bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of a recombinant bacterial l-asparaginase in human cells
Authors: Dantas Raquel Caminha , Caetano Ludmilla Freire , Torres Ariany Lima Sousa , Alves Matheus Soares , Silva Emanuelly Thays Muniz Figueiredo , Teixeira Louhanna Pinheiro Rodrigues , Teixeira Daniel Câmara , de Azevedo Moreira Renato , Fonseca Marcela Helena Gambim , Gaudêncio Neto Saul , Martins Leonardo Tondello , Furtado Gilvan Pessoa , Tavares Kaio Cesar Simiano 
Published: December 2019

Abstract
Objective
l-Asparaginase (ASNase) is an enzyme used in the treatment of acute lymphoblastic leukemia (ALL). As the therapeutic ASNases has bacterial origin, severe side effects are associated with its use, among them hypersensitivity and inactivation of the enzyme. In this context, the objective of this work was to produce a recombinant ASNase of bacterial origin in human cells in order to determine the presence and consequences of potential post-translational modifications on the enzyme.

Results
Recombinant ASNase was expressed in human cells with a molecular weight of 60 kDa, larger than in Escherichia coli, which is 35 kDa. N-glycosylation analysis demonstrated that the increased molecular weight resulted from the addition of glycans to the protein by mammalian cells. The glycosylated ASNase presented in vitro activity at physiological pH and temperature. Given that glycosylation can act to reduce antigenicity by masking protein epitopes, our data may contribute to the development of an alternative ASNase in the treatment of ALL in patients who demonstrate side effects to currently marketed enzymes.
Wharton’s jelly mesenchymal stem cell-based or umbilical vein endothelial cell-based serum-free coculture with cytokines supports the ex vivo expansion/maintenance of cord blood hematopoietic stem/progenitor cells
Authors: Li Qiuyang , Zhao Dewan , Chen Qiang , Luo Maowen , Huang Jingcao , Yang Cao , Wang Fangfang , Li Wenxian , Liu Ting 
Published: December 2019

Abstract
Background
The umbilical cord blood (UCB) has been widely accepted as an alternative source of hematopoietic stem/progenitor cells (HSPCs) for transplantation, and its use in adults is still restricted because of low absolute numbers. To overcome this obstacle, expansion of UCB-HSPCs under feeder cell-based coculture is a promising possibility. In this study, we explored UCB-CD34+ cells ex vivo expansion using Wharton’s jelly mesenchymal stem cells (WJ-MSCs) or umbilical vein endothelial cells (UVECs) as feeder layer-based serum-free coculture system with a cocktail of cytokines.

Methods
UCB-CD34+ cells were cultured in five different coculture conditions composed of umbilical cord stromal cells (WJ-MSCs or UVECs) with or without a cocktail of cytokines (SCF, FLT3L, and TPO). The cultured cells were harvested at day 10 and analyzed for phenotypes and functionalities, including total nuclear cells (TNCs), CD34+ cells, CD34+CD38− cells, colony-forming unit (CFU) for committed progenitors, and long-term culture initiating cells (LTC-ICs) for HSPCs.

Results
Our work showed the numbers of TNC cells, CD34+ cells, and CD34+CD38− cells were expanded under five coculture conditions, and the feeder layer-based cocultures further promoted the expansion. The numbers of colonies of CFU-GM, CFU-E/BFU-E, and CFU-GEMM in the cocultures with cytokines were significantly higher than their counterparts at day 0 (p < 0.05), while no significant difference (p > 0.05) in those without the addition of cytokines. The numbers of LTC-ICs were increased both under the WJ-MSCs and UVECs with cytokine cocultures, but only in the UVECs group showed a significant difference (p < 0.05), and were decreased under conditions without cytokine (p < 0.05).

Conclusion
Our data demonstrate that both WJ-MSCs and UVECs as feeder layer could efficiently support the expansion of UCB-CD34+ cells in synergy with SCF, FLT3L, and TPO under serum-free culture condition. The UVECs combined with the 3GF cytokine cocktail could maintain the growth of LTC-ICs derived from UCB-CD34+ cells and even expand to some extent.
The chemfp project
Authors: Dalke Andrew 
Published: December 2019

AbstractThe chemfp project has had four main goals: (1) promote the FPS format as a text-based exchange format for dense binary cheminformatics fingerprints, (2) develop a high-performance implementation of the BitBound algorithm that could be used as an effective baseline to benchmark new similarity search implementations, (3) experiment with funding a pure open source software project through commercial sales, and (4) publish the results and lessons learned as a guide for future implementors. The FPS format has had only minor success, though it did influence development of the FPB binary format, which is faster to load but more complex. Both are summarized. The chemfp benchmark and the no-cost/open source version of chemfp are proposed as a reference baseline to evaluate the effectiveness of other similarity search tools. They are used to evaluate the faster commercial version of chemfp, which can test 130 million 1024-bit fingerprint Tanimotos per second on a single core of a standard x86-64 server machine. When combined with the BitBound algorithm, a k = 1000 nearest-neighbor search of the 1.8 million 2048-bit Morgan fingerprints of ChEMBL 24 averages 27 ms/query. The same search of 970 million PubChem fingerprints averages 220 ms/query, making chemfp one of the fastest CPU-based similarity search implementations. Modern CPUs are fast enough that memory bandwidth and latency are now important factors. Single-threaded search uses most of the available memory bandwidth. Sorting the fingerprints by popcount improves memory coherency, which when combined with 4 OpenMP threads makes it possible to construct an N × N similarity matrix for 1 million fingerprints in about 30 min. These observations may affect the interpretation of previous publications which assumed that search was strongly CPU bound. The chemfp project funding came from selling a purely open-source software product. Several product business models were tried, but none proved sustainable. Some of the experiences are discussed, in order to contribute to the ongoing conversation on the role of open source software in cheminformatics.
Molecular characterization of a Trichinella spiralis enolase and its interaction with the host’s plasminogen
Authors: Jiang Peng , Zao You Jiao , Yan Shu Wei , Song Yan Yan , Yang Dong Min , Dai Li Yuan , Liu Ruo Dan , Zhang Xi , Wang Zhong Quan , Cui Jing 
Published: December 2019

AbstractThe binding and activation of host plasminogen (PLG) by worm surface enolases has been verified to participate in parasite invasion, but the role of this processes duringTrichinella spiralisinfection has not been clarified. Therefore, the expression and immunolocalization of aT. spiralisenolase (TsENO) and its binding activity with PLG were evaluated in this study. Based on the three-dimensional (3D) molecular model of TsENO, the protein interaction between TsENO and human PLG was analysed by the ZDOCK server. The interacting residues were identified after analysis of the protein–protein interface by bioinformatics techniques. The key interacting residues were confirmed by a series of experiments. The qPCR analysis results demonstrated that Ts-enowas transcribed throughout the whole life cycle ofT. spiralis. The immunofluorescence assay (IFA) results confirmed that TsENO was distributed on theT. spiralissurface. The binding assays showed that recombinant TsENO (rTsENO) and native TsENO were able to bind PLG. Four lysine residues (90, 289, 291 and 300) of TsENO were considered to be active residues for PLG interaction. The quadruple mutant (Lys90Ala + Lys289Ala + Lys291Ala + Lys300Ala) TsENO, in which the key lysine residues were substituted with alanine (Ala) residues, exhibited a reduction in PLG binding of nearly 50% (45.37%). These results revealed that TsENO has strong binding activity with human PLG. The four lysine residues (90, 289, 291 and 300) of TsENO play an important role in PLG binding and could accelerate PLG activation and invasion of the host’s intestinal wall byT. spiralis.
Effectiveness of physical activity promotion and exercise referral in primary care: protocol for a systematic review and meta-analysis of randomised controlled trials
Authors: Laake Jean-Pierre , Fleming Joanna 
Published: December 2019

Abstract
Background
Physical inactivity is the fourth leading risk factor for global mortality. Reducing sedentary behaviour and increasing physical activity are efficacious for improving many physical and mental health conditions including cardiovascular disease, type 2 diabetes and depression. Reducing sedentary behaviour and increasing physical activity can also be effective at reducing obesity; however, sedentary behaviour and reduced physical activity are also associated with mortality independently. Despite this, most adults in the UK do not currently meet the UK Chief Medical Officers’ guidelines for weekly physical activity. As most adults visit their general practitioner at least once a year, the primary care consultation provides a unique opportunity to deliver exercise referral or physical activity promotion interventions. This is a protocol for a systematic review of randomised controlled trials for the effectiveness of physical activity promotion and referral in primary care.

Methods
A comprehensive literature search of Embase, MEDLINE (Ovid), Web of Science (Core Collection), Scopus, CINAHL, PsycINFO, and The Cochrane Library (CENTRAL) will be conducted for studies with a minimum follow-up of 12 months that report physical activity as an outcome measure (by either self-report or objective measures) including an intention to treat analysis. The authors will screen papers, first by title and abstract and then by full text, independently assess studies for inclusion, appraise risk of bias and extract data. The quality of the evidence will be assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluations) approach. The primary outcome will be participation in physical activity at 12 months. Pooled effects will be calculated using random effects models. Results will be submitted for publication in a peer-reviewed journal and for presentation at UK national primary care conferences.

Discussion
This systematic review and meta-analyses will summarise the evidence for the effectiveness of physical activity promotion and referral as interventions for improving physical activity, as well as whether studies using objective measures of physical activity have similar effects to those studies using self-report measures. This knowledge has importance for primary care clinicians, patients and, given the focus of the recent NHS long-term plan on preventive medicine, those making policy decisions.

Systematic review registration
The protocol is registered with PROSPERO the international prospective register of systematic reviews, ID CRD42019130831
Antibiotic regimens for neonatal sepsis - a protocol for a systematic review with meta-analysis
Authors: Korang Steven Kwasi , Safi Sanam , Gluud Christian , Lausten-Thomsen Ulrik , Jakobsen Janus C. 
Published: December 2019

Abstract
Background
Sepsis is a major cause of morbidity and mortality among neonates and infants. Antibiotics are a central part of the first line treatment for sepsis in neonatal intensive care units worldwide. However, the evidence on the clinical effects of the commonly used antibiotic regimens for sepsis in neonates remains scarce. This systematic review aims to assess the efficacy and harms of antibiotic regimens for neonatal sepsis.

Methods
Electronic searches will be conducted in MEDLINE, Embase, The Cochrane Library, CINAHL, ZETOC and clinical trial registries (clinicaltrials.gov and ISRCTN). We will include randomised controlled trials of different antibiotic regimens for sepsis of neonates and infants. Eligible interventions will be any antibiotic regimen. Two reviewers will independently screen, select, and extract data. The methodological quality of individual studies will be appraised following Cochrane methodology. Primary outcomes will be ‘all-cause mortality’ and ‘serious adverse events’. Secondary outcomes will be ‘need for respiratory support’, ‘need for circulatory support’, ‘neurodevelopmental impairment’, ototoxicity, nephrotoxicity and necrotizing enterocolitis. We plan to perform a meta-analysis with trial sequential analysis.

Discussion
This is the study protocol for a systematic review on the effects of different antibiotic regimens for neonatal sepsis. The results of this systematic review intent to adequately inform stakeholders or health care professionals in the field of neonatal sepsis, and to aid appropriate development of treatment guidelines.

Systematic review registration
PROSPERO reference number: CRD42019134300.
Estimation for random coefficient integer-valued autoregressive model under random environment
Authors: Cui Yan , Wang Yun Y. 
Published: December 2019

AbstractA first-order random coefficient integer-valued autoregressive model based on the negative binomial thinning operator under r states random environment is introduced. This paper derives numerical characteristics of the proposed model, establishes Yule–Walker estimators of model parameters, and discusses the strong consistency of the obtained estimators. Finally, a simulation is carried out to verify the feasibility of parameter estimation.
Molecular characterization of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates identifies local transmission of infection in Kuwait, a country with a low incidence of TB and MDR-TB
Authors: Al-Mutairi Noura M. , Ahmad Suhail , Mokaddas Eiman M. 
Published: December 2019

AbstractBackgroundIncreasing incidence of multidrug-resistantMycobacterium tuberculosisinfections is hampering global tuberculosis control efforts. Kuwait is a low-tuberculosis-incidence country, and ~ 1% ofM. tuberculosisstrains are resistant to rifampicin and isoniazid (MDR-TB). This study detected mutations in seven genes predicting resistance to rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin in MDR-TB strains. Sequence data were combined with spoligotypes for detecting local transmission of MDR-TB in Kuwait.MethodsNinety-three MDR-TB strains isolated from 12 Kuwaiti and 81 expatriate patients and 50 pansusceptible strains were used. Phenotypic drug susceptibility was determined by MGIT 460 TB/960 system. Mutations conferring resistance to rifampicin, isoniazid, pyrazinamide, ethambutol and streptomycin were detected by genotype MTBDRplusassay and/or PCR sequencing of threerpoBregions, katGcodon 315 (katG315) + inhAregulatory region,pncA, threeembBregions andrpsL + rrs-500–900 regions. Spoligotyping kit was used, spoligotypes were identified by SITVIT2, and phylogenetic tree was constructed by using MIRU-VNTRplus software. Phylogenetic tree was also constructed from concatenated sequences by MEGA7 software. Additional PCR sequencing ofgidBandrpsAwas performed for cluster isolates.ResultsPansusceptible isolates contained wild-type sequences. Mutations inrpoBandkatGand/orinhAwere detected in 93/93 and 92/93 MDR-TB strains, respectively. Mutations were also detected for pyrazinamide resistance, ethambutol resistance and streptomycin resistance in MDR-TB isolates inpncA,embBandrpsL + rrs, respectively. Spoligotyping identified 35 patterns with 18 isolates exhibiting unique patterns while 75 isolates grouped in 17 patterns. Beijing genotype was most common (32/93), and 11 isolates showed nine orphan patterns. Phylogenetic analysis of concatenated sequences showed unique patterns for 51 isolates while 42 isolates grouped in 16 clusters. Interestingly, 22 isolates in eight clusters by both methods were isolated from TB patients typically within a span of 2 years. Five of eight clusters were confirmed by additionalgidBandrpsAsequence data.ConclusionsOur study provides the first insight into molecular epidemiology of MDR-TB in Kuwait and identified several potential clusters of local transmission of MDR-TB involving 2–6 subjects which had escaped detection by routine surveillance studies. Prospective detection of resistance-conferring mutations can identify possible cases of local transmission of MDR-TB in low MDR-TB settings.
Molecular biogeography of planktonic and benthic diatoms in the Yangtze River
Authors: Wang Jiawen , Liu Qingxiang , Zhao Xianfu , Borthwick Alistair G. L. , Liu Yuxin , Chen Qian , Ni Jinren 
Published: December 2019

Abstract
Background
Diatoms are of great significance to primary productivity in oceans, yet little is known about their biogeographic distribution in oligotrophic rivers.

Results
With the help of metabarcoding analysis of 279 samples from the Yangtze River, we provided the first integral biogeographic pattern of planktonic and benthic diatoms over a 6030 km continuum along the world’s third largest river. Our study revealed spatial dissimilarity of diatoms under varying landforms, including plateau, mountain, foothill, basin, foothill-mountain, and plain regions, from the river source to the estuary. Environmental drivers of diatom communities were interpreted in terms of photosynthetically active radiation, temperature, channel slope and nutrients, and human interference. Typical benthic diatoms, such as Pinnularia, Paralia, and Aulacoseira, experienced considerable reduction in relative abundance downstream of the Three Gorges Dam and the Xiluodu Dam, two of the world’s largest dams.

Conclusions
Our study revealed that benthic diatoms are of particular significance in characterizing motile guild in riverine environments, which provides insights into diatom biogeography and biogeochemical cycles in large river ecosystems.
EFTUD2 gene deficiency disrupts osteoblast maturation and inhibits chondrocyte differentiation via activation of the p53 signaling pathway
Authors: Wu Jing , Yang Yi , He You , Li Qiang , Wang Xu , Sun Chengjun , Wang Lishun , An Yu , Luo Feihong 
Published: December 2019

Abstract
Background
Mandibulofacial dysostosis with microcephaly (MFDM) is characteristic of multiple skeletal anomalies comprising craniofacial anomalies/dysplasia, microcephaly, dysplastic ears, choanal atresia, and short stature. Heterozygous loss of function variants of EFTUD2 was previously reported in MFDM; however, the mechanism underlying EFTUD2-associated skeletal dysplasia remains unclear.

Results
We identified a novel frameshift variant of EFTUD2 (c.1030_1031delTG, p.Trp344fs*2) in an MFDM Chinese patient with craniofacial dysmorphism including ear canal structures and microcephaly, mild intellectual disability, and developmental delay. We generated a zebrafish model of eftud2 deficiency, and a consistent phenotype consisting of mandibular bone dysplasia and otolith loss was observed. We also showed that EFTUD2 deficiency significantly inhibited proliferation, differentiation, and maturation in human calvarial osteoblast (HCO) and human articular chondrocyte (HC-a) cells. RNA-Seq analysis uncovered activated TP53 signaling with increased phosphorylation of the TP53 protein and upregulation of five TP53 downstream target genes (FAS, STEAP3, CASP3, P21, and SESN1) both in HCO and in eftud2−/− zebrafish. Additionally, inhibition of p53 by morpholino significantly reduced the mortality of eftud2−/− larvae.

Conclusions
Our results confirm a novel de novo variant of the EFTUD2 gene and suggest that EFTUD2 may participate in the maturation and differentiation of osteoblasts and chondrocytes, possibly via activation of the TP53 signaling pathway. Thus, mutations in this gene may lead to skeletal anomalies in vertebrates.
Epidemiological pathology of Aβ deposition in the ageing brain in CFAS: addition of multiple Aβ-derived measures does not improve dementia assessment using logistic regression and machine learning approaches
Authors:   on behalf of the Cognitive Function and Ageing Neuropathology Study Group, Wharton S. B. , Wang D. , Parikh C. , Matthews F. E. , Brayne C. , Ince P. G. 
Published: December 2019

AbstractAβ-amyloid deposition is a key feature of Alzheimer’s disease, but Consortium to Establish a Registry for Alzheimer's Disease (CERAD) assessment, based on neuritic plaque density, shows a limited relationships to dementia. Thal phase is based on a neuroanatomical hierarchy of Aβ-deposition, and in combination with Braak neurofibrillary tangle staging also allows derivation of primary age-related tauopathy (PART). We sought to determine whether Thal Aβ phase predicts dementia better than CERAD in a population-representative cohort (n = 186) derived from the Cognitive Function and Ageing Study (CFAS). Cerebral amyloid angiopathy (CAA) was quantitied as the number of neuroanatomical areas involved and cases meeting criteria for PART were defined to determine if they are a distinct pathological group within the ageing population. Agreement with the Thal scheme was excellent. In univariate analysis Thal phase performed less well as a predictor of dementia than CERAD, Braak or CAA. Logistic regression, decision tree and linear discriminant analysis were performed for multivariable analysis, with similar results. Thal phase did not provide a better explanation of dementia than CERAD, and there was no additional benefit to including more than one assessment of Aβ in the model. Number of areas involved by CAA was highly correlated with assessment based on a severity score (p < 0.001). The presence of capillary involvement (CAA type I) was associated with higher Thal phase and Braak stage (p < 0.001). CAA was not associated with microinfarcts (p = 0.1). Cases satisfying pathological criteria for PART were present at a frequency of 10.2% but were not older and did not have a higher likelihood of dementia than a comparison group of individuals with similar Braak stage but with more Aβ. They also did not have higher hippocampal-tau stage, although PART was weakly associated with increased presence of thorn-shaped astrocytes (p = 0.048), suggesting common age-related mechanisms. Thal phase is highly applicable in a population-representative setting and allows definition of pathological subgroups, such as PART. Thal phase, plaque density, and extent and type of CAA measure different aspects of Aβ pathology, but addition of more than one Aβ measure does not improve dementia prediction, probably because these variables are highly correlated. Machine learning predictions reveal the importance of combining neuropathological measurements for the assessment of dementia.