bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of asthma phenotypes based on extrapulmonary treatable traits
Authors: Freitas Patricia Duarte , Xavier Rafaella França , McDonald Vanessa Marie , Gibson Peter Gerard , Cordova-Rivera Laura , Furlanetto Karina Couto , de Oliveira Joice Mara , Carvalho-Pinto Regina Maria , Cukier Alberto , Stelmach Rafael , Carvalho Celso Ricardo Fernandes 
Published: July 2020

Asthma is a heterogeneous and complex disease, and a description of asthma phenotypes based on extrapulmonary treatable traits has not been previously reported.The objective of this study was to identify and characterise clusters based on clinical, functional, anthropometrical and psychological characteristics in participants with moderate-to-severe asthma.This was a cross-sectional multicentre study involving centres from Brazil and Australia. Participants (n=296) with moderate-to-severe asthma were consecutively recruited. Physical activity and sedentary time, clinical asthma control, anthropometric data, pulmonary function and psychological and health status were evaluated. Participants were classified by hierarchical cluster analysis and the clusters compared using ANOVA, Kruskal­–Wallis and Chi-squared tests. Multiple logistic and linear regression models were performed to evaluate the association between variables.We identified four clusters: 1) participants with controlled asthma who were physically active; 2) participants with uncontrolled asthma who were physically inactive and more sedentary; 3) participants with uncontrolled asthma and low physical activity, who were also obese and experienced anxiety and/or depression symptoms; and 4) participants with very uncontrolled asthma who were physically inactive, more sedentary, obese and experienced anxiety and/or depression symptoms. Higher levels of sedentary time, female sex and anxiety symptoms were associated with increased odds of exacerbation risk, while being more active showed a protective factor for hospitalisation. Asthma control was associated with sex, the occurrence of exacerbation, physical activity and health status.Physical inactivity, obesity and symptoms of anxiety and/or depression were associated with worse asthma outcomes, and closely and inextricably associated with asthma control. This cluster analysis highlights the importance of assessing extrapulmonary traits to improve personalised management and outcomes for people with moderate and severe asthma.
Exhaled breath analysis by use of eNose technology: a novel diagnostic tool for interstitial lung disease
Authors: Moor Catharina C. , Oppenheimer Judith C. , Nakshbandi Gizal , Aerts Joachim G.J.V. , Brinkman Paul , Maitland-van der Zee Anke-Hilse , Wijsenbeek Marlies S. 
Published: July 2020

IntroductionEarly and accurate diagnosis of interstitial lung diseases (ILDs) remains a major challenge. Better noninvasive diagnostic tools are much needed. We aimed to assess the accuracy of exhaled breath analysis using eNose technology to discriminate between ILD patients and healthy controls, and to distinguish ILD subgroups.MethodsIn this cross-sectional study, exhaled breath of consecutive ILD patients and healthy controls was analysed using eNose technology (SpiroNose). Statistical analyses were done using partial least square discriminant analysis and receiver operating characteristic analysis. Independent training and validation sets (2:1) were used in larger subgroups.ResultsA total of 322 ILD patients and 48 healthy controls were included: sarcoidosis (n=141), idiopathic pulmonary fibrosis (IPF) (n=85), connective tissue disease-associated ILD (n=33), chronic hypersensitivity pneumonitis (n=25), idiopathic nonspecific interstitial pneumonia (n=10), interstitial pneumonia with autoimmune features (n=11) and other ILDs (n=17). eNose sensors discriminated between ILD and healthy controls, with an area under the curve (AUC) of 1.00 in the training and validation sets. Comparison of patients with IPF and patients with other ILDs yielded an AUC of 0.91 (95% CI 0.85–0.96) in the training set and an AUC of 0.87 (95% CI 0.77–0.96) in the validation set. The eNose reliably distinguished between individual diseases, with AUC values ranging from 0.85 to 0.99.ConclusionseNose technology can completely distinguish ILD patients from healthy controls and can accurately discriminate between different ILD subgroups. Hence, exhaled breath analysis using eNose technology could be a novel biomarker in ILD, enabling timely diagnosis in the future.
Fine mapping of the BnUC2 locus related to leaf up-curling and plant semi-dwarfing in Brassica napus
Authors: Huang Chengwei , Yang Mao , Shao Danlei , Wang Yangming , Wan Shubei , He Jianbo , Meng Zuqing , Guan Rongzhan 
Published: July 2020

Abstract
Background
Studies of leaf shape development and plant stature have made important contributions to the fields of plant breeding and developmental biology. The optimization of leaf morphology and plant height to improve lodging resistance and photosynthetic efficiency, increase planting density and yield, and facilitate mechanized harvesting is a desirable goal in Brassica napus.

Results
Here, we investigated a B. napus germplasm resource exhibiting up-curled leaves and a semi-dwarf stature. In progeny populations derived from NJAU5737 and Zhongshuang 11 (ZS11), we found that the up-curled leaf trait was controlled by a dominant locus, BnUC2. We then fine mapped the BnUC2 locus onto an 83.19-kb interval on chromosome A05 using single nucleotide polymorphism (SNP) and simple sequence repeat (SSR) markers. We further determined that BnUC2 was a major plant height QTL that explained approximately 70% of the phenotypic variation in two BC5F3 family populations derived from NJAU5737 and ZS11. This result implies that BnUC2 was also responsible for the observed semi-dwarf stature. The fine mapping interval of BnUC2 contained five genes, two of which, BnaA05g16700D (BnaA05.IAA2) and BnaA05g16720D, were revealed by comparative sequencing to be mutated in NJAU5737. This result suggests that the candidate gene mutation (BnaA05g16700D, encoding Aux/IAA2 proteins) in the conserved Degron motif GWPPV (P63S) was responsible for the BnUC2 locus. In addition, investigation of agronomic traits in a segregated population indicated that plant height, main inflorescence length, and branching height were significantly reduced by BnUC2, whereas yield was not significantly altered. The determination of the photosynthetic efficiency showed that the BnUC2 locus was beneficial to improve the photosynthetic efficiency. Our findings may provide an effective foundation for plant type breeding in B. napus.

Conclusions
Using SNP and SSR markers, a dominant locus (BnUC2) related to up-curled leaves and semi-dwarf stature in B. napus has been fine mapped onto an 83.19-kb interval of chromosome A05 containing five genes. The BnaA05.IAA2 is inferred to be the candidate gene responsible for the BnUC2 locus.
Molecular characterization of B. anthracis isolates from the anthrax outbreak among cattle in Karnataka, India
Authors: Roonie Akanxa , Majumder Saugata , Kingston Joseph J. , Parida Manmohan 
Published: July 2020

AbstractBackgroundAnthrax, a zoonotic disease is caused by the Gram positive bacteriumBacillus anthracis. During January 2013, an anthrax outbreak among cattle was reported in Gundlupet Taluk, neighboring Bandipur National Park and tiger reserve, India. The present study aims at the molecular identification and characterization of 12B. anthracisisolates from this outbreak by 16S rRNA gene sequencing, screeningB. anthracisspecific prophages and chromosomal markers, protective antigen (pag) gene and canonical single nucleotide polymorphism (canSNP) analysis to subtype the isolates into one of the twelve globally identified clonal sub-lineages ofB. anthracis.ResultsThese isolates had identical 16S rDNA nucleotide sequences withB. anthracisspecific dual peaks showing mixed base pair R (G/A) at position 1139 with visual inspection while the automated basecaller software indicated a G. Alternatively the nucleotide A at 1146 position was indicative of the 16S rDNA type 7. Multiple sequence alignment with additional 170 (16S rDNA) sequences ofB. cereussensulatogroup from GenBank database revealed 28 new 16S types in addition to eleven 16S types reported earlier. The twelveB. anthracisisolates were found to harbor the fourB. anthracisspecific prophages (lambdaBa01, lambdaBa02, lambdaBa03, and lambdaBa04) along with its four specific loci markers (dhp 61.183, dhp 77.002, dhp 73.019, and dhp 73.017). Thepaggene sequencing identified the isolates as protective antigen (PA) genotype I with phenylalanine-proline-alanine phenotype (FPA phenotype). However, sequence clustering with additional 34pagsequences from GenBank revealed two additional missense mutations at nucleotide positions 196 bp and 869 bp of the 2294 bppagsequence among the 5B. cereusstrains with pXO1 like plasmids. The canSNP analysis showed that the isolates belong to A.Br.Aust94 sub-lineage that is distributed geographically in countries of Asia, Africa, Europe and Australia.ConclusionsThe analysis of 16S rDNA sequences reiterated the earlier findings that visual inspection of electropherogram for position 1139 having nucleotide R could be used forB. anthracisidentification and not the consensus sequence from base caller. The canSNP results indicated that the anthrax outbreak among cattle was caused byB. anthracisof A.Br.Aust94 sub-lineage.
Doubly robust estimator of risk in the presence of censoring dependent on time-varying covariates: application to a primary prevention trial for coronary events with pravastatin
Authors: Kawahara Takuya , Shinozaki Tomohiro , Matsuyama Yutaka 
Published: July 2020

Abstract
Background
In the presence of dependent censoring even after stratification of baseline covariates, the Kaplan–Meier estimator provides an inconsistent estimate of risk. To account for dependent censoring, time-varying covariates can be used along with two statistical methods: the inverse probability of censoring weighted (IPCW) Kaplan–Meier estimator and the parametric g-formula estimator. The consistency of the IPCW Kaplan–Meier estimator depends on the correctness of the model specification of censoring hazard, whereas that of the parametric g-formula estimator depends on the correctness of the models for event hazard and time-varying covariates.

Methods
We combined the IPCW Kaplan–Meier estimator and the parametric g-formula estimator into a doubly robust estimator that can adjust for dependent censoring. The estimator is theoretically more robust to model misspecification than the IPCW Kaplan–Meier estimator and the parametric g-formula estimator. We conducted simulation studies with a time-varying covariate that affected both time-to-event and censoring under correct and incorrect models for censoring, event, and time-varying covariates. We applied our proposed estimator to a large clinical trial data with censoring before the end of follow-up.

Results
Simulation studies demonstrated that our proposed estimator is doubly robust, namely it is consistent if either the model for the IPCW Kaplan–Meier estimator or the models for the parametric g-formula estimator, but not necessarily both, is correctly specified. Simulation studies and data application demonstrated that our estimator can be more efficient than the IPCW Kaplan–Meier estimator.

Conclusions
The proposed estimator is useful for estimation of risk if censoring is affected by time-varying risk factors.
What role does the GP play for emergency department utilizers? A qualitative exploration of respiratory patients’ perspectives in Berlin, Germany
Authors: Oslislo Sarah , Heintze Christoph , Möckel Martin , Schenk Liane , Holzinger Felix 
Published: July 2020

AbstractBackgroundWhile motives for emergency department (ED) self-referrals have been investigated in a number of studies, the relevance of general practitioner (GP) care for these patients has not been comprehensively evaluated. Respiratory symptoms constitute an important utilization trigger in both EDs and in primary care. In this qualitative study, we aimed to explore the role of GP care for patients visiting EDs as outpatients for respiratory complaints and the relevance of the relationship between patient and GP in the decision making process leading up to an ED visit.MethodsQualitative descriptive study. Semi-structured, face-to-face interviews with a sample of 17 respiratory ED patients in Berlin, Germany. Interviews were recorded and transcribed verbatim. Qualitative content analysis was performed. The study was embedded into the EMACROSS (Emergency and Acute Care for Respiratory Diseases beyond Sectoral Separation) cohort of ED patients with respiratory symptoms, which is part of EMANet (Emergency and Acute Medicine Network for Health Care Research).ResultsThree patterns of GP utilization could be differentiated: long-term regular consulters, sporadic consulters and patients without GP. In sporadic consulters and patients without GP, an ambivalent or even aversive view of GP care was prevalent, with lack of confidence in GPs’ competence and a deficit in trust as seemingly relevant influencing factors. Regardless of utilization or relationship type, patients frequently made contact with a GP before visiting an ED.ConclusionsWith regard to respiratory symptoms, our qualitative data suggest a hypothesis of limited relevance of patients’ primary care utilization pattern and GP-patient relationship for ED consultation decisions.
Covered metallic stent for the treatment of malignant esophageal fistula combined with stricture
Authors: Bi Yonghua , Yi Mengfei , Yu Zepeng , Han Xinwei , Ren Jianzhuang 
Published: July 2020

Abstract
Background
Esophageal fistula and stricture is rare but life-threatening complication for esophageal cancer. The management of esophageal fistula and stricture remains challenging. We aimed to determine the safety, feasibility and efficacy of covered metallic stent and three tubes placement for the management of esophageal fistula and stricture.

Methods
Between May 2012 and March 2018, all patients with esophageal fistula and stricture were treated using three tubes or covered metallic stent placement. Patients in group A received covered stents and three tubes placement. Patients in group B only received three tubes placement. Continue abscess drainage and nutritional support was performed after procedure. Three tubes or esophageal stents were removed once esophageal fistula heals. The related medical records were retrospectively assessed.

Results
Thirty-seven consecutive patients with esophageal fistula and stricture were enrolled, including 26 patients in group A and 11 patients in group B. Stent placement procedure was technically successful in 25 patients (96.2%). A total of 42 covered stents were inserted. Seventeen esophageal stents were successfully removed from 10 patients. The median retention duration was 3.3 months and 3.4 months for stent and abscess drainage tubes, respectively. One perioperative death due to massive hemorrhage was observed 21 days after stent placement. The abscess cavity was decreased or disappeared in 17 cases and 4 cases in group A and group B, respectively. During follow up, patients in group A still showed a significant better condition of normal diet than that in group B (p < 0.05). Fourteen patients died of cancer recurrence, 3 patients died of massive digestive bleeding and 2 patients died of severe pulmonary infection. The median survivals were 14.8 months and 13.2 months for group A and group B, respectively.

Conclusions
Covered metallic stent placement is safe, feasible and efficacious for treatment of esophageal fistula and stricture, with a better condition of normal diet than patients only received three tubes placement.
Predictive value of TNF-α, IFN-γ, and IL-10 for tuberculosis among recently exposed contacts in the United States and Canada
Authors: Reichler Mary R. , Hirsch Christina , Yuan Yan , Khan Awal , Dorman Susan E. , Schluger Neil , Sterling Timothy R. ,   the Tuberculosis Epidemiologic Studies Consortium Task Order 2 Team, Bakhtawar I. , LeDoux C. , McAuley J. , Beison J. , Fitzgerald M. , Naus M. , Nakajima M. , Schluger N. , Hirsch-Moverman Y. , Moran J. , Blumberg H. , Tapia J. , Singha L. , Hershfeld E. , Roche B. , Mangura B. , Sevilla A. , Sterling T. , Chavez-Lindell T. , Maruri F. , Dorman S. , Cronin W. , Munk E. , Khan A. , Yuan Y. , Chen B. , Yan F. , Shen Y. , Zhao H. , Zhang H. , Bessler P. , Fagley M. , Reichler M. , Sterling T. , Tapia J. , Hirsch C. , Luo C. 
Published: July 2020

Abstract
Background
We examined cytokine immune response profiles among contacts to tuberculosis patients to identify immunologic and epidemiologic correlates of tuberculosis.

Methods
We prospectively enrolled 1272 contacts of culture-confirmed pulmonary tuberculosis patients at 9 United States and Canadian sites. Epidemiologic characteristics were recorded. Blood was collected and stimulated with Mycobacterium tuberculosis culture filtrate protein, and tumor necrosis factor (TNF-α), interferon gamma (IFN-γ), and interleukin 10 (IL-10) concentrations were determined using immunoassays.

Results
Of 1272 contacts, 41 (3.2%) were diagnosed with tuberculosis before or < 30 days after blood collection (co-prevalent tuberculosis) and 19 (1.5%) during subsequent four-year follow-up (incident tuberculosis). Compared with contacts without tuberculosis, those with co-prevalent tuberculosis had higher median baseline TNF-α and IFN-γ concentrations (in pg/mL, TNF-α 129 versus 71, P < .01; IFN-γ 231 versus 27, P < .001), and those who subsequently developed incident tuberculosis had higher median baseline TNF-α concentrations (in pg/mL, 257 vs. 71, P < .05). In multivariate analysis, contact age < 15 years, US/Canadian birth, and IFN or TNF concentrations > the median were associated with co-prevalent tuberculosis (P < .01 for each); female sex (P = .03) and smoking (P < .01) were associated with incident tuberculosis. In algorithms combining young age, positive skin test results, and elevated CFPS TNF-α, IFN-γ, and IL-10 responses, the positive predictive values for co-prevalent and incident tuberculosis were 40 and 25%, respectively.

Conclusions
Cytokine concentrations and epidemiologic factors at the time of contact investigation may predict co-prevalent and incident tuberculosis.
Efficacy and safety of cinacalcet compared with other treatments for secondary hyperparathyroidism in patients with chronic kidney disease or end-stage renal disease: a meta-analysis
Authors: Sun Yiting , Tian Binyao , Sheng Zitong , Wan Pengzhi , Xu Tianhua , Yao Li 
Published: July 2020

Abstract
Background
It is controversial for the effect and safety between cinacalcet and other treatments in treating secondary hyperparathyroidism for patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD).

Methods
Embase, PubMed, and Cochrane Library were searched through Feb 2017. 21 randomized controlled trials were included. We calculated the pooled mean difference (MD), relative risk (RR) and corresponding 95% confidence interval (CI).

Result
Patients received calcimimetic agents had significantly decreased serum parathyroid hormone (MD = − 259.24 pg/mL, 95% CI: − 336.23 to − 182.25), calcium (MD = − 0.92 mg/dL, 95% CI: − 0.98 to − 0.85) and calcium phosphorus product (MD = − 5.97 mg2/dL2, 95% CI: − 9.77 to − 2.16) concentration compared with control treatment. However, the differences in cardiovascular mortality and all-cause mortality between calcimimetics agents and control group were not statistically significant. The incidence of nausea (RR = 2.13, 95% CI: 1.62 to 2.79), vomiting (RR = 1.99, 95% CI: 1.78 to 2.23) and hypocalcemia (RR = 10.10, 95% CI: 7.60 to 13.43) in CKD patients with calcimimetics agents was significantly higher than that with control treatment.

Conclusion
Cinacalcet improved the biochemical parameters in CKD patients, but did not improve all-cause mortality and cardiovascular mortality. Moreover, cinacalcet can cause some adverse events.
Evaluating different adoption scenarios for TIL-therapy and the influence on its (early) cost-effectiveness
Authors: Lindenberg Melanie , Retèl Valesca , Rohaan Maartje , van den Berg Joost , Haanen John , van Harten Wim 
Published: July 2020

Abstract
Background
Treatment with tumor-Infiltrating Lymphocytes (TIL) is an innovative therapy for advanced melanoma with promising clinical phase I/II study results and likely beneficial cost-effectiveness. As a randomized controlled trial on the effectiveness of TIL therapy in advanced melanoma compared to ipilimumab is still ongoing, adoption of TIL therapy by the field is confronted with uncertainty. To deal with this, scenario drafting can be used to identify potential barriers and enables the subsequent anticipation on these barriers. This study aims to inform adoption decisions of TIL by evaluating various scenarios and evaluate their effect on the cost-effectiveness.

Methods
First, 14 adoption scenarios for TIL-therapy were drafted using a Delphi approach with a group of involved experts. Second, the likelihood of the scenarios taking place within 5 years was surveyed among international experts using a web-based questionnaire. Third, based on the questionnaire results and recent literature, scenarios were labeled as being either “likely” or “-unlikely”. Finally, the cost-effectiveness of TIL treatment involving the “likely” scored scenarios was calculated.

Results
Twenty-nine experts from 12 countries completed the questionnaire. The scenarios showed an average likelihood ranging from 29 to 58%, indicating that future developments of TIL-therapy were surrounded with quite some uncertainty. Eight of the 14 scenarios were labeled as “likely”. The net monetary benefit per patient is presented as a measure of cost-effectiveness, where a positive value means that a scenario is cost-effective. For six of these scenarios the cost-effectiveness was calculated: “Commercialization of TIL production” (the price was assumed to be 3 times the manufacturing costs in the academic setting) (−€51,550), “Pharmaceutical companies lowering the prices of ipilimumab” (€11,420), “Using TIL-therapy combined with ipilimumab” (−€10,840), “Automatic TIL production” (€22,670), “TIL more effective” (€23,270), “Less Interleukin-2” (€20,370).

Conclusions
Incorporating possible future developments, TIL-therapy was calculated to be cost-effective compared to ipilimumab in the majority of “likely” scenarios. These scenarios could function as facilitators for adoption. Contrary, TIL therapy was expected to not be cost-effective when sold at commercial prices, or when combined with ipilimumab. These scenarios should be considered in the adoption decision as these may act as crucial barriers.