bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of MFGE8 and KLK5/7 as mediators of breast tumorigenesis and resistance to COX-2 inhibition
Authors: Tian Jun , Wang Vivian , Wang Ni , Khadang Baharak , Boudreault Julien , Bakdounes Khldoun , Ali Suhad , Lebrun Jean-Jacques 
Published: February 2021

Abstract
Background
Cyclooxygenase 2 (COX-2) promotes stemness in triple negative breast cancer (TNBC), highlighting COX-2 as a promising therapeutic target in these tumors. However, to date, clinical trials using COX-2 inhibitors in breast cancer only showed variable patient responses with no clear significant clinical benefits, suggesting underlying molecular mechanisms contributing to resistance to COX-2 inhibitors.

Methods
By combining in silico analysis of human breast cancer RNA-seq data with interrogation of public patient databases and their associated transcriptomic, genomic, and clinical profiles, we identified COX-2 associated genes whose expression correlate with aggressive TNBC features and resistance to COX-2 inhibitors. We then assessed their individual contributions to TNBC metastasis and resistance to COX-2 inhibitors, using CRISPR gene knockout approaches in both in vitro and in vivo preclinical models of TNBC.

Results
We identified multiple COX-2 associated genes (TPM4, RGS2, LAMC2, SERPINB5, KLK7, MFGE8, KLK5, ID4, RBP1, SLC2A1) that regulate tumor lung colonization in TNBC. Furthermore, we found that silencing MFGE8 and KLK5/7 gene expression in TNBC cells markedly restored sensitivity to COX-2 selective inhibitor both in vitro and in vivo.

Conclusions
Together, our study supports the establishment and use of novel COX-2 inhibitor-based combination therapies as future strategies for TNBC treatment.
Coexistence of the Entner–Doudoroff and Embden–Meyerhof–Parnas pathways enhances glucose consumption of ethanol-producing Corynebacterium glutamicum
Authors: Jojima Toru , Igari Takafumi , Noburyu Ryoji , Watanabe Akira , Suda Masako , Inui Masayuki 
Published: February 2021

Abstract
Background
It is interesting to modify sugar metabolic pathways to improve the productivity of biocatalysts that convert sugars to value-added products. However, this attempt often fails due to the tight control of the sugar metabolic pathways. Recently, activation of the Entner–Doudoroff (ED) pathway in Escherichia coli has been shown to enhance glucose consumption, though the mechanism underlying this phenomenon is poorly understood. In the present study, we investigated the effect of a functional ED pathway in metabolically engineered Corynebacterium glutamicum that metabolizes glucose via the Embden–Meyerhof–Parnas (EMP) pathway to produce ethanol under oxygen deprivation. This study aims to provide further information on metabolic engineering strategies that allow the Entner–Doudoroff and Embden–Meyerhof–Parnas pathways to coexist.

Results
Three genes (zwf, edd, and eda) encoding glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydratase, and 2-keto-3-deoxy-6-phosphogluconate aldolase from Zymomonas mobilis were expressed in a genetically modified strain, C. glutamicum CRZ2e, which produces pyruvate decarboxylase and alcohol dehydrogenase from Z. mobilis. A 13C-labeling experiment using [1-13C] glucose indicated a distinctive 13C distribution of ethanol between the parental and the ED-introduced strains, which suggested an alteration of carbon flux as a consequence of ED pathway introduction. The ED-introduced strain, CRZ2e-ED, consumed glucose 1.5-fold faster than the parental strain. A pfkA deletion mutant of CRZ2e-ED (CRZ2e-EDΔpfkA) was also constructed to evaluate the effects of EMP pathway inactivation, which showed an almost identical rate of glucose consumption compared to that of the parental CRZ2e strain. The introduction of the ED pathway did not alter the intracellular NADH/NAD+ ratio, whereas it resulted in a slight increase in the ATP/ADP ratio. The recombinant strains with simultaneous overexpression of the genes for the EMP and ED pathways exhibited the highest ethanol productivity among all C. glutamicum strains ever constructed.

Conclusions
The increased sugar consumption observed in ED-introduced strains was not a consequence of cofactor balance alterations, but rather the crucial coexistence of two active glycolytic pathways for enhanced glucose consumption. Coexistence of the ED and EMP pathways is a good strategy for improving biocatalyst productivity even when NADPH supply is not a limiting factor for fermentation.
Overexpression of vesicle-associated membrane protein PttVAP27-17 as a tool to improve biomass production and the overall saccharification yields in Populus trees
Authors: Gandla Madhavi Latha , Mähler Niklas , Escamez Sacha , Skotare Tomas , Obudulu Ogonna , Möller Linus , Abreu Ilka N. , Bygdell Joakim , Hertzberg Magnus , Hvidsten Torgeir R. , Moritz Thomas , Wingsle Gunnar , Trygg Johan , Tuominen Hannele , Jönsson Leif J. 
Published: February 2021

AbstractBackgroundBioconversion of wood into bioproducts and biofuels is hindered by the recalcitrance of woody raw material to bioprocesses such as enzymatic saccharification. Targeted modification of the chemical composition of the feedstock can improve saccharification but this gain is often abrogated by concomitant reduction in tree growth.ResultsIn this study, we report on transgenic hybrid aspen (Populus tremula×tremuloides) lines that showed potential to increase biomass production both in the greenhouse and after 5 years of growth in the field. The transgenic lines carried an overexpression construct forPopulus tremula×tremuloidesvesicle-associated membrane protein (VAMP)-associated proteinPttVAP27-17that was selected from a gene-mining program for novel regulators of wood formation. Analytical-scale enzymatic saccharification without any pretreatment revealed for all greenhouse-grown transgenic lines, compared to the wild type, a 20–44% increase in the glucose yield per dry weight after enzymatic saccharification, even though it was statistically significant only for one line. The glucose yield after enzymatic saccharification with a prior hydrothermal pretreatment step with sulfuric acid was not increased in the greenhouse-grown transgenic trees on a dry-weight basis, but increased by 26–50% when calculated on a whole biomass basis in comparison to the wild-type control. Tendencies to increased glucose yields by up to 24% were present on a whole tree biomass basis after acidic pretreatment and enzymatic saccharification also in the transgenic trees grown for 5 years on the field when compared to the wild-type control.ConclusionsThe results demonstrate the usefulness of gene-mining programs to identify novel genes with the potential to improve biofuel production in tree biotechnology programs. Furthermore, multi-omic analyses, including transcriptomic, proteomic and metabolomic analyses, performed here provide a toolbox for future studies on the function of VAP27 proteins in plants.
Assessing the sweet sorghum-based ethanol potential on saline–alkali land with DSSAT model and LCA approach
Authors: Fu Jingying , Yan Xiaoxi , Jiang Dong 
Published: February 2021

Abstract
Background
The key problem of non-grain energy plants’ scale development is how to estimate the potential of GHG emission reduction accurately and scientifically. This study presents a method coupled DSSAT (the Decision Support System for Agrotechnology Transfer) and the life cycle assessment (LCA) method to simulate the spatial distribution of sweet sorghum-based ethanol production potential on saline–alkali land. The GHG (greenhouse gas) emission mitigation and net energy gains of the whole life of sweet sorghum-based ethanol production were then analyzed.

Results
The results of the case study in Dongying, Shandong Province, China showed that developing sweet sorghum-based ethanol on saline–alkali land had GHG emission mitigation and energy potentials. The LC-GHG emission mitigation potential of saline–alkali land in Dongying was estimated at 63.9 thousand t CO2 eq, equivalent to the carbon emission of 43.4 Kt gasoline. The LC-NEG potential was predicted at 5.02 PJ, equivalent to the caloric value of 109 Kt gasoline. On average, LC-GHG emission mitigation and LC-NEG were predicted at 55.09 kg CO2 eq/t ethanol and 4.33 MJ/kg ethanol, respectively.

Conclusions
The question of how to evaluate the potential of sweet sorghum-based ethanol development scientifically was solved primarily in this paper. The results will provide an important theoretical support for planning the bioenergy crops on saline–alkali land and develop the fuel ethanol industry.
Risk factors for mortality of diffuse alveolar hemorrhage in systemic lupus erythematosus: a systematic review and meta-analysis
Authors: Jiang Mengdi , Chen Ruxuan , Zhao Lidan , Zhang Xuan 
Published: February 2021

AbstractBackgroundDiffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). The current knowledge of the prognostic factors for SLE-associated DAH is controversial. This meta-analysis was undertaken to investigate the relevant risk factors for mortality in SLE-associated DAH.MethodsStudies were searched from PubMed, EMBASE, and Web of Science databases published up to May 27, 2020, and were selected or removed according to the inclusion and exclusion criteria. Two reviewers extracted data independently from the enrolled studies, and the odds ratios (OR) or the standardized mean difference (SMD) was utilized to identify and describe the prognostic factors for mortality.ResultsEight studies encompassing 251 patients with SLE-associated DAH were included in the meta-analysis. No significant publication bias was shown. Age at the diagnosis of DAH (SMD = 0.35, 95% confidence interval (CI) (0.08, 0.61),P = 0.01,I2 = 0.0%) was found to be an independent risk factor of mortality. Longer lupus disease duration (SMD = 0.28, 95% CI (0.01, 0.55),P = 0.042,I2 = 0.0%), concurrent infection (OR = 2.77, 95% CI (1.55, 4.95),P = 0.001,I2 = 37.5%), plasmapheresis treatment (OR = 1.96, 95% CI (1.04, 3.70),P = 0.038,I2 = 14.6%), and mechanical ventilation (OR = 6.11, 95% CI (3.27, 11.39),P < 0.0001,I2 = 23.3%) were also related to poor survival, whereas no noticeable relationships were revealed between survival and concurrent lupus nephritis (OR = 5.45, 95% CI (0.52, 56.95),P = 0.16,I2 = 58.4%) or treatment of cyclophosphamide (CTX) (OR = 0.74, 95% CI (0.16, 3.41),P = 0.70,I2 = 75.5%).ConclusionsOlder age at the diagnosis of DAH, longer disease duration of SLE, concurrent infection, plasmapheresis treatment, and mechanical ventilation were found related to increased mortality in patients with SLE-associated DAH according to our meta-analysis. However, due to limited studies with heterogeneity, these results should be interpreted cautiously. Notably, severe diseases rendered the requirement of plasmapheresis treatment and mechanical ventilation are themselves associated with poor outcome. Randomized trials of therapeutics are needed to determine the most efficacious strategies for SLE-associated DAH for better management of this life-threatening complication.
Bariatric surgery can acutely modulate ER-stress and inflammation on subcutaneous adipose tissue in non-diabetic patients with obesity
Authors: Ferraz-Bannitz Rafael , Welendorf Caroline Rossi , Coelho Priscila Oliveira , Salgado Wilson , Nonino Carla Barbosa , Beraldo Rebeca A. , Foss-Freitas Maria Cristina 
Published: February 2021

AbstractBackgroundBariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the most effective and durable treatment option for severe obesity. The mechanisms involving adipose tissue may be important to explain the effects of surgery.MethodsWe aimed to identify the genetic signatures of adipose tissue in patients undergoing RYGB. We evaluated 13 obese, non-diabetic patients (mean age 37 years, 100% women, Body mass index (BMI) 42.2 kg/m2) one day before surgery, 3 and 6 months (M) after RYGB.ResultsAnalysis of gene expression in adipose tissue collected at surgery compared with samples collected at 3 M and 6 M Post-RYGB showed that interleukins [Interleukin 6, Tumor necrosis factor-α(TNF-α), and Monocyte chemoattractant protein-1(MCP1)] and endoplasmic reticulum stress (ERS) genes [Eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) and Calreticulin (CALR)] decreased during the follow-up (P ≤ 0.01 for all). Otherwise, genes involved in energy homeostasis [Adiponectin and AMP-activated protein kinase (AMPK)], cellular response to oxidative stress [Sirtuin 1, Sirtuin 3, and Nuclear factor erythroid 2-related factor 2 (NRF2)], mitochondrial biogenesis [Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)] and amino acids metabolism [General control nonderepressible 2 (GCN2)] increased from baseline to all other time points evaluated (P ≤ 0.01 for all). Also, expression of Peroxisome proliferator-activated receptor gamma (PPARϒ) (adipogenesis regulation) was significantly decreased after RYGB (P < 0.05). Additionally, we observed that PGC1α, SIRT1 and AMPK strongly correlated to BMI at 3 M (P ≤ 0.01 for all), as well as ADIPOQ and SIRT1 to BMI at 6 M (P ≤ 0.01 for all).ConclusionsOur findings demonstrate that weight loss is associated with amelioration of inflammation and ERS and increased protection against oxidative stress in adipose tissue. These observations are strongly correlated with a decrease in BMI and essential genes that control cellular energy homeostasis, suggesting an adaptive process on a gene expression level during the caloric restriction and weight loss period after RYGB.Trial registrationCAAE: 73,585,317.0.0000.5440
Association between ventilatory efficiency, oxygen uptake, and Glittre-ADL test results in patients with chronic heart failure: a preliminary study
Authors: Olímpio Júnior Hebert , Lopes Agnaldo José , Guimarães Fernando Silva , da Cunha Chermont Sergio Luiz Soares Marcos , de Menezes Sara Lúcia Silveira 
Published: February 2021

Abstract
Objective
The Glittre-ADL test (GA-T) is a functional capacity test that stands out for encompassing multiple tasks similar to activities of daily living. As ventilatory efficiency is one of the variables valued in the prognosis of chronic heart failure (CHF), this study aimed to evaluate associations between functional capacity and ventilatory variables in patients with CHF during the GA-T.

Results
Eight patients with CHF and New York Heart Association (NYHA) functional classification II–III underwent the GA-T coupled with metabolic gas analysis to obtain data by means of telemetry. The median total GA-T time was 00:04:39 (00:03:29–00:05:53). Borg dyspnoea scale scores before and after the GA-T were 2 (0–9) and 3 (1–10), respectively (P = 0.011). The relationship between the regression slope relating minute ventilation to carbon dioxide output (VE/VCO2 slope) was correlated with the total GA-T time (rs = 0.714, P = 0.047) and Borg dyspnoea score (rs = 0.761, P = 0.028). The other ventilatory variables showed no significant correlations. Our results suggest that the total GA-T time can be applied to estimate the ventilatory efficiency of patients with CHF. Future studies may use the GA-T in conjunction with other functional capacity tests to guide the treatment plan and evaluate the prognosis.
Clinical characteristics and risk factors for cefaclor-induced immediate hypersensitivity: a retrospective observation at two university hospitals in Korea
Authors: Rhyou Hyo-In , Doo Go-Eun , Yoon Jiwon , Ha Chae-Yeon , Nam Hee-Joo , Woo Sung-Dae , Lee Youngsoo , Nam Young-Hee , Ye Young-Min 
Published: February 2021

Abstract
Background
Cefaclor, a second-generation oral cephalosporin, is widely prescribed to treat infectious diseases. Immediate hypersensitivity (HS) reactions to cefaclor have continuously been reported and are expected to increase with its greater use. This study aimed to investigate the clinical characteristics and risk factors of immediate HS to cefaclor over the most recent 5 years.

Methods
This retrospective study investigated 521 adverse drug reactions (ADRs) to cefaclor at pharmacovigilance centers at two tertiary hospitals from January 2014 to December 2018. In total, 459 patients with immediate HS to cefaclor were reviewed.

Results
A total of 459 cases of cefaclor immediate HS were included among 521 cefaclor ADRs, and anaphylaxis was recorded in 61.2%. Female sex (odds ratio 2.917, 95% confidence interval 2.397–3.550, P < 0.001), age under 65 years (4.225, 3.017–5.916, P < 0.001), hypertension (2.520, 1.875–3.388, P < 0.001), liver diseases (2.189, 1.208–3.967, P = 0.010), asthma (8.075, 5.301–12.302, P < 0.001), and concomitant use of nonsteroidal anti-inflammatory drugs (1.888, 1.554–2.294, P < 0.001) were significantly associated with cefaclor immediate HS.

Conclusions
Cefaclor was found to elicit high proportions of immediate HS and anaphylaxis. Physicians ought to be cautious with prescribing cefaclor to females, individuals with hypertension, liver diseases, or asthma, and patients taking nonsteroidal anti-inflammatory drugs.

Trial registration
This study was retrospectively registered.
Incorporating structural similarity into a scoring function to enhance the prediction of binding affinities
Authors: Ji Beihong , He Xibing , Zhang Yuzhao , Zhai Jingchen , Man Viet Hoang , Liu Shuhan , Wang Junmei 
Published: February 2021

AbstractIn this study, we developed a novel algorithm to improve the screening performance of an arbitrary docking scoring function by recalibrating the docking score of a query compound based on its structure similarity with a set of training compounds, while the extra computational cost is neglectable. Two popular docking methods, Glide and AutoDock Vina were adopted as the original scoring functions to be processed with our new algorithm and similar improvement performance was achieved. Predicted binding affinities were compared against experimental data from ChEMBL and DUD-E databases. 11 representative drug receptors from diverse drug target categories were applied to evaluate the hybrid scoring function. The effects of four different fingerprints (FP2, FP3, FP4, and MACCS) and the four different compound similarity effect (CSE) functions were explored. Encouragingly, the screening performance was significantly improved for all 11 drug targets especially when CSE = S4(S is the Tanimoto structural similarity) and FP2 fingerprint were applied. The average predictive index (PI) values increased from 0.34 to 0.66 and 0.39 to 0.71 for the Glide and AutoDock vina scoring functions, respectively. To evaluate the performance of the calibration algorithm in drug lead identification, we also imposed an upper limit on the structural similarity to mimic the real scenario of screening diverse libraries for which query ligands are general-purpose screening compounds and they are not necessarily structurally similar to reference ligands. Encouragingly, we found our hybrid scoring function still outperformed the original docking scoring function. The hybrid scoring function was further evaluated using external datasets for two systems and we found the PI values increased from 0.24 to 0.46 and 0.14 to 0.42 for A2AR and CFX systems, respectively. In a conclusion, our calibration algorithm can significantly improve the virtual screening performance in both drug lead optimization and identification phases with neglectable computational cost.
Multimodal temporal-clinical note network for mortality prediction
Authors: Yang Haiyang , Kuang Li , Xia FengQiang 
Published: February 2021

Abstract
Background
Mortality prediction is an important task to achieve smart healthcare, especially for the management of intensive care unit. It can provide a reference for doctors to quickly predict the course of disease and customize early intervention programs for the patients in need. With the development of the electronic medical records, deep learning methods are introduced to deal with the prediction task. In the electronic medical records, clinical notes always contain rich and diverse medical information, including the clinical histories and reports during admission. Mortality prediction methods mostly rely on the temporal events such as medical examinations and ignore the related reports and history information in the clinical notes. We hope that we can utilize both temporal events and clinical notes information to get better mortality prediction results.

Results
We propose a multimodal temporal-clinical note network to model both temporal and clinical notes. Specifically, the clinical text are further processed for differentiating the chronic illness patients in the historical information of clinical notes from non-chronic illness patients. In order to further mine the information related to the mortality in the text, we learn the time series embedding with Long Short Term Memory networks and the clinical notes embedding with a label aware convolutional neural network. We also propose a scoring function to measure the importance of clinical note sections. Our approach achieved a better AUCPR and AUCROC than competing methods and visual explanations for word importance showed the interpretability improvement of the model.

Conclusions
We have tested our methodology on the MIMIC-III dataset. Contributions of different clinical note sections were uncovered by visualization methods. Our work demonstrates that the introduction of the medical history related information can improve the performance of the mortality prediction. Using label aware convolutional neural networks can further improve the results.
The control algorithm of whole angle mode for HRG based on the vector composition
Authors: Zhao Wanliang , Cheng Yuxiang , Li Shaoliang , Song Lijun 
Published: February 2021

AbstractThe Hemispherical Resonator Gyroscope (HRG) has many advantages such as high precision, high reliability and long life-time, it is widely used in the space-launcher and the satellites. The HRG has been mechanized to operate in the distinct operating modes, the Force to Rebalanced (FTR) mode and the Whole Angle (WA) mode. In the paper, different from the traditional control algorithm is based on average methods which usually used for the WA mode, a new electrostatic control algorithm is presented, which based on the vector composition and decomposition method to control the equivalent drive force in order to track the phase of the standing wave. The mathematics model and the control algorithm are presented in the paper, and the hardware experimental circuit system is implemented, the HRG has a range of more than 300°/s with the linearity of 40 ppm. Meanwhile, the energy transition efficiency increases by an order of magnitude.
Clusters as institutional entrepreneurs: lessons from Russia
Authors: Lupova-Henry Evgeniya , Blili Sam , Dal Zotto Cinzia 
Published: February 2021

AbstractIn this article, we explore whether organized clusters can act as institutional entrepreneurs to create conditions favorable to innovation in their constituent members. We view self-aware and organized clusters as “context-embedded meta-organizations” which engage in deliberate decision- and strategy-making. As such, clusters are not only shaped by their environments, as “traditional” cluster approaches suggest but can also act upon these. Their ability to act as “change agents” is crucial in countries with high institutional barriers to innovation, such as most transition economies. Focusing on Russia, we conduct two cluster case studies to analyze the strategies these adopt to alter and shape their institutional environments. We find that clusters have a dual role as institutional entrepreneurs. First, these can act collectively to shape their environments due to the power they wield. Second, they can be mechanisms empowering their constituent actors, fostering their reflexivity and creativity, and allowing them to engage in institutional entrepreneurship. Moreover, both collective and individual cluster actors adopt “bricolage” approaches to institutional entrepreneurship to compensate for the lack of resources or institutional frameworks or avoid the pressures of ineffective institutions.