bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of indacaterol/glycopyrronium on ventilation and perfusion in COPD: a randomized trial
Authors: Singh Dave , Wild Jim M. , Saralaya Dinesh , Lawson Rod , Marshall Helen , Goldin Jonathan , Brown Matthew S. , Kostikas Konstantinos , Belmore Kristin , Fogel Robert , Patalano Francesco , Drollmann Anton , Machineni Surendra , Jones Ieuan , Yates Denise , Tillmann Hanns-Christian 
Published: February 2022

Abstract
Rationale
The long-acting β2-agonist/long-acting muscarinic antagonist combination indacaterol/glycopyrronium (IND/GLY) elicits bronchodilation, improves symptoms, and reduces exacerbations in COPD. Magnetic resonance imaging (MRI) of the lung with hyperpolarized gas and gadolinium contrast enhancement enables assessment of whole lung functional responses to IND/GLY.

Objectives
The primary objective was assessment of effect of IND/GLY on global ventilated lung volume (%VV) versus placebo in COPD. Lung function, regional ventilation and perfusion in response to IND/GLY were also measured.

Methods
This double-blind, randomized, placebo-controlled, crossover study assessed %VV and pulmonary perfusion in patients with moderate-to-severe COPD after 8 days of once-daily IND/GLY treatment (110/50 µg) followed by 8 days of placebo, or vice versa, using inhaled hyperpolarized 3He gas and gadolinium contrast-enhanced MRI, respectively. Lung function measures including spirometry were performed for each treatment after 8 days.

Measurements and main results
Of 31 patients randomized, 29 completed both treatment periods. IND/GLY increased global %VV versus placebo (61.73% vs. 56.73%, respectively, least squares means treatment difference: 5.00% [90% CI 1.40 to 8.60]; P = 0.025). IND/GLY improved whole lung index of ventilation volume to perfusion volume (V/Q) ratio versus placebo; 94% (90% CI 83 to 105) versus 86% (90% CI 75 to 97; P = 0.047), respectively. IND/GLY showed a trend to improve diffusing capacity for carbon monoxide (DLCO) (+ 0.66 mL/min/mmHg; P = 0.082). By Day 8, forced expiratory volume in 1 s (FEV1) was increased by 0.32 L versus placebo (90% CI 0.26 to 0.38; P < 0.0001), substantiating earlier findings and providing evidence of assay sensitivity for this trial.

Conclusions
IND/GLY improved lung ventilation assessed by 3He MRI after 1 week of treatment. This observation may provide mechanistic support for the symptomatic clinical benefit shown with IND/GLY in COPD.
Clinical trial registered with www.clinicaltrials.gov (NCT02634983).
A novel immune-related lncRNA pair signature for prognostic prediction and immune response evaluation in gastric cancer: a bioinformatics and biological validation study
Authors: Wang Jun , Wang Beidi , Zhou Biting , Chen Jing , Qi Jia , Shi Le , Yu Shaojun , Chen Guofeng , Kang Muxing , Jin Xiaoli , Wang Lie , Xu Jinghong , Zhu Linghua , Chen Jian 
Published: February 2022

Abstract
Background
Gastric cancer (GC), the most commonly diagnosed cancer worldwide with poor 5-year survival rate in advanced stages. Although immune-related and survival-related biomarkers, which typically comprise aberrantly expressed long non-coding RNAs (lncRNAs) and genes, have been identified, there are no reports of immune-related lncRNA pair (IRLP) signatures for GC.

Methods
In this study, we acquired lncRNA expression profiles from The Cancer Genome Atlas (TCGA) and used the least absolute shrinkage and selection operator (LASSO) Cox proportional hazards model (iteration = 1000) to develop a IRLP prognostic signature. The area under curve (AUC) was used to assess the prognosis predictive power. The multivariate Cox regression analysis was performed to identify whether this signature was an independent prognostic factor. The immune cell infiltration analysis was performed between the two risk groups. Last, molecular experiments were performed to explore LINC01082 is involved in the development of GC.

Results
We acquired lncRNA expression profiles and used the LASSO Cox model to develop an 18-IRLP signature with a strong prognostic predictive power. The 5-year AUC values of the training, validation, and overall TCGA datasets were 0.77, 0.86, and 0.80, respectively. The different prognostic outcomes between the high- and low-risk groups were determined using our 18-IRLP signature. Moreover, our 18-IRLP signature was an independent prognostic factor as per the multivariate Cox regression analysis, and showed better prognostic evaluation than the traditional TNM staging system as well as other clinical features. We also found differences in cancer-associated fibroblast and macrophage M2 infiltration and the expression of PD-L1, CTLA4, LAG3, and HLA were also observed between the two risk groups (P < 0.05). Analysis of biological functions revealed that target genes of the lncRNAs in the IRLP signature were enriched in focal adhesion and regulation of actin cytoskeleton. Finally, as one of significant candidates of IRLP signature, overexpression of LINC01082 suppressed the invasion ability of GC cells as well as PD-L1 expression profiles.

Conclusions
Our novel 18-IRLP signature provides new insights regarding immunological biomarkers, imparts a better understanding of the tumor immune microenvironment, and can be used for predicting prognosis and evaluating immune response in GC.
Clinical pharmacokinetics of quinine and its relationship with treatment outcomes in children, pregnant women, and elderly patients, with uncomplicated and complicated malaria: a systematic review
Authors: Saeheng Teerachat , Na-Bangchang Kesara 
Published: February 2022

Abstract
Background
Standard dosage regimens of quinine formulated for adult patients with uncomplicated and complicated malaria have been applied for clinical uses in children, pregnant women, and elderly. Since these populations have anatomical and physiological differences from adults, dosage regimens formulated for adults may not be appropriate. The study aimed to (i) review existing information on the pharmacokinetics of quinine in children, pregnant women, and elderly populations, (ii) identify factors that influence quinine pharmacokinetics, and (iii) analyse the relationship between the pharmacokinetics and treatment outcomes (therapeutic and safety) of various dosage regimens of quinine.

Methods
Web of Sciences, Cochrane Library, Scopus, and PubMed were the databases applied in this systematic search for relevant research articles published up to October 2020 using the predefined search terms. The retrieved articles were initially screened by titles and abstracts to exclude any irrelevant articles and were further evaluated based on full-texts, applying the predefined eligibility criteria. Excel spreadsheet (Microsoft, WA, USA) was used for data collection and management. Qualitative data are presented as numbers and percentages, and where appropriate, mean + SD or median (range) or range values.

Results
Twenty-eight articles fulfilled the eligibility criteria, 19 in children, 7 in pregnant women, and 2 in elderly (14 and 7 articles in complicated and uncomplicated malaria, respectively). Severity of infection, routes of administration, and nutritional status were shown to be the key factors impacting quinine pharmacokinetics in these vulnerable groups.

Conclusions
The recommended dosages for both uncomplicated and complicated malaria are, in general, adequate for elderly and children with uncomplicated malaria. Dose adjustment may be required in pregnant women with both uncomplicated and complicated malaria, and in children with complicated malaria. Pharmacokinetics studies relevant to clinical efficacy in these vulnerable groups of patients with large sample size and reassessment of MIC (minimum inhibitory concentration) should be considered.
Association between increasing agricultural use of 2,4-D and population biomarkers of exposure: findings from the National Health and Nutrition Examination Survey, 2001–2014
Authors: Freisthler Marlaina S. , Robbins C. Rebecca , Benbrook Charles M. , Young Heather A. , Haas David M. , Winchester Paul D. , Perry Melissa J. 
Published: February 2022

Abstract
Background
2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most extensively used herbicides in the United States. In 2012, 2,4-D was the most widely used herbicide in non-agricultural settings and the fifth most heavily applied pesticide in the US agricultural sector. The objective of this study was to examine trends in 2,4-D urinary biomarker concentrations to determine whether increases in 2,4-D application in agriculture are associated with increases in biomonitoring levels of urine 2,4-D.

Methods
Data from the National Health and Nutrition Examination Survey (NHANES) with available urine 2,4-D biomarker measurements from survey cycles between 2001 and 2014 were utilized. Urine 2,4-D values were dichotomized using the highest limit of detection (LOD) across all cycles (0.40 μg/L or 0.4 ppb). Agricultural use of 2,4-D was estimated by compiling publicly available federal and private pesticide application data. Logistic regression models adjusted for confounders were fitted to evaluate the association between agricultural use of 2,4-D and urine 2,4-D level above the dichotomization threshold.

Results
Of the 14,395 participants included in the study, 4681 (32.5%) had urine 2,4-D levels above the dichotomization threshold. The frequency of participants with high 2,4-D levels increased significantly (p < .0001), from a low of 17.1% in 2001–2002 to a high of 39.6% in 2011–2012. The adjusted odds of high urinary 2,4-D concentrations associated with 2,4-D agricultural use (per ten million pounds applied) was 2.268 (95% CI: 1.709, 3.009). Children ages 6–11 years (n = 2288) had 2.1 times higher odds of having high 2,4-D urinary concentrations compared to participants aged 20–59 years. Women of childbearing age (age 20–44 years) (n = 2172) had 1.85 times higher odds than men of the same age.

Conclusions
Agricultural use of 2,4-D has increased substantially from a low point in 2002 and it is predicted to increase further in the coming decade. Because increasing use is likely to increase population level exposures, the associations seen here between 2,4-D crop application and biomonitoring levels require focused biomonitoring and epidemiological evaluation to determine the extent to which rising use and exposures cause adverse health outcomes among vulnerable populations (particularly children and women of childbearing age) and highly exposed individuals (farmers, other herbicide applicators, and their families).
Population snapshot of the extended-spectrum β-lactamase-producing Escherichia coli invasive strains isolated from a Hungarian hospital
Authors: Tóth Kinga , Tóth Ákos , Kamotsay Katalin , Németh Viktória , Szabó Dóra 
Published: February 2022

Abstract
Background
This study was carried out to determine the prevalence and the genetic background of extended-spectrum β-lactamase-producing Escherichia coli invasive isolates obtained from a tertiary-care hospital in Budapest, Hungary.

Methods
Between October–November 2018, all invasive ESBL-producing E. coli isolates were collected from Central Hospital of Southern Pest. The antimicrobial susceptibility testing was performed according to the EUCAST guidelines. The possible clonal relationships were investigated by core genome (cg)MLST (SeqSphere +) using whole-genome sequencing (WGS) data of isolates obtained from Illumina 251-bp paired-end sequencing. From WGS data acquired antimicrobial resistance genes, virulence genes and replicon types were retrieved using ResFinder3.1, PlasmidFinder2.1, pMLST-2.0, VirulenceFinder2.0 and Virulence Factors Database online tools.

Results
Overall, six E. coli isolates proved to be resistant to third-generation cephalosporins and ESBL-producers in the study period. Full genome sequence analysis showed that five E. coli isolates belonged to the ST131 clone: two to C1-M27 subclade with blaCTX-M-27 and three to C2/H30Rx subclade with blaCTX-M-15. One isolate belonged to ST1193 with blaCTX-M-27. According to cgMLST, all C2/H30Rx isolates formed a cluster (≤ 6 allele differences), while the blaCTX-M-27-producing C1-M27 isolates differed at least 35 alleles from each other. Both C2/H30Rx and C1-M27 ST131 isolates harbored similar antimicrobial resistance gene sets. However, only C2/H30Rx isolates had the qnrB and aac(3)-IIa. The isolates carried similar extraintestinal virulence gene set but differed in some genes encoding siderophores, protectins and toxins. Moreover, only one C2/H30Rx isolate carried salmochelin siderophore system and showed virotype B. All isolates showed resistance against ceftriaxone, cefotaxime, and ciprofloxacin, and the C2/H30Rx isolates were also resistant to gentamicin, tobramycin, and ceftazidime.

Conclusions
Out of six ESBL-producing E. coli, five belonged to the ST131 clone. This study indicates, that the C2/H30Rx and C1-M27 subclades of the ST131 appear to be the dominant clones collected in a Hungarian hospital.
Causes, clinical findings and therapeutic options in chylomicronemia syndrome, a special form of hypertriglyceridemia
Authors: Paragh György , Németh Ákos , Harangi Mariann , Banach Maciej , Fülöp Péter 
Published: February 2022

AbstractThe prevalence of hypertriglyceridemia has been increasing worldwide. Attention is drawn to the fact that the frequency of a special hypertriglyceridemia entity, named chylomicronemia syndrome, is variable among its different forms. The monogenic form, termed familial chylomicronemia syndrome, is rare, occuring in 1 in every 1 million persons. On the other hand, the prevalence of the polygenic form of chylomicronemia syndrome is around 1:600. On the basis of the genetical alterations, other factors, such as obesity, alcohol consumption, uncontrolled diabetes mellitus and certain drugs may significantly contribute to the development of the multifactorial form. In this review, we aimed to highlight the recent findings about the clinical and laboratory features, differential diagnosis, as well as the epidemiology of the monogenic and polygenic forms of chylomicronemias. Regarding the therapy, differentiation between the two types of the chylomicronemia syndrome is essential, as well. Thus, proper treatment options of chylomicronemia and hypertriglyceridemia will be also summarized, emphasizing the newest therapeutic approaches, as novel agents may offer solution for the effective treatment of these conditions.
Interleukin-4 can play a role in allergic rhinitis patient during treatment with Zataria multiflora
Authors: Ariaee Nazila , Yadegari Yaser , Shabestari Mohamad , Asili Javad , Panahi Maryam , Ghorbani Jalal , Jabbari Farahzad 
Published: February 2022

Abstract
Background
Allergic rhinitis is a widespread disorder across the globe. The Shirazi thyme (Zataria multiflora) has been shown to have considerable antioxidant and anti-inflammatory properties. This study assessed the effect of this herbal product on alterations in inflammatory/anti-inflammatory cytokines.

Method
This study was conducted on the bank sample before and after the intervention to measure interleukin-4, interleukin-5, and interferon -γ levels with the ELISA test method in a supernatant taken from the PBMC cell culture from 30 allergic rhinitis patients.

Results
The IL-4 level had no significant difference between the two groups before the treatment. However, it had a significant increase in the case group after the treatment. The IL-5 level was significantly higher in the case group before the treatment. Nevertheless, there were no significant differences between the case and control groups after the treatment. Similarly, no significant differences were observed between the two groups considering IFN-γ before and after the treatment.

Conclusion
Consuming thyme with an increase in anti-inflammatory cytokine IL-4 and a decrease in IL-5 cytokine control inflammation and improvement in allergic rhinitis symptoms.
Clinical trial details This clinical trial study was recorded at 22.5.2014 in the Iran Registry of Clinical Trials code: (IRCT2016121823235N6) https://www.irct.ir/trial/19852
Psychometric properties of the kidney disease quality of life-36 (KDQOL-36) in Ethiopian patients undergoing hemodialysis
Authors: Gebrie Mignote Hailu , Asfaw Hussen Mekonnen , Bilchut Workagegnehu Hailu , Lindgren Helena , Wettergren Lena 
Published: February 2022

Abstract
Background
Health-related quality of life (HRQOL) has a direct association with increased morbidity and mortality among end stage renal disease patients. Valid and reliable instruments to measure the HRQOL of patients with end stage renal disease are therefore required. This study aimed to translate, culturally adapt and evaluate the psychometric properties of the Amharic version of the Kidney Disease Quality of Life-36 (KDQOL-36) instrument in Ethiopian patients with end stage renal disease undergoing hemodialysis.

Methods
The KDQOL-36 instrument was developed for individuals with kidney disease who are being treated with dialysis and includes both generic and disease-specific components. The KDQOL-36 was translated to Amharic language and distributed to a cross-sectional sample of 292 hemodialysis patients. The psychometric evaluation included construct validity through corrected item-total correlation, confirmatory factor analysis and known group analysis. Convergent validity was evaluated by correlations between each of the three kidney disease targeted scales (symptoms/problems list, burden of kidney disease and effects of kidney diseases) and the European Quality of Life 5D-5L and Visual Analog Scales. Regarding reliability, internal consistency and test–retest reliability were assessed.

Results
Two hundred ninety-two patients with a mean age of 48 (SD ± 14.7) completed the questionnaire. Corrected item- total correlation scores were > 0.4 for all items. Confirmatory factor analysis revealed a two χ2 /df was 4.4, Root Mean Square Error of Approximation (RMSEA) = 0.108 (90% CI 0.064–0.095), Comparative Fit Index (CFI) = 0.922, Tucker Lewis Index (TLI) = 0.948 and Standardized Root mean-squared residual (SRMR) = 0.058) and three χ2 /df = 3.1, RMSEA = 0.085 (90% CI 0.064–0.095), CFI = 0.854, TLI = 0.838 and SRMR = 0.067) factor models for the generic and disease specific components respectively. The mean scores of the three kidney disease targeted domains were correlated to the EQ-5D-5L & VAS with correlation coefficients of large magnitude (0.55–0.81). The reliability of the instrument was satisfactory (Cronbach’s alpha = 0.81–0.91) and Intra-class correlation (ICC) = 0.90–0.96).

Conclusion
The Amharic version of the KDQOL-36 is a reliable and valid instrument recommended for assessment of HRQOL of Ethiopian patients on hemodialysis.
Interleukin-17A pretreatment attenuates the anti-hepatitis B virus efficacy of interferon-alpha by reducing activation of the interferon-stimulated gene factor 3 transcriptional complex in hepatitis B virus-expressing HepG2 cells
Authors: Zhang Jiaxuan , Liu Kai , Zhang Gaoli , Ling Ning , Chen Min 
Published: February 2022

Abstract
Background
Some cytokine signaling pathways can interact with interferon (IFN)-α pathway and thus regulate cell responses to IFN-α. Levels of the pro-inflammatory cytokine interleukin-17A (IL-17A) were found to be elevated in both the peripheral blood and liver in chronic hepatitis B (CHB) patients. However, how IL-17A affects the anti-HBV activity of IFN-α remains unclear.

Methods
The effects of IL-17A on anti-HBV activity of IFN-α were evaluated in HBV-expressing HepG2 cells (HepG2-HBV1.3) with IL-17A pretreatment and IFN-α stimulation. Culture supernatant levels of HBsAg, HBeAg, and HBV DNA, or intracellular expression of HBsAg and HBcAg were detected by ELISA, real-time quantitative PCR (RT-qPCR), or western blotting (WB). The expression of canonical IFN-α signaling pathway components, including the interferon-α/β receptor (IFNAR), Janus Kinase 1 (JAK1), Tyrosine Kinase 2 (TYK2), the Interferon Stimulated Gene Factor 3 complex (ISGF3) and IFN-stimulated genes (ISGs), was also examined by RT-qPCR, Immunofluorescence or WB. The effects of IL-17A were further investigated by the suppression of the IL-17A pathway with a TRAF6 inhibitor.

Results
Compared to IFN-α stimulation alone, IL-17A pretreatment followed by IFN-α stimulation increased the levels of HBsAg, HBeAg, and HBV DNA, and decreased the levels of ISGF3 complex (phosphorylated (p)-signal transducer and activator of transcription (STAT1)/p-STAT2/IRF9) and antiviral-related ISGs (ISG15, ISG20 and Mx1). Interestingly, IL-17A pretreatment increased the expression of suppressor of cytokine signaling (SOCS) 1, SOCS3 and USP18, which were also the ISGs negatively regulating activity of ISGF3. Moreover, IFNAR1 protein expression declined more sharply in the group with IL-17A pretreatment than in the group with IFN-α stimulation alone. Blocking the IL-17A pathway reversed the effects of IL-17A on the IFN-α-induced activation of ISGF3 and anti-HBV efficacy.

Conclusions
Our results demonstrate that IL-17A pretreatment could attenuate IFN-α-induced anti-HBV activity by upregulating negative regulators of the critical transcriptional ISGF3 complex. Thus, this might be a potential target for improving response to IFN-α therapy.
A UV-LED module that is highly effective at inactivating human coronaviruses and HIV-1
Authors: Persaud Arvin T. , Burnie Jonathan , Thaya Laxshaginee , DSouza Liann , Martin Steven , Guzzo Christina 
Published: February 2022

AbstractUltraviolet (UV) light has previously been established as useful method of disinfection, with demonstrated efficacy to inactivate a broad range of microorganisms. The advent of ultraviolet light-emitting diodes provides advantages in ease of disinfection, in that there can be delivery of germicidal UV with the same light unit that delivers standard white light to illuminate a room. Herein we demonstrate the efficacy and feasibility of ultraviolet light-emitting diodes as a means of decontamination by inactivating two distinct virus models, human coronavirus 229E and human immunodeficiency virus. Importantly, the same dose of ultraviolet light that inactivated human viruses also elicited complete inactivation of ultraviolet-resistant bacterial spores (Bacillus pumilus), a gold standard for demonstrating ultraviolet-mediated disinfection. This work demonstrates that seconds of ultraviolet light-emitting diodes (UV-LED) exposure can inactivate viruses and bacteria, highlighting that UV-LED could be a useful and practical tool for broad sanitization of public spaces.