bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractOsteoarthritis (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

AbstractNon–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.
Communication pitfalls in interpreted genetic counseling sessions
Authors: Ault Rachel , Morales Ana , Ault Russell , Spitale Allison , Martinez Glenn A. 
Published: May 2019

AbstractThe 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

AbstractBackgroundAlthough 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.MethodsThis 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.ResultsEight 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.ConclusionsThis 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: 2Technical Efficacy: Stage 1J. 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

AbstractThis 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

AbstractBackgroundOral 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.MethodsBacterial 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.ResultsCompared 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.ConclusionsNeutrophil 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

AbstractBackgroundPatient perceptions and preferences related to postoperative surveillance are not yet well defined.MethodsA 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.ResultsAmong 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.ConclusionAttitudes 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

AbstractTyrosine 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

AbstractOver 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.
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

PurposeInternal 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.MethodsThe 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.ResultsOur 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.ConclusionsThe 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

PurposeTo 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.MethodsA 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.ResultsThe 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.ConclusionThe 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

AimsIn 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 ResultsLDLr−/−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.ConclusionsCine‐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.