bluuebunny/crossref_metadata_2025_split huggingface dataset:
Periostin: contributor to abnormal airway epithelial function in asthma?
Authors: Burgess Janette K. , Jonker Marnix R. , Berg Marijn , ten Hacken Nick T.H. , Meyer Kerstin B. , van den Berge Maarten , Nawijn Martijn C. , Heijink Irene H. 
Published: September 2020

Periostin (POSTN) may serve as a biomarker for Type-2 mediated eosinophilic airway inflammation in asthma. We hypothesised that a Type-2 cytokine, interleukin (IL)-13, induces airway epithelial expression ofPOSTN, which in turn contributes to epithelial changes observed in asthma.We studied the effect of IL-13 onPOSTNexpression in BEAS-2B and air–liquid interface differentiated primary bronchial epithelial cells (PBECs). Additionally, the effects of recombinant human POSTN on epithelial-to-mesenchymal transition (EMT) markers and mucin genes were assessed.POSTNsingle cell gene expression and protein levels were analysed in bronchial biopsies and induced sputum from asthma patients and healthy controls.IL-13 increasedPOSTNexpression in both cell types and this was accompanied by EMT-related features in BEAS-2B. In air–liquid interface differentiated PBECs, IL-13 increased POSTN basolateral and apical release. Apical administration of POSTN increased the expression ofMMP-9,MUC5BandMUC5AC. In bronchial biopsies,POSTNexpression was mainly confined to basal epithelial cells, ionocytes, endothelial cells and fibroblasts, showing higher expression in basal epithelial cells from asthma patientsversusthose from controls. A higher level of POSTN protein expression in epithelial and subepithelial layers was confirmed in bronchial biopsies from asthma patients when compared to healthy controls. Although sputum POSTN levels were not higher in asthma, levels correlated with eosinophil numbers and with the coughing-up of mucus.POSTNexpression is increased by IL-13 in bronchial epithelial cells and is higher in bronchial biopsies from asthma patients. This may have important consequences, as administration of POSTN increases epithelial expression of mucin genes, supporting the relationship of POSTN with Type-2 mediated asthma and mucus secretion.
Elevated D-dimers and lack of anticoagulation predict PE in severe COVID-19 patients
Authors: Mouhat Basile , Besutti Matthieu , Bouiller Kevin , Grillet Franck , Monnin Charles , Ecarnot Fiona , Behr Julien , Capellier Gilles , Soumagne Thibaud , Pili-Floury Sébastien , Besch Guillaume , Mourey Guillaume , Lepiller Quentin , Chirouze Catherine , Schiele François , Chopard Romain , Meneveau Nicolas 
Published: September 2020

BackgroundCoronavirus disease 2019 (COVID-19) may predispose to venous thromboembolism. We determined factors independently associated with computed tomography pulmonary angiography (CTPA)-confirmed pulmonary embolism (PE) in hospitalised severe COVID-19 patients.MethodsAmong all (n=349) patients hospitalised for COVID-19 in a university hospital in a French region with a high rate of COVID-19, we analysed patients who underwent CTPA for clinical signs of severe disease (oxygen saturation measured by pulse oximetry ≤93% or breathing rate ≥30 breaths·min−1) or rapid clinical worsening. Multivariable analysis was performed using Firth penalised maximum likelihood estimates.Results162 (46.4%) patients underwent CTPA (mean±sdage 65.6±13.0 years; 67.3% male (95% CI 59.5–75.5%). PE was diagnosed in 44 (27.2%) patients. Most PEs were segmental and the rate of PE-related right ventricular dysfunction was 15.9%. By multivariable analysis, the only two significant predictors of CTPA-confirmed PE were D-dimer level and the lack of any anticoagulant therapy (OR 4.0 (95% CI 2.4–6.7) per additional quartile and OR 4.5 (95% CI 1.1–7.4), respectively). Receiver operating characteristic curve analysis identified a D-dimer cut-off value of 2590 ng·mL−1to best predict occurrence of PE (area under the curve 0.88, p<0.001, sensitivity 83.3%, specificity 83.8%). D-dimer level >2590 ng·mL−1was associated with a 17-fold increase in the adjusted risk of PE.ConclusionElevated D-dimers (>2590 ng·mL−1) and absence of anticoagulant therapy predict PE in hospitalised COVID-19 patients with clinical signs of severity. These data strengthen the evidence base in favour of systematic anticoagulation, and suggest wider use of D-dimer guided CTPA to screen for PE in acutely ill hospitalised patients with COVID-19.
ERS International Congress, Madrid, 2019: highlights from the Pulmonary Vascular Diseases Assembly
Authors: Ramjug Sheila , Weatherald Jason , Sahay Sandeep , Khoury Johad , Foris Vasile , Chandran Nagaraj , Bokan Aleksandar , Godinas Laurent , Delcroix Marion 
Published: September 2020

The 2019 European Respiratory Society (ERS) International Congress, held in Madrid, Spain, had exciting sessions regarding the field of pulmonary vascular disease. The symposia related to the new ERS/European Society of Cardiology (ESC) Guidelines for the diagnosis and management of acute pulmonary embolism were well received, as were sessions on pulmonary hypertension related to lung disease, demonstrating the concept of pulmonary hypertension not being the rarity that it was previously thought to be. The use of risk stratification in relation to pulmonary arterial hypertension (PAH) was heavily featured and the scientific sessions informing the respiratory community of potential biomarkers and targets for future therapies were thought-provoking.This article discusses highlights of the 2019 pulmonary vascular disease sessions as a summary of current knowledge and practice. We have summarised the key points from the sessions pertaining to the new ERS/ESC Guidelines for the management of acute pulmonary embolism. We have also focused on prognostic factors and potential therapies in pulmonary hypertension related to interstitial lung disease. Relating to PAH, we have reviewed the symposia on risk stratification, along with the use of noninvasive measures and the sessions relating to biomarkers in PAH.
Determinants of person-centered maternity care at the selected health facilities of Dessie town, Northeastern, Ethiopia: community-based cross-sectional study
Authors: Dagnaw Fentaw Teshome , Tiruneh Sofonyas Abebaw , Azanaw Melkalem Mamuye , Desale Aragaw Tesfaw , Engdaw Melaku Tadege 
Published: September 2020

Abstract
Background
Person-centered maternity care is providing care that is respectful and responsive to individual women’s preferences, needs, and values and ensuring that their values guide all clinical decisions during childbirth. Although person-centered health care is one of the factors that increase client satisfaction and increased health service utilization in Ethiopia, little is known about predictors of person-centered maternity care. Therefore, the aim of this study was to identify the determinant factors of person-centered maternity care among mothers who gave birth in selected health facilities in Dessie town, Northeastern, Ethiopia.

Methods
A community-based cross-sectional study was conducted with a total of 317 study participants at Dessie town selected by a simple random sampling technique. The data was coded and entered Epi-data version 4.4 and analyzed using SPSS version 23. Descriptive statistics was presented using tables and figures. Multivariable linear regression analysis was used to identify factors associated with Person-Centered Maternity Care. Two sides P-value < 0.05 was taken to declare statistically significant.

Results
Overall, 310 study participants participated with a response rate of 97.8%. In multivariable linear regression, rural residence (β = -4.12; 95% CI: -7.60, -0.67), family average monthly income ≤ 3000 birr (β = -6.20, 95% CI: -9.40, -3.04), night time delivery(β = -2.98, 95%CI: -5.90, -0.06), dead fetus outcome during delivery (β = -12.7; 95% CI: -21.80, -3.50), and 2–7 days health facility length of stay (β = -5.07, 95% CI: -9.20, -0.92) were significantly decreased Person Center Maternity Care score, whereas private health institution delivery (β = 14.13, 95% CI: 7.70, 20.60) is significantly increased Person centered maternity care score.

Conclusions
This study revealed that most of the factors that affect person-centered maternity care are modifiable factors. Therefore, Primary attention should be given to improve the quality of care through effective communication between clients and providers at each level of the health care delivery system to increase the uptake of high-quality facility-based births.
Validation of the PHQ-9 depression scale in Ethiopian cancer patients attending the oncology clinic at Tikur Anbessa specialized hospital
Authors: Degefa Mikyas , Dubale Benyam , Bayouh Fikirte , Ayele Biniyam , Zewde Yared 
Published: September 2020

Abstract
Background
Although depression is highly prevalent among cancer patients, it is often underdiagnosed and poorly managed particularly in developing nations. These shortcomings can have substantial adverse effects not only on the disease prognosis but also on patients’ quality of life. The Patient Health Questionnaire-9 is a widely used depression screening tool but it has not been validated among patients with chronic illnesses such as cancer in Ethiopia. We aim to validate the PHQ-9 among Ethiopian cancer patients in an outpatient setting.

Methods
A cross-sectional study was conducted among cancer patients attending the oncology clinic at Tikur Anbessa Specialized Hospital (TASH). We assessed criterion validity and performance of the PHQ-9 test against the gold standard Mini-International Neuropsychiatric Interview (MINI) diagnostic tool among patients with cancer. The MINI was administered by psychiatric nurses who were blind to the initial PHQ-9 screening tool.

Results
A total of 163 patients completed the 2 stages of a diagnostic interview in the study. The majority (64%) of the participants were women, the mean age was 46 (13.5) years. Using the gold standard MINI test the prevalence of Major Depressive Episode (MDE) was 15%. The internal consistency (Cronbach’s α) for PHQ-9 was 0.78 suggesting good (acceptable) internal consistency for the reliability of the test scores. When the total PHQ-9 score was used to identify cases of MDE, the Area under the Curve (AUC) was 0.93 (95% confidence interval [CI], 0.88–0.97) on Receiver Operating Characteristic (ROC) analysis. This shows evidence for the excellent discriminating power of the PHQ-9 between cases and non-cases of MDE. At cutoff point ≥4, the PHQ-9 had a sensitivity of 88% and specificity of 78.1% on the ROC curve to detect MDE.

Conclusion
PHQ-9 is a reliable and valid instrument to detect MDE among individuals with chronic conditions such as cancer patients in outpatient settings and it can be used in resource-limited settings for early diagnosis and proper therapy of such patients.
Real-world treatment patterns and survival outcomes for advanced non-small cell lung cancer in the pre-immunotherapy era in Portugal: a retrospective analysis from the I-O Optimise initiative
Authors: Soares Marta , Antunes Luís , Redondo Patrícia , Borges Marina , Hermans Ruben , Patel Dony , Grimson Fiona , Munro Robin , Chaib Carlos , Lacoin Laure , Daumont Melinda , Penrod John R. , O’Donnell John C. , Bento Maria José , Rocha Gonçalves Francisco 
Published: September 2020

Abstract
Background
As part of the multinational I-O Optimise research initiative, this retrospective cohort study of patients with advanced non-small cell lung cancer (NSCLC) evaluated real-world treatment patterns and survival prior to immunotherapy reimbursement in Portugal.

Methods
This study utilized a database held by IPO-Porto, Portugal’s largest oncology hospital. Adult patients diagnosed with stage IIIB or IV NSCLC from January 2012 to December 2016 at IPO-Porto, with follow-up to June 2017, were included. Treatment analyses were performed from 2015 onwards. Kaplan–Meier methods were used for overall survival (OS). Factors associated with OS and systemic anti-cancer therapy (SACT) treatment were assessed using multivariate statistical models.

Results
Of 1524 patients diagnosed with NSCLC at IPO-Porto, 1008 patients had advanced disease (stage IIIB: 10.1%, 154/1524, stage IV: 56.0%, 854/1524). For those with advanced disease, median age was 65 years (range: 21–92) and 75.6% (762/1008) were male. Median OS (interquartile range [IQR]) was 11.4 (5.2–26.9) months for stage IIIB and 6.3 (2.4–15.0) months for stage IV. Factors associated with decreased risk of death included female sex and epidermal growth factor receptor gene (EGFR)/anaplastic lymphoma kinase gene (ALK) mutations/rearrangements; factors associated with increased risk of death included older age and stage IV disease. Among patients diagnosed in 2015 or 2016, 75.8% (297/392) received ≥1 line of SACT. Platinum-based chemotherapy was the most common first-line therapy (non-squamous cell carcinoma [NSQ]: 72.9%; squamous cell carcinoma [SQ] 87.3%, 55/63; patients with EGFR/ALK mutations/rearrangements primarily received tyrosine kinase inhibitors). The likelihood of receiving SACT was lower in older patients and those diagnosed with stage IV disease. Patients not receiving SACT had poor survival outcomes (median OS [IQR]: NSQ, 1.8 [1.1–3.1] months; SQ, 2.3 (1.3–3.4) months), while median OS (IQR) in SACT-treated patients was 12.6 (6.1–24.5) months for NSQ and 10.3 (5.7–15.9) months for SQ.

Conclusions
This real-world data analysis from a large Portuguese oncology hospital demonstrates a high disease burden for advanced NSCLC in the pre-immunotherapy era, with nearly one-quarter of patients not receiving SACT. Even in patients receiving SACT, median survival was only about 1 year.
Anti-trichomonad activities of different compounds from foods, marine products, and medicinal plants: a review
Authors: Friedman Mendel , Tam Christina C. , Cheng Luisa W. , Land Kirkwood M. 
Published: September 2020

AbstractHuman trichomoniasis, caused by the pathogenic parasitic protozoan Trichomonas vaginalis, is the most common non-viral sexually transmitted disease that contributes to reproductive morbidity in affected women and possibly to prostate cancer in men. Tritrichomonas foetus strains cause the disease trichomoniasis in farm animals (cattle, bulls, pigs) and diarrhea in domestic animals (cats and dogs). Because some T. vaginalis strains have become resistant to the widely used drug metronidazole, there is a need to develop alternative treatments, based on safe natural products that have the potential to replace and/or enhance the activity of lower doses of metronidazole. To help meet this need, this overview collates and interprets worldwide reported studies on the efficacy of structurally different classes of food, marine, and medicinal plant extracts and some of their bioactive pure compounds against T. vaginalis and T. foetus in vitro and in infected mice and women. Active food extracts include potato peels and their glycoalkaloids α-chaconine and α-solanine, caffeic and chlorogenic acids, and quercetin; the tomato glycoalkaloid α-tomatine; theaflavin-rich black tea extracts and bioactive theaflavins; plant essential oils and their compounds (+)-α-bisabolol and eugenol; the grape skin compound resveratrol; the kidney bean lectin, marine extracts from algae, seaweeds, and fungi and compounds that are derived from fungi; medicinal extracts and about 30 isolated pure compounds. Also covered are the inactivation of drug-resistant T. vaginalis and T. foetus strains by sensitized light; anti-trichomonad effects in mice and women; beneficial effects of probiotics in women; and mechanisms that govern cell death. The summarized findings will hopefully stimulate additional research, including molecular-mechanism-guided inactivations and human clinical studies, that will help ameliorate adverse effects of pathogenic protozoa.
Evaluation of the antimicrobial activity and safety of Rhus vulgaris (Anacardiaceae) extracts
Authors: Mutuku Angela , Mwamburi Lizzy , Keter Lucia , Ondicho Joyce , Korir Richard , Kuria James , Chemweno Timothy , Mwitari Peter 
Published: September 2020

AbstractBackgroundMedicinal plants have been used in the treatment of various ailments in most developing countries. Oral infections are the most prevalent diseases in man. The Rhus family has been found to have antimicrobial, antimalarial, and anti-inflammatory properties. Few studies have been done onRhus vulgarisMeikle. A study was conducted to determine the effect ofRhus vulgarisMeikle stem bark extracts against selected oral pathogenic microorganisms and the safety of the extracts in vitro and in vivo.MethodsMethanol:dichloromethane (1:1), methanol and aqueous extracts were tested for bacteriostatic and bactericidal effects against Methicillin ResistantStaphylococcus aureus(MRSA),Staphylococcus aureus, Streptococcus mutansandCandida albicans. Cytotoxicity of the active extracts was determined using Vero E6 cell lines while safety was evaluated in mice and rats. Phytochemical screening was performed on the methanol extracts. One-way ANOVA and Tukey’s multiple comparisons tests were performed using IBM SPSS statistics 20.0 for antimicrobial assay and acute toxicity testing. One-way ANOVA and Dunnett’s multiple comparison tests were conducted using GraphPad Prism 8.0 for cytotoxicity assay.ResultsMethanol extract ofRhus vulgarisshowed significant antimicrobial activity against MRSA (12.00 ± 0.00 mm;p-value of < 0.005; Minimum Inhibitory Concentration of 0.391 mg/ml; Minimum Bactericidal Concentration of 1.563 mg/ml). The extract were not cytotoxic at 100 μg/ml which was the highest tested concentration. In acute dermal irritation testing, the methanol extract resulted in mild irritation with erythema and flaking that cleared within 8 days. There were no observable adverse effects from oral administration of the extracts (acute oral toxicity testing) at concentrations of 50 mg/kg, 300 mg/kg and 2000 mg/kg. Tannins, saponins, flavonoids, terpenoids, glycosides, alkaloids and phenols were detected in the methanol extract.ConclusionsAntimicrobial activity ofR. vulgarisextracts supports its traditional use as a toothbrush. Cytotoxicity demonstrated by the extracts as well as the mild skin irritation warrants further study beforeR. vulgariscan be recommended for the development of effective and safe mouthwashes.
A botanical from the antiproliferative Cameroonian spice, Imperata cylindrica is safe at lower doses, as demonstrated by oral acute and sub-chronic toxicity screenings
Authors: Nayim Paul , Mbaveng Armelle T. , Ntyam Arsene M. , Kuete Victor 
Published: September 2020

Abstract
Background
The cytotoxicity of the root’s methanol extract of Imperata cylindrica (ICR). was previously reported in a panel of human cancer cell lines, including multi-drug resistant phenotypes. The aim of this study was to assess the acute and sub-chronic oral toxicity of methanol root extract of Imperata cylindrica.

Methods
The acute toxicity was carried out according to the experimental protocol of OECD. The plant extract was administered orally to female rats at a single dose of 5000 mg/kg for 14 days and the animals were observed for any behavioral changes or mortality. For sub-chronic toxicity study, ICR was orally administered daily to male and female rats at different doses (250, 500 and 1000 mg/kg per b.w.) for 30 days. During these treatment days the animals were observed for any appearance of toxicity symptoms; following the treatment period, animals were sacrificed for hematological, biochemical and histopathology analysis.

Results
From the results of the acute oral toxicity assay, ICR was found to be non-toxic at the dose of 5000 mg/kg b.w. During the period of sub-chronic toxicity test, observation of signs, behavior and health status of the animals showed no abnormality in the groups of animals treated with ICR as compared to the controls. Significant variation of the relative body weights of heart and kidney were observed at dose a 1000 mg/kg b.w. Significant decrease of aspartate aminotransferase, creatinine level, low density lipoprotein concentration, triglyceride and total cholesterol were observed. In males, we noticed a significant decrease of the level of granulocytes with an increase of lymphocytes and mean corpuscular hemoglobin concentration levels. Histological examinations performed on kidney and liver showed a normal kidney architecture and liver also presented a normal hepatic architecture with slight degeneration at a dose 1000 mg/kg b.w.

Conclusion
ICR is safe for acute oral administration; however, for long-term oral administration, safety measures should be taken. Thus, oral sub-chronic exposure of ICR at lower doses are recommended while higher doses around 1000 mg/kg b.w. should be discouraged.
Navafenterol (AZD8871) in healthy volunteers: safety, tolerability and pharmacokinetics of multiple ascending doses of this novel inhaled, long-acting, dual-pharmacology bronchodilator, in two phase I, randomised, single-blind, placebo-controlled studies
Authors: Balaguer Victor , Albayaty Muna , Jimenez Eulalia , Wählby-Hamrén Ulrika , Astbury Carol , Seoane Beatriz , Malice Marie-Pierre , Lei Alejhandra , Aggarwal Ajay , Psallidas Ioannis 
Published: September 2020

Abstract
Background
Navafenterol (AZD8871) is a novel, long-acting, dual-pharmacology (muscarinic receptor antagonist and β2−adrenoceptor agonist) molecule in development for chronic obstructive pulmonary disease and asthma.

Methods
These two phase I, randomised, single-blind, multiple-ascending-dose studies evaluated inhaled navafenterol and placebo (3:1 ratio) in healthy, male, non-Japanese (study A; NCT02814656) and Japanese (study B; NCT03159442) volunteers. In each study, volunteers were dosed in three cohorts, allowing gradual dose escalation from 300 μg to 600 μg to 900 μg. The primary objective was to investigate the safety and tolerability of navafenterol at steady state. Pharmacokinetics were also assessed.

Results
Twenty-four volunteers completed each study (navafenterol, n = 6; placebo, n = 2 in each cohort). There were no deaths, serious adverse events (AEs) or treatment-emergent AEs (TEAEs) leading to discontinuation of navafenterol. The most frequent TEAEs were vessel puncture-site bruise (placebo, n = 2; navafenterol 900 μg; n = 3) in study A and diarrhoea (placebo, n = 1; navafenterol 300 μg, n = 2; navafenterol 900 μg, n = 3) in study B. No dose-response relationship was observed for TEAEs. There was a dose-dependent increase in mean heart rate on day 16 in both studies. The pharmacokinetics of navafenterol were similar between non-Japanese and Japanese volunteers.

Conclusions
Multiple ascending doses of navafenterol were well-tolerated and the safety and pharmacokinetics of navafenterol were similar in non-Japanese and Japanese volunteers. The findings support navafenterol clinical development.

Trial registration
ClinicalTrials.gov; Nos.: NCT02814656 and NCT03159442; URL: www.clinicaltrials.gov.