bluuebunny/crossref_metadata_2025 huggingface dataset:
Radar plots facilitate differential diagnosis of acute promyelocytic leukemia and NPM1+ acute myeloid leukemia by flow cytometry
Authors: Gupta Monali , Jafari Katayoon , Rajab Amr , Wei Cuihong , Mazur Joanna , Tierens Anne , Hyjek Elizabeth , Musani Rumina , Porwit Anna
Published: December 2020

Background

Acute promyelocytic leukemia (APL) is one of the most life‐threatening hematological emergencies and requires a prompt correct diagnosis by cytomorphology and flow cytometry (FCM) with later confirmation by cytogenetics/molecular genetics. However, nucleophosmin 1 muted acute myeloid leukemia (NPM1+ AML) can mimic APL, especially the hypogranular variant of APL. Our study aimed to develop a novel, Radar plot‐based FCM strategy to distinguish APLs and NPM1+ AMLs quickly and accurately.

Method

Diagnostic samples from 52 APL and 32 NPM1+ AMLs patients were analyzed by a 3‐tube panel of 10‐color FCM. Radar plots combining all markers were constructed for each tube. Percentages of positive leukemic cells and mean fluorescence intensity were calculated for all the markers.

Results

APL showed significantly higher expression of CD64, CD2, and CD13, whereas more leukemic cells were positive for CD11b, CD11c, CD15, CD36, and HLA‐DR in NPM1+ AMLs. Radar plots featured CD2 expression, a lack of a monocytic component, lack of expression of HLA‐DR and CD15, and a lack of a prominent CD11c+ population as recurring characteristics of APL. The presence of blasts with low SSC, presence of at least some monocytes, some expression of HLA‐DR and/or CD15, and a prominent CD11c population were recurrent characteristics of NPM1+ AMLs. Radar plot analysis could confidently separate all hypergranular APL cases from any NPM1+ AML and in 90% of cases between variant APL and blastic NPM1+ AML.

Conclusion

Radar plots can potentially add to differential diagnostics as they exhibit characteristic patterns distinguishing APL and different types of NPM1+ AMLs.
Parental emotional support and social buffering in previously institutionalized and typically developing children and adolescents
Authors: Perry Nicole , Johnson Anna , Hostinar Camelia , Gunnar Megan
Published: December 2020

The current study tested the hypothesis that variation in parental emotional support explains differences in cortisol reactivity among 159 youth, including both previously institutionalized (PI; N = 78) and non‐adopted (NA; N = 81) children (ages 9–10) and adolescents (ages 15–16). Youth participated in a Modified Trier Social Stress Test after a period of preparation with either their parent or a supportive stranger. Saliva samples were collected to derive a measure of cortisol reactivity. Our findings revealed that parents buffered the cortisol stress response for PI children and adolescents only if they were high on emotional support. Our results also suggest that simply preparing with a parent might buffer the stress response for NA children; for NA adolescents, however, only emotionally supportive parents significantly buffered their adolescents’ stress.
Toward the conservation of the endemic monotypic fish genus Aulopyge from the Balkan Dinaric karst: Integrative assessment of introduced and natural population
Authors: Ludoški Jasmina , Francuski Ljubinka , Lukač Milica , Dekić Radoslav , Milankov Vesna
Published: December 2020

The complex biogeographical history of the Balkan Peninsula caused remarkable freshwater fish diversity and endemism, among which Cyprinidae fish dominate. The Dinaric karst was a Pleistocene refugium and it harbors ancient and endemic cyprinids, including Aulopyge huegelii, a sole representative of its genus. Being highly distributionally restricted, it faces various threats that promote a critical decline in population abundance and even population extinction. Phenotypic and molecular diversity of the introduced (Šator Lake, Šator Mountain) and natural (Studena River, Duvanjsko Polje) populations of Dalmatian barbelgudgeon from Bosnia and Herzegovina was studied by using two mitochondrial genes and morphometric traits (linear and geometric morphometrics). Nonparametric ANOVA showed that two analyzed populations significantly differed in six linear measurements, except snout length and postorbital head length. Contrary to centroid size, two populations were found to be significantly different in body shape. Deformation grids indicated that individuals from Studena River are characterized by wider and slightly shorter body comparing to individuals from Šator Lake. Incongruence in cytochrome c oxidase subunit I (COI) and cytochrome b (cyt b) mitochondrial DNA (mtDNA) variation was observed since a common COI haplotype was observed, while four and three cyt b haplotypes were registered in Šator Lake and Studena River, respectively. Since it was demonstrated that cyt b mtDNA was a faster evolving gene, we encourage its use in intraspecies studies, especially for evaluating the connectivity of fragmented populations and for studying the evolutionary footprint of the processes incorporated into the distinctive evolution of Aulopyge. Finally, findings herewith provide a firm basis for designing a long‐term sustainable conservation strategy for endemic species in Dinaric karst.
Wideband microstrip antenna for the detection of solutes in water
Authors: Mahajan Rajshri C. , Vyas Vibha
Published: December 2020

Effective detection of solutes in water has always been a challenging issue in real‐time. This article presents a technique to detect solutes such as table sugar (CHOO3), common salt (NaCl), and combinations thereof in water using a wideband microstrip antenna with an electromagnetic band gap ground structure. An antenna is designed and fabricated to operate at the bandwidth of 3 GHz with a stable gain of 9 dBi maintaining voltage standing wave ratio ≤ 2. The uniquely designed antenna works as a sensor in its near field to sense solutes in water as a function of the resonant frequency. Apart from sensing solutes, the proposed technique also efficiently detects temperature of soft drinks. As temperature of soft drinks changes, reflection characteristics of an antenna change too. The results of the experiments show that as the concentration of the solute increases, the return loss decreases. The beauty of this technique is its efficient detection without any physical contact with a solution and without disturbing the chemical processes inside the solution. This method can be quite useful for food regulation boards to analyze and detect the contents of beverages, soft drinks and any consumable liquid, whether hot or cold.
An Effective Way of Improving the Performance of Ni‐Rich LiNi0.82Co0.12Mn0.06O2 Cathode in Lithium‐Ion Battery via Borate Coating
Authors: Lin Jianxiong , Fang Liang
Published: December 2020

Nickel‐rich cathode materials are competitive materials for their low cost and high specific capacity without charging at high potentials. However, structure instability, especially the side reaction, still needs to be further solved. Herein, an effective way of improving the performance of nickel‐rich cathode materials via borate coated on the water‐washed sample is introduced. The boron elements can both easily form a membrane and diffuse into the whole particle to form lithium boron oxides. This Li+ conductor network makes the lithium transfer more efficiently and acts as an artificial solid‐state electrolyte interface (SEI), which increases the discharge capacity. A lithium boron oxides barrier film is formed between electrode and electrolyte, which effectively suppresses the side reaction and improves the capacity retention. Moreover, the reduction of residual lithium compound and pH value, which leads to more stable electrode slurry, making it more attractive for practical applications.
Investigation of Drying Curves of Lithium‐Ion Battery Electrodes with a New Gravimetrical Double‐Side Batch Dryer Concept Including Setup Characterization and Model Simulations
Authors: Kumberg Jana , Baunach Michael , Eser Jochen C. , Altvater Andreas , Scharfer Philip , Schabel Wilhelm
Published: December 2020

Herein, an experimental setup comprised of a stationary convection dryer (Comb Nozzle Dryer) supplemented by a measurement for gravimetric drying curves is introduced. The drying process of anodes for lithium‐ion batteries is experimentally investigated and compared to modeling results, showing very good agreement for the investigated films. Heat transfer coefficients of the issued impinging nozzles are characterized and measured quantitatively and are used for the drying simulation of the gravimetric drying experiments. In situ temperature changes in the films are measured and presented using an infrared camera setup.
Tyrosinase inhibition by p‐coumaric acid ethyl ester identified from camellia pollen
Authors: Li Lijun , Cai Yuchen , Sun Xu , Du Xiping , Jiang Zedong , Ni Hui , Yang Yuanfan , Chen Feng
Published: December 2020

A tyrosinase inhibitor was separated from camellia pollen with the aid of solvent fraction, macroporous adsorptive resin chromatography, and high‐speed countercurrent chromatography. The inhibitor was identified to be p‐coumaric acid ethyl ester (p‐CAEE) by nuclear magnetic resonance and mass spectrum. Its inhibitory activity (IC50 = 4.89 μg/ml) was about 10‐fold stronger than arbutin (IC50 = 51.54 μg/ml). The p‐CAEE inhibited tyrosinase in a noncompetitive model with the KI and Km of 1.83 μg/ml and 0.52 mM, respectively. Fluorescence spectroscopy analysis showed the p‐CAEE quenched an intrinsic fluorescence tyrosinase. UV‐Vis spectroscopy analysis showed the p‐CAEE did not interact with copper ions of the enzyme. Docking simulation implied the p‐CAEE induced a conformational change in the catalytic region and thus changed binding forces of L‐tyrosine. Our findings suggest that p‐CAEE plays an important role in inhibiting tyrosinase and provides a reference for developing pharmaceutical, cosmetic, and fruit preservation products using pollen.
Modification of postcombustion CO2 capture process: A techno‐economic analysis
Authors: Sultan Haider , Bhatti Umair Hassan , Muhammad Hafiz Ali , Nam Sung Chan , Baek Il Hyun
Published: December 2020

Postcombustion CO2 separation using aqueous amine solution has a great potential to minimize CO2 emissions but is expensive due to huge energy requirement for solvent regeneration. Several structural modifications can be implemented to minimize the regeneration energy requirement and optimize the energy efficiency. In this study, we evaluated the techno‐economic benefits of three stripping modifications, namely lean vapor compression (LVC), stripper overhead exchanger (SOE), and an advanced hybrid configuration (LVCSOE) in a single flowsheet aimed at reducing the energy consumption of CO2 separation process using 30 wt.% monoethanolamine (MEA) solution. All the configurations were simulated using Aspen Plus® rate‐based modeling, while capital investment was evaluated using Aspen Economic Analyzer®. All the modifications reduced the energy consumption and showed economic benefit compared to the base case. The optimal configuration was LVCSOE, which reduced the energy requirement for solvent regeneration and the CO2 capture cost by 18% and 5.3%, respectively, and can save 5.4 million USD annually. Additionally, sensitivity analysis of economic variables suggested that CO2 capture cost is more sensitive to regeneration steam cost than any other economic parameter. Furthermore, the effect of regeneration steam cost revealed that the implementation of an advanced process configuration can result in higher net savings as compared to the base case at high fuel price. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd.
What happens when you wait? Effects of Social Security Disability Insurance wait time on health and financial well‐being
Authors: Prenovitz Sarah
Published: December 2020

While waiting for a decision, individuals who apply for Social Security Disability Insurance face strong incentives to remain out of the labor force and receive no support from the program. An extended period with low income, high uncertainty, and lowered access to health insurance has the potential to harm applicants' well‐being along many dimensions. In this study, I estimate the effect of initial wait time on health, healthcare access, and financial well‐being, using the prevailing wait at the time an applicant applied as an instrument for their own initial wait. I find that a longer wait decreases the likelihood that an applicant has benefits terminated at the time of survey and increases the likelihood that they are currently receiving benefits, consistent with prior findings that longer waits decrease future work and earnings. Wait time also increases the number of conditions causing activity limitations. This suggests that new or worsening medical conditions contribute to the effect of wait time on employment and earnings, and that wait time has effects that extend beyond labor force outcomes.
Proposal of a TNM classification–based staging system for esthesioneuroblastoma: More precise prediction of prognosis
Authors: Sun Meng , Wang Kai , Qu Yuan , Zhang Jianghu , Zhang Shiping , Chen Xuesong , Wang Jingbo , Wu Runye , Zhang Ye , Yi Junlin , Xiao Jianping , Xu Guozhen , Huang Xiaodong , Luo Jingwei
Published: December 2020

Background

Esthesioneuroblastoma (ENB) is a rare malignant neoplasm. Currently, no consistent and universal staging system for ENB exists. The aim of this study is to propose a TNM‐based classification.

Subjects and methods

Hundred and forty‐two patients from our institution, with ENB pathologically confirmed between July 1978 and December 2018, were reviewed. All patients were restaged according to the Kadish stage, Morita stage and American Joint Committee on Cancer (AJCC) T classification from clinical and radiological data. Multivariate Cox proportional hazard regression analyses were performed to determine the impact of various factors. The goodness‐of‐fit and predictive accuracy of the different staging systems were calculated using R software.

Results

The median follow‐up time was 57 months (range: 4‐229 months). According to the Kadish system, the 5‐year overall survival (OS) for patients with stage A, B and C was 100%, 83.6% and 64.2%, respectively (P = .055). With respect to the Morita classification, 5‐year OS for stages A, B, C and D was 100%, 83.6%, 70.7% and 50.0%, respectively (P = .004). Analysis based on the proposed staging model demonstrated 5‐year OS for stage I, II, III and IV disease was 100%, 88.9%, 75.9% and 49.0%, respectively (P < .001). In separate multivariate Cox regression models, only the novel staging system exhibited independent effects on OS (P = .004); the Akaike information criterion and Harrell's concordance index were also superior to those calculated for the Kadish or Morita systems.

Conclusions

The proposed TNM‐based staging system offers an improved prognostic assessment for patients with ENB. Further verification and refinement from additional dataset application is required.
Were the hospital bed reductions proposed by English Clinical Commissioning Groups (CCGs) in the sustainability and transformation plans (STPs) achievable? Insights from a new model to compare international bed numbers
Authors: Jones Rodney P.
Published: December 2020

A new model for hospital bed numbers which adjusts for end‐of‐life care and age structure is used to demonstrate that England has 20% fewer occupied beds than the other countries in the United Kingdom. It also shows that occupied beds in English Clinical Commissioning Groups (CCGs) lie parallel to a line of equivalence with New Zealand and Singapore. This is despite New Zealand and Singapore having invested many years into developing integrated care, while England has not. In addition, England has around half the number of nursing home beds per death available in these two countries. Large bed reductions proposed in the sustainability and transformation plans were likely to have been manipulated to meet financial cost‐saving targets rather than a result of genuine modelling of demand. The ways in which bed demand models can be manipulated to give whatever answer is required are discussed. Trends in occupied acute medical beds in England over the past 20 years show no real reduction, despite a large reduction in available beds. This has resulted in daytime occupancy for adult beds being close to 100% and with resulting queues to admission. The ways to improve the small‐area application of the model including the use of deprivation or social groups are discussed.
Examining the social influence of reputation for partner productivity level on the collaborative task performance of young children
Authors: Hamamoto Hikaru , Mizobata Risa , Ishikawa Mitsuhiko , Itakura Shoji
Published: December 2020

Humans adjust behaviour in the presence of others in a phenomenon called social influence, which can be categorized into social facilitation (promotional effects) and social loafing (inhibitory effects). The study examined whether the productivity level of the partner in individual and collaborative tasks produced a social influence on children's task performance. The participants were aged 4‐ to 6‐years‐old and grouped as high‐productivity, low‐productivity, and control according to the productivity level of the partners. Experiments 1 and 2 assigned adults and young peers as partners, respectively. Children's performance in the collaborative task decreased compared with the individual task. This effect was unobserved when the adult partner was highly productive but occurred regardless of productivity level when the partner was a peer. Positive correlations were also observed between children's and partners' performance in both experiments. The results thus suggested that young children adjust their behaviour based on the partner's actions.

Highlights

The social influence of partner's productivity level on young children's task performance was examined during a collaborative task.

Children performed individual and collaborative tasks with an adult (Experiment 1) or child partner (Experiment 2).

Positive correlations were observed between children's and partners' performance in both experiments.
Efficacy of bone formation of microporous sphere‐shaped biphasic calcium phosphate in a rabbit skull bone defect model
Authors: Ryu Dong Jin , Jung Eui Yub , Hong Da Hee , Kwon Kyeu Baek , Park Sang Jun , Kim Joo Hwan , Wang Joon Ho
Published: December 2020

Bone graft is required in various surgical procedures. Although autograft is the gold standard, it has limited availability. Various compounds have been proposed as alternatives such as biphasic calcium phosphate (BCP), which is the most widely used compound. The newly synthesized microporous sphere‐shaped BCP has the advantage of increasing contact surface, and it can induce the formation of microbone structures. A putty‐type contains the addition of a fluid carrier to the sphere‐shaped BCP and can be easily used for a small orifice large bone defect. To compare the widely used BCP products, new bone formation and residual graft materials (RGM) were evaluated for 6 and 12 weeks in a rabbit calvarial bone defect model. Although existing BCP products and the microporous sphere‐type product did not differ significantly with respect to new bone formation and RGM, the putty‐type product was largely washed out and had low new bone formation at 6 and 12 weeks. Overall, the results suggest that microporous sphere‐shaped BCP showed similar bone formation capability to existing products and was able to maintain higher initial mechanical stability.
Improving Women's Self‐Compassion Through an Online Program: A Randomized Controlled Trial
Authors: Nadeau Miranda M. , Caporale‐Berkowitz Norian A. , Rochlen Aaron B.
Published: December 2020

The benefits of self‐compassion interventions have been well documented in the counseling literature. Despite these benefits, access to such interventions remains a considerable barrier for a range of populations. We addressed the issue of limited access by using a randomized controlled trial to evaluate an online, self‐guided course on self‐compassion specifically targeted toward women. Fifty‐seven women were randomly assigned to receive immediate or delayed access to a 10‐week course designed to increase self‐compassion and reduce self‐judgment, shame, and perfectionism. Analysis of the data revealed that participants in the treatment condition experienced significant increases in self‐compassion and decreases in self‐judgment, shame, and perfectionism compared with participants in the wait‐list group. Results provide evidence that self‐compassion can be fostered in a nonclinical population of women through participation in a self‐paced online course. Related findings and potential implications, including the use of such interventions to address accessibility concerns, are discussed within the existing literature.
An Exploration of Young Clients' Experiences in Counseling With Post‐Master's Counselors
Authors: Sackett Corrine R. , Cook Ryan M.
Published: December 2020

This phenomenological study adds to current literature about clients' meaningful experiences in counseling by exploring the experiences of eight young clients (ages 8–18) in individual counseling with post‐master's counselors in an outpatient setting. Interviews with these clients revealed the following six themes: (a) the process of growth, (b) having a safe place to talk, (c) counselor accepts and meets the client where they are, (d) counseling is a team effort, (e) supportive accountability from the counselor, and (f) understanding self and others. The final theme includes two subthemes: learning coping and emotion management skills, and learning better ways to communicate and behave. Findings and implications for counselors are discussed.
Influence of Sr2+ ion substitution on structural, morphological, optical, thermal, and magnetic behavior of MgFe2O4 cubic spinel
Authors: Baskar S , Yuvaraj S , Partha Sarathi Subudhi , Sundararajan M , Chandra Sekhar Dash
Published: December 2020

Utilizing L‐arginine as a fuel, Mg1‐xSrxFe2O4 (0 ≤ x ≤ 0.5) spinel nanoparticles were prepared by the microwave combustion process. Impact of Sr2+ ion substitution on structural, morphology, optical, thermal, and magnetic characteristics is investigated by following techniques such as X‐ray diffraction (XRD), HR‐SEM, energy dispersive X‐ray analysis (EDX), diffused reflectance spectroscopy‐Ultra Violet (DRS‐UV), TG‐DTA, and VSM. XRD ensures the formation of the cubic spinel structure, and the average crystallite size was determined utilizing the Debye Scherer equation, which was found to be lying between 33.10 and 24.11 nm. HR‐SEM images exhibited agglomerated morphology, and the samples were observed to be highly crystalline in nature. EDX spectra confirmed the formation of pure and strontium doped magnesium ferrite, ensuring the existence of all the elements. The bandgap was observed to lie in between 2.02 and 1.57 eV, respectively. TG‐DTA spectra provide information regarding the total weight loss, endothermic, and exothermic transitions. From M‐H loops, it is observed that pure and strontium doped magnesium ferrite exhibits ferromagnetic behavior.
Tumor‐agnostic inhibitors in oncology: A new phase for precision medicine
Authors: Li Mu‐Chun , Hsieh Hsing‐Pang
Published: December 2020

The study of precision medicine is flourishing in recent decades. Tumor‐agnostic therapy is one of the targeted therapies, which can treat the malignant cells regardless of where they grow. Herein we reviewed currently the U.S. FDA‐approved tumor‐agnostic therapies: one monoclonal antibody as a PD‐1 inhibitor called pembrolizumab and four small‐molecule kinase inhibitors, larotrectinib, entrectinib, selpercatinib, and pralsetinib. We also summarized the reported synthetic routes toward three drugs and some developing candidates under clinical trials as tumor‐agnostic therapy.
Molecular design, property prediction, and intermolecular interactions for high‐energy cage compounds based on the skeletons of RDX and HMX
Authors: Tang Li , Zhu Weihua
Published: December 2020

We designed nine new cage compounds by using different numbers of linkages –N(NO2)– and –N(NH2)– to connect the two skeletons of 1,3,5‐trinitro‐1,3,5‐triazinane (RDX) or 1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocane (HMX) to construct the cage frameworks, similar to the skeleton of hexanitrohexaazaisowurtzitane (CL‐20). Then, their electronic structures, heats of formation, energetic properties, and impact sensitivities were studied using density functional theory. The types of intermolecular interactions and the changes in sensitivity were analyzed. Compared to the parent compounds RDX, HMX, and CL‐20, all the designed compounds present extraordinary high detonation properties (D > 9.70 km/s and P > 44.30 GPa). Considering the detonation performance and impact sensitivity, the four compounds may be regarded as potential candidates of high‐energy‐density compounds . Our results will contribute to a new strategy for the theoretical design of new energetic compounds.
Charge transfer enhanced magnetic correlations in type‐II multiferroic Co3TeO6
Authors: Lee Chi‐Hung , Batsaikhan Erdembayalag , Ma Ma‐Hsuan , Li Wen‐Hsien , Wang Chin‐Wei , Wu Chun‐Min , Yang Hung‐Duen , Lynn Jeffrey W. , Berger Helmuth
Published: December 2020

Magnetic structure of the Co ions in monoclinic Co3TeO6 in the antiferroelectric state at 16 K has been determined by neutron powder together with single‐crystal diffractions. The indices of the magnetic reflections that appear at the incommensurate positions were determined by diffractions from a single crystal, which allow to uniquely identify the magnetic modulation vector. There are two crystallographically distinct Co layers. Magnetic incommensurability appears in the Co spins in the layers comprising zig‐zag chains, with a magnetic modulation vector of (0.357, 0.103, 0.121) at 3 K but changes to (0.4439, 0, 0.137) at 16 K, while the Co ions in the honeycomb webs form a collinear antiferromagnetic structure. Thermal reduction rate of the Co moments in the honeycomb webs was found to be much smaller than those in the zig‐zag chains. Shifting of large amounts of electronic charge into the CoO bonds in the honeycomb webs on warming is used to understand the behavior.
VE1 immunohistochemistry is an adjunct tool for detection of BRAFV600E mutation: Validation in thyroid cancer patients
Authors: Rashid Faiza A. , Tabassum Sobia , Khan Mosin S. , Ansari Hifzur R. , Asif Muhammad , Sheikh Ahmareen K. , Sameer Aga Syed
Published: December 2020

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy among other endocrine tumors, and BRAFV600E is a frequent genetic mutation occurring in the disease. Although different molecular techniques, most importantly sequencing has been widely recognized as a gold standard but molecular diagnosis remains an expensive, laborious, and time‐intensive process. Recently, immunohistochemistry (IHC) with anti‐BRAF V600E (VE1) antibody has increased practical utility and implemented clinically for the detection of BRAFV600E mutation. Therefore, the study aimed to evaluate diagnostic accuracy of VE1 IHC for detecting the BRAFV600E mutation frequency and clinical implementation in diagnostic laboratories. In this study, 72 formalin fixed paraffin‐embedded tissues (FFPE) were used to determine the BRAFV600E mutation status using IHC and Sanger sequencing. The mutation was found in 29% and 28% cases using IHC and Sanger sequencing, respectively. Furthermore, the results showed 100% sensitivity, 98.07% specificity, 95.2% positive predictive value, and 100% negative predictive value. Notably, significant associations were found between BRAFV600E status and tumor stage, tumor focality, and extrathyroidal extensions, respectively. VE1 IHC was found to be a highly sensitive, specific, and diagnostically accurate method in this cohort. Therefore, BRAFV600E detection through IHC has been considered as the best tailored technique for routine pathology laboratories.
Integrin α2β1 inhibition attenuates prostate cancer cell proliferation by cell cycle arrest, promoting apoptosis and reducing epithelial–mesenchymal transition
Authors: Salemi Zahra , Azizi Reza , Fallahian Faranak , Aghaei Mahmoud
Published: December 2020

Integrin α2β1 plays an important role in cellular migration and metastasis processes associated with prostate cancer. The aim of this study was to assess whether selective inhibition of integrin α2β1 is an effective strategy to target metastatic prostate cancer cells. In this regard, we examined the effects of the inhibitor BTT‐3033, which selectively interferes with the connection between integrin a2b1 and its ligand, on migration, epithelial–mesenchymal transition (EMT), cell cycle arrest, apoptosis, and specific intracellular signaling pathways using LNcap‐FGC and DU‐145 prostate cancer cell lines. Western blot analysis and immunocytochemistry assays showed that inhibition of integrin a2b1 inhibits EMT, through the increased expression of E‐cadherin and decreased expression of N‐cadherin and vimentin. Scratch wound healing assays revealed a direct effect on integrin α2β1 in the migration capacity of cells. In addition, treatment with BTT‐3033 induced a reduction in cell viability and proliferation, as assessed by MTT and BrdU assays. In addition, the results show that BTT‐3033 inhibits cell proliferation by inducing G1 cell cycle arrest. Moreover, inhibition of integrin α2β1 induces apoptosis through the activation of ROS, Bax protein upregulation, caspase‐3 activation, and depletion of ΔΨm.  Molecular signaling studies showed that integrin α2β1 was a positive regulator of MKK7 phosphorylation. In conclusion, our results reveal a critical role for integrin a2b1 in the proliferation of prostate cancer cells, as demonstrated by EMT inhibition, cell cycle arrest, and apoptosis induction in response to treatment with its specific inhibitor BT‐3033.
The impact of culture dimensionality on behavioral epigenetic memory contributing to pluripotent state of iPS cells
Authors: Thanuthanakhun Naruchit , Kino‐oka Masahiro , Borwornpinyo Suparerk , Ito Yuzuru , Kim Mee‐Hae
Published: December 2020

Three‐dimensional (3D) culture platforms have been explored to establish physiologically relevant cell culture environment and permit expansion scalability; however, little is known about the mechanisms underlying the regulation of pluripotency of human induced pluripotent stem cells (hiPSCs). This study elucidated epigenetic modifications contributing to pluripotency of hiPSCs in response to 3D culture. Unlike two‐dimensional (2D) monolayer cultures, 3D cultured cells aggregated with each other to form ball‐like aggregates. 2D cultured cells expressed elevated levels of Rac1 and RhoA; however, Rac1 level was significantly lower while RhoA level was persisted in 3D aggregates. Compared with 2D monolayers, the 3D aggregates also exhibited significantly lower myosin phosphorylation. Histone methylation analysis revealed remarkable H3K4me3 upregulation and H3K27me3 maintenance throughout the duration of 3D culture; in addition, we observed the existence of naïve pluripotency signatures in cells grown in 3D culture. These results demonstrated that hiPSCs adapted to 3D culture through alteration of the Rho‐Rho kinase‐phospho‐myosin pathway, influencing the epigenetic modifications and transcriptional expression of pluripotency‐associated factors. These results may help design culture environments for stable and high‐quality hiPSCs.
Chemotherapy triggers cachexia by deregulating synergetic function of histone‐modifying enzymes
Authors: Amrute‐Nayak Mamta , Pegoli Gloria , Holler Tim , Lopez‐Davila Alfredo Jesus , Lanzuolo Chiara , Nayak Arnab
Published: December 2020

Background

Chemotherapy is the first line of treatment for cancer patients. However, the side effects cause severe muscle atrophy or chemotherapy‐induced cachexia. Previously, the NF‐κB/MuRF1‐dependent pathway was shown to induce chemotherapy‐induced cachexia. We hypothesized that acute collateral toxic effects of chemotherapy on muscles might involve other unknown pathways promoting chemotherapy‐induced muscle atrophy. In this study, we investigated differential effects of chemotherapeutic drugs and probed whether alternative molecular mechanisms lead to cachexia.

Methods

We employed mouse satellite stem cell‐derived primary muscle cells and mouse C2C12 progenitor cell‐derived differentiated myotubes as model systems to test the effect of drugs. The widely used chemotherapeutic drugs, such as daunorubicin (Daun), etoposide (Etop), and cytarabine (Ara‐C), were tested. Molecular mechanisms by which drug affects the muscle cell organization at epigenetic, transcriptional, and protein levels were measured by employing chromatin immunoprecipitations, endogenous gene expression profiling, co‐immunoprecipitation, complementation assays, and confocal microscopy. Myotube function was examined using the electrical stimulation of myotubes to monitor contractile ability (excitation–contraction coupling) post drug treatment.

Results

Here, we demonstrate that chemotherapeutic drugs disrupt sarcomere organization and thereby the contractile ability of skeletal muscle cells. The sarcomere disorganization results from severe loss of molecular motor protein MyHC‐II upon drug treatment. We identified that drugs impede chromatin targeting of SETD7 histone methyltransferase and disrupt association and synergetic function of SETD7 with p300 histone acetyltransferase. The compromised transcriptional activity of histone methyltransferase and acetyltransferase causes reduced histone acetylation and low occupancy of active RNA polymerase II on MyHC‐II, promoting drastic down‐regulation of MyHC‐II expression (~3.6‐fold and ~4.5‐fold reduction of MyHC‐IId mRNA levels in Daun and Etop treatment, respectively. P < 0.0001). For MyHC‐IIa, gene expression was down‐regulated by ~2.6‐fold and ~4.5‐fold in Daun and Etop treatment, respectively (P < 0.0001). Very interestingly, the drugs destabilize SUMO deconjugase SENP3. Reduction in SENP3 protein level leads to deregulation of SETD7–p300 function. Importantly, we identified that SUMO deconjugation independent role of SENP3 regulates SETD7–p300 functional axis.

Conclusions

The results show that the drugs critically alter SENP3‐dependent synergistic action of histone‐modifying enzymes in muscle cells. Collectively, we defined a unique epigenetic mechanism targeted by distinct chemotherapeutic drugs, triggering chemotherapy‐induced cachexia.
Sonographic characteristics and follow‐up of pancreatic cysts
Authors: Guo Yang , Asch Elizabeth , Benson Carol B.
Published: December 2020

Objectives

To assess sonographic characteristics and outcome of patients with pancreatic cystic lesions seen by ultrasound.

Methods

From our ultrasound electronic reporting database we identified all patients in which “pancreatic cyst” or “pancreatic cysts” were reported from 1995 to 2018. In patients with more than one sonogram, the first was used for our study. For each case, we recorded sonographic characteristics, maximal diameter, cyst location, and results of follow‐up ultrasound, CT or magnetic resonance imaging, as well as patient sex, age, relative clinical history, and endoscopic ultrasound (EUS) or surgical findings when available.

Results

Our study included 177 patients of whom 121 were female (68.4%). Mean age at diagnosis was 65 (±16, SD, range 22‐99). Ultrasound was the initial diagnostic test in 122 (68.9%). Mean diameter of the index cyst was 13.7 mm (±11.5 mm, SD, range 2‐91 mm). Among 177 index cysts, 155 were simple and 22 complex. Three complex cysts were surgically resected, yielding a primary pancreatic malignancy, a metastasis, and an epithelial‐lined cyst. One simple cyst was resected, yielding a benign intraductal papillary mucinous neoplasm. Seventeen patients underwent EUS showing six mucinous cysts and 11 nonmucinous cysts. One hundred‐eighteen patients had follow‐up imaging for a mean time of 5.6 years (±3.8, range 0.25‐21 years). One patient was presumed to have primary pancreatic cancer. The overall rate for primary pancreatic malignancy was 1.7% (2/118).

Conclusions

Cystic pancreatic lesions seen on ultrasound are most often benign, with a low risk of pancreatic malignancy. Ultrasound is an excellent method to follow‐up these cysts.
COVID‐19: Virology, biology and novel laboratory diagnosis
Authors: Mohamadian Malihe , Chiti Hossein , Shoghli Alireza , Biglari Sajjad , Parsamanesh Negin , Esmaeilzadeh Abdolreza
Published: December 2020

Background

At the end of December 2019, a novel coronavirus tentatively named SARS‐CoV‐2 in Wuhan, a central city in China, was announced by the World Health Organization. SARS‐CoV‐2 is an RNA virus that has become a major public health concern after the outbreak of the Middle East Respiratory Syndrome‐CoV (MERS‐CoV) and Severe Acute Respiratory Syndrome‐CoV (SARS‐CoV) in 2002 and 2012, respectively. As of 29 October 2020, the total number of COVID‐19 cases had reached over 44 million worldwide, with more than 1.17 million confirmed deaths.

Discussion

SARS‐CoV‐2 infected patients usually present with severe viral pneumonia. Similar to SARS‐CoV, the virus enters respiratory tract cells via the angiotensin‐converting enzyme receptor 2. The structural proteins play an essential role in budding the virus particles released from different host cells. To date, an approved vaccine or treatment option of a preventive character to avoid severe courses of COVID‐19 is still not available.

Conclusions

In the present study, we provide a brief review of the general biological features of CoVs and explain the pathogenesis, clinical symptoms and diagnostic approaches regarding monitoring future infectivity and prevent emerging COVID‐19 infections.
CircADAMTS6/miR‐431‐5p axis regulate interleukin‐1β induced chondrocyte apoptosis
Authors: Fu Qiwei , Li Lexiang , Wang Bo , Wu Jun , Li Haobo , Han Yaguang , Xiang Dong , Chen Yi , Zhu Jun
Published: December 2020

Background

Growing evidence suggests that circular RNAs (circRNAs) are involved in the development of osteoarthritis (OA). The present study aimed to explore the CircADAMTS6/miR‐431‐5p axis with respect to regulating interleukin‐1β (IL‐1β) induced chondrocyte apoptosis.

Methods

We first evaluated the differentially expressed circRNAs between normal chondrocytes and interleukin (IL)‐1β‐stimulated chondrocytes. Then, bioinformatic analysis was performed to identify the role and function of circADAMTS6. Small interfering RNA‐expressing or overexpressing circADAMTS6 lentiviral vectors were used for transduction of chondrocytes. Annexin‐V‐fluorescein isothiocyanate (FITC) double staining was performed to measure the apoptotic rate of the chondrocytes in each group. Finally, a dual luciferase reporter assay was performed to identify the target relationship between circADAMTS6 and miR‐431‐5p.

Results

After treatment with IL‐1β, circADAMTS6 was down‐regulated compared to the normal chondrocyte group. The overexpression of circADAMTS6 inhibited apoptosis in human chondrocytes, as indicated by annexin‐V‐FITC double staining. However, overexpression of miR‐431‐5p had the opposite effect. A dual luciferase reporter assay indicated that circADAMTS6 could directly binding with miR‐431‐5p.

Conclusions

Our findings demonstrate that the circADAMTS6/miR‐431‐5p axis comprises a new target for OA. Bioinformatic analysis suggested that circADAMTS6 acted as a sponge of miR‐431‐5p.
Longitudinal Assessment of Patients With Cystic Fibrosis Lung Disease With Multivolume Noncontrast MRI and Spirometry
Authors: Pennati Francesca , Borzani Irene , Moroni Laura , Russo Maria Chiara , Faelli Nadia , Aliverti Andrea , Colombo Carla
Published: December 2020

Background

MRI has been suggested as a radiation‐free imaging modality to investigate early structural alterations and regional functional impairment in cystic fibrosis (CF) lung disease.

Purpose/Hypothesis

To compare functional and morphological MRI changes over the course of the disease to changes in spirometry.

Study Type

Longitudinal retrospective study.

Population

Twenty patients with CF lung disease (at baseline, age = 16.5 (13.3–20.6) years, forced expiratory volume in 1 second (as % of predicted [%pred]) FEV1 = 71 (59–87) %pred, forced expiratory flow at 25–75% of forced vital capacity FEF25‐75 = 39 (25–63) %pred.

Field Strength/Sequence

1.5T / T2‐weighted HASTE; T2‐weighted TSE‐PROPELLER; T2‐weighted bSSFP; T1‐weighted 3D GRE.

Assessment

Nonenhanced chest MRI and spirometry were retrospectively collected over a 3‐year period from the initial recruitment visit. Images acquired at end‐inspiration and end‐expiration were registered by software using the optical flow method to measure expiratory‐inspiratory differences in MR signal‐intensity (Δ1H‐MRI). Measures of CF functional impairment were defined from Δ1H‐MRI: Δ1H‐MRI median, Δ1H‐MRI quartile coefficient of variation (QCV), and percent low‐signal‐variation volume (LVV). MR images were also evaluated by three readers using a CF‐specific scoring system.

Statistical Tests

Spearman correlation analysis, Spearman rank correlation analysis, linear mixed‐effect model analysis, intraclass correlation coefficient.

Results

Functional imaging parameters and total morphological score correlated with all spirometric measures, as did subscores of bronchial wall thickening/bronchiectasis, mucus plugging, and consolidation. Overall, the percent change of Δ1H‐MRI median correlated with the percent change of FEV1 (ΔFEV1, r = 0.41, P < 0.01) and the percent change of FEF25‐75 (ΔFEF25‐75%, r = 0.38, P < 0.01). The percent change of LVV correlated with ΔFEV1 (r = –0.47, P < 0.001) and ΔFEF25‐75 (r = –0.50, P < 0.001).

Data Conclusion

These preliminary results suggest that nonenhanced multivolume MRI may provide a feasible tool to regionally map early pulmonary alterations for longitudinal evaluation of CF lung disease, without exposing the patients to ionizing radiation.

Level of Evidence

3T

Technical Efficacy Stage

5
Periodontal regenerative therapy in patients with type 2 diabetes using minimally invasive surgical technique with enamel matrix derivative under 3‐year observation: A prospective cohort study
Authors: Mizutani Koji , Shioyama Hidehiro , Matsuura Takanori , Mikami Risako , Takeda Kohei , Izumi Yuichi , Aoki Akira , Iwata Takanori
Published: December 2020

Background

Information regarding periodontal regenerative therapy in patients with diabetes mellitus (DM) is limited. This pilot study compared the regenerative outcomes of minimally invasive periodontal surgery using enamel matrix derivative (EMD) between DM and non‐DM patients.

Methods

This prospective study included deep intrabony defects in patients with or without type 2 DM. Minimally invasive surgical technique (MIST) or modified MIST (M‐MIST) using EMD, without bone graft materials, was performed. Periodontal examination and intraoral radiography were performed at baseline, 6 months, and 1 and 3 years after surgery.

Results

Ten sites of 10 subjects in the DM group, and 20 sites of 18 subjects in non‐DM group were evaluated (mean age; 67.5 ± 7.6 and 63.1 ± 9.7, respectively). Probing depth significantly decreased from 7.1 ± 1.6 and 7.0 ± 1.3 mm to 2.2 ± 0.9 and 2.3 ± 1.1 mm at the 1‐year examination in the DM and non‐DM groups, respectively. Clinical attachment level (CAL) gain and radiographical defect fill at the 3‐year examination were 3.8 ± 1.1 mm and 58.3% ± 10.4%, respectively, in the DM group, and 4.1 ± 1.1 mm and 65.5% ± 18.8%, respectively, in the non‐DM group, showing no significant differences between the groups. Multiple regression analysis showed no significant association of CAL gain with DM or age after adjustments for relevant confounders.

Conclusions

This is the first documented study of successful periodontal tissue regeneration in patients with DM. Minimally invasive surgery combined with EMD yielded significant clinical attachment gain and bone fill in the DM and non‐DM groups at comparable levels.
Effects of cultivar and growing degree day accumulations on forage partitioning and nutritive value of common vetch (Vicia sativa L.) on the Tibetan plateau
Authors: Huang Yafeng , Zhang Zhixin , Nan Zhibiao , Unkovich Murray , Coulter Jeffrey A
Published: December 2020

BACKGROUND

The use of common vetch in grassland‐livestock systems has expanded greatly within recent years, partly because of its value as a high‐quality forage crop but also to improve the soil nitrogen availability. In‐field estimation of forage yield potential and nutritional characteristics is required for providing management decision to farmers on how to optimize the management and use of common vetch forages. The aim of this work was to study changes in forage partitioning and nutritive value responses of a late‐maturing and an early maturing cultivar of common vetch in a two‐year study on the Tibetan Plateau.

RESULTS

This study provided evidence for differential patterns of forage accumulation for common vetch with contrasting maturity over 2 years. The late‐maturing cultivar exhibited greater forage yield and a lower proportion of pods, compared to the early maturing cultivar. There was a tendency towards lower forage nutritive value with the late‐maturing cultivar. Regressions of nutritive value parameters of common vetch forages on growing degree days were explained by the cubic (P < 0.001) models, all with high coefficients of determination (R2 ≥ 0.792).

CONCLUSION

This study shows that the late‐maturing cultivar harvested at end of the pod‐filling stage produces high forage yield, increasing the availability of high‐quality forage for ruminants, thereby improving the self‐sufficiency of farmers, in terms of forage yield and high‐concentration protein. For early maturing cultivars, it may be better to harvest at the early flowering stage for better nutritive value and in part to enable a subsequent double crop of oat. © 2020 Society of Chemical Industry
Research progress on sample pretreatment methods for migrating substances from food contact materials
Authors: Ouyang Xiaoyan , Lu Zicheng , Hu Yuling , Xie Zenghui , Li Gongke
Published: December 2020

Excessive absorption of migrating substances from food contact materials can affect human health. Thus, it is essential to analyze the migration of contaminant from food contact materials. However, comprehensive analysis has been challenged by low concentration of migrating substances, manifold and complex matrix interference of food contact materials. Therefore, appropriate sample pretreatment methods should be applied before instrumental detection, which is essential to improve the analytical efficiency, sensitivity, and reliability. This paper systematically reviews the development of sample pretreatment methods for analysis of migrating substances from food contact materials in the past decade. To extract volatile and semi‐volatile substances, headspace extraction, headspace solid phase microextraction, and purge and trap technique are discussed. For non‐volatile substances, solid–liquid extraction and field‐assisted extraction are usually used to extract them from food contact materials, while liquid–liquid extraction, solid phase extraction, and their corresponding microextraction techniques play important roles on enrichment process. In addition, new progress in developments of sample pretreatment methods of food contact materials is summarized, covering new devices, specific adsorbents, and sample preparation methods for rapid detection. An outlook of future prospect of sample pretreatment, especially for non‐targeted analysis of non‐intentionally added substances is briefly discussed.