bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast and Efficient Rmap Assembly using the Bi-labelled de Bruijn Graph
Authors: Mukherjee Kingshuk , Rossi Massimiliano , Salmela Leena , Boucher Christina 
Published: January 2021

Abstract
Genome wide optical maps are high resolution restriction maps that give a unique numeric representation to a genome. They are produced by assembling hundreds of
thousands of single molecule optical maps, which are called Rmaps. Unfortunately, there exists very few choices for assembling Rmap data. There exists only one publicly-available non-proprietary method for assembly and one proprietary method that is available via an executable. Furthermore, the publicly-available method, by Valouev et al. (2006), follows the overlap-layout-consensus (OLC) paradigm, and therefore, is unable to scale for relatively large genomes. The algorithm behind the proprietary method, Bionano Genomics' Solve, is largely unknown. In this paper, we extend the definition of bi-labels in the paired de Bruijn graph to the context of optical mapping data, and present the first de Bruijn graph based method for Rmap assembly. We implement our approach, which we refer to as Rmapper, and compare its performance against the assembler of Valouev et al. (2006) and Solve by Bionano Genomics on data from three genomes - E. coli, human, and climbing perch fish (Anabas Testudineus). Our method was able to successfully run on all three genomes. The method of Valouev et al.(2006) only successfully ran on E. coli. Moreover, on the human genome Rmapper was at least 130 times faster than Bionano Solve, used five times less memory and produced the highest genome fraction with zero mis-assemblies. Our software, RMAPPER is written in C++ and is publicly available under GNU General Public License at https://github.com/kingufl/Rmapper.
Exploring the Pharmacological Mechanisms of Tripterygium Wilfordii Hook F against Cardiovascular Disease Using Network Pharmacology and Molecular Docking
Authors: Huang Bingwu , Huang Chengbin , Zhu Liuyan , Xie Lina , Wang Yi , Zhu Ning 
Published: January 2021

Abstract
Background

Tripterygium wilfordii Hook F (TwHF) has been used in traditional Chinese medicines (TCM) for treating cardiovascular disease (CVD). However, the underlying pharmacological mechanisms of the effects of TwHF against CVD remain elusive. This study revealed the pharmacological mechanisms of TwHF acting on CVD based on a pharmacology approach.
Materials and Methods

The active compounds were selected by Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) according to the absorption, distribution, metabolism, and excretion (ADME). The potential targets of TwHF were obtained by SwissTargetPrediction database. The CVD-related therapeutic targets were collected by the DrugBank, the GeneCards database and the OMIM database. Protein–protein interaction (PPI) network was generated by STITCH database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by R package. The network of drug-targets-diseases-pathways was constructed by Cytoscape software.
Results

The 51 effective ingredients of TwHF and the 178 common targets of TwHF and CVD-related were collected. Furthermore, AKT1, amyloid precursor protein (APP), Mitogen-activated protein kinase 1 (MAPK), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) and cellular tumor antigen p53 (TP53) was identified the core targets involved in the mechanism of TwHF on CVD. Top ten GO (biological processes, cellular components and molecular functions) and KEGG pathways were screened with a P value ≤ 0.01. Finally, we constructed the network of TwHF-targets-CVD-GO-KEGG.
Conclusions

These findings demonstrate that the main active compound of TwHF, the core targets and pathways maybe provide new insights into the development of a natural therapy for the prevention and treatment of CVD.
Food Security among People who Inject Drugs in West Virginia
Authors: Rouhani Saba , Allen Sean T , Whaley Sarah , White Rebecca H , O'Rourke Allison , Schneider Kristin E , Kilkenny Michael E , Weir Brian W , Sherman Susan G 
Published: January 2021

Abstract
Background. The substance use epidemic in the United States continues to drive high levels of morbidity and mortality, particularly among people who inject drugs (PWID). Poor access to food co-occurs with illicit drug use and contributes to associated sequelae, such as HIV and diabetes. The objective of this study was to examine factors associated with food security among PWID in a rural Appalachian community. Methods. Cross-sectional surveys were used to collect data in a sample of 420 PWID aged 18 and older Cabell County, West Virginia. Frequency of food access and sociodemographic, structural and drug use characteristics were measured. Food security was defined as reporting ‘never’ going to bed hungry at night in the past six months. Pearson’s χ2 and t-tests were used to identify factors associated with food security. Multivariable logistic regression was employed to estimate adjusted odds of being food secure.Results. Only 71 individuals (17%) reported never going to bed hungry night in the past six months. Adjusted odds of being food secure were higher among PWID who completed high school (aOR 2.94; P=0.010) and usually using drugs alone (aOR 1.97; P=0.025), and lower among PWID who were female (aOR 0.51; P=0.037), experienced homelessness (aOR 0.23, P<0.001), were recently arrested (aOR 0.50 P=0.049), and engaged in receptive sharing of injection equipment (aOR 0.52, P=0.035).Conclusions. We found extremely low levels of food security in a population of PWID in Appalachia who are vulnerable to overdose and infectious disease transmission. Integrated interventions that approach food provision as harm reduction are needed to address the overlapping factors that jeopardize the health and wellbeing of people who inject drugs.
Prevalence and Molecular Characteristics of Drug-Resistant Mycobacterium Tuberculosis in Hainan, China: From 2014 to 2019
Authors: zhao xiujuan , Liu Lin , Wu Xingyong , Li Sijing , Liu Biao , Rajaofera Mamy Jayne Nelly , Zeng Yingfei , Dong Sufang , Bei Zheng , Pei Hua , Xia Qianfeng 
Published: January 2021

Abstract
BackgroundThe emergence of antimicrobial resistance against mycobacterium tuberculosis has become the major concern in global tuberculosis control due to its limited therapy options and high mortality. However, the clinical and molecular characteristics of drug-resistant strains vary in different geographical areas. Hainan Island located in southern China, is a high drug-resistant tuberculosis burden area. This study aimed to determine the dynamic changes of drug-resistance patterns and drug-related gene mutation types of mycobacterium tuberculosis in Hainan from 2014 to 2019. ResultsA total of 1484 culture-confirmed mycobacterium tuberculosis were included in this study. It was found that the proportions of drug resistance to isoniazid and rifampin were 31.3% and 31.1% respectively. Overall, the proportion of multidrug resistant mycobacterium tuberculosis was 24.9%. Multivariate logistic regression analysis showed that age and the treatment history were independent influencing factors of drug resistant tuberculosis. The proportions of drug-resistant tuberculosis in retreatment patients were considerably higher than those in new patients. The most common mutation types of isoniazid were Ser315 → Thr (66.3%), and the most common mutation types of rifampin were Ser 531 → Leu (41.5%). ConclusionsOur data suggests that the prevalence of drug resistant TB remains high in Hainan, and the risks for developing drug resistance with diversified and complicated mutation types increased significantly in retreatment patients. These results contribute to the knowledge of the prevalence of drug resistance in Hainan Province and also expand the molecular characteristics of drug resistance in China.
The Study of Laccase Immobilization Optimization and Stability Improvement on CTAB-KOH Modified Biochar
Authors: Wang Zhaobo , Ren Dajun , Li Zihang , Yu Hongyan , Zhang Shuqin , Zhang Xiaoqing , Chen Wangsheng 
Published: January 2021

Abstract
Background: In this paper, cetyltrimethylammonium bromide (CTAB)-KOH modified biochar (CKMB) was used to immobilize laccase by adsorption method (laccase@CKMB). Based on the results of the single-factor experiments, the optimal loading conditions of laccase@CKMB were studied with the assistance of Design-Expert 12 and response surface methods. Results: The predicted optimal experimental conditions were laccase dosage 1.78 mg/mL, pH 3.1 and 312 K. Under these conditions, the activity recovery of laccase@CKMB was the highest, reaching 61.78 %. Then, the CKMB and laccase@CKMB were characterized by TGA, FT-IR, XRD, BET and SEM, and the results showed that laccase could be well immobilized on CKMB, the maximum enzyme loading could reach 57.5 mg/g. Compared to free laccase, the storage and pH stability of laccase@CKMB was improved greatly. The laccase@CKMB retained about 40 % of relative activity (4 ℃, 30 days) and more than 50 % of relative activity at pH 2-6. In addition, the laccase@CKMB indicated the reusability up to 6 reaction cycles while retaining 45.1 % of relative activity. Moreover, the thermal deactivation kinetic studies of laccase@CKMB showed a lower k value (0.00275 min-1) and higher t1/2 values (252.0 min) than the k value (0.00573 min-1) and t1/2 values (121.0 min) of free laccase. Conclusions: In summary, we explored scientific and reasonable immobilization conditions of laccase@CKMB, and the laccase@CKMB possessed relatively better stabilities, which gave the immobilization of laccase on this cheap and easily available carrier material the possibility of industrial applications.
Effects of inducible and constitutive expression vectors on heterologous expression of LEH mutants BE3 and BG5
Authors: Yong Jie , Liu Binghuan , Wang Kunlun , Yang Hui , Tian Yun , Zhou Haiyan 
Published: January 2021

Abstract
Background

Limonene epoxide hydrolase (LEH) is a class of enzymes in Epoxide hydrolases (EHs) that can form chiral products only by one step catalysis. High purity S or R chiral intermediates play an important role in the application of biomedical industry, and can be used to synthesize various drugs such as ibuprofen, linezoline, cilastatin, etc. Therefore, it has application value to find the expression system which can realize the stable and efficient conversion of LEH to produce high purity S and R chiral products.
Results

We explored the constitutive expression system of LEH for the first time, and tried to realize the expression of LEH in B.subtilis WB800. Firstly, the LEH mutant on the original inducible vector pBAD-Myc-HisA was obtained and connected to the constitutive vector pHY-p43 containing strong promoter p43. E. coli TOP10 and B.subtilis WB800 were used as the host bacteria to realize the non induced and secretory expression of LEH.
Conclusions

The results showed that the non induced expression of LEH could be achieved successfully by using the constitutive promoter vector pHY-p43, and the substrate affinity and enzyme catalytic efficiency of the mutants have increased. The catalytic decomposition of the substrate and the formation of chiral products by LEH were determined by GC-MS, which also had stable enzyme activity in the system. This study laid a foundation for large-scale fermentation of LEH and catalytic production of chiral products.
Impact of Maternal Chronodisruption on Female Offspring Puberty. A Role of Kisspeptin and Irisin
Authors: Alonso Ana , Medina Beatriz , González Celestino , Díaz Elena 
Published: January 2021

Abstract
The neuroendocrine mechanisms regulating the onset of puberty are unclear. Kisspeptin is a potent gatekeeper of pubertal onset, but it has also been proposed that the time of puberty is dictated by kisspeptin independent mechanism. In this way, the myokine irisin could be involved in the puberty onset process serving as a metabolic trigger. Puberty is influenced by environmental factors like photoperiod. Maternal photoperiod influences postnatal development; thus alterations in maternal melatonin rhythm may affect the offspring’s reproductive axis development, especially at puberty. There is no research regarding the influence of maternal photoperiod on kisspeptin and irisin profile in offspring close to puberty. We investigated the influence of maternal photoperiod on serum kisspeptin and irisin levels during sexual development in female rat offspring.The study was carried out on female offspring Wistar rats at 25 and 30 days of age and in the vaginal opening day. Pregnant mother rats were included in three groups; control (12L/12 D), other exposed to continuous light during pregnancy (24L/0D), and the third exposed to continuous light as well as receiving daily melatonin during pregnancy. Serum kisspeptin and irisin were determined and vaginal opening day were registered. The results demonstrated that both continuous light exposure and melatonin treatment during intrauterine life affects kisspeptin and irisin secretion in the offspring during sexual maturation; these point out to an important role of the cytokine irisin in the onset of puberty.
Dexmedetomidine might improve postoperative cognitive dysfunction in older patients undergoing pulmonary surgery
Authors: LIU Tao , Liu Chao Fang , Luo Jun Tai , YU Xia , Chen Bin , Wang Chun , Gao Kuo Guang , Shi Guo Zhi , Zhai Ting Wen , Liu Wei 
Published: January 2021

Abstract
Background

The effect of dexmedetomidine on cognitive function after various surgeries were reported, however no consensus is made on pulmonary surgery. In this study we aimed at investigating the effect of dexmedetomidine anesthesia on postoperative cognitive function (POCD) in pulmonary surgery.
Methods

A prospective randomized placebo-controlled study was conducted with blinded to patients. The study was performed on 60 patients (29 in the dexmedetomidine group; 31 in the placebo group). Dexmedetomidine-group patients received dexmedetomidine (1 µg/kg, i.v.) and Placebo-group patients received an equal volume of physiologic (0.9%) saline for 20 min before anesthesia induction. Cognitive function was evaluated using Montreal Cognitive Assessment (MoCA) 1 day before surgery, as well as on postoperative day (POD)1, POD3 and POD7. The regional cerebral oxygen saturation (rSO2) was monitored continuously by near-infrared spectroscopy before anesthesia.
Results

The MoCA score between the two groups was significantly different on POD1 (Dex 26.4 ± 0.73 vs Placebo 25.5 ± 0.96, p < 0.001) and POD3 (Dex 27.1 ± 0.79 vs Placebo 26.6 ± 0.80, p = 0.032). In detail, attention and orientation scores were increased in the dexmedetomidine group on POD1 and POD3. The rSO2 between the dexmedetomidine group or placebo group was not significantly different (Dex 64.9 ± 2.73 vs. Placebo 64.3 ± 3.29, p = 0.483), and no significant difference was found before drug administration and after regaining consciousness (Dex 63.5 ± 2.52 vs. Placebo 64.2 ± 3.22; p = 0.390).
Conclusion

We showed, for the first time, that dexmedetomidine (1.0 µg/kg) could reduce the risk of POCD and might not decrease rSO2. Hence, dexmedetomidine could be employed in pulmonary surgical procedures, especially for older patients facing high risk of delirium.
Determination of the median effective dose of dexmedetomidine for the prevention of emergence agitation in geriatric patients undergoing major open surgery with general anesthesia: A prospective, double-blinded, dose-response trial
Authors: wang weibing , Sun AiJiao , Xiao JingBo , Dong JingChun , Xu Huang , Zhou Hui 
Published: January 2021

Abstract
BackgroundDexmedetomidine can effectively decrease the incidences of emergence agitation (EA) in adult patients, but there are major side effects related to increased dose of dexmedetomidine. The purpose of this study was to determine of the median effective dose of dexmedetomidine in the prevention of EA among geriatric patients undergoing major open surgery with general anesthesia.MethodsA total of 50 geriatric patients were enrolled in this study. Dexmedetomidine 0.5µg·kg-1·h-1 continuous intravenous infusion was administered to the first patient. The next dose was increased or decreased by 0.05 depending on the response of the previous patient, according to the Dixon up-and-down method. An “effective” or “ineffective” response was determined based on the Riker sedation-agitation score(RSAS), we defined “effective” as RSAS < 5, and “ineffective” as RSAS ≥ 5.ResultsThe ED50 of dexmedetomidine in prevention of EA was 0.30µg·kg-1·h-1 (95% CI, 0.27–0.33) and the predicted ED95 was 0.42µg·kg-1·h-1(95% CI, 0.38–0.51). The incidence of bradycardia was significant increased in group without EA compared to the group with EA (57.1% vs 13.6%, P = 0.002).ConclusionsThe ED50 of dexmedetomidine in prevention of EA was 0.30µg·kg-1·h-1 (95% CI, 0.27–0.33) and the predicted ED95 was 0.42µg·kg-1·h-1 (95% CI, 0.38–0.51). Bradycardia was the main complication.Trial registrationThis study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR1900023769) on June 11th, 2019.
Identifying Contextual Determinants of Problems in Tuberculosis Care Provision in South Africa: A Theory-Generating Case Study
Authors: Murdoch Jamie , Curran Robyn , Rensburg André J van , Awotiwon Ajibola , Dube Audry , Bachmann Max , Petersen Inge , Fairall Lara 
Published: January 2021

Abstract
BackgroundDespite progress towards meeting End TB strategy targets for reducing tuberculosis (TB) incidence and deaths by 2035, South Africa remains among the top ten high-burden tuberculosis countries globally. A large challenge lies in how policies to improve detection, diagnosis and treatment completion interact with social and structural drivers of TB. Detailed understanding and theoretical development of the contextual determinants of problems in TB care is required for developing effective interventions. This article reports findings from the pre-implementation phase of a study of TB care in South Africa, contributing to ASSET - a broader five-year research programme developing and evaluating health system strengthening interventions in sub-Saharan Africa. The study aimed to develop hypothetical propositions regarding the contextual determinants of problems in TB care to inform intervention development to reduce TB deaths and incidence whilst ensuring the delivery of quality integrated, respectful person-centred care. MethodsTheory-building case study design using the Context and Implementation of Complex Interventions (CICI) framework to identify contextual determinants of problems in TB care. Between February and November 2019, we used mixed methods in six public- sector primary healthcare facilities and one public sector hospital serving impoverished urban and rural communities in the Amajuba district of KwaZulu-Natal province, South Africa. Qualitative data included stakeholder interviews, observations and documentary analysis. Quantitative data included routine data on sputum testing and TB deaths. Data were inductively analysed and mapped onto the seven CICI contextual domains. ResultsDelayed diagnosis was caused by interactions between fragmented healthcare provision; limited resources; verticalised care provision; poor TB screening, sputum collection and record-keeping. One nurse responsible for TB care, limited integration with other conditions, and policy focus on treatment adherence contributed to staff stress and limited focus on patients’ psychosocial needs. Patients were lost to follow up due to discontinuity of information, poverty, employment restrictions and limited support for treatment side-effects. Infection control measures appeared to be compromised by efforts to integrate care.ConclusionInterventions are required that strengthen early detection, diagnosis, treatment initiation and completion. TB policy needs to promote person-centred support for healthcare professionals and patients through the TB treatment pathway.
ZRANB1 Drives Hepatocellular Carcinoma Progression through SP1-LOXL2 Axis
Authors: Xie Peiyi , Li Qing , Chao Qing , Fang Jiayu , Xie Jing , Liu Yue , Zhen Jing , Ding Yongqi , Fu Bidong , Ke Yun , Xiao Fan , Wu Honghu , Huang Zhaoxia , Hao Haibin , Huang Da 
Published: January 2021

Abstract
BackgroundDeubiquitinase (DUB) zinc finger RANBP2-type containing 1 (ZRANB1/TRABID) has been reported to have a close relationship with cancers. However, its underlying role and molecular mechanisms in hepatocellular carcinoma (HCC) remain elusive. MethodsGene and protein expression of ZRANB1 in HCC tissues were determined by qRT-PCR, western blot and immunohistochemistry. A series of gain- and loss-of-function assays were used to investigated the role of ZRANB1 in HCC cells progression. Moreover, RNA-seq were used to identify the downstream targets of ZRANB1 in HCC cells. The interaction between ZRANB1 and SP1 was examined through co-IP experiment and in vitro ubiquitination assay.ResultsZRANB1 was highly expressed in HCC tissues and ZRANB1 can regulate HCC cell growth and metastasis in vitro and in vivo. Through RNA-seq, we identified that Lysyl oxidase-like 2 (LOXL2) was the most significantly downregulated gene after ZRANB1 knockdown. Furthermore, the scatter plots indicated a significant positive correlation between ZRANB1 and LOXL2 expression in clinical HCC specimens. Additionally, LOXL2 was essential for ZRANB1-mediated HCC growth and metastasis. More importantly, specificity protein 1 (SP1) was critical in ZRANB1-mediated regulation of LOXL2 expression. Mechanistically, ZRANB1 bound with SP1 directly and stabilized the SP1 protein by deubiquitinating it. The expression patterns of ZRANB1, SP1 and LOXL2 were evaluated in HCC patients. ConclusionZRANB1 overexpression facilitates the carcinogenesis of HCC through stabilizing and upregulating SP1 to promote LOXL2 expression, suggesting ZRANB1 can be novel prognostic biomarker for HCC treatment.