bluuebunny/crossref_metadata_2025 huggingface dataset:
Klf4 Promotes Dentinogenesis and Odontoblastic Differentiation via Modulation of TGF-β Signaling Pathway and Interaction With Histone Acetylation
Authors: Tao Huangheng , Lin Heng , Sun Zheyi , Pei Fei , Zhang Jie , Chen Shuo , Liu Huan , Chen Zhi
Published: May 2019

Transcription factors bind to cell-specific cis-regulatory elements, such as enhancers and promoters, to initiate much of the gene expression program of different biological process. Odontoblast differentiation is a necessary step for tooth formation and is also governed by a complex gene regulatory network. Our previous in vitro experiments showed that Krüppel-like factor 4 (KLF4) can promote odontoblastic differentiation of both mouse dental papillary cells (mDPCs) and human dental pulp cells; however, its mechanism remains unclear. We first used Wnt1-Cre; KLF4fx/fx (Klf4 cKO) mice to examine the role of KLF4 during odontoblast differentiation in vivo and demonstrated significantly impaired dentin mineralization and enlarged pulp/root canals. Additionally, combinatory analysis using RNA-seq and ATAC-seq revealed genomewide direct regulatory targets of KLF4 in mouse odontoblasts. We found that KLF4 can directly activate the TGF-β signaling pathway at the beginning of odontoblast differentiation with Runx2 as a cofactor. Furthermore, we found that KLF4 can directly upregulate the expression levels of Dmp1 and Sp7, which are markers of odontoblastic differentiation, through binding to their promoters. Interestingly, as a transcription factor, KLF4 can also recruit histone acetylase as a regulatory companion to the downstream target genes to positively or negatively regulate transcription. To further investigate other regulatory companions of KLF4, we chose histone acetylase HDAC3 and P300. Immunoprecipitation demonstrated that KLF4 interacted with P300 and HDAC3. Next, ChIP analysis detected P300 and HDAC3 enrichment on the promoter region of KLF4 target genes Dmp1 and Sp7. HDAC3 mainly interacted with KLF4 on day 0 of odontoblastic induction, whereas P300 interacted on day 7 of induction. These temporal-specific interactions regulated Dmp1 and Sp7 transcription, thus regulating dentinogenesis. Taken together, these results demonstrated that KLF4 regulates Dmp1 and Sp7 transcription via the modulation of histone acetylation and is vital to dentinogenesis. © 2019 American Society for Bone and Mineral Research.
Development of α4 integrin DNA aptamer as a potential therapeutic tool for multiple sclerosis
Authors: Kouhpayeh Shirin , Hejazi Zahra , Boshtam Maryam , Mirian Mina , Rahimmanesh Ilnaz , Darzi Leila , Rezaei Abbas , Shariati Laleh , Khanahmad Hossein
Published: May 2019

One of the most important molecules for multiple sclerosis pathogenesis is α4 integrin, which is responsible for autoreactive leukocytes migration into the brain. The monoclonal antibody, natalizumab, was introduced to market for blocking the extravasation of autoreactive leukocytes via inhibition of α4 integrin. However, the disadvantages of antibodies provided a suitable background for other agents to be replaced with antibodies. Considering the profound advantages of aptamers over antibodies, aptamer isolation against α4 integrin was intended in the current study. The α4 integrin‐specific aptamers were selected using cell‐systematic evolution of ligands by exponential enrichment (SELEX) method with human embryonic kidney (HEK)‐293T overexpressing α4 integrin and HEK‐293T as target and control cells, respectively. Evaluation of selected aptamer was performed through flow cytometric analysis. The selected clones were then sequenced and analyzed for any possible secondary structure and affinity. The results of this study led to isolation of 13 different single‐stranded DNA clones in 11 rounds of selection which were categorized to three clusters based on common structural motifs and the equilibrium dissociation constant (K
d) of the most stable structure was calculated. The evaluation of SELEX progress showed growth in aptamer affinity with increasing of the number of cycles. Taken together, the findings of this study demonstrated the isolation of α4‐specific single‐stranded DNA aptamers with suitable affinity for ligand, which can further be replaced with natalizumab.
Impaired spermatogenesis associated with changes in spatial arrangement of Sertoli and spermatogonial cells following induced diabetes
Authors: Sajadi Ensieh , Dadras Sara , Bayat Mohammad , Abdi Shabnam , Nazarian Hamid , Ziaeipour Sanaz , Mazini Fatemeh , Kazemi Mahsa , Bagheri Mohammad , Valizadeh Aida , Abdollahifar Mohammad‐Amin
Published: May 2019

The current study was conducted to assess the relationship between testicular cells in spermatogenesis, through which the production of healthy and mature sperm is essential. However, it seems necessary to obtain more information about the three‐dimensional pattern of the testis cells arrangement, which is directly related to the function of the testis after induction of diabetes.

Twelve adult mice (28‐30 g) were assigned into two experimental groups: (1) control and (2) diabetic (40 mg/kg STZ). The epididymal sperm collected from the tail of the epididymis and testes samples were taken for stereology, immunocytochemistry and RNA extraction. Our data showed that diabetes could notably decrease the number of testicular cells, together with a reduction of total sperm count. In addition, the results from the second‐order stereology indicated the significant changes in the spatial arrangement of Sertoli cells and spermatogonial cells in the diabetic groups, in comparison with the control (P < .05). Moreover, the immunohistochemistry results showed a significant reduction in Sex‐determining Region Y (SRY) box 9 gene (SOX9), vimentin, occludin, and connexin‐43 positive cells in the diabetic groups compared with the control (P < .05). Furthermore, our data showed that the expression of steroidogenic acute regulatory protein steroidogenic acute regulatory protein (StAR) and peripheral benzodiazepine receptor peripheral benzodiazepine receptor (PBR) was significantly reduced in the diabetic groups, in comparison with the control (P < .05). These findings suggest that structural and functional changes of testis cells after induction of diabetes cause the alterations in the spatial arrangement of Sertoli and spermatogonial cells, ultimately influencing the normal spermatogenesis in mice.
Circular RNA expression profile of knee condyle in osteoarthritis by illumina HiSeq platform
Authors: Xiao Ke , Xia Zenan , Feng Bin , Bian Yanyan , Fan Yu , Li Zeng , Wu Zhihong , Qiu Guixing , Weng Xisheng
Published: May 2019

Osteoarthritis (OA) is the utmost commonly arising joint disease. Knee condyles play an essential role during OA progression. Circular RNA (or circRNA) is a novel kind of RNA, which, unlike the well‐known linear RNA, plays an important regulatory role in OA on the basis of a previous research. In our study, expression of circRNAs in OA knee condyle was measured by illumine sequencing platform. A total of 197 differentially expressed circRNAs, such as hg38_circ_0007474 and hg38_circ_0000118 were identified, and 21 target miRNAs, 2466 source genes and 166 394 circRNA‐miRNA‐mRNA pairs were predicted. Further analysis was applied on three OA‐related circRNAs (hsa_circ_0045714, hsa_circ_0002485, and hsa_circ_0005567). The results were partly verified by previous studies. Further biological research is needed to unfold the possible pathway and therapeutic target of OA.
Retracted: Overexpression of miR‐4286 is an unfavorable prognostic marker in individuals with non–small cell lung cancer
Authors: An Xian , Ge Jiwen , Guo Huihui , Mi Huaixue , Zhou Jinhua , Liu Yongrui , Weiyue  , Wu Zhilian
Published: May 2019

Non–small cell lung cancer (NSCLC) is still an unresolved source of tumor‐related death internationally. Current studies have discovered that microRNAs (miRNAs) are associated with diverse cancers development, including NSCLC. Our paper focused on the functional character of miR‐4286 in NSCLC. miR‐4286 level in 68 cases of NSCLC tissues, matched neighboring nontumor tissues and different cancer cell lines were inspected by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The connection concerning miR‐4286 expression and clinicopathological features of patients with NSCLC were further determined. After knockdown or overexpression of miR‐4286, cell viability, cell cycle, and/or apoptotic cells were examined by 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) and flow cytometry assay, respectively. Moreover, the cell cycle‐ and apoptosis‐related proteins were estimated by qRT‐PCR and Western blot. In comparison with the matched nontumor tissues, miR‐4286 was significantly enhanced in lung malignancy tissues and different cell lines. miR‐4286 expression was related with the tumor‐node‐metastasis stage, lymphatic metastasis, and distant metastasis. Cell viability was ominously weakened by suppression of miR‐4286 in A549 cells, whereas was statistically upregulated by overexpression of miR‐4286 in NCI‐H1299 cells. Additionally, we detected that suppression of miR‐4286 tempted cell cycle arrest in G1 stage and fortified apoptosis in A549 cells. Runx3 was recognized as one target gene of miR‐4286, and the impacts of suppression of miR‐4286 on cell viability and apoptosis were through regulation of Runt‐related transcription factor 3. Our study suggests that miR‐4286 overexpression represents a tumor promoter role in NSCLC cells.
Disconfirming Expectations: Incorrect Imprecise (vs. Precise) Estimates Increase Source Trustworthiness and Consumer Loyalty
Authors: Pena‐Marin Jorge , Wu Ruomeng
Published: May 2019

Estimations that include numerical information are ubiquitous in our daily lives, for example, housing prices, calories, etc. In the present work, we investigate how the type of information used in an estimate, particularly its level of imprecision, influences evaluations of source trustworthiness after the target value of the estimate is revealed. Specifically, building upon prior work suggesting that (a) imprecise estimates are perceived to be less accurate than precise estimates and (b) performing below expectations results in negative source evaluations, we hypothesize that if the estimate is revealed to be incorrect, imprecise estimates (i.e., 400) elicit higher source trustworthiness than precise estimates (i.e., 417), even if the imprecise estimate is objectively more incorrect (i.e., target value: 570). In addition, we find that this effect also influences consumers’ loyalty toward the source of the estimate. Four studies and a single‐paper meta‐analysis offer triangulating evidence for this prediction and its underlying psychological mechanism. Overall, this work contributes to research on estimates, source evaluations, numerical information, and the influence of errors on consumer behavior.
Communication pitfalls in interpreted genetic counseling sessions
Authors: Ault Rachel , Morales Ana , Ault Russell , Spitale Allison , Martinez Glenn A.
Published: May 2019

The impact of language interpretation on interactive communication in genetic counseling sessions is not well studied. We sought to determine whether interpretation affects communication in genetic counseling sessions using communication analysis. With a sample of pregnant patients of advanced maternal age, we audiotaped, analyzed, and compared seven Spanish‐speaking patients with limited‐English proficiency to seven English‐speaking patients on length of session, English words spoken, and number of questions asked. An analysis of verbal listening cues, including back‐channels and questions asked was performed to evaluate the level of engagement by both provider and patient. Session length did not differ between groups (p > 0.05), however, English‐speaking sessions involved significantly more words (mean: 4,798 vs. 2,524) exchanged over the course of the conversation than interpreter‐mediated sessions (p < 0.001). The number of back‐channeling responses was significantly greater in English‐speaking compared to Spanish‐speaking sessions. We found the same information was covered, but there was less provider–patient interaction when the session was interpreter‐mediated. The patient asked fewer questions and the genetic counselor spoke in condensed ideas. Overall, our observations suggest diminished levels of interactive communication in interpreter‐mediated sessions. Our work highlights the need for further evaluation in how genetic counselors communicate during interpreter‐mediated sessions.
A qualitative study of socially isolated patients’ perceptions of primary care
Authors: Aoki Takuya , Urushibara‐Miyachi Yuka
Published: May 2019

Background

Although the previous quantitative study revealed that social isolation was negatively associated with patient experience of primary care, the underlying reasons for this phenomenon remain unclear. In the present study, we aimed to explore the reasons underlying the influence of social isolation on patient experience in the primary care setting.

Methods

This study was a qualitative study and part of a mixed methods research. Semistructured telephone interviews were performed. We recruited participants among eligible participants in the previous quantitative survey who were classified as being socially isolated. Data were transcribed verbatim and analyzed thematically by two independent researchers until saturation was reached.

Results

Eight socially isolated patients in the research were interviewed. In the thematic analysis, three major themes emerged as reasons underlying the influence of social isolation on patient experience of primary care: restriction of information about local primary care physicians, finding a usual primary care physician haphazardly, and superficial relationship with a usual primary care physician.

Conclusions

This study identified three major themes, which are beneficial to expand our understanding of socially isolated patients’ perceptions of primary care. These findings can be used to improve patient experience of primary care in socially isolated patients.
Quantitative cardiac MRI
Authors: Seraphim Andreas , Knott Kristopher D. , Augusto Joao , Bhuva Anish N. , Manisty Charlotte , Moon James C.
Published: May 2019

Cardiac MRI has become an indispensable imaging modality in the investigation of patients with suspected heart disease. It has emerged as the gold standard test for cardiac function, volumes, and mass and allows noninvasive tissue characterization and the assessment of myocardial perfusion. Quantitative MRI already has a key role in the development and incorporation of machine learning in clinical imaging, potentially offering major improvements in both workflow efficiency and diagnostic accuracy. As the clinical applications of a wide range of quantitative cardiac MRI techniques are being explored and validated, we are expanding our capabilities for earlier detection, monitoring, and risk stratification of disease, potentially guiding personalized management decisions in various cardiac disease models. In this article we review established and emerging quantitative techniques, their clinical applications, highlight novel advances, and appraise their clinical diagnostic potential.

Level of Evidence: 2

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2020;51:693–711.
An approach for determining thermal resistance model parameters of SiGe HBT
Authors: Wang Boran , Zhang Ao , Zhang Yixin , Gao Jianjun
Published: May 2019

This paper presents an improved method for determining the thermal resistance and junction temperature for silicon germanium heterojunction bipolar transistors. This method is a full analytical procedure without any iteration based on a set of accurate expressions. The thermal resistance is tested against iterative and analytic methods reported before. Good agreement is obtained between simulated and measured results for three SiGe devices with different emitter geometries.
Toll‐like receptor‐2 and ‐4 responses regulate neutrophil infiltration into the junctional epithelium and significantly contribute to the composition of the oral microbiota
Authors: Chang Ana M. , Liu Quanhui , Hajjar Adeline M. , Greer Ara , McLean Jeffrey S. , Darveau Richard P.
Published: May 2019

Background

Oral gingival tissue, especially the junctional epithelium (JE), is constantly exposed to sub‐gingival plaque. A key component of gingival health is the regulation of the number of neutrophils that migrate into the gingival crevice to counteract its harmful effects. This report investigates the contribution of innate defense receptors, Toll‐like receptor (TLR)2, TLR4, and both (TLR2/4) to the maintenance of neutrophil homeostasis in the JE.

Methods

Bacterial composition was analyzed from whole oral swabs collected from 12‐ to 14‐week‐old TLR2, TLR4, TLR2/4 double knock‐out (KO) mice using a MiSeq platform targeting the V3‐V4 region of the 16S ribosomal RNA gene. Mandibles were histologically examined for quantification of neutrophils in the JE and bone loss. Lastly, total bacterial load was quantitated using quantitative real‐time PCR.

Results

Compared with wild‐type, all TLR KO mice displayed significantly increased recruitment of neutrophils (P = 0.0079) into the JE. In addition, TLR4 and TLR2/4 KO mice demonstrated a significant increase in the number of bacteria (P = 0.0022 and P = 0.0152, respectively). Lastly, comparative compositional analyses of the oral microbiome revealed that each KO strain harbored unique microbial communities that are distinct from each other but maintained similar levels of alveolar bone.

Conclusions

Neutrophil migration into healthy mouse JE does not require TLR2 or TLR4. However, a significant increase in the number of neutrophils as well as a significant change in the oral microbial composition in both TLR2 and TLR4 KO mice demonstrate that these TLRs contribute to the homeostatic relationship between bacteria and the host in healthy mice periodontal tissue.
Identifying subgroups of well‐being among patients with cancer: Differences in attitudes and preferences around surveillance after curative‐intent surgery
Authors: Kelly Elizabeth Palmer , Hyer J. Madison , Onuma Amblessed E. , Paredes Anghela Z. , Tsilimigras Diamantis I. , Pawlik Timothy M.
Published: May 2019

Background

Patient perceptions and preferences related to postoperative surveillance are not yet well defined.

Methods

A cross‐sectional analysis of the surveillance practice preferences and attitudes was undertaken based on subgroups derived from clustering participants for measures of well‐being, including financial toxicity, emotional, family/social, and functional well‐being.

Results

Among 212 participants, the average age was 58.1 years and most patients were female (57.1%) and white (90.2%). Common malignancies included melanoma/sarcoma (26.4%), thyroid (25.5%), breast (18.9%), gastrointestinal (18.4%), and lung (7.5%) cancer. Respondents within the highest well‐being subgroup rated their perception of communication as being the highest more consistently compared with the other well‐being subgroups (P = .005). Participants with the highest level of well‐being felt more reassured by follow‐up appointments (Subgroup 1, Med = 4.00, interquartile range (IQR) = 0.25 vs subgroup 4, Med = 3.75, IQR = 0.73, P = .023). In contrast, patients with the lowest sense of well‐being had the highest level of nervousness related to surveillance (subgroup 1, Med = 1.60, IQR = 1.00 vs subgroup 4, Med = 2.20, IQR = 1.15, P < .001). There were no differences in surveillance frequency preferences among different well‐being subgroups.

Conclusion

Attitudes towards postoperative surveillance varied with regard to perception of provider communication, nervous anticipation, and assuredness depending on overall patient well‐being. Providers should attempt to assess patient well‐being as part of a tailored approach to postcancer surgery surveillance.
Identifying the reactive metabolites of tyrosine kinase inhibitors in a comprehensive approach: Implications for drug‐drug interactions and hepatotoxicity
Authors: Paludetto Marie‐Noëlle , Puisset Florent , Chatelut Etienne , Arellano Cécile
Published: May 2019

Tyrosine kinase inhibitors (TKI) are small heterocyclic molecules targeting transmembrane and cytoplasmic tyrosine kinases that have met with considerable success in clinical oncology. TKI are associated with toxicities including liver injury that may be serious and even life‐threatening. Many of them require warnings in drug labeling against liver injury, and five of them have Black Box Warning (BBW) labels. Although drug‐induced liver injury is a matter of clinical and industrial concern, little is known about the underlying mechanisms that likely involve reactive metabolites (RM). RM are electrophiles or radicals originating from the metabolic activation of particular functional groups, known as structural alerts or toxicophores. RM are able to covalently bind to proteins and macromolecules, causing cellular damage and even cell death. If the adducted protein is the enzyme involved in RM formation, time‐dependent inhibition of the enzyme—also called mechanism‐based inhibition (MBI) or inactivation—can occur and lead to pharmacokinetic drug‐drug interactions. To mitigate RM liabilities, common practice in drug development includes avoiding structural alerts and assessing RM formation via RM trapping screens with soft and hard nucleophiles (glutathione, potassium cyanide, and methoxylamine) in liver microsomes. RM‐positive derivatives are further optimized to afford drug candidates with blocked or minimized bioactivation potential. However, different structural alerts are still commonly used scaffolds in drug design, including in TKI structures. This review focuses on the current state of knowledge of the relations among TKI structures, bioactivation pathways, RM characterization, and hepatotoxicity and cytochrome P450 MBI in vitro.
Repurposing drugs as pro‐oxidant redox modifiers to eliminate cancer stem cells and improve the treatment of advanced stage cancers
Authors: Ralph Stephen J. , Nozuhur Sam , ALHulais Reem Ali , Rodríguez‐Enríquez Sara , Moreno‐Sánchez Rafael
Published: May 2019

Over the last decade, three major advances have contributed in improving the response rates against cancer including, immunotherapy; greater understanding of the molecular, biochemical, and cellular mechanisms in carcinogenesis thereby providing drug targets; and identification of reliable biomarkers for early detection to facilitate the earlier stage treatment of disease. However, no single universal cancer cure has yet been found, although combinations from the above areas have steadily improved survival outcomes. Hence, chemotherapy remains a key component in the oncologist's arsenal for cancer therapy, despite frequent development of drug resistance and more aggressive cancers with onset of advanced stage metastases. The focus here is to explore the repurposing of old drugs that cause pro‐oxidative overload to overcome onset of resistance to chemotherapy and enhance chemotherapeutic responses, particularly against metastatic cancer. Excellent examples of US Food and Drug Administration approved drugs suitable for repurposing are the potent and specific thioreductase inhibitor auranofin and the nonsteroidal anti‐inflammatory drug, celecoxib. Recently, both drugs were shown to selectively target and kill metastatic cancer cells and cancer stem cells (CSCs), predominantly by promoting excessive mitochondrial reactive oxygen species. Thus, targeting intracellular redox systems of advanced stage metastatic cancer cells and CSCs can promote an overload of pro‐oxidative stress to activate the intrinsic pathway for programmed cell death. It is envisaged that more clinical studies will incorporate longer term use of repurposed drugs, such as auranofin or celecoxib, to target redox systems in cancer cells as part of common practice postcancer diagnosis, providing enhanced chemotherapeutic responses and increased cancer survival.
APA practice guidelines for females focus on their strength, resilience
Authors: Canady Valerie A.
Published: May 2019

The American Psychological Association (APA) announced new treatment guidelines for girls and women earlier this month, taking into account their strength and resilience and the changes in their lives in recent decades regarding education, reproductive and caregiving roles, and personal relationships. The guidelines apply to girls and women of diverse ethnicities and races, abilities, social classes, sexual orientations, gender identities and life experiences.
Mental health therapy program to allow teens school credit
Authors: Canady Valerie A.
Published: May 2019

An intensive outpatient therapy program in California for teens with significant anxiety or depression at risk of harming themselves recently received accreditation allowing its participants to receive high school credit.
Extragradient and linesearch methods for solving split feasibility problems in Hilbert spaces
Authors: Jouymandi Zeynab , Moradlou Fridoun
Published: May 2019

Utilizing the Tikhonov regularization method and extragradient and linesearch methods, some new extragradient and linesearch algorithms have been introduced in the framework of Hilbert spaces. In the presented algorithms, the convexity of optimization subproblems is assumed, which is weaker than the strong convexity assumption that is usually supposed in the literature, and also, the auxiliary equilibrium problem is not used. Some strong convergence theorems for the sequences generated by these algorithms have been proven. It has been shown that the limit point of the generated sequences is a common element of the solution set of an equilibrium problem and the solution set of a split feasibility problem in Hilbert spaces. To illustrate the usability of our results, some numerical examples are given. Optimization subproblems in these examples have been solved by FMINCON toolbox in MATLAB.
Strong solutions to 1D compressible Navier‐Stokes/Allen‐Cahn system with free boundary
Authors: Ding Shijin , Li Yinghua , Tang Ying
Published: May 2019

This paper is concerned with a diffuse interface model for two‐phase flow of compressible fluids with a type of free boundary. We establish the existence and uniqueness of global strong solutions of a coupled Navier‐Stokes/Allen‐Cahn system in 1D.
General decay of nonlinear viscoelastic Kirchhoff equation with Balakrishnan‐Taylor damping and logarithmic nonlinearity
Authors: Boulaaras Salah , Draifia Alaeddin , Zennir Khaled
Published: May 2019

This work deals with the study of a new class of nonlinear viscoelastic Kirchhoff equation with Balakrishnan‐Taylor damping and logarithmic nonlinearity. A decay result of the energy of solutions for the problem without imposing the usual relation between a certain relaxation function and its derivative is established. This result generalizes earlier ones to an arbitrary rate of decay, which is not necessarily of exponential or polynomial decay.
Objective assessment of the effects of tumor motion in radiation therapy
Authors: Ding Yijun , Barrett Harrison H. , Kupinski Matthew A. , Vinogradskiy Yevgeniy , Miften Moyed , Jones Bernard L.
Published: May 2019

Purpose

Internal organ motion reduces the accuracy and efficacy of radiation therapy. However, there is a lack of tools to objectively (based on a medical or scientific task) assess the dosimetric consequences of motion, especially on an individual basis. We propose to use therapy operating characteristic (TOC) analysis to quantify the effects of motion on treatment efficacy for individual patients. We demonstrate the application of this tool with pancreatic stereotactic body radiation therapy (SBRT) clinical data and explore the origin of motion sensitivity.

Methods

The technique is described as follows. (a) Use tumor‐motion data measured from patients to calculate the motion‐convolved dose of the gross tumor volume (GTV) and the organs at risk (OARs). (b) Calculate tumor control probability (TCP) and normal tissue complication probability (NTCP) from the motion‐convolved dose–volume histograms. (c) Construct TOC curves from TCP and NTCP models. (d) Calculate the area under the TOC curve (AUTOC) and use it as a figure of merit for treatment efficacy. We used tumor motion data measured from patients to calculate the relation between AUTOC and motion magnitude for 25 pancreatic SBRT treatment plans. Furthermore, to explore the driving factor of motion sensitivity of a given plan, we compared the dose distribution of motion‐sensitive plans and motion‐robust plans and studied the dependence of motion sensitivity to motion directions.

Results

Our technique is able to recognize treatment plans that are sensitive to motion. Under the presence of motion, the treatment efficacy of some plans changes from providing high tumor control and low risks of complications to providing no tumor control and high risks of side effects. Several treatment plans experience falloffs in AUTOC at a smaller magnitude of motion than other plans. In our dataset, a potential indicator of a motion‐sensitive treatment plan is that the duodenum is in proximity to the tumor in the SI direction.

Conclusions

The TOC framework can serve as a tool to quantify the effects of internal organ motion in radiation therapy. With pancreatic SBRT clinical data, we applied this tool to study the change in treatment efficacy induced by motion for individual treatment plans. This framework could potentially be used clinically to understand the effects of motion in an individual patient and to design a patient‐specific motion management plan. This framework could also be used in research to evaluate different components of the treatment process, such as motion‐management techniques, treatment‐planning algorithms, and treatment margins.
Robust contour propagation using deep learning and image registration for online adaptive proton therapy of prostate cancer
Authors: Elmahdy Mohamed S. , Jagt Thyrza , Zinkstok Roel Th. , Qiao Yuchuan , Shahzad Rahil , Sokooti Hessam , Yousefi Sahar , Incrocci Luca , Marijnen C.A.M. , Hoogeman Mischa , Staring Marius
Published: May 2019

Purpose

To develop and validate a robust and accurate registration pipeline for automatic contour propagation for online adaptive Intensity‐Modulated Proton Therapy (IMPT) of prostate cancer using elastix software and deep learning.

Methods

A three‐dimensional (3D) Convolutional Neural Network was trained for automatic bladder segmentation of the computed tomography (CT) scans. The automatic bladder segmentation alongside the computed tomography (CT) scan is jointly optimized to add explicit knowledge about the underlying anatomy to the registration algorithm. We included three datasets from different institutes and CT manufacturers. The first was used for training and testing the ConvNet, where the second and the third were used for evaluation of the proposed pipeline. The system performance was quantified geometrically using the dice similarity coefficient (DSC), the mean surface distance (MSD), and the 95% Hausdorff distance (HD). The propagated contours were validated clinically through generating the associated IMPT plans and compare it with the IMPT plans based on the manual delineations. Propagated contours were considered clinically acceptable if their treatment plans met the dosimetric coverage constraints on the manual contours.

Results

The bladder segmentation network achieved a DSC of 88% and 82% on the test datasets. The proposed registration pipeline achieved a MSD of 1.29 ± 0.39, 1.48 ± 1.16, and 1.49 ± 0.44 mm for the prostate, seminal vesicles, and lymph nodes, respectively, on the second dataset and a MSD of 2.31 ± 1.92 and 1.76 ± 1.39 mm for the prostate and seminal vesicles on the third dataset. The automatically propagated contours met the dose coverage constraints in 86%, 91%, and 99% of the cases for the prostate, seminal vesicles, and lymph nodes, respectively. A Conservative Success Rate (CSR) of 80% was obtained, compared to 65% when only using intensity‐based registration.

Conclusion

The proposed registration pipeline obtained highly promising results for generating treatment plans adapted to the daily anatomy. With 80% of the automatically generated treatment plans directly usable without manual correction, a substantial improvement in system robustness was reached compared to a previous approach. The proposed method therefore facilitates more precise proton therapy of prostate cancer, potentially leading to fewer treatment‐related adverse side effects.
Characterizing valve dynamics in mice by high‐resolution cine‐MRI
Authors: Weisell Jonna , Ruotsalainen Anna‐Kaisa , Laakso Hanne , Ylä‐Herttuala Elias , Näpänkangas Juha , Levonen Anna‐Liisa , Liimatainen Timo , Rysä Jaana
Published: May 2019

Aims

In calcific aortic valve disease (CAVD), progressive valvular sclerosis and calcification cause narrowing of the orifice and an impairment of the valve's function. We applied high‐resolution cine‐MRI to perform quantitative analysis of the dynamics of the aortic valve in a mice model of CAVD.

Methods and Results

LDLr−/−ApoB100/100 mice were fed a Western diet (WD) or a standard diet (control) for 22 weeks. The mice were imaged in a 7 T horizontal MRI scanner, and aortic valve dynamics was examined by imaging the cross‐section of the aorta at valve level using cine sequences. From these images, the area of the aortic valve orifice was determined during the heart cycle. MRI results were compared with echocardiographic and histopathologic results. The data revealed evidence of clear aortic valve dysfunction in WD mice as compared with control mice (interaction P < 0.001). MRI showed narrowing (14%, P < 0.05) of the orifice area, and this was also seen in histology (34%, P < 0.05), indicating more severe aortic stenosis after WD than in controls. Additionally, MRI revealed a reduction in the ejection fraction (EF) (−11%, P < 0.01), a result confirmed with echocardiography (−27%, P < 0.001) in mice fed with WD. EF detected by MRI and echocardiography also correlated strongly with the degree of stenosis assessed by histology.

Conclusions

Cine‐MRI can be used for quantitative analysis of the aortic valve orifice over the cardiac cycle in mice. MRI showed the cusps clearly, and we were able to detect aortic valve dysfunction over time through the cardiac cycle.
Exiled to Main Street: How government's use of social media diminishes public space
Authors: Piccorelli Justin T. , Stivers Camilla
Published: May 2019

Public administrators have long treated their connections with citizens as tools for efficiently achieving results. As Dwight Waldo once commented, their key political concern has been, “How much democracy can we afford?” Increasing use of social media technologies appears to expand citizen input at greatly reduced cost. On the basis of phenomenological investigation of virtual citizen–government relationships, we argue that the political consequences of social media have yet to be noticed fully. Social media exile citizens to Main Street—everyday life—instead of fostering connections in public space.
Preparation and properties of antibacterial ABS plastics based on polymeric quaternary phosphonium salts antibacterial agents
Authors: Zeng Weizhen , He Jingwei , Liu Fang
Published: May 2019

Antibacterial acrylonitrile‐butadiene‐styrene (ABS) plastics were prepared by adding polymeric quaternary phosphonium salts as antibacterial agents through a double screw extruder. The novel polymeric quaternary phosphonium salts (PBrMAP‐n) with alkyl chain length ranging from 3 to 11 were synthesized, and their chemical structures were confirmed by Nuclear magnetic resonance hydrogen spectroscopy (1H‐NMR) and Fourier transform infrared spectroscopy (FT‐IR) spectra. The thermogravimetric analysis (TGA) results showed that all of the antibacterial agents had good thermal stability. The influence of addition amount as well as the alkyl chain length on mechanical properties and antibacterial properties was investigated. Compared with the pure ABS, all of PBrMAP‐n containing specimens had comparable tensile strength and flexural properties but reduced impact strength. Only samples with 10 wt% of PBrMAP‐11 exhibited more than 90% antibacterial efficiency against Escherichia coli and Staphylococcus aureus.
Enoxaparin Thromboprophylaxis Dosing and Anti–Factor Xa Levels in Low‐Weight Patients
Authors: Yam Lily , Bahjri Khaled , Geslani Van , Cotton Adrian , Hong Lisa
Published: May 2019

Introduction

Enoxaparin is a widely used anticoagulant to prevent venous thromboembolism (VTE). A fixed dose is recommended for VTE prophylaxis. However, fixed prophylactic doses of enoxaparin in low‐weight patients may be close to the weight‐based dosing recommended for VTE treatment.

Objective

To evaluate peak anti–factor Xa (aFXa) levels in low‐weight patients receiving enoxaparin for VTE prophylaxis.

Methods

Retrospective cohort of adult patients weighing < 55 kg who were hospitalized at Loma Linda University Medical Center between January 2008 and February 2017. All patients received enoxaparin for VTE prophylaxis with a peak aFXa level drawn. The primary endpoint was the proportion of patients achieving peak aFXa levels within the goal range of 0.2–0.5 unit/ml.

Results

Of 35 patients receiving enoxaparin for VTE prophylaxis with an appropriately timed peak aFXa level, 74% achieved goal peak aFXa levels and the median daily dose of enoxaparin was 30 mg. The mean weight was approximately 44 kg. No significant correlations between aFXa level and body mass index or body weight were found.

Conclusion

A lower dose of enoxaparin may be reasonable in low‐weight patients for VTE prophylaxis. There appears to be no safety concerns with reduced enoxaparin dosing in low‐weight patients. More robust data are needed to confirm these findings.
Substituent effects on the stretching vibration of C═N in multi‐substituted benzylideneanilines
Authors: Wang Linyan , Cao Chaotun , Cao Chenzhong
Published: May 2019

Forty‐nine samples of 3,4′/4,3′/3,3′‐disubstituted benzylideneanilines (XBAYs) and 52 samples of multi‐substituted XBAYs were synthesized, and their infrared absorption spectra were recorded in this paper. On the basis of the stretching vibration frequencies νC═N of C═N bridging bond of 158 samples of substituted XBAYs (including 57 samples of 4,4′‐disubstituted XBAYs from reference and 101 samples of substituted XBAYs synthesized in this paper), an extensional research of substituent effects on the νC═N values from 4,4′‐disubstituted XBAYs to multi‐substituted XBAYs was made. A modified equation for quantifying the νC═N values of multi‐substituted XBAYs was obtained (shown as Equation (3)). Equation (3) indicates that the excited‐state substituent constant of Y and the substituent specific cross‐interaction effect between X and X cannot be ignored for the quantitative regression analysis of the νC═N values of multi‐substituted XBAYs. Compared with Equation (1), Equation (3) has a wider application and more accuracy in quantifying the νC═N values of substituted XBAYs.
Effects of water nanochannel diameter on proton transport in proton‐exchange membranes
Authors: Mabuchi Takuya , Tokumasu Takashi
Published: May 2019

The effects of water nanochannel diameter on proton transport pathways and properties have been studied using reactive molecular dynamics simulations. The proton distributions and diffusivities have been evaluated using the cylinder model of water domains at various diameters that is the most typical proposed morphological model in proton‐exchange membranes. The proton distributions are analyzed to clarify proton pathways by classifying the water channel into two regions in parallel: an inner channel (free water) and an outer channel (bound water). For all the water contents, the nonmonotonic trends that show a peak at a certain diameter are found to be observed in the proton diffusivity, which is dominated by the proton diffusivity in the free water region and has a strong correlation with the proton distribution that is controlled by the balance between the volume fraction of free water and the surface density of sulfonate groups. The electroosmotic drag coefficients are found to increase monotonically with increasing channel diameter as a result of the increase in the volume fraction of free water. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 867–878
Graphene–CNT hybrids by thermal and plasma‐enhanced chemical vapor deposition process: Numerical modeling of growth and energy kinetics
Authors: Tewari Aarti , Ghosh Santanu , Srivastava Pankaj
Published: May 2019

The numerical computations for the species density and energy kinetics are used to elaborate the growth mechanism and differences between the graphene–carbon nanotube (CNT) hybrids grown by the chemical vapor deposition (CVD) and plasma‐enhanced CVD (PECVD) process. The modeling results show that the CNT, graphene, and graphene–CNT hybrids have enhanced growth rates in a plasma medium than in a neutral gas environment of a CVD method. Plasma enables low‐temperature growth of graphene–CNT hybrids and offers a broad temperature range for the growth than the CVD technique that operates only at elevated temperatures. The underlying reasons and mechanisms behind the better growth rates and temperature range offered by the PECVD process (~400–1,600 K) are explained through the results.
Effect of In/Zn Ratios on Resistive Switching Behavior of IZO/TiO2 Thin Film Devices
Authors: Shan Fei , Kim Sung‐Jin
Published: May 2019

The fabrication of a memristor device based on various indium zinc oxide (IZO) solution ratios is demonstrated. Titanium oxide (TiO2) thin film is deposited using an atomic layer deposition technique, and then, an IZO thin film is grown on the TiO2 layer with spin‐coating and vacuum annealing at 400 °C. An aluminum (Al)/IZO/TiO2/Al device fabricated with an indium/zinc (In/Zn) solution ratio of 6:4 exhibits high electrical conductivity and excellent cycling stability. The work presented here can provide a new method for exploring the possibility of a high‐performance memristor for electronic applications.
An MEDT study of the mechanism and selectivities of the [3+2] cycloaddition reaction of tomentosin with benzonitrile oxide
Authors: Zeroual Abdellah , Ríos‐Gutiérrez Mar , El Idrissi Mohammed , El Alaoui El Abdallaoui Habib , Domingo Luis R.
Published: May 2019

The [3+2] cycloaddition (32CA) reaction of tomentosin with benzonitrile oxide yielding a spiro‐isoxazoline has been studied within the Molecular Electron Density Theory at the B3LYP/6‐31(d,p) computational level. Given the multifunctionality of tomentosin, this 32CA reaction can take place along 16 competitive reaction paths. The chemo‐, regio‐, and stereoisomeric reaction paths involving the two CC double bonds of tomentosin have been studied. Density functional theory (DFT) calculations account for the total chemo‐ and regioselectivity, in complete agreement with the experimental outcomes, being suggestive of low diastereofacial selectivity. Analysis of the conceptual DFT indices accounts for the nonpolar character of this 32CA reaction. On the other hand, the topological analysis of the electron localization function of the selected points of the intrinsic reaction coordinate associated with the formation of the CC and CO single bonds emphasizes the zw‐type reactivity of the phenyl nitrile oxide; the reaction taking place through a non‐concerted two‐stage one‐step mechanism initialized with the formation of the CC single bond involving the β‐conjugated carbon of tomentosin.
CO2 Hydrogenation to Methanol via In‐situ Reduced Cu/ZnO Catalyst Prepared by Formic acid Assisted Grinding
Authors: Lu Peng , Chizema Linet Gapu , Hondo Emmerson , Tong Mingliang , Xing Chuang , Lu Chengxue , Mei Yongfei , Yang Ruiqin
Published: May 2019

Methanol is an essential chemical raw material and potential alternative energy source. In this paper, Cu based catalyst was prepared by the noble solid phase grinding method for CO2 hydrogenation to methanol. The influence of chelating agent, heating rate, calcination temperature and calcination period of the precursor on catalyst performance were studied in depth. The catalyst precursor with formic acid as a chelating agent was reduced in‐situ when calcined in nitrogen (N2) at 573 K. The formic acid was decomposed, releasing the reducing agents, CO and H2, resulting in continuous in‐situ CuO reduction to metallic Cu0. XRD, XPS, BET, TG‐DSC, H2‐TPR and other characterization techniques were employed to analyze the catalyst properties. Results revealed that CuO was successfully reduced in‐situ to Cu0 during calcination process in a nitrogen atmosphere without further reduction. The catalyst prepared by formic acid grinding (F/I−Cu/ZnO) showed highest catalytic activity compared with the conventional catalyst which was further reduced by 5% H2 (F/H−Cu/ZnO). CO2 conversion and methanol selectivity reached 33.44% and 84.26%respectively.
3D Hierarchical structure Electrodes of MnO2 Nanosheets Decorated on Needle‐like NiCo2O4 Nanocones on Ni Foam as a cathode material for Asymmetric Supercapacitors
Authors: Ren Bo , Fan Meiqing , Yang Xiaodong , Wang Lei , Yu Haixia
Published: May 2019

In this work, three dimensional (3D) hierarchical structure electrode of MnO2 nanosheets decorated on needle‐like NiCo2O4 nanocones hybrid arrays on Ni foam is designed by a two‐step hydrothermal process. In this special structure, 3D hierarchical NiCo2O4/MnO2 core/shell composites have high specific surface area and large pore structure, which makes it easier to reach the active site, and shorten the ion transport path. Used as electrode for supercapacitors, the composites can develop their respective strengths, and the synergies between different components can also improve capacitance and speed capacity. The electrochemical results exhibit that the NiCo2O4/MnO2 core/shell electrodes display a large capacitance of 816 F⋅g−1 at the current density of 5 mA⋅cm−2, and show an excellent cycling stability (81% retention after 5000 cycles). Four Asymmetric supercapacitors (NiCo2O4/MnO2//BPC (banana peel), NiCo2O4/MnO2//BHC (buckwheat husk), NiCo2O4/MnO2//PPC (pomelo peel), and NiCo2O4/MnO2//AC (activated carbon)) using the NiCo2O4/MnO2 core/shell as a positive electrode and biochar as a negative electrode are assembled. The results indicate that all the asymmetric supercapacitors deliver a high operation voltage of 1.6 V, and NiCo2O4/MnO2//BPC exhibits excellent specific capacitance (85.4 F⋅g−1 at the current density of 5 mA⋅cm−2), high energy density (30.4 Wh⋅kg−1 at the power density of 133.5 W⋅kg−1) and remarkable cycling stability (only decrease by 12% after 5000 cycles).
Synthesis of 1,3‐Disubstituted Imidazo[1,5‐a]pyridines through Oxidative C‐N Bond Formation from Aryl‐2‐pyridylmethanols and Their Fluorescent Study
Authors: Chandrasekar Selvaraj , Sangeetha Subramani , Sekar Govindasamy
Published: May 2019

A simple, effortless, and efficacious protocol for the synthesis of highly fluorescing imidazo[1,5‐a]pyridines via copper catalyzed inter‐/intramolecular C−N bond formation between readily available pyridyl alcohols with either benzyl amines or amino acids has been developed. This domino reaction is involved with alcohol oxidation/condensation/oxidative amination sequence to synthesize imidazo[1,5‐a]pyridines in good to excellent yields. The fluorescence studies of these compounds indicated a bathochromic shift for the electron donating substituents, whereas a hypsochromic shift for the electron withdrawing substituents. Synthetic modification of the groups attached to the heterocyclic core showed a profound impact on the emission properties when subjected to pH and solvent polarity change.