bluuebunny/crossref_metadata_2025_split huggingface dataset:
Slide‐free imaging of hematoxylin‐eosin stained whole‐mount tissues using combined third‐harmonic generation and three‐photon fluorescence microscopy
Authors: Sun Chi‐Kuang , Kao Chien‐Ting , Wei Ming‐Liang , Chia Shih‐Hsuan , Kärtner Franz X. , Ivanov Anatoly , Liao Yi‐Hua 
Published: January 2019

Intraoperative margin assessment of surgical tissues during cancer surgery is clinically important, especially in the case of tissue conserving surgery like Mohs micrographic surgery in which minimization of the surgical area is considered crucial. Frozen pathology is the gold standard of assessing excised tissues for signs of remaining cancerous lesions. The current protocol, however, is time‐consuming and labor‐intensive. Instead of the complex frozen sectioning, staining, and traditional white light microscopy imaging protocol, optically sectioned histopathological imaging of hematoxylin‐eosin stained whole‐mount skin tissues with a subfemtoliter resolution is demonstrated by using nonlinear microscopy in this study. With our proposed method, the reagents of staining and the contrast of imaging are fully consistent with the current clinical standard of frozen pathology, thus facilitating rapid intraoperative assessment of surgical tissues for future applications.Image: Slide‐free nonlinear microscopy imaging of H&E stained whole‐mount skin tissue showing the morphology of sweat glands.
In vitro interaction of human Wharton's jelly mesenchymal stem cells with biomimetic 3D scaffold
Authors: Jamalpoor Zahra , Taromi Nafise , Soleimani Mansooreh , Koudehi Masoumeh Foroutan , Asgari Alireza 
Published: January 2019

AbstractStudy of cell‐biomaterial interaction is a crucial aspect of bone tissue engineering to find a state‐of‐the‐art functional substitute. In present study, the Wharton's jelly mesenchymal stem cells (hWJ‐MSCs) behavior on three‐dimensional biomimetic nano‐hydroxyapatite/chitosan/gelatin (nHA/CS/Gel) scaffolds was investigated. The outcome was assessed by histological, biochemical and morphological tests. Results indicated that hWJ‐MSCs attached onto the scaffold surface through membrane filopodia, uniformly spread throughout the contacting surface. It only took 3 days for the seeded cells to appear deep inside the scaffold, reflecting proper hWJ‐MSCs adhesion and migration, evidenced by both scanning electron microscope and hematoxilin and eosin assessments. Additionally, the present fabricated nHA/CS/Gel scaffold proved to be non‐toxic as it supported cell proliferation measured by 3‐(4,5‐dimethylthiazoyl‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Moreover, 3‐week culture of hWJ‐MSCs on scaffolds, immersed in osteogenic medium, rendered the microenvironment in favor of hWJ‐MSCs differentiation into osteoblast cells and extracellular matrix secretion. Finally, osteoblasts were immunologically positive for various osteogenic markers including osteocalcin, osteopontin, osteonectin, and alkaline phosphatase. Present findings indicate that nHA/CS/Gel scaffold appropriately harbored hWJ‐MSCs, stimulating their growth, migration, proliferation, and differentiation. hWJ‐MSCs‐loaded nHA/CS/gel substitute may therefore be considered as a suitable platform for the rising demand in in vivo bone repair studies. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1166–1175, 2019.
Synthetic fluorinated polyamides as efficient gene vectors
Authors: Wang Mian , Xue Han , Gao Min , Wang Qingli , Yang Haijie 
Published: January 2019

AbstractLinear fluorinated polyamides with reversible cationic charges are feasibly prepared to be used as highly efficient gene vectors in HEK293 cell line. Due to the uniform polymer structure, the relationship between the physicochemical properties and transfection efficiency could be unambiguously investigated. The different efficiency in the application of gene delivery between the parent polyethylenimine (PEI) and the polyamides is directly associated with the differences in chemical and physical properties between secondary amines and fluorinated amides. We found that fluorination not only increases the cellular uptake of polymer/DNA polyplexes, but it also decreases cytotoxicity in terms of inducing lower concentrations of proinflammatory cytokine TNF‐α. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2132–2139, 2019.
HGFAC expression decreased in liver cancer and its low expression correlated with DNA hypermethylation and poor prognosis
Authors: Yin Li , Mu Yudong , Lin Yingzi , Xia Qianfeng 
Published: January 2019

AbstractAs the activator of hepatocyte growth factor (HGF), hepatocyte growth factor activator (HGFAC) has been previously reported to involve in liver, kidney, and stomach regeneration in response to injury and several types of cancers. This study aimed to explore the expression of HGFAC and the correlation between decreased HGFAC and DNA methylation in liver cancer and its clinical significance. The molecular profiling of HGFAC in liver cancer was analyzed using genomic, transcriptomic, immunohistochemistry, and patient survival information from databases, including oncomine, HPA, COSMIC, UCSC Xena, MPRESS, and Kaplan‐Meier plotter. It was found that HGFAC expression at transcriptional and translational level decreased in liver cancer compared with normal tissues. There is a negative correlation between the HGFAC expression and methylation around the promoter region which indicated that HGFAC expression might be controlled by DNA methylation. Moreover, the decreased HGFAC is associated with significantly short over survival time in liver cancer patients. In conclusion, decreased HGFAC expression in liver cancer associated with poor survival outcome. Hypermethylation around the promoter region contributed to the decreased expression of HGFAC. HGFAC may be a useful and predictive biomarker for the prognosis of liver cancer patients. To the best of our knowledge, this is the first report describing the relationship between HGFAC DNA methylation and its expression.
Long noncoding RNA AK088388 regulates autophagy through miR‐30a to affect cardiomyocyte injury
Authors: Wang Jing‐jing , Bie Zi‐dong , Sun Chao‐feng 
Published: January 2019

AbstractFinding ways to reduce myocardial ischemia/reperfusion injury in the process of myocardial infarction has been an area of intense study in the field of heart disease. Recent studies have shown that long noncoding RNA (lncRNA) and autophagy play important roles in cardiovascular diseases. In our study, software analysis and dual‐luciferase reporter assays have shown that miR‐30a has binding sites on both AK088388 and Beclin‐1. Continuing experiments found that miR‐30a expression is downregulated, while the expressions of AK088388, Beclin‐1, and LC3‐II are upregulated in hypoxia/reoxygenation (H/R) cardiomyocytes; miR‐30a inhibits the expression of AK088388, Beclin‐1, and LC3‐II in H/R cardiomyocytes, while AK088388 promotes the expression of Beclin‐1 and LC3‐II and inhibits miR‐30a expression. AK088388 small interfering RNA and miR‐30a mimics can promote the viability of H/R cardiomyocytes, reduce lactate dehydrogenase release, and reduce apoptosis. Mutations of the miR‐30a binding site in AK088388 could not block the effects of miR‐30a mentioned above. Therefore, AK088388 can competitively bind to miR‐30a, promoting the expression of Beclin‐1 and LC3‐II, autophagy, and eventually cell damage. This finding provides new evidence for understanding the role of lncRNA in myocardial ischemia/reperfusion injury.
HIF1A‐AS2 predicts poor prognosis and regulates cell migration and invasion in triple‐negative breast cancer
Authors: Wang Yufei , Zhang Guochao , Han Jie 
Published: January 2019

AbstractThe aberrant expression of hypoxia‐inducible factor 1 alpha (HIF1A)‐antisense RNA 2 (HIF1A‐AS2) was found in various human cancers including breast cancer. The aim of this study was to present more evidence about the role HIF1A‐AS2 on triple‐negative breast cancer (TNBC). In our results, HIF1A‐AS2 was also found to be upregulated in TNBC tissues compared with non‐TNBC tissues or adjacent normal tissues. Besides, HIF1A‐AS2 expression was also elevated in TNBC cell lines compared with the normal breast epithelial cell line. Moreover, high expression of HIF1A‐AS2 was associated with lymph node metastasis, distant metastasis and unfavorable histological grade in TNBC patients. Survival analysis showed a TNBC patient with high HIF1A‐AS2 expression had shorter overall survival than patients with low HIF1A‐AS2 expression, and HIF1A‐AS2 high expression acted as an independent poor prognostic factor for overall survival in TNBC patients. The cell migration and invasion assays suggested inhibition of HIF1A‐AS2 obviously depressed TNBC cell migration and invasion. In conclusion, HIF1A‐AS2 serves as a novel biomarker for predicting clinical progression and prognosis in TNBC.
GDF‐15 promotes mitochondrial function and proliferation in neuronal HT22 cells
Authors: Liu Hong , Liu Jiahui , Si Lei , Guo Cunju , Liu Wei , Liu Yiming 
Published: January 2019

AbstractThe neuronal cell line HT22 is an excellent model for studying Parkinson's disease. Growth differentiation factor 15 (GDF15) plays a critical role in Parkinson's disease, but the molecular mechanism involved are not well understood. We constructed the GDF15 overexpression HT22 cells and detected the effects of overexpression of GDF15 on the viability, oxygen consumption, mitochondrial membrane potential of oligomycin‐treated HT22 cells. In addition, we used a high‐throughput RNA‐sequencing to study the lncRNA and mRNA expression profiling and obtained key lncRNAs, mRNA, gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway. The expression of selected DElncRNAs was validated by quantitative real‐time PCR (qRT‐PCR). Our results showed that overexpression of GDF15 significantly reversed the cells viability, oxygen consumption, and mitochondrial membrane potential effect caused by oligomycin in HT22 cells. The 1093 DEmRNAs and 395 DElncRNAs in HT22 cells between GDF15‐oligomycin non‐intervention group and a normal control‐oligomycin un‐intervention group were obtained, and 394 DEmRNAs and 271 DElncRNAs in HT22 cells between GDF15‐oligomycin intervention group and normal control‐oligomycin intervention group were identified. Base on the GO and KEGG enrichment analysis of between GDF15‐oligomycin intervention group and normal control‐oligomycin intervention group, positive regulation of cell proliferation was most significantly enriched GO terms, and Cav1 was enriched in positive regulation of cell proliferation pathway. PI3K‐Akt signaling pathway was one significantly enriched pathway in GDF15‐oligomycin intervention group. The qRT‐PCR results were consistent with RNA‐sequencing, generally. GDF15 might promote mitochondrial function and proliferation of HT22 cells by regulating PI3K/Akt signaling pathway. Our study may be helpful in understanding the potential molecular mechanism of GDF15 in Parkinson's disease.
Understanding grief reactions, thwarted belongingness, and suicide ideation in bereaved adolescents: Toward a unifying theory
Authors: Hill Ryan M. , Kaplow Julie B. , Oosterhoff Benjamin , Layne Christopher M. 
Published: January 2019

AbstractObjectiveChildhood bereavement is linked to suicide‐related behaviors in adolescence and adulthood, but candidate mechanisms through which bereavement may lead to suicide‐related behaviors have not been explored. One candidate pathway is that grief reaction arising from bereavement lead to increased perceived burdensomeness and/or thwarted belongingness, resulting in increased suicide ideation. This cross‐sectional study of bereaved adolescents explored indirect effects between grief reactions as distal predictors, perceived burdensomeness and thwarted belongingness as proximal predictors, and suicide ideation.MethodParticipants were 58 bereaved youth, 12–17 years of age (mean = 14.21, SD = 1.65; 81.0% female; 51.7% Hispanic, 17.2% African American, and 22.4% Caucasian), and their parents/guardians seeking services at a trauma and grief specialty outpatient clinic.ResultsThe indirect effect of grief reactions on suicide ideation via thwarted belongingness, but not perceived burdensomeness, was statistically significant.ConclusionsClinicians may wish to consider signs of thwarted belongingness as possible indicators of suicide risk among bereaved youth.
Proteomics analysis indicated the protein expression pattern related to the development of fetal conotruncal defects
Authors: Wu Yun , Zhang Jingjing , Wang Mei , Yang Ling , Wang Yongmei , Hu Tao , Liu An , Cheng Qing , Fu Ziyi , Zhang Pingyang , Cao Li 
Published: January 2019

AbstractAbnormal development of embryonic conus arteriosus could lead to conotruncal defects in fetal heart, and increase the incidence of fetal congenital heart disease. Tetralogy of Fallot (TOF) is one of the most common forms of congenital heart disease. It may be helpful for us to solve this clinical problem through exploring the molecular mechanisms of development in embryonic congenital heart disease. Proteomics has attracted much attention in understanding the development of human diseases during the past decades. However, there is still little information about the relationship between protein expression pattern and TOF. In this study, we aimed to explore the potential linkage of proteomics and TOF development. Briefly, 121 differentially expressed proteins were identified from a TOF group, compared with a control group. The expression levels of 34 of these proteins were significantly different (>1.5 absolute fold change, p < 0.05) between the two groups. Gene ontology (GO) and pathway analysis showed that these proteins were mainly associated with carbon metabolism, biosynthesis of antibodies, positive regulation of transcription from RNA polymerase II promoter, nucleus, ATP binding, and so on. The ingenuity pathway analysis (IPA) results indicated that 435 of upstream regulators were identified of these differentially expressed proteins, which might be involved in the development of TOF. Data of string analysis showed the protein–protein interaction network among the differentially expressed proteins and regulators, which are related to TOF. In conclusion, our study explored the protein expression pattern of TOF, which might provide new insights into understanding the mechanism of TOF development and afford potential targets for TOF diagnosis and therapy.
A new rhodopsin R135W mutation induces endoplasmic reticulum stress and apoptosis in retinal pigment epithelial cells
Authors: Yu Yixin , Xia Xiaobo , Li Haibo , Zhang Yangzhou , Zhou Xiaoyun , Jiang Haibo 
Published: January 2019

AbstractRhodopsin mutations are associated with the autosomal‐dominant form of retinitis pigmentosa (RP). Here we report simultaneous occurrence of RP associated with bilateral nanophthalmos and acute angle‐closure glaucoma in patient with a new mutation in rhodopsin (R135W). ARPE‐19 cells were transfected with myc‐tagged wild‐type (WT) and R135W rhodopsin constructs. The half‐life of WT and R135W rhodopsin was analyzed via cycloheximide chase analysis. We found that R135W rhodopsin was accumulated in the endoplasmic reticulum (ER) and induced unfolded protein response (UPR) and apoptosis. Moreover, chaperone HSP70 alleviated ER stress and prevented apoptosis induced by R135W rhodopsin by attenuating UPR signaling. These findings reveal the novel pathogenic mechanism of RP and suggest that chaperone HSP70 has potential therapeutic significance for RP.
Identification of a giant mediastinal teratoma by echocardiography: A case report
Authors: Xiao‐dong Li , Li Zhang , Xiu‐mei Duan , Ming‐bo Tang , Xiao‐cong Wang 
Published: January 2019

AbstractThe diagnosis of mediastinal space‐occupying lesions largely relies on X‐ray and computed tomography. However, thanks to technological progress, transthoracic echocardiography can clearly display the mediastinal structures surrounding the heart and great vessels, thereby improving the detection rate of mediastinal space‐occupying lesions. Primary mediastinal teratoma is relatively rare, and removal of giant mediastinal teratoma by thoracoscopic surgery has rarely been reported. Here, we report a case of giant mediastinal teratoma diagnosed by transthoracic echocardiography, which was treated by complete thoracoscopic resection and confirmed by histology.
Morphological and microscopic identification of three major medicinal Dendrobium species in Ta‐pieh Mountains area
Authors: Yuan Yingdan , Liu Xin , Wang Jinping , Zhang Jinchi 
Published: January 2019

Abstract
Dendrobium is an important medicinal material in China. It has the effect of nourishing the stomach, nourishing yin and clearing heat. In China, there are many types of Dendrobium, and different Dendrobium species have different efficacy. The present study is aimed at distinguishing three major Dendrobium species from morphological and microscopic identification in Ta‐pieh mountains area. In this article, the roots, stems and leaves of Dendrobium huoshanense, Dendrobium officinale, and Dendrobium moniliforme are used as materials to compare the differences of tissues of these three Dendrobium species by morphological indexes and microscopic identification of different Dendrobium. The stem morphology of these three Dendrobium species was significantly different except for stem internodes number and the middle part of the stem diameter by measuring the stems of Dendrobium. To ensure the safe use of Dendrobium, we built a fast and convenient method combining normal and fluorescence microscopy was applied in the present study to distinguish D. huoshanense, D. officinale, and D. moniliforme. The microscopic results show that different types of Dendrobium exhibit different states that can be distinguished under normal light normal and fluorescence microscopy. This comparative study of morphology and microscopy contributes to the development of identification and quality evaluation of Dendrobium.
Patients' perspectives of variants of uncertain significance and strategies for uncertainty management
Authors: Makhnoon Sukh , Shirts Brian H. , Bowen Deborah J. 
Published: January 2019

AbstractVariants of uncertain significance (VUS) are a well‐recognized source of uncertainty in genomic medicine. Despite the existence of straightforward clinical management recommendations, patients report feeling anxiety, worry, and uncertainty in response to VUS. We report the first structured analysis of patient perspectives of VUS‐related uncertainty in genome sequencing using Han's taxonomy of genomic uncertainty. We conducted in‐depth semi‐structured interviews with 11 patients to elicit their thoughts regarding implications of the result for themselves and their family members. Patients' primary concern with VUS‐related uncertainty involved personal and practical issues as they directly inform health‐care decisions. Patients demonstrated good understanding of the epistemic nature of VUS uncertainty—that information about such variant is currently unknown. However, between‐provider discordance in explanations of the implication of this uncertainty for patients' diagnosis, prognosis, and therapy was a major contributor to the overall experience of uncertainty. Strategies for uncertainty reduction involved periodically checking back for reclassification and receiving concordant and clear recommendation from providers. Other proactive strategies of uncertainty reduction—such as information seeking and reading the genetic test report—were not helpful. Collectively, these findings offer previously unreported insight into uncertainty management strategies used by patients which have the potential to guide clinical management practices.
Ovarian structure, folliculogenesis and oogenesis of the annual killifish Millerichthys robustus (Cyprinodontiformes: Cynolebiidae)
Authors: Domínguez‐Castanedo Omar , Uribe Mari Carmen 
Published: January 2019

AbstractCellular aspects of oocyte development of the Mexican rivulus Millerichthys robustus were morphologically described in order to analyze ovarian function and the cellular recruitment dynamics associating it with life history strategies of annual killifishes. Millerichthys is an iteroparous batch spawner with continuous oocyte recruitment and indeterminate fecundity with asynchronous development of the follicles. It has two ovaries of cystovarian type, with a central lumen, which communicates with the outside through the caudal region of the ovary, that is, the gonoduct. From the walls of the ovary, irregular lamellae composed of germinal epithelium and vascularized stroma project. Oogenesis starts with oogonial proliferation, found alone or in nests within the germinal epithelium. The oogonia come into meiosis becoming oocytes and advancing to the chromatin nucleolus stage and to early primary growth stage. Folliculogenesis is completed in the primary growth stage and cortical alveoli step. Follicles moves toward the stroma, but they continue to be attached to the germinal epithelium through the basement membrane until ovulation. The inclusion of fluid yolk in the follicles during the secondary growth stage was observed. During ovulation, the follicle collapsed, the oocyte was released into the lumen, and the constitutive elements of the post‐ovulatory follicle complex remained in the stroma.
Analysis of cavopulmonary and cardiac flow characteristics in fontan Patients: Comparison with healthy volunteers
Authors: Rutkowski David R. , Barton Gregory , François Christopher J. , Bartlett Heather L. , Anagnostopoulos Petros V. , Roldán‐Alzate Alejandro 
Published: January 2019

BackgroundCharacterizing the flow of the Fontan circuit, and correlating flow characteristics with the development of complications, is an important clinical challenge. Past work has analyzed the flow characteristics of Fontan circulation on a component‐by‐component basis. 4D flow MRI with radial projections allows for large volumetric coverage, and therefore can be used to analyze the flow through many codependent cardiovascular components in a single imaging session.PurposeTo describe flow characteristics across the entire Fontan circuit and to compare these with the flow characteristics in healthy volunteers.Study TypeProspective.SubjectsEleven single ventricle patients with a Fontan connection and 15 healthy controls.SequencePhase contrast with vastly undersampled isotropic projection reconstruction (PC‐VIPR) at a field strength of 3 T.AssessmentCavopulmonary and ventricular flow distributions, blood flow kinetic energy, vorticities, efficiency indices, and other flow parameters were analyzed using Ensight and MatLab.Statistical TestsThe results were compared across Fontan subjects, between respiratory phases, and between Fontan subjects and healthy volunteers using a Student's t‐test for unequal sample sizes and linear regression.ResultsCava‐specific pulmonary flow distributions of Fontan patients varied significantly between respiratory phases (P < 0.05). Ventricular kinetic energy (KE) was significantly higher in Fontan patients than it was in healthy controls, leading to a lower cardiac efficiency metric in the Fontan group. A significant diastolic KE time‐shift was also observed in the Fontan patient group. Peak diastolic KE was significantly higher in the single ventricle of patients with right ventricle morphology than it was in left ventricle morphology patients.Data ConclusionRadial 4D flow MRI can be used for comprehensive analysis of single ventricle Fontan flow characteristics.Level of Evidence: 2Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019.