bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-term effects of Lumacaftor/Ivacaftor (Orkambi™) on exertional symptoms, exercise performance, and ventilatory responses in adults with cystic fibrosis
Authors: Quon Bradley S. , Ramsook Andrew H. , Dhillon Satvir S. , Mitchell Reid A. , Boyle Kyle G. , Wilcox Pearce G. , Guenette Jordan A. 
Published: June 2020

Abstract
Rationale
Lumacaftor/ivacaftor (LUM/IVA) modestly improves lung function following 1 month of treatment but it is unknown if this translates into improvements in exercise endurance and exertional symptoms.

Methods
Adult CF participants completed a symptom-limited constant load cycling test with simultaneous assessments of dyspnea and leg discomfort ratings pre- and 1 month post-initiation of LUM/IVA.

Results
Endurance time, exertional dyspnea and leg discomfort ratings at submaximal exercise did not change significantly. There was a significant inverse correlation between changes in leg discomfort and endurance time (r = − 0.88; p = 0.009) following 1-month of LUM/IVA.

Conclusions
Overall, 1-month of LUM/IVA did not increase endurance time or modify exertional dyspnea or leg discomfort ratings. However, individuals who experienced a reduction in leg discomfort following LUM/IVA had an improvement in endurance time. Future studies with a larger sample size are needed to verify these findings and to assess the long-term effects of LUM/IVA on exercise outcomes.

Trial registration
ClinicalTrials.gov Identifier: NCT02821130. Registered July 1, 2016.
Obtaining a series of native gradient promoter-5′-UTR sequences in Corynebacterium glutamicum ATCC 13032
Authors: Li Ning , Zeng Weizhu , Xu Sha , Zhou Jingwen 
Published: June 2020

Abstract
Background
Corynebacterium glutamicum is an important industrial microorganism used for the production of many valuable compounds, especially amino acids and their derivatives. For fine-tuning of metabolic pathways, synthetic biological tools are largely based on the rational application of promoters. However, the limited number of promoters make it difficult.

Results
In this study, according to the analysis of RNA-Seq data, 90 DNA fragments with lengths of 200-500 bp that may contain promoter-5′-UTR (PUTR) sequences were amplified and linked to a fluorescent protein gene. When compared with the common strong PUTR PsodUTR, 17 strong PUTRs were obtained, which maintained stable expression strengths from the early to post stationary phase. Among them, PNCgl1676UTR was the strongest and its fluorescent protein expression level was more than five times higher than that of PsodUTR. Furthermore, nine typical chemicals related to the biosynthesis of sulfur-containing amino acids (such as l-methionine, l-cysteine) were selected as stress substances to preliminarily explore the stress on these PUTRs. The results showed that the expression of PbrnFUTR was activated by l-methionine, while that of PNCgl1202UTR was severely inhibited by l-lysine.

Conclusions
These findings demonstrated that the selected PUTRs can stably express different genes, such as the red fluorescence protein gene, and can be useful for fine-tuning regulation of metabolic networks in C. glutamicum or for establishing high-throughput screening strategies through biosensor for the production of useful compounds.
A robust twelve-gene signature for prognosis prediction of hepatocellular carcinoma
Authors: Ouyang Guoqing , Yi Bin , Pan Guangdong , Chen Xiang 
Published: June 2020

Abstract
Background
The prognosis of hepatocellular carcinoma (HCC) patients remains poor. Identifying prognostic markers to stratify HCC patients might help to improve their outcomes.

Methods
Six gene expression profiles (GSE121248, GSE84402, GSE65372, GSE51401, GSE45267 and GSE14520) were obtained for differentially expressed genes (DEGs) analysis between HCC tissues and non-tumor tissues. To identify the prognostic genes and establish risk score model, univariable Cox regression survival analysis and Lasso-penalized Cox regression analysis were performed based on the integrated DEGs by robust rank aggregation method. Then Kaplan–Meier and time-dependent receiver operating characteristic (ROC) curves were generated to validate the prognostic performance of risk score in training datasets and validation datasets. Multivariable Cox regression analysis was used to identify independent prognostic factors in liver cancer. A prognostic nomogram was constructed based on The Cancer Genome Atlas (TCGA) dataset. Finally, the correlation between DNA methylation and prognosis-related genes was analyzed.

Results
A twelve-gene signature including SPP1, KIF20A, HMMR, TPX2, LAPTM4B, TTK, MAGEA6, ANX10, LECT2, CYP2C9, RDH16 and LCAT was identified, and risk score was calculated by corresponding coefficients. The risk score model showed a strong diagnosis performance to distinguish HCC from normal samples. The HCC patients were stratified into high-risk and low-risk group based on the cutoff value of risk score. The Kaplan–Meier survival curves revealed significantly favorable overall survival in groups with lower risk score (P < 0.0001). Time-dependent ROC analysis showed well prognostic performance of the twelve-gene signature, which was comparable or superior to AJCC stage at predicting 1-, 3-, and 5-year overall survival. In addition, the twelve-gene signature was independent with other clinical factors and performed better in predicting overall survival after combining with age and AJCC stage by nomogram. Moreover, most of the prognostic twelve genes were negatively correlated with DNA methylation in HCC tissues, which SPP1 and LCAT were identified as the DNA methylation-driven genes.

Conclusions
We identified a twelve-gene signature as a robust marker with great potential for clinical application in risk stratification and overall survival prediction in HCC patients.
Construction of a metastasis-associated ceRNA network reveals a prognostic signature in lung cancer
Authors: Cao Qing , Dong Zewen , Liu Shuzhen , An Guoyan , Yan Bianbian , Lei Lei 
Published: June 2020

Abstract
Background
Lung cancer is the most common cancer worldwide, and metastasis is the leading cause of lung cancer related death. However, the molecular network involved in lung cancer metastasis remains incompletely described. Here, we aimed to construct a metastasis-associated ceRNA network and identify a lncRNA prognostic signature in lung cancer.

Methods
RNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and gene set enrichment analysis (GSEA) were performed to investigate the function of these genes. Using Cox regression analysis, we found that a 6 lncRNA signature may serve as a candidate prognostic factor in lung cancer. Finally, we used Transwell assays with lung cancer cell lines to verify that LINC01010 acts as a tumor suppressor.

Results
We identified 1249 differentially expressed (DE) mRNAs, 440 DE lncRNAs and 26 DE miRNAs between nonmetastatic and metastatic lung cancer tissues. GO and KEGG analyses confirmed that the identified DE mRNAs are involved in lung cancer metastasis. Using bioinformatics tools, we constructed a metastasis-associated ceRNA network for lung cancer that includes 117 mRNAs, 23 lncRNAs and 22 miRNAs. We then identified a 6 lncRNA signature (LINC01287, SNAP25-AS1, LINC00470, AC104809.2, LINC00645 and LINC01010) that had the greatest prognostic value for lung cancer. Furthermore, we found that suppression of LINC01010 promoted lung cancer cell migration and invasion.

Conclusions
This study might provide insight into the identification of potential lncRNA biomarkers for diagnosis and prognosis in lung cancer.
Adverse reaction to Ficus Carica: reported case of a possible cross-reactivity with Der p1
Authors: Urbani S. , Aruanno A. , Nucera E. 
Published: June 2020

Abstract
Background
Ficus carica is an edible fruit, belonging to the Moraceae family, rarely described as cause of food allergy. We describe the first case of fig allergy that occurred as a cross-reactivity between fig and Derp 1.

Case presentation
We present a case of a 10-years-old-girl, with a history of no-seasonal mild intermittent rhinitis, who experienced an immediate reaction after ingestion of a fresh fig. Skin prick tests (SPT) with commercial extracts of food, airborne allergens, latex and panallergens (profilin, PR-10 and lipid transfer protein) were performed. SPT revealed a sensitization only for dermatophagoides farina and dermatophagoides pteronyssinus which was then confirmed with by specific IgE assay (UniCAP, Phadia, Uppsala, Sweden). We also carried out a positive SPT with a commercial fig allergen (Lofarma, Milan, Italy) and prick-by-prick (PBP) both with skin and pulp of green raw and cooked fig. Fig specific serum IgE levels were 1.08 U/ml and specific IgE for rDer p1 was 16.20 U/ml (total serum IgE = 377 U/ml). In contrast specific IgE levels for latex, LTP, profilin, PR-10 and pollen allergens were negative.

Conclusion
The ficin, the major fig allergen, belongs to cysteine protease family like Der p 1. The symptoms presented by our patient could be related to a cross reactivity between these two proteins which present a structural homology.
Serum metabolites may be useful markers to assess vascular invasion and identify normal alpha-fetoprotein in hepatocellular carcinoma undergoing liver resection: a pilot study
Authors: Lee Chao-Wei , Yu Ming-Chin , Lin Gigin , Chiu Jo-Chu , Chiang Meng-Han , Sung Chang-Mu , Hsieh Yi-Chung , Kuo Tony , Lin Cheng-Yu , Tsai Hsin-I 
Published: June 2020

Abstract
Purpose
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with a dismal prognosis. Vascular invasion, among others, is the most robust indicator of postoperative recurrence and overall survival after liver resection for HCC. Few studies to date have attempted to search for effective markers to predict vascular invasion before the operation. The current study would examine the plasma metabolic profiling via 1H-NMR of HCC patients undergoing liver resection and aim to search for potential biomarkers in the early detection of HCC with normal alpha-fetoprotein (AFP) and the diagnosis of vascular invasion preoperatively.

Materials and methods
HCC patients scheduled to receive liver resections for their HCC were recruited and divided into two separate groups, investigation cohort and validation cohort. Their preoperative blood samples were collected and subjected to a comprehensive metabolomic profiling using 1H-nuclear magnetic resonance spectroscopy (NMR).

Results
There were 35 HCC patients in the investigation group and 22 patients in the validation group. Chronic hepatitis B remained the most common etiology of HCC, followed by chronic HCV infection. The two study cohorts were essentially comparable in terms of major clinicopathological variables. After 1H-nuclear NMR analysis, we found in the investigation cohort that HCC with normal alpha-fetoprotein (AFP < 15 ng/mL) had significantly higher serum level of O-acetylcarnitine than those with higher AFP (AFP ≥ 15 ng/mL, P = 0.025). In addition, HCC with microscopic vascular invasion (VI) had significantly higher preoperative serum level of formate than HCC without microscopic VI (P = 0.023). These findings were similar in the validation cohort.

Conclusion
A comprehensive metabolomic profiling of HCC demonstrated that serum metabolites may be utilized to assist the early diagnosis of AFP-negative HCC patients and recognition of microvascular invasion in order to facilitate preoperative surgical planning and postoperative follow-up. Further, larger scale prospective studies are warranted to consolidate our findings.
Implementing performance-based financing in peripheral health centres in Mali: what can we learn from it?
Authors: Coulibaly Abdourahmane , Gautier Lara , Zitti Tony , Ridde Valéry 
Published: June 2020

AbstractIntroductionNumerous sub-Saharan African countries have experimented with performance-based financing (PBF) with the goal of improving health system performance. To date, few articles have examined the implementation of this type of complex intervention in Francophone West Africa. This qualitative research aims to understand the process of implementing a PBF pilot project in Mali's Koulikoro region.MethodWe conducted a contrasted multiple case study of performance in 12 community health centres in three districts. We collected 161 semi-structured interviews, 69 informal interviews and 96 non-participant observation sessions. Data collection and analysis were guided by the Consolidated Framework for Implementation Research adapted to the research topic and local context.ResultsOur analysis revealed that the internal context of the PBF implementation played a key role in the process. High-performing centres exercised leadership and commitment more strongly than low-performing ones. These two characteristics were associated with taking initiatives to promote PBF implementation and strengthening team spirit. Information regarding the intervention was best appropriated by qualified health professionals. However, the limited duration of the implementation did not allow for the emergence of networks or champions. The enthusiasm initially generated by PBF quickly dissipated, mainly due to delays in the implementation schedule and the payment modalities.ConclusionPBF is a complex intervention in which many actors intervene in diverse contexts. The initial level of performance and the internal and external contexts of primary healthcare facilities influence the implementation of PBF. Future work in this area would benefit from an interdisciplinary approach combining public health and anthropology to better understand such an intervention. The deductive–inductive approach must be the stepping-stone of such a methodological approach.
The urgency of utilizing COVID-19 biospecimens for research in the heart of the global pandemic
Authors: Osman Iman , Cotzia Paolo , Moran Una , Donnelly Douglas , Arguelles-Grande Carolina , Mendoza Sandra , Moreira Andre 
Published: June 2020

AbstractThe outbreak of the novel coronavirus disease 2019 (COVID-19) and consequent social distancing practices have disrupted essential clinical research functions worldwide. Ironically, this coincides with an immediate need for research to comprehend the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the pathology of COVID-19. As the global crisis has already led to over 15,000 deaths out of 175,000 confirmed cases in New York City and Nassau County, NY alone, it is increasingly urgent to collect patient biospecimens linked to active clinical follow up. However, building a COVID-19 biorepository amidst the active pandemic is a complex and delicate task. To help facilitate rapid, robust, and regulated research on this novel virus, we report on the successful model implemented by New York University Langone Health (NYULH) within days of outbreak in the most challenging hot spot of infection globally. Using an amended institutional biobanking protocol, these efforts led to accrual of 11,120 patients presenting for SARS-CoV-2 testing, 4267 (38.4%) of whom tested positive for COVID-19. The recently reported genomic characterization of SARS-CoV-2 in the New York City Region, which is a crucial development in tracing sources of infection and asymptomatic spread of the novel virus, is the first outcome of this effort. While this growing resource actively supports studies of the New York outbreak in real time, a worldwide effort is necessary to build a collective arsenal of research tools to deal with the global crisis now, and to exploit the virus’s biology for translational innovation that outlasts humanity’s current dilemma.
Exploration of anti-inflammatory mechanism of forsythiaside A and forsythiaside B in CuSO4-induced inflammation in zebrafish by metabolomic and proteomic analyses
Authors: Gong Lihong , Yu Linyuan , Gong Xiaohong , Wang Cheng , Hu Naihua , Dai Xuyang , Peng Cheng , Li Yunxia 
Published: June 2020

AbstractBackgroundInflammation is a general pathological phenomenon during severe disturbances to the homeostasis. Forsythiaside A (FA) and forsythiaside B (FB), isolated from the dried fruit ofForsythia suspensa(Thunb.) Vahl, are phenylethanoid compounds that show a significant anti-inflammatory effect. However, the properties and therapeutic mechanisms of this effect have not yet been systematically elucidated.MethodsIn this study, the anti-inflammatory effects of FA and FB were investigated in CuSO4-induced inflammation in zebrafish larvae. Intracellular generation of reactive oxygen species (ROS) and nitric oxide (NO) was investigated using fluorescence probes. Metabolomic and proteomic analyses using liquid chromatography-mass spectrometry were carried out to identify the expressions of metabolites and proteins associated with the anti-inflammatory mechanism of FA and FB. Quantitative polymerase chain reaction (PCR) was performed to detect the progressive changes in gene expression.ResultsFA and FB inhibited neutrophils migration to the damaged neuromasts and remarkably reduced CuSO4-induced ROS and NO generation in zebrafish larvae. Metabolomic analysis pointed to the involvement of nicotinate and nicotinamide metabolism, energy metabolism, pyrimidine metabolism, and purine metabolism. Proteomic analysis identified 146 differentially expressed proteins between the control and model groups. These included collagen [collagen type II alpha 1b precursor (col2a1b), collagen alpha-2(IX) chain precursor (col9a2), collagen type IX alpha I precursor (col9a1b)], nucleoside diphosphate kinase 3 isoform X1 (Nme3), WD repeat-containing protein 3 (Wdr3), and 28S ribosomal protein S7 mitochondrial precursor (Mrps7). FA and FB were shown to reverse the abnormal expressions of potential metabolite and protein biomarkers and alleviate CuSO4-induced damage to the neuromasts in the zebrafish lateral line.ConclusionsOur results indicate that FA and FB possess remarkable anti-inflammatory properties, protecting against CuSO4-induced neuromasts damage in zebrafish larvae. The results also suggest a multi-component and multi-regulatory therapeutic mechanism for FA and FB.
Role of immune cells in the removal of deleterious senescent cells
Authors: Kale Abhijit , Sharma Amit , Stolzing Alexandra , Desprez Pierre-Yves , Campisi Judith 
Published: June 2020

AbstractCellular senescence is an essentially irreversible arrest of cell proliferation coupled to a complex senescence-associated secretory phenotype (SASP). The senescence arrest prevents the development of cancer, and the SASP can promote tissue repair. Recent data suggest that the prolonged presence of senescent cells, and especially the SASP, could be deleterious, and their beneficial effects early in life can become maladaptive such that they drive aging phenotypes and pathologies late in life. It is therefore important to develop strategies to eliminate senescent cells. There are currently under development or approved several immune cell-based therapies for cancer, which could be redesigned to target senescent cells. This review focuses on this possible use of immune cells and discusses how current cell-based therapies could be used for senescent cell removal.
Advances in blood–brain barrier modeling in microphysiological systems highlight critical differences in opioid transport due to cortisol exposure
Authors: Brown Jacquelyn A. , Faley Shannon L. , Shi Yajuan , Hillgren Kathleen M. , Sawada Geri A. , Baker Thomas K. , Wikswo John P. , Lippmann Ethan S. 
Published: June 2020

Abstract
Background
The United States faces a national crisis involving opioid medications, where currently more than 130 people die every day. To combat this epidemic, a better understanding is needed of how opioids penetrate into the central nervous system (CNS) to facilitate pain relief and, potentially, result in addiction and/or misuse. Animal models, however, are a poor predictor of blood–brain barrier (BBB) transport and CNS drug penetration in humans, and many traditional 2D cell culture models of the BBB and neurovascular unit have inadequate barrier function and weak or inappropriate efflux transporter expression. Here, we sought to better understand opioid transport mechanisms using a simplified microfluidic neurovascular unit (NVU) model consisting of human brain microvascular endothelial cells (BMECs) co-cultured with astrocytes.

Methods
Human primary and induced pluripotent stem cell (iPSC)-derived BMECs were incorporated into a microfluidic NVU model with several technical improvements over our previous design. Passive barrier function was assessed by permeability of fluorescent dextrans with varying sizes, and P-glycoprotein function was assessed by rhodamine permeability in the presence or absence of inhibitors; quantification was performed with a fluorescent plate reader. Loperamide, morphine, and oxycodone permeability was assessed in the presence or absence of P-glycoprotein inhibitors and cortisol; quantification was performed with mass spectrometry.

Results
We first report technical and methodological optimizations to our previously described microfluidic model using primary human BMECs, which results in accelerated barrier formation, decreased variability, and reduced passive permeability relative to Transwell models. We then demonstrate proper transport and efflux of loperamide, morphine, and oxycodone in the microfluidic NVU containing BMECs derived from human iPSCs. We further demonstrate that cortisol can alter permeability of loperamide and morphine in a divergent manner.

Conclusions
We reveal a novel role for the stress hormone cortisol in modulating the transport of opioids across the BBB, which could contribute to their abuse or overdose. Our updated BBB model represents a powerful tool available to researchers, clinicians, and drug manufacturers for understanding the mechanisms by which opioids access the CNS.
Should autism spectrum disorder be considered part of CHARGE syndrome? A cross-sectional study of 46 patients
Authors: Abadie Véronique , Hamiaux Priscilla , Ragot Stéphanie , Legendre Marine , Malecot Gaelle , Burtin Alexia , Attie-Bitach Tania , Lyonnet Stanislas , Bilan Frédéric , Gilbert-Dussardier Brigitte , Vaivre-Douret Laurence 
Published: June 2020

Abstract
Background
Behavioral problems are an important issue for people with CHARGE syndrome. The similarity of their behavioral traits with those of people with autism raises questions. In a large national cross-sectional study, we used specific standardized tools for diagnosing autism (Autism Diagnostic Interview-Revised and Diagnostic and Statistical Manual of Mental Disorders, 5th edition, DSM-5) and evaluating behavioral disorders (Developmental Behavior Checklist-Parents, DBC-P) to investigate a series of individuals with CHARGE syndrome, defined by Verloes’s criteria. We evaluated their adaptive functioning level and sensory particularities and extracted several data items from medical files to assess as potential risk factors for autism and/or behavioral disorders.

Results
We investigated 64 individuals with CHARGE syndrome (35 females; mean age 10.7 years, SD 7.1 years). Among 46 participants with complete results for the Autism Diagnostic Interview-Revised (ADI-R), 13 (28%) had a diagnosis of autism according to the ADI-R, and 25 (54%) had a diagnosis of autism spectrum disorder (ASD) according to the DSM-5 criteria. The frequency of autistic traits in the entire group was a continuum. We did not identify any risk factor for ASD but found a negative correlation between the ADI-R score and adaptive functioning level. Among 48 participants with data for the DBC-P, 26 (55%) had behavioral disorders, which were more frequent in patients with radiological brain anomalies, impaired adaptive functioning, later independent walking, and more sensory particularities.

Conclusions
ASD should be considered to be an independent risk requiring early screening and management in children born with CHARGE syndrome.