bluuebunny/crossref_metadata_2025 huggingface dataset:
Solid‐Phase Protein Modifications: Towards Precision Protein Hybrids for Biological Applications
Authors: Kuan Seah Ling , Raabe Marco
Published: July 2020

Proteins have attracted increasing attention as biopharmaceutics and diagnostics due to their high specificity, biocompatibility, and biodegradability. The biopharmaceutical sector in particular is experiencing rapid growth, which has led to an increase in the production and sale of protein drugs and diagnostics over the last two decades. Since the first‐generation biopharmaceutics dominated by native proteins, both recombinant and chemical technologies have evolved and transformed the outlook of this rapidly developing field. This review article presents updates on the fabrication of covalent and supramolecular fusion hybrids, as well as protein‐polymer hybrids using solid‐phase approaches that hold great promise for preparing protein hybrids with precise control at the macromolecular level to incorporate additional features. In addition, the applications of the resultant protein hybrids in medicine and diagnostics are highlighted where possible.
Heterogeneous Catalytic Synthesis of Methyl Lactate and Lactic Acid from Sugars and Their Derivatives
Authors: Mäki‐Arvela Päivi , Aho Atte , Murzin Dmitry Yu.
Published: July 2020

Recent developments in sugar transformations to methyl lactate and lactic acid are critically summarized. The highest yield of methyl lactate from glucose obtained over Sn(salen)/octylmethyl imidazolium bromide catalyst was 68 % at 160 °C whereas the highest yield of lactic acid of 58 % was achieved over hierarchical Lewis acidic Sn‐Beta catalysts at 200 °C under inert atmosphere. In addition to the desired products also humins are formed in water whereas in methanol alkyl glucosides‐ and ‐fructosides as well as acetals were generated, especially in the presence of Brønsted‐acidic sites. The main challenges limiting the industrial feasibility of these reactions are incomplete liquid phase mass balance closure, complicated product analysis and a lack of kinetic data. In addition to reporting optimized reaction conditions and catalyst properties also catalyst reuse and regeneration as well as kinetic modelling and continuous operation are summarized.
Boosting Electrocatalytic Water Oxidation by Creating Defects and Lattice‐Oxygen Active Sites on Ni‐Fe Nanosheets
Authors: Chen Chi , Zhang Peili , Wang Mei , Zheng Dehua , Chen Junchi , Li Fusheng , Wu Xiujuan , Fan Ke , Sun Licheng
Published: July 2020

Layered nickel‐iron oxide/hydroxide nanosheets have proven to be the most efficient catalyst for the water oxidation reaction. Introducing structural defects to the nanosheets is a particularly attractive method for increasing the number of active sites and tailoring the intrinsic electronic properties. Herein, defects were introduced on Ni−Fe nanosheets through sequentially electrodoping and dedoping the surface of the material with tetramethylammonium ions. The as‐prepared defect‐rich Ni−Fe nanosheets showed an enhanced catalytic performance for the oxygen evolution reaction (OER) compared with conventional NiFe layered double hydroxides (LDHs), exhibiting an overpotential of only 172 mV at the current density of 10 mA cm−2. The relationship between pH and OER activity indicated that the lattice oxygens participated in the catalytic OER process as active sites. This work provides new insights into the understanding of the structure‐activity relationship of layered materials and helps to develop new methods to implement defects on such frameworks aided by organic molecules.
Metal‐Organic Framework‐Derived Fe‐Doped Co1.11Te2 Embedded in Nitrogen‐Doped Carbon Nanotube for Water Splitting
Authors: He Bin , Wang Xin‐Chao , Xia Li‐Xue , Guo Yue‐Qi , Tang Ya‐Wen , Zhao Yan , Hao Qing‐Li , Yu Tao , Liu Hong‐Ke , Su Zhi
Published: July 2020

A rational design is reported of Fe‐doped cobalt telluride nanoparticles encapsulated in nitrogen‐doped carbon nanotube frameworks (Fe‐Co1.11Te2@NCNTF) by tellurization of Fe‐etched ZIF‐67 under a mixed H2/Ar atmosphere. Fe‐doping was able to effectively modulate the electronic structure of Co1.11Te2, increase the reaction activity, and further improve the electrochemical performance. The optimized electrocatalyst exhibited superior hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) performances in an alkaline electrolyte with low overpotentials of 107 and 297 mV with a current density of 10 mA cm−2, in contrast to the undoped Co1.11Te2@NCNTF (165 and 360 mV, respectively). The overall water splitting performance only required a voltage of 1.61 V to drive a current density of 10 mA cm−2. Density function theory (DFT) calculations indicated that the Fe‐doping not only afforded abundant exposed active sites but also decreased the hydrogen binding free energy. This work provided a feasible way to study non‐precious‐metal catalysts for an efficient overall water splitting.
Fast and Chemoselective Addition of Highly Polarized Lithium Phosphides Generated in Deep Eutectic Solvents to Aldehydes and Epoxides
Authors: Cicco Luciana , Fombona‐Pascual Alba , Sánchez‐Condado Alba , Carriedo Gabino A. , Perna Filippo M. , Capriati Vito , Presa Soto Alejandro , García‐Álvarez Joaquín
Published: July 2020

Highly polarized lithium phosphides (LiPR2) were synthesized, for the first time, in deep eutectic solvents as sustainable reaction media, at room temperature and in the absence of protecting atmosphere, through direct deprotonation of both aliphatic and aromatic secondary phosphines (HPR2) by n‐BuLi. The subsequent addition of in‐situ generated LiPR2 to aldehydes or epoxides proceeded quickly and chemoselectively, thereby allowing the straightforward access to the corresponding α‐ or β‐hydroxy phosphine oxides, respectively, under air and at room temperature (bench conditions), which are traditionally considered as textbook‐prohibited conditions in the field of polar organometallic chemistry of s‐block elements.
Direct Transformation of Glycerol to Propanal using Zirconium Phosphate‐Supported Bimetallic Catalysts
Authors: Gong Honghui , Zhou Chuan , Cui Yan , Dai Sheng , Zhao Xiuge , Luo Ruihan , An Pengfei , Li Huan , Wang Haifeng , Hou Zhenshan
Published: July 2020

Selective transformation of glycerol to propanal (PA) provides a feasible route towards the sustainable synthesis of high value‐added chemicals. In this work, zirconium phosphate (ZrP) was studied as support and Ru and Co as metal sites for glycerol hydrogenolysis in a continuous‐flow reactor. It was found that ZrP‐supported Co−O species had a moderate selectivity to PA (49.5 %) in glycerol hydrogenolysis. Notably, once Ru species were doped into CoO/ZrP, the resulting catalyst exhibited not only an outstanding catalytic performance for glycerol hydrogenolysis to PA (a selectivity of 80.2 % at full conversion), but also a high stability at least a 50 h long‐term performance. The spent catalyst could be regenerated by calcining in air to remove carbonaceous deposits. Characterization indicated that the acid sites on ZrP played a very critical role in the dehydration of glycerol into acrolein (AE), that the distribution of Co was uniform, basically consistent with that of Zr, P and Ru, and that an especially close contact between Co−O and Ru species was formed on Ru/CoO/ZrP catalyst. The further activity tests and characterizations confirmed that there was a strong interaction between the dispersed Co−O species and Ru0 nanoparticles, which endowed Ru sites with high electronic density. This effect could play a role in facilitating the dissociation of H2, and thus in promoting the hydrogenation reaction. Besides, DFT calculations suggested that the Co−O species can adsorb more strongly the C=C bond of the intermediate AE on a highly coordinatively unsaturated Co (Cocus) site and thus lead to preferential hydrogenation at the C=C bond of AE to PA.
Targeting CD83 in mantle cell lymphoma with anti‐human CD83 antibody
Authors: Li Ziduo , Abadir Edward , Lee Kenneth , Clarke Candice , Bryant Christian E , Cooper Wendy , Pietersz Geoffrey , Favaloro James , Silveira Pablo A , NJ Hart Derek , Ju Xinsheng , Clark Georgina J
Published: July 2020

Objectives

Effective antibody–drug conjugates (ADCs) provide potent targeted cancer therapies. CD83 is expressed on activated immune cells including B cells and is a therapeutic target for Hodgkin lymphoma. Our objective was to determine CD83 expression on non‐Hodgkin lymphoma (NHL) and its therapeutic potential to treat mantle cell lymphoma (MCL) which is currently an incurable NHL.

Methods

We analysed CD83 expression on MCL cell lines and the lymph node/bone marrow biopsies of MCL patients. We tested the killing effect of CD83 ADC in vitro and in an in vivo xenograft MCL mouse model.

Results

CD83 is expressed on MCL, and its upregulation is correlated with the nuclear factor κB (NF‐κB) activation. CD83 ADC kills MCL in vitro and in vivo. Doxorubicin and cyclophosphamide (CP), which are included in the current treatment regimen for MCL, enhance the NF‐κB activity and increase CD83 expression on MCL cell lines. The combination of CD83 ADC with doxorubicin and CP has synergistic killing effect of MCL.

Conclusion

This study provides evidence that a novel immunotherapeutic agent CD83 ADC, in combination with chemotherapy, has the potential to enhance the efficacy of current treatments for MCL.
SOS: Socially omitting selfishness in IoT for smart and connected communities
Authors: Rehman Ghani ur , Ghani Anwar , Zubair Muhammad , Saeed Muhammad Imran , Singh Dhananjay
Published: July 2020

Smart and connected communities (SCC) is an emerging field of internet of things (IoT), and it has potential applications to improve human life. The improvement may be in terms of preservation, revitalization, livability, and sustainability of a community. The resources of the nodes and devices in the SCC have certain constraints that may not allow the devices and nodes to cooperate to save their resources such as memory, energy, and buffer, or simply maximize their performance. Thus, to stimulate the nodes to avoid selfish behavior, SSC needs a novel and well‐organized solution to motivate nodes for cooperation. This article aims to resolve the issue of selfish behaviors in SCC and to encourage the nodes for cooperation. A novel mechanism, socially omitting selfishness (SOS), has been proposed to manage/eradicate selfishness using a socially oriented election process. The election process elects different heads based on weight and cooperation (using Vickrey, Clarke, and Groves model). The election of heads and incentive mechanism encourages the nodes to show participation and behave as highly cooperative members of the community. Furthermore, an extended version of the Dempster Shafer model has been used to discourage the selfish behavior of the participating nodes in the SOS scheme. It uses different monitoring and gateway nodes to efficiently employ the proposed scheme. A mathematical model has been developed for the aforementioned aspects and simulated through NS2 simulation environment to analyze the performance of SOS. The results of the proposed scheme outperform the contemporary schemes in terms of average delivery delay, packet delivery ratio, throughput, and average energy.
HSDN‐GRA: A hybrid software‐defined networking‐based geographic routing protocol with multi‐agent approach
Authors: Alouache Lylia , Nguyen Nga , Aliouat Makhlouf , Chelouah Rachid
Published: July 2020

We propose in this paper a Hybrid Software‐Defined Networking‐based Geographical Routing Protocol (HSDN‐GRA) with a clustering approach. It takes into account three different criteria to select the best relay to send data: (1) the contact duration between vehicles, (2) the available load of each vehicle, (3) and the log of encountered communication errors embedded in each cluster head. The multi‐criteria strategy allows the selection of the most reliable vehicles by avoiding communication problems and ensuring connection availability. Once the hybrid control plane has found out the next eligible neighbor, the data plane will be in charge of dividing and sending data. To validate our approach, HSDN‐GRA has been modeled and implemented in JADE, a multi‐agent platform, to be compared to other multi‐agent based protocols. Simulation results show that HSDN‐GRA achieves good performance with respect to the average routing overhead, the packet drop rate, and the throughput.
Exploring context dependency in eco‐evolutionary patterns with the stick insect Timema cristinae
Authors: Montejo‐Kovacevich Gabriela , Farkas Timothy , Beckerman Andrew , Nosil Patrik
Published: July 2020

Rapid evolution can influence the ecology of populations, communities, and ecosystems, but the importance of evolution for ecological dynamics remains unclear, largely because the contexts in which evolution is powerful are poorly resolved. Here, we carry out a large observational study to test hypotheses about context dependency of eco‐evolutionary patterns previously identified on the stick insect Timema cristinae. Experiments and observations conducted in 2011 and 2012 documented predator‐mediated negative effects of camouflage maladaptation (i.e., evolutionary dynamics) on: (a) T. cristinae abundance and, (b) species richness and abundance of other arthropods. Here we show that camouflage maladaptation does not correlate with T. cristinae abundance and, instead, is associated with increased abundance and species richness of cohabitating arthropods. We furthermore find that plants with high levels of Timema maladaptation tend to have higher foliar nitrogen, that is, higher nutritional value, and more positive mass‐abundance slopes in the coexisting arthropod communities. We propose explanations for the observed contrasting results, such as negative density‐ and frequency‐dependent selection, feedbacks between herbivore abundance and plant nutritional quality, and common effects of predation pressure on selection and prey abundance. Our results demonstrate the utility of observational studies to assess the context dependency of eco‐evolutionary dynamics patterns and provide testable hypotheses for future work.
Research on design and optimization of the pitching float wave energy converter
Authors: Ma Yong , Ai Shan , Yang Lele , Zhang Aiming , Liu Sen , Zhou Binghao
Published: July 2020

Wave power generation has been the object of extensive renewable energy research and development all over the world. Concerning the application of a wave energy converter to the harsh environment of the South China Sea, a study of the shape and internal layout of a pitching float wave energy converter was performed based on the mechanism of the oscillating‐float generator. Research methods based on potential flow theory and the use of ANSYS‐AQWA software were applied to predict the hydrodynamic performance and energy conversion of the pitching float wave energy converter. The influence of the float shape, width, side radius, and centroid position on the hydrodynamic performance of the float was analyzed. The results show that the pitching performance of the spherical‐bottom float was the best among the three basic shapes examined. The width of the float had the greatest impact on the pitching performance of the float, and the effect of the radius of the float on the pitching performance was also significant. The pitching performance of the float was improved with the realization of a larger radius in the pitching direction. The centroid position and rotational inertia also had a great impact on the pitching performance of the float. The wave energy converter designed in this study lays the foundation and provides reference for further research on the novel, efficient, and stable wave energy converter.
Valorization of the green waste parts from sweet potato (Impoea batatas L.): Nutritional, phytochemical composition, and bioactivity evaluation
Authors: Hong Jingyang , Mu Taihua , Sun Hongnan , Richel Aurore , Blecker Christophe
Published: July 2020

In the present study, leaves from 13 sweet potato cultivars were collected as raw materials. The nutritional and functional composition, antioxidant activity, and sunscreen activity of different sweet potato leaf samples were determined, and the comprehensive nutritional quality was calculated by gray relational analysis. Results showed that the nutritional and functional components are significantly different between different cultivars. Tainong71 showed the highest comprehensive nutritional quality, followed by Fu22, Ningcai, Fu23, Ecai10, Zhecai726, Ecai1, Fu18, Pushu53, Guangcai5, Shulv1, Guangcai2, and Zhecai1. The antioxidant activity varied from 3.94 to 16.75 g Trolox equivalent/100 g dry weight. Pushu53 showed the highest sunscreen activity, with the sun protection factor 24.65. There was a positive correlation between antioxidant activity and sunscreen activity (r = .737, p = .004). In conclusion, sweet potato leaves possess high nutritional and functional properties, and have the huge potential to be used as green leafy vegetables and sunscreen agent.
Antidepressant use and orthostatic hypotension in older adults living with mild‐to‐moderate Alzheimer disease
Authors: Dyer Adam H , Murphy Claire , Briggs Robert , Lawlor Brian , Kennelly Sean P ,   for the NILVAD Study Group
Published: July 2020

Objectives

Antidepressant use is often reported as a risk factor for Orthostatic Hypotension (OH), however this relationship has never been explored in those with mild/moderate Alzheimer Disease (AD), who may represent a particularly vulnerable cohort.

Methods

We performed a cross‐sectional analysis of baseline data from the NILVAD study. Participants with mild‐moderate AD were recruited from 23 centres in nine countries. Systolic and Diastolic Blood Pressure (SBP/DBP) was recorded in the seated position and after both 1 and 5 minutes of standing. OH was defined as a drop of ≥20 mmHg SBP/≥10 mmHg DBP. We examined the relationship between antidepressant use, orthostatic BP drop and the presence of OH, controlling for important covariates.

Results

Of 509 participants (72.9 ± 8.3 years, 61.9% female), two‐fifths (39.1%; 199/509) were prescribed a regular antidepressant. Antidepressant use was associated with a significantly greater SBP and DBP drop at 5 minutes (β: 1.83, 0.16‐3.50, P = .03 for SBP; β: 1.13, 0.02‐2.25, P < .05 for DBP). Selective Serotonin Reuptake Inhibitor (SSRI) use was associated with a significantly greater likelihood of OH (OR 2.0, 1.1‐3.6, P = .02). Both findings persisted following robust covariate adjustment.

Conclusions

In older adults with AD, antidepressants were associated with a significantly greater SBP/DBP drop at 5 minutes. SSRI use in particular may be a risk factor for OH. This emphasises the need to screen older antidepressant users, and particularly those with AD, for ongoing orthostatic symptoms in order to reduce the risk of falls in this vulnerable cohort.
Decreased expression of interferon‐stimulated genes in B cells of patients with chronic hepatitis C during interferon‐free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort study
Authors: Arai Jun , Ito Takayoshi , Shimozuma Yuu , Uchikoshi Manabu , Nakajima Yoko , Sakaki Masashi , Uozumi Shojiro , Kajiwara Atsushi , Sugiura Ikuya , Otoyama Yumi , Nozawa Hisako , Kurihara Toshikazu , Eguchi Junichi , Nomura Norihiro , Sakuma Dai , Sato Masashi , Deguchi Yoshio , Yoshida Hitoshi
Published: July 2020

Aims

Hepatitis C virus (HCV) infection is monitored by the host innate immunity that includes the endogenous interferon (IFN), which up‐regulates IFN‐stimulated genes (ISGs). HCV is both hepatotropic and lymphotropic, but HCV replication in lymphoid cells is a controversial issue. Here, we analyzed the mRNA levels of the ISGs in B cells of HCV‐infected patients during antiviral therapy and investigated the effects of viral eradication.

Methods

One hundred and eighty‐one patients with chronic hepatitis C and 26 healthy volunteers were enrolled in this study. Levels of HCV RNA and mRNA of ISGs in B cells isolated from the patients were monitored before, during, and after antiviral therapy.

Results

HCV RNA was detected in B cells of 133/175 (76.0%) patients who achieved sustained virologic response (SVR) before therapy was started. The positive ratio of HCV RNA in B cells was higher in patients with genotype 1 and the non‐major genotype of interleukin 28B. HCV RNA in B cells of most patients disappeared 1 week after antiviral therapy was started. The baseline expression of ISG mRNA was significantly higher in the patients than in the healthy volunteers. Levels of ISG mRNA were increased and remained high throughout the IFN‐based therapy. In contrast, levels of ISG mRNA in patients who achieved SVR were significantly decreased 1 week after the IFN‐free therapy was started and remained low during the therapy.

Conclusions

These results suggested that IFN‐free therapy potentially eradicated HCV in the B cells, leading to the down‐regulation of endogenous ISGs. The level of ISG mRNA could be used as a marker for viral eradication in B cells.
Rainwater harvesting for supplemental irrigation under tropical inland valley swamp conditions*
Authors: Blango Mohamed M. , Cooke Richard A.C. , Moiwo Juana P. , Sawyerr Patrick A. , Kangoma Emmanuel
Published: July 2020

Agricultural water management, if well implemented, could increase water supply and food security across the developing world. Simple earth dams or reservoirs are sufficient in this case for gravity‐driven irrigation to support agricultural production throughout the year. This is critical for regions with little energy and limited farm irrigation, but abundant precipitation. In Sierra Leone, energy especially as electricity is hardly available and farming is over 80% rainfed. This critical shortfall has limited crop cultivation to almost entirely the wet season in the country. Here, we developed an earthen micro‐dam and analysed its potential for rainwater harvesting and supplemental irrigation in the dry season in an inland valley swamp at Njala University. For the 2014–2017 dry season cropping period, average daily evaporation, seepage and irrigation from the 4.2 × 104 m3 dam were respectively 2.84, 0.51 and 7.76 mm. Thus, with 124 mm (79.5 m3) dam water irrigation and 409 mm precipitation in the dry season, grain yield increased by 67% (1430 kg ha¯¹) over that (2130 kg ha¯¹). This implies that the additional rice harvest in the dry season in excess of the rice harvest in the wet season was 67%. In other words, the harvest in the dry season was 3560 kg ha¯¹. The higher harvest in the dry season was attributed to the more favourable crop growth conditions (including solar radiation and supplemental irrigation) in the dry season than in the wet season. The additional harvest in the dry season could be significant in closing food security gaps, especially in tropical Africa where rainfall is plenty and energy availability limited.
Evaluation of corneal structures in myopic eyes more than twenty‐two years after photorefractive keratectomy
Authors: Montorio Daniela , Cennamo Gilda , Menna Feliciana , Donna Piero , Napolitano Pasquale , Breve Maria Angelica , Fiore Ugo , Cennamo Giovanni , Rosa Nicola
Published: July 2020

The aim of this study is to evaluate corneal epithelial thickness (CET), corneal densitometry (CD) in 84 myopic eyes (57 patients) more than 22 years after photorefractive keratectomy, using anterior segment‐optical coherence tomography (AS‐OCT) and Scheimpflug imaging system. The CET was significantly higher in all operated eyes than in unoperated eyes in central sector. A statistically significant increase in CD in corneal anterior layer of central sector was shown in groups of operated eyes with greater ablation depth respect to unoperated eyes. While there was no significant difference in CD between the operated eyes groups with lower ablation depth and unoperated eyes. A significant trend toward higher values in anterior CD with deeper ablations in central sector was found. These noninvasive imaging techniques allow to better understand the corneal remodeling process after photoablation and to monitor the patients over time.
Legendre G‐array pairs and the theoretical unification of several G‐array families
Authors: Arasu K. T. , Bulutoglu D. A. , Hollon J. R.
Published: July 2020

We investigate how Legendre ‐array pairs are related to several different perfect binary ‐array families. In particular we study the relations between Legendre ‐array pairs, Sidelnikov‐Lempel‐Cohn‐Eastman ‐arrays, Yamada‐Pott ‐array pairs, Ding‐Helleseth‐Martinsen ‐arrays, Yamada ‐arrays, Szekeres ‐array pairs, Paley ‐array pairs, and Baumert ‐array pairs. Our work also solves one of the two open problems posed by Ding. Moreover, we provide several computer search‐based existence and nonexistence results regarding Legendre ‐array pairs. Finally, by using cyclotomic cosets, we provide a previously unknown Legendre ‐array pair.
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

Objective

This 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.

Methods

210 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.

Results

Hsa_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).

Conclusion

Tumor 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

Background and Aim

Alcohol 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.

Methods

We 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.

Results

We 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.

Conclusions

Differentially 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

A 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

An 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

Immune‐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

Background

Huntington's disease is a rare, severe, inherited neurodegenerative disease in which we assessed the safety and efficacy of grafting human fetal ganglionic eminence intrastriatally.

Methods

Patients 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.

Results

Of 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.

Conclusion

No 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

Ensemble 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

Background

Neural 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.

Methods

Nano‐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).

Results

A 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.

Conclusion

Our 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.
Internal Bernstein functions and Lévy‐Laplace exponents
Authors: Basalim Kholoud , Bridaa Safa , Jedidi Wissem
Published: July 2020

Bertoin, Roynette and Yor (2004) described new connections between the class
of Lévy‐Laplace exponents Ψ (also called the class of (sub)critical branching mechanism) and the class of Bernstein functions (
) which are internal, that is, those Bernstein functions ϕ s.t. Ψ∘ϕ remains a Bernstein function for every Ψ. We complete their work and illustrate how the class of internal function is rich from the stochastic point of view. It is well known that every
corresponds to (i) a subordinator (Xt)t ≥ 0 (or equivalently to transition semigroups
and (ii) a Lévy measure μ (which controls the jumps of the subordinator). It is also known that, on (0,∞), the measure
converges vaguely to dδ0(dx)+μ(dx) as t→0, where d is the drift term, but rare are the situations where we can compare the transition semigroups with the Lévy measure. Our extensive investigations on the composition of Lévy‐Laplace exponents Ψ with Bernstein functions show, for instance, these remarkable facts: ϕ is internal is equivalent to (a)
or to (b)
is a positive measure on (0,∞). We also provide conditions on μ insuring internality for ϕ and illustrate how Lévy‐Laplace exponents are closely connected to the class of Thorin Bernstein function.
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

Inventory 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

Although 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

Objectives

To evaluate the performance of noninvasive prenatal sequencing for multiple Mendelian monogenic disorders (NIPS‐M) among fetuses with skeletal abnormalities or increased nuchal translucency (NT).

Methods

Pregnancies 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.

Results

Among 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%.

Conclusions

Our 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

In 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.