bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response to mepolizumab treatment is sustained across 4-weekly dosing periods
Authors: Pavord Ian D. , Bleecker Eugene R. , Buhl Roland , Chanez Pascal , Bel Elisabeth H. , Howarth Peter , Bratton Daniel J. , Albers Frank C. , Yancey Steven 
Published: September 2020

BackgroundMepolizumab (100 mg delivereds.c.every 4 weeks) is indicated for add-on maintenance treatment for patients with severe eosinophilic asthma. Mepolizumab has been shown to reduce exacerbations and the requirement for daily oral corticosteroids, and improve asthma control and symptoms. However, data on the durability of the response to mepolizumab during dosing periods are limited. The aim of this study was to investigate the efficacy profile in patients with severe eosinophilic asthma over the 4-weekly dosing period for various fixed mepolizumab doses.MethodsThis was apost hocanalysis of data from the phase IIb/III DREAM study. Patients ≥12 years of age with severe eosinophilic asthma were randomised (1:1:1:1) to receive intravenous mepolizumab 75 mg (equivalent to 100 mgs.c.),250 mg, 750 mg or placebo, plus standard of care, every 4 weeks for 52 weeks. The number of exacerbations and eDiary data (peak expiratory flow, rescue medication use and symptom scores) from two periods in each 4-weekly dosing interval (days 1–14 and 15–28) over the 52-week treatment period were analysed.FindingseDiary data and the proportion of patients experiencing ≥1 exacerbation were similar during the first and second 2 weeks of a dosing period across all mepolizumab doses.InterpretationThese results demonstrate that the response to mepolizumab is sustained over the 4-weekly dosing period with no differences across a 10-fold dose range and supports the use of the current mepolizumab dosing regimen in patients with severe eosinophilic asthma.
Clinical course of asymptomatic small enhancing brain nodules in patients with nonsmall cell lung cancer: do we have to follow them up?
Authors: Lee Hyun Woo , Cho Jaeyoung , Kwak Nakwon , Hwang Inpyeong , Park Young Sik , Lee Chang-Hoon , Lee Sang-Min , Yoo Chul-Gyu , Kim Young Whan , Choi Sun Mi 
Published: September 2020

AimsBrain magnetic resonance imaging (MRI) is recommended during the initial work-up for nonsmall cell lung cancer (NSCLC). Although small enhancing brain nodules not radiologically confirmed as metastatic lesions have often been detected, their clinical course has not been well studied.MethodsThis nested case–control study included NSCLC patients who had small enhancing brain nodules detected by serial brain MRIs from January 2014 through December 2018 at a tertiary university hospital. Small enhancing brain nodules were defined as round enhancing nodules of ≤10 mm diameter without oedema in thin-section (1 mm) contrast MRIs. The incidence, natural course and risk factors of growing nodules were evaluated.ResultsA total of 171 small enhancing brain nodules in 123 patients were observed over an average of 22.1 months. The incidence of nodule growth was 49.1% with mean growth rate of 11 mm·year−1. We found that 25.0% of the growing nodules contributed to clinical upstaging compared to the initial stage. Cerebral events were more common in growing nodules; therefore, local therapy was performed more often. However, there was no difference in the cerebral event-related mortality. Nodule growth was more frequent in younger individuals, multiple nodules, advanced disease, poorly differentiated carcinoma, rim enhancement and larger initial size. In multivariable analysis, predictors of growth were N stage ≥1, existence of epidermal growth factor receptor mutation and larger initial size.ConclusionConsidering the clinical course of small enhancing brain nodules, more intensive evaluation is required for early detection and pre-emptive intervention when accompanied by risk factors.
Somatotypes trajectories during adulthood and their association with COPD phenotypes
Authors: Divo Miguel J. , Marin Oto Marta , Casanova Macario Ciro , Cabrera Lopez Carlos , de-Torres Juan P. , Marin Trigo Jose Maria , Hersh Craig P. , Ezponda Casajús Ana , Maguire Cherie , Pinto-Plata Victor M. , Polverino Francesca , Ross James C. , DeMeo Dawn , Bastarrika Gorka , Silverman Edwin K. , Celli Bartolome R. 
Published: September 2020

RationaleChronic obstructive pulmonary disease (COPD) comprises distinct phenotypes, all characterised by airflow limitation.ObjectivesWe hypothesised that somatotype changes – as a surrogate of adiposity – from early adulthood follow different trajectories to reach distinct phenotypes.MethodsUsing the validated Stunkard's Pictogram, 356 COPD patients chose the somatotype that best reflects their current body build and those at ages 18, 30, 40 and 50 years. An unbiased group-based trajectory modelling was used to determine somatotype trajectories. We then compared the current COPD-related clinical and phenotypic characteristics of subjects belonging to each trajectory.Measurements and main resultsAt 18 years of age, 88% of the participants described having a lean or medium somatotype (estimated body mass index (BMI) between 19 and 23 kg·m−2) while the other 12% a heavier somatotype (estimated BMI between 25 and 27 kg·m−2). From age 18 onwards, five distinct trajectories were observed. Four of them demonstrating a continuous increase in adiposity throughout adulthood with the exception of one, where the initial increase was followed by loss of adiposity after age 40. Patients with this trajectory were primarily females with low BMI andDLCO(diffusing capacity of the lung for carbon monoxide). A persistently lean trajectory was seen in 14% of the cohort. This group had significantly lower forced expiratory volume in 1 s (FEV1),DLCO, more emphysema and a worse BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) score thus resembling the multiple organ loss of tissue (MOLT) phenotype.ConclusionsCOPD patients have distinct somatotype trajectories throughout adulthood. Those with the MOLT phenotype maintain a lean trajectory throughout life. Smoking subjects with this lean phenotype in early adulthood deserve particular attention as they seem to develop more severe COPD.
Identification of target zones for lung volume reduction surgery using three-dimensional computed tomography rendering
Authors: Caviezel Claudio , Froehlich Tamara , Schneiter Didier , Muehlematter Urs , Frauenfelder Thomas , Guglielmetti Laura-Chiara , Opitz Isabelle , Weder Walter 
Published: September 2020

BackgroundThe key issues for performing lung volume reduction surgery (LVRS) is the identification of the target zones. Recently introduced three-dimensional computed tomography rendering methods are used to identify the morphological distribution and its severity of lung emphysema by densitometry. We demonstrate a new software for emphysema imaging and show the pre- and post-operative results in patients undergoing LVRS planned based on this new technology.MethodsA real-time three-dimensional image analysis software system was used pre- and 3 months post-operatively in five patients with heterogeneous emphysema and a single patient with homogeneous morphology scheduled for LVRS. Focus was on low attenuation areas with <950 HU, distribution on both lungs and the value of the three-dimensional images for planning surgery. Functional outcome was assessed by pulmonary function tests after 3 months.ResultsFive patients underwent bilateral LVRS and one patient had unilateral LVRS. All patients showed a median increase in forced expiratory volume in 1 s of 70% (range 30–120%), compared with baseline values. Hyperinflation (expressed as residual volume/total lung capacity ratio) was reduced by 30% (range 5–32%). In the patients with heterogeneous emphysema, the pre- and post-operative computed tomography scans and the densitometries showed a decrease in low attenuation areas by 23% (right side) and by 17% (left side), respectively.ConclusionWe demonstrate three-dimensional computed tomography-rendered images for planning personalised remodelling of hyperinflated lungs using LVRS. This user-friendly software has the potential to assist surgeons and interventional pulmonologists to select patients and to visualise target areas in LVRS procedures.
Personalised exhaled nitric oxygen fraction (FENO)-driven asthma management in primary care: aFENOsubgroup analysis of the ACCURATE trial
Authors: Boer Suzanne , Honkoop Persijn J. , Loijmans Rik J.B. , Snoeck-Stroband Jiska B. , Assendelft Willem J.J. , Schermer Tjard R.J. , Sont Jacob K. 
Published: September 2020

BackgroundThe aim of this study was to identify patients who benefit most from exhaled nitric oxide fraction (FENO)-driven asthma management in primary care, based on prespecified subgroups with different levels ofFENO.MethodsWe used data from 179 adults with asthma from a 12-month primary care randomised controlled trial with 3-monthly assessments ofFENO, asthma control, medication usage, costs of medication, severe asthma exacerbations and quality of life. In the original study, patients were randomised to either a symptom-driven treatment strategy (controlled asthma (Ca) strategy) or aFENO+symptom-driven strategy (FCa). In both groups, patients were categorised by their baseline level ofFENOas low (<25 ppb), intermediate (25–50 ppb) and high (>50 ppb). At 12 months, we compared, for each prespecifiedFENOsubgroup, asthma control, asthma-related quality of life, medication usage, and costs of medication between the Ca and FCa strategy.ResultsWe found a difference between the Ca and FCa strategy for the mean dosage of beclomethasone strategy of 223 µg (95% CI 6–439), p=0.04) and for the total costs of asthma medication a mean reduction of US$159 (95% CI US$33–285), p=0.03) in patients with a low baselineFENOlevel. No differences were found for asthma control, severe asthma exacerbations and asthma-related quality of life in patients with a low baselineFENOlevel. Furthermore, in patients with intermediate or high level ofFENO, no differences were found.ConclusionsIn primary care,FENO-driven asthma management is effective in patients with a lowFENOlevel, for whom it is possible to down-titrate medication, while preserving asthma control and quality of life.
Genome-wide characterization and expression profiling of MAPK cascade genes in Salvia miltiorrhiza reveals the function of SmMAPK3 and SmMAPK1 in secondary metabolism
Authors: Xie Yongfeng , Ding Meiling , Zhang Bin , Yang Jie , Pei Tianlin , Ma Pengda , Dong Juane 
Published: September 2020

Abstract
Background
The contribution of mitogen-activated protein kinase (MAPK) cascades to plant growth and development has been widely studied, but this knowledge has not yet been extended to the medicinal plant Salvia miltiorrhiza, which produces a number of pharmacologically active secondary metabolites.

Results
In this study, we performed a genome-wide survey and identified six MAPKKK kinases (MAPKKKKs), 83 MAPKK kinases (MAPKKKs), nine MAPK kinases (MAPKKs) and 18 MAPKs in the S. miltiorrhiza genome. Within each class of genes, a small number of subfamilies were recognized. A transcriptional analysis revealed differences in the genes’ behaviour with respect to both their site of transcription and their inducibility by elicitors and phytohormones. Two genes were identified as strong candidates for playing roles in phytohormone signalling. A gene-to-metabolite network was constructed based on correlation analysis, highlighting the likely involvement of two of the cascades in the synthesis of two key groups of pharmacologically active secondary metabolites: phenolic acids and tanshinones.

Conclusion
The data provide insight into the functional diversification and conservation of MAPK cascades in S. miltiorrhiza.
RNA-seq analysis of galaninergic neurons from ventrolateral preoptic nucleus identifies expression changes between sleep and wake
Authors: Guo Xiaofeng , Gao Xiaoling , Keenan Brendan T. , Zhu Jingxu , Sarantopoulou Dimitra , Lian Jie , Galante Raymond J. , Grant Gregory R. , Pack Allan I. 
Published: September 2020

AbstractBackgroundPrevious studies show that galanin neurons in ventrolateral preoptic nucleus (VLPO-Gal) are essential for sleep regulation. Here, we explored the transcriptional regulation of the VLPO-Gal neurons in sleep by comparing their transcriptional responses between sleeping mice and those kept awake, sacrificed at the same diurnal time.ResultsRNA-sequencing (RNA-seq) analysis was performed on eGFP(+) galanin neurons isolated using laser captured microdissection (LCM) from VLPO. Expression ofGalwas assessed in our LCM eGFP(+) neurons via real time qPCR and showed marked enrichment when compared to LCM eGFP(−) cells and to bulk VLPO samples. Gene set enrichment analysis utilizing data from a recent single-cell RNA-seq study of the preoptic area demonstrated that our VLPO-Gal samples were highly enriched with galanin-expressing inhibitory neurons, but not galanin-expressing excitatory neurons. A total of 263 genes were differentially expressed between sleep and wake in VLPO-Gal neurons. When comparing differentially expressed genes in VLPO-Gal neurons to differentially expressed genes in a wake-active neuronal region (the medial prefrontal cortex), evidence indicates that both systemic and cell-specific mechanisms contribute to the transcriptional regulation in VLPO-Gal neurons. In both wake-active and sleep-active neurons, ER stress pathways are activated by wake and cold-inducible RNA-binding proteins are activated by sleep. In contrast, expression of DNA repair genes is increased in VLPO-Gal during wakefulness, but increased in wake-active cells during sleep.ConclusionOur study identified transcriptomic responses of the galanin neurons in the ventrolateral preoptic nucleus during sleep and sleep deprivation. Data indicate that VLPO contains mainly sleep-active inhibitory galaninergic neurons. The VLPO galanin neurons show responses to sleep and wake similar to wake-active regions, indicating these responses, such as ER stress and cold-inducible RNA-binding proteins, are systemic affecting all neuronal populations. Region-specific differences in sleep/wake responses were also identified, in particular DNA repair. Our study expands knowledge about the transcriptional response of a distinct group of neurons essential for sleep.
Characterization of carbapenem-resistant hypervirulent Acinetobacter baumannii strains isolated from hospitalized patients in the mid-south region of China
Authors: Li Jun , Yu Ting , Luo Yi , Peng Jing-Yi , Li Yu-Jia , Tao Xiao-Yan , Hu Yong-Mei , Wang Hai-Chen , Zou Ming-Xiang 
Published: September 2020

Abstract
Background
Acinetobacter baumannii has traditionally been considered an opportunistic pathogen with low virulence. In this study, we characterized the carbapenem-resistant hypervirulent A. baumannii (CR-hvAB) stains isolated from our hospital in mid-south region of China.

Results
Blood samples collected between January 2017 and May 2019 were used for virulence experiments and biofilm assays of individual carbapenem-resistant A. baumannii (CR-AB) strains, performed using a Galleria mellonella infection model and crystal violet staining method, respectively. CR-AB isolates that induced high mortality in the G. mellonella infection model were subjected to genotyping, susceptibility testing, and clinical data analysis, and the genetic characterization of these isolates was performed by whole-genome sequencing (WGS). Among the 109 CR-AB clinical strains, the survival rate of G. mellonella larvae infected with 7 (6.4%) CR-AB isolates (number of strains with mortality of 0, 10 and 20% was 4, 1, and 2, respectively), was significantly lower than that of A. baumannii ATCC 19606 (100.0%) and the remaining CR-AB isolates (> 80.0%). Consistent with these results, patients infected with these seven isolates had an average 7-day mortality rate of 42.9%, suggesting that the isolates were CR-hvAB. These seven isolates belonged to four sequence types (STs): ST457, ST195, ST369, and ST2088 (a new ST), and mainly ST457 (n = 4). The results of the biofilm study showed that eight strains had powerful biofilm ability (strong [n = 1] and moderate [n = 7] biofilm producers) including these seven CR-hvAB isolates.

Conclusions
CR-hvAB isolates that induced a high mortality rate were cloned in our hospital, most of which belonged to ST457; thus, monitoring of these strains, particularly ST457, should be strengthened in the future. Meanwhile, A. baumannii, which was isolated from blood specimens and found to powerful biofilm-forming ability, is a probable hvAB isolate.
Clinical characteristics of adult T-cell leukemia/lymphoma infiltration in the gastrointestinal tract
Authors: Miike Tadashi , Kawakami Hiroshi , Kameda Takuro , Yamamoto Shojiro , Tahara Yoshihiro , Hidaka Tomonori , Kubuki Yoko , Yorita Kenji , Akiyama Yutaka , Arimura Yasuji , Kubota Yoshimasa , Kataoka Hiroaki , Shimoda Kazuya 
Published: September 2020

AbstractBackgroundAdult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type 1. The clinical course of ATLL is very heterogeneous, and many organs, including the gastrointestinal (GI) tract, can be involved. However, there are few detailed reports on ATLL infiltration in the GI tract. We investigated the clinical characteristics of ATLL infiltration in the GI tract.MethodsThis retrospective observational single-center study included 40 consecutive ATLL patients who underwent GI endoscopy. The patients’ demographic and clinical characteristics and endoscopic findings were analyzed retrospectively. Patients with ATLL who were diagnosed by histological examination were divided into two groups based on GI tract infiltration.ResultsMultivariate analysis revealed that the absence of skin lesions was significantly associated with GI infiltration (P < 0.05). Furthermore, the infiltration group tended to have similar macroscopic lesions in the upper and lower GI tracts, such as diffuse type, tumor-forming type, and giant-fold type.ConclusionsGI endoscopy may be considered for ATLL patients without skin lesions.
Overcoming existential loneliness: a cross-cultural study
Authors: Chung B. P. M. , Olofsson J. , Wong F. K. Y. , Rämgård M. 
Published: September 2020

Abstract
Background
Moving into a long-term care facility (LTCF) can reduce the ability for older adults to engage in meaningful roles and activities and the size of their social network. These changes and losses can lead them to experience existential loneliness (EL)—the intolerable emptiness and lack of meaningful existence resulted from the losses they have experienced. While EL has often been understood as a universal human experience, it has primarily been studied in people from Western cultures; little is known about how EL may be experienced by and manifested in people from Eastern cultures. Hence, this qualitative study aimed to describe the experience and coping of EL in Hong Kong Chinese and Swedish older adults living in LTCFs.

Methods
A qualitative study using Thorne’s (2004) interpretive description was conducted. Thirteen Chinese and 9 Swedes living in LTCFs in Hong Kong, China and Malmo, Sweden, respectively were interviewed about their experience of EL in two series of semi-structured interviews. Data were analyzed using thematic analysis.

Results
The core theme of “overcoming EL” described the participants’ experience of EL, which came about through the combined process of “Feeling EL” and “Self-Regulating”. Both Chinese and Swedish participants had similar experience with EL. Realizing that they did not want to living with EL anymore, they coped by reframing their experience and identifying new meaning in their life.

Conclusions
The study findings suggested that early and clear counselling support that help older adults to define new meaning in life may help them cope. In addition, more opportunities should be available at the LTCFs to promote quality relationships, enable older adults to reflect on their lives with pride, and support their ability to do the things they enjoy.
Establishment of a novel nomogram for the clinically diagnostic prediction of minimal change disease, −a common cause of nephrotic syndrome
Authors: Yan Gaofei , Liu Guanzhi , Tian Xuefei , Tian Lifang , Wang Hao , Ren Peiyao , Ma Xiaotao , Fu Rongguo , Chen Zhao 
Published: September 2020

Abstract
Background
Minimal change disease (MCD) is one of the major causes of nephrotic syndrome (NS). A confirmed MCD diagnosis mainly depends on renal biopsy at present, which is an invasive procedure with many potential risks. The overall incidence of complications caused by renal biopsy procedures has been reported as approximately 11 and 6.6% outside and within China, respectively. Unfortunately, there is currently no noninvasive procedure or practical classification method for distinguishing MCD from other primary glomerular diseases available.

Method
A total of 1009 adult patients who underwent renal biopsy between January 2017 and November 2019 were enrolled in this study. Twenty-five parameters extracted from patient demographics, clinical manifestations, and laboratory test results were statistically analysed. LASSO regression analysis was further performed on these parameters. The parameters with the highest area under the curve (AUC) were selected and used to establish a logistic diagnostic prediction model.

Results
Of the 25 parameters, 14 parameters were significantly different (P < 0.05). MCD patients were mostly younger (36 (22, 55) vs. 41 (28.75, 53)) and male (59% vs. 52%) and had lower levels of diastolic blood pressure (DBP) (79 (71, 85.5) vs. 80 (74, 89)) and IgG (5.42 (3.17, 6.36) vs. 9.38 (6.79, 12.02)) and higher levels of IgM (1.44 (0.96, 1.88) vs. 1.03 (0.71, 1.45)) and IgE (160 (46.7, 982) vs. 47.3 (19, 126)) than those in the non-MCD group. Using the LASSO model, we established a classifier for adults based on four parameters: DBP and the serum levels of IgG, IgM, IgE. We were able to clinically classify adult patients with NS into MCD and non-MCD using this model. The validation accuracy of the logistic regression model was 0.88. A nomogram based on these four classifiers was developed for clinical use that could predict the probability of MCD in adult patients with NS.

Conclusions
A LASSO model can be used to distinguish MCD from other primary glomerular diseases in adult patients with NS. Combining the model and the nomogram potentially provides a novel and valuable approach for nephrologists to diagnose MCD, avoiding the complications caused by renal biopsy.