bluuebunny/crossref_metadata_2025 huggingface dataset:
Novelmulti‐element DOPOderivative towardlow‐flammabilityepoxy resin
Authors: Luo Haiqiang , Rao Wenhui , Liu Yuanli , Zhao Peng , Wang Liang , Yu Chuanbai
Published: June 2020

In order to obtain cured epoxy resin (EP) with satisfactory thermal stability and flame retardancy, a multi‐element P/N/Si‐containing flame retardant (DPAK) was synthesized by a facile way and was used as a reactive flame retardant to prepare flame‐retardant EP. The flame‐retardant efficiency of DPAK was subsequently evaluated by limiting oxygen index (LOI), UL‐94, and cone calorimeter (CC) test. With a low incorporation amount of DPAK (4 wt%), the resultant EP achieve to UL‐94 V‐0 rating, and the corresponding LOI value reached to 30%, which was higher than that of EP containing DOPO (2.9 wt%). More importantly, the thermogravimetric analysis (TGA) revealed their higher thermal stability than those of EP containing DOPO. Furthermore, dynamic mechanical analysis (DMA) shown the maintained glass transition temperature of DPAK‐EP. The increase of CO/CO2ratio in the CC test for the DPAK‐EP samples proved the gas‐phase activity of DPAK. Additionally, DPAK showed evidence of condensed phase activity by increasing char residue in TGA and CC test. The scanning electronic microscope together with the energy dispersive X‐ray spectrometer (SEM–EDX) and X‐ray photoelectron spectroscopy (XPS) exhibited that DPAK promoted the formation of compacted phosphorus‐silicon char layer. Subsequently, TG‐FTIR results indicated that DPAK‐EP produced lesser combustible gases than neat sample did, improving flame‐retardant properties of epoxy resin.
Seismic and non‐invasive geophysical surveys for the renovation project of Branciforte Palace in Palermo
Authors: Martorana Raffaele , Capizzi Patrizia
Published: June 2020

The renovation project of the historic Branciforte Palace (16th–17th century) in Palermo (Italy) was owned by the Banco di Sicilia Foundation, with the aim for it to become a multi‐purpose centre for the promotion of exhibitions and cultural events. In the context of the restoration work, a multi‐methodological and non‐invasive geophysical study has been carried out. The seismic characterization of the foundation soils was obtained by means of joint interpretations of a vertical seismic profile (VSP), multichannel analysis of surface waves (MASW) and horizontal to vertical spectral ratio (HVSR) microtremor analysis. The mutually constrained inversion of seismic surveys carried out with different techniques made it possible to obtain a robust interpretation of the foundation soils. Moreover, indoor geophysical surveys have been carried out to identify critical issues in the state of conservation of the floors and wall structures. In particular ground penetrating radar (GPR) profiles and an electrical resistivity tomography (ERT) have been carried out on the floor of the stable of the Palace, to evaluate in detail the state of consolidation of the foundation soil, in correspondence of a double row of marble columns, some of which were affected by differential subsidence. The joint interpretation allowed to generate a three‐dimensional (3D) model of the foundation's subsoil, highlighting the irregular surface of the foundation rock and to identify the main structural voids responsible for subsidence. Furthermore, some supporting columns have been investigated by means of ultrasonic tomography (UST) to verify their state of degradation. Finally, infrared thermography (IRT) images of the internal and external walls and of the vaults highlighted differences in the type of masonry and in the state of the plaster.
Ökosystem Darm
Authors: Brüssow Harald
Published: June 2020

Die Analyse des menschlichen Mikrobioms hat ein neues Kapitel der Humanbiologie eröffnet. Die Zusammensetzung speziell des Darmmikrobioms wurde mit einer Vielzahl menschlicher Erkrankungen in Verbindung gebracht. Nach Abschluss einer beschreibenden Forschungsphase, wird nun nach Mitteln für therapeutische Eingriffe gesucht. Die hohe Komplexität des Darmmikrobioms und zu wenige Verlaufsstudien erweisen sich dabei als Barrieren, um Kausalzusammenhänge von bloßen Assoziationen zu trennen. Gezielte gesundheitsfördernde Veränderungen des Mikrobioms erweisen sich dabei als schwierig.
Pollenkuchen mit Blütenöl: Die Auen‐Schenkelbiene ist Wildbiene des Jahres
Authors: Petrischak Hannes
Published: June 2020

Im Hochsommer kann man in den leuchtend gelb blühenden Beständen des Gewöhnlichen Gilbweiderichs (Lysimachia vulgaris) auf Feuchtwiesen, in Niedermooren, am Ufer von Bächen und Gräben oder in Flussauen nach der Auen‐Schenkelbiene (Macropis europaea) Ausschau halten. Sie nutzt neben dem Gilbweiderich‐Pollen dessen Blütenöle als Nahrungsquelle für ihren Nachwuchs. Von ihren Aktivitäten profitiert mit der Schmuckbiene (Epeoloides coecutiens) eine bemerkenswert hübsche Kuckucksbiene.
Flucht durch Rolle vorwärts
Authors: Sander Johannes
Published: June 2020

Viele Tiere entziehen sich durch Flucht möglichen Gefahren. Jetzt wurde gezeigt, dass eine Ameisenart sich auf geneigten Oberflächen durch rasches Wegrollen schützt.
Eye Tracking – Visuelle Wahrnehmung sichtbar machen
Authors: Kastaun Marit , Hunold Christin , Meier Monique
Published: June 2020

Was noch vor 100 Jahren technologisch undenkbar erschien – den Menschen hinsichtlich seiner Wahrnehmung, Aufmerksamkeit oder seiner kognitiven Belastung im Lernprozess analysieren zu können – ist heute durch den Einsatz hochauflösender Kameras schier einfach. In der Konsum‐ und Marktforschung, in medizinischen und psychologischen Bereichen ist die Eye‐Tracking‐Technologie eine etablierte Forschungsmethode, die zunehmend auch in das Interessensgebiet der Bildungsforschung rückt.
Left ventricular ejection fraction as an independent predictor of poor outcome in acute intracerebral hemorrhage
Authors: Yang Guang , Wang Lu , Sun Jingxian , Zhang Daming , Zhang Ruotian , Yuan Chao , Long Meixin , Zhong Yingqiang , Li Chunmei , Wang Xiaoxiong , Chen Xin , Zhou Qi , Liu Bo , Jiang Hongquan , Lian Ailing , Gareev Ilgiz , Li Lili , Zhao Shiguang
Published: June 2020

Introduction

Few studies of the effect of cardiac abnormalities on acute intracerebral hemorrhage (ICH) outcomes have been published. We sought to determine whether the left ventricular ejection fraction (LVEF) is associated with the functional outcome and mortality of acute ICH patients.

Methods

We conducted a retrospective study on 364 acute ICH patients from January to December 2016. The primary outcome was defined by the modified Rankin Scale and mortality at 3 months. The associations between LVEF and outcome were investigated using univariable and multivariable logistic regression models.

Results

Depressed LVEF was significantly associated with a poor functional outcome with an odds ratio [OR] of 0.966, 95% confidence interval (CI) 0.942–0.991, p = .008, and high mortality (OR 0.968 [95% CI 0.943–0.994], p = .015) at 3 months for acute ICH patients by univariate analysis. Multivariable logistic regression analysis indicated that LVEF was an independent predictor of a poor functional outcome (OR 0.961 [95% CI 0.935–0.988], p = .005) and mortality (OR 0.949 [95% CI 0.918–0.981], p = .002). The percentage of acute ICH patients with poor functional outcome (p = .005) and mortality (p = .002) was obviously higher in the group of patients with a LVEF of <50%.

Conclusions

LVEF is an independent predictor of functional outcome and mortality at 3 months for acute ICH patients. These findings could provide the evidence needed for prognosis prediction in acute ICH patients.
Breast‐conserving therapy shows better prognosis in mucinous breast carcinoma compared with mastectomy: A SEER population‐based study
Authors: Yu Ping , Liu Peng , Zou Yutian , Xie Xinhua , Tang Hailin , Li Na , Xie Xiaoming , Ye Feng
Published: June 2020

Background

Mucinous breast carcinoma (MBC) is a relatively rare pathological type of breast cancer. Compared with mastectomy in MBC, the effect and safety of breast‐conserving therapy (BCT) remains unclear. Therefore, we investigated the long‐term prognosis of BCT and mastectomy in T1‐2 stage mucinous breast carcinoma via the Surveillance, Epidemiology, and End Results (SEER) database.

Methods

Totally, 8830 patients who were diagnosed of mucinous breast carcinoma between 2004 and 2014 from SEER database were reviewed retrospectively. Cox proportional hazards model and Kaplan‐Meier method were performed for evaluating the relationship between surgical method and prognosis.

Results

One thousand three hundred and twenty (14.9%) patients underwent mastectomy and 7510 (85.1%) underwent BCT. The median follow‐up time was 77 months. There were more non‐Hispanic white, married, and younger (<65 years) patients, as well as lower stage of tumor sizes, lymph nodes and more favorable histologic grade, ER positive, and PR positive in BCT group (P < .05). Patients in BCT group had relatively better overall survival (OS) than those in mastectomy group. The risk of death from any cause in BCT group was lower than that in mastectomy group significantly (HR = 0.786, 95% CI: 0.703‐0.879, P < .001), while no difference significantly was observed in breast cancer‐specific survival (BCSS) between BCT and mastectomy groups. In stratified analysis according to T stage, BCT group had better OS than mastectomy group for patients of T1 stage (HR = 0.679, 95% CI: 0.589‐0.781, P < .001) or T2 stage (HR = 0.769, 95% CI: 0.646‐0.915, P = .003). In stratified analysis according to the different ages, BCT showed OS benefit in patients at the age of 50‐64 years (HR = 0.587, 95% CI: 0.408‐0.846, P = .004) and the age of 65‐79 years (HR = 0.636, 95% CI: 0.535‐0.758, P = .001). For patients younger than 50 years or not younger than 80 years, there was no difference significantly observed in OS between BCT and mastectomy groups (P > .05).While for patients who received BCT, the use of radiotherapy showed OS benefit.

Conclusions

This large population‐based study indicated patients who received BCT had better prognosis than those received mastectomy in T1‐2 stage MBC, especially in patients at the age of 50‐79 years. The use of radiotherapy showed OS benefit in patients receiving BCT. Breast‐conserving therapy might be preferred over mastectomy especially in locoregional treatment of T1‐2 stage MBC.
Cofactors as Molecular Fossils To Trace the Origin and Evolution of Proteins
Authors: Chu Xin‐Yi , Zhang Hong‐Yu
Published: June 2020

Due to their early origin and extreme conservation, cofactors are valuable molecular fossils for tracing the origin and evolution of proteins. First, as the order of protein folds binding with cofactors roughly coincides with protein‐fold chronology, cofactors are considered to have facilitated the origin of primitive proteins by selecting them from pools of random amino acid sequences. Second, in the subsequent evolution of proteins, cofactors still played an important role. More interestingly, as metallic cofactors evolved with geochemical variations, some geochemical events left imprints in the chronology of protein architecture; this provides further evidence supporting the coevolution of biochemistry and geochemistry. In this paper, we attempt to review the molecular fossils used in tracing the origin and evolution of proteins, with a special focus on cofactors.
An Effective Method for Quantifying RNA Expression of IbsC‐SibC, a Type I Toxin‐Antitoxin System in Escherichia coli
Authors: Jahanshahi Shahrzad , Li Yingfu
Published: June 2020

Toxin and antitoxin (TA) systems are small genetic modules consisting of a toxin protein and an RNA or protein antitoxin. It is difficult to study their functions in a large part due to the lack of effective methods to study toxin RNAs, which usually exist at exceptionally low levels. Herein, we describe a sensitive reverse transcription quantitative PCR (RT‐qPCR) method that is able to quantitate such RNA species. The method was directed at detection of the toxin mRNA of the ibsC‐sibC TA pair, and its high specificity was validated by sequencing. The approach was used to determine relative expression of the IbsC and SibC RNAs at different cell‐growth phases; this revealed an expression pattern that cannot be explained by the prevailing notion of growth stasis by the toxin and rescue by the antitoxin. The usefulness of the method was further showcased by the determination of average cellular copy numbers of the IbsC‐SibC RNAs in wild‐type E. coli cells and RNA abundance in E. coli cells engineered with extra copies of the ibsC‐sibC genes. With a robust method to quantitate cellular small RNAs at very low concentrations, we are now equipped to study the expression of TA systems under different conditions to gain useful insights about their functions.
Two‐Dimensional Nanosheet Structure of Co, S Co‐Doped Carbon‐Framework Supported MoO2 for Hydrogen Evolution Reaction in Alkaline Solutions
Authors: Zhang Ying , Hu Guojing , Li Jing , Zhu Xingqun , Liu Ping , Xiang Bin
Published: June 2020

Searching a low‐cost and excellent performance catalyst for hydrogen evolution reaction (HER) is important for enhancing the efficiency of water splitting. In this manuscript, we report the Co, S co‐doped carbon‐framework supported MoO2 nanosheets (Co, S/MoO2−C) for HER. The carbon‐framework improves the distribution of the MoO2, which causes a large number of exposed active sites. The synergistic effect of Co and S enhances the electron transport of the MoO2. As a result, the Co, S/MoO2−C exhibits a low overpotential (62 mV vs. RHE) and enhanced stability in 1 M KOH for HER. Our work puts forward a novel method to improve the catalytic performance of MoO2 and provides a new option to prepare excellent catalysts.
In Situ Synthesized Silica‐Supported Co@N‐Doped Carbon as Highly Efficient and Reusable Catalysts for Selective Reduction of Halogenated Nitroaromatics
Authors: Sheng Yao , Wang Xueguang , Yue Shengnan , Cheng Gonglin , Zou Xiujing , Lu Xionggang
Published: June 2020

Silica‐supported Co@N‐doped carbon (Co@CN/SiO2) catalysts were first prepared by a one‐step impregnation with a mixed solution of cobalt nitrate, glucose and urea, followed by in situ carbonization and reduction. The Co@CN/SiO2 catalysts were investigated for the selective reduction of nitro aromatics to the corresponding anilines using hydrazine hydrate. The Co@CN/SiO2‐500 carbonized at 500 °C exhibited the highest catalytic activity and excellent stability without any decay of activity after 6 cycles for the reduction of nitrobenzene. Both metallic Co atoms and Co−N species formed in the Co@CN/SiO2 catalysts were active, but the Co−N species were dominant active sites. The high activities of the Co@CN/SiO2 catalysts were attributed to the synergistic effect between the Co and N atoms, promoting heterolytic cleavage of hydrazine to form H+/H− pairs. Representative examples demonstrated that the Co@CN/SiO2‐500 could completely transform various halogen‐substituted nitro aromatics to the corresponding halogenated anilines with high TOFs and selectivity of >99.5 %.
The Development and Evaluation of the Intersectional Privilege Screening Inventory for Use With Counselors‐in‐Training
Authors: Pester Danielle A. , Lenz A. Stephen , Watson Joshua C.
Published: June 2020

As counselor preparation programs are compelled to demonstrate student social and cultural competence, valid inventories are needed to measure development consistent with contemporary standards. The Intersectional Privilege Screening Inventory was created for this purpose, was assessed using 4 types of validity evidence, and has results supporting its use in student development.
Supervisor Cultural Humility Predicts Intentional Nondisclosure by Post‐Master's Counselors
Authors: Cook Ryan M. , Jones Connie T. , Welfare Laura E.
Published: June 2020

The authors examined supervisor cultural humility as a predictor of supervisee intentional nondisclosure. Using multiple regression in a sample of 101 post‐master's counselors, the authors found that 20% of supervisees' intentional nondisclosure was explained by their perceptions of their supervisors' level of cultural humility.
Production of Recombinant Transmembrane Proteins from Mammalian Cells for Biochemical and Structural Analyses
Authors: Puthenveetil Robbins , Lee Chul‐Jin , Banerjee Anirban
Published: June 2020

Eukaryotic integral membrane proteins are key components of various biological processes. Because they are implicated in multiple diseases, it is important to understand their mechanism of action by elucidating their structure and function. Complex technical challenges associated with the generation of recombinant membrane proteins severely impair our ability to understand them using structural and biochemical methods. Here, we provide a detailed procedure to address and mitigate difficulties involved in the large‐scale heterologous overexpression and purification of eukaryotic membrane proteins using HEK293S GnTi− cells transduced with baculovirus. Two human proteins, hDHHC15 and hPORCN, are presented as examples, with step‐by‐step instructions for transient transfection and generation of baculoviruses, followed by overexpression and purification from HEK293S GnTi− cells. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: Small‐scale protein expression in mammalian HEK293T cells

Basic Protocol 2: Generation of baculovirus from Sf9 (insect) cells

Alternate Protocol: Enumeration‐free method for generating P2 viral stock

Support Protocol 1: Small‐scale transduction of HEK293T cells with P2 baculovirus

Basic Protocol 3: Large‐scale viral transduction of HEK293S GnTi− cells

Support Protocol 2: Large‐scale membrane preparation from HEK293S GnTi− cells

Basic Protocol 4: Large‐scale purification of membrane proteins from HEK293S GnTi− cells
Flexible task‐DAG management in PHAST library: Data‐parallel tasks and orchestration support for heterogeneous systems
Authors: Peccerillo Biagio , Bartolini Sandro
Published: June 2020

Heterogeneous architectures proved successful in achieving unprecedented performance and energy‐efficiency. However, taking advantage of these diverse processing elements is still hard. Programmers need to code through the different approaches suitable for each target architecture and need to decide the distribution of activities on the different resources. The majority of current frameworks focuses on either performance or productivity. The former mainly provides low‐level target‐specific programming interfaces, and the latter offers high‐level tools that often fail in achieving high‐performance. In both cases, the design is usually data‐parallel, as task‐parallelism is not supported. In this work, we propose a task‐based solution within the data‐parallel heterogeneous single‐source PHAST library. Tasks can be coded in a target‐agnostic fashion, can be compiled and parallelized on multi‐core CPUs and NVIDIA GPUs automatically and support the choice of the execution platform at runtime. We evaluate the capabilities of the proposed task‐directed acyclic graph support in case of an extensive set of randomly generated task‐based applications with different sizes and characteristics. We compare it against a SYCL implementation in terms of performance and complexity metrics, highlighting that PHAST achieves about 1.56× and 2.60× speedup over SYCL for multi‐core CPU and GPU, respectively, while improving also code complexity metrics.
Crosstalk reduction in copper on‐chip interconnects with graphene barrier for ternary logic applications
Authors: Badugu Divya Madhuri , S. Sunithamani
Published: June 2020

This paper presents the investigations of crosstalk effects in ternary logic‐based coupled interconnects. The crosstalk analysis is investigated for coupled copper interconnects and copper‐multilayer graphene (Cu‐MLG) interconnects. In Cu‐MLG interconnects, the Cu interconnect is enclosed with MLG barrier and standard ternary inverter is used to drive the interconnect. Based on the industry standard HSPICE simulation results, the crosstalk effects such as noise peak and delay are lower compared with conventional Cu interconnects. Moreover, the Cu‐MLG interconnects show reduced power dissipation, power delay product (PDP), and energy delay product (EDP) over the Cu interconnects. From the simulation results, it is observed that the Cu‐MLG interconnects provides the performance improvements up to 30.67% compared with the Cu interconnects. Thus, the Cu‐MLG interconnects are more compatible for ternary logic integrated circuits compared with traditional Cu interconnects.
Calreticulin couples with immune checkpoints in pancreatic cancer
Authors: Huang Xing , Tang Tianyu , Wang Xun , Bai Xueli , Liang Tingbo
Published: June 2020

Although immune checkpoint blockade is considered to be the dominant approach in future cancer immunotherapy, whether it will apply to pancreatic cancer remains largely unknown. To address this issue, pancreatic cancer–associated datasets were individually collected by Gene Expression Profiling Interactive Analysis 2 (GEPIA2), cBioPortal, and Tumor and Immune System Interaction Database (TISIDB), and subsequently subjected to prognostic, genomic, and immunologic analyses of all well‐established immune checkpoints. The results indicate that immune checkpoints might not be ideal targets for pancreatic cancer therapy. Intriguingly, the genomic alteration of calreticulin, the key mediator of chemotherapy‐induced cancer immunogenic cell death, was found to couple with immune checkpoints in pancreatic cancer. Moreover, calreticulin was observed to be highly expressed in pancreatic adenocarcinoma, and high calreticulin expression significantly favors both overall survival and disease‐free survival of patients with pancreatic adenocarcinoma. Importantly, calreticulin was further revealed to be closely related to anti‐tumor immunity in pancreatic adenocarcinoma, including multiple immune effector molecules and T‐cell signatures. Taken together, calreticulin‐based therapy may represent a more promising prospect for pancreatic cancer immunotherapy than immune checkpoint blockade therapy.
The distribution of immune cells within combined hepatocellular carcinoma and cholangiocarcinoma predicts clinical outcome
Authors: Zheng Bo‐Hao , Ma Jia‐Qiang , Tian Ling‐Yu , Dong Liang‐Qing , Song Guo‐He , Pan Jiao‐Men , Liu Yu‐Ming , Yang Shuai‐Xi , Wang Xiao‐Ying , Zhang Xiao‐Ming , Zhou Jian , Fan Jia , Shi Jie‐Yi , Gao Qiang
Published: June 2020

Background

This study aimed to investigate the clinical relevance of the immune microenvironment in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC‐ICC).

Patients and Methods

The density of tumor‐infiltrating CD3+, CD8+, CD163+, and Foxp3+ immune cells, as well as Programmed cell death 1, Programmed cell death‐ligand 1, and Tumor necrosis factor receptor superfamily member 4, was measured in the peritumor liver, tumor invasive margin, and intratumor subregions of 56 cHCC‐ICC by immunohistochemistry. The immune index was established to stratify patients. Prognostic significance of immune cell subsets and immune indices was evaluated.

Results

The distribution of immune cells was highly heterogeneous among different subregions of cHCC‐ICC. As compared with the hepatocellular carcinoma (HCC) component, the lower density of CD8+ T cells and higher intensity of Foxp3+ Tregs and immune checkpoints in the intrahepatic cholangiocarcinoma (ICC) component may indicate a stronger immune evasive ability of ICC. Based on clustering classification or a combination of random forest and lasso‐cox, two models of immune indices were established and both were identified as independent prognostic factors for cHCC‐ICC patients. The selected immune variables in the immune prognostic models derived from both HCC and ICC subregions, indicating that the prognosis of cHCC‐ICC patients was a complex interaction of both components.

Conclusions

The immune contexture was heterogeneous among different subregions of cHCC‐ICC patients and contributed differently to patient prognosis. Immune score based on the densities of immune cells might serve as a promising prognostic predictor for cHCC‐ICC patients.
ATPase copper transporter A, negatively regulated by miR‐148a‐3p, contributes to cisplatin resistance in breast cancer cells
Authors: Yu Ze , Cao Weifan , Ren Yuan , Zhang Qijia , Liu Jia
Published: June 2020

Background

Breast cancer is the leading cause of death among women. Cisplatin is an effective drug for breast cancer, but resistance often develops during long term chemotherapy. While the mechanism of chemotherapy resistance is still not fully understood.

Methods

Survival analyses of ATP7A and ATP7B were used to evaluate their effects on the development of Breast invasive carcinoma (BRCA). Immunostaining, flow cytometry, and IC50 assay were utilized to examine the effects of ATP7A‐siRNA combined with cisplatin on apoptosis in breast cancer cells. Q‐PCR, western blotting, and dual‐luciferase assay were employed to confirm ATP7A is a novel target gene of miR‐148a‐3p.

Results

In this current study, we identified knocking‐down ATP7A could enhance cytotoxicity treatment of cisplatin in breast cancer cells. We also demonstrated miR‐148a‐3p overexpression in BRCA cells increased the sensitivity to cisplatin, and subsequently enhanced DNA damage and apoptosis. Moreover, we found ATP7A is a novel target gene of miR‐148a‐3p. In brief, our results showed miR‐148a could accelerate chemotherapy induced‐apoptosis in breast cancer cells by inhibiting ATP7A expression.

Conclusions

Our results highlight that inhibition of ATP7A is a potential strategy for targeting breast cancer resistant to cisplatin, and we provided an interesting method to compare the involvement of various genes in the assessment of cisplatin resistance.
Erythrocyte microRNAs show biomarker potential and implicate multiple sclerosis susceptibility genes
Authors: Groen Kira , Maltby Vicki E. , Scott Rodney J. , Tajouri Lotti , Lechner‐Scott Jeannette
Published: June 2020

Background

Multiple sclerosis is a demyelinating autoimmune disease, for which there is no blood‐borne biomarker. Erythrocytes may provide a source of such biomarkers as they contain microRNAs. MicroRNAs regulate protein translation through complementary binding to messenger RNA. As erythrocytes are transcriptionally inactive, their microRNA profiles may be less susceptible to variation. The aim of this study was to assess the biomarker potential of erythrocyte microRNAs for multiple sclerosis and assess the potential contribution of erythrocyte‐derived extracellular vesicle microRNAs to pathology.

Methods

Erythrocytes were isolated from whole blood by density gradient centrifugation. Erythrocyte microRNAs of a discovery cohort (23 multiple sclerosis patients and 22 healthy controls) were sequenced. Increased expression of miR‐183 cluster microRNAs (hsa‐miR‐96‐5p, hsa‐miR‐182‐5p and hsa‐miR‐183‐5p) was validated in an independent cohort of 42 patients and 45 healthy and pathological (migraine) controls. Erythrocyte‐derived extracellular vesicles were created ex vivo and their microRNAs were sequenced. Targets of microRNAs were predicted using miRDIP.

Results

Hsa‐miR‐182‐5p and hsa‐miR‐183‐5p were able to discriminate relapsing multiple sclerosis patients from migraine patients and/or healthy controls with 89‐94% accuracy and around 90% specificity. Hsa‐miR‐182‐5p and hsa‐miR‐183‐5p expression correlated with measures of physical disability and hsa‐miR‐96‐5p expression correlated with measures of cognitive disability in multiple sclerosis. Erythrocytes were found to selectively package microRNAs into extracellular vesicles and 34 microRNAs were found to be differentially packaged between healthy controls and multiple sclerosis patients. Several gene targets of differentially expressed and packaged erythrocyte microRNAs overlapped with multiple sclerosis susceptibility genes. Gene enrichment analysis indicated involvement in nervous system development and histone H3‐K27 demethylation.

Conclusions

Erythrocyte miR‐183 cluster members may be developed into specific multiple sclerosis biomarkers that could assist with diagnosis and disability monitoring. Erythrocyte and their extracellular microRNAs were shown to target multiple sclerosis susceptibility genes and may be contributing to the pathophysiology via previously identified routes.
Prostate‐specific antigen modulates the osteogenic differentiation of MSCs via the cadherin 11‐Akt axis
Authors: Wu Longxiang , Xiang Shiqi , Hu Xiheng , Mo Miao , Zhao Cheng , Cai Yi , Tong Shiyu , Jiang Huichuan , Chen Linxiao , Wang Zhi , Xiong Wei , Ou Zhenyu
Published: June 2020

Background

A high prevalence of osteoblastic bone metastases is characteristic of prostate cancer. Prostate‐specific antigen (PSA) is a serine protease uniquely produced by prostate cancer cells and is an important serological marker for prostate cancer. However, whether PSA modulates the osteogenic process remains largely unknown. In this study, we explored the effect of PSA on modulating the osteoblastic differentiation of mesenchymal stem cells (MSCs). In this study, we used flow cytometry, CCK‐8 assay, Alizarin red S (ARS) staining and quantification, alkaline phosphatase (ALP) activity and staining, Western blotting, and quantitative real‐time PCR (qRT‐PCR) to explore the effect of PSA on osteogenic differentiation of MSCs.

Results

We first demonstrated that although PSA did not affect the proliferation, morphology, or phenotype of MSCs, it significantly promoted the osteogenic differentiation of MSCs in a concentration‐dependent manner. Furthermore, we demonstrated that PSA promoted the osteogenic differentiation of MSCs by elevating the expression of Cadherin 11 in MSCs and, thus, activating the Akt signaling pathway.

Conclusions

In conclusion, we demonstrated that PSA could promote the osteogenesis of MSCs through Akt signaling pathway activation by elevating the expression of cadherin‐11 in MSCs. These findings imply a possible role of PSA in osteoblastic bone metastases in prostate cancer.
Prognostic validation and therapeutic decision‐making of the AJCC eighth pathological prognostic staging for T3N0 breast cancer after mastectomy
Authors: Wu San‐Gang , Wang Jun , Lei Jian , Lian Chen‐Lu , Hua Li , Zhou Juan , He Zhen‐Yu
Published: June 2020

Background

T3N0 breast cancer might be a distinct clinical and biological entity, with higher heterogeneity and presenting diverse responses to locoregional and systemic therapy. The aim of the current study was to validate the prognostic effect and assess the treatment decision‐making of the American Joint Committee on Cancer (AJCC) eighth pathological prognostic staging in T3N0 breast cancer after mastectomy.

Methods

We retrospectively included 2465 patients with stage T3N0 breast cancer who had undergone mastectomy between 2010 and 2014 using the data from Surveillance, Epidemiology, and End Results program. The primary endpoint of this study was breast cancer–specific survival (BCSS).

Results

Of the entire cohort, 76.0% of patients in the seventh AJCC staging system were restaged to the eighth AJCC pathological prognostic staging system. A total of 1431 (58.1%) and 1175 (47.7%) of them received chemotherapy and postmastectomy radiotherapy (PMRT), respectively. Pathological staging was an independent prognostic factor for BCSS. Using pathological prognostic stage IA as the reference, BCSS gradually became worse with increased hazard ratios. The 5‐years BCSS was 96.9%, 95.5%, 91.1%, 85.6%, and 75.5% in pathological prognostic stage IA, IB, IIA, IIB, and IIIA breast cancers, respectively (P < .001). In pathological prognostic stage IA, IB, and IIA breast cancers, the receipt of PMRT or chemotherapy was not correlated with better BCSS. However, PMRT was correlated with better BCSS in pathological prognostic stage IIB disease (P = .006), but not in pathological prognostic IIIA disease. Moreover, chemotherapy was correlated with better BCSS in pathological prognostic stage IIIA disease (P = .006), but not in pathological prognostic stage IIB disease.

Conclusions

The eighth AJCC pathological prognostic staging system provides more risk stratification of T3N0 breast cancers after mastectomy and might affect individualized decision‐making for chemotherapy and PMRT in this patient subset.
Classification of gastric cancer by EBV status combined with molecular profiling predicts patient prognosis
Authors: He Cai‐Yun , Qiu Miao‐Zhen , Yang Xin‐Hua , Zhou Da‐Lei , Ma Jiang‐Jun , Long Ya‐Kang , Ye Zu‐Lu , Xu Bo‐Heng , Zhao Qi , Jin Ying , Lu Shi‐Xun , Wang Zhi‐Qiang , Guan Wen‐Long , Zhao Bai‐Wei , Zhou Zhi‐Wei , Shao Jian‐Yong , Xu Rui‐Hua
Published: June 2020

Purpose

To identify how Epstein‐Barr virus (EBV) status combined with molecular profiling predicts the prognosis of gastric cancer patients and their associated clinical actionable biomarkers.

Experimental Design

A next‐generation sequencing assay targeting 295 cancer‐related genes was performed in 73 EBV‐associated gastric cancer (EBVaGC) and 75 EBV‐negative gastric cancer (EBVnGC) specimens and these results were compared with overall survival (OS).

Results

PIK3CA, ARID1A, SMAD4, and PIK3R1 mutated significantly more frequently in EBVaGC compared with their corresponding mutation rate in EBVnGC. As the most frequently mutated gene in EBVnGC (62.7%), TP53 also displayed a mutation rate of 15.1% in EBVaGC. PIK3R1 was revealed as a novel mutated gene (11.0%) associated almost exclusively with EBVaGC. PIK3CA, SMAD4, PIK3R1, and BCOR were revealed to be unique driver genes in EBVaGC. ARID1A displayed a significantly large proportion of inactivated variants in EBVaGC. A notable finding was that integrating the EBV status with tumor mutation burden (TMB) and large genomic instability (LGI) categorized the tumors into four distinct molecular subtypes and optimally predicted patient prognosis. The corresponding median OSs for the EBV+/TMB‐high, EBV+/TMB‐low, EBV‐/LGI‐, and EBV‐/LGI+ subtypes were 96.2, 75.3, 44.4, and 20.2 months, respectively. The different subtypes were significantly segregated according to distinct mutational profiles and pathways.

Conclusions

Novel mutations in PIK3R1 and TP53 genes, driver genes such as PIK3CA, SMAD4, PIK3R1, BCOR, and ARID1A, and distinguished genomic profiles from EBVnGC were identified in EBVaGC tumors. The classification of gastric cancer by EBV, TMB, and LGI could be a good prognostic indicator, and provides distinguishing, targetable markers for treatment.
Molecular mechanisms, off‐target activities, and clinical potentials of genome editing systems
Authors: Zheng Nannan , Li Liyang , Wang Xiangdong
Published: June 2020

Methodologies of genome editing are rapidly developing with the improvement of gene science and technology, mechanism‐based understanding, and urgent needs. In addition to the specificity and efficiency of on‐target sites, one of the most important issues is to find and avoid off‐targets before clinical application of gene editing as a therapy. Various algorithms, modified nucleases, and delivery vectors are developed to localize and minimize off‐target sites. The present review aimed to clarify off‐targets of various genome editing and explore potentials of clinical application by understanding structures, mechanisms, clinical applications, and off‐target activities of genome editing systems, including CRISPR/Cas9, CRISPR/Cas12a, zinc finger nucleases, transcription activator‐like effector nucleases, meganucleases, and recent developments. Current genome editing in cancer therapy mainly targeted immune systems in tumor microenvironment by ex vivo modification of the immune cells in phases I/II of clinical trials. We believe that genome editing will be the critical part of clinical precision medicine strategy and multidisciplinary therapy strategy by integrating gene sequencing, clinical transomics, and single cell biomedicine. There is an urgent need to develop on/off‐target‐specific biomarkers to monitor the efficacy and side‐effects of gene therapy. Thus, the genome editing will be an alternative of clinical therapies for cancer with the rapid development of methodology and an important part of clinical precision medicine strategy.
HK3 is correlated with immune infiltrates and predicts response to immunotherapy in non‐small cell lung cancer
Authors: Tuo Zhan , Zheng Xin , Zong Yan , Li Jie , Zou Chunyan , Lv Yi , Liu Jun
Published: June 2020

Background

With the knowledge of tumor immunobiology deepening among researchers, the breakthroughs in the field of tumor immunotherapy in recent years have provided new approaches for cancer therapy. While patients who receive treatment are all at risk of side effects, about one‐fifth of them have sustained responses. It is crucial to figure out the underlying mechanism of how the immune system regulates the nonsmall cell lung cancer (NSCLC) microenvironment to improve the benefit of immunotherapy. Regarding glucose metabolism, the initial step is to generate glucose‐6‐phosphate by phosphorylating glucose with hexokinases‐3 (HK3). According to a recent study, HK3 has a functional role in the treatment of acute promyelocytic leukemia and colorectal cancer.

Results

Here, we studied the co‐expression relationship between the glycolytic pathway gene and the immune checkpoint gene and found that the expression of HK3 in tumor tissues may be related to immune status. By analyzing The Cancer Genome Atlas (TCGA) data, we found that the expression of HK3 was closely related to the main clinical features as well as to molecular characteristics. We also predicted that cases with low expression of HK3 were usually malignant entities and were shown to be obvious genomic aberrations of driver oncogenes. At the same time, gene ontology analysis based on significantly related genes in HK3 expression showed that HK3 expression was linked to inflammatory activity and immune response. Additionally, HK3 showed a remarkable trend in predicting the efficacy of immunotherapy for patients receiving Keytruda (PD‐1 monoclonal antibody) treatment.

Conclusions

This is the first comprehensive study to characterize HK3 expression in NSCLC from molecular and clinical aspects.
Collaborated effort against SARS‐CoV‐2 outbreak in China
Authors: Yang Qiwen , Zhou Yang , Ai Jingwen , Ma Jinmin , Cao Fenglin , Cao Weifan , Zhang Wengeng , Wang Shifu , Chen Weijun , Ma Xiaoling , Zhang Wenhong , Li Weimin
Published: June 2020

A previously unknown beta coronavirus, SARS‐CoV‐2, was discovered from a cluster of patients with pneumonia of unknown cause in Wuhan since the end of 2019. Ever since the start of COVID‐19, government administrations, academic institutions, and technology enterprises are under unprecedented cooperation in controlling this outbreak from pathogen identification, epidemic situation assessment, to outbreak containment. Timely identification, isolation, and whole‐genome sequencing of SARS‐CoV‐2 have laid the foundation for effective control of this novel infection. With the increasing case numbers worldwide, more real‐time information is emerging, changing our understandings to SARS‐CoV‐2 outbreak, and nonetheless refining the outbreak control responses. The efficient management of COVID‐19 requires global collaboration and an efficient share of information.
New focuses of clinical and translational medicine in 2020
Authors: Cheng Xin , Wu Duojiao , Cheng Yunfeng , Qiao Tiankui , Wang Xiangdong
Published: June 2020

Clinical and translational medicine is an ongoing opportunity and challenge to transition science from bench to patient, from patient to bench, and from patient to policy for scientists and clinicians. Of the many objectives, the most important one is to improve the quality of life in patients, including living duration, dignity, emotional well‐being, psychiatric and physical health, as well as independency. Emphasis and redefining concepts has allowed clinical and translational medicine to experience exciting and productive developments. Further discoveries, innovations, validations, and developments in clinical and translational medicine are expected in 2020. The present editorial aims to present the top three most discussed topics with high expectations for translation from clinical investigations and trials into practice and application.
Qualitative and quantitative assessment of extracted oil from Camelina sativa seed treated by dielectric‐barrier discharge cold plasma
Authors: Rezaei Shabnam , Ghobadian Barat , Ebadi Mohammad‐Taghi , Ghomi Hamid
Published: June 2020

This study aimed to investigate the effects of dielectric‐barrier discharge (DBD) cold plasma (CP) pretreatment on Camelina sativa “Soheil cultivar” seed. A DBD plasma reactor system was employed for this purpose. The experiments were performed by taking into account variables including voltages of 15, 18, and 21 kV and times of 2, 4, 8, and 16 min. The measured properties were oil yield extraction (%), oil colour parameters (CIEL*a*b*), protein content (meal) (%), surface analysis using Scanning Electron Microscopy (SEM), and fatty acids profile of Camelina sativa. The results revealed that the CP treatment had a significant improvement in different properties of the extracted oil. It was observed that the extracted oil was increased, with the increasing time of CP exposure. The treatments of CP enhanced the oil yield from 24.3 to 31.5%, and the optimal conditions were identified as 21 kV and 16 min. Also, the maximum protein amount was observed for the samples treated by CP (39.5%). The SEM analysis showed that the cell structures of pre‐treated Camelina samples were damaged, thereby improved the oil extraction efficiency. The variations in the values of L*, a*, and b* (max‐min) were calculated to be 3.9, −2.5, and 9.7, respectively, which indicated minor changes of CP treatment on the oil colour parameters. The treated samples showed considerable changes of enhancement in linolenic and linoleic acids among poly‐unsaturated fatty acids; and a reduction in palmitic acid content, among saturated fatty acids.
Label‐Free Four‐Dimensional Visualization of Anaerobically Growing Electroactive Biofilms
Authors: Koch Christin , Kuchenbuch Anne , Marosvölgyi Maria , Weisshart Klaus , Harnisch Falk
Published: June 2020

Light sheet fluorescence microscopy (LSFM) allows nondestructive, label‐free and in vivo imaging of large specimen, even at nontransparent surfaces. We show that LSFM can be applied for label‐free analyses of prokaryotes on the example of electroactive biofilms. Biofilm growth is linked to the production of current serving as measure of metabolic activity in vivo by monitoring with high spatial and temporal resolution. After 35 h of exponential growth, a homogeneous biofilm with a thickness of 9 μm was formed. This was followed by a stratification of the biofilm including the formation of 3D structures over the next 100 h. Light reflection was sufficient to visualize the biofilm structure and development over time and the terminal morphology was confirmed using fluorescence staining. This proof of concept on using LSFM for investigation of biofilms opens the door for its application in the entire field of microbial ecology. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals LLC. on behalf of International Society for Advancement of Cytometry.
Anaplastic thyroid carcinoma with rhabdoid phenotype: An unusual case and a comprehensive review
Authors: Bansal Saloni , Sancheti Sankalp , Kaur Sukhjinder , Somal Puneet , Kalra Supreet Kaur , Sali Akash Pramod
Published: June 2020

Anaplastic thyroid carcinoma (ATC) is a highly aggressive thyroid malignancy predominantly affecting the elderly with a fatal outcome. ATC with rhabdoid phenotype is a rare variant, with only a few cases reported in the literature to date. We herein report a case of a 44‐year old female diagnosed as ATC with rhabdoid phenotype. She had a slow‐growing neck mass with no gross extrathyroidal extension (ETE) or nodal/distant metastasis at presentation. Computed tomography of the neck showed a well‐defined heterogeneously hypodense nodule in the right lobe of the thyroid. On cytology, a diagnosis of papillary thyroid carcinoma (PTC) with possible anaplastic transformation was made based on the presence of vague papillae with focal nuclear features of PTC and atypical pleomorphic/rhabdoid cells. The total thyroidectomy specimen showed a relatively circumscribed lesion with no gross ETE. Histopathological examination revealed sheets of rhabdoid cells with a focus of poorly differentiated thyroid carcinoma. On immunohistochemistry, rhabdoid cells were positive for AE1/AE3, focally positive for PAX8 and were negative for TTF‐1, synaptophysin, desmin, myogenin, S100P, and SMA. The neck lymph nodes were non‐metastatic. The patient was further treated with adjuvant radioactive iodine. Four‐months post‐operatively, the patient developed pulmonary metastasis which on biopsy examination revealed metastatic ATC. Apart from being a rare tumor type, this case is unusual with its presentation too; wherein, unlike described earlier in the literature the patient had a relatively mitigated clinical course with no gross ETE or nodal/distant metastatic disease. We also review the relevant literature along with this case.
EUS‐FNA, ancillary studies and their clinical utility in patients with mediastinal, pancreatic, and other abdominal lesions
Authors: Saqib Muhammad , Maruf Maheen , Bashir Sehar , Mehmood Shafqat , Akhter Noreen , Yusuf Muhammed Aasim , Loya Asif
Published: June 2020

Background

Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) is an important modality to obtain tissue diagnosis from mediastinal, pancreatic, and intra‐abdominal lesions in close proximity to the pulmonary and gastrointestinal tract. It is considered to be a relatively safe, rapid, and minimally invasive technique with low complication rates.

Aims

To determine the diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and outcome of EUS‐FNA, with histological correlation where applicable.

Methods

Data of all 1059 consecutive patients who underwent EUS‐FNA from 1 January 2005 to 31 December 2017 at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore was reviewed in this retrospective study. The major sites that were targeted for EUS‐FNA were pancreatic (423), mediastinal (376), and other abdominal lesions (260).

Results

The average number of passes per patient was 2.22. Rapid on‐site evaluation (ROSE) was adequate in 969 patients (91.4%). Concordance between ROSE and final cytology was 99.5%. Follow‐up was available in 810 patients (76.4%). The overall diagnostic yield was 94.3%. Ancillary studies, including immunohistochemical stains and flow cytometry, helped to increase the diagnostic yield from 78.1% to 94.3%. The overall sensitivity, specificity, PPV, NPV, and diagnostic accuracy for EUS‐FNA were 94.8%, 98.6%, 99.9%, 65.5%, and 95.1%, respectively. Seven of 1059 patients (0.6%) developed complications.

Conclusion

EUS‐FNA is a very sensitive and specific diagnostic tool with a minimal complication rate. Ancillary studies helped to increase the sensitivity, as well as the diagnostic yield.