method. All the electrochemical measurements have been performed through cyclic voltammetry and galvanometric charging/discharging (GCD) method, but primarily, we focus on GCD due to the accuracy of the technique. Moreover, the as-synthesized AC material shows a maximum specific capacitance as 218 F g−1 in the potential window ranging from − 0.35 to + 0.45 V. Also, the AC exhibits an excellent energy density of ~ 19.3 Wh kg−1 and power density of ~ 277.92 W kg−1, respectively, in the same operating potential window. It has also shown very good capacitance retention capability even after 5000th cycles. The fabricated supercapacitor shows a good energy density and power density, respectively, and good retention in capacitance at remarkably higher charging/discharging rates with excellent cycling stability. Henceforth, bio-waste Kusha grass-derived activated carbon (DP-AC) shows good promise and can be applied in supercapacitor applications due to its outstanding electrochemical properties. Herein, we envision that our results illustrate a simple and innovative approach to synthesize a bio-waste Kusha grass-derived activated carbon (DP-AC) as an emerging supercapacitor electrode material and widen its practical application in electrochemical energy storage fields.
“Old wine in a new bottle” - post COVID-19 infection, central serous chorioretinopathy and the steroids
Authors: Sanjay Srinivasan , Gowda Poornachandra B. , Rao Bhimasena , Mutalik Deepashri , Mahendradas Padmamalini , Kawali Ankush , Shetty Rohit 
Published: May 2021

Abstract
Introduction
Corona virus disease (COVID-19) pandemic can cause myriad of ocular manifestations.
We report a case of unilateral multi focal central serous retinopathy, post COVID-19 infection in an Asian Indian female.

Case presentation
A 42-year-old female presented to us with unilateral blurring, in the right eye (OD), 12 days after COVID-19 infection. She had fever, chills, shortness of breath and cough with tiredness and was COVID- RT PCR positive. She was administered intravenous and oral antibiotics with injection heparin/remdesivir, during her 7 day stay at the hospital. She was also on steroid inhalers. She had no systemic history of note.
On ocular evaluation, her corrected distance visual acuity was 20/40 in OD and 20/20 in left eye (OS). Anterior segment was normal. Anterior vitreous was clear. Fundus examination of the OD showed central serous retinopathy (CSCR) with OS being normal.

Conclusion
CSCR can occur post COVID-19 due to steroid administration and physicians administering it should be aware of this and refer the patients to an ophthalmologist earlier.
A novel essential protein identification method based on PPI networks and gene expression data
Authors: Zhong Jiancheng , Tang Chao , Peng Wei , Xie Minzhu , Sun Yusui , Tang Qiang , Xiao Qiu , Yang Jiahong 
Published: May 2021

AbstractBackgroundSome proposed methods for identifying essential proteins have better results by using biological information. Gene expression data is generally used to identify essential proteins. However, gene expression data is prone to fluctuations, which may affect the accuracy of essential protein identification. Therefore, we propose an essential protein identification method based on gene expression and the PPI network data to calculate the similarity of "active" and "inactive" state of gene expression in a cluster of the PPI network. Our experiments show that the method can improve the accuracy in predicting essential proteins.ResultsIn this paper, we propose a new measure named JDC, which is based on the PPI network data and gene expression data. The JDC method offers a dynamic threshold method to binarize gene expression data. After that, it combines the degree centrality and Jaccard similarity index to calculate the JDC score for each protein in the PPI network. We benchmark the JDC method on four organisms respectively, and evaluate our method by using ROC analysis, modular analysis, jackknife analysis, overlapping analysis, top analysis, and accuracy analysis. The results show that the performance of JDC is better than DC, IC, EC, SC, BC, CC, NC, PeC, and WDC. We compare JDC with both NF-PIN and TS-PIN methods, which predict essential proteins through active PPI networks constructed from dynamic gene expression.ConclusionsWe demonstrate that the new centrality measure, JDC, is more efficient than state-of-the-art prediction methods with same input. The main ideas behind JDC are as follows: (1) Essential proteins are generally densely connected clusters in the PPI network. (2) Binarizing gene expression data can screen out fluctuations in gene expression profiles. (3) The essentiality of the protein depends on the similarity of "active" and "inactive" state of gene expression in a cluster of the PPI network.
Metabolome and transcriptome analysis reveals the molecular profiles underlying the ginseng response to rusty root symptoms
Authors: Bian Xingbo , Zhao Yan , Xiao Shengyuan , Yang He , Han Yongzhong , Zhang Lianxue 
Published: May 2021

AbstractBackgroundGinseng rusty root symptoms (GRS) is one of the primary diseases of ginseng. This disease leads to a severe decline in the quality of ginseng. It has been shown that the occurrence of GRS is associated with soil environmental degradation, which may involve changes in soil microbiology and physicochemical properties.ResultsIn this study, GRS and healthy ginseng (HG) samples were used as experimental materials for comparative analysis of transcriptome and metabolome. Compared with those in HG samples, 949 metabolites and 9451 genes were significantly changed at the metabolic and transcriptional levels in diseased samples. The diseased tissues’ metabolic patterns changed, and the accumulation of various organic acids, alkaloids, alcohols and phenols in diseased tissues increased significantly. There were significant differences in the expression of genes involved in plant hormone signal transduction, phenylpropanoid biosynthesis, the peroxidase pathway, and the plant-pathogen interaction pathway.ConclusionThe current study involved a comparative metabolome and transcriptome analysis of GRS and HG samples. Based on the findings at the transcriptional and metabolic levels, a mechanism model of the ginseng response to GRS was established. Our results provide new insights into ginseng’s response to GRS, which will reveal the potential molecular mechanisms of this disease in ginseng.
Exploring polypharmacy burden among elderly patients with chronic diseases in Chinese community: a cross-sectional study
Authors: Wang Yongli , Li Xiaodan , Jia Dongmei , Lin Beilei , Fu Bo , Qi Bei , Zhang Zhenxiang 
Published: May 2021

Abstract
Background
In the long-term use of multiple medications for elderly patients diagnosed with chronic diseases, medication problems are prominent, which seriously reduces their quality of life. The burden of medications of patients critically affects their medication beliefs, behaviors and disease outcomes. It may be a solution to stress the burden of medications of patients. Its medication issues develops a novel perspective. The present study aimed to exploit the Chinese version of Living with Medicines Questionnaire-3(C-LMQ-3) to quantify the medicines burden of elderly patients diagnosed with chronic diseases in China, and evaluate the relevant demographic characteristics of sub-populations with high medicines burden.

Methods
The survey was distributed to elderly patients aged ≥ 60 years with chronic disease by using ≥ 5 medicines, C-LMQ-3 scores and domain scores were compared by the characteristics of elderly patients by employing descriptive statistics and performing statistical tests.

Results
On the whole, 430 responses were analyzed, and the participants were aged between 60 and 91 years, with the average age of 73.57 years (SD: 7.87). Most of the responses were female (61.7 %) with middle school education (38.5 %). Moreover, 54.1 % of the participants lived with spouse only, 16.2 % had both spouse and children, and 10.0 % lived alone. As indicated from regression analysis, higher C-LMQ-3 scores were associated with those who were with low education level, 60–69 years-old, using ≥ 11 medicines, using medicines ≥ 3 times a day, income per month (RMB) ≤ 3000, and who having higher monthly self-paid medication (RMB) ≥ 300 (p < 0.01). Burden was mainly driven by cost-related burden, concerns about medicines, and the lack of autonomy over medicine regimens.

Conclusions
This study presents the preliminary evidence to elderly patients diagnosed with chronic diseases in mainland China that pay attention to multiple medications burden may help reduce the Drug Related Problems, whereas some elderly patients have a higher burden of medication. Chinese health care providers are required to primarily evaluate and highlight such patients, and formulate relevant intervention strategies to ensure medication adherence and daily medication management of elderly patients with polypharmacy.
A nomogram incorporating functional and tubular damage biomarkers to predict the risk of acute kidney injury for septic patients
Authors: Ma Jianchao , Deng Yujun , Lao Haiyan , Ouyang Xin , Liang Silin , Wang Yifan , Yao Fen , Deng Yiyu , Chen Chunbo 
Published: May 2021

Abstract
Background
Combining tubular damage and functional biomarkers may improve prediction precision of acute kidney injury (AKI). Serum cystatin C (sCysC) represents functional damage of kidney, while urinary N-acetyl-β-D-glucosaminidase (uNAG) is considered as a tubular damage biomarker. So far, there is no nomogram containing this combination to predict AKI in septic cohort. We aimed to compare the performance of AKI prediction models with or without incorporating these two biomarkers and develop an effective nomogram for septic patients in intensive care unit (ICU).

Methods
This was a prospective study conducted in the mixed medical-surgical ICU of a tertiary care hospital. Adults with sepsis were enrolled. The patients were divided into development and validation cohorts in chronological order of ICU admission. A logistic regression model for AKI prediction was first constructed in the development cohort. The contribution of the biomarkers (sCysC, uNAG) to this model for AKI prediction was assessed with the area under the receiver operator characteristic curve (AUC), continuous net reclassification index (cNRI), and incremental discrimination improvement (IDI). Then nomogram was established based on the model with the best performance. This nomogram was validated in the validation cohort in terms of discrimination and calibration. The decision curve analysis (DCA) was performed to evaluate the nomogram’s clinical utility.

Results
Of 358 enrolled patients, 232 were in the development cohort (69 AKI), while 126 in the validation cohort (52 AKI). The first clinical model included the APACHE II score, serum creatinine, and vasopressor used at ICU admission. Adding sCysC and uNAG to this model improved the AUC to 0.831. Furthermore, incorporating them significantly improved risk reclassification over the predictive model alone, with cNRI (0.575) and IDI (0.085). A nomogram was then established based on the new model including sCysC and uNAG. Application of this nomogram in the validation cohort yielded fair discrimination with an AUC of 0.784 and good calibration. The DCA revealed good clinical utility of this nomogram.

Conclusions
A nomogram that incorporates functional marker (sCysC) and tubular damage marker (uNAG), together with routine clinical factors may be a useful prognostic tool for individualized prediction of AKI in septic patients.