bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value of circular RNA 0007385 in disease monitoring and prognosis estimation in non–small‐cell lung cancer patients
Authors: Lin Yijian , Su Weiming , Lan Guocui 
Published: July 2020

AbstractObjectiveThis study aimed to assess the circular RNA_0007385 (hsa_circ_0007385) expression in tumor/adjacent non‐tumor tissues, and the correlation of its tumor expression with clinicopathological features as well as survival in non–small‐cell lung cancer (NSCLC) patients.Methods210 NSCLC patients who underwent tumor resection were reviewed in this retrospective study. 210 tumor specimens and 81 paired adjacent specimens were collected, in which the hsa_circ_0007385 expression was detected by reverse transcription‐quantitative polymerase chain reaction assay. Disease‐free survival (DFS) and overall survival (OS) were recorded, and the last follow‐up date was June 30, 2019.ResultsHsa_circ_0007385 was upregulated in tumor tissue compared with adjacent non‐tumor tissue (P < .001), and ROC curve analysis revealed that hsa_circ_0007385 expression had an excellent value in distinguishing tumor tissue from adjacent non‐tumor tissue with an area under curve of 0.922 (95% CI: 0.890‐0.953). Tumor hsa_circ_0007385 high expression correlated with lymph node metastasis (P = .007) and higher TNM stage (P = .004). In addition, DFS (P = .028) and OS (P = .008) were both less favorable in patients with tumor hsa_circ_0007385 high expression compared to patients with tumor hsa_circ_0007385 low expression. Besides, the DFS (P = .008) and OS (P = .012) were also the worst in patients with tumor hsa_circ_0007385 high+++ expression, followed by patients with tumor hsa_circ_0007385 high++ expression and patients with tumor hsa_circ_0007385 high + expression, and the best in patients with tumor hsa_circ_0007385 low expression. Multivariate regression analysis elucidated that tumor hsa_circ_0007385 high expression independently predicted worse OS (P = .033).ConclusionTumor hsa_circ_0007385 could be a novel biomarker for disease monitoring and prognosis prediction in NSCLC patients.
Pilot study identifying circulating miRNA signature specific to alcoholic chronic pancreatitis and its implication on alcohol‐mediated pancreatic tissue injury
Authors: Chhatriya Bishnupriya , Sarkar Piyali , Nath Debashis , Ray Sukanta , Das Kshaunish , Mohapatra Saroj K , Goswami Srikanta 
Published: July 2020

AbstractBackground and AimAlcohol exerts its effects on organs in multiple ways. Alcoholic chronic pancreatitis (ACP) is a disease in which alcohol triggers the pathological changes in pancreas, leading to chronic inflammation and fibrosis. The molecular mechanism behind these changes is not clear. Identification of key circulating miRNA changes in ACP patients and determination of the fraction that is secreted from diseased pancreas not only could serve as potential biomarker for assessing disease severity, but also could help identifying the molecular alterations prevailing in the organ precipitating the disease, to some extent.MethodsWe performed microRNA microarray using the Affymetrix miRNA 4.0 platform to identify differentially expressed miRNAs in serum of ACP patients as compared to alcoholic control individuals and then found out how many of them could be pancreas‐specific and exosomally secreted. We further analyzed a pancreatitis‐specific gene expression data set to find out the differentially expressed genes in diseased pancreas and explored the possible role of those selected miRNAs in regulation of gene expression in ACP.ResultsWe identified 14 miRNAs differentially expressed in both serum and pancreas and also identified their experimentally validated targets. Transcription factors modulating the miRNA expression in an alcohol‐dependent manner were also identified and characterized to derive the miRNA–gene–TF interaction network responsible for progression of the disease.ConclusionsDifferentially expressed miRNA signature demonstrated significant changes in both pro‐ and anti‐inflammatory pathways probably balancing the chronic inflammation in the pancreas. Our findings also suggested possible involvement of pancreatic stellate cells in disease progression.
Synthesis of 1,2,4,5‐tetrasubstituted imidazoles and 2,4,5,6‐tetrasubstituted pyrimidines: three‐component, the one‐pot reaction of arylamidines, malononitrile, and arylglyoxals or aryl aldehydes
Authors: Mehrabi Hossein , Hajipour Mina , Rezazadeh‐Jabalbarezi Fatemeh , Alizadeh‐Bami Farzaneh 
Published: July 2020

AbstractA highly efficient one‐pot synthesis of the 1,2,4,5‐tetrasubstituted imidazoles and 2,4,5,6‐tetrasubstituted pyrimidines through an arylamidine, malononitrile, and carbonyl compound by using Et3N in CH3CN at reflux conditions was developed. The nature of the carbonyl compounds were different; when the carbonyl compound was arylglyoxal or aryl aldehyde, 1,2,4,5‐tetrasubstituted imidazole and 2,4,5,6‐tetrasubstituted pyrimidine were achieved respectively.
Glyphosate and other highly polar pesticides in fruit, vegetables and honey using ion chromatography coupled with high resolution mass spectrometry: Method validation and its applicability in an official laboratory
Authors: Gasparini Mara , Angelone Barbara , Ferretti Enrica 
Published: July 2020

AbstractAn analytical method, using ion chromatography coupled to high resolution mass spectrometry was developed and validated to quantify glyphosate, glufosinate, ethephon, fosetyl aluminium and their related metabolites. This method allows multiresidue analysis of 11 highly polar molecules in a single chromatographic run, without derivatization step, using acidified water with low level of acetonitrile as extraction solvent. Three different matrices that are representative of commodity group were studied and validated: one fruit (grapes), one cereal (wheat) and honey, according to the criteria established by SANTE/12682/2019 taking into account maximum residue limits indicated by Regulation (EC) No. 396/2005, confirming that the procedure was selective, repeatable and robust. Matrix effect was studied and linearity was evaluated comparing analytical response differences between solvent standard solutions and matrix‐matched calibration curve. Due to the relevant matrix effect observed, the use of response factor (RF) approach to quantify analytical batch was evaluated, using isotopically labelled internal standardisation. The in‐depth study, validation results and several proficiency tests, used to verify procedure performance, demonstrated that the method is fit for purpose to routine analysis in an official laboratory. Moreover, it allows surveillance activities in fruits and vegetables control, as indicated by European Community, furthermore monitoring presence of polar pesticides, at low level, in some particular food as honey that could become environmental pollution indicator.
Treatment experience of Taiwanese patients with anti‐3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase myopathy
Authors: Liang Wen‐Chen , Wang Chen‐Hua , Chen Wan‐Zi , Kuo Yun‐Ting , Lin Hsiu‐Fen , Suzuki Shigeaki , Nishino Ichizo , Jong Yuh‐Jyh 
Published: July 2020

AbstractImmune‐mediated necrotizing myopathy (IMNM) has emerged as a new subgroup of idiopathic inflammatory myopathy in the past decade, associated with the presence of two autoantibodies against signal recognition particle and 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR). We aim to analyze the clinical, pathological, and imaging phenotypes of the patients with anti‐HMGCR myopathy in our cohort. Five patients with anti‐HMGCR myopathy have been enrolled who were all female; three were pediatric and two were adult patients. The muscle pathology of patients met the diagnostic criteria of IMNM. On muscle magnetic resonance imaging, adductors were earliest affected while lower legs were relatively preserved with highest degree of involvement in medial head of gastrocnemius. In upper extremities, biceps brachii was the most severely involved, followed by triceps. All patients were refractory to steroid mono‐therapy. For pediatric patients, all three patients eventually became responsive to steroid with either intravenous immunoglobulin or rituximab despite variable motor function recovered at present due to different intervention timing. For adult patients, one with statin exposure responded well to steroid and azathioprine use and the motor function returned to the baseline. The other adult patient finally got stabilized and slowly improved with steroid and methotrexate 13 years after the start of therapy. The creatine kinase (CK) levels of all patients were decreased along with clinical severity. In conclusion, muscle imaging might be of help for the diagnosis. Treatment with immuno‐suppressants could be considered together with steroid from the beginning.
Human Fetal Cell Therapy in Huntington's Disease: A Randomized, Multicenter, Phase II Trial
Authors: Bachoud‐Lévi Anne‐Catherine ,   on behalf the Multicentric Intracerebral Grafting in Huntington's Disease Group
Published: July 2020

AbstractBackgroundHuntington's disease is a rare, severe, inherited neurodegenerative disease in which we assessed the safety and efficacy of grafting human fetal ganglionic eminence intrastriatally.MethodsPatients at the early stage of the disease were enrolled in the Multicentric Intracerebral Grafting in Huntington's Disease trial, a delayed‐start phase II randomized study. After a run‐in period of 12 months, patients were randomized at month 12 to either the treatment group (transplanted at month 13–month 14) or the control group and secondarily treated 20 months later (month 33–month 34). The primary outcome was total motor score compared between both groups 20 months postrandomization (month 32). Secondary outcomes included clinical, imaging, and electrophysiological findings and a comparison of pregraft and postgraft total motor score slopes during the entire study period (month 0–month 52) regardless of the time of transplant.ResultsOf 54 randomized patients, 45 were transplanted; 26 immediately (treatment) and 19 delayed (control). Mean total motor score at month 32 did not differ between groups (treated controls difference in means adjusted for M12: +2.9 [95% confidence interval, −2.8 to 8.6]; P = 0.31). Its rate of decline after transplantation was similar to that before transplantation. A total of 27 severe adverse events were recorded in the randomized patients, 10 of which were related to the transplant procedure. Improvement of procedures during the trial significantly decreased the frequency of surgical events.We found antihuman leucocytes antigen antibodies in 40% of the patients.ConclusionNo clinical benefit was found in this trial. This may have been related to graft rejection. Ectopia and high track number negatively influence the graft outcome. Procedural adjustments substantially improved surgical safety. (ClinicalTrials.gov NCT00190450.) © 2020 International Parkinson and Movement Disorder Society
Intercomparison of multiple statistical methods in post‐processing ensemble precipitation and temperature forecasts
Authors: Li Xiangquan , Chen Jie , Xu Chong‐Yu , Chen Hua , Guo Shenglian 
Published: July 2020

AbstractEnsemble weather forecasting generally suffers from bias and under‐dispersion, which limit its predictive power. Several post‐processing methods have been developed to overcome these limitations, and an intercomparison is needed to understand their performance. Four state‐of‐the‐art methods are compared in post‐processing precipitation and air temperature of the Global Ensemble Forecasting System (GEFS) reforecasts using a simple bias correction (BC) method as a reference. These methods include extended logistic regression (ExLR), generator‐based post‐processing (GPP), Bayesian model averaging (BMA) and affine kernel dressing (AKD). All these methods are tested over 659 national standard meteorological stations in China. The research concerns are the influence of region and forecast date and the role of BC on ensemble weather forecasting. It was found that: (1) the deterministic methods (GPP and ExLR) are more skilful than the probabilistic methods (BMA and AKD) in obtaining the well‐calibrated and skilful ensemble forecasts; (2) the forecast skill of the post‐processed ensemble weather forecasts is comparably high in the northern arid areas for precipitation, while the forecast skill for air temperature is only low in the Qinghai‐Tibetan Plateau area; (3) the skill difference of the post‐processed forecasts on different forecast date is only evident for air temperature, while not apparent for precipitation; and (4) only correcting bias for the ensemble weather forecasts can achieve about 0–70% (for precipitation) and 30–100% (for air temperature) forecast skill improvement for deterministic methods.
Identification of histone malonylation in the human fetal brain and implications for diabetes‐induced neural tube defects
Authors: Zhang Qin , Cai Tanxi , Xiao Zonghui , Li Dan , Wan Chunlei , Cui Xiaodai , Bai Baoling 
Published: July 2020

AbstractBackgroundNeural tube defects (NTDs) are severe congenital malformations. Diabetes during pregnancy is a risk factor for NTDs, but its mechanism remains elusive. Emerging evidence suggests that protein malonylation is involved in diabetes. Here, we report the correlation between histone lysine malonylation in diabetes‐induced NTDs.MethodsNano‐HPLC/MS/MS was used to screen the histone malonylation profile in human embryonic brain tissue. Then, the histone malonylation level was compared between the brains of normal control mice and mice with diabetes‐induced NTDs. Finally, the histone malonylation level was compared under high glucose exposure in an E9 neuroepithelial cell line (NE4C).ResultsA total of 30 histone malonylation sites were identified in human embryonic brain tissue, including 18 novel sites. Furthermore, we found an increased histone malonylation level in brain tissues from mice with diabetes‐induced NTDs. Finally, both the histone malonylation modified sites and the modified levels were proved to be increased in the NE4C treated with high glucose.ConclusionOur results present a comprehensive map of histone malonylation in the human fetal brain. Furthermore, we provide experimental evidence supporting a relationship between histone malonylation and NTDs caused by high glucose‐induced diabetes. These findings offer new insights into the pathological role of histone modifications in human NTDs.
Inventory transshipment game with limited supply: Trap or treat
Authors: Wang Ziteng , Dai Yue , Fang Shu‐Cherng , Jiang Zhong‐Zhong , Xu Yifan 
Published: July 2020

AbstractInventory transshipment is generally shown to be beneficial to retailers by matching their excess demand with surplus inventory. We investigate an inventory transshipment game with two newsvendor‐type retailers under limited total supply and check whether the retailers are better off than the case without transshipment. We derive the ordering strategies for the retailers and show that unlike the unlimited supply case, a pure Nash equilibrium only exists under certain conditions. Furthermore, contrary to the conventional wisdom, we show that inventory transshipment may not always benefit both retailers. Although one of the retailers is guaranteed to be better off, the other could be worse off. The decision criteria are then provided for the retailers to determine if they will benefit from the exercise of inventory transshipment. Numerical study indicates that the carefully chosen transshipment prices play an important role in keeping inventory transshipment beneficial to both retailers. Subsequently, a coordinating mechanism is designed for the retailers to negotiate transshipment prices that maximize the total profit of the two retailers while keeping each of them in a beneficial position.
Gastrointestinal Manifestations of COVID‐19: Impact on Nutrition Practices
Authors: Aguila Enrik John T. , Cua Ian Homer Y. , Fontanilla Joy Arabelle C. , Yabut Vince Leenard M. , Causing Marion Frances P. 
Published: July 2020

AbstractAlthough Coronavirus disease 2019 (COVID‐19) is primarily a respiratory disease, growing evidence shows that it can affect the digestive system and present with gastrointestinal (GI) symptoms. Various nutrition societies have recently published their guidelines in context of the pandemic, and several points emphasize the impact of these GI manifestations on nutrition therapy. In patients with COVID‐19, the normal intestinal mucosa can be disrupted by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus, and this could result in GI symptoms and a compromise in nutrient absorption. Optimization of oral diet is still recommended. However, given the GI effects of COVID‐19, a fraction of infected patients have poor appetite and would not be able to meet their nutrition goals with oral diet alone. For this at‐risk group, which includes those who are critically ill, enteral nutrition is the preferred route to promote gut integrity and immune function. In carrying this out, nutrition support practices have been revised in such ways to mitigate viral transmission and adapt to the pandemic. All measures in the GI and nutrition care of patients are clustered to limit exposure of healthcare workers. Among patients admitted to intensive care units, a significant barrier is GI intolerance, and it appears to be exacerbated by significant GI involvement specific to the SARS‐CoV‐2 infection. Nevertheless, several countermeasures can be used to ease side effects. At the end of the spectrum in which intolerance persists, the threshold for switching to parenteral nutrition may need to be lowered.
Noninvasive prenatal sequencing for multiple Mendelian monogenic disorders among fetuses with skeletal dysplasia or increased nuchal translucency
Authors: Yan Huanchen , Zhu Xiaofan , Chen Jingsi , Cao Ye , Kwok Yvonne Ka Yin , Chen Zihan , Leung Tak Yeung , Chen Min , Choy Kwong Wai 
Published: July 2020

AbstractObjectivesTo evaluate the performance of noninvasive prenatal sequencing for multiple Mendelian monogenic disorders (NIPS‐M) among fetuses with skeletal abnormalities or increased nuchal translucency (NT).MethodsPregnancies with fetal skeletal abnormalities or increased NT (≥3.0 mm) observed by ultrasonography were recruited between October 2017 and March 2019. Parental blood from 13 couples were collected for NIPS‐M testing reported. All the NIPS‐M results were followed up by invasive diagnostic testing or neonatal examination.ResultsAmong the 13 cases, 8 (61.5%) yielded positive results for pathogenic variants in the FGFR3, COL1A1, RAF1, PTPN11 and SOS1 genes by NIPS‐M. One case was excluded for further analysis due to insufficient fetal DNA (<4.5%). De novo mutations were reported in six of the eight positive cases (75%). The other two were inconclusive as the pathogenic variants were detected in both plasma and genomic DNA of the mothers. The sensitivity of NIPS‐M was 100%.ConclusionsOur pilot study demonstrates that NIPS‐M is an accurate approach for detection of multiple monogenic disorders among fetuses with skeletal abnormalities or increased NT. It serves as an alternative and highly sensitive method to provide valuable molecular information for these groups of women who are reluctant to undergo invasive procedure.
Lipophilic signals lead to organ‐specific gene expression changes in Arabidopsis seedlings
Authors: Cannon Ashley E. , Yan Chengshi , Burks David J. , Rao Xiaolan , Azad Rajeev K. , Chapman Kent D. 
Published: July 2020

AbstractIn plants, N‐acylethanolamines (NAEs) are most abundant in desiccated seeds and their levels decline during germination and early seedling establishment. However, endogenous NAE levels rise in seedlings when ABA or environmental stress is applied, and this results in an inhibition of further seedling development. When the most abundant, polyunsaturated NAEs of linoleic acid (18:2) and linolenic acid (18:3) were exogenously applied, seedling development was affected in an organ‐specific manner. NAE 18:2 primarily affected primary root elongation and NAE 18:3 primarily affected cotyledon greening and expansion and overall seedling growth. The molecular components and signaling mechanisms involved in this pathway are not well understood. In addition, the bifurcating nature of this pathway provides a unique system in which to study the spatial aspects and interaction of these lipid‐specific and organ‐targeted signaling pathways. Using whole transcriptome sequencing (RNA‐seq) and differential expression analysis, we identified early (1–3 hr) transcriptional changes induced by the exogenous treatment of NAE 18:2 and NAE 18:3 in cotyledons, roots, and seedlings. These two treatments led to a significant enrichment in ABA‐response and chitin‐response genes in organs where the treatments led to changes in development. In Arabidopsis seedlings, NAE 18:2 treatment led to the repression of genes involved in cell wall biogenesis and organization in roots and seedlings. In addition, cotyledons, roots, and seedlings treated with NAE 18:3 also showed a decrease in transcripts that encode proteins involved in growth processes. NAE 18:3 also led to changes in the abundance of transcripts involved in the modulation of chlorophyll biosynthesis and catabolism in cotyledons. Overall, NAE 18:2 and NAE 18:3 treatment led to lipid‐type and organ‐specific gene expression changes that include overlapping and non‐overlapping gene sets. These data will provide future, rich opportunities to examine the genetic pathways involved in transducing early signals into downstream physiological changes in seedling growth.
From monomer to fibril: Abeta‐amyloid binding to Aducanumab antibody studied by molecular dynamics simulation
Authors: Frost Christina V. , Zacharias Martin 
Published: July 2020

AbstractAlzheimer's disease is one of the most common causes of dementia. It is believed that the aggregation of short Aβ‐peptides to form oligomeric and protofibrillar amyloid assemblies plays a central role for disease‐relevant neurotoxicity. In recent years, passive immunotherapy has been introduced as a potential treatment strategy with anti‐amyloid antibodies binding to Aβ‐amyloids and inducing their subsequent degradation by the immune system. Although so far mostly unsuccessful in clinical studies, the high‐dosed application of the monoclonal antibody Aducanumab has shown therapeutic potential that might be attributed to its much greater affinity to Aβ‐aggregates vs monomeric Aβ‐peptides. In order to better understand how Aducanumab interacts with aggregated Aβ‐forms compared to monomers, we have generated structural model complexes based on the known structure of Aducanumab in complex with an Aβ2 − 7‐eptitope. Structural models of Aducanumab bound to full‐sequence Aβ1 − 40‐monomers, oligomers, protofilaments and mature fibrils were generated and investigated using extensive molecular dynamics simulations to characterize the flexibility and possible additional interactions. Indeed, an aggregate‐specific N‐terminal binding motif was found in case of Aducanumab binding to oligomers, protofilaments and fibrils that is located next to but not overlapping with the epitope binding site found in the crystal structure with Aβ2 − 7. Analysis of binding energetics indicates that this motif binds weaker than the epitope but likely contributes to Aducanumab's preference for aggregated Aβ‐species. The predicted aggregate‐specific binding motif could potentially serve as a basis to reengineer Aducanumab for further enhanced preference to bind Aβ‐aggregates vs monomers.
Self‐catalytic mechanism of prebiotic reactions: From formamide to purine bases
Authors: Slavova Sofia , Enchev Venelin 
Published: July 2020

AbstractComplete reaction pathway of prebiotic reactions for formation of the purine nucleobases adenine, hypoxanthine, guanine, isoguanine, 2,6‐diaminopurine, and xanthine from pure formamide are presented. All reactants (hydrogen cyanide, ammonia, water, formic acid, urea) and catalysts (formamide and formimidic acid) needed in the self‐catalyzed reactions are available from a starting compound, formamide. The required raw materials are obtained by partial decomposition of formamide.