bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Production of Germacrene A, a Direct Precursor of ß-elemene, in Engineered Saccharomyces Cerevisiae by Expressing a Cyanobacterial Germacrene A Synthase&nbsp;
Authors: Zhang Weixin , Guo Junqi , Wang Zheng , Li Yanwei , Meng Xiangfeng , Shen Yu , Liu Weifeng 
Published: October 2020

Abstract
BackgroundThe sesquiterpene germacrene A is a direct precursor of ß-elemene that is a major component of the Chinese medicinal herb Curcuma wenyujin with prominent antitumor activity. The microbial platform for germacrene A production was previously established in Saccharomyces cerevisiae using the germacrene A synthase (LTC2) of Lactuca sativa. ResultsWe evaluated the performance of LTC2 as well as nine other identified or putative germacrene A synthases from different sources for the production of germacrene A. AvGAS, a synthase of Anabaena variabilis, was found to be the most efficient in germacrene A production in yeast. AvGAS expression alone in S. cerevisiae CEN.PK2-1D already resulted in a substantial production of germacrene A while LTC2 expression did not. Further metabolic engineering the yeast using known strategies including overexpression of tHMGR1, repression of squalene synthesis pathway and decreasing farnesol synthesis, led to an 11-fold increase in germacrene A production. Site-directed mutagenesis of AvGAS revealed that while changes of several residues located within the active site cavity severely compromised germacrene A production , substitution of Phe23 located on the lateral surface with tryptophan or valine led to a 35.2% and 21.8% increase in germacrene A production, respectively. Finally, the highest production titer of germacrene A reached 309.8 mg/L in shake-flask batch culture. ConclusionsOur study highlights the potential of applying bacterial sesquiterpene synthases with improved performance by mutagenesis engineering in producing germacrene A.
The association of food insecurity with diabetes control and self-care in diabetes type 2 patients: A cross-sectional study
Authors: Mohammadi Marjan , Djazayeri Seyyed Abolghasem , Jafari Asal Ataie 
Published: October 2020

Abstract
Background

Food insecurity can increase risks of health and nutritional problems, leading to difficulties in self-care and poor glycemic control in diabetic patients. This study assessed food insecurity and its association with diabetes control and self-care in type 2 diabetes patients.
Methods

In this cross sectional study, 148 adults with type 2 diabetes participated. Food insecurity and self-care were determined using the 18-item USDA household food security status questionnaire and self-care (SDSCA) questionnaire. Data were analyzed using logistic and linear regression tests (SPSS 20 software).
Results

Thirty-seven percent of the participants were food-insecure and significantly more likely than food-secure participants to have poor glycemic control (OR = 3.02; CI: 1.45–2.65). No significant association was found between food-insecurity and overall self-care score.
Conclusion

Food-insecurity was directly associated with poor glycemic control in type 2 diabetes patients. Since economic status was significantly better in the food-secure group, it can be postulated that financial problems will eventually lead to poor glycemic control. Policy strategies to increase access to diabetes-appropriate foods may reduce socioeconomic inequalities in glycemic control.
An Unusual Case of Myasthenia-Like Presentation in Erdheim-Chester Disease
Authors: Lauricella Eleonora , d'Amati Antonio , Ingravallo Giuseppe , Foresio Maurizio , Ribatti Domenico , de Tommaso Marina , Cives Mauro , Girolamo Francesco 
Published: October 2020

Abstract
Background: Erdheim-Chester disease (ECD), a rare disorder of monocyte/macrophage lineage, has been related to cerebellar dysfunction. To increase the awareness of this rare, protean disease, an unusual, myasthenia-like onset of ECD is reported.Case presentation: A 42-year-old man presented with a 6-year history of mild evening fatigability in his four limbs followed by motor and cognitive symptoms associated with cerebellar atrophy, dentate nuclei and dentato-thalamic pathway degeneration. Magnetic resonance imaging revealed hyperintense signals in T2 and fluid-attenuated inversion recovery sequences within the pons, cerebellar white matter, dentate nuclei and globi pallidi in the absence of any contrast enhancement. Whole-body bone scintigraphy with 99Technetium - methylene diphosphonate and fluorodeoxyglucose-positron emission tomography both revealed symmetric uptake in the lower extremities a finding suggestive of a diagnosis of ECD. Histological examination revealed diffuse infiltration of CD 68+ histiocytes with foamy cytoplasms in the presence of B-type of Rapidly Accelerated Fibrosarcoma protein kinase (BRAF)V600E activating mutation in tumor cells.Conclusion: In patients with myasthenia-like symptoms who test negatively for myasthenia gravis, neurodegenerative diseases, and disorders of the hypothalamus, a diagnosis of ECD should be taken into consideration.
A Newly Generated DOCK8-expressing T Follicular Helper Cell Type, aiCD4 T Cell, Causes Systemic Lupus Erythematosus: Self-Organized Criticality Theory
Authors: Shiozawa Shunichi , Tsumiyama Ken , Sakurai Keiichi , Horiuchi Takahiko , Matsubara Tsukasa , Oribe Motohiro , Yamane Takashi , Kagawa Hidetoshi , Li Quan-Zhen , Mukai Yohei , Miyazawa Masaaki 
Published: October 2020

Abstract
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease of unknown cause. We show here that a novel T follicular helper cell type expressing the guanine nucleotide exchange factor DOCK8 on the cell surface causes SLE. These cells, which we have designated autoantibody-inducing CD4 T (aiCD4 T) cells, are generated after resuscitation from anergy following strong TCR stimulation by antigen. When mice normally not prone to autoimmune disease were repeatedly immunized with an antigen such as OVA, they generated DOCK8+ CD4 T cells. These DOCK8+ CD4 T cells, in vivo and also upon transfer to naïve mice, induced a variety of autoantibodies and lesions characteristic of SLE. TCR repertoire analyses showed that a substantial number of novel TCR repertoires were generated in the DOCK8+ CD4 T cells, which induced novel autoantibodies upon transfer to naïve mice. DOCK8+ CD4 T cells are localized in splenic red pulp, the space immunoreactive against a variety of antigens, and specifically increased in the peripheral blood of SLE patients in association with disease activity. Anti-DOCK8 antibody treatment ameliorated the lesions induced by DOCK8+ CD4 T cells and in lupus model (NZB x W) F1 mice. Thus, when CD4 T cells are overstimulated by an external disturbance, i.e., repeatedly stimulated with antigen, to levels that surpass the system’s self-organized criticality, these cells express DOCK8 on the cell surface and acquire autoreactivity via TCR re-revision at the periphery. These DOCK8+ CD4 T cells subsequently induce a variety of autoantibodies and SLE.
The Clinical Significance and Biological Function of PCDH7 in Cervical Cancer
Authors: Zhang Shitong , Fu Xianhu 
Published: October 2020

Abstract
Background: Cervical cancer is a common malignant tumor in women that is prone to recurrence and metastasis. Recently, many people have explored the role of protocadherin 7 (PCDH7) in cancer, and found that PCDH7 is abnormally expressed in many cancers. The purpose of this study is to investigate the expression and mechanism of PCDH7 in cervical cancer and evaluate its clinical prognostic significance.Methods: The expression of PCDH7 in cervical cancer and cells was detected by qRT-PCR. The relationship between PCDH7 expression and clinical prognosis was calculated by the Kaplan-Meier method and Cox regression analyses. The effects of PCDH7 on cancer cell proliferation, migration, and invasion were studied by MTT assay and transwell assays.Results: The expression of PCDH7 in cervical cancer tissues and cell lines was significantly down-regulated compared with the control. Low PCDH7 expression was associated with low survival rate. PCDH7 expression was significantly correlated with lymph node metastasis, cell differentiation, and FIGO staging. PCDH7 can be used as an independent prognostic factor for cervical cancer. Up-regulation of PCDH7 significantly inhibited the proliferation, migration, and invasion of cancer cells.Conclusions: PCDH7 may be used as a biomarker for the prognosis of cervical cancer.
An assessment of recently released high-degree global geopotential models based on heterogeneous geodetic and ocean data
Authors: Wu Yihao , Abulaitijiang Adili , He Xiufeng , Luo Zhicai , Wang Haihong , Zhou Boyang 
Published: October 2020

Abstract
The development of the state-of-the-art global geopotential model (GGM) broadens its applications in ocean science, which emphasizes the importance for model assessment. We validate the recently released high-degree GGMs over the South China Sea using geodetic observations and synthetic/ocean reanalysis data. The assessment against a recently conducted high resolution (~ 3 km) airborne gravimetric survey over the Paracel Islands shows that XGM2019e_2159 has the highest accuracy (~ 3.1 mGal). However, the comparison with airborne/shipborne data hardly discriminate the qualities of other GGMs that have or truncated to same degree and order. Whereas, the validation results of GGMs against synthetic/ocean data are not identical. XGM2019e_2159/XGM2019 has the best quality, and the accuracy of associated mean dynamic topography (MDT) is 2.5 cm, and this value changes to 7.1 cm/s (6.8 cm/s) when the zonal (meridian) geostrophic currents are assessed. In contrast, the assessments of other GGMs show that they have deteriorated accuracies compared to XGM2019e_2159/XGM2019; in particular, the widely used EGM2008 has the worst performance, and the accuracies of associated MDT and zonal (meridian) currents are reduced by 3.9 cm and 4.0 cm/s (5.5 cm/s), respectively, compared to results derived from XGM2019e_2159/XGM2019. These results suggest that the choice of GGM in oceanographic research is crucial, especially in coastal zones and regions that only fill-in data were used for GGM development. Moreover, the existing synthetic/ocean data may be served as an additional data source for global/regional gravity field assessment, which is especially useful in regions that lack of control data.
Cardiovascular Disease Risk Prevention Services by Pharmacists in Saudi Arabia: What Do Policymakers and Opinion Leaders Think?
Authors: Almansour Hadi A. , Aloudah Nouf M. , Alhawassi Tariq M. , Chaar Betty , Krass Ines , Saini Bandana 
Published: October 2020

Abstract
Background: Cardiovascular disease (CVD) is an emerging contributor to national morbidity and mortality in Saudi Arabia. CVD risk prevention services are limited, particularly with an over-utilised public health sector and an under-utilised and under-resourced primary care sector. Globally, there is evidence that community pharmacists can play a key role in CVD prevention within primary care. However, the perspectives of policymakers and opinion leaders are critical to successful translation of evidence into practice. Thus, the aim was to engage policymakers and professional leaders in discussions about implementing high-quality CVD risk prevention services in community pharmacy. Methods: Qualitative semi-structured interviews were conducted, audio-recorded and transcribed verbatim. All transcripts were thematically analysed. Results: A total of 23 participants (87% male) from government and non-government sectors were interviewed. Of these, almost 65% had pharmacy qualifications. Limited provision of CVD risks preventative services in primary care was acknowledged. However, most participants favoured the concept of utilising community pharmacist’s capacity to assist in preventive health services. The data yielded four key themes: 1) Future pharmacy CVD health service models, 2) Demonstrable outcomes, 3) Professional engagement and advocacy and 4) Implementability. CVD health services roles (health screening, primary and secondary prevention services), pragmatic factors and tiered models of care (minimal, medium and comprehensive pharmacist involvement) were discussed. The need for humanistic, clinical and cost effectiveness outcomes and activation of professional bodies were deemed important. Professional pharmacy governance to develop pharmacy careers and workforce, pharmacy curricular reform and ongoing education were posed as key success factors for pharmacy roles. Practice policies, standards and guidelines were seen as required to adhere to stringent quality control for future pharmacy services provision. Participants implementation vision for such services included scalability, affordability, access, adoption and health system reform. Most discussion focused on the need for structural improvement with limited input regarding processes or outcomes required to establish such models. Conclusions: Most participants favoured pharmacy-based CVD risk prevention services, despite the variability in proposed service models. However, prior to developing such services, support structures at the health system and health professional level are needed as well as building public support and acceptability for pharmacy services.
De novo Propagation of Alfalfa Under Hydroponics
Authors: Yang Liu , Wenyu Zhang , Shuai Li , Yao Wu , Xiaohui Sun , Siyu Li , Zongyu Wang , Lichao Ma , Juan Sun , Cong Lili , Guofeng Yang 
Published: October 2020

Abstract
Background: The legume plant alfalfa (Medicago sativa L.) is a widely cultivated perennial forage due to its high protein levels, palatability, and strong adaptability to diverse soil types and agro-ecological zones. This forage plant is a self-incompatible, cross-pollinated autotetraploid with tetrasomic inheritance. Therefore, maintaining excellent traits through seed reproduction is challenging in alfalfa. However, the cutting propagation technology could enable consistent multiplication of quality plants that are genetically identical to the parent plant, for use in breeding and other research applications. Most of previous alfalfa omics researches used varieties as material on omics and gene mining experiment due to poor growth consistency of cuttings by existing cutting methods, which generate genetically un-identical cuttings and thus compromise on the reliability of the results. Therefore, this study aimed to develop a simple, cost-effective, reproducible, and efficient hydroponic cutting method for the preservation of alfalfa plants and molecular research applications such as genomic, transcriptomic, and proteomic analyses. Results: Alfalfa cultivar ‘Wudi’ grown under hydroponics for 30 days was used as source material for cuttings. The top, middle and bottom sections of its stem were used as cuttings. The rooting rate, root length, and stem height of the different stem sections were compared to determine the best segment for alfalfa propagation in four nutrient solutions (HM, HM+1/500H, HM+1/1000H and d HM+1/2000H). After 21 days of culture, the rooting rates of all the three stem types under four cutting nutrient solutions were above 78%, The rooting rate of the middle and bottom parts in HM +1/1000 H and HM +1/2000 H nutrient solutions reached more than 93% with higher health survey score (>4.70). Besides, root length and stem height in these two sections was exemplary. Conclusions: This study developed a de novo cutting propagation method that can be used to conserve and propagate germplasm in breeding programs and research. This article is the first report on the cutting propagation of alfalfa by hydroponics, which could supplement the existing cutting propagation methods.
Continuous Infusion Compared with Intermittent Intravenous Infusion of Beta-Lactam Antibiotics for Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Trials
Authors: Huang Chien-Huei , Shih Ching-Yao , Tsay Meng Keng , Hsuan Shen-Pei , Tseng Yung-Hsin , Tsai Wen-Shan , Cheng Ching-Lan 
Published: October 2020

Abstract
Background: The pathophysiologic changes during critical illness and high minimal inhibitory concentration (MIC) pathogens are important risk factors of mortality and bacterial eradication in critical care. Beta-lactam antibiotics have a time-dependent effect on bactericidal activity. The continuous infusion (CIF) of beta-lactam antibiotics achieves sufficient drug concentration above the MIC, especially for critically ill patients. However, the superiority of CIF over intermittent infusion (IIF) of beta-lactam antibiotics is yet to be clearly established. Thus, we aimed to investigate the effects on mortality of CIF of beta-lactams antibiotics in comparison to those of IIF of beta-lactams antibiotics in patients with sepsis admitted to the intensive care unit (ICU).Methods: We systematically searched PUBMED, MEDLINE, Cochrane Library, EMBASE, Web of Science, and ICTRP for randomized controlled trials (RCTs) comparing CIF with IIF of beta-lactam antibiotics in critically ill populations. All RCTs published until October 2019 were eligible. The primary outcome measure was the relative risk (RR) of mortality, while the secondary outcome measures were bacterial eradication rate, length of ICU stay, and length of admission. Results: In total, 6 RCTs comprising 974 patients were analyzed. We found a significantly lower mortality for critically ill patients on CIF (RR: 0.79; 95% CI: 0.63, 0.98) compared with those on IIF of beta-lactam antibiotics. The pooled RR for the bacterial eradication rate was 1.16 (95% CI: 1.03, 1.29) for CIF compared with IIF administration. Conclusion: CIF of beta-lactam antibiotics for critically ill patients significantly reduces mortality and yields a better bacterial eradication rate than IIF. These findings support the clinical and bacterial eradication benefits in adult critically ill patients, and may guide clinical discussions and decisions.
Interpretable Machine Learning Model for Mortality Prediction in ICU: A Multicenter Study
Authors: Fong Ka Man , Au Shek Yin , Ng George Wing Yiu , Leung Anne Kit Hung 
Published: October 2020

Abstract
Background: Researchers have long been struggling to improve the disease severity score in mortality prediction in ICU. The digitalization of medical health records and advancement of computation power have promoted the use of machine learning in critical care. This study aimed to develop an interpretable machine learning model using datasets from multicenters, and to compare with the APACHE IV, in predicting hospital mortality of patients admitted to ICU.Method: The datasets were assembled from the eICU database including 136145 patients across 208 hospitals throughout the U.S. and 5 ICUs in Hong Kong, including 10909 patients. The two datasets were first combined into one large dataset before 80:20 stratified split into the training set and the test set. The XGBoost machine algorithm was chosen to predict the hospital mortality. The variables in the model were the same as those included in the APACHE IV score. The discrimination and calibration of the model were assessed. The model would be interpreted using the Shapley Additive explanations values.Results: Of the 147054 patients in the whole cohort, the hospital mortality was 9.3%. The area under the precision-recall curve for the XGBoost algorithm was 0.57, and 0.49 for APACHE IV. Similarly, the XGBoost reached an area under the receiving operating curve (AUROC) of 0.90, while APACHE IV had an AUROC of 0.87. Additionally, the XGBoost algorithm showed better calibration than the APACHE IV. The three most important variables were age, heart rate, and whether the patient was on ventilator.Conclusions: The severity score developed by machine learning model using mutlicenter datasets outperformed the APACHE IV in predicting hospital mortality for patients admitted to ICU.
Strategies to Maximize the Wood Production in Amazon Forest
Authors: Canetti Aline , Braz Evaldo Muñoz , Mattos Patricia , Basso Renato Olivir , Filho Afonso Figueiredo 
Published: October 2020

Abstract
BackgroundThis study aimed to develop a procedure to determine which logging diameter would achieve optimal wood production by species, aiming to support sustainable management of the Amazon forest. Two main methodologies of analysis by species were combined: probability density function (PDF) and growth modeling. The growth models were used to derive the volume increment curves at the individual tree level. To detect the points of maximum annual increment in volume at the population tree level we used PDF with adjusted growth equations.ResultsThe population maximum annual volumetric increments occurred in smaller diameters compared to that of the individual-level. When combining shorter cutting cycles with the population biological rotation point considered as the minimum cutting diameter (MCD), we observed higher annual increments in volume than that achieved using the Brazilian law criteria (MCD = 50 cm) or other MCD tested.Conclusion﻿The procedure proposed may be used by forest managers and forest law-makers, aiming to maximize sustainable wood production in the Amazon forest.
Conjoint analysis of m6A regulators and copy number variations in thyroid carcinoma
Authors: Han Hui , Yu Jian-Yi , Fu Xiao-Dan , Ni Ye-Qin , Luo Ding-Cun , Zhang Xian-Feng 
Published: October 2020

Abstract
Background: Most patients with thyroid carcinoma have a good prognosis, but some thyroid carcinomas are aggressive and prone to recurrence and metastasis. Further, concomitant overdiagnosis and overtreatment are important issues. This study aimed to investigate the relationship between mutations and copy number variations in m6A regulatory genes and the clinicopathological features of thyroid carcinoma.Results: Advanced pathological stage and T stage were significantly correlated with changes in m6A regulatory genes (p<0.05). Patients with abnormal copy numbers of m6A regulatory genes had a significantly shorter progression-free interval than patients with normal copy numbers. Mutations and copy number variations in m6A regulatory genes were significantly correlated with advanced pathological stage and T stage. Conclusions: Copy number variations were a poor prognostic factor for thyroid carcinoma as evidenced by the significantly short progression-free interval in patients with copy number variations in m6A regulatory genes. Further, the ZC3H13 gene may be involved in the occurrence and development of thyroid carcinoma by regulating cancer-associated signaling pathways and biological processes. These findings may help distinguish patients with poor prognoses who may need more aggressive treatment from patients who have better prognoses.