bluuebunny/crossref_metadata_2025_split huggingface dataset:
Azithromycin for sarcoidosis cough: an open-label exploratory clinical trial
Authors: Fraser Simon D. , Thackray-Nocera Susannah , Shepherd Marica , Flockton Rachel , Wright Caroline , Sheedy Wayne , Brindle Kayleigh , Morice Alyn H. , Kaye Paul M. , Crooks Michael G. , Hart Simon P. 
Published: October 2020

BackgroundChronic cough is a distressing symptom for many people with pulmonary sarcoidosis. Continuous treatment with a macrolide antibiotic may improve cough. We aimed to assess the potential efficacy of azithromycin in patients with sarcoidosis and self-reported cough.MethodsWe conducted a noncontrolled, open-label clinical trial of azithromycin 250 mg once daily for 3 months in patients with pulmonary sarcoidosis who reported a chronic cough. The primary outcome was number of coughs in 24 h. Secondary outcomes were cough visual analogue scales and quality of life measured using the Leicester Cough Questionnaire and King's Sarcoidosis Questionnaire. Safety outcomes included QTc interval on ECG. Measurements were made at baseline and after 1 and 3 months of treatment.ResultsAll 21 patients were white, median age 57 years, 9 males, 12 females, median 3 years since diagnosis. Four were taking oral corticosteroids and none were taking other immunosuppressants. Twenty patients completed the trial. The median (range) number of coughs in 24 h was 228 (43–1950) at baseline, 122 (20–704) at 1 month, and 81 (16–414) at 3 months (p=0.002, Friedman's test). The median reduction in cough count at 3 months was 49.6%. There were improvements in all patient-reported outcomes. Azithromycin was well tolerated.ConclusionIn a noncontrolled open-label trial in people with sarcoidosis who reported a chronic cough, 3 months of treatment with azithromycin led to improvements in a range of cough metrics. Azithromycin should be tested as a treatment for sarcoidosis cough in a randomised placebo-controlled trial.
Diagnosing COVID-19 pneumonia in a pandemic setting: Lung UltrasoundversusCT (LUVCT) – a multicentre, prospective, observational study
Authors: Lieveld Arthur W.E. , Kok Bram , Schuit Frederik H. , Azijli Kaoutar , Heijmans Jarom , van Laarhoven Arjan , Assman Natascha L. , Kootte Ruud S. , Olgers Tycho J. , Nanayakkara Prabath W.B. , Bosch Frank H. 
Published: October 2020

BackgroundIn this coronavirus disease 2019 (COVID-19) pandemic, fast and accurate testing is needed to profile patients at the emergency department (ED) and efficiently allocate resources. Chest imaging has been considered in COVID-19 workup, but evidence on lung ultrasound (LUS) is sparse. We therefore aimed to assess and compare the diagnostic accuracy of LUS and computed tomography (CT) in suspected COVID-19 patients.MethodsThis multicentre, prospective, observational study included adult patients with suspected COVID-19 referred to internal medicine at the ED. We calculated diagnostic accuracy measures for LUS and CT using both PCR and multidisciplinary team (MDT) diagnosis as reference. We also assessed agreement between LUS and CT, and between sonographers.ResultsOne hundred and eighty-seven patients were recruited between March 19 and May 4, 2020. Area under the receiver operating characteristic (AUROC) was 0.81 (95% CI 0.75–0.88) for LUS and 0.89 (95% CI 0.84–0.94) for CT. Sensitivity and specificity for LUS were 91.9% (95% CI 84.0–96.7) and 71.0% (95% CI 61.1–79.6), respectively,versus88.4% (95% CI 79.7–94.3) and 82.0% (95% CI 73.1–89.0) for CT. Negative likelihood ratio was 0.1 (95% CI 0.06–0.24) for LUS and 0.14 (95% CI 0.08–0.3) for CT. No patient with a false negative LUS required supplemental oxygen or admission. LUS specificity increased to 80% (95% CI 69.9–87.9) compared to MDT diagnosis, with an AUROC of 0.85 (95% CI 0.79–0.91). Agreement between LUS and CT was 0.65. Interobserver agreement for LUS was good: 0.89 (95% CI 0.83–0.93).ConclusionLUS and CT have comparable diagnostic accuracy for COVID-19 pneumonia. LUS can safely exclude clinically relevant COVID-19 pneumonia and may aid COVID-19 diagnosis in high prevalence situations.
A foundation for reference models for drug combinations with an application to Loewe’s reference model
Authors: De Mulder Wim , Kuiper Martin 
Published: October 2020

Abstract
Background
Treating patients with combinations of drugs that have synergistic effects has become widespread practice in the clinic. Drugs work synergistically when the observed effect of a drug combination is larger than the effect predicted by the reference model. The reference model is a theoretical null model that returns the combined effect of given doses of drugs under the assumption that these drugs do not interact. There is ongoing debate on what it means for drugs to not interact. The controversy transcends mathematical punctuality, as different non-interaction principles result in different reference models. A famous reference model that has been in existence for already a long time is Loewe’s reference model. Loewe’s vision on non-interaction was purely intuitive: two drugs do not interact if all combinations of doses that result in a certain given effect lie on a straight line.

Results
We show that Loewe’s reference model can be obtained from much more fundamental principles. First, we introduce the new notion of complementary dose. Secondly, we reformulate the existing concept of equivalent dose, whereby our formulation is more general than existing ones. Finally, a very general non-interaction principle is put forward. The proposed non-interaction principle represents a certain interplay between complementary and equivalent doses: drugs are non-interacting if complementarity is preserved under equivalence. It is then shown that Loewe’s reference model naturally follows from these principles by an appropriate choice of complementarity.

Conclusions
The presented work increases insight into Loewe’s reference model for drug combinations, which is realized by the introduction of a very general non-interaction principle that does not refer to any specific dose-response curve, nor to any property of applicable dose-response curves.
Identification of fruit size associated quantitative trait loci featuring SLAF based high-density linkage map of goji berry (Lycium spp.)
Authors: Rehman Fazal , Gong Haiguang , Li Zhong , Zeng Shaohua , Yang Tianshun , Ai Peiyan , Pan Lizhu , Huang Hongwen , Wang Ying 
Published: October 2020

Abstract
Background
Goji (Lycium spp., 2n = 24) is a fruit bearing woody plant popular as a superfood for extensive medicinal and nutritional advantages. Fruit size associated attributes are important for evaluating small-fruited goji berry and plant architecture. The domestication traits are regulated quantitatively in crop plants but few studies have attempted on genomic regions corresponding to fruit traits.

Results
In this study, we established high-resolution map using specific locus amplified fragment (SLAF) sequencing for de novo SNPs detection based on 305 F1 individuals derived from L. chinense and L. barbarum and performed quantitative trait loci (QTL) analysis of fruit size related traits in goji berry. The genetic map contained 3495 SLAF markers on 12 LGs, spanning 1649.03 cM with 0.47 cM average interval. Female and male parents and F1 individuals` sequencing depth was 111.85-fold and 168.72-fold and 35.80-fold, respectively. The phenotype data were collected for 2 successive years (2018–2019); however, two-year mean data were combined in an extra year (1819). Total 117 QTLs were detected corresponding to multiple traits, of which 78 QTLs in 2 individual years and 36 QTLs in extra year. Six Promising QTLs (qFW10–6.1, qFL10–2.1, qLL10–2.1, qLD10–2.1, qLD12–4.1, qLA10–2.1) were discovered influencing fruit weight, fruit length and leaf related attributes covering an interval ranged from 27.32–71.59 cM on LG10 with peak LOD of 10.48 and 14.6% PVE. Three QTLs targeting fruit sweetness (qFS3–1, qFS5–2) and fruit firmness (qFF10–1) were also identified. Strikingly, various traits QTLs were overlapped on LG10, in particular, qFL10–2.1 was co-located with qLL10–2.1, qLD10–2.1 and qLA10–2.1 among stable QTLs, harbored tightly linked markers, while qLL10–1 was one major QTL with 14.21 highest LOD and 19.3% variance. As LG10 harbored important traits QTLs, we might speculate that it could be hotspot region regulating fruit size and plant architectures.

Conclusions
This report highlights the extremely saturated linkage map using SLAF-seq and novel loci contributing fruit size-related attributes in goji berry. Our results will shed light on domestication traits and further strengthen molecular and genetic underpinnings of goji berry; moreover, these findings would better facilitate to assemble the reference genome, determining potential candidate genes and marker-assisted breeding.
The association of genetic polymorphisms with nonalcoholic fatty liver disease in a longitudinal study
Authors: Chung Goh Eun , Shin Eunsoon , Kwak Min-Sun , In Yang Jong , Lee Jong-Eun , Choe Eun Kyung , Yim Jeong Yoon 
Published: October 2020

Abstract
Background
Several genetic variants are known to be associated with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the longitudinal associations between genetic variants and NAFLD.

Methods
We performed a genome-wide association study (GWAS) in Korean individuals who underwent repeated health check-ups. NAFLD was defined by ultrasonography and exclusion of secondary causes.

Results
The subjects had a median age of 50.0 years, and 54.8% were male. The median follow-up duration was 39 months. Among the 3905 subjects without NAFLD at baseline, 874 (22.4%) subjects developed NAFLD, and among the 1818 subjects with NAFLD at baseline, NAFLD regressed in 336 (18.5%) subjects during the follow-up period. After adjusting for age, sex and body mass index, no single-nucleotide polymorphism (SNP) passed Bonferroni correction for genome-wide significance in the development or regression of NAFLD. Among the SNPs that passed the genome-wide suggestiveness threshold (p = 1E-04) in the discovery set in the GWAS, only 1 SNP (rs4906353) showed an association with the development of NAFLD, with marginal significance in the validation set (p-value, discovery set = 9.68E-5 and validation set = 0.00531).

Conclusions
This exploratory study suggests that longitudinal changes in NAFLD are not associated with genetic variants in the Korean population. These findings provide new insight into genetic mechanisms in the pathogenesis of NAFLD.
Interpretation of serial interferon-gamma test results to measure new tuberculosis infection among household contacts in Zambia and South Africa
Authors: Sloot Rosa , Shanaube Kwame , Claassens Mareli , Telisinghe Lily , Schaap Ab , Godfrey-Faussett Peter , Ayles Helen , Floyd Sian 
Published: October 2020

AbstractBackgroundA more stringent QuantiFERON-TB Gold In-Tube (QFT) conversion (from negative to positive) definition has been proposed to allow more definite detection of recent tuberculosis (TB) infection. We explored alternative conversion definitions to assist the interpretation of serial QFT results and estimate incidence of TB infection in a large cohort study.MethodsWe used QFT serial results from TB household contacts aged ≥15 years, collected at baseline and during two follow-up visits (2006–2011) as part of a cohort study in 24 communities in Zambia and South Africa (SA). Conversion rates using the manufacturers’ definition (interferon-gamma (IFN-g) < 0.35 to ≥0.35, ‘def1’) were compared with stricter definitions (IFN-g < 0.2 to ≥0.7 IU/ml, ‘def2’; IFN-g < 0.2 to ≥1.05 IU/ml, ‘def3’; IFN-g < 0.2 to ≥1.4 IU/ml, ‘def4’). Poisson regression was used for analysis.ResultsOne thousand three hundred sixty-five individuals in Zambia and 822 in SA had QFT results available. Among HIV-negative individuals, the QFT conversion rate was 27.4 per 100 person-years (CI:22.9–32.6) using def1, 19.0 using def2 (CI:15.2–23.7), 14.7 using def3 (CI:11.5–18.8), and 12.0 using def4 (CI:9.2–15.7). Relative differences across def1-def4 were similar in Zambia and SA. Using def1, conversion was less likely if HIV positive not on antiretroviral treatment compared to HIV negative (aRR = 0.7, 95%CI = 0.4–0.9), in analysis including both countries. The same direction of associations were found using def 2–4.ConclusionHigh conversion rates were found even with the strictest definition, indicating high incidence of TB infection among household contacts of TB patients in these communities. The trade-off between sensitivity and specificity using different thresholds of QFT conversion remains unknown due to the absence of a reference standard. However, we identified boundaries within which an appropriate definition might fall, and our strictest definition plausibly has high specificity.
Dimensions of women’s empowerment on access to skilled delivery services in Nepal
Authors: Khatiwada Januka , Muzembo Basilua Andre , Wada Koji , Ikeda Shunya 
Published: October 2020

AbstractBackgroundEach day, approximately 810 women die during pregnancy and childbirth and 94% of the deaths take place in low and middle income countries. Only 45% of the births in South Asia are attended by skilled professionals, which is lower than that in other Asian regions. Antenatal and postnatal care received from skilled providers can help prevent maternal and neonatal mortality by identifying pregnancy-related complications. Women’s empowerment is considered to be a significant determinant of maternal health care outcomes; however, studies on the contextual influences of different dimensions of empowerment in Nepal are relatively limited. Therefore, this study analyzed nationwide survey data to examine the influence of women’s economic empowerment, sociocultural empowerment, familial/interpersonal empowerment and media and information technology empowerment on accessing skilled delivery services among the married women in Nepal.MethodsThis study examined the influence of women’s empowerment on skilled delivery services among married women (n = 4400) aged 15–49 years using data from the 2016 Nepal Demographic and Health Survey. Descriptive analysis and binary logistic regression analysis were employed to analyze the data.ResultsSignificant associations were found between women’s media and information technology empowerment, economic empowerment and sociocultural empowerment and access to skilled birth attendants. Specifically, the education of women, their occupation, owning a bank account, media exposure, and internet use were significantly associated with the use of skilled birth attendants.ConclusionFocusing on women’s access to media and information technology, economic enhancement and education may increase the use of skilled birth attendants in Nepal.
CircRNAs as potential biomarkers for the clinicopathology and prognosis of glioma patients: a meta-analysis
Authors: Ding Xiangqian , Yang Luyao , Geng Xin , Zou Yanghong , Wang Zhigang , Li Yao , Qi Renli , Wang Wei , Li Jinghui , Yu Hualin 
Published: October 2020

Abstract
Background
An increasing number of studies have reported circular RNAs (circRNAs) as new potential biomarkers for the prognosis of gliomas. However, the overall prognostic value of circRNAs for glioma remains unclear. Therefore, this study is the first comprehensive evaluation of the clinicopathological and prognostic value of dysregulated circRNAs in the treatment of glioma patients.

Methods
We systematically reviewed the online databases of PubMed, Web of Science, EMBASE, and Cochrane Library to identify studies that explored the relationship between circRNA expression and clinicopathological and prognostic factors in glioma through April 11, 2020. The quality of the included studies was evaluated by the Newcastle-Ottawa Scale (NOS) checklists. Clinicopathological features were assessed by pooled odds ratios (ORs) and 95% confidence intervals (CIs), and overall survival (OS) was assessed by hazard ratios (HRs) and 95% CIs.

Results
Twenty-four eligible studies, including 22 studies of clinicopathological features, 1 diagnostic study, and 18 studies of prognosis, that included a total of 1390 patients were ultimately included in this study. Meta-analysis showed that highly expressed oncogenic circRNAs were significantly related to poor clinicopathological features (age: P = 0.026; tumor size: P ≤ 0.001; tumor grade: P ≤ 0.001; KPS: P = 0.012) and worse overall survival (OS) (HR = 2.01, 95% CI: 1.61–2.50, P ≤ 0.001). Moreover, we found that highly expressed tumor-suppressor circRNAs were related to better clinicopathological features (gender: P = 0.042; age: P = 0.014; tumor size: P = 0.022; tumor grade: P ≤ 0.001) and longer OS (HR = 2.70, 95% CI: 1.82–3.99, P ≤ 0.001).

Conclusions
In conclusion, there is a significant correlation between the dysregulated expression of circRNAs and the clinicopathology and prognosis of glioma patients.
Internet non-use among Canadian Indigenous older adults: Aboriginal Peoples Survey (APS)
Authors: Ali-Hassan Hossam , Eloulabi Rama , Keethakumar Asvini 
Published: October 2020

Abstract
Background
Older adults benefit considerably from Internet use, as it can improve their overall health and quality of life, for example through accessing healthcare services and reducing social isolation. The aim of this study is to assess the prevalence and characteristics of Indigenous older adults in Canada who do not use the Internet.

Methods
The Aboriginal Peoples Survey (APS) 2017 was used and analysis was restricted to those above 65 years of age. The main outcome variable was non-use of the internet in a typical month. Multivariable logistic regression was conducted to assess the relationship between each of the sociodemographic, socioeconomic, lifestyle and health factors and internet non-use.

Results
The prevalence of Indigenous older adults who reported never using the Internet in a typical month was 33.6% with the highest prevalence reported by residents of the Canadian territories while the lowest prevalence was reported in British Columbia. After adjustment, results indicated that older age (OR = 4.02, 95% CI 3.54–4.57 comparing 80+ to 65–69 years of age), being a male (OR = 1.52, 95% CI 1.41–1.63), married (OR = 1.34, 95% CI 1.25–1.44), and living in rural areas (OR = 1.95, 95% CI 1.79–2.13) increased the odds of not using the Internet. First Nation individuals and those who have a strong sense of belonging to the Indigenous identity were more likely to not use the Internet compared to their counterparts. In addition, those who were less educated (OR = 8.74, 95% CI 7.03–1 0.87 comparing less than secondary education to Bachelor’s Degree and above), unemployed (OR = 1.41, 95% CI 1.26–1.57), smoked cigarettes, used marijuana and those with lower self-perceived mental health and unmet health needs were at increased odds of Internet non-use compared to their counterparts.

Conclusions
Findings from this study show that a large proportion of the Indigenous older adults in Canada do not use the internet. It is necessary to address Indigenous communities’ lack of internet access and to create interventions that are consistent with Indigenous values, traditions, and goals.
Operative invasiveness does not affect the prognosis of patients with non-small cell lung cancer
Authors: Motono Nozomu , Iwai Shun , Iijima Yoshihito , Usuda Katsuo , Uramoto Hidetaka 
Published: October 2020

Abstract
Background
The relationship between operative invasiveness and the prognosis in non-small cell lung cancer (NSCLC) patients who have undergone surgery has been controversial.

Methods
Clinical data were analyzed for 463 NSCLC patients. Operative invasiveness was defined by wound length, operation time, and the postoperative C-reactive protein (postCRP) level. The operative approach was divided into video-assisted thoracic surgery (VATS) and thoracotomy.

Results
The wound length and operation time were significantly correlated with the postCRP level (correlation coefficient (CC) = 0.39, p <  0.01; CC = 0.54, p <  0.01, respectively). The postCRP level in the VATS group was significantly lower than that in the thoracotomy group (12.2 mg/dl vs 20.58 mg/dl, p <  0.01). The relapse-free survival differed significantly based on wound length (p <  0.01), operation time (p = 0.01), CRP level (p <  0.01), and operative approach (p <  0.01). The carcinoembryonic antigen level (hazard ratio [HR], 1.58; p = 0.02), pathological stage (pStage) (HR, 2.57; p <  0.01), vascular invasion (HR, 1.95; p = 0.01), and preoperative CRP level (preCRP) (HR, 1.91; p <  0.01) were identified as significant prognostic factors for relapse-free survival in a multivariate analysis. Furthermore, the multivariate analysis showed that smoking history (HR, 2.36; p = 0.03), pStage (HR, 3.26; p <  0.01), and preCRP level were significant prognostic factors for overall survival.

Conclusion
Preoperative CRP level was associated with poor prognosis. Although the VATS approach might be less invasive procedure for NSCLC patients, operative invasiveness does not affect the prognosis.
Optimal specimen type for accurate diagnosis of infectious peripheral pulmonary lesions by mNGS
Authors: Wang Qing , Wu Bo , Yang Donglin , Yang Chao , Jin Zhixian , Cao Jie , Feng Jing 
Published: October 2020

Abstract
Background
Reports on the application of metagenomic next-generation sequencing (mNGS) to the diagnosis of peripheral pulmonary lesions (PPLs) are scarce. There have been no studies investigating the optimal specimen type for mNGS.

Methods
We used mNGS to detect pathogens in matched transbronchial lung biopsy (TBLB), bronchoalveolar lavage fluid (BALF), and bronchial needle brushing (BB) specimens from 39 patients suspected of having infectious PPLs. We explored differences in microbial composition and diagnostic accuracy of mNGS for the 3 specimen types.

Results
mNGS was more sensitive than conventional culture for detection of bacteria and fungi in TBLB, BALF, and BB specimens, with no difference in the sensitivity of mNGS across the different specimen types. mNGS showed higher sensitivity for fungi or uncategorized pulmonary pathogens in TBLB+BALF+BB compared to TBLB but not BALF or BB specimens. There were no significant differences between the 3 specimen types in the relative abundance of pathogens, or between TBLB and BB specimens in the relative abundance of 6 common lower respiratory tract commensals.

Conclusions
mNGS has a higher sensitivity than the conventional culture method for detecting pathogens in TBLB, BALF, or BB specimens. mNGS of BB samples is a less invasive alternative to TBLB for the diagnosis of infectious PPLs.