bluuebunny/crossref_metadata_2025_split huggingface dataset:
De novo resveratrol production through modular engineering of an Escherichia coli–Saccharomyces cerevisiae co-culture
Authors: Yuan Shuo-Fu , Yi Xiunan , Johnston Trevor G. , Alper Hal S. 
Published: July 2020

Abstract
Background
Resveratrol is a plant secondary metabolite with diverse, potential health-promoting benefits. Due to its nutraceutical merit, bioproduction of resveratrol via microbial engineering has gained increasing attention and provides an alternative to unsustainable chemical synthesis and straight extraction from plants. However, many studies on microbial resveratrol production were implemented with the addition of water-insoluble phenylalanine or tyrosine-based precursors to the medium, limiting in the sustainable development of bioproduction.

Results
Here we present a novel coculture platform where two distinct metabolic background species were modularly engineered for the combined total and de novo biosynthesis of resveratrol. In this scenario, the upstream Escherichia coli module is capable of excreting p-coumaric acid into the surrounding culture media through constitutive overexpression of codon-optimized tyrosine ammonia lyase from Trichosporon cutaneum (TAL), feedback-inhibition-resistant 3-deoxy-d-arabinoheptulosonate-7-phosphate synthase (aroGfbr) and chorismate mutase/prephenate dehydrogenase (tyrAfbr) in a transcriptional regulator tyrR knockout strain. Next, to enhance the precursor malonyl-CoA supply, an inactivation-resistant version of acetyl-CoA carboxylase (ACC1S659A,S1157A) was introduced into the downstream Saccharomyces cerevisiae module constitutively expressing codon-optimized 4-coumarate-CoA ligase from Arabidopsis thaliana (4CL) and resveratrol synthase from Vitis vinifera (STS), and thus further improve the conversion of p-coumaric acid-to-resveratrol. Upon optimization of the initial inoculation ratio of two populations, fermentation temperature, and culture time, this co-culture system yielded 28.5 mg/L resveratrol from glucose in flasks. In further optimization by increasing initial net cells density at a test tube scale, a final resveratrol titer of 36 mg/L was achieved.

Conclusions
This is first study that demonstrates the use of a synthetic E. coli–S. cerevisiae consortium for de novo resveratrol biosynthesis, which highlights its potential for production of other p-coumaric-acid or resveratrol derived biochemicals.
Comprehensive analysis of the expression of sodium/potassium-ATPase α subunits and prognosis of ovarian serous cystadenocarcinoma
Authors: Huang Wei , Zhang Yongjian , Xu Ye , Yang Shaoyou , Li Bing , Huang Lan , Lou Ge 
Published: July 2020

Abstract
Background
Ovarian serous cystadenocarcinoma (OSC) is the most common and lethal gynecological cancer in women worldwide; however, biomarkers to diagnose and predict prognosis of OSC remain limited. Therefore, the present study aimed to investigate whether sodium/potassium adenosine triphosphate (Na+/K+-ATP)ase α-subunits (ATP1As) are helpful diagnostic and prognostic markers of OSC.

Methods
Gene expression data (RNA-Seq) of 376 patients with OSC were downloaded from The Cancer Genome Atlas (TCGA) program database. Additional databases used in our analysis included the Gene Expression Omnibus, International Cancer Genome Consortium, Genotype-Tissue Expression, the Human Protein Atlas, cBioPortal for Cancer Genomics, and Cancer Cell Line Encyclopedia.

Results
The expression levels of ATP1A1 and ATP1A3 were higher in OSC tissues than in normal ovarian tissues, whereas the expression levels of ATP1A2 and ATP1A4 were lower in OSC tissues than in normal ovarian tissues. Overexpression of ATP1A2 was significantly associated with a higher Federation of Gynecology and Obstetrics (FIGO) stage and histological grade. Increased mRNA expression of ATP1A3 was significantly associated with shorter overall survival (OS) and disease-specific survival (DSS) in patients with OSC, whereas higher expression of ATP1A4 was associated with favorable OS and DSS. Multivariate analysis showed that primary therapy outcome, residual tumor, and mRNA expressions of ATP1A3 and ATP1A4 were independent prognostic factors for both OS and DSS in patients with OSC. Moreover, ATP1A1 staining was abundant in tumor tissues. A high expression of ATP1A3 was significantly correlated with poor OS and DSS in the subgroup of patients aged ≥ 60 years and with FIGO stage III, histological grade G3, and TP53 mutation. Mutation frequencies of the ATP1As were 3–5%.

Conclusions
These results indicate that the ATP1A gene family could be potential diagnostic or prognostic markers of OSC. In addition, ATP1As may be effective therapeutic targets in the treatment of OSC.
The effects of green coffee extract supplementation on glycemic indices and lipid profile in adults: a systematic review and dose-response meta-analysis of clinical trials
Authors: Asbaghi Omid , Sadeghian Mehdi , Nasiri Morteza , Khodadost Mahmoud , Shokri Azad , Panahande Bahman , Pirouzi Aliyar , Sadeghi Omid 
Published: July 2020

Abstract
Background
The role of coffee consumption in the risk of cardiovascular diseases has been debated for many years. The current study aimed to summarize earlier evidence on the effects of green coffee extract (GCE) supplementation on glycemic indices and lipid profile.

Methods
We searched available online databases for relevant clinical trials published up to October 2019. All clinical trials investigating the effect of GCE supplementation, compared with a control group, on fasting blood glucose (FBG), serum insulin, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were included. Overall, 14 clinical trials with a total sample size of 766 participants were included in the current meta-analysis.

Results
We found a significant reducing effect of GCE supplementation on FBG (weighted mean difference (WMD): -2.35, 95% CI: − 3.78, − 0.92 mg/dL, P = 0.001) and serum insulin (WMD: -0.63, 95% CI: − 1.11, − 0.15 μU/L, P = 0.01). With regard to lipid profile, we observed a significant reduction only in serum levels of TC following GCE supplementation in the overall meta-analysis (WMD: -4.51, 95% CI: − 8.39, − 0.64, P = 0.02). However, subgroup analysis showed a significant reduction in serum TG in studies enrolled both genders. Also, such a significant reduction was seen in serum levels of LDL and HDL when the analyses confined to studies with intervention duration of ≥8 weeks and those included female subjects. In the non-linear dose-response analyses, we found that the effects of chlorogenic acid (CGA) dosage, the main polyphenol in GCE, on FBG, TG and HDL were in the non-linear fashions.

Conclusion
In conclusion, we found that GCE supplementation improved FBG and serum levels of insulin and TC. Also, there was a significant improvement in other markers of lipid profile in some subgroups of clinical trials.
A critical realist synthesis of cross-disciplinary health policy and systems research: defining characteristic features, developing an evaluation framework and identifying challenges
Authors: Dugle Gordon , Wulifan Joseph Kwame , Tanyeh John Paul , Quentin Wilm 
Published: July 2020

Abstract
Background
Health policy and systems research (HPSR) is an inherently cross-disciplinary field of investigation. However, conflicting conceptualisations about inter-, multi- and transdisciplinary research have contributed to confusion about the characteristics of cross-disciplinary approaches in HPSR. This review was conducted to (1) define the characteristic features of context–mechanism–outcome (CMO) configurations in cross-disciplinary HPSR, (2) develop criteria for evaluating cross-disciplinarity and (3) synthesise emerging challenges of the approach.

Method
The paper is a critical realist synthesis conducted in three phases, as follows: (1) scoping the literature, (2) searching for and screening the evidence, and (3) extracting and synthesising the evidence. Five databases, namely the International Bibliography of the Social Sciences and Web of Science, PubMed central, Embase and CINHAL, and reference lists of studies that qualified for inclusion in the review were searched. The search covered peer-reviewed original research, reviews, commentary papers, and institutional or government reports published in English between January 1998 and January 2020.

Results
A total of 7792 titles were identified in the online search and 137 publications, comprising pilot studies as well as anecdotal and empirical literature were selected for the final review. The review draws attention to the fact that cross-disciplinary HPSR is not defined by individual characteristics but by the combination of a particular type of research question and setting (context), a specific way of researchers working together (mechanism), and research output (outcome) that is superior to what could be achieved under a monodisciplinary approach. This CMO framework also informs the criteria for assessing whether a given HPSR is truly cross-disciplinary. The challenges of cross-disciplinary HPSR and their accompanying coping mechanisms were also found to be context driven, originating mainly from conceptual disagreements, institutional restrictions, communication and information management challenges, coordination problems, and resource limitations.

Conclusion
These findings have important implications. First, the CMO framework of cross-disciplinary HPSR can provide guidance for researchers engaging in new projects and for policy-makers using their findings. Second, the proposed criteria for evaluating theory and practice of cross-disciplinary HPSR may inform the systematic development of new research projects and the structured assessment of existing ones. Third, a better understanding of the challenges of cross-disciplinary HPSR and potential response mechanisms may help researchers to avoid these problems in the future.
Proceedings from the 2nd Next Gen Therapies for Systemic Juvenile Idiopathic Arthritis and Macrophage Activation Syndrome symposium held on October 3-4, 2019
Authors: Canna Scott W. , Schulert Grant S. , de Jesus Adriana , Pickering Alex , Brunner Hermine , Gadina Massimo , Levine Stewart , Goldbach-Mansky Raphaela , Boutelle Jonathan , Sinha Rashmi , DeBenedetti Fabrizio , Grom Alexei ,   on behalf of the NextGen 2019 Participants, Gottlieb Beth , Yeung Rae , Riskalla Mona , Prahalad Sampath , Alehashemi Sara , Chandrakasan Shan , Vastert Bas , Kimura Yuki , Carlson Anna , Schumacher Emily , Minerva Regina , Pierce Jonathan , Pierce Kate , Martinez Zulayka , Cupp Kari , Bush Leah , Costello Wendy , DelGaizo Vincent 
Published: July 2020

AbstractFor reasons poorly understood, and despite the availability of biological medications blocking IL-1 and IL-6 that have markedly improved overall disease control, children with Systemic Juvenile Idiopathic Arthritis (SJIA) are now increasingly diagnosed with life-threatening chronic complications, including hepatitis and lung disease (SJIA-LD). On October 3–4, 2019, a two-day meeting, NextGen Therapies for Systemic Juvenile Idiopathic Arthritis (SJIA) & macrophage activation syndrome (MAS) organized by the Systemic JIA Foundation (www.systemicjia.org/) in Washington, DC brought together scientists, clinicians, parents and FDA representatives with the objectives (1) to integrate clinical and research findings in MAS and SJIA-LD, and (2) to develop a shared understanding of this seemingly new pulmonary complication of SJIA. The current manuscript summarizes discussions and conclusions of the meeting.
Robotics-assisted visual-motor training influences arm position sense in three-dimensional space
Authors: Valdés Bulmaro A. , Khoshnam Mahta , Neva Jason L. , Menon Carlo 
Published: July 2020

Abstract
Background
Performing activities of daily living depends, among other factors, on awareness of the position and movements of limbs. Neural injuries, such as stroke, might negatively affect such an awareness and, consequently, lead to degrading the quality of life and lengthening the motor recovery process. With the goal of improving the sense of hand position in three-dimensional (3D) space, we investigate the effects of integrating a pertinent training component within a robotic reaching task.

Methods
In the proof-of-concept study presented in this paper, 12 healthy participants, during a single session, used their dominant hand to attempt reaching without vision to two targets in 3D space, which were placed at locations that resembled the functional task of self-feeding. After each attempt, participants received visual and haptic feedback about their hand’s position to accurately locate the target. Performance was evaluated at the beginning and end of each session during an assessment in which participants reached without visual nor haptic feedback to three targets: the same two targets employed during the training phase and an additional one to evaluate the generalization of training.

Results
Collected data showed a statistically significant [39.81% (p=0.001)] reduction of end-position reaching error when results of reaching to all targets were combined. End-position error to the generalization target, although not statistically significant, was reduced by 15.47%.

Conclusions
These results provide support for the effectiveness of combining an arm position sense training component with functional motor tasks, which could be implemented in the design of future robot-assisted rehabilitation paradigms to potentially expedite the recovery process of individuals with neurological injuries.
Right-sided double valve replacement in an adult patient who underwent surgery for pulmonary stenosis in childhood: a case report
Authors: Kobayashi Kimihiro , Uchida Tetsuro , Kuroda Yoshinori , Yamashita Atsushi , Ohba Eiichi , Nakai Shingo , Ochiai Tomonori , Sadahiro Mitsuaki 
Published: July 2020

Abstract
Background
Pulmonary regurgitation and the subsequent functional tricuspid regurgitation are frequently observed in adult patients who previously underwent pulmonary valvular operations. Pulmonary valve replacement, in combination with tricuspid annuloplasty, is frequently performed in adult patients. However, postoperative worsening or recurrence of tricuspid regurgitation is a major concern after pulmonary valve replacement with tricuspid annuloplasty.

Case presentation
Herein, we describe the case of a 56-year-old woman with severe pulmonary regurgitation and functional tricuspid regurgitation after congenital pulmonary stenosis surgery in childhood. Functional tricuspid regurgitation was due to tricuspid annular dilatation, marked right ventricle enlargement, and significant tethering. We performed a bioprosthetic double valve replacement, and the postoperative course was uneventful. The patient is doing well one year after the surgery without prosthetic valve dysfunction.

Conclusions
When functional tricuspid regurgitation is severe and is associated with right ventricular dilatation and subsequent tethering, tricuspid valve replacement rather than annuloplasty should be considered.
Risk factors for postoperative delirium in patients with triple-branched stent graft implantation
Authors: Lin Yanjuan , Chen Qiong , Zhang Haoruo , Chen Liang-Wan , Peng Yanchun , Huang Xizhen , Chen Yiping , Li Sailan , Lin Lingyu 
Published: July 2020

Abstract
Background
Neurological complications is a common complication following novel triple-branched stent graft implantation in patients with Stanford type A aortic dissection (AAD). But the incidence and risk factors of postoperative delirium (POD) are not completely clear. The aim of this study was to investigate the incidence and risk factors of POD after novel triple-branched stent graft implantation.

Methods
An observational study of AAD patients who underwent novel triple-branched stent graft implantation between January 2017 and July 2019 were followed up after surgery. Patients’ delirium was screened by the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the intensive care unit from the first day after the operation, lasted 5 days. The risk factors of POD were analyzed by the Cox proportional hazard models.

Results
A total of 280 AAD patients were enrolled in this research, the incidence of POD was 37.86%. Adjusting for age, body mass index, and mechanical ventilation duration, multivariate Cox regression analysis model revealed that non-manual work (adjusted hazard ratio [AHR] = .554; 95% CI: 0.335–0.915; P = .021), Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores > 20 (AHR = 3.359, 95% CI: 1.707–6.609, P < .001), hypoxemia (AHR = 1.846, 95% CI: 1.118–3.048, P = .017), and more than two types of analgesics and sedatives were independently associated with POD.

Conclusions
This study showed that risk factors independently associated with POD were APACHE-II score > 20, hypoxemia, and more types of analgesics and sedatives, and non-manual work was the protective factor.

Trial registration
This study was retrospectively registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR1900022408; Date: 2019/4/10).
Hemodynamic response during endotracheal suctioning predicts awakening and functional outcome in subarachnoid hemorrhage patients
Authors: Rass Verena , Ianosi Bogdan-Andrei , Lindner Anna , Kofler Mario , Schiefecker Alois J. , Pfausler Bettina , Beer Ronny , Schmutzhard Erich , Helbok Raimund 
Published: July 2020

Abstract
Background
Endotracheal suctioning (ES) provokes a cumulative hemodynamic response by activation of sympathetic and parasympathetic circuits in the central nervous system. In this proof-of-concept study, we aimed to analyze hemodynamic changes during ES in ventilated subarachnoid hemorrhage (SAH) patients and investigated whether the associated hemodynamic changes relate to the time to arousal and functional outcome.

Methods
For the current observational study, 191 SAH patients admitted to the neurological intensive care unit of a tertiary hospital requiring mechanical ventilation were included. One thousand eighty ES episodes during the first 72 h of admission were analyzed. Baseline median heart rate (HR) and mean arterial pressure (MAP) were compared to peak HR and MAP during ES based on 5-min averaged data (ΔHR and ΔMAP). Multivariable analysis to assess associations between ΔHR and ΔMAP and time to arousal (time to Richmond Agitation Sedation Scale ≥ 0, RASS) and poor functional outcome (modified Rankin Scale Score > 2, mRS) was performed using generalized estimating equations.

Results
Patients were 59 (IQR, 50–70) years old and presented with a median admission H&H grade of 4 (IQR, 3–5). In-hospital mortality was 22% (25% at 3 months) and median time to arousal was 13 (IQR, 4–21) days. HR increased by 2.3 ± 7.1 beats per minute (bpm) from 75.1 ± 14.8 bpm at baseline. MAP increased by 3.2 ± 7.8 mmHg from baseline 80.9 ± 9.8 mmHg. In multivariable analysis, ΔHR (p < 0.001) was significantly lower in patients who regained consciousness at a later time point and a lower ΔHR was associated with poor functional 3-month outcome independent of RASS (adjOR = 0.95; 95% CI = 0.93–0.98) or midazolam dose (adjOR = 0.96; 95% CI = 0.94–0.98). ΔMAP was neither associated with the time to regain consciousness (p = 0.087) nor with functional outcome (p = 0.263).

Conclusion
Augmentation in heart rate may quantify the hemodynamic response during endotracheal suctioning in brain-injured patients. The value as a biomarker to early discriminate the time to arousal and functional outcome in acutely brain-injured patients needs prospective confirmation.
PWAS: proteome-wide association study—linking genes and phenotypes by functional variation in proteins
Authors: Brandes Nadav , Linial Nathan , Linial Michal 
Published: July 2020

AbstractWe introduce Proteome-Wide Association Study (PWAS), a new method for detecting gene-phenotype associations mediated by protein function alterations. PWAS aggregates the signal of all variants jointly affecting a protein-coding gene and assesses their overall impact on the protein’s function using machine learning and probabilistic models. Subsequently, it tests whether the gene exhibits functional variability between individuals that correlates with the phenotype of interest. PWAS can capture complex modes of heritability, including recessive inheritance. A comparison with GWAS and other existing methods proves its capacity to recover causal protein-coding genes and highlight new associations. PWAS is available as a command-line tool.
CORAZON: a web server for data normalization and unsupervised clustering based on expression profiles
Authors: Ramos Thaís A. R. , Maracaja-Coutinho Vinicius , Ortega J. Miguel , do Rêgo Thaís G. 
Published: July 2020

AbstractObjectiveData normalization and clustering are mandatory steps in gene expression and downstream analyses, respectively. However, user-friendly implementations of these methodologies are available exclusively under expensive licensing agreements, or in stand-alone scripts developed, reflecting on a great obstacle for users with less computational skills.ResultsWe developed an online tool called CORAZON (Correlations Analyses Zipper Online), which implements three unsupervised learning methods to cluster gene expression datasets in a friendly environment. It allows the usage of eight gene expression normalization/transformation methodologies and the attribute’s influence. The normalizations requiring the gene length only could be performed to RNA-seq, meanwhile the others can be used with microarray and/or NanoString data. Clustering methodologies performances were evaluated through five models with accuracies between 92 and 100%. We applied our tool to obtain functional insights of non-coding RNAs (ncRNAs) based on Gene Ontology enrichment of clusters in a dataset generated by the ENCODE project. The clusters where the majority of transcripts are coding genes were enriched in Cellular, Metabolic, Transports, and Systems Development categories. Meanwhile, the ncRNAs were enriched in the Detection of Stimulus, Sensory Perception, Immunological System, and Digestion categories. CORAZON source-code is freely available athttps://gitlab.com/integrativebioinformatics/corazonand the web-server can be accessed athttp://corazon.integrativebioinformatics.me.
Seizure and coma secondary to Conn’s syndrome: a case report
Authors: Alseddeeqi Eiman , Altinoz Ajda , Ghashir Najla Ben 
Published: July 2020

Abstract
Background
Conn’s syndrome is a curable condition if identified properly. It is characterized by autonomous secretion of aldosterone from the adrenal gland cortex. Its morbidity is related to the increased risk of cardiovascular diseases.

Case presentation
We report the case of a 48-year-old man of African descent presenting with generalized tonic-clonic seizure and coma secondary to hypertensive encephalopathy. A biochemical evaluation revealed a very high aldosterone level and an undetectable renin level, both are compatible with primary aldosteronism. The presentation of the following confirms the diagnosis of primary aldosteronism: spontaneous hypokalemia, an undetectable renin level, and a high aldosterone level. Abdominal computed tomography revealed a left adrenal adenoma. Adrenal venous sampling confirmed lateralization of aldosterone excretion from the left adrenal gland. Our patient underwent left laparoscopic adrenalectomy that confirmed a left functional adrenal adenoma. After 12 months of follow up, his hypertension was controlled on only one antihypertensive drug which was down from four drugs preoperatively.

Conclusion
Conn’s syndrome, in this case, was complicated by coma secondary to seizure. Adrenalectomy normalized the hypokalemia and improved resistant hypertension. Potassium supplementation and several antihypertensives were discontinued as our patient became normokalemic and normotensive on one antihypertensive agent.