bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calculation of the potential production of methane and chemicals using anaerobic digestion
Authors: Dionisi Davide , Bolaji Ifeoluwa , Nabbanda Diana , Silva Igor MO 
Published: May 2018

AbstractThe aim of this paper is to calculate the amount of energy or chemicals that can be produced using anaerobic digestion (AD). Five feedstocks were considered: the organic fraction of municipal solid waste (OFMSW); cattle, pig and poultry manure; energy crops; agricultural residues, and sewage sludge. Carbohydrates, proteins, and lipids were assumed to be the biodegradable components of the feedstocks. Chemical oxygen demand (COD) was assumed as a basis for the calculations of the production of methane and other chemicals. Methane production was calculated assuming that AD converts the biodegradable COD to methane with a yield of 80% COD/COD. The potential production of chemicals, i.e. acetic, propionic, butyric, and lactic acids, ethanol, and hydrogen, was calculated assuming conversion yields of carbohydrates, proteins, and lipids from the literature. Globally, with the assumptions made in this study, the AD of the feedstocks considered here can potentially satisfy 17–20% of the total energy consumption and 33–39% of the electrical energy requirements. Potentially, AD can generate organic acids at rates that are hundreds or thousands of times their current production rates. Ethanol and hydrogen can be produced by AD at rates that are up to 2–3 times their current production rate. This paper also discusses the main challenges that must be overcome to achieve the potential of AD. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd
Gene variants in the folate pathway are associated with increased levels of folate receptor autoantibodies
Authors: Dong Yuqi , Wang Linlin , Lei Yunping , Yang Na , Cabrera Robert M. , Finnell Richard H. , Ren Aiguo 
Published: May 2018

BackgroundFolate receptors (FRs) facilitate embryonic uptake of folates and are important for proper early embryonic development. There is accumulating evidence that blocking FR autoantibodies contribute to developmental diseases. However, genetic factors associated with the expression of FR autoantibodies remain unknown.ObjectiveWe investigated the effects of genetic polymorphisms in folate pathway genes on FR autoantibody titers in women.MethodsWe recruited 302 pregnant women in China. The FR antigen‐down immunoassay was used to measure levels of FR autoantibodies including human immunoglobulin G (IgG) and immunoglobulin M (IgM) in maternal plasma. Genotypes were identified by matrix‐assisted laser desorption/ionization time of flight mass spectrometry and polymerase chain reaction methods. General linear model was used to analyze the effects of genetic variants on FR autoantibody levels.ResultsSignificant associations were observed between genotypic variations and levels of FR autoantibodies. Plasma levels of FR autoantibodies in women with the TT genotype at MTHFR rs1801133 were significantly higher than those of women with the CC genotype (IgG: β = 0.62, 95% CI 0.21–1.04; IgM: β = 0.42, 95% CI 0.12–0.72). For DNMT3A rs7560488, the level of FR autoantibody IgG significantly increased in the TT genotype compared with CC genotype (β = 0.90, 95% CI 0.20–1.59). For MTHFD2 rs828903, genotype GG was associated with elevated levels of FR autoantibody IgM compared to the AA genotype (β = 0.60, 95% CI 0.10–1.10). No association was detected between genetic variants of the DHFR gene with FR autoantibodies levels.ConclusionGenetic variations in MTHFR, DNMT3A, and MTHFD2 genes were associated with elevated plasma levels of FR autoantibodies.
Modeling clustered long‐term survivors using marginal mixture cure model
Authors: Niu Yi , Song Lixin , Liu Yufeng , Peng Yingwei 
Published: May 2018

AbstractThere is a great deal of recent interests in modeling right‐censored clustered survival time data with a possible fraction of cured subjects who are nonsusceptible to the event of interest using marginal mixture cure models. In this paper, we consider a semiparametric marginal mixture cure model for such data and propose to extend an existing generalized estimating equation approach by a new unbiased estimating equation for the regression parameters in the latency part of the model. The large sample properties of the regression effect estimators in both incidence and the latency parts are established. The finite sample properties of the estimators are studied in simulation studies. The proposed method is illustrated with a bone marrow transplantation data and a tonsil cancer data.
Protein purification by chemo‐selective precipitation using thermoresponsive polymers
Authors: Wu Yuanzi , Cai Zhen , Wu Shuigen , Xiong Wenli , Ma Shanyun 
Published: May 2018

AbstractA recoverable and thermoresponsive polymer‐protein bioconjugate is synthesized and employed in the purification of protein with free sulfhydryl groups. Initiator with disulphide was modified on the cysteine residue of the target protein. Poly(N‐isopropylacrylamide) exhibiting a lower critical solution temperature was grown from the protein. The resulting protein–polymer conjugate was successfully thermoprecipitated and separated from other proteins. The approach was demonstrated with bovine serum albumin with the recycling yield of 76.4%. Enzyme activity test with papain verified the reversible polymer modification protected protein under extreme environments without affecting the functionality of the protein. This study implies the favorable potential of chemo‐selective enriching and purification of proteins.
Osteostimulation scaffolds of stem cells: BMP‐7‐derived peptide‐decorated alginate porous scaffolds promote the aggregation and osteo‐differentiation of human mesenchymal stem cells
Authors: Yang Yue , Luo Zuyuan , Zhao Ying 
Published: May 2018

AbstractThe scaffolds for stem cell‐based bone tissue engineering should hold the ability to guide stem cells osteo‐differentiating. Otherwise, stem cells will differentiate into unwanted cell types or will form tumors in vivo. Alginate, a natural polysaccharide with great biocompatibility, was widely used in biomedical applications. However, the limited bioactivity and poor osteogenesis capability of pristine alginate hampered its further application in tissue engineering. In this work, a bone forming peptide‐1 (BFP‐1), derived from bone morphogenetic protein‐7, was grafted to alginate polymer chains to prepare peptide‐decorated alginate porous scaffolds (pep‐APS) for promoting osteo‐differentiation of human mesenchymal stem cells (hMSCs). SEM images of pep‐APS exhibited porous structure with about 90% porosity (pore size 100–300 μm), which was appropriate for hMSCs ingrowth. The adhesion, proliferation and aggregation of hMSCs grown on pep‐APS were enhanced in vitro. Moreover, pep‐APS promoted the alkaline phosphatase (ALP) activity of hMSCs, and the osteo‐related genes expression was obviously up‐regulated. The immunochemical staining and western blot analysis results showed high expression level of OCN and Col1a1 in the hMSCs grown on pep‐APS. This work provided a facile and valid strategy to endow the alginate polymers themselves with specific bioactivity and prepare osteopromoting scaffold with enhanced osteogenesis ability, possessing potential applications in stem cell therapy and regenerative medicine.
Combinatorial synthetic pathway fine‐tuning and comparative transcriptomics for metabolic engineering of Raoultella ornithinolytica BF60 to efficiently synthesize 2,5‐furandicarboxylic acid
Authors: Yuan Haibo , Liu Yanfeng , Li Jianghua , Shin Hyun‐dong , Du Guocheng , Shi Zhongping , Chen Jian , Liu Long 
Published: May 2018

AbstractThe compound 5‐hydroxymethylfurfural (HMF) has attracted much attention due to its versatility as an important bio‐based platform chemical. Here, we engineered Raoultella ornithinolytica BF60 as a whole‐cell biocatalyst for a highly efficient synthesis of 2,5‐furandicarboxylic acid (FDCA) from HMF. Specifically, various expression cassettes of key genes, such as hmfH (gene encoding HMF/furfural oxidoreductase [HmfH]) and hmfo (gene encoding HMF oxidase), were designed and constructed for fine‐tuning FDCA synthesis from HMF. The FDCA titer reached 108.9 mM with a yield of 73% when 150 mM HMF was used as the substrate. This yield was 16% higher than that without balancing key gene expression in FDCA synthetic pathways. Additionally, to strengthen HmfH expression at the translational level, ribosomal binding site (RBS) sequences, which were computationally designed using the RBS calculator, were assembled into HmfH expression cassettes. The HmfH expression in the presence of these sequences enhanced FDCA titer to 139.6 mM with a yield of 93%. Next, previously unknown candidate genes, such as aldR, dkgA, akR, AdhP1, and AdhP2, which encode enzymes that catalyze the reactions leading to the formation of the undesired product 2,5‐bis(hydroxymethyl)furan (HMF alcohol) from HMF, were identified by RNA‐sequencing‐based transcriptomics. Combinatorial deletion of these five candidate genes led to an 88% reduction in HMF alcohol formation and 12% enhancement in FDCA production (175.6 mM). Finally, FDCA synthesis was further improved by the substrate pulse‐feeding strategy, and 221.5 mM FDCA with an 88.6% yield was obtained. The combinatorial synthetic pathway fine‐tuning and comparative transcriptomics approach may be useful for improving the biocatalysis efficiency of other industrially useful compounds.
Survival analysis of adult patients with ALL in Mexico City: first report from the Acute Leukemia Workgroup (ALWG) (GTLA)
Authors: Crespo‐Solis Erick , Espinosa‐Bautista Karla , Alvarado‐Ibarra Martha , Rozen‐Fuller Etta , Pérez‐Rocha Fernando , Nava‐Gómez Chantal , Ortiz‐Zepeda Maricela , Álvarez‐Vera José Luis , Ramos‐Peñafiel Christian Omar , Meillón‐García Luis Antonio , Rodríguez‐Rodríguez Sergio , Pomerantz‐Okon Alan , Turrubiates‐Hernández Francisco Javier , Demichelis‐Gómez Roberta 
Published: May 2018

AbstractAcute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the clonal expansion of hematopoietic lymphoid progenitors. With new target therapies, the survival of adults with ALL has improved in the past few decades. Unfortunately, there are no large ALL patient series in many Latin American countries. Data from the Acute Leukemia Workgroup that includes five Mexico City referral centers were used. Survival was estimated for adult patients with ALL during 2009–2015. In total, 559 adults with ALL were included. The median age was 28 years; 67% were classified into the adolescent and young adult group. Cytogenetic information was available in 54.5% of cases. Of the 305 analyzed cases, most had a normal caryotype (70.5%) and Philadelphia‐positive was present in 16.7%. The most commonly used treatment regimen was hyper‐CVAD. In approximately 20% of cases, there was considerable delay in the administration of chemotherapy. Primarily refractory cases accounted for 13.1% of patients. At the time of analysis, 26.7% of cases had survived. The 3‐year overall survival was 22.1%. The main cause of death was disease progression in 228 (55.6%). Clinical and public health strategies are needed to improve diagnosis, treatment and survivorship care for adult with ALL. This multicentric report represents the largest series in Mexico of adult ALL patients in which a survival analysis and risk identification were obtained.
Assessment of the prognostic factors in patients with pulmonary carcinoid tumor: a population‐based study
Authors: Huang Yiwei , Yang Xiaodong , Lu Tao , Li Ming , Zhao Mengnan , Yang Xingyu , Ma Ke , Wang Shuai , Zhan Cheng , Liu Yu , Wang Qun 
Published: May 2018

AbstractPrevious studies have identified potential risk factors for pulmonary carcinoid tumors and evaluated the effect of various treatments; however, the results were not entirely consistent. We conducted a population‐based study to further explore relevant prognostic issues. We extracted cases with pulmonary carcinoid tumors from the Surveillance Epidemiology and End Results database. Cox proportional hazard regression was utilized to identify potential significant risk factors, which helped establish a nomogram for predicting long‐term survival. Survival analysis and a competing risk study were conducted to evaluate the value of different surgical approaches. There were 7057 cases included in the study. Univariate and multivariate analyses showed that age, sex, tumor size, stage, histology, surgical type, chemotherapy, and radiation therapy were all significant prognostic factors. A nomogram with good accuracy for predicting 10‐year survival was formulated. Furthermore, patients who had undergone surgery had a significantly better survival than those who did not undergo surgery. There was no significant prognostic difference between lobectomy and sublobectomy stratified by tumor stage; however, lobectomy was associated with a significantly better survival in atypical tumors, especially those with regional disease. Our research identified possible risk factors in a large cohort and constructed a nomogram to visually predict 10‐year survival of pulmonary carcinoid tumors. We showed that lobectomy and sublobectomy should be considered as the mainstay of treatment, especially lobectomies for atypical tumor.
Anti‐PD‐1 therapy redirects macrophages from an M2 to an M1 phenotype inducing regression of OS lung metastases
Authors: Dhupkar Pooja , Gordon Nancy , Stewart John , Kleinerman Eugenie S. 
Published: May 2018

AbstractOsteosarcoma (OS) pulmonary metastasis translates into poor patient survival. The implication of PD‐1‐PD‐L1 pathway in the context of NK cells and/or macrophages in OS is unknown. We investigated the effect of anti‐PD‐1 in OS lung metastasis and the role of NK cells and/or macrophages in anti‐PD‐1 responses. A human LM7 OS mouse model was used. Immunohistochemistry for tissues (PD‐L1, caspase‐3, Ki‐67, NK cells, macrophages), and Western blotting for OS lung tumors (p‐Stat3, p‐Erk1/2) was performed. NK and macrophages were assessed using flow cytometry. NK cell and macrophage depletion were conducted using anti‐asialo GM1 and clodrosome, respectively. PD‐L1 expression was observed in human OS cells and OS patient lung metastases. Anti‐PD1 antibody led to a significant decrease in the number of OS lung metastases, enhanced tumor apoptosis, decreased tumor cell proliferation, and p‐STAT‐3/p‐Erk1/2 signaling blockade in OS lung tumors. NK cells and macrophages in OS lung tumors expressed PD‐1 and anti‐PD1 increased NK cell and macrophage tumor infiltration. Increased numbers of antitumor M1 macrophages and decreased pro‐inflammatory M2 macrophages were seen. NK depletion did not affect therapeutic effect of anti‐PD‐1, suggesting that NK cells were not directly involved. However, macrophage depletion significantly compromised anti‐PD1 efficacy, confirming their role in efficacy of anti‐PD‐1 against OS lung metastasis. Our findings suggest that OS lung metastases regression by anti‐PD1 can be attributed to activated tumor M1 macrophages and reduced M2 macrophages. Owing to the co‐relation of M1 macrophages with OS patient outcome, we provide a novel mechanism of PD‐1 blockade and a basis for future clinical trials for anti‐PD‐1 antibodies in OS.
Contralateral prophylactic mastectomy rate and predictive factors among patients with breast cancer who underwent multigene panel testing for hereditary cancer
Authors: Elsayegh Nisreen , Webster Rachel D. , Gutierrez Barrera Angelica M. , Lin Heather , Kuerer Henry M. , Litton Jennifer K. , Bedrosian Isabelle , Arun Banu K. 
Published: May 2018

AbstractAlthough multigene panel testing is increasingly common in patients with cancer, the relationship between its use among breast cancer patients with non‐BRCAmutations or variants of uncertain significance (VUS) and disease management decisions has not been well described. This study evaluated the rate and predictive factors of CPM patients who underwent multigene panel testing. Three hundred and fourteen patients with breast cancer who underwent multigene panel testing between 2014 and 2017 were included in the analysis. Of the 314 patients, 70 elected CPM. Election of CPM by gene status was as follows:BRCAcarriers (42.3%), non‐BRCAcarriers (30.1%), and VUS (10.6%). CPM election rates did not differ between non‐BRCAcarriers andBRCAcarriers (P = 0.6205). Among non‐BRCAcarriers, negative hormone receptor status was associated with CPM (P = 0.0115). For those with a VUS, hormone receptor status was not associated with CPM (P = 0.1879). Although the rate of CPM betweenBRCAcarriers and non‐BRCAcarriers was not significantly different, the predictors of CPM were different in each group. Our analyses shed the light on the increasing use of CPM among patients who are non‐BRCAcarriers as well those with a VUS. Our study elucidates the differing predictive factors of CPM election amongBRCAcarriers, non‐BRCAcarries, and those with a VUS. Our findings reveal the need for providers to be cognizant that non‐BRCAgenes and VUS drive women to elect CPM despite the lack of data for contralateral breast cancer risk associated with these genes.
MiRNA‐545 negatively regulates the oncogenic activity of EMS1 in gastric cancer
Authors: Ma Min , Zhao Juanxia , Wu Qunfeng , Xiao Ke , Li Shuang , Zhu Haizhen , Liu Chen , Xie Hailong , Zuo Chaohui 
Published: May 2018

AbstractGastric cancer (GC) is a common malignant tumor of the digestive system. In addition, GC metastasis is an extremely complicated process. In this article, high expression levels of EMS1 mRNA and protein were found to be positively correlated with an enhanced malignant potential of GC cells and a poor clinical prognosis of GC patients. Interestingly, the expression levels of EMS1 mRNA and protein in GC cells were inhibited by microRNA‐545 (miR‐545), which was identified by a bioinformatics analysis. The expression level of miR‐545 in carcinoma tissues was significantly lower than that in para‐carcinoma tissues. The proliferation and epithelial‐mesenchymal transition (EMT) of GC cells were suppressed by exogenous oligonucleotides of miR‐545 mimics. In addition, the expression levels of EMT‐associated markers were altered with the expression of miR‐545. Notably, the growth rates of tumors in nude mice were seriously restrained by an intratumoral injection of oligonucleotides of the miR‐545 mimics. These results suggest a negative regulatory role of miR‐545 on the oncogenic activity of EMS1. In addition, EMS1 and miR‐545 may be potential biomarkers for GC diagnosis. Synthesized oligonucleotides of miR‐545 mimics may be developed as important gene medicines for GC therapy in the future.
Radiotherapy vs surgery for T1‐2N0M0 laryngeal squamous cell carcinoma: A population‐based and propensity score matching study
Authors: Zhan Cheng , Yang Xiaodong , Song Xinmao , Yan Li 
Published: May 2018

AbstractThere are conflicting reports about whether radiotherapy or surgery is optimal for early‐stage laryngeal squamous cell carcinoma (LSCC), although both have recently been recommended. Patients with T1‐2N0M0 LSCC in the population‐based SEER database who underwent radiotherapy or surgery were reviewed. Propensity score matching was used to eliminate the baseline variations. After matching, 1913 pairs of patients were included. Overall, patients who received radiotherapy had worse cancer‐specific survival than patients with surgery. After stratification, the survival in patients who received radiotherapy was worse with respect to the following characteristics: ≤60 years of age; T1a glottis cancer; well‐differentiated tumors; and with married status. In other patients, survival outcomes were similar in patients who received radiotherapy and underwent surgery. Our results indicate that radiotherapy is not preferable in early‐stage LSCC patients who are ≤60 years of age, have T1a glottis cancer or well‐differentiated tumors, or are married. In other patients, both radiotherapy and surgery are comparable. However, our results cannot be a reference before controlled, prospective trials are performed.
HMGA2 promotes glioma invasion and poor prognosis via a long‐range chromatin interaction
Authors: Zhang Shanshan , Zhang Huibian , Yu Lin 
Published: May 2018

AbstractTo identify the function and underlying mechanisms of HMGA2 on the prognosis and invasion of gliomas, HMGA2 was detected by immunohistochemistry. The Kaplan‐Meier and Cox's regression analysis results showed that higher HMGA2 level predicted the poorer outcomes of glioma patients. ChIP‐qPCR, DNA electrophoretic mobility shift assay, chromosome conformation capture, and co‐immunoprecipitation were applied to identify HMGA2‐activated target sites, which were further verified by mRNA and protein expression detection. Transwell and orthotopic implantation were used to investigate the roles of HMGA2 in glioma cells. HMGA2 shRNA transfection inhibited glioblastoma invasion. Mechanistically, we first discovered that HMGA2, together with GCN5, facilitated the invasion of glioma cells via inducing chromatin conformational remodeling of the MMP2 gene promoter and epigenetically activating MMP2 gene transcription. Our results indicated that HMGA2, as a novel GCN5 recognition partner and histone acetylation modulator, may be novel prognostic indicator and promising glioma treatment target.
Generation of Polar Semi‐Saturated Bicyclic Pyrazoles for Fragment‐Based Drug‐Discovery Campaigns.
Authors: Luise Nicola , Wyatt Paul G. 
Published: May 2018

AbstractSynthesising polar semi‐saturated bicyclic heterocycles can lead to better starting points for fragment‐based drug discovery (FBDD) programs. We report the application of diverse chemistry to construct bicyclic systems from a common intermediate, where pyrazole, a privileged heteroaromatic able to bind effectively to biological targets, is fused to diverse saturated counterparts. The generated fragments can be further developed either after confirmation of their binding pose or early in the process, as their synthetic intermediates. Essential quality control (QC) for selection of small molecules to add to a fragment library is discussed.
Direct Enantioselective α‐Allylation of Unfunctionalized Cyclic Ketones with Alkynes through Pd‐Amine Cooperative Catalysis
Authors: Lee Jin Tu Danence , Zhao Yu 
Published: May 2018

AbstractThe first direct enantioselective α‐allylation of unfunctionalized cyclic ketones using alkynes as an economical choice of reagent is reported. This transformation uses a simple procedure with commercially available palladium, chiral bisphosphine ligand and chiral amine catalysts, and affords valuable ketones with a α‐tertiary stereocenter in good to high enantiopurity. In this transformation, a chiral palladium complex containing the (S)‐DIFLUORPHOS ligand catalyzes the isomerization of alkynes into an electrophilic allylpalladium species, which is attacked by the enamine generated in situ from the condensation of (R)‐prolinol with the ketone substrate.