bluuebunny/crossref_metadata_2025 huggingface dataset:
The Causal Relationship between Type 2 Diabetes Mellitus and Ovarian Cancer: Two-Sample Mendelian Randomization
Authors: Victor Langat Kipkirui , Lang’at Reuben Cheruiyot , Okango Ayubu Anapapa
Published: June 2021

Aims: This research aimed at determining the causal relationship between type 2 diabetes mellitus (T2DM) and ovarian cancer using two-sample Mendelian randomization technique. This is because there is an assumption that type 2 diabetes mellitus (T2DM) has a causal relationship with ovarian cancer due to the alarming rising incidence statistics.

Study design: This study used a two-sample Mendelian Randomization (MR) design to undertake the causal relationship investigation. Mendelian randomization technique uses genetic variants as instrumental variables, which undergo random allocation at conception and are non-modifiable. This makes it not to be affected by confounding factors and reverse causation. The MR techniques employed are MR-Egger and Inverse Variance Weighted (IVW.)

Data sources: The outcome (ovarian cancer) summary statistics was retrieved from Ovarian Cancer Association Consortium (OCAC), which has 66,450 samples (number of cases=25,509, number of controls=40,941) of European population. The exposure (T2DM) summary genetic data came from DIAGRAM plus Metabochip consortium which involved approximately 149,821 samples (number of cases=34,840, number of controls=114,981) of mixed population.

Results: The study indicated that there was no evidence of causal relationship between T2DM and ovarian cancer (MR-Egger: b= -0.0476, se = 0.0619, p-value = 0.4479, IVW: b = -0.0165, se = 0.0257, p-value = 0.5217). The odds ratios indicated that the two-sample Mendelian randomization had the power to detect 0.0464 and 0.0164 decrease in variability per 1 SD for MR-Egger and IVW respectively (MR-Egger: OR = 0.9536, CI: 0.8447, 1.0765, IVW: OR = 0.9836, CI: 0.9352, 1.0345).

Conclusion: This approach alleviated the usual problem of reverse causation and confounding factors hence depicting clearly that there is no causal relationship between T2DM and Ovarian cancer.
Different Vacuum Pad Design Effects with Z-Picker Assembly
Authors: Kumawit Allen Jay D. , S. Buera Maria Virginia , Mendoza Mariane A. , Gomez Frederick Ray I.
Published: June 2021

After singulation process where the strips are being cut into single units, unit tray loading comes next. Unit tray loading is the process where the singulated units will be picked up from the table and then place it in a tray pocket. Z-picker assembly executes the pick and placing activity through vacuum suction. Vacuum pads were installed on the Z-picker’s vacuum pad holder area, and it contacts with the unit. Vacuum pads come with different design depending on dimension and configuration of the device in process. Pick and place process is prone for unit dislodge as it transfers the unit from one place to another. These unit dislodges will result to missing units and will be accounted for yield loss. In this study, the authors were driven to understand the Z-picker mechanism together with the effect of vacuum pad designs, aiming to find the best match that would lessen the occurrence of unit dislodges.
Follicle‐stimulating hormone worsens osteoarthritis by causing inflammation and chondrocyte dedifferentiation
Authors: Huan Zhikun , Wang Yan , Zhang Mengqi , Zhang Xiujuan , Liu Yaping , Kong Lei , Xu Jin
Published: June 2021

Previous studies have found follicle‐stimulating hormone (FSH) receptors on chondrocytes (cartilage cells), but the mechanism of FSH action on chondrocytes is not clear. The purpose of this experiment is to study whether FSH affects chondrocytes and how it causes changes in these cells. Our results show that osteoarthritis became worse after FSH injection in the knee joint of mice. After the stimulation of chondrocytes by FSH, a total of 664 up‐regulated genes, such as Col12a1 and Col1a1, and 644 down‐regulated genes, such as MGP, were screened by transcriptomics. A subset of extracellular matrix (ECM)‐related genes and pathways underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the downregulation of MGP, the upregulation of EGR1 and Col1a1, and the increase of IL‐6 were verified. It was also observed that FSH can inhibit the cAMP/PKA and MKK4/JNK signaling pathway. In conclusion, we demonstrated that FSH can increase cartilage inflammatory response and promote chondrocyte dedifferentiation by inhibiting the cAMP/PKA and MKK4/JNK signaling pathways.
Engineering Janus Chemoreactive Nanosonosensitizers for Bilaterally Augmented Sonodynamic and Chemodynamic Cancer Nanotherapy
Authors: Xu Wenwen , Dong Caihong , Hu Hui , Qian Xiaoqin , Chang Ling , Jiang Qvzi , Yu Luodan , Chen Yu , Zhou Jianqiao
Published: June 2021

As a non‐invasive treatment modality with high tissue‐penetration depth, ultrasound‐triggered sonodynamic therapy (SDT) has been extensively explored and is regarded as the alternative choice to overcome the drawbacks of conventional photo‐triggered therapies. Nevertheless, the low quantum yield of sonosensitizer, tumor hypoxia, and undesirable therapeutic efficiency are still the major concerns of SDT. It is highly challenging but necessary to explore the SDT‐based synergistic, augmented, and noninvasive therapeutic modalities. Herein, a distinct TiO2Fe3O4@PEG Janus nanostructure composed of the typical sonosensitizer TiO2 and nanoenzyme Fe3O4 is rationally designed and engineered for bilaterally enhanced SDT and chemodynamic therapy (CDT). The deposition of Fe3O4 component on the surface of TiO2 can not only endow the Janus nanosonosensitizers with Fenton‐catalytic activity to generate hydroxyl radicals (•OH) from tumor‐endogenous overexpressed H2O2 for CDT but also enhance the SDT performance of TiO2 via narrowing the band gap of TiO2 and reducing the recombination rate of the electrons (e–/h+) pair. In turn, the US activation can both accelerate mass transfer and chemical reaction rates of the Fenton reaction to enhance the CDT effect. The high efficacy of bilaterally enhanced SDT and CDT is systematically demonstrated both in vitro and in vivo.
Magnetic‐Field Tunable Intertwined Checkerboard Charge Order and Nematicity in the Surface Layer of Sr2RuO4
Authors: Marques Carolina A. , Rhodes Luke C. , Fittipaldi Rosalba , Granata Veronica , Yim Chi Ming , Buzio Renato , Gerbi Andrea , Vecchione Antonio , Rost Andreas W. , Wahl Peter
Published: June 2021

In strongly correlated electron materials, the electronic, spin, and charge degrees of freedom are closely intertwined. This often leads to the stabilization of emergent orders that are highly sensitive to external physical stimuli promising opportunities for technological applications. In perovskite ruthenates, this sensitivity manifests in dramatic changes of the physical properties with subtle structural details of the RuO6octahedra, stabilizing enigmatic correlated ground states, from a hotly debated superconducting state via electronic nematicity and metamagnetic quantum criticality to ferromagnetism. Here, it is demonstrated that the rotation of the RuO6octahedra in the surface layer of Sr2RuO4generates new emergent orders not observed in the bulk material. Through atomic‐scale spectroscopic characterization of the low‐energy electronic states, four van Hove singularities are identified in the vicinity of the Fermi energy. The singularities can be directly linked to intertwined nematic and checkerboard charge order. Tuning of one of these van Hove singularities by magnetic field is demonstrated, suggesting that the surface layer undergoes a Lifshitz transition at a magnetic field of ≈32T. The results establish the surface layer of Sr2RuO4as an exciting 2D correlated electron system and highlight the opportunities for engineering the low‐energy electronic states in these systems.
Construction of Aramid Engineering Materials via Polymerization‐Induced para‐Aramid Nanofiber Hydrogel
Authors: Xie Chunjie , Guo Zhao‐Xia , Qiu Teng , Tuo Xinlin
Published: June 2021

The processing of poly(p‐phenylene terephthalamide) (PPTA) has long been a great challenge. This work reports a simple “monomers‐nanofibers‐macroscopic product” (MNM) hierarchical self‐assembly approach to build 3D all‐PPTA engineering materials. This approach mainly includes the preparation of polymerization‐induced aramid nanofibers (PANFs) from monomers and the fabrication of all‐PPTA materials from PANF hydrogel. Various 3D architectures, including simple solid bulks and sophisticated honeycombs (HCs), are obtained after the dehydration and shrinking of the PANF hydrogel. The tensile strength and compressive yield strength of PANF bulk are more than 62 and 90 MPa, respectively, which are comparable to typical engineering plastics. The compressive strength of PANF HC with a density of 360 kg m−3 is more than 24 MPa. The thermal stability of PANF bulk and PANF HC are as good as that of Kevlar fiber and almost no decomposition occurred before 500 °C in a nitrogen atmosphere. Furthermore, the MNM process is performed under mild conditions, without high temperature, high pressure, or corrosive solvent. The MNM process is a novel strategy for the processing of all aromatic polyamide materials with complex structures and high performances and would be another development since the breakthrough of liquid crystal spinning technology of PPTA.
Electrostatically Tunable Near‐Infrared Plasmonic Resonances in Solution‐Processed Atomically Thin NbSe2
Authors: Zhao Meng , Li Jing , Sebek Matej , Yang Le , Liu Yan Jun , Bosman Michel , Wang Qian , Zheng Xinting , Lu Jiong , Teng Jinghua
Published: June 2021

In the broad spectral range, near‐infrared (NIR) plasmonics find applications in telecommunication, energy harvesting, sensing, and more, all of which would benefit from an electrostatically controllable NIR plasmon source. However, it is difficult to control bulk NIR plasmonics directly with electrostatics because of the strong electric‐field screening effect and high carrier concentration required to support NIR plasmons. Here, this constraint is overcome and the observation of NIR plasmonic resonances that can be modulated electrostatically over a range of ≈360 cm–1 in few‐layer NbSe2 gratings is reported, thanks to the enhanced electrostatics of atomically thin 2D materials and the high‐quality film produced by a solution method. NbSe2 plasmons also render strong field confinement due to their atomic thickness and provide an extra degree of resonance frequency modulation from the layered structure. This study identifies metallic 2D materials as promising (easily produced and well‐performing) candidates to extend electrostatically tunable plasmonics to the technologically important NIR range.
Tunable Photocatalytic Activity of PEO‐Stabilized ZnO–Polyoxometalate Nanostructures in Aqueous Solution
Authors: Bernhardt Sarah , Düring Jasmin , Haschke Sandra , Barr Maissa K. S. , Stiegler Lisa , Schühle Patrick , Bachmann Julien , Hirsch Andreas , Gröhn Franziska
Published: June 2021

The photocatalytic activity and selectivity of novel binary and ternary composite nanostructures from polyethylene oxide‐stabilized zinc oxide (PEO–ZnO) with and without polyoxometalate (H4[Si(W3O10)4], POM) are determined in aqueous solution under UV‐light. Mono‐ and di‐COOH‐end‐functionalized PEO polymers are used as surface modifiers, influencing the morphology and stability of the ZnO nanoparticles being synthesized in water. POM acts as an additional versatile photocatalytically active building block resulting in a ternary hybrid structure with tunable photocatalytic activity. Catalytic selectivity is demonstrated by studying photocatalytic dye degradations as model reactions, where the chemical backbone of the dyes and their charge turn out to be the basis for the selectivity. All samples are characterized with dynamic light scattering, transmission electron microscopy, scanning electron microscopy, light microscopy, and ζ‐potential measurements. With the functionalized PEOs, large ZnO clusters consisting of leaves are formed while 2‐[2‐(2‐methoxyethoxy) ethoxy] acetic acid (TODA) yields ZnO flower‐like structures.
Integrating Conductive Metal–Organic Framework with Graphene Oxide to Highly Sensitive Platform for Electrochemical Sensing
Authors: Shi Xiaofei , Xu Yulong , Zhao Bo , Li Pingping , Song Min , Jia Jingjing , Yu Huijun , Lu Guang
Published: June 2021

The rational selection and integration of materials play important roles in advancing electrochemical sensing. Herein, a highly sensitive electrochemical platform based on composites of graphene oxide (GO) and conductive YbHHTP metal–organic framework (HHTP = 2,3,6,7,10,11‐hexahydroxytriphenylene) for the detection of dopamine (DA) and uric acid (UA) is reported. The composites are prepared by the introduction of GO into the hydrothermal synthesis of YbHHTP. The morphology, structure, and property of the resultant GO/YbHHTP composites are characterized by scanning electron microscopy, transmission electron microscopy, X‐ray diffraction, ultraviolet–visible spectroscopy, X‐ray photoelectron spectroscopy, electrochemical impedance spectroscopy, and cycle voltammetry. The results show that this in situ integration strategy facilitates the homogeneous anchoring of YbHHTP nanorods on the surface of GO sheets to achieve a considerable conductivity in the composites and fast electrochemical kinetics for probe molecules. As a result, the GO(2.0)/YbHHTP‐modified electrodes exhibit ultrahigh sensitivity in detection of DA (3.62 µA µm−1) and UA (1.97 µA µm−1) as well as excellent reproducibility, stability, and anti‐interfere ability.
Fast Water Evaporation from Nanopores
Authors: Huang Zhi , Chen Bo , Mo Xiaobao , Yang Xuelong , Yu Liangying , Hu Xuejiao , Liu Kang
Published: June 2021

Fast water evaporation is of fundamental importance for natural biological regulation and industry applications. Here, for the first time, it is demonstrated that fast evaporation can be facilely achieved by putting a membrane with perpendicularly ordered pores on the water surface. Compared with the evaporation rate of bulk water, evaporation of water from nanopores is 6.4 to 0.5 times faster at the relative humidity range from 90% to 25%. Additionally, the evaporation rate Jnano exhibits a negative correlation with the pore size and the normalized evaporation rate Jnano/Jbulk displays no obvious relation with the liquid species. Further analysis shows that the evaporation enhancement is induced by the enhanced vapor density close to the evaporating surface. These results provide a simple geometrical method for evaporation enhancement and may stimulate new inspirations on phase change phenomena and applications.
Curvature and Stress Effects on the Performance of Contour‐Mode Resonant ΔE Effect Magnetometers
Authors: Matyushov Alexei D. , Spetzler Benjamin , Zaeimbashi Mohsen , Zhou James , Qian Zhenyun , Golubeva Elizaveta V. , Tu Cheng , Guo Yingxue , Chen Brian F. , Wang Damo , Will‐Cole Alexandria , Chen Huaihao , Rinaldi Matteo , McCord Jeffrey , Faupel Franz , Sun Nian X.
Published: June 2021

Miniaturized piezoelectric/magnetostrictive contour‐mode resonators are effective magnetometers by exploiting the ΔE effect. With dimensions of ≈100–200 µm across and <1 µm thick, they offer high spatial resolution, portability, low power consumption, and low cost. However, a thorough understanding of the magnetic material behavior in these devices is lacking, hindering performance optimization. This manuscript reports on the strong, nonlinear correlation observed between the frequency response of these sensors and the stress‐induced curvature of the resonator plate. The resonance frequency shift caused by DC magnetic fields drops off rapidly with increasing curvature: about two orders of magnitude separate the highest and lowest frequency shift in otherwise identical devices. Similarly, an inverse correlation with the quality factor is found, suggesting a magnetic loss mechanism. The mechanical and magnetic properties are theoretically analyzed using magnetoelastic finite‐element and magnetic domain‐phase models. The resulting model fits the measurements well and is generally consistent with additional results from magneto‐optical domain imaging. Thus, the origin of the observed behavior is identified and broader implications for the design of nanomagnetoelastic devices are derived. By fabricating a magnetoelectric nanoplate resonator with low curvature, a record‐high DC magnetic field sensitivity of 5 Hz nT–1 is achieved.
Key Considerations for the Development of Safe and Effective SARS‐CoV‐2 Subunit Vaccine: A Peptide‐Based Vaccine Alternative
Authors: Shalash Ahmed O. , Hussein Waleed M. , Skwarczynski Mariusz , Toth Istvan
Published: June 2021

COVID‐19 is disastrous to global health and the economy. SARS‐CoV‐2 infection exhibits similar clinical symptoms and immunopathological sequelae to SARS‐CoV infection. Therefore, much of the developmental progress on SARS‐CoV vaccines can be utilized for the development of SARS‐CoV‐2 vaccines. Careful antigen selection during development is always of utmost importance for the production of effective vaccines that do not compromise recipient safety. This holds especially true for SARS‐CoV vaccines, as several immunopathological disorders are associated with the activity of structural and nonstructural proteins encoded in the virus's genetic material. Whole viral protein and RNA‐encoding full‐length proteins contain both protective and “dangerous” sequences, unless pathological fragments are deleted. In light of recent advances, peptide vaccines may present a very safe and effective alternative. Peptide vaccines can avoid immunopathological pro‐inflammatory sequences, focus immune responses on neutralizing immunogenic epitopes, avoid off‐target antigen loss, combine antigens with different protective roles or mechanisms, even from different viral proteins, and avoid mutant escape by employing highly conserved cryptic epitopes. In this review, an attempt is made to exploit the similarities between SARS‐CoV and SARS‐CoV‐2 in vaccine antigen screening, with particular attention to the pathological and immunogenic properties of SARS proteins.
The Role of the Internal Capacitance in Organic Memristive Device for Neuromorphic and Sensing Applications
Authors: Battistoni Silvia , Cocuzza Matteo , Marasso Simone Luigi , Verna Alessio , Erokhin Victor
Published: June 2021

Organic electronics has recently emerged as a promising candidate for the emulation of brain‐like functionalities, especially at the device level. Among the proposed technologies, memristive devices have gained an increasing attention due to their non‐volatile behavior which makes them suitable for the implementation of artificial neuronal networks. However, most of them have an energy‐costly switching mechanism which limits the approach of brain like energy efficiency. Different from them, organic memristive devices (OMDs) have a narrow switching window and implement neuromorphic characteristics at voltages ≤ 1 V. Despite OMDs potentialities in bioinspired electronics, guidelines for the design of devices and materials are still missing. Here it is shown that the device capacitance represents a significant degree of freedom for targeting devices applications. It is also shown that a single OMD emulates activity dependent synaptic functions and neuronal temporal and spatial summation, taking advantage of its three‐terminals configuration. Interestingly, despite the neuromorphic applications, OMDs can also sense and amplify incoming signals on the basis of their capacitive and/or resistive values. This spectrum of applications, ranging from volatile to non‐volatile characteristics and from neuromorphic computing to bio signals sensing, sets the stage for the realization of integrated circuits for adaptive sensing.
Base cation saturation ratios vs. sufficiency level of nutrients: A false dichotomy in practice
Authors: Culman Steve W. , Brock Caroline , Doohan Douglas , Jackson‐Smith Douglas , Herms Catherine , Chaganti Vijayasatya N. , Kleinhenz Matthew , Sprunger Christine D. , Spargo John
Published: June 2021

Base cation saturation ratio (BCSR) or “soil balancing” is a soil management philosophy which strives to maintain targeted base cation saturation percentages in soil. Despite lack of Land Grant University (LGU) endorsement for decades, BCSR is widely practiced by many farmers in the United States, particularly in the organic farming community. Here, we explore BCSR persistence and present a framework around BCSR that reflects how it is conceived and practiced on working farms, with a key premise that BCSR practitioners typically use both LGU‐endorsed sufficiency level of available nutrients (SLAN) and BCSR in a hybrid approach. Drawing on (a) a survey of LGU soil fertility scientists’ perspectives on BCSR, (b) decades of published literature on impacts of lime and gypsum application, (c) soil test data from organic corn fields in a four‐state region of the Midwest, and (d) a large state‐wide soil test dataset from Ohio, we examined and tested five unique hypotheses about BCSR. We provide evidence to support the following statements: (a) published peer‐reviewed literature on BCSR is limited and dated, (b) there is widespread agreement among soil fertility scientists that BCSR is not a legitimate practice of soil management, (c) studies of lime and gypsum application on soils can lend insight into the efficacy of BCSR, and (d) in many soils, managing soil acidity will also balance soils in BCSR ideal saturation percentages. Collectively, we summarize key findings from our interdisciplinary effort to provide an updated overview and a more nuanced perspective of BCSR in practice.
An integrated dimensionality reduction and surrogate optimization approach for plant‐wide chemical process operation
Authors: Savage Thomas R. , Almeida‐Trasvina Fernando , del‐Rio Chanona Ehecatl A. , Smith Robin , Zhang Dondga
Published: June 2021

With liquefied natural gas becoming increasingly prevalent as a flexible source of energy, the design and optimization of industrial refrigeration cycles becomes even more important. In this article, we propose an integrated surrogate modeling and optimization framework to model and optimize the complex CryoMan Cascade refrigeration cycle. Dimensionality reduction techniques are used to reduce the large number of process decision variables which are subsequently supplied to an array of Gaussian processes, modeling both the process objective as well as feasibility constraints. Through iterative resampling of the rigorous model, this data‐driven surrogate is continually refined and subsequently optimized. This approach was not only able to improve on the results of directly optimizing the process flow sheet but also located the set of optimal operating conditions in only 2 h as opposed to the original 3 weeks, facilitating its use in the operational optimization and enhanced process design of large‐scale industrial chemical systems.
Chemistry of lignin and hemicellulose structures interacts with hydrothermal pretreatment severity and affects cellulose conversion
Authors: Deralia Parveen Kumar , Jensen Anders , Felby Claus , Thygesen Lisbeth Garbrecht
Published: June 2021

Understanding of how the plant cell walls of different plant species respond to pretreatment can help improve saccharification in bioconversion processes. Here, we studied the chemical and structural modifications in lignin and hemicellulose in hydrothermally pretreated poplar and wheat straw using wet chemistry and 2D heteronuclear single quantum coherence nuclear magnetic resonance (NMR) and their effects on cellulose conversion. Increased pretreatment severity reduced the levels of β─O─4 linkages with concomitant relatively increased levels of β─5 and β─β structures in the NMR spectra. β─5 structures appeared at medium and high severities for wheat straw while only β─β structures were observed at all pretreatment severities for poplar. These structural differences accounted for the differences in cellulose conversion for these biomasses at different severities. Changes in the hemicellulose component include a complete removal of arabinosyl and 4‐O‐methyl glucuronosyl substituents at low and medium pretreatment severities while acetyl groups were found to be relatively resistant toward hydrothermal pretreatment. This illustrates the importance of these groups, rather than xylan content, in the detrimental role of xylan in cellulose saccharification and helps explain the higher poplar recalcitrance compared to wheat straw. The results point toward the need for both enzyme preparation development and pretreatment technologies to target specific plant species.
Base‐Promoted Synthesis of 3‐Alkenyl‐2‐pyridones from N‐Propargyl‐β‐enaminones and Aryl Aldehydes
Authors: Tian Qingyu , Xiao Shangyun , Cheng Guolin
Published: June 2021

Main observation and conclusion

In this article, we report a base‐promoted sequential cyclization/aldol‐type condensation/isomerization cascade reaction of N‐propargyl‐β‐enaminones with aryl aldehydes. The key step in this protocol is the generation of 1,4‐oxazepine anions from N‐propargyl‐β‐enaminones under basic conditions, which are captured by aryl aldehydes. The method allows the formation of one pyridone core and one C—C double bond in “one pot”, and the preparation of a variety of densely decorated pyridone derivatives in moderate to good yields with broad functional group tolerance.
An Experimental Toolbox for Structure‐Based Hit Discovery for P. aeruginosa FabF, a Promising Target for Antibiotics
Authors: Espeland Ludvik Olai , Georgiou Charis , Klein Raphael , Bhukya Hemalatha , Haug Bengt Erik , Underhaug Jarl , Mainkar Prathama S. , Brenk Ruth
Published: June 2021

FabF (3‐oxoacyl‐[acyl‐carrier‐protein] synthase 2), which catalyses the rate limiting condensation reaction in the fatty acid synthesis II pathway, is an attractive target for new antibiotics. Here, we focus on FabF from P. aeruginosa (PaFabF) as antibiotics against this pathogen are urgently needed. To facilitate exploration of this target we have set up an experimental toolbox consisting of binding assays using bio‐layer interferometry (BLI) as well as saturation transfer difference (STD) and WaterLOGSY NMR in addition to robust conditions for structure determination. The suitability of the toolbox to support structure‐based design of FabF inhibitors was demonstrated through the validation of hits obtained from virtual screening. Screening a library of almost 5 million compounds resulted in 6 compounds for which binding into the malonyl‐binding site of FabF was shown. For one of the hits, the crystal structure in complex with PaFabF was determined. Based on the obtained binding mode, analogues were designed and synthesised, but affinity could not be improved. This work has laid the foundation for structure‐based exploration of PaFabF.
Real‐world emetic risk of chemotherapy and the corresponding antiemetic therapy in Japan: A study based on a nationwide database
Authors: Okuyama Ayako , Boku Narikazu , Higashi Takahiro
Published: June 2021

Background

Chemotherapy‐induced nausea and vomiting (CINV) is a major concern of patients with cancer, leading to suboptimal treatment.

Aim

This study assessed the emetic risk associated with intravenous and oral chemotherapy and the prophylactic antiemetic drugs by cancer type in a real‐world setting.

Methods and Results

We used the health services utilisation data for patients with cancer diagnosed in 2016. Patients aged at least 20 years at the time of diagnosis and who started their first course of chemotherapy were included. The emetic risk of chemotherapy was determined according to the cancer type and was classified based on clinical practice guidelines. The prescription of antiemetic drugs was assessed. Overall, 172 133 patients were evaluated, of whom 121 103 (70.4%) received intravenous chemotherapy. High‐emetic‐risk chemotherapy (HEC) was prescribed in 46 458 (27.0%) patients. HEC was prescribed most for patients with oesophageal cancer (80.3%), followed by malignant lymphoma (60.2%) and breast cancer (53.8%). Moderate‐emetic‐risk chemotherapy (MEC) was prescribed in 60 528 (35.2%) patients and was mostly prescribed for small cell lung cancer (59.9%). Meanwhile, more than 50% of the chemotherapy prescribed for patients with gastric, colorectal, and pancreatic cancer was low‐emetic‐risk chemotherapy. HEC was accompanied by three‐drug antiemetic prophylaxis in more than 90% of patients with small cell lung, non‐small cell lung, breast, and oesophageal cancer, whereas only 13.5% of patients with malignant lymphoma were administered CHOP (cyclophosphamide, doxorubicin, vincristine sulphate, and prednisolone) with prophylaxis.

Conclusion

The risk of CINV differs with cancer type. HEC was less prescribed compared with MEC. Most patients received the recommended anti‐emetic prophylaxis.
Oncogenetic network estimation with disjunctive Bayesian networks
Authors: Nicol Phillip B. , Coombes Kevin R. , Deaver Courtney , Chkrebtii Oksana , Paul Subhadeep , Toland Amanda E. , Asiaee Amir
Published: June 2021

Motivation: Cancer is the process of accumulating genetic alterations that confer selective advantages to tumor cells. The order in which aberrations occur is not arbitrary, and inferring the order of events is challenging due to the lack of longitudinal samples from tumors. Moreover, a network model of oncogenesis should capture biological facts such as distinct progression trajectories of cancer subtypes and patterns of mutual exclusivity of alterations in the same pathways.

In this paper, we present the disjunctive Bayesian network (DBN), a novel oncogenetic model with a phylogenetic interpretation. DBN is expressive enough to capture cancer subtypes' trajectories and mutually exclusive relations between alterations from unstratified data.

Results: In cases where the number of studied alterations is small (), we provide an efficient dynamic programming implementation of an exact structure learning method that finds a best DBN in the superexponential search space of networks. In rare cases that the number of alterations is large, we provided an efficient genetic algorithm in our software package, OncoBN. Through numerous synthetic and real data experiments, we show OncoBN's ability in inferring ground truth networks and recovering biologically meaningful progression networks.

Availability: OncoBN is implemented in R and is available at https://github.com/phillipnicol/OncoBN.
Integrative multiomics analysis of human atherosclerosis reveals a serum response factor‐driven network associated with intraplaque hemorrhage
Authors: Jin Han , Goossens Pieter , Juhasz Peter , Eijgelaar Wouter , Manca Marco , Karel Joël M. H. , Smirnov Evgueni , Sikkink Cornelis J. J. M. , Mees Barend M. E. , Waring Olivia , van Kuijk Kim , Fazzi Gregorio E. , Gijbels Marion J. J. , Kutmon Martina , Evelo Chris T. A. , Hedin Ulf , Daemen Mat J. A. P. , Sluimer Judith C. , Matic Ljubica , Biessen Erik A. L.
Published: June 2021

Background

While single‐omics analyses on human atherosclerotic plaque have been very useful to map stage‐ or disease‐related differences in expression, they only partly capture the array of changes in this tissue and suffer from scale‐intrinsic limitations. In order to better identify processes associated with intraplaque hemorrhage and plaque instability, we therefore combined multiple omics into an integrated model.

Methods

In this study, we compared protein and gene makeup of low‐ versus high‐risk atherosclerotic lesion segments from carotid endarterectomy patients, as judged from the absence or presence of intraplaque hemorrhage, respectively. Transcriptomic, proteomic, and peptidomic data of this plaque cohort were aggregated and analyzed by DIABLO, an integrative multivariate classification and feature selection method.

Results

We identified a protein‐gene associated multiomics model able to segregate stable, nonhemorrhaged from vulnerable, hemorrhaged lesions at high predictive performance (AUC >0.95). The dominant component of this model correlated with αSMA−PDGFRα+fibroblast‐like cell content (p = 2.4E‐05) and Arg1+macrophage content (p = 2.2E‐04) and was driven by serum response factor (SRF), possibly in a megakaryoblastic leukemia‐1/2 (MKL1/2) dependent manner. Gene set overrepresentation analysis on the selected key features of this model pointed to a clear cardiovascular disease signature, with overrepresentation of extracellular matrix synthesis and organization, focal adhesion, and cholesterol metabolism terms, suggestive of the model's relevance for the plaque vulnerability. Finally, we were able to corroborate the predictive power of the selected features in several independent mRNA and proteomic plaque cohorts.

Conclusions

In conclusion, our integrative omics study has identified an intraplaque hemorrhage‐associated cardiovascular signature that provides excellent stratification of low‐ from high‐risk carotid artery plaques in several independent cohorts. Further study revealed suppression of an SRF‐regulated disease network, controlling lesion stability, in vulnerable plaque, which can serve as a scaffold for the design of targeted intervention in plaque destabilization.
Diversity and intratumoral heterogeneity in human gallbladder cancer progression revealed by single‐cell RNA sequencing
Authors: Chen Peizhan , Wang Yueqi , Li Jingquan , Bo Xiaobo , Wang Jie , Nan Lingxi , Wang Changcheng , Ba Qian , Liu Houbao , Wang Hui
Published: June 2021

Background

Gallbladder cancer (GC) is a malignant disease characterized with highly cellular heterogeneity and poor prognosis. Determining the intratumoral heterogeneity and microenvironment (TME) can provide novel therapeutic strategies for GC.

Methods

We performed the single‐cell RNA sequencing on the primary and lymph node metastatic gallbladder tumors and the adjacent normal tissues of five patients. The transcriptomic atlas and ligand–receptor‐based intercellular communication networks of the single cells were characterized.

Results

The transcriptomic landscape of 24,887 single cells was obtained and characterized as 10 cellular clusters, including epithelial, neuroendocrine tumor cells, T&NK cells, B cells, RGS5+ fibroblasts, POSTN+ fibroblasts, PDGFRA+ fibroblasts, endothelial, myeloid cells, and mast cells. Different types of GC harbored distinct epithelial tumor subpopulations, and squamous cell carcinoma could be differentiated from adenocarcinoma cells. Abundant immune cells infiltrated into adenocarcinoma and squamous cell carcinoma, rather than neuroendocrine neoplasms, which showed significant enrichment of stromal cells. CD4+/FOXP3+ T‐reg and CD4+/CXCL13+ T helper cells with higher exhausting biomarkers, as well as a dynamic lineage transition of tumor‐associated macrophages from CCL20hi/CD163lo, CCL20lo/CD163hi to APOE+, were identified in GC tissues, suggesting the immunosuppressive and tumor‐promoting status of immune cells in TME. Two distinct endothelial cells (KDR+ and ACKR1+), which were involved in angiogenesis and lymphangiogenesis, showed remarkable ligand–receptor interactions with primary GC cells and macrophages in gallbladder tumors.

Conclusions

This study reveals a widespread reprogramming across multiple cell populations in GC progression, dissects the cellular heterogeneity and interactions in gallbladder TME, and provides potential therapeutic targets for GC.
Activated neutrophils polarize protumorigenic interleukin‐17A‐producing T helper subsets through TNF‐α‐B7‐H2‐dependent pathway in human gastric cancer
Authors: Shan Zhi‐guo , Chen Jun , Liu Jin‐shan , Zhang Jin‐yu , Wang Ting‐ting , Teng Yong‐sheng , Mao Fang‐yuan , Cheng Ping , Zou Quan‐ming , Zhou Wei‐ying , Peng Liu‐sheng , Zhao Yong‐liang , Zhuang Yuan
Published: June 2021

Rationale

Neutrophils constitute massive cellular constituents in inflammatory human gastric cancer (GC) tissues, but their roles in pathogenesis of inflammatory T helper (Th) subsets are still unknown.

Methods

Flow cytometry analysis and immunohistochemistry were used to analyze the responses and phenotypes of neutrophils in different samples from 51 patients with GC. Kaplan‐Meier plots and Multivariate analysis for the survival of patients were used by log‐rank tests and Cox proportional hazards models. Neutrophils and CD4+ T cells were purified and cultured for ex vivo, in vitro and in vivo regulation and function assays.

Results

GC patients exhibited increased tumoral neutrophil infiltration with GC progression and poor patient prognosis. Intratumoral neutrophils accumulated in GC tumors via CXCL6/CXCL8‐CXCR1‐mediated chemotaxis, and expressed activated molecule CD54 and co‐signaling molecule B7‐H2. Neutrophils induced by tumors strongly expressed CD54 and B7‐H2 in both dose‐ and time‐dependent manners, and a close correlation was obtained between the expressions of CD54 and B7‐H2 on intratumoral neutrophils. Tumor‐derived tumor necrosis factor‐α (TNF‐α) promoted neutrophil activation and neutrophil B7‐H2 expression through ERK‐NF‐κB pathway, and a significant correlation was found between the levels of TNF‐α and CD54+ or B7‐H2+ neutrophils in tumor tissues. Tumor‐infiltrating and tumor‐conditioned neutrophils effectively induced IL‐17A‐producing Th subset polarization through a B7‐H2‐dependent manner ex vivo and these polarized IL‐17A‐producing Th cells exerted protumorigenic roles by promoting GC tumor cell proliferation via inflammatory molecule IL‐17A in vitro, which promoted the progression of human GC in vivo; these effects could be reversed when IL‐17A is blocked. Moreover, increased B7‐H2+ neutrophils and IL‐17A in tumors were closely related to advanced GC progression and predicted poor patient survival.

Conclusion

We illuminate novel underlying mechanisms that TNF‐α‐activated neutrophils link B7‐H2 to protumorigenic IL‐17A‐producing Th subset polarization in human GC. Blocking this pathological TNF‐α‐B7‐H2‐IL‐17A pathway may be useful therapeutic strategies for treating GC.
Impact of beta‐blocker use on the long‐term outcomes of heart failure patients with chronic obstructive pulmonary disease
Authors: Kubota Yoshiaki , Tay Wan Ting , Teng Tiew‐Hwa Katherine , Asai Kuniya , Noda Takashi , Kusano Kengo , Suzuki Atsushi , Hagiwara Nobuhisa , Hisatake Shinji , Ikeda Takanori , Yasuoka Ryobun , Kurita Takashi , Shimizu Wataru ,   ASIAN‐HF Executive Committee
Published: June 2021

Aims

The number of patients with both chronic obstructive pulmonary disease (COPD) and heart failure (HF) is increasing in Asia, and these conditions often coexist. We previously revealed a tendency of beta‐blocker underuse among patients with HF with reduced ejection fraction (HFrEF) and COPD in Asian countries other than Japan. Here, we evaluated the impact of cardio‐selective beta‐blocker use on the long‐term outcomes of patients with HF and COPD.

Methods and results

Among the 5232 patients with HFrEF (left ventricular ejection fraction of <40%) prospectively enrolled from 11 Asian regions in the ASIAN‐HF registry, 412 (7.9%) had a history of COPD. We compared the clinical characteristics and long‐term outcomes of the patients with HF and COPD according to the use and type of beta‐blockers used: cardio‐selective beta‐blockers (n = 149) vs. non‐cardio‐selective beta‐blockers (n = 124) vs. no beta‐blockers (n = 139). The heart rate was higher, and the outcome was poorer in the no beta‐blocker group than in the beta‐blocker groups. The 2 year all‐cause mortality was significantly lower in the non‐cardio‐selective beta‐blocker group than in the no beta‐blocker group. Further, the cardiovascular mortality significantly decreased in the non‐cardio‐selective beta‐blocker group before (hazard ratio: 0.36; 95% confidence interval: 0.18–0.73; P = 0.004) and after adjustments (hazard ratio: 0.37; 95% confidence interval: 0.19–0.73; P = 0.005), but not in the cardio‐selective beta‐blocker group.

Conclusions

Beta‐blockers reduced the all‐cause mortality of patients with HFrEF and COPD after adjusting for age and heart rate, although the possibility of selection bias could not be completely excluded due to multinational prospective registry.
Synthesis of Emulsion by Using Vegetable Oil Modified by Titanium Dioxide (TiO2) Nanoparticles: A Peculiar Source for Synthesis of Bio‐Based Lubricant and Novel Approach to Enhance the Efficiency of Emulsion
Authors: Ajmal Muhammad , Ali Syed Abid , Tahir Hajira , Shah Muhammad Raza , Saad Muhammad
Published: June 2021

Many advanced methods are developed for the synthesis of emulsions in the literature, but the effect of imperative parameters of emulsion like oil concentration, pH, temperature, and time on the emulsion stability index (ESI) by design of experiments have not been studied previously. The ESI is an important parameter of emulsion to run the industrial process extensively and reflects the emulsion efficiency to sustain against instability like creaming, coalescence, and flocculation. In the present study, the research plan consists of three phases. In the first phase, the synthesis of an eco‐friendly and cost‐effective mustard oil‐based nanoemulsion with a suitable selection of the surfactant on the bases of the polydispersity index (PDI) is developed. In the next phase emulsions, characteristic properties are scanned by employing various techniques and antirust property compared with reference emulsion. Finally, the impact of emulsion's parameters on ESI is studied by factorial design. The findings that depict the impact of parameters of oil concentration and time on ESI are found influential, whereas the effect of pH and temperature is insignificant. Therefore, good characteristic results, stability, and the inhibition against rust of newly developed emulsion can be adapted to run the cold rolling process smoothly.

Practical Application: In the present era, metal processing industries are forced to explore the environmentally friendly oil‐in‐water emulsions (that used as an interface, lubricant, cooling, and antifrictional agents in cold rolling industries) to overcome increasing environmental pollution. Mustard oil‐based emulsion modified by nanoparticles (Nps) offers a good source of eco‐friendly, cost‐effective, and economic booster for metal processing industries. The antimicrobial properties of mustard oil are well defined in previous research articles. Such oil is a magnificent source for the synthesis of the emulsion and modification of mustard oil‐based emulsion with titanium dioxide. Nps provide significant protection against rust. Such applications can encourage the use of mustard oil‐based nanoemulsion for metal processing industries.
Bad mood food? Increased versus decreased food cue reactivity in anorexia nervosa and bulimia nervosa during negative emotions
Authors: Schnepper Rebekka , Richard Anna , Georgii Claudio , Arend Ann‐Kathrin , Naab Silke , Voderholzer Ulrich , Wilhelm Frank H. , Blechert Jens
Published: June 2021

Objective

Emotion regulation difficulties in anorexia nervosa (AN) and bulimia nervosa (BN) might underlie bingeing and purging in BN, extreme fasting in AN, or combinations of these symptoms in binge‐purge type AN. In this study, we tested for decreased food cue reactivity in response to negative emotions in AN, and the opposite pattern for BN. Furthermore, we explored subgroup differences (restrictive vs. binge‐purging AN; history of AN in BN).

Method

Patients with AN (n = 41), BN (n = 39), and matched controls (n = 70) completed an emotional eating questionnaire. In a laboratory experiment, we induced negative emotions and measured food cue reactivity (pleasantness, desire to eat (DTE), and corrugator muscle activity).

Results

AN reported emotional undereating, while BN reported emotional overeating. In the laboratory task, BN showed increased DTE and an appetitive corrugator response during negative emotions, selectively towards high‐calorie foods. AN showed generalized reduced cue reactivity to high‐calorie food regardless of emotional state. This pattern appears to be characteristic of restrictive AN, while cue reactivity of both BN subgroups pointed towards emotional overeating.

Conclusions

The emotional over‐ versus undereating framework might help to explain bingeing and restricting along the anorectic‐bulimic disorder spectrum, which calls for novel transdiagnostic theories and subgroup‐specific treatments.
Heat‐induced compounds development in processed tomato and their influence on corrosion initiation in metal food cans
Authors: Dhuey Elliot , Castada Hardy Z. , Barringer Sheryl , Joseph Jojo , Hadad Christopher M. , Ruffley Ken , Pascall Melvin A.
Published: June 2021

Selected ion flow tube mass spectrometry (SIFT‐MS) and ion chromatography (IC) were used to investigate the presence of volatile and nonvolatile compounds in canned tomatoes and in the polymeric lining before and after retorting the cans. This allowed us to observe if these compounds contributed to corrosion and the migration of iron and tin compounds from the cans to the tomatoes. Diced Roma tomatoes and other simulant treatment groups were sealed in two‐piece tinplated cans (controls in glass jars), retorted at 121℃ for 30 min, then stored at 49℃ for 50 days. Results showed that thermal degradation of amino acids in the tomatoes gave rise to volatile methyl sulfides and nonvolatile nitrogenous compounds which were subsequently sorbed by the can lining. SIFT‐MS showed a 20‐fold increase in dimethyl sulfide concentration. Inductively coupled plasma (ICP‐MS) results showed fourfold and 16‐fold increases in iron and tin compounds, respectively, that migrated from the metal to the tomatoes as a result of acid and electrolyte interactions.
Association study of taste preference: Analysis in the Lithuanian population
Authors: Kavaliauskienė Ingrida , Domarkienė Ingrida , Ambrozaitytė Laima , Barauskienė Lina , Meškienė Raimonda , Arasimavičius Justas , Irnius Algimantas , Kučinskas Vaidutis
Published: June 2021

Taste has strong evolutionary basis in the sense of survival by influencing our behavior to obtain food/medicine or avoid poisoning. It is a complex trait and varies among individuals and distinct populations. We aimed to investigate the association between known genetic factors (673 SNPs) and taste preference in the Lithuanian population, as well as to determine a reasonable method for qualitative evaluation of a specific taste phenotype for further genetic analysis. Study group included individuals representing six ethnolinguistic regions of Lithuania. Case and control groups for each taste were determined according to the answers selected to the taste‐specific and frequency of specific food consumption questions. Sample sizes (case/control) for each taste are as follows: sweetness (55/179), bitterness (82/208), sourness (32/259), saltiness (42/249), and umami (96/190). Genotypes were extracted from the Illumina HumanOmniExpress‐12v1.1 arrays’ genotyping data. Analysis was performed using PLINK v1.9. We found associations between the main known genetic factors and four taste preferences in the Lithuanian population: sweetness—genes TAS1R3, TAS1R2, and GNAT3 (three SNPs); bitterness—genes CA6 and TAS2R38 (six SNPs); sourness—genes PKD2L1, ACCN2, PKD1L3, and ACCN1 (48 SNPs); and saltiness—genes SCNN1B and TRPV1 (five SNPs). We found our questionnaire as a beneficial aid for qualitative evaluation of taste preference. This was the first initiative to analyze genetic factors related to taste preference in the Lithuanian population. Besides, this study reproduces, supports, and complements results of previous limited taste genetic studies or ones that lack comprehensive results concerning distinct (ethnic) human populations.