bluuebunny/crossref_metadata_2025 huggingface dataset:
Epistatic effect of TLR3 and cGAS‐STING‐IKKε‐TBK1‐IFN signaling variants on colorectal cancer risk
Authors: Catalano Calogerina , da Silva Filho Miguel Inacio , Frank Christoph , Lu Shun , Jiraskova Katerina , Vymetalkova Veronika , Levy Miroslav , Liska Vaclav , Vycital Ondrej , Naccarati Alessio , Vodickova Ludmila , Hemminki Kari , Vodicka Pavel , Weber Alexander N. R. , Försti Asta
Published: December 2019

Objective

The TLR3/cGAS‐STING‐IFN signaling has recently been reported to be disturbed in colorectal cancer due to deregulated expression of the genes involved. Our study aimed to investigate the influence of potential regulatory variants in these genes on the risk of sporadic colorectal cancer (CRC) in a Czech cohort of 1424 CRC patients and 1114 healthy controls.

Methods

The variants in the TLR3, CGAS, TMEM173, IKBKE, and TBK1 genes were selected using various online bioinformatic tools, such as UCSC browser, HaploReg, Regulome DB, Gtex Portal, SIFT, PolyPhen2, and miRNA prediction tools.

Results

Logistic regression analysis adjusted for age and sex detected a nominal association between CRC risk and three variants, CGAS rs72960018 (OR: 1.68, 95% CI: 1.11‐2.53, P‐value = .01), CGAS rs9352000 (OR: 2.02, 95% CI: 1.07‐3.84, P‐value = .03) and TMEM173 rs13153461 (OR: 1.53, 95% CI: 1.03‐2.27, P‐value = .03). Their cumulative effect revealed a threefold increased CRC risk in carriers of 5‐6 risk alleles compared to those with 0‐2 risk alleles. Epistatic interactions between these genes and the previously genotyped IFNAR1, IFNAR2, IFNA, IFNB, IFNK, IFNW, IRF3, and IRF7 genes, were computed to test their effect on CRC risk. Overall, we obtained nine pair‐wise interactions within and between the CGAS, TMEM173, IKBKE, and TBK1 genes. Two of them remained statistically significant after Bonferroni correction. Additional 52 interactions were observed when IFN variants were added to the analysis.

Conclusions

Our data suggest that epistatic interactions and a high number of risk alleles may play an important role in CRC carcinogenesis, offering novel biological understanding for the CRC management.
Aroma Profile of Two Populations of Salvia verbenaca Collected from Two Bio‐Geographical Zones from Jordan
Authors: Al‐Jaber Hala I. , Obeidat Safwan M. , Afifi Fatma U. , Abu Zarga Musa H.
Published: December 2019

The aroma emitted from the different organs of two Salvia verbenaca L. populations from Jordan were extracted by Solid Phase Micro‐Extraction (SPME) and then analyzed by GC/MS. The emission profile of the stem, leaf and sepal samples from the Mediterranean zone (Al‐Salt) was dominated by monoterpene hydrocarbons (68.0 %, 33.7 %, and 42.2 %, respectively). The emission profile of flowering parts including pre‐flowering buds, fully expanded flowers and petals was dominated by oxygenated monoterpenes (58.6 %, 59.3 % and 87.1 %, respectively). The major constituent detected in these organs was trans‐sabinene hydrate acetate (range 14.5 %–87.0 %). On the other hand, samples collected from Irano‐Turanian zone showed different emission patterns. While the stems, leaves and petal emissions were dominated by sesquiterpene hydrocarbons (54.9 %, 76.8 % and 52.6 %, respectively), monoterpene hydrocarbons dominated the emission profiles of the pre‐flowering buds (75.1 %) and fully expanded flowers (73.6 %). Petals emissions were characterized by high concentrations of oxygenated monoterpenes (58.8 %). Notably, trans‐sabinene hydrate dominated most organs emissions except for leaves (range 20.0 %–58.8 %). Principle Component Analysis (PCA) and Cluster Analysis (CA) revealed two different clusters related to the two different geographical zones. The current investigation revealed two ecotypes of S. verbenaca that could result in two different chemotypes. Trans‐sabinene hydrate acetate and trans‐sabinene hydrate are suggested compounds for identifying these two chemotypes.
Peptide Bond Cleavage by Ni(II) Ions within the Nuclear Localization Signal Sequence
Authors: Frączyk Tomasz , Bonna Arkadiusz , Stefaniak Ewelina , Wezynfeld Nina E. , Bal Wojciech
Published: December 2019

Nickel is harmful to humans, being both carcinogenic and allergenic. However, the mechanisms of this toxicity are still unresolved. We propose that Ni(II) ions disintegrate proteins by hydrolysis of peptide bonds preceding the Ser/Thr‐Xaa‐His sequences. Such sequences occur in nuclear localization signals (NLSs) of human phospholipid scramblase 1, Sam68‐like mammalian protein 2, and CLK3 kinase. We performed spectroscopic experiments showing that model nonapeptides derived from these NLSs bind Ni(II) at physiological pH. We also proved that these sequences are prone to Ni(II) hydrolysis. Thus, the aforementioned NLSs may be targets for nickel toxicity. This implies that Ni(II) ions disrupt the transport of some proteins from cytoplasm to cell nucleus.
Incidence, outcomes, and predictors of in‐hospital acute coronary syndrome following endovascular transcatheter aortic valve replacement in the United States
Authors: Nazir Salik , Ahuja Keerat R. , Donato Anthony , Grande Robert D. , Changal Khalid , Gad Mohamed M. , Saad Anas , Verma Beni R. , Syed Mubbasher A. , Sheikh Mujeeb , Kapadia Samir , Ramanathan P. Kasi
Published: December 2019

Background

Incidence and outcomes of acute coronary syndrome (ACS) immediately following transcatheter aortic valve replacement (TAVR) remain largely unknown.

Objectives

This study sought to assess the incidence, clinical characteristics, and outcomes of ACS following TAVR.

Methods

We queried the National Readmission Database from January 2012 to September 2015 for TAVR admissions with and without ACS, creating a propensity‐matched cohort to compare outcomes.

Results

A total of 48,454 patients underwent TAVR, with 1,332 (2.75%) developing ACS. TAVR patients with ACS compared to those without ACS had a significantly higher incidence of acute kidney injury (24.7 vs. 19.2%; p = .001), ischemic stroke (3.7 vs. 2.3%; p = .04), vascular complications (8.6 vs. 5.8%; p = .008), cardiogenic shock (9.8 vs. 1.9%; p < .001), cardiac arrest (5.1 vs. 2.8%; p = .002), mechanical circulatory support (8.1 vs. 1.5%; p < .001), and in‐hospital mortality (9.6 vs. 3.4%; p < .001). Additionally, TAVR with ACS had longer lengths of stay (median 10 days vs. 6 days; p < .001) and hospital charges (median $23,200 vs. $19,000; p < .001). Positive predictors of ACS were history of PCI (odds ratio, 1.43; 95% CI: 1.25–1.63), hyperlipidemia (odds ratio, 1.20; 95% CI: 1.07–1.34), chronic blood loss anemia (odds ratio, 2.16; 95% CI: 1.54–3.03), chronic kidney disease (odds ratio, 1.17; 95% CI: 1.04–1.31), fluid and electrolyte disorders (odds ratio, 1.65; 95% CI: 1.47–1.85), and weight loss (odds ratio, 1.53; 95% CI: 1.22–1.91). Heart failure (34%) was the most common reason for readmission in the ACS cohort.

Conclusion

ACS after TAVR is uncommon but is associated with worse clinical outcomes and increased healthcare resource utilization.
The effect of stenting on blood pressure in hypertensive patients with symptomatic proximal subclavian or vertebral artery stenosis
Authors: Che Wuqiang , Dong Hui , Jiang Xiongjing , Xiong Hongliang , Chen Yang , Zou Yubao , Xu Bo , Gao Runlin
Published: December 2019

Objective

This study aimed to evaluate the effect of stenting on blood pressure in hypertensive patients with symptomatic proximal subclavian or vertebral artery stenosis.

Background

Whether posterior circulation revascularization could reduce blood pressure in hypertensive patients with posterior circulation hypoperfusion has not been investigated in humans.

Methods

A total of 48 patients with essential hypertension (33 males; mean age 63.0 ± 8.7 years) with symptomatic proximal subclavian or vertebral artery stenosis who underwent stenting successfully at the Fuwai Hospital were prospectively enrolled between January 2014 and December 2015. All 48 patients were followed up at 1, 3, and 6 months after the procedure. Blood pressure, use of antihypertensive agents, and complications were investigated.

Results

Baseline values included office blood pressure of 132/77 ± 10/8 mmHg, mean 24‐hr blood pressure of 127/75 ± 12/9 mmHg, and mean antihypertensive agents used of 1.6 ± 0.8. Stenosis of the subclavian and vertebral arteries decreased from 88.9 ± 9.5% and 85.8 ± 7.4% to 5.5 ± 3.5% and 4.6 ± 3.7%, respectively, immediately after the procedure. Reductions in office blood pressure were − 7/−3 (SD 3/2), −9/−4 (5/3), and − 10/−5 (7/5) mmHg at 1, 3, and 6 months, respectively. While 24‐hr blood pressures after the procedure reduced by −5/−3 mmHg at 6 months, the total number of antihypertensive agents used at the aforementioned time points was unchanged.

Conclusion

This first prospective cohort study in humans showed that posterior circulation stenting is apparently effective in reducing blood pressure in hypertensive patients with symptomatic proximal subclavian or vertebral artery stenosis.
Drug‐coated balloon after subintimal plaque modification in failed coronary chronic total occlusion percutaneous coronary intervention: A novel concept
Authors: Ybarra Luiz F. , Dandona Sonny , Daneault Benoit , Rinfret Stéphane
Published: December 2019

Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is a technically challenging procedure. In failed cases, plaque modification strategy (also known as “investment procedure”), defined as the intentional dilation of the subintimal space through the CTO segment, can be applied. The typical dilation device used in this strategy is a regular angioplasty balloon (either semi‐ or noncompliant). Performing this technique with a drug‐coated balloon (DCB) may facilitate a staged procedure by promoting a better vessel healing. Herein, we present three cases of failed CTO PCI, managed with DCB plaque modification, and their follow‐up staged procedure.
Aortic stenosis and the pulse contour: A true marker of severity?
Authors: Eleid Mackram F. , Nishimura Rick A.
Published: December 2019

The aortic pulse contour displays characteristic changes associated with the progression of aortic stenosis (AS). A diminished and delayed aortic pulse contour is indicative of significant AS, but the aortic contour may also be affected by factors including aging, hypertension and increased peripheral arterial elastance. This review describes the components of the aortic pulse contour in AS and how it can be affected by different conditions and interventions.
Case report of patient experience influenced by inadequate interactions between primary, secondary, and tertiary healthcare services in the south of Saudi Arabia
Authors: Gosadi Ibrahim M.
Published: December 2019

This report explains how health system failure can hinder provision of healthcare for a common health problem. Inadequate healthcare delivery can create barriers, lead to stress, prolong waiting time, and affect overall well‐being of patients.
A Facile Method for the Separation of Methionine Sulfoxide Diastereomers, Structural Assignment, and DFT Analysis
Authors: Raskatov Jevgenij A. , Virgil Scott , Lee Hsiau‐Wei , Henling Lawrence M. , Chan Ka , Kuhn Ariel J. , Foley Alejandro R.
Published: December 2019

Methionine (Met) oxidation is an important biological redox node, with hundreds if not thousands of protein targets. The process yields methionine oxide (MetO). It renders the sulfur chiral, producing two distinct, diastereomerically related products. Despite the biological significance of Met oxidation, a reliable protocol to separate the resultant MetO diastereomers is currently lacking. This hampers our ability to make peptides and proteins that contain stereochemically defined MetO to then study their structural and functional properties. We have developed a facile method that uses supercritical CO2 chromatography and allows obtaining both diastereomers in purities exceeding 99 %. 1H NMR spectra were correlated with X‐ray structural information. The stereochemical interconversion barrier at sulfur was calculated as 45.2 kcal mol−1, highlighting the remarkable stereochemical stability of MetO sulfur chirality. Our protocol should open the road to synthesis and study of a wide variety of stereochemically defined MetO‐containing proteins and peptides.
Macroscopic Change in Luminescent Color by Thermally Driven Sliding Motion in [3]Rotaxanes
Authors: Inamori Daiki , Masai Hiroshi , Tamaki Takashi , Terao Jun
Published: December 2019

Systematic investigation of rotaxane structures has revealed a rational design for thermally driven switching of their macroscopic properties. At low temperature, the luminophore is insulated by the macrocycles and displays monomer emission, whereas at high temperature, the luminophore is exposed owing to a change in the macrocyclic location distribution and interacts with external molecules, affording a thermally driven luminescent color change with high reversibility and responsiveness. This macroscopic switching through efficient thermal sliding was made possible by appropriate tuning of both the macrocycle–luminophore interactions within the rotaxane and the coupling between the excited luminophore and external molecules in an exciplex. The ability to switch properties by a simple and clean thermal stimuli should expand the utilization of rotaxanes as components of thermally driven molecular systems.
Disparities in risk perception of thyroid cancer recurrence and death
Authors: Chen Debbie W. , Reyes‐Gastelum David , Wallner Lauren P. , Papaleontiou Maria , Hamilton Ann S. , Ward Kevin C. , Hawley Sarah T. , Zikmund‐Fisher Brian J. , Haymart Megan R.
Published: December 2019

Background

To the authors' knowledge, studies regarding risk perception among survivors of thyroid cancer are scarce.

Methods

The authors surveyed patients who were diagnosed with differentiated thyroid cancer from the Surveillance, Epidemiology, and End Results registries of Georgia and Los Angeles County (2632 patients; 63% response rate). The analytic cohort was defined by a ≤5% risk of disease recurrence and mortality (1597 patients). Patients estimated their recurrence and mortality risks separately (increments of 10% and endpoints of ≤5% and ≥95%). Both outcomes were dichotomized between reasonably accurate estimates (risk perception of ≤5% or 10%) versus overestimation (risk perception of ≥20%). Multivariable logistic regression was used to identify factors associated with risk overestimation, and the relationships between overestimation and both worry and quality of life were evaluated.

Results

In the current study sample, 24.7% of patients overestimated their recurrence risk and 12.5% overestimated their mortality risk. A lower educational level was associated with overestimating disease recurrence (≤high school diploma: odds ratio [OR], 1.64 [95% CI, 1.16‐2.31]; and some college: OR, 1.36 [95% CI, 1.02‐1.81]) and mortality (≤high school diploma: OR, 1.86 [95% CI, 1.18‐2.93]) risk compared with those attaining at least a college degree. Hispanic ethnicity was found to be associated with overestimating recurrence risk (OR, 1.44, 95% CI 1.02‐2.03) compared with their white counterparts. Worry about recurrence and death was found to be greater among patients who overestimated versus those who had a reasonably accurate estimate of their risk of disease recurrence and mortality, respectively (P < .001). Patients who overestimated mortality risk also reported a decreased physical quality of life (mean T score, 43.1; 95% CI, 41.6‐44.7) compared with the general population.

Conclusions

Less educated patients and Hispanic patients were more likely to report inaccurate risk perceptions, which were associated with worry and a decreased quality of life.
The emerging role of mediator complex subunit 12 in tumorigenesis and response to chemotherapeutics
Authors: Zhang Shengjie , O’Regan Ruth , Xu Wei
Published: December 2019

Transcriptional dysregulation induced by disease‐defining genetic alterations of proteins in transcriptional machinery is a key feature of cancers. Mediator complex subunit 12 (MED12) is the central architectural subunit in the kinase module of Mediator, a large transcriptional regulatory complex that controls essential steps of transcription. Emerging evidence links deregulated MED12 to human cancers. MED12 is frequently mutated in benign tumors and cancers. Although the missense mutations of MED12 in benign tumors disrupt the kinase activity of Mediator, MED12 mutations in cancers could eliminate the interaction between Mediator complex and RNA polymerase II, leading to severe transcriptional misregulation. Aberrant expression of MED12 is associated with the prognosis of various types of human cancers. Loss of MED12 function has been associated with the development of resistance to chemotherapeutics. Moreover, MED12 is modified by posttranscriptional regulations. Arginine methylation of MED12 has been shown to regulate MED12‐mediated transcriptional regulation and response to chemotherapeutics in human cancer cell lines. In this mini‐review, the authors provide an overview of the roles of MED12 in the development of benign and malignant tumors as well as its roles in chemoresistance. The studies of MED12 exemplify that aberrant transcriptional programming is a therapeutic vulnerability for certain types of cancer.
Hierarchically Organized NiCo2O4 Microflowers Anchored on Multiwalled Carbon Nanotubes: Efficient Bifunctional Electrocatalysts for Oxygen and Hydrogen Evolution Reactions
Authors: Umeshbabu Ediga , Hari Krishna Charan P. , Justin Ponniah , Ranga Rao G.
Published: December 2019

Hierarchical flower‐like NiCo2O4 anchored on multiwalled carbon nanotubes (NiCo2O4‐MCNTs) act as robust bifunctional electrocatalysts towards O2 (OER) and H2 (HER) evolution reactions. The NiCo2O4‐MCNTs hybrid is synthesized in a facile surfactant‐free hydrothermal process, and its flower‐like morphology was shown to consist of 1D nanowires. The MCNT support is beneficial for enhanced reactive sites, efficient charge transfer, and durability of the composite. The material shows low overpotentials of 350 mV and 209 mV for OER and HER, respectively at 10 mA cm−2. Such values are comparable to contemporary noble‐metal catalysts and even lower than reported non‐precious catalysts. Moreover, this hybrid shows high current density, lower Tafel slope, and excellent stability. The synergistic coupling effects between the MCNTs and NiCo2O4 are key factors for the superior catalytic activity of these hybrid materials.
Genetic Factors Influencing Warfarin Dose in Black‐African Patients: A Systematic Review and Meta‐Analysis
Authors: Asiimwe Innocent G. , Zhang Eunice J. , Osanlou Rostam , Krause Amanda , Dillon Chrisly , Suarez‐Kurtz Guilherme , Zhang Honghong , Perini Jamila A. , Renta Jessicca Y. , Duconge Jorge , Cavallari Larisa H. , Marcatto Leiliane R. , Beasly Mark T. , Perera Minoli A. , Limdi Nita A. , Santos Paulo C.J.L. , Kimmel Stephen E. , Lubitz Steven A. , Scott Stuart A. , Kawai Vivian K. , Jorgensen Andrea L. , Pirmohamed Munir
Published: December 2019

Warfarin is the most commonly used oral anticoagulant in sub‐Saharan Africa. Dosing is challenging due to a narrow therapeutic index and high interindividual variability in dose requirements. To evaluate the genetic factors affecting warfarin dosing in black‐Africans, we performed a meta‐analysis of 48 studies (2,336 patients). Significant predictors forCYP2C9and stable dose included rs1799853 (CYP2C9*2), rs1057910 (CYP2C9*3), rs28371686 (CYP2C9*5), rs9332131 (CYP2C9*6), and rs28371685 (CYP2C9*11) reducing dose by 6.8, 12.5, 13.4, 8.1, and 5.3 mg/week, respectively.VKORC1variants rs9923231 (‐1639G>A), rs9934438 (1173C>T), rs2359612 (2255C>T), rs8050894 (1542G>C), and rs2884737 (497T>G) decreased dose by 18.1, 21.6, 17.3, 11.7, and 19.6 mg/week, respectively, whereas rs7294 (3730G>A) increased dose by 6.9 mg/week. Finally, rs12777823 (CYP2Cgene cluster) was associated with a dose reduction of 12.7 mg/week. Few studies were conducted in Africa, and patient numbers were small, highlighting the need for further work in black‐Africans to evaluate genetic factors determining warfarin response.
Oxidative Fluorocyclization of Vinyl Azides Leading to 5‐Azido,5‐fluoro‐1,3‐oxolan‐2‐one
Authors: Li Lin , Cao Shanshan , Lin Fanyi , Liao Peiqiu , Ning Yongquan
Published: December 2019

Vinyl azides have become versatile building blocks in organic synthesis. Most of their transformations usually undergo a fast release of molecular N2 to generate 2H‐aziridine and vinyl nitrene intermediates. However, retaining the azides group in the final product is quite rare and challenging. Herein, we design and validate a new alkene difunctionalization strategy that involves an oxidative fluorocyclization of vinyl azides for the synthesis of a variety of 5‐azido,5‐fluoro‐1,3‐oxolan‐2‐ones with broad substrate scope and good functional group tolerance in good to excellent yields. The in situ removal of a leaving group in this difunctionalization reaction is a key to retain azide moiety in the final product.
Contact mechanical behaviors of radial metal seal for the interval control valve in intelligent well: Modeling and theoretical study
Authors: Yang Yiwei , Zhu Hongwu , He Dongsheng , Du Changcheng , Xu Liangbin , He Yufa , Zheng Yan , Ye Zhewei
Published: December 2019

Intelligent wells equipped with the interval control valve (ICV), which have the potential applications to significantly improve oil production or control the water production of wells and fields, are more and more widely utilized in the oilfields. The radial metal seal of an ICV is intended to isolate the flow of produced fluids between the casing annulus and the well tubing. The contact mechanical behaviors of the radial metal seal are essential to the structural design and reliability of ICVs in the intelligent well. In this paper, the two‐dimensional axisymmetric assembly of the radial metal seal and the closure member is abstracted as a combination of interference fit model and cantilever beam model. Based on that, the related theoretical model, between the radial metal seal's contact stress and its independent variables, has been derived. Next, numerically simulations of contact stress between the radial metal seal and the closure member for different independent variables are conducted by the finite element method (FEM) to validate the theoretical model. It is found that the mean absolute value of relative error between the numerical and theoretical results of the contact stress is approximately 10%. Additionally, the structural parameters of the radial metal seal are proposed with the absolute value of relative error <10%. Furthermore, the value of the contact stress based on the cantilever beam model can be used to calculate an approximation theoretical solution. In summary, the proposed theoretical model provides a foundation for the design, improvement, and selection of radial metal seal under the known oilfield conditions.
Experimental determination of the dielectric constant of wheat grain and cluster straw in different moisture contents
Authors: Jafari Mohammad , Chegini Gholamreza , Rezaeealam Behrooz , Shaygani Akmal Amir Abbas
Published: December 2019

One of the new methods in the removal of impurities from the wheat grains is the electrostatic separation of particles based on the differences in their conductivity and permittivity. The moisture content of particles directly influences their electrical properties. In this study, by developing a cylindrical capacitor in an electrical circuit, the electrical capacitance of wheat grain and cluster straw particles in two varieties at four levels of moisture content (8%, 14%, 20%, and 25%) and five frequency levels (1, 10, 20, 100, and 500 kHz) is estimated and their dielectric constant is calculated. Results showed that increasing the moisture content of straw particles and reducing the frequency compared to the seeds had significant effects on dielectric constant. The dielectric constant of grain particles was higher than the straw at lower moisture content and in high values of moisture content, the dielectric constant of straw particles was higher than the seeds.
Connexin 43 deletion in astrocytes promotes CNS remyelination by modulating local inflammation
Authors: Li Tao , Niu Jianqin , Yu Guangdan , Ezan Pascal , Yi Chenju , Wang Xiaorui , Koulakoff Annette , Gao Xing , Chen Xianjun , Sáez Juan C. , Giaume Christian , Xiao Lan
Published: December 2019

As the most abundant gap junction protein in the central nervous system (CNS), astrocytic connexin 43 (Cx43) maintains astrocyte network homeostasis, affects oligodendroglial development and participates in CNS pathologies as well as injury progression. However, its role in remyelination is not yet fully understood. To address this issue, we used astrocyte‐specific Cx43 conditional knockout (Cx43 cKO) mice generated through the use of a hGFAP‐cre promoter, in combination with mice carrying a floxed Cx43 allele that were subjected to lysolecithin so as to induce demyelination. We found no significant difference in the demyelination of the corpus callosum between Cx43 cKO mice and their non‐cre littermate controls, while the remyelination process in Cx43 cKO mice was accelerated. Moreover, an increased number of mature oligodendrocytes and an unaltered number of oligodendroglial lineage cells were found in Cx43 cKO mouse lesions. This indicates that oligodendrocyte precursor cell (OPC) differentiation was facilitated by astroglial Cx43 depletion as remyelination progressed. Underlying the latter, there was a down‐regulated glial activation and modulated local inflammation as well as a reduction of myelin debris in Cx43 cKO mice. Importantly, 2 weeks of orally administrating boldine, a natural alkaloid that blocks Cx hemichannel activity in astrocytes without affecting gap junctional communication, obviously modulated local inflammation and promoted remyelination. Together, the data suggest that the astrocytic Cx43 hemichannel is negatively involved in the remyelination process by favoring local inflammation. Consequently, inhibiting Cx43 hemichannel functionality may be a potential therapeutic approach for demyelinating diseases in the CNS.
A neurocognitive model of perceptual decision‐making on emotional signals
Authors: Dricu Mihai , Frühholz Sascha
Published: December 2019

Humans make various kinds of decisions about which emotions they perceive from others. Although it might seem like a split‐second phenomenon, deliberating over which emotions we perceive unfolds across several stages of decisional processing. Neurocognitive models of general perception postulate that our brain first extracts sensory information about the world then integrates these data into a percept and lastly interprets it. The aim of the present study was to build an evidence‐based neurocognitive model of perceptual decision‐making on others' emotions. We conducted a series of meta‐analyses of neuroimaging data spanning 30 years on the explicit evaluations of others' emotional expressions. We find that emotion perception is rather an umbrella term for various perception paradigms, each with distinct neural structures that underline task‐related cognitive demands. Furthermore, the left amygdala was responsive across all classes of decisional paradigms, regardless of task‐related demands. Based on these observations, we propose a neurocognitive model that outlines the information flow in the brain needed for a successful evaluation of and decisions on other individuals' emotions.

Highlights

Emotion classification involves heterogeneous perception and decision‐making tasks

Decision‐making processes on emotions rarely covered by existing emotions theories

We propose an evidence‐based neuro‐cognitive model of decision‐making on emotions

Bilateral brain processes for nonverbal decisions, left brain processes for verbal decisions

Left amygdala involved in any kind of decision on emotions
Examining the initial usability, acceptability and feasibility of a digital mental health intervention for college students in India
Authors: Kanuri Nitya , Arora Prerna , Talluru Sai , Colaco Bona , Dutta Rohan , Rawat Abhimanyu , Taylor Barr C. , Manjula M. , Newman Michelle G.
Published: December 2019

Generalised anxiety disorder (GAD) is prevalent among college students in India; however, barriers like stigma, treatment accessibility and cost prevent engagement in treatment. Web‐ and mobile‐based, or digital, mental health interventions have been proposed as a potential solution to increasing treatment access. With the ultimate goal of developing an engaging digital mental health intervention for university students in India, the current study sought to understand students' reactions to a culturally and digitally adapted evidence‐based cognitive behavioural therapy (CBT) for GAD intervention. Specifically, through theatre testing and focus groups with a non‐clinical sample of 15 college students in India, the present study examined initial usability, acceptability and feasibility of the “Mana Maali Digital Anxiety Program.” Secondary objectives comprised identifying students' perceived barriers to using the program and eliciting recommendations. Results indicated high usability, with the average usability rating ranking in the top 10% of general usability scores. Participants offered actionable changes to improve usability and perceived acceptability among peers struggling with mental health issues. Findings highlight the benefits of offering digital resources that circumvent barriers associated with accessing traditional services. Results build on existing evidence that digital interventions can be a viable means of delivering mental healthcare to large, defined populations.
The role of risk‐benefit and privacy analysis to understand different uses of social media by Generations X, Y, and Z in Indonesia
Authors: Nuzulita Nania , Subriadi Apol Pribadi
Published: December 2019

This research aims to analyse how perceived benefits and risks drive social media use despite the concern for privacy violations in Indonesia. The focus of the study is to investigate the pattern of social media use based on generational age groups. An approach based on the combination of Privacy Calculus Theory and Communication Privacy Management is used to explain the patterns of social media use. Privacy awareness and information manipulation help solving the constant social media use despite the concern for privacy violations. The findings show that Generation X uses social media mainly to maintain existing relationships. Generation Y uses social media for business and building self‐image. Generation Z uses social media for more varied purposes, eg, developing and maintaining connections, building self‐image, expressing thoughts and emotions, and seeking entertainment. Further research can use the proposed conceptual model as a quantitative approach to get broader perspectives on the issue and add demographic factors. Future research can also highlight the types of social media to generate more real results.
Cytotoxicity of vanadium oxide nanoparticles and titanium dioxide‐coated vanadium oxide nanoparticles to human lung cells
Authors: Xi Wen‐Song , Tang Huan , Liu Yuan‐Yuan , Liu Chun‐Yuan , Gao Yanfeng , Cao Aoneng , Liu Yuanfang , Chen Zhang , Wang Haifang
Published: December 2019

Due to excellent metal–insulator transition property, vanadium dioxide nanoparticles (VO2 NPs)‐based nanomaterials are extensively studied and applied in various fields, and thus draw safety concerns of VO2 NPs exposure through various routes. Herein, the cytotoxicity of VO2 NPs (N‐VO2) and titanium dioxide‐coated VO2 NPs (T‐VO2) to typical human lung cell lines (A549 and BEAS‐2B) was studied by using a series of biological assays. It was found that both VO2 NPs induced a dose‐dependent cytotoxicity, and the two cell lines displayed similar sensitivity to VO2 NPs. Under the same conditions, T‐VO2 NPs showed slightly lower cytotoxicity than N‐VO2 in both cells, indicating the surface coating of titanium dioxide mitigated the toxicity of VO2 NPs. Titanium dioxide coating changed the surface property of VO2 NPs and reduced the vanadium release of particles, and thus helped lowing the toxicity of VO2 NPs. The induced cell viability loss was attributed to apoptosis and proliferation inhibition, which were supported by the assays of apoptosis, mitochondrial membrane damage, caspase‐3 level, and cell cycle arrest. The oxidative stress, i.e., enhanced reactive oxygen species generation and suppressed reduced glutathione , in A549 and BEAS‐2B cells was one of the major mechanisms of the cytotoxicity of VO2 NPs. These findings provide safety guidance for the practical applications of vanadium dioxide‐based materials.
Preclinical safety evaluation of ET‐26 hydrochloride, a novel intravenous anesthetic agent, in beagle dogs
Authors: Zhang YuJun , Deng ChaoYi , Gong DeYing , Kang Yi , Liu Jin , Zhang WenSheng
Published: December 2019

ET‐26 hydrochloride (ET‐26HCl) is a novel etomidate analogue, approved for clinical trials, which has an effective sedative‐hypnotic effect, a stable myocardial performance, and milder adrenocortical suppression than etomidate in rats and beagle dogs. Additionally, ET‐26HCl showed similar hemodynamic stability as etomidate in the rat uncontrolled hemorrhagic shock model. Furthermore, ET‐26HCl, in the rat lipopolysaccharide‐induced sepsis model, was found to have a higher survival rate, a lower inflammatory reaction, and less organ injury. In the present study, we measured the potential adverse effects of ET‐26HCl in beagle dogs in accordance with the Guidance on single‐ and repeated‐dose toxicity published by the China Food and Drug Administration. In toxicity studies, single and repeated (14 days) intravenous doses of up to 16 mg/kg were well tolerated, with only pharmacologically related clinical signs seen in both studies. Thus, the no‐observed‐adverse‐effect level (NOAEL) of ET‐26HCl was found at 16 mg/kg/day. Toxicokinetic examination demonstrated that ET‐26HCl showed a dose‐dependent increase to exposure, no gender difference, and no evidence of accumulation. These results provide useful information for guiding a phase I clinical trial of ET‐26HCl in healthy volunteers.
A novel de novo dominant mutation of NOTCH1 gene in an Iranian family with non‐syndromic congenital heart disease
Authors: Kalayinia Samira , Maleki Majid , Mahdavi Mohammad , Mahdieh Nejat
Published: December 2019

Background

Congenital heart disease (CHD) is the most common birth defect which can arises from different genetic defects. The genetic heterogeneity of this disease leads to restricted success in candidate genes screening method. Emerging approaches such as next‐generation sequencing (NGS)‐based genetic analysis might provide a better understating of CHD etiology in the patients who are left undiagnosed. To this aim, in this study, we survived the causes of CHD in an Iranian family who was consanguineous and had two affected children.

Methods

Affected individuals of this family were checked previously by PCR‐direct sequencing for six candidate genes (NKX2‐5, ZIC3, NODAL, FOXH1, GJA1, GATA4) and had not revealed any reported CHD causative mutations. Whole‐exome sequencing (WES) was performed on this family probond to determine the underlying cause of CHD, and the identified variants were confirmed and segregated by Sanger sequencing.

Results

We identified one heterozygous missense mutation, c.T6797C (p.Phe2266Ser), in the NOTCH1 gene, which seems to be the most probably disease causing of this family patients. This mutation was found to be novel and not reported on 1000 Genomes Project, dbSNP, and ExAC.

Conclusion

Worldwide, mutations in NOTCH1 gene are considered as one of the most known causes of CHD. The found NOTCH1 variant in this family affected individuals was the first report from Iran. Yet again, this result indicates the importance of NOTCH1 screening in CHD patients.
Values of 5mC, 5hmC, and TET2 for identifying the presence and progression of breast precancerous lesion
Authors: Zhang Zijing , Jin Yiting , Zhang Wei , Chu Chengyu , Zhang Ke , Gao Xingyan , Zhou Jian , Zou Liping , Tang Feng , Wang Hongying , Zou Qiang
Published: December 2019

Background

This study aimed to evaluate the correlations of 5‐methylcytosine (5mC), 5‐hydroxymethylcytosine (5hmC), and ten‐eleven translocation enzyme 2 (TET2) expressions in lesion tissue with histological classification of breast precancerous lesion.

Methods

Eighty‐three patients with breast ductal intraepithelial neoplasia (DIN), 20 patients with breast ductal carcinoma in situ with microinvasion (DCIS‐MI), and 10 patients with invasive breast cancer were included. Histological classification of the DIN patients was classified as DIN1A, DIN1B, DIN1C, DIN2, and DIN3. 5mC, 5hmC, and TET2 expressions in lesion tissues from biopsy were assessed by immunohistochemistry (IHC) assay.

Results

5hmC and TET2 were negatively associated with histological classification as validated by both IHC score and IHC semi‐quantification expression grades in total patients (all P < .05); however, no correlation of 5mC with histological classification was found (all P > .05). 5mC (P = .004) was negatively but 5hmC (P < .001) was positively correlated with TET2, while no association of 5mC with 5hmC was discovered in total patients (P = .078). In addition, 5mC was positively associated with ER expression in total patients (P = .040). In subgroups, 5mC was negatively correlated with 5hmC in DIN1C patients (P = .023) and invasive cancer patients (P = .044), and 5mC was negatively associated with TET2 in DIN1B patients (P = .004) as well as DCIS‐MI patients (P = .003).

Conclusion

5hmC and TET2 have the potentials to serve as biomarkers that could assist in the identification of presence and progression of breast precancerous lesion.
The epigenetic reader Brd4 is required for osteoblast differentiation
Authors: Paradise Christopher R. , Galvan M. Lizeth , Kubrova Eva , Bowden Sierra , Liu Esther , Carstens Mason F. , Thaler Roman , Stein Gary S. , van Wijnen Andre J. , Dudakovic Amel
Published: December 2019

Transcription networks and epigenetic mechanisms including DNA methylation, histone modifications, and noncoding RNAs control lineage commitment of multipotent mesenchymal progenitor cells. Proteins that read, write, and erase histone tail modifications curate and interpret the highly intricate histone code. Epigenetic reader proteins that recognize and bind histone marks provide a crucial link between histone modifications and their downstream biological effects. Here, we investigate the role of bromodomain‐containing (BRD) proteins, which recognize acetylated histones, during osteogenic differentiation. Using RNA‐sequencing (RNA‐seq) analysis, we screened for BRD proteins (n = 40) that are robustly expressed in MC3T3 osteoblasts. We focused functional follow‐up studies on Brd2 and Brd4 which are highly expressed in MC3T3 preosteoblasts and represent “bromodomain and extra terminal domain” (BET) proteins that are sensitive to pharmacological agents (BET inhibitors). We show that small interfering RNA depletion of Brd4 has stronger inhibitory effects on osteoblast differentiation than Brd2 loss as measured by osteoblast‐related gene expression, extracellular matrix deposition, and alkaline phosphatase activity. Similar effects on osteoblast differentiation are seen with the BET inhibitor +JQ1, and this effect is reversible upon its removal indicating that this small molecule has no lasting effects on the differentiation capacity of MC3T3 cells. Mechanistically, we find that Brd4 binds at known Runx2 binding sites in promoters of bone‐related genes. Collectively, these findings suggest that Brd4 is recruited to osteoblast‐specific genes and may cooperate with bone‐related transcription factors to promote osteoblast lineage commitment and maturation.
Manganese oxides supported on ACFN by a one‐step redox method for the low‐temperature NOx reduction with NH3: effect of acid addition
Authors: Tang Xiaolong , Gu Tian , Yi Honghong , Zhao Shunzheng , Gao Fengyu , Zhang Runcao , Wang Yuhe
Published: December 2019

BACKGROUND

In this study, manganese dioxide (MnO2) was formed in situ on the surface of ACFN (nitric acid modified activated carbon fibres) by a one‐step redox method for the selective catalytic reduction (SCR) of nitric oxides (NOx) with ammonia (NH3) at low temperature. Meanwhile, the water and sulfur dioxide (H2O and SO2) deactivation mechanism were investigated.

RESULTS

Each acid, including hydrochloric, nitric and acetic (HCl, HNO3 and CH3COOH), released H+ in solution at different rates, which lead to distinct pH environments. As the driving force, it has an effect on the redox reaction, resulting in the different MnO2 amount and performance of the MnO2/ACFN catalysts. The MnO2/ACFN (CH3COOH) catalyst exhibited good NH3‐SCR activity, water resistance and sulfur resistance.

CONCLUSION

The MnO2/ACFN (CH3COOH) catalyst showed 3D growth and uniform distribution of MnO2 sheets on the surface of the support, which resulted in a larger specific surface area and better redox properties. The CH3COOH can gradually decompose H+ so that H+ is given priority to internal diffusion. The redox reaction preferentially took place in the interior, thereby promoting the formation of more MnO2, which is beneficial to the NH3‐SCR reaction. © 2019 Society of Chemical Industry
Development of a Novel Multiparametric MRI Radiomic Nomogram for Preoperative Evaluation of Early Recurrence in Resectable Pancreatic Cancer
Authors: Tang Tian‐Yu , Li Xiang , Zhang Qi , Guo Cheng‐Xiang , Zhang Xiao‐Zhen , Lao Meng‐Yi , Shen Yi‐Nan , Xiao Wen‐Bo , Ying Shi‐Hong , Sun Ke , Yu Ri‐Sheng , Gao Shun‐Liang , Que Ri‐Sheng , Chen Wei , Huang Da‐Bing , Pang Pei‐Pei , Bai Xue‐Li , Liang Ting‐Bo
Published: December 2019

Background

In pancreatic cancer, methods to predict early recurrence (ER) and identify patients at increased risk of relapse are urgently required.

Purpose

To develop a radiomic nomogram based on MR radiomics to stratify patients preoperatively and potentially improve clinical practice.

Study Type

Retrospective.

Population

We enrolled 303 patients from two medical centers. Patients with a disease‐free survival ≤12 months were assigned as the ER group (n = 130). Patients from the first medical center were divided into a training cohort (n = 123) and an internal validation cohort (n = 54). Patients from the second medical center were used as the external independent validation cohort (n = 126).

Field Strength/Sequence

3.0T axial T1‐weighted (T1‐w), T2‐weighted (T2‐w), contrast‐enhanced T1‐weighted (CET1‐w).

Assessment

ER was confirmed via imaging studies as MRI or CT. Risk factors, including clinical stage, CA19‐9, and radiomic‐related features of ER were assessed. In addition, to determine the intra‐ and interobserver reproducibility of radiomic features extraction, the intra‐ and interclass correlation coefficients (ICC) were calculated.

Statistical Tests

The area under the receiver‐operator characteristic (ROC) curve (AUC) was used to evaluate the predictive accuracy of the radiomic signature in both the training and test groups. The results of decision curve analysis (DCA) indicated that the radiomic nomogram achieved the most net benefit.

Results

The AUC values of ER evaluation for the radiomics signature were 0.80 (training cohort), 0.81 (internal validation cohort), and 0.78 (external validation cohort). Multivariate logistic analysis identified the radiomic signature, CA19‐9 level, and clinical stage as independent parameters of ER. A radiomic nomogram was then developed incorporating the CA19‐9 level and clinical stage. The AUC values for ER risk evaluation using the radiomic nomogram were 0.87 (training cohort), 0.88 (internal validation cohort), and 0.85 (external validation cohort).

Data Conclusion

The radiomic nomogram can effectively evaluate ER risks in patients with resectable pancreatic cancer preoperatively, which could potentially improve treatment strategies and facilitate personalized therapy in pancreatic cancer.

Level of Evidence: 4

Technical Efficacy: Stage 4

J. Magn. Reson. Imaging 2020;52:231–245.
Characterization of synovial fluid from periprosthetic infection in revision total joint arthroplasty by single‐molecule microscopy
Authors: Kohlhof Hendrik , Fröschen Frank S. , Randau Thomas M. , Hischebeth Gunnar , Kehrer Michael , Wirtz Dieter C. , Schildberg Frank A. , Kaminski Tim P.
Published: December 2019

Periprosthetic joint infection is among the most common and severe complications in total joint arthroplasty. Today, a combination of different methods is used for diagnosis because no single method with sufficient sensitivity and specificity is available. In this study, we explored the usability of single‐molecule microscopy to characterize synovial fluid samples from periprosthetic joint infections. Patients (n = 27) that needed revision arthroplasty underwent the routine diagnostic procedures for periprosthetic joint infection of the University Hospital in Bonn. Additionally, the diffusion rate of two probes, dextran and hyaluronan, was measured in small volumes of periprosthetic synovial fluid samples using single‐molecule microscopy. To evaluate the suitability of single‐molecule microscopy to detect PJI the AUC for both markers was calculated. The diffusion rate of hyaluronan in periprosthetic synovial fluid from patients with septic loosening was faster than in samples from patients with aseptic loosening. Single‐molecule microscopy showed excellent diagnostic performance, with an area under the receiver operating characteristic curve of 0.93, and allowed the detection of periprosthetic joint infection in patients that would be challenging to diagnose with current methods. For the first time, single‐molecule microscopy was used to detect periprosthetic joint infection. Our results are encouraging to study the value of single‐molecule microscopy in a larger patient cohort. The speed and accuracy of single‐molecule microscopy can be used to further characterize synovial fluid, potentially allowing intraoperative diagnosis of periprosthetic joint infections in the future.
Combination of high‐resolution accurate mass spectrometry and network pharmacology provides a new method for the chemical constituents’ study and target prediction in vivo of Garcinia multiflora
Authors: Li Zhuolun , Zuo Lihua , Shi Yingying , Tian Dongsong , Liu Liwei , Yang Yantao , Zhou Lin , Zhang Xiaojian , Kang Jian , Hao Xiaojiang , Yuan Chunmao , Sun Zhi
Published: December 2019

Garcinia multiflora is a kind of evergreen tree which is widely distributed in the south of China. However, few researches focused on the constituents in different parts of G. multiflora as well as their potential targets and pathways in vivo. To clarify the chemical constituents of G. multiflora rapidly and predict the potential targets as well as pathways in vivo that this plant may have effects on, a feasible and accurate strategy was developed to identify the chemical constituents in fruits, leaves, and branches of G. multiflora by ultra‐high performance liquid chromatography with Q‐Exactive hybrid quadrupole‐orbitrap high‐resolution accurate mass spectrometry. Network pharmacology was then employed and a “compounds‐targets‐diseases” network was established. Sixty‐one compounds including polycyclic polyprenylated acylphloroglucinols, xanthones, and flavonoids were finally identified in different parts of G. multiflora, and the contents of seven constituents were quantified, respectively. On the basis of the network pharmacology analysis results, compounds in this plant were speculated to have potential pharmacodynamic effect on cancer, inflammatory, respiratory diseases, cardiovascular diseases, and metabolic diseases. This research will provide a new method for the advanced study on the pharmacodynamic materials basis of G. multiflora, and offer valuable evidences for medicinal purpose of this plant.