bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational analysis to repurpose drugs for COVID-19 based on transcriptional response of host cells to SARS-CoV-2
Authors: Li Fuhai , Michelson Andrew P. , Foraker Randi , Zhan Ming , Payne Philip R. O. 
Published: January 2021

Abstract
Background
The Coronavirus Disease 2019 (COVID-19) pandemic has infected over 10 million people globally with a relatively high mortality rate. There are many therapeutics undergoing clinical trials, but there is no effective vaccine or therapy for treatment thus far. After affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), molecular signaling pathways of host cells play critical roles during the life cycle of SARS-CoV-2. Thus, it is significant to identify the involved molecular signaling pathways within the host cells. Drugs targeting these molecular signaling pathways could be potentially effective for COVID-19 treatment.

Methods
In this study, we developed a novel integrative analysis approach to identify the related molecular signaling pathways within host cells, and repurposed drugs as potentially effective treatments for COVID-19, based on the transcriptional response of host cells.

Results
We identified activated signaling pathways associated with the infection caused SARS-CoV-2 in human lung epithelial cells through integrative analysis. Then, the activated gene ontologies (GOs) and super GOs were identified. Signaling pathways and GOs such as MAPK, JNK, STAT, ERK, JAK-STAT, IRF7-NFkB signaling, and MYD88/CXCR6 immune signaling were particularly activated. Based on the identified signaling pathways and GOs, a set of potentially effective drugs were repurposed by integrating the drug-target and reverse gene expression data resources. In addition to many drugs being evaluated in clinical trials, the dexamethasone was top-ranked in the prediction, which was the first reported drug to be able to significantly reduce the death rate of COVID-19 patients receiving respiratory support.

Conclusions
The integrative genomics data analysis and results can be helpful to understand the associated molecular signaling pathways within host cells, and facilitate the discovery of effective drugs for COVID-19 treatment.
Participation in the Cardiovascular Health Awareness Program (CHAP) by older adults residing in social housing in Quebec: Social network analysis
Authors: Deville-Stoetzel Nadia , Kaczorowski Janusz , Agarwal Gina , Lussier Marie-Thérèse , Girard Magali 
Published: January 2021

Abstract
Background
The Cardiovascular Health Awareness Program (CHAP) is as a community-based cardiovascular disease prevention program recently adapted to target older adults living in 14 social housing buildings in Ontario (7) and Quebec (7). Social network analysis (SNA) has been used successfully to assess and strengthen participation in health promotion programs. We applied SNA methods to investigate whether interpersonal relationships among residents within buildings influenced their participation in CHAP.

Methods
Our aim was to examine relational dynamics in two social housing buildings in Quebec with low and high CHAP attendance rates, respectively. We used sociometric questionnaires and network analysis for the quantitative phase of the study, supplemented by a phase of qualitative interviews. All residents of both buildings were eligible for the sociometric questionnaire. Respondents for the qualitative interviews were purposively selected to represent the different attendance situations following the principle of content saturation.

Results
In total, 69 residents participated in the study, 37 through sociometric questionnaires and 32 in qualitative interviews. Of the latter, 10 attended almost all CHAP sessions, 10 attended once, and 12 attended none. Results of the quantitative analysis phase identified well-known and appreciated local leaders. In Building 1, which had a high attendance rate (34.3%), there was a main leader (in-degree or ‘named by others’ frequency 23.2%) who had attended all CHAP sessions. In Building 2, which had a low attendance rate (23.9%), none of the leaders had attended CHAP sessions. Results of the qualitative analysis phase showed that residents who did not attend CHAP sessions (or other activities in the building) generally preferred to avoid conflicts, vindictiveness, and gossip and did not want to get involved in clans and politics within their building.

Conclusion
We identified four potential strategies to increase attendance at CHAP sessions by residents of subsidized housing for older adults: strengthen confidentiality for those attending the sessions; use community peer networks to enhance recruitment; pair attendees to increase the likelihood of participation; and intervene through opinion leaders or bridging individuals.
Genome-wide survey of tandem repeats by nanopore sequencing shows that disease-associated repeats are more polymorphic in the general population
Authors: Mitsuhashi Satomi , Frith Martin C. , Matsumoto Naomichi 
Published: January 2021

AbstractBackgroundTandem repeats are highly mutable and contribute to the development of human disease by a variety of mechanisms. It is difficult to predict which tandem repeats may cause a disease. One hypothesis is that changeable tandem repeats are the source of genetic diseases, because disease-causing repeats are polymorphic in healthy individuals. However, it is not clear whether disease-causing repeats are more polymorphic than other repeats.MethodsWe performed a genome-wide survey of the millions of human tandem repeats using publicly available long read genome sequencing data from 21 humans. We measured tandem repeat copy number changes using . Length variation of known disease-associated repeats was compared to other repeat loci.ResultsWe found that known Mendelian disease-causing or disease-associated repeats, especially CAG and 5′UTR GGC repeats, are relatively long and polymorphic in the general population. We also show that repeat lengths of two disease-causing tandem repeats, inATXN3andGLS, are correlated with near-by GWAS SNP genotypes.ConclusionsWe provide a catalog of polymorphic tandem repeats across a variety of repeat unit lengths and sequences, from long read sequencing data. This method especially if used in genome wide association study, may indicate possible new candidates of pathogenic or biologically important tandem repeats in human genomes.
Empagliflozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular filling pressure in patients with type 2 diabetes: a randomized controlled study
Authors: Rau Matthias , Thiele Kirsten , Hartmann Niels-Ulrik Korbinian , Schuh Alexander , Altiok Ertunc , Möllmann Julia , Keszei András P. , Böhm Michael , Marx Nikolaus , Lehrke Michael 
Published: January 2021

Abstract
Background
In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial) treatment with the sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin significantly reduced heart failure hospitalization (HHF) in patients with type 2 diabetes mellitus (T2D) and established cardiovascular disease. The early separation of the HHF event curves within the first 3 months of the trial suggest that immediate hemodynamic effects may play a role. However, hitherto no data exist on early effects of SGLT2 inhibitors on hemodynamic parameters and cardiac function. Thus, this study examined early and delayed effects of empagliflozin treatment on hemodynamic parameters including systemic vascular resistance index, cardiac index, and stroke volume index, as well as echocardiographic measures of cardiac function.

Methods
In this placebo-controlled, randomized, double blind, exploratory study patients with T2D were randomized to empagliflozin 10 mg or placebo for a period of 3 months. Hemodynamic and echocardiographic parameters were assessed after 1 day, 3 days and 3 months of treatment.

Results
Baseline characteristics were not different in the empagliflozin (n = 22) and placebo (n = 20) group. Empagliflozin led to a significant increase in urinary glucose excretion (baseline: 7.3 ± 22.7 g/24 h; day 1: 48.4 ± 34.7 g/24 h; p < 0.001) as well as urinary volume (1740 ± 601 mL/24 h to 2112 ± 837 mL/24 h; p = 0.011) already after one day compared to placebo. Treatment with empagliflozin had no effect on the primary endpoint of systemic vascular resistance index, nor on cardiac index, stroke volume index or pulse rate at any time point. In addition, echocardiography showed no difference in left ventricular systolic function as assessed by left ventricular ejections fraction and strain analysis. However, empagliflozin significantly improved left ventricular filling pressure as assessed by a reduction of early mitral inflow velocity relative to early diastolic left ventricular relaxation (E/eʹ) which became significant at day 1 of treatment (baseline: 9.2 ± 2.6; day 1: 8.5 ± 2.2; p = 0.005) and remained apparent throughout the study. This was primarily attributable to reduced early mitral inflow velocity E (baseline: 0.8 ± 0.2 m/s; day 1: 0.73 ± 0.2 m/sec; p = 0.003).

Conclusions
Empagliflozin treatment of patients with T2D has no significant effect on hemodynamic parameters after 1 or 3 days, nor after 3 months, but leads to rapid and sustained significant improvement of diastolic function.
Trial registration EudraCT Number: 2016-000172-19; date of registration: 2017-02-20 (clinicaltrialregister.eu)
Study on the isoprene-producing co-culture system of Synechococcus elongates–Escherichia coli through omics analysis
Authors: Liu Hui , Cao Yujin , Guo Jing , Xu Xin , Long Qi , Song Lili , Xian Mo 
Published: January 2021

Abstract
Background
The majority of microbial fermentations are currently performed in the batch or fed-batch manner with the high process complexity and huge water consumption. The continuous microbial production can contribute to the green sustainable development of the fermentation industry. The co-culture systems of photo-autotrophic and heterotrophic species can play important roles in establishing the continuous fermentation mode for the bio-based chemicals production.

Results
In the present paper, the co-culture system of Synechococcus elongates–Escherichia coli was established and put into operation stably for isoprene production. Compared with the axenic culture, the fermentation period of time was extended from 100 to 400 h in the co-culture and the isoprene production was increased to eightfold. For in depth understanding this novel system, the differential omics profiles were analyzed. The responses of BL21(DE3) to S. elongatus PCC 7942 were triggered by the oxidative pressure through the Fenton reaction and all these changes were linked with one another at different spatial and temporal scales. The oxidative stress mitigation pathways might contribute to the long-lasting fermentation process. The performance of this co-culture system can be further improved according to the fundamental rules discovered by the omics analysis.

Conclusions
The isoprene-producing co-culture system of S. elongates–E. coli was established and then analyzed by the omics methods. This study on the co-culture system of the model S. elongates–E. coli is of significance to reveal the common interactions between photo-autotrophic and heterotrophic species without natural symbiotic relation, which could provide the scientific basis for rational design of microbial community.
Effect of overexpression of SNF1 on the transcriptional and metabolic landscape of baker’s yeast under freezing stress
Authors: Meng Lu , Yang Xu , Lin Xue , Jiang Huan-Yuan , Hu Xiao-Ping , Liu Si-Xin 
Published: January 2021

Abstract
Background
Freezing stress is the key factor that affecting the cell activity and fermentation performance of baker’s yeast in frozen dough production. Generally, cells protect themselves from injury and maintain metabolism by regulating gene expression and modulating metabolic patterns in stresses. The Snf1 protein kinase is an important regulator of yeast in response to stresses. In this study, we aim to study the role of the catalytic subunit of Snf1 protein kinase in the cell tolerance and dough leavening ability of baker’s yeast during freezing. Furthermore, the effects of SNF1 overexpression on the global gene expression and metabolite profile of baker’s yeast before and after freezing were analysed using RNA-sequencing and untargeted UPLC − QTOF-MS/MS, respectively.

Results
The results suggest that overexpression of SNF1 was effective in enhancing the cell tolerance and fermentation capacity of baker’s yeast in freezing, which may be related to the upregulated proteasome, altered metabolism of carbon sources and protectant molecules, and changed cell membrane components. SNF1 overexpression altered the level of leucin, proline, serine, isoleucine, arginine, homocitrulline, glycerol, palmitic acid, lysophosphatidylcholine (LysoPC), and lysophosphatidylethanolamine (LysoPE) before freezing, conferring cells resistance in freezing. After freezing, relative high level of proline, lysine, and glycerol maintained by SNF1 overexpression with increased content of LysoPC and LysoPE.

Conclusions
This study will increase the knowledge of the cellular response of baker’s yeast cells to freezing and provide new opportunities for the breeding of low-temperature resistant strains.
CircRNA PIP5K1A promotes the progression of glioma through upregulation of the TCF12/PI3K/AKT pathway by sponging miR-515-5p
Authors: Zheng Kebin , Xie Haipeng , Wu Wensong , Wen Xichao , Zeng Zhaomu , Shi Yanfang 
Published: January 2021

AbstractBackgroundIncreasing studies have revealed that circular RNAs (CircRNAs) make great contributions to regulating tumor progression. Therefore, we intended to explore the expression characteristics, function, and related mechanisms of a novel type of circRNA, PIP5K1A, in glioma.MethodsFirstly, reverse transcription-polymerase chain reaction (RT-PCR) was carried out to examine CircPIP5K1A expression in glioma tissues and adjacent normal tissues, and the correlation between CircPIP5K1A level and the clinical-pathological indicators of glioma was analyzed. Then, the CircPIP5K1A expression in various glioma cell lines was detected, and CircPIP5K1A overexpression and knockdown cell models were constructed. Subsequently, cell proliferation and viability were detected by the CCK8 method and BrdU staining. Cell apoptosis was detected by flow cytometry, and cell invasion was examined by Transwell assay. The expression of TCF12, PI3K/AKT pathway apoptotic related proteins (Caspase3, Bax, and Bcl2) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, Vimentin, and N-cadherin) was determined by western blot or RT-PCR.ResultsThe results manifested that CircPIP5K1A was upregulated in glioma tissues (compared with that in normal adjacent tissues), and overexpressed CircPIP5K1A was related to glioma volume and histopathological grade. Functionally, overexpressing CircPIP5K1A notably elevated glioma cell proliferation, invasion, and EMT and inhibited apoptosis both in vivo and in vitro. Besides, CircPIP5K1A upregulated TCF12 and PI3K/AKT activation. Bioinformatics analysis testified that miR-515-5p was a common target of CircPIP5K1A and TCF12, while the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) experiment further confirmed that CircPIP5K1A targeted miR-515-5p, which bound the 3′-untranslated region (UTR) of TCF12.ConclusionsOverall, the study illustrated that CircPIP5K1A is a potential prognostic marker in glioma and regulates glioma evolvement by modulating the miR-515-5p-mediated TCF12/PI3K/AKT axis.
Suppression of TCAB1 expression induced cellular senescence by lessening proteasomal degradation of p21 in cancer cells
Authors: Niu Jing , Gao Rui-Qi , Cui Meng-Tian , Zhang Chen-Guang , Li Shen-Tao , Cheng Shan , Ding Wei 
Published: January 2021

Abstract
Background
TCAB1, a.k.a. WRAP53β or WDR79, is an important molecule for the maintenance of Cajal bodies and critically involved in telomere elongation and DNA repair. Upregulation of TCAB1 were discovered in a variety types of cancers. However, the function of TCAB1 in tumor cell senescence remains absent.

Methods
The TCAB1 knockdown cell lines were constructed. The expression levels of TCAB1, p21, p16 and p53 were detected by qRT-PCR and western blotting. Staining of senescence-associated β-galactosidase was used to detect senescent cells. The ubiquitination of the p21 was analysed by immunoprecipitation and in vivo ubiquitination assay. TCGA databases were employed to perform in silico analyses for the mRNA expression of TCAB1, p21, p16 and p53.

Results
Here, we discovered that knockdown of TCAB1 induced rapid progression of cellular senescence in A549, H1299 and HeLa cells. In exploiting the mechanism underlining the role of TCAB1 on senescence, we found a significant increase of p21 at the protein levels upon TCAB1 depletion, whereas the p21 mRNA expression was not altered. We verified that TCAB1 knockdown was able to shunt p21 from proteasomal degradation by regulating the ubiquitination of p21. In rescue assays, it was demonstrated that decreasing the expression of p21 or increasing the expression of TCAB1 were able to attenuate the cellular senescence process induced by TCAB1 silencing.

Conclusions
This study revealed the importance of TCAB1 for its biological functions in the regulation of cell senescence. Our results will be helpful to understand the mechanisms of senescence in cancer cells, which could provide clues for designing novel strategies for developing effective treatment regimens.
Multi-view 3D skin feature recognition and localization for patient tracking in spinal surgery applications
Authors: Manni Francesca , Mamprin Marco , Holthuizen Ronald , Shan Caifeng , Burström Gustav , Elmi-Terander Adrian , Edström Erik , Zinger Svitlana , de With Peter H. N. 
Published: January 2021

AbstractBackgroundMinimally invasive spine surgery is dependent on accurate navigation. Computer-assisted navigation is increasingly used in minimally invasive surgery (MIS), but current solutions require the use of reference markers in the surgical field for both patient and instruments tracking.PurposeTo improve reliability and facilitate clinical workflow, this study proposes a new marker-free tracking framework based on skin feature recognition.MethodsMaximally Stable Extremal Regions (MSER) and Speeded Up Robust Feature (SURF) algorithms are applied for skin feature detection. The proposed tracking framework is based on a multi-camera setup for obtaining multi-view acquisitions of the surgical area. Features can then be accurately detected using MSER and SURF and afterward localized by triangulation. The triangulation error is used for assessing the localization quality in 3D.ResultsThe framework was tested on a cadaver dataset and in eight clinical cases. The detected features for the entire patient datasets were found to have an overall triangulation error of 0.207 mm for MSER and 0.204 mm for SURF. The localization accuracy was compared to a system with conventional markers, serving as a ground truth. An average accuracy of 0.627 and 0.622 mm was achieved for MSER and SURF, respectively.ConclusionsThis study demonstrates that skin feature localization for patient tracking in a surgical setting is feasible. The technology shows promising results in terms of detected features and localization accuracy. In the future, the framework may be further improved by exploiting extended feature processing using modern optical imaging techniques for clinical applications where patient tracking is crucial.
Maternal education and equity in breastfeeding: trends and patterns in 81 low- and middle-income countries between 2000 and 2019
Authors: Neves Paulo A. R. , Barros Aluisio J. D. , Gatica-Domínguez Giovanna , Vaz Juliana S. , Baker Phillip , Lutter Chessa K. 
Published: January 2021

Abstract
Background
In low- and middle-income countries (LMICs), low levels of formal maternal educational are positively associated with breastfeeding whereas the reverse is true among women with higher levels of formal education. As such, breastfeeding has helped to reduce health equity gaps between rich and poor children. Our paper examines trends in breastfeeding and formula consumption by maternal educational in LMICs over nearly two decades.

Methods
We used 319 nationally representative surveys from 81 countries. We used WHO definitions for breastfeeding indicators and categorized maternal education into three categories: none, primary, and secondary or higher. We grouped countries according to the World Bank income groups and UNICEF regions classifications. The trend analyses were performed through multilevel linear regression to obtain average absolute annual changes in percentage points.

Results
Significant increases in prevalence were observed for early initiation and exclusive breastfeeding across all education categories, but more prominently in women with no formal education for early breastfeeding and in higher level educated women for exclusive breastfeeding. Small decreases in prevalence were seen mostly for women with no formal education for continued breastfeeding at 1 and 2 years. Among formula indicators, only formula consumption between 6 and 23 months decreased significantly over the period for women with primary education. Analysis by world regions demonstrated that gains in early and exclusive breastfeeding were almost universally distributed among education categories, except in the Middle East and North Africa where they decreased throughout education categories. Continued breastfeeding at 1 and 2 years increased in South Asia, Latin America and the Caribbean, and Eastern Europe and Central Asia for primary or higher education categories. Declines occurred for the group of no formal education in South Asia and nearly all education categories in the Middle East and North Africa with a decline steeper for continued breastfeeding at 2 years. With a few exceptions, the use of formula is higher among children of women at the highest education level in all regions.

Conclusions
Over the course of our study, women with no formal education have worsening breastfeeding indicators compared to women with primary and secondary or higher education.