bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the burden of dengue and the impact of release of wMel Wolbachia-infected mosquitoes in Indonesia: a modelling study
Authors: O’Reilly Kathleen M. , Hendrickx Emilie , Kharisma Dinar D. , Wilastonegoro Nandyan N. , Carrington Lauren B. , Elyazar Iqbal R. F. , Kucharski Adam J. , Lowe Rachel , Flasche Stefan , Pigott David M. , Reiner Robert C. , Edmunds W. John , Hay Simon I. , Yakob Laith , Shepard Donald S. , Brady Oliver J. 
Published: September 2019

AbstractBackgroundWolbachia-infected mosquitoes reduce dengue virus transmission, and city-wide releases in Yogyakarta city, Indonesia, are showing promising entomological results. Accurate estimates of the burden of dengue, its spatial distribution and the potential impact ofWolbachiaare critical in guiding funder and government decisions on its future wider use.MethodsHere, we combine multiple modelling methods for burden estimation to predict national case burden disaggregated by severity and map the distribution of burden across the country using three separate data sources. An ensemble of transmission models then predicts the estimated reduction in dengue transmission following a nationwide roll-out of wMelWolbachia.ResultsWe estimate that 7.8 million (95% uncertainty interval [UI] 1.8–17.7 million) symptomatic dengue cases occurred in Indonesia in 2015 and were associated with 332,865 (UI 94,175–754,203) lost disability-adjusted life years (DALYs). The majority of dengue’s burden was due to non-severe cases that did not seek treatment or were challenging to diagnose in outpatient settings leading to substantial underreporting. Estimated burden was highly concentrated in a small number of large cities with 90% of dengue cases occurring in 15.3% of land area. Implementing a nationwideWolbachiapopulation replacement programme was estimated to avert 86.2% (UI 36.2–99.9%) of cases over a long-term average.ConclusionsThese results suggest interventions targeted to the highest burden cities can have a disproportionate impact on dengue burden. Area-wide interventions, such asWolbachia, that are deployed based on the area covered could protect people more efficiently than individual-based interventions, such as vaccines, in such dense environments.
Engineering Pseudomonas putida for isoprenoid production by manipulating endogenous and shunt pathways supplying precursors
Authors: Hernandez-Arranz Sofía , Perez-Gil Jordi , Marshall-Sabey Dominic , Rodriguez-Concepcion Manuel 
Published: September 2019

Abstract

Background
The soil bacterium Pseudomonas putida is a promising platform for the production of industrially valuable natural compounds. In the case of isoprenoids, the availability of biosynthetic precursors is a major limiting factor. In P. putida and most other bacteria, these precursors are produced from pyruvate and glyceraldehyde 3-phosphate by the methylerythritol 4-phosphate (MEP) pathway, whereas other bacteria synthesize the same precursors from acetyl-CoA using the unrelated mevalonate (MVA) pathway.

Results
Here we explored different strategies to increase the supply of isoprenoid precursors in P. putida cells using lycopene as a read-out. Because we were not aiming at producing high isoprenoid titers but were primarily interested in finding ways to enhance the metabolic flux to isoprenoids, we engineered the well-characterized P. putida strain KT2440 to produce low but detectable levels of lycopene under conditions in which MEP pathway steps were not saturated. Then, we compared lycopene production in cells expressing the Myxococcus xanthus MVA pathway genes or endogenous MEP pathway genes (dxs, dxr, idi) under the control of IPTG-induced and stress-regulated promoters. We also tested a shunt pathway producing isoprenoid precursors from ribulose 5-phosphate using a mutant version of the Escherichia coli ribB gene.

Conclusions
The most successful combination led to a 50-fold increase in lycopene levels, indicating that P. putida can be successfully engineered to substantially increase the supply of metabolic substrates for the production of industrially valuable isoprenoids.
PD-1 and PD-L1 correlated gene expression profiles and their association with clinical outcomes of breast cancer
Authors: Jiang Cui , Cao SunRun , Li Na , Jiang Lei , Sun Tao 
Published: September 2019

Abstract

Background
Immunotherapies that targeting programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have obtained prominent success in breast cancer (BC). However, not all the patients benefit from the antibody therapy. This study aimed to identify PD-1/PD-L1 correlated genes and pathways as well as investigate their potential as prognostic marker in BC.

Materials and methods
By analysing transcriptional data of BC from TCGA, we identified PD-1 and PD-L1 correlated genes by WGCNA analysis and explored the biological process as well as pathways they enriched. Co-expression analysis were performed for PD-1/PD-L1 with immune infiltration and checkpoints. The prognostic value of PD-1 and PD-L1 were also investigated.

Results
PD-1 and PD-L1 expression showed significant difference in different molecular subtypes and stages. PD-1 correlated genes enriched in T cell activation, lymphocyte activation, leukocyte migration while PD-L1 correlated genes demonstrated enrichment including T cell apoptotic process, tolerance induction and cytolysis. Immune infiltration analysis suggested that PD-1 and PD-L1 were related with Neutrophils (r = 0.65, r = 0.48) and Fibroblasts (r = 0.59, r = 0.47). For immune checkpoints analysis, PD-1 was associated with HLA-A (r = 0.804) and INPP5D (r = 0.782) while PD-L1 correlated with CTLA4 (r = 0.843) and CD27 (r = 0.823). PD-1 was associated favorable survival of BC (HR = 0.67, P = 0.012) while PD-L1 did not demonstrate significant association with BC prognosis (HR = 0.85, P = 0.313).

Conclusion
PD-1 and PD-L1 correlated genes participated in biological process including T cell activation, lymphocyte activation, leukocyte migration, T cell apoptotic process, tolerance induction and cytolysis. PD-1/PD-L1 expression also demonstrated relation with immune infiltration and immune checkpoints. High PD-1 expression predicted better survival of breast cancer patients.
Nonlytic exocytosis of Cryptococcus neoformans from neutrophils in the brain vasculature
Authors: Yang Xiaofan , Wang Huijuan , Hu Fan , Chen Xichen , Zhang Mingshun 
Published: September 2019

Abstract

Background
Cryptococcus neoformans (C. neoformans) is an encapsulated budding yeast that causes life-threatening meningoencephalitis in immunocompromised individuals, especially those with acquired immunodeficiency syndrome (AIDS). To cause meningoencephalitis, C. neoformans circulating in the bloodstream must first be arrested in the brain microvasculature. Neutrophils, the most abundant phagocytes in the bloodstream and the first leukocytes to be recruited to an infection site, can ingest C. neoformans. Little is known about how neutrophils interact with arrested fungal cells in the brain microvasculature.

Methods
A blood-brain barrier (BBB) in vitro model was established. The interactions between neutrophils adhering to brain endothelial cells and fungi were observed under a live cell imaging microscope. A flow cytometry assay was developed to explore the mechanisms. Immunofluorescence staining of brain tissues was utilized to validate the in vitro phenomena.

Results
Using real-time imaging, we observed that neutrophils adhered to a monolayer of mouse brain endothelial cells could expel ingested C. neoformans without lysis of the neutrophils or fungi in vitro, demonstrating nonlytic exocytosis of fungal cells from neutrophils. Furthermore, nonlytic exocytosis of C. neoformans from neutrophils was influenced by either the fungus (capsule and viability) or the neutrophil (phagosomal pH and actin polymerization). Moreover, nonlytic exocytosis of C. neoformans from neutrophils was recorded in brain tissue.

Conclusion
These results highlight a novel function by which neutrophils extrude C. neoformans in the brain vasculature.

Graphical abstract
CXCL1-LCN2 paracrine axis promotes progression of prostate cancer via the Src activation and epithelial-mesenchymal transition
Authors: Lu Yongning , Dong Baijun , Xu Fan , Xu Yunze , Pan Jiahua , Song Jiajia , Zhang Jin , Huang Yiran , Xue Wei 
Published: September 2019

Abstract

Background
Mechanisms driving the progression of castration-resistant prostate cancer are believed to relate substantially to the tumor microenvironment. However, the cross-talks between tumor epithelial cell, stromal cells, and immune cells are yet to be fully elucidated. The present study aims to determine the role of chemokine and neutrophil derived cytokine paracrine axis in mediating the interaction between tumor cells, stromal myofibroblasts, and neutrophils in the tumor microenvironment of prostate cancer.

Methods
To identify myofibroblasts and neutrophil derived specific proteins affecting progression of prostate cancer, bioinformatics analyses were firstly performed in independent human prostate cancer gene expression data sets from the GEO data bank. Expression of stromal myofibroblasts secretory chemokine CXCL1 and neutrophil derived cytokine LCN2 was evaluated in prostate tissues via immunohistochemistry assay. We further investigated the effect of CXCL1 and LCN2 on prostate cancer using in vivo and in vitro models, and explored the underlying signal transduction pathways.

Results
A CXCL1-LCN2 paracrine network was confirmed in prostate cancer tissue samples, which was correlated with the biochemical recurrence of prostate cancer. Of note, CXCL1-LCN2 axis activates Src signaling, triggers the epithelial-mesenchymal transition (EMT), consequently promotes the migration of prostate cancer cells, leading to enhanced tumor metastasis.

Conclusions
Our findings may provide enhanced insight into the interactions of carcinoma-stromal cells and immune cells linked to prostate cancer progression, wherein CXCL1-LCN2 axis is a key contributor to prostate cancer cells migration. These data indicate tumor microenvironment and Src signaling pathway may be potential therapeutic targets of prostate cancer treatment.
Biofluid quantification of TWEAK/Fn14 axis in combination with a selected biomarker panel improves assessment of prostate cancer aggressiveness
Authors: Ruiz-Plazas Xavier , Rodríguez-Gallego Esther , Alves Marta , Altuna-Coy Antonio , Lozano-Bartolomé Javier , Portero-Otin Manel , García-Fontgivell Joan Francesc , Martínez-González Salomé , Segarra José , Chacón Matilde R. 
Published: September 2019

AbstractBackgroundConventional clinical biomarkers cannot accurately differentiate indolent from aggressive prostate cancer (PCa). We investigated the usefulness of a biomarker panel measured exclusively in biofluids for assessment of PCa aggressiveness.MethodsWe collected biofluid samples (plasma/serum/semen/post-prostatic massage urine) from 98 patients that had undergone radical prostatectomy. Clinical biochemistry was performed and several cytokines/chemokines including soluble(s) TWEAK, sFn14, sCD163, sCXCL5 and sCCL7 were quantified by ELISA in selected biofluids. Also, the expression ofKLK2,KLK3,Fn14,CD163,CXCR2andCCR3was quantified by real-time PCR in semen cell sediment. Univariate, logistic regression, and receiver operating characteristic (ROC) analyses were used to assess the predictive ability of the selected biomarker panel in conjunction with clinical and metabolic variables for the evaluation of PCa aggressiveness.ResultsTotal serum levels of prostate-specific antigen (PSA), semen levels of sTWEAK, fasting glycemia and mRNA levels ofFn14,KLK2,CXCR2andCCR3in semen cell sediment constituted a panel of markers that was significantly different between patients with less aggressive tumors [International Society of Urological Pathology (ISUP) grade I and II] and those with more aggressive tumors (ISUP grade III, IV and V). ROC curve analysis showed that this panel could be used to correctly classify tumor aggressiveness in 90.9% of patients. Area under the curve (AUC) analysis revealed that this combination was more accurate [AUC = 0.913 95% confidence interval (CI) 0.782–1] than a classical non-invasive selected clinical panel comprising age, tumor clinical stage (T-classification) and total serum PSA (AUC = 0.721 95% CI 0.613–0.830).ConclusionsTWEAK/Fn14 axis in combination with a selected non-invasive biomarker panel, including conventional clinical biochemistry, can improve the predictive power of serum PSA levels and could be used to classify PCa aggressiveness.
The reliability and validity of the Patient Health Questionnaire-9 (PHQ-9) and PHQ-2 in patients with infertility
Authors: Maroufizadeh Saman , Omani-Samani Reza , Almasi-Hashiani Amir , Amini Payam , Sepidarkish Mahdi 
Published: September 2019

Abstract

Background
Depression in patients with infertility often goes undiagnosed and untreated. The Patient Health Questionnaire-9 (PHQ-9) and its ultra-brief version (i.e. PHQ-2) are widely used measures of depressive symptoms. These scales have not been validated in patients with infertility. The aim of the present study was to examine the reliability and validity of the PHQ-9 and PHQ-2 in patients with infertility.

Methods
In this cross-sectional study, a total of 539 patients with infertility from a referral infertility clinic in Tehran, Iran completed the PHQ-9, along with other relevant scales: the WHO-five Well-being Index (WHO-5), the Hospital Anxiety and Depression Scale (HADS), and the Generalized Anxiety Disorder-7 (GAD-7). Factor structure and internal consistency of PHQ-9 were examined via confirmatory factor analysis (CFA) and Cronbach’s alpha, respectively. Convergent validity was evaluated by relationship with WHO-5, HADS and GAD-7.

Results
The mean total PHQ-9 and PHQ-2 scores were 8.47 ± 6.17 and 2.42 ± 1.86, respectively, and using a cut-off value of 10 (for PHQ-9) and 3 (for PHQ-2), the prevalence of depressive symptoms was 38.6 and 43.6%, respectively. The Cronbach’s alphas for PHQ-9 and PHQ-2 were, respectively, 0.851 and 0.767, indicating good internal consistency. The CFA results confirmed the one-factor model of the PHQ-9 (χ2/df = 4.29; CFI = 0.98; RMSEA = 0.078 and SRMR = 0.044). Both PHQ-9 and PHQ-2 showed moderate to strong correlation with the measures of WHO-5, HADS-depression, HADS-anxiety, and the GAD-7, confirming convergent validity. In univariate analysis, female sex, long infertility duration, and unsuccessful treatment were significantly associated with depression symptoms.

Conclusion
Both PHQ-9 and PHQ-2 are brief and easy to use measures of depressive symptoms with good psychometric properties that appear suitable for routine use in patients with infertility.
Endoscopic hemostasis followed by preventive transarterial embolization in high-risk patients with bleeding peptic ulcer: 5-year experience
Authors: Kaminskis Aleksejs , Ivanova Patricija , Kratovska Aina , Ponomarjova Sanita , Ptašņuka Margarita , Demičevs Jevgenijs , Demičeva Renate , Boka Viesturs , Pupelis Guntars 
Published: September 2019

AbstractBackgroundUpper gastrointestinal bleeding (UGIB) due to peptic ulcer disease is one of the leading causes of death in patients with non-variceal bleeding, resulting in up to 10% mortality rate, and the patient group at high risk of rebleeding (Forrest IA, IB, and IIA) often requires additional therapy after endoscopic hemostasis. Preventive transarterial embolization (P-TAE) after endoscopic hemostasis was introduced in our institution in 2014. The aim of the study is an assessment of the intermediate results of P-TAE following primary endoscopic hemostasis in patients with serious comorbid conditions and high risk of rebleeding.MethodsDuring the period from 2014 to 2018, a total of 399 patients referred to our institution with a bleeding peptic ulcer, classified as type Forrest IA, IB, or IIA with the Rockall score ≥ 5, after endoscopic hemostasis was prospectively included in two groups—P-TAE group and control group, where endoscopy alone (EA) was performed. The P-TAE patients underwent flow-reducing left gastric artery or gastroduodenal artery embolization according to the ulcer type. The rebleeding rate, complications, frequency of surgical interventions, transfused packed red blood cells (PRBC), amount of fresh frozen plasma (FFP), and mortality rate were analyzed.ResultsFrom 738 patients with a bleeding peptic ulcer, 399 were at high risk for rebleeding after endoscopic hemostasis. From this cohort, 58 patients underwent P-TAE, and 341 were allocated to the EA. A significantly lower rebleeding rate was observed in the P-TAE group, 3.4% vs. 16.2% in the EA group;p= 0.005. The need for surgical intervention reached 10.3% vs. 20.6% in the P-TAE and EA groups accordingly;p= 0.065. Patients that underwent P-TAE required less FFP, 1.3 unit vs. 2.6 units in EA;p= 0.0001. The mortality rate was similar in groups with a tendency to decrease in the P-TAE group, 5.7% vs. 8.5% in EA;p= 0.417.ConclusionP-TAE is a feasible and safe procedure, and it may reduce the rebleeding rate and the need for surgical intervention in patients with a bleeding peptic ulcer when the rebleeding risk remains high after primary endoscopic hemostasis.
Skeletonisation contributing to a reduction of sternal wound complications: a retrospective study in OPCAB patients
Authors: Van den Eynde Jef , Heeren Astrid , Szecel Delphine , Meuris Bart , Jacobs Steven , Verbrugghe Peter , Oosterlinck Wouter 
Published: September 2019

Abstract

Background
Sternal wound complications (SWC) are a rare but potentially life-threatening complication after coronary artery bypass grafting (CABG) surgery. Especially the use of bilateral IMA (BIMA) grafts as opposed to single IMA (SIMA) grafts is associated with an increased risk of SWC. Skeletonised harvesting has been proposed to reduce this risk. The purpose of this study was to retrospectively investigate the effect of skeletonisation on SWC after off-pump coronary artery bypass grafting (OPCAB) in a centre with a high volume of off-pump procedures and high frequencies of BIMA.

Methods
From January 2010 to November 2016, 1900 consecutive patients underwent OPCAB surgery at the University Hospitals of Leuven. The first group (n = 1487) received non-skeletonised IMA grafts, whereas the second group (n = 413) received skeletonised grafts. Optimal wound management was pursued in all patients. A new four-grade classification for SWC was developed. Incidence and grade of SWC as well as overall survival were assessed.

Results
Analysis of diabetic patients showed a lower incidence of SWC in the skeletonised (12/141, 8.5%) compared to the non-skeletonised group (82/414, 19.8%) [odds ratio 0.46, 95% confidence interval (0.23;0.88), p = 0.019] as well as a lower grade [0.45 (0.24;0.871), p = 0.018]. There was no significant effect on overall survival [0.67 (0.19;2.32), p = 0.529]. Subanalysis of this population revealed that the observed effects were most prominent in patients receiving BIMA grafts, with 6/56 (10.7%) SWC in the skeletonised and 62/252 (24.6%) in the non-skeletonised group [0.37 (0.15;0.90), p = 0.028 for incidence], as well as a lower grade [0.36 (0.15;0.88), p = 0.025]. These advantages were not significant in diabetic patients receiving SIMA grafts nor in the full study population.

Conclusions
This study, using a more sensitive classification of SWC, shows in a large group of patients that, in combination with optimized wound management, the skeletonisation technique is associated with a clear reduction in the incidence and grade of SWC in diabetic patients receiving BIMA grafts. This encourages the extension of BIMA use in OPCAB to this risk population.
Gingival metastasis of a mediastinal pulmonary sarcomatoid carcinoma: a case report
Authors: Qin Zhonghua , Huang Bin , Yu Guiping , Zheng Yongqiang , Zhao Ke 
Published: September 2019

AbstractBackgroundPulmonary sarcomatoid carcinoma (PSC) is a rare malignancy with both epithelial and sarcoma components, and high tumor metastasis potential.Case presentationA 63-year-old male patient had a tumor in the right posterior mediastinum, and was eventually diagnosed with PSC and gingival metastasis. The patient underwent thoracoscopic right upper pneumonectomy with lymph node dissections, and the subsequent gingival biopsy revealed a metastatic PSC. The immunohistochemistry revealed that both PSC site tissues were positive for vimentin, CKAE1/AE3 and Ki-67. The patient received radiotherapy and chemotherapy after surgery, and deceased two months later due to systemic tumor metastases.ConclusionPSC metastasis is variable, and leads to diagnostic dilemma or erroneous diagnosis. A differential diagnosis can help to distinguish it from gingival cancer.
A comparison of automatic cell identification methods for single-cell RNA sequencing data
Authors: Abdelaal Tamim , Michielsen Lieke , Cats Davy , Hoogduin Dylan , Mei Hailiang , Reinders Marcel J. T. , Mahfouz Ahmed 
Published: September 2019

Abstract

Background
Single-cell transcriptomics is rapidly advancing our understanding of the cellular composition of complex tissues and organisms. A major limitation in most analysis pipelines is the reliance on manual annotations to determine cell identities, which are time-consuming and irreproducible. The exponential growth in the number of cells and samples has prompted the adaptation and development of supervised classification methods for automatic cell identification.

Results
Here, we benchmarked 22 classification methods that automatically assign cell identities including single-cell-specific and general-purpose classifiers. The performance of the methods is evaluated using 27 publicly available single-cell RNA sequencing datasets of different sizes, technologies, species, and levels of complexity. We use 2 experimental setups to evaluate the performance of each method for within dataset predictions (intra-dataset) and across datasets (inter-dataset) based on accuracy, percentage of unclassified cells, and computation time. We further evaluate the methods’ sensitivity to the input features, number of cells per population, and their performance across different annotation levels and datasets. We find that most classifiers perform well on a variety of datasets with decreased accuracy for complex datasets with overlapping classes or deep annotations. The general-purpose support vector machine classifier has overall the best performance across the different experiments.

Conclusions
We present a comprehensive evaluation of automatic cell identification methods for single-cell RNA sequencing data. All the code used for the evaluation is available on GitHub (https://github.com/tabdelaal/scRNAseq_Benchmark). Additionally, we provide a Snakemake workflow to facilitate the benchmarking and to support the extension of new methods and new datasets.
scBFA: modeling detection patterns to mitigate technical noise in large-scale single-cell genomics data
Authors: Li Ruoxin , Quon Gerald 
Published: September 2019

Abstract
Technical variation in feature measurements, such as gene expression and locus accessibility, is a key challenge of large-scale single-cell genomic datasets. We show that this technical variation in both scRNA-seq and scATAC-seq datasets can be mitigated by analyzing feature detection patterns alone and ignoring feature quantification measurements. This result holds when datasets have low detection noise relative to quantification noise. We demonstrate state-of-the-art performance of detection pattern models using our new framework, scBFA, for both cell type identification and trajectory inference. Performance gains can also be realized in one line of R code in existing pipelines.