bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biocatalytic synthesis of 2-fluoro-3-hydroxypropionic acid
Authors: Liu Wei , Yuan Shan , Jin Miaomiao , Xian Mo 
Published: August 2022

Fluorine has become an important element for the design of synthetic molecules for use in medicine, agriculture, and materials. The introduction of fluorine atoms into organic compound molecules can often give these compounds new functions and make them have better performance. Despite the many advantages provided by fluorine for tuning key molecular properties, it is rarely found in natural metabolism. We seek to expand the molecular space available for discovery through the development of new biosynthetic strategies that cross synthetic with natural compounds. Towards this goal, 2-fluoro-3-hydroxypropionic acid (2-F-3-HP) was first synthesized using E. coli coexpressing methylmalonyl CoA synthase (MatBrp), methylmalonyl CoA reductase (MCR) and malonate transmembrane protein (MadLM). The concentration of 2-F-3-HP reached 50.0 mg/L by whole-cell transformation after 24 h. 2-F-3-HP can be used as the substrate to synthesize other fluorides, such as poly (2-fluoro-3-hydroxypropionic acid) (FP3HP). Being entirely biocatalytic, our procedure provides considerable advantages in terms of environmental and safety impacts over reported chemical methods.
Advances in Research at Synthesis Process Optimization and Quality Standard Improvement of O-desmethylvenlafaxine Succinate
Authors: Yang Shiwei , Chen Shiyun , Wang Cheng , Zhang Shibo , Li Shuaifei , Yuan Xinsong , Peng Fuyun , He Yong 
Published: August 2022

We herein describe an optimal approach for the efficient synthesis of O-desmethylvenlafaxine succinate monohydrate (DVS) with high yield and high purity through 5-step reactions, including benzyl protection of the phenolic hydroxyl group, cyclohexanone condensation, deprotection, cyano reduction, dimethylation, and succinic acid salt formation from p-hydroxybenzene acetonitrile as a starting material. 4-Benzyloxyphenylacetonitrile (Intermediate I) was prepared by the hydroxyl protection of the bromide benzyl-p-hydroxyphenylacetonitrile catalyzed by potassium carbonate with 99.83% purity and 98.92% yields. The 1, 2-nucleophilic addition of intermediate I to cyclohexanone promoted by sodium hydroxide with the homogeneous catalyst (n-Bu)4N+Br− to the preparation of 1-[Cyano(4-benzyloxyphenyl)methyl]cyclohexanol (Intermediate II) was obtained by 99.13% purity and 99.71% yields. Cyclohexanone residues and benzyl bromide residues were trace, and tetrabutylammonium bromide residues were UNDER 0.7 ppm, which further improves the residual standards for genotoxic impurities (GIs). 1-[2-amino-1-(4-hydroxyphenyl)ethyl]cyclohexanol hydrochloride (Intermediate III) was prepared by 10% palladium-carbon under 2.0 MPa up to 98.32% purity and 94.20% yields. O-desmethylvenlafaxine (ODV) was synthesized by dimethylation of intermediate III with 37% formaldehyde solution and 85% formic acid solution. The highest purity was up to 99.20% and the yield was up to 84.77%. O-desmethylvenlafaxine succinate monohydrate (DVS) was formed from succinic acid and O-desmethylvenlafaxine (ODV) and crystallized in a mixed solvent of acetone and water (3:1) to obtain 99.92% purity and 90.27% yields. The 5-step total yields of desvenlafaxine succinate monohydrate is 71.09%, and its crystal form has characteristic peaks at 5, 10, 21, and 26 min by XRD powder diffraction, which is consistent with the crystalline form I. Compared with conventional synthesis strategy, we revealed a novel and green process with a high total yield, high atomic economy, low environmental pollution, high operational safety, and high residual standards for genotoxic impurities (GIs), which improves drug safety.
A nomogram predicting 30-day mortality in patients undergoing percutaneous coronary intervention
Authors: Song Jingjing , Liu Yupeng , Wang Wenyao , Chen Jing , Yang Jie , Wen Jun , Gao Jun , Shao Chunli , Tang Yi-Da 
Published: August 2022

Background and aimsEarly detection of mortality after percutaneous coronary intervention (PCI) is crucial, whereas most risk prediction models are based on outdated cohorts before the year 2000. This study aimed to establish a nomogram predicting 30-day mortality after PCI.Materials and methodsIn total, 10,444 patients undergoing PCI in National Center for Cardiovascular Diseases in China were enrolled to establish a nomogram to predict 30-day mortality after PCI. The nomogram was generated by incorporating parameters selected by logistic regression with the stepwise backward method.ResultsFive features were selected to build the nomogram, including age, male sex, cardiac dysfunction, STEMI, and TIMI 0–2 after PCI. The performance of the nomogram was evaluated, and the area under the curves (AUC) was 0.881 (95% CI: 0.8–0.961). Our nomogram exhibited better performance than a previous risk model (AUC = 0.7, 95% CI: 0.586–0.813) established by Brener et al. The survival curve successfully stratified the patients above and below the median score of 4.ConclusionA novel nomogram for predicting 30-day mortality was established in unselected patients undergoing PCI, which may help risk stratification in clinical practice.
Investigating the paradox of increasing obesity and declining heart disease mortality in the United States: Age-period-cohort model
Authors: Yu Bin , Chen Xinguang , Lu Dandan , Yan Hong , Wang Peigang 
Published: August 2022

BackgroundObesity as a risk factor of heart disease (HD) is confirmed through observational, laboratory, and intervention studies. However, it cannot explain why HD declines, but obesity increases in the United States in recent decades. This study attempted to understand this paradox.MethodsAnnual data of national HD mortality (1999–2018) were derived from Wide-Ranging Online Data for Epidemiologic Research, biannual obesity data (1999–2016) from the National Health and Nutrition Examination Survey, and smoking data (1965–1990) were from the National Health Interview Survey. Age-period-cohort method was used to decompose HD mortality into age, period, and cohort effects, and to estimate age-cohort adjusted mortality rates. To explain the paradox, age-cohort adjusted rates were associated with obesity rates to verify the positive obesity-HD relationship, while smoking rates were associated with cohort effects to explain the current declines in HD mortality.ResultsDuring 1999–2018, the prevalence of obesity increased while the crude HD mortality rate declined for both sex and all races. After controlling for the curvilinear age effect and consistent declining cohort effect, the age-cohort adjusted HD mortality sustained stable in 1999–2007 and increased thereafter. The age-cohort adjusted rate in 1999–2018 (per 100,000) increased from 189.31 to 238.56 for males, 67.23 to 90.28 for females, 115.54 to 157.39 for White, 246.40 to 292.59 for Black, 79.79 to 101.40 for Hispanics, and 49.95 to 62.86 for Asian. The age-cohort adjusted HD mortality rates were positively associated with obesity rates (r = 0.68 for males, 0.91 for females, 0.89 for White, and 0.69 for Hispanic, p &lt; 0.05), but not significant for Black and Asian. Further, during 1965–1990, the estimated cohort effect showed a decline in HD risk and was positively associated with smoking rates (r = 0.98 for both sex, 0.99 for White, and 0.98 for Black, p &lt; 0.01).ConclusionStudy findings reveal potential increase of HD risk and support the positive relationship between obesity and HD risk. Declines in HD mortality in the past two decades are primarily due to tobacco use reduction and this protective effect was entangled in the mortality rates as cohort effect.
The feasibility and efficacy of ultrasound-guided percutaneous laser ablation for multifocal papillary thyroid microcarcinoma
Authors: Zhang Lu , Zhang Gui Ping , Zhan Wei Wei , Zhou Wei 
Published: August 2022

ObjectiveThe aim of this study was to evaluate the feasibility and efficacy of percutaneous laser ablation (PLA) for patients with multifocal papillary thyroid microcarcinoma (PTMC).Materials and methodsA cohort of patients who underwent ultrasound (US)-guided PLA for primary PTMC were enrolled in this study. The patients were divided into a multifocal PTMC (multi-PTMC) group and a unifocal PTMC (uni-PTMC) group. Before PLA, conventional US and contrast-enhanced ultrasound (CEUS) were performed to evaluate the PTMC and cervical lymph nodes. The operation time, energy, power, amount of isolation liquid, and complications during PLA were recorded. Patients were followed up at 2 days, 1 month, 3 months, and 6 months, and every 6 months after that. Volume reduction rate (VRR), local tumor recurrence, and lymph node metastasis after PLA were observed.ResultsThe study included 12 patients with 26 PTMCs and 60 patients with 60 PTMCs. The operation time, total energy, and amount of isolation liquid in the multi-PTMC group were more than those in the uni-PTMC group (p = 0.000, 0.007, and 0.020, respectively). The mean follow-up durations in multi-PTMC and uni-PTMC groups were 19.75 ± 11.46 months (6–36 months) and 16.33 ± 10.01 months (4–40 months), with a similar VRR of the ablated lesions in the two groups. One and three cases with newly developed PTMCs were observed in the multi-PTMC group and the uni-PTMC group during follow-up, respectively. There was no regrowth of treated lesions, lymph node metastasis, or distant metastasis. At the end of the follow-up, all the ablated lesions in the two groups completely disappeared or only remained scar strips.ConclusionPLA is a safe and effective technique for treating multifocal PTMC, which might be an alternative technique for patients who are not eligible or are unwilling to undergo surgery.
An evaluation of domestic electric water heaters for frequency control
Authors: Xiang Sheng , Yang Hongming , Cao Bo 
Published: August 2022

Maintaining the frequency of a power system close to its nominal value (50 Hz or 60 Hz) is critical, which comes mainly from generators and flexible loads in traditional power systems. Direct load control (DLC) is a method to control controllable loads for power system optimization. In general, it is used to reduce or shave peak demand. Nonetheless, DLC also can be used to provide frequency control services. Domestic electric water heater (DEWH) is an important kind of controllable load, which takes a high percentage of domestic electric power consumption and has a large thermal energy storage capacity. Hence, DEWH can be a prime candidate for DLC. This study proposes a framework to provide frequency control service with DEWHs. A virtual battery pack system (VBPS) is introduced to be equivalent to the capacity of DEWHs, and a series of measurable indicators are proposed to show the capacity of the VBPS when providing frequency control services. An adaptive criterion is applied to classify controllable DEWHs, which helps to maintain end-user comfort. The performances of the proposed frequency control method during normal and contingency conditions are verified through case studies in CYME.
Construction, bioinformatics analysis, and validation of competitive endogenous RNA networks in ulcerative colitis
Authors: Dong Longcong , Zhang Ruibin , Huang Qin , Shen Yuan , Li Hongying , Yu Shuguang , Wu Qiaofeng 
Published: August 2022

Background: Ulcerative colitis (UC) is a common chronic disease of the digestive system. Recently, competitive endogenous RNAs (ceRNAs) have been increasingly used to reveal key mechanisms for the pathogenesis and treatment of UC. However, the role of ceRNA in UC pathogenesis has not been fully clarified. This study aimed to explore the mechanism of the lncRNA-miRNA-mRNA ceRNA network in UC and identify potential biomarkers and therapeutic targets.Materials and Methods: An integrative analysis of mRNA, microRNA (miRNA), and long non-coding RNA (lncRNA) files downloaded from the Gene Expression Omnibus (GEO) was performed. Differentially expressed mRNA (DE-mRNAs), miRNA (DE-miRNAs), and lncRNA (DE-lncRNAs) were investigated between the normal and UC groups by the limma package. A weighted correlation network analysis (WGCNA) was used to identify the relative model for constructing the ceRNA network, and, concurrently, miRWalk and DIANA-LncBase databases were used for target prediction. Consecutively, the Gene Ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway, and Reactome pathway enrichment analyses, protein-protein interaction (PPI) network, Cytohubba, and ClueGO were performed to identify hub genes. Additionally, we examined the immune infiltration characteristics of UC and the correlation between hub genes and immune cells using the immuCellAI database. Finally, the expression of potential biomarkers of ceRNA was validated via qRT-PCR in an experimental UC model induced by dextran sulfate sodium (DSS).Result: The ceRNA network was constructed by combining four mRNAs, two miRNAs, and two lncRNAs, and the receiver operating characteristic (ROC) analysis showed that two mRNAs (CTLA4 and STAT1) had high diagnostic accuracy (area under the curve [AUC] &gt; 0.9). Furthermore, CTLA4 up-regulation was positively correlated with the infiltration of immune cells. Finally, as a result of this DSS-induced experimental UC model, CTLA4, MIAT, and several associate genes expression were consistent with the results of previous bioinformatics analysis, which proved our hypothesis.Conclusion: The investigation of the ceRNA network in this study could provide insight into UC pathogenesis. CTLA4, which has immune-related properties, can be a potential biomarker in UC, and MIAT/miR-422a/CTLA4 ceRNA networks may play important roles in UC.
Integrating cell cycle score for precise risk stratification in ovarian cancer
Authors: Chen Lingying , Gu Haiyan , Zhou Lei , Wu Jingna , Sun Changdong , Han Yonggui 
Published: August 2022

Background: Ovarian cancer (OC) is a highly heterogeneous disease, of which the mesenchymal subtype has the worst prognosis, is the most aggressive, and has the highest drug resistance. The cell cycle pathway plays a vital role in ovarian cancer development and progression. We aimed to screen the key cell cycle genes that regulated the mesenchymal subtype and construct a robust signature for ovarian cancer risk stratification.Methods: Network inference was conducted by integrating the differentially expressed cell cycle signature genes and target genes between the mesenchymal and non-mesenchymal subtypes of ovarian cancer and identifying the dominant cell cycle signature genes.Results: Network analysis revealed that two cell cycle signature genes (POLA2 and KIF20B) predominantly regulated the mesenchymal modalities of OC and used to construct a prognostic model, termed the Cell Cycle Prognostic Signature of Ovarian Cancer (CCPOC). The CCPOC-high patients showed an unfavorable prognosis in the GSE26712 cohort, consistent with the results in the seven public validation cohorts and one independent internal cohort (BL-OC cohort, qRT-PCR, n = 51). Functional analysis, drug-sensitive analysis, and survival analysis showed that CCPOC-low patients were related to strengthened tumor immunogenicity and sensitive to the anti-PD-1/PD-L1 response rate in pan-cancer (r = −0.47, OC excluded), which indicated that CCPOC-low patients may be more sensitive to anti-PD-1/PD-L1.Conclusion: We constructed and validated a subtype-specific, cell cycle-based prognostic signature for ovarian cancer, which has great potential for predicting the response of anti-PD-1/PD-L1.
Steroid implants for the induction of vitellogenesis in feminized European silver eels (Anguilla anguilla L.)
Authors: Palstra Arjan P. , Bouwman Lotte J. , Jéhannet Pauline , Kruijt Leo , Schipper Henk , Blokland Marco H. , Swinkels William , Heinsbroek Leon T. N. , Lokman P. Mark 
Published: August 2022

Assisted propagation of the European eel will lead to a closed production cycle supplying the aquaculture industry with juvenile glass eels. Females require long-term weekly treatment with pituitary extract (PE), which is stressful and causes abnormalities in oogenesis. We tested the effects of 17α-methyltestosterone (17 MT), as potent androgen activating the androgen receptor, and 17β-estradiol (E2), as an inducer of vitellogenesis, to shorten the duration of PE treatment.Four groups of feminized eels were subjected to a simulated migration and subsequent injection with implants containing 17 MT (17 MT-group), E2 (E2-group) or 17 MT plus E2 (17 MT + E2-group) to test for synergistic effects, or without any steroids as controls (C-group). The effects of a 2-months treatment were investigated by determining the eye index (EI), hepatosomatic and gonadosomatic index (HSI and GSI, respectively), plasma steroid concentrations by liquid chromatography mass spectrometry (LCMS), gonadal histology, expression of androgen receptors a and b (ara,arb); estrogen receptor 1 (esr1); FSH receptor (fshr); vitellogenin receptor (vtgr) and aromatase (cyp19), and the required number of weekly PE injections to fully mature. For many parameters, both the 17 MT and E2 groups showed an increase vs. controls, with the 17 MT + E2 group showing a synergistic effect, as seen for EI, GSI (3.4 for 17 MT and for E2, 6.6 for 17 MT + E2), oocyte diameter andara,arbandesr1expression. Concentrations of almost all focal steroids decreased with simulated migration and steroid treatment. Only eels of the 17 MT-group showed increased expression ofcyp19and offshr, whilefshrexpression increased 44-fold in the 17 MT + E2 group, highlighting that co-implantation is most effective in raisingfshrmRNA levels. Specific for eels of the E2 groups were vitellogenesis-associated changes such as an increase of HSI, plasma E2, and presence of yolk in the oocytes. Steroid treatments reduced the duration of PE treatment, again synergistically for co-implantation. In conclusion, E2 is necessary to start vitellogenesis, but 17 MT has specific effects oncyp19andfshrexpression. The combination is necessary for synergistic effects and as such, steroid implants could be applied in assisted reproduction protocols for European eel to improve oocyte quality leading to the production of more vital larvae.
Dynamic risk prediction of BK polyomavirus reactivation after renal transplantation
Authors: Fang Yiling , Zhang Chengfeng , Wang Yuchen , Yu Zhiyin , Wu Zhouting , Zhou Yi , Yan Ziyan , Luo Jia , Xia Renfei , Zeng Wenli , Deng Wenfeng , Xu Jian , Chen Zheng , Miao Yun 
Published: August 2022

PurposeTo construct a dynamic prediction model for BK polyomavirus (BKV) reactivation during the early period after renal transplantation and to provide a statistical basis for the identification of and intervention for high-risk populations.MethodsA retrospective study of 312 first renal allograft recipients with strictly punctual follow-ups was conducted between January 2015 and March 2022. The covariates were screened using univariable time-dependent Cox regression, and those with P&lt;0.1 were included in the dynamic and static analyses. We constructed a prediction model for BKV reactivation from 2.5 to 8.5 months after renal transplantation using dynamic Cox regression based on the landmarking method and evaluated its performance using the area under the curve (AUC) value and Brier score. Monte-Carlo cross-validation was done to avoid overfitting. The above evaluation and validation process were repeated in the static model (Cox regression model) to compare the performance. Two patients were presented to illustrate the application of the dynamic model.ResultsWe constructed a dynamic prediction model with 18 covariates that could predict the probability of BKV reactivation from 2.5 to 8.5 months after renal transplantation. Elder age, basiliximab combined with cyclophosphamide for immune induction, acute graft rejection, higher body mass index, estimated glomerular filtration rate, urinary protein level, urinary leukocyte level, and blood neutrophil count were positively correlated with BKV reactivation, whereas male sex, higher serum albumin level, and platelet count served as protective factors. The AUC value and Brier score of the static model were 0.64 and 0.14, respectively, whereas those of the dynamic model were 0.79 ± 0.05 and 0.08 ± 0.01, respectively. In the cross-validation, the AUC values of the static and dynamic models decreased to 0.63 and 0.70 ± 0.03, respectively, whereas the Brier score changed to 0.11 and 0.09 ± 0.01, respectively.ConclusionDynamic Cox regression based on the landmarking method is effective in the assessment of the risk of BKV reactivation in the early period after renal transplantation and serves as a guide for clinical intervention.
Effect of a reduced fat and sugar maternal dietary intervention during lactation on the infant gut microbiome
Authors: Sindi Azhar S. , Stinson Lisa F. , Lean Soo Sum , Chooi Yit-Heng , Leghi Gabriela E. , Netting Merryn J. , Wlodek Mary E. , Muhlhausler Beverly S. , Geddes Donna T. , Payne Matthew S. 
Published: August 2022

ObjectiveA growing body of literature has shown that maternal diet during pregnancy is associated with infant gut bacterial composition. However, whether maternal diet during lactation affects the exclusively breastfed infant gut microbiome remains understudied. This study sets out to determine whether a two-week of a reduced fat and sugar maternal dietary intervention during lactation is associated with changes in the infant gut microbiome composition and function.DesignStool samples were collected from four female and six male (n = 10) infants immediately before and after the intervention. Maternal baseline diet from healthy mothers aged 22–37 was assessed using 24-h dietary recall. During the 2-week dietary intervention, mothers were provided with meals and their dietary intake was calculated using FoodWorks 10 Software. Shotgun metagenomic sequencing was used to characterize the infant gut microbiome composition and function.ResultsIn all but one participant, maternal fat and sugar intake during the intervention were significantly lower than at baseline. The functional capacity of the infant gut microbiome was significantly altered by the intervention, with increased levels of genes associated with 28 bacterial metabolic pathways involved in biosynthesis of vitamins (p = 0.003), amino acids (p = 0.005), carbohydrates (p = 0.01), and fatty acids and lipids (p = 0.01). Although the dietary intervention did not affect the bacterial composition of the infant gut microbiome, relative difference in maternal fiber intake was positively associated with increased abundance of genes involved in biosynthesis of storage compounds (p = 0.016), such as cyanophycin. Relative difference in maternal protein intake was negatively associated with Veillonella parvula (p = 0.006), while positively associated with Klebsiella michiganensis (p = 0.047). Relative difference in maternal sugar intake was positively associated with Lactobacillus paracasei (p = 0.022). Relative difference in maternal fat intake was positively associated with genes involved in the biosynthesis of storage compounds (p = 0.015), fatty acid and lipid (p = 0.039), and metabolic regulator (p = 0.038) metabolic pathways.ConclusionThis pilot study demonstrates that a short-term maternal dietary intervention during lactation can significantly alter the functional potential, but not bacterial taxonomy, of the breastfed infant gut microbiome. While the overall diet itself was not able to change the composition of the infant gut microbiome, changes in intakes of maternal protein and sugar during lactation were correlated with changes in the relative abundances of certain bacterial species.Clinical trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12619000606189).