bluuebunny/crossref_metadata_2025 huggingface dataset:
Dihalogenated Methylperoxy Radicals: Spectroscopic Characterization and Photodecomposition by Release of HO.
Authors: Lu Bo , Song Chao , Liu Jie , Trabelsi Tarek , Francisco Joseph S. , Wang Lina , Zeng Xiaoqing
Published: January 2020

Two atmospherically relevant dihalogenated methylperoxy radicals CHX2OO. (X=F and Cl) have been generated through O2‐oxidation of the corresponding alkyl radicals CHX2. in the gas phase. The IR spectroscopic characterization of both radicals in cryogenic Ar‐ and N2‐matrices (15 K) is supported by 18O‐labeling and ab initio calculations at the UCCSD(T)/aug‐cc‐pVTZ level. Upon 266 nm laser irradiation, both radicals decompose mainly by releasing hydroxyl radicals (→HO.+X2CO) via the intermediacy of intriguing α‐hydroperoxyalkyl radicals (.CX2OOH), implying that the photooxidation of dihalogenated hydrocarbons might serve as important sources of HO. radicals in the atmosphere.
Multimodal psychosocial intervention for family caregivers of patients undergoing hematopoietic stem cell transplantation: A randomized clinical trial
Authors: El‐Jawahri Areej , Jacobs Jamie M. , Nelson Ashley M. , Traeger Lara , Greer Joseph A. , Nicholson Showly , Waldman Lauren P. , Fenech Alyssa L. , Jagielo Annemarie D. , D’Alotto Jennifer , Horick Nora , Spitzer Thomas , DeFilipp Zachariah , Chen Yi‐Bin A. , Temel Jennifer S.
Published: January 2020

Background

Caregivers of patients undergoing hematopoietic stem cell transplantation (HCT) experience an immense caregiving burden before, during, and after HCT.

Methods

We conducted an unblinded, randomized trial of a psychosocial intervention (BMT‐CARE) for caregivers of patients undergoing autologous and allogeneic HCT at Massachusetts General Hospital. Caregivers were randomly assigned to BMT‐CARE or usual care. BMT‐CARE was tailored to the HCT trajectory and integrated treatment‐related education and self‐care with cognitive‐behavioral skills to promote coping. Caregivers assigned to BMT‐CARE met with a trained interventionist (a psychologist or a social worker) in person, via telephone, or via videoconferencing for 6 sessions starting before HCT and continuing up to day +60 after HCT. The primary endpoint was feasibility, which was defined as at least 60% of eligible caregivers enrolling and completing 50% or more of the intervention sessions. We assesed caregiver quality of life (QOL; Caregiver Oncology Quality of Life Questionnaire), caregiving burden (Caregiver Reaction Assessment), psychological distress (Hospital Anxiety and Depression Scale), self‐efficacy (Cancer Self‐Efficacy Scale–Transplant), and coping (Measures of Current Status) at baseline and 30 and 60 days after HCT. We used mixed linear effect models to assess the effect of BMT‐CARE on outcomes longitudinally.

Results

We enrolled 72.5% of eligible caregivers (100 of 138), and 80% attended 50% or more of the intervention sessions. Caregivers randomized to BMT‐CARE reported improved QOL (B = 6.11; 95% CI, 3.50‐8.71; P < .001), reduced caregiving burden (B = –6.02; 95% CI, –8.49 to –3.55; P < .001), lower anxiety (B = –2.18; 95% CI, –3.07 to –1.28; P < .001) and depression symptoms (B = –1.23; 95% CI, –1.92 to –0.54; P < .001), and improved self‐efficacy (B = 7.22; 95% CI, 2.40‐12.03; P = .003) and coping skills (B = 4.83; 95% CI, 3.04‐6.94; P < .001) in comparison with the usual‐care group.

Conclusions

A brief multimodal psychosocial intervention tailored for caregivers of HCT recipients is feasible and may improve QOL, mood, coping, and self‐efficacy while reducing the caregiving burden during the acute HCT period.
Understanding the ability, and inability, of high‐resolution ultrasound to guide thyroid nodule evaluation
Authors: Alexander Erik K.
Published: January 2020

Ultrasound is the primary tool used to initially guide clinical decisions about newly detected thyroid nodules, and numerous ultrasound‐based risk stratification systems have been developed that allow low to high cancer risk stratification. These systems can similarly assist with risk assessment for follicular thyroid carcinoma, but with important cautionary caveats.
Simulation of the influence of voltage level and pulse spacing on the efficiency, aggressiveness and uniformity of the electroporation process in tissues using meshless techniques
Authors: Vélez Salazar Fabián M. , Patiño Arcila Iván D. , Ruiz Villa Carlos A.
Published: January 2020

Electroporation is a widely used method consisting of application of high‐voltage, short‐duration electric pulses to increase cell membrane permeability, allowing cellular internalization of medications. In this work, the influence of two primary parameters, voltage level (V) and pulse spacing (N), on electroporation efficiency, uniformity and aggressiveness, as quantified by the total mass transport to viable cells, intracellular concentration gradients and an aggressiveness factor introduced here, is studied by means of numerical simulations of drug transport in electroporated tissues. The global method of approximate particular solutions (Global MAPS) is used to solve the governing equations, together with domain scaling, singular value decomposition and smoothing algorithms, to address the ill‐conditioning of the final system and suppress small scale oscillations. The accuracy of Global MAPS is evaluated by comparing the initial extracellular concentration, Ce, and final intracellular concentration, Ci, with previous finite volume method results, obtaining similar behavior of Ce and Ci along the tissue domain, with some differences for Ci in high‐gradient zones. According to the Global MAPS results, the influence of V and N on Ci is only significant over a certain range, within which the largest drug transport to viable cells occurs. In general, both electroporation efficiency and aggressiveness change in nonuniform manner with V and decrease with N, whereas the electroporation uniformity decreases as V increases and N decreases. The contour plots obtained here can be considered useful tools to compare electroporation‐based treatments in terms of their efficiency, aggressiveness and uniformity, assisting in the selection of a suitable treatment plan for cancer.
Continuous Radio Amplification by Stimulated Emission of Radiation using Parahydrogen Induced Polarization (PHIP‐RASER) at 14 Tesla
Authors: Pravdivtsev Andrey N. , Sönnichsen Frank D. , Hövener Jan‐Bernd
Published: January 2020

Nuclear Magnetic Resonance (NMR) is an intriguing quantum‐mechanical effect that is used for routine medical diagnostics and chemical analysis alike. Numerous advancements have contributed to the success of the technique, including hyperpolarized contrast agents that enable real‐time imaging of metabolism in vivo. Herein, we report the finding of an NMR radio amplification by stimulated emission of radiation (RASER), which continuously emits 1H NMR signal for more than 10 min. Using parahydrogen induced hyperpolarization (PHIP) with 50 % para‐hydrogen, we demonstrated the effect at 600 MHz but expect that it is functional across a wide range of frequencies, e.g. 101–103 MHz. PHIP‐RASER occurs spontaneously or can be triggered with a standard NMR excitation. Full chemical shift resolution was maintained, and a linewidth of 0.6 ppb was achieved. The effect was reproduced by simulations using a weakly coupled, two spin‐
system. All devices used were standard issue, such that the effect can be reproduced by any NMR lab worldwide with access to liquid nitrogen for producing parahydrogen.
A Near‐Infrared Absorption Small Molecule Acceptor for High‐Performance Semitransparent and Colorful Binary and Ternary Organic Photovoltaics
Authors: Wang Chun‐Kai , Jiang Bing‐Huang , Lu Jong‐Hong , Cheng Ming‐Tsang , Jeng Ru‐Jong , Lu Yu‐Wei , Chen Chih‐Ping , Wong Ken‐Tsung
Published: January 2020

An acceptor–donor–acceptor (A–D–A)‐type non‐fullerene acceptor (NFA), PTTtID‐Cl, featuring thieno[3,2‐b]thieno[2′′′,3′′′:4′′,5′′]‐pyrrolo[2′′,3′′:4′,5′]thieno[2′,3′:4,5]thieno‐[2,3‐d]pyrrole (DTPTt) as the electron‐rich core and 2‐(5,6‐dichloro‐3‐oxo‐2,3‐dihydro‐1H‐inden‐1‐ylidene)malononitrile (ID‐Cl) as the peripheral electron‐deficient terminal group was synthesized and characterized. PTTtID‐Cl exhibited strong absorption in the range of 700–850 nm in CHCl3 and redshifted absorption centered at 881 nm in a thin film. The near infrared (NIR)‐absorption of PTTtID‐Cl was combined with a low‐bandgap polymer donor (PTB7‐Th) to achieve binary and semitransparent organic photovoltaics (OPVs) with a power conversion efficiency (PCE) of 8.9 % and 7.7 % (with an average visible transmittance (AVT) of 16.7 %), respectively. A ternary device with a ratio of PM7/PTTtID‐Cl/IT‐4F=1:0.15:0.85 (w/w) achieved a short‐circuit current density of 19.46 mA cm−2, an open‐circuit voltage of 0.87 V, and a fill factor of 71.2 %, giving a PCE of 12.0 %. In addition, by employing the Ag/ITO/Ag microcavity structure, semitransparent colorful binary organic photovoltaics (OPVs) with superior transparency of 27.9 % at 427 nm and 22.7 % at 536 nm for blue and green devices, respectively, were prepared. The semitransparent colorful devices based on the optimized ternary blend gave PCEs of 8.7 %, 8.4 %, and 9.1 % for blue, green, and red devices, respectively. These results indicate the promising potential of PTTtID‐Cl as a NIR‐absorption NFA for applications in semitransparent colorful binary and ternary OPVs.
Legitimacy assessment throughout the life of collaborative water governance
Authors: Melnychuk Natalya , de Loë Robert
Published: January 2020

Collaborative governance arrangements involving a diversity of groups (e.g., governments, civil society, industry) are increasingly being used to make decisions or give advice to decision‐makers on water issues. Legitimacy is a critical factor for the effectiveness, efficiency, stability, and popular approval of collaborative efforts. However, as a concept, legitimacy remains contested with various meanings, theoretical backgrounds, and source norms. Clarity is particularly needed around the changing sources of legitimacy as collaborative efforts mature. Drawing on case‐study research of five collaborations in British Columbia, Canada, we present a framework of legitimacy sources as collaborations evolve. Legitimacy during the establishment of a collaboration depends principally on community readiness to collaborate, a sense of need, and the perceived potential for goal achievement. As a collaboration continues to grow, its legitimacy forms mainly from normative processes—the perceived quality of factors such as accountability, transparency, consensus‐building, and representation of relevant discourses. Once a collaboration reaches maturity and faces questions of its future existence, legitimacy is largely result‐based—tangible and contextually meaningful outcomes must be easily identifiable and promoted. Increased understanding of the dynamics of legitimacy can help collaborative efforts strategically plan and work toward their goals as they evolve.
Exploring the Reactivity and Biological Effects of Heteroleptic N‐Heterocyclic Carbene Gold(I)‐Alkynyl Complexes
Authors: Oberkofler Jens , Aikman Brech , Bonsignore Riccardo , Pöthig Alexander , Platts James , Casini Angela , Kühn Fritz E.
Published: January 2020

With the aim to explore the effects of different organometallic ligands on the reactivity and biological properties of a series of twelve heteroleptic AuI complexes, of general formula [Au(NHC)(alkynyl)] (NHC = benzimidazolylidene or 1,3‐dihydroimidazolylidene) were synthesized and characterized by 1H and 13C NMR and elemental analysis, and in some cases also by X‐ray diffraction. The compounds were all stable in H2O/DMSO as established by NMR spectroscopy, while they could react with model thiols (EtSH) in the presence of water to undergo ligand‐substitution reactions. 1H NMR experiments showed that dissociation of the more labile alkynyl ligand was possible for all compounds, while in the case of the benzimidazolylidene series also dissociation of the NHC ligand could be observed. DFT calculations suggest that, depending on the steric hindrance exerted by both the NHC wingtip groups and the alkynyl substituents, the reaction can proceed either via a π‐stabilized intermediate or with the alkynyl ligand remaining purely σ‐coordinated to the AuI center until completely dissociated. The most stable compounds in PBS buffer (pH 7.4), as assessed by UV‐Visible spectrophotometry, were further investigated for their ability to stabilize G4 DNA by FRET DNA melting assay, showing only moderate activity. Moreover, two derivatives were tested in vitro for their anticancer activities in three different human cancer cell lines and showed cytotoxicity in the low micromolar range.
A new method for determining weathering rates in weathering pits
Authors: Wang Wei , Huang Rihui , Feng Jing
Published: January 2020

Determining the rates of rock weathering is difficult because, firstly, the weathering rate of rocks is usually so slow that it is difficult to measure; secondly, it is also difficult to determine the start time and duration of weathering. The Shanxi River Valley in Fujian, China dried up after a reservoir was built upstream in 1959, and became a stone quarry site. Quarrying ceased in 1977, so a large amount of quarry wastes with artificially excavated surfaces were left in the valley. The concave‐upward curved rocky surface, broken by manual excavation, easily contains rainwater in its central part, which was easily weathered into a more concave surface. Plaster mould casting was performed in situ on such a concave surface of an excavated stone rock in the valley and scanned with a high‐precision 3D scanner to obtain 3D data of the concave‐upward rock surface and its more concave middle part, which was considered as an initial weathering pit. The 3D model provided an in‐depth understanding of the initial formation process of weathering pits, indicating that: (1) the average weathering rate of a weathering pit is 10.8 ± 0.49 cm ka−1; (2) weathering pits are generally formed by standing water in depressions on a flat near‐horizontal rock surface due to weathering actions involving water; (3) the deepening rate of a weathering pit is about four times greater than that of the surrounding area; (4) the growth of a weathering pit can begin in some small concavities on the flat rock surface without pre‐existing depressions and gradually expands; (5) a weathering pit is generally wider than deep or with a flat bottom due to expansion with a lateral weathering rate that is greater than that of the vertical, and the lamination of the host rock is not necessary for the formation of flat‐floored weathering pits. © 2020 John Wiley & Sons, Ltd.
Reactive oxygen/nitrogen species (ROS/RNS) and oxidative stress in arthroplasty
Authors: Hameister Rita , Kaur Charanjit , Dheen Shaikali Thameem , Lohmann Christoph H. , Singh Gurpal
Published: January 2020

The interplay between implant design, biomaterial characteristics, and the local microenvironment adjacent to the implant is of utmost importance for implant performance and success of the joint replacement surgery. Reactive oxygen and nitrogen species (ROS/RNS) are among the various factors affecting the host as well as the implant components. Excessive formation of ROS and RNS can lead to oxidative stress, a condition that is known to damage cells and tissues and also to affect signaling pathways. It may further compromise implant longevity by accelerating implant degradation, primarily through activation of inflammatory cells. In addition, wear products of metallic, ceramic, polyethylene, or bone cement origin may also generate oxidative stress themselves. This review outlines the generation of free radicals and oxidative stress in arthroplasty and provides a conceptual framework on its implications for soft tissue remodeling and bone resorption (osteolysis) as well as implant longevity. Key findings derived from cell culture studies, animal models, and patients' samples are presented. Strategies to control oxidative stress by implant design and antioxidants are explored and areas of controversy and challenges are highlighted. Finally, directions for future research are identified. A better understanding of the host‐implant interplay and the role of free radicals and oxidative stress will help to evaluate therapeutic approaches and will ultimately improve implant performance in arthroplasty.
Wellness, Emotion Regulation, and Relapse During Substance Use Disorder Treatment
Authors: Clarke Philip B. , Lewis Todd F. , Myers Jane E. , Henson Robert A. , Hill Brent
Published: January 2020

Using a cross‐sectional study design, the authors investigated the impact of wellness and emotion regulation on relapse in 179 individuals currently enrolled in substance use disorder treatment. An integration of the indivisible self model of wellness (Myers & Sweeney, 2004) and the covert antecedents model of relapse (Marlatt, 1985) informed the study hypothesis that emotion regulation mediates the wellness‐relapse relationship. Binomial logistic regressions revealed that Creative Self wellness (odds ratio [OR] = 1.09, p = .002), reappraisal (OR = 1.08, p = .008), difficulties in emotion regulation (OR = 1.03, p = .007), and Physical Self wellness (OR = 0.95, p < .001) were associated with the odds of relapse on any given day during treatment. Sobel tests indicated 2 occurrences of full mediation, including that difficulties in emotion regulation mediated the relationship between Coping Self wellness and relapse (OR = 0.97, p = .015).
Retracted: LINC00657 activates PD‐L1 to promote osteosarcoma metastasis via miR‐106a
Authors: Zhang Jun , Chou Xubin , Zhuang Ming , Zhu Chenlei , Hu Yong , Cheng Dong , Liu Zhiwei
Published: January 2020

Osteosarcoma (OS) cells are one of the primary cancer‐related causes of death around the world. Long noncoding RNAs are key for OS progression; however, the detailed molecular mechanism remains unknown. LINC00657, miR‐106a, and programmed death ligand‐1 (PD‐L1) genes expression were detected by reverse transcription‐quantitative PCR (RT‐qPCR) and Western blot approaches. Invasion and lymphangiogenesis were studied using transwell invasion assay and lymphatic vessel formation assay, respectively. We used bioinformatic analyses to identify putative targets of LINC00657 and miR‐106a. Luciferase activity was measured by dual‐luciferase reporter assay. PD‐L1 protein levels were examined by flow cytometry experiments. LINC00657 knockdown attenuates cell invasion and tumor growth of MG63 and lymphatic vessel formation. miR‐106a directly binds LINC00657 and they regulate each other. Furthermore, miR‐106a inhibitor strikingly enhanced lymphatic vessel formation and invasion of shLINC00657 MG63 cells. miR‐106a mimic directly targeted and downregulated PD‐L1. PD‐L1 overexpression largely rescued miR‐106a mimic‐modulated OS cell metastasis. LINC00657 and PD‐L1 were upregulated in clinical OS tumors compared to normal tissues. Lower expression levels of LINC00657 and PD‐L1 were closely associated with higher overall survival of patients with OS. Here, we suggest a novel mechanism for LINC00657‐regulated metastasis of OS cells by regulating the miR‐106a/PD‐L1 axis. Our conclusions facilitate the development of therapeutical approaches by targeting LINC00657.
Transcription factor RUNX3 promotes CD8+ T cell recruitment by CCL3 and CCL20 in lung adenocarcinoma immune microenvironment
Authors: Song Qian , Shang Jun , Zhang Chufan , Chen Jianing , Zhang Lanlin , Wu Xianghua
Published: January 2020

Considering the existence of immune‐desert in tumor microenvironment, the clinical efficacy of immunotherapy for lung adenocarcinoma is limited. This study aims to investigate the ability of transcription factors in regulating tumor immune microenvironment in lung adenocarcinoma. RNA‐seq data were collected from the The Cancer Genome Atlas database. The relationships between transcription factors and immune infiltrates were assessed. Runt‐related transcription factor 3 (RUNX3)‐associated immune pathways were investigated by the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Gene set enrichment analysis. Upregulated chemokines in the RUNX3‐overexpressed cell line were determined by quantitative real‐time polymerase chain reaction, western blot, and enzyme‐linked immunosorbent assay. These chemokines were further confirmed in RUNX3‐downregulated cell lines. Immunochemistry was conducted to determine the expression of RUNX3, CCL3, CCL20, and the numbers of CD8+ T lymphocytes in human lung cancer tissues. Chemokine receptors in CD8+ T cells were explored by flow cytometry and immunofluorescence. T cell recruitment was investigated by transwell assay. After screening 406 transcription factors, RUNX3 was found strongly correlated T cells, cytotoxic lymphocytes, and CD8+ T cells. RUNX3 was associated with a variety of immunomodulators, including LAG3, CTLA‐4, PD‐1, and TIGIT. More importantly, RUNX3 was involved in immune‐related pathways, especially immune cell migration‐related pathways. Further investigation exhibited RUNX3 could upregulate CCL3 and CCL20 whose receptors CCR5 and CCR6 were upregulated in CD8+ effector T cells, while downregulation of RUNX3 decreased the expression of CCL3 and CCL20 and the infiltration of CD8+ T cells in RUNX3‐downregulated lung cancer cell lines. Immunochemistry exhibited positive correlations of RUNX3 with CCL3 and CD8+ T cells in clinical lung adenocarcinoma samples. The chemotaxis assay proved RUNX3 could promote CD8+ T cell recruitment by upregulating CCL3 and CCL20. This study unearths RUNX3 related molecular mechanisms of tumor immune microenvironment and may reverse the immune‐desert condition in lung adenocarcinoma and be combined with immune checkpoint blockade and adoptive cell therapy.
Comprehensive analysis of biological networks and the eukaryotic initiation factor 4A‐3 gene as pivotal in hepatocellular carcinoma
Authors: Lin Yan , Liang Rong , Mao Yingwei , Ye Jiazhou , Mai Rongyun , Gao Xing , Liu Ziyu , Wainwright Taylor , Li Qian , Luo Min , Ge Lianying , Li Yongqiang , Zou Donghua
Published: January 2020

Eukaryotic initiation factor 4A‐3 (EIF4A3) is a core component of the exon junction complex (EJC). Abnormalities in EIF4A3 are associated with carcinogenesis. The present study aimed to determine the biological role of EIF4A3 in hepatocellular carcinoma (HCC). Our study is based on the analysis of HCC sequencing data from public databases. We first used the Gene Expression Profiling Interactive Analysis tool and ONCOMINE to analyze the EIF4A3 expression, and the results were validated in human clinical tissues by a quantitative real‐time polymerase chain reaction, Western blot, and immunohistochemical. Then, we used cBioPortal to identify EIF4A3 alterations and function networks. Finally, we created a network of genes that were positively correlated with EIF4A3 using LinkedOmics, and analyzed this network using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. For the genes identified, we also analyzed the relevant kinase and transcription factor target networks as well as the protein‐protein interaction networks. Our results show that EIF4A3 was overexpressed in HCC tissues in comparison with normal tissues, and high EIF4A3 expression was significantly associated with poor prognosis. Analysis of the functional networks of genes that were co‐occurring with EIF4A3 amplification revealed connections with several chemokine signaling pathways. Furthermore, genes that positively correlated with EIF4A3 were mainly related to cell cycle and spliceosome pathways, several cell cycle regulatory kinases, and tumor‐associated transcription factors. Finally, crosslinking‐immunoprecipitation and high‐throughput sequencing (CLIP‐seq) data showed that EIF4A3 protein binds to multiple exon regions of the cell cycle regulatory genes cyclin‐dependent kinases 1 and 2 and transcription factor E2F1. Our study unveils potential biological networks in HCC and the pivotal role of EIF4A3 as a bridging protein, highlighting the need for an in‐depth study of EIF4A3 in carcinogenesis.
LncRNA CRNDE is activated by SP1 and promotes osteosarcoma proliferation, invasion, and epithelial‐mesenchymal transition via Wnt/β‐catenin signaling pathway
Authors: Ding Qiuyue , Mo Fengbo , Cai Xianyi , Zhang Wenda , Wang Jinglong , Yang Shuhua , Liu Xianzhe
Published: January 2020

Long noncoding RNAs (lncRNAs) were identified as a vital part in the development and progression of cancer in recent years. Colorectal neoplasia differentially expressed (CRNDE), a lncRNA, functions as an oncogene in some malignant neoplasias, but its role in the progression of osteosarcoma (OS) is still poorly understood. To dissect the difference in the expression of CRNDE, quantitative real‐time polymerase chain reaction was utilized to evaluate it in OS tissues and cell lines (U2OS, MG63, and MNNG/HOS) compared with that in the adjacent normal tissues/osteoblast cells (hFOB1.19). The role of CRNDE in OS lines was assessed using Cell Counting Kit‐8, colony formation, 5‐ethynyl‐2′‐deoxyuridine staining, terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labeling staining, flow cytometry, Transwell assays, and Western blot, respectively. The results demonstrated that the expression of CRNDE was high in OS tissues and cell lines, and partly induced by SP1. CRNDE knockdown attenuated OS cell proliferation and invasion and induced apoptosis and G0/G1 arrest. Moreover, the expression of mesenchymal markers N‐cadherin, Vimentin and Snail were downregulated, while the expression of epithelial markers E‐cadherin and ZO‐1 were conversely upregulated due to CRNDE knockdown. The mechanistic investigations showed that CRNDE promoted glycogen synthase kinase‐3β phosphorylation to activate the Wnt/β‐catenin pathway. The results suggested that lncRNA CRNDE indeed contributed to OS proliferation, invasion, and epithelial‐mesenchymal transition, working as an oncogene, demonstrating that lncRNA CRNDE may be a valid therapeutic target for the OS.
A novel miRNA located in the GATA4 gene regulates the expression of IGF‐1R and AKT1/2 genes and controls cell proliferation
Authors: Medlej Abdallah , Mohammad Soltani Bahram , Javad Mowla Seyed , Hosseini Saeid , Baharvand Hossein
Published: January 2020

GATA4 gene is a zinc‐finger transcription factor known to be involved in cardiogenesis and the progression of different cancer types. Its diverse functions might be attributed to noncoding RNAs that could be embedded within its sequence. Here, we predicted a stable RNA stem‐loop structure that is located in the second intron of the GATA4 gene. Available microRNA (miRNA) sequencing data and molecular genetics tools confirmed the identity of a mature miRNA (named GATA4‐miR1) originating from the predicted stem‐loop. In silico analysis predicted IGF‐1R and AKT1/2 genes as potential targets for GATA4‐miR1. Indeed, direct interactions between GATA4‐miR1 and 3′ untranslated regions sequences of IGF‐1R and AKT1/2 genes were documented by dual luciferase assay. In addition, overexpression of GATA4‐miR1 in SW480 cells resulted in the reduction of IGF‐1R and AKT1/2 genes’ expression, detected by reverse transcription quantitative (RT‐q) polymerase chain reaction and Western blot analysis. This observation was consistent with a deduced negative correlation between the expression patterns of GATA4‐miR1 and IGF‐1R genes during cardiomyocyte differentiation. Moreover, overexpressing GATA4‐miR1 in SW480 and PC3 cells resulted in a significant increase of the sub‐G1 population in both cell lines, as detected by propidium iodide flow cytometry. Further analysis by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide assay indicated a reduction in the survival and proliferation rates of SW480 cells overexpressing GATA4‐miR1, but no impact was observed on apoptosis progression, as indicated by Annexin‐V flow cytometry. Overall, GATA4‐miR1 represents a promising candidate for further research in the fields of cancer and cardiovascular therapeutics.
A switch in bidirectional histone mark leads to differential modulation of lincRNAs involved in neuronal and hematopoietic cell differentiation from their progenitors
Authors: Murad Md. Wahid , Khan Md. Abdullah‐Al‐Kamran , Islam Md. Sajedul , Islam Abul Bashar Mir Md. Khademul
Published: January 2020

Long intergenic noncoding RNAs (lincRNAs) are more than 200 bases long, transcribed from intergenic genomic regions and do not undergo translation. They have regulatory roles in differentiation and development. However, how their transcription is activated and how their expression is differentially modulated in differentiation is quite unclear. In this study, we explored and analyzed data at the transcriptomic and epigenetic level to address these questions. Here, we identified novel lincRNAs that are differentially expressed in neuronal and hematopoietic differentiation and showed that such differential modulations are achieved under epigenetic regulations. lincRNAs that are upregulated in mature cells than in progenitor are activated from a bivalent poised state where activating H3K4me3/H3K9ac/H3K27ac and suppressive H3K9me3/H3K27me3 marks are colocalized. And, lincRNAs that are downregulated in mature cells after differentiation are suppressed by the addition of H3K9me3/H3K27me3 marks. Moreover, here we show a tissue‐specific expression pattern of lincRNAs in various cell lines and normal tissues. The study reveals bidirectional histone marks as an epigenetic means of directing the differential expression of lincRNAs which are found to be involved in the process of cellular differentiation.
Long‐term cultivation of human amniotic fluid stem cells: The impact on proliferative capacity and differentiation potential
Authors: Gasiūnienė Monika , Valatkaitė Elvina , Navakauskienė Rūta
Published: January 2020

Human amniotic fluid mesenchymal stem cells (AF‐MSCs) are a valuable, easily obtainable alternative source of SCs for regenerative medicine. Usually, amounts of cells required for the translational purposes are large thus the goal of this study was to assess the potency of AF‐MSCs to proliferate and differentiate during long‐term cultivation in vitro. AF‐MSCs were isolated from amniotic fluid of healthy women in the second trimester of pregnancy and cultivated in vitro. AF‐MSCs were cultivated up to 42 passages and they still maintained pluripotency genes, such as OCT4, SOX2, and NANOG, expression at a similar level as in the initial passages as determined by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Fluorescence‐activated cell sorting analysis demonstrated that the cell surface markers CD34 (negative), CD44, and CD105 (positive) expression was also stable, only the expression of SCs marker CD90 decreased during the cultivation. The morphology of AF‐MSCs changed over passage, acridine orange/ethidium bromide staining revealed that more cells entered into apoptosis and the first signs of aging were detected only at late passages (later than p33) using SA‐β‐gal assay. Concomitantly, the differentiation potential towards cardiomyogenic lineage, induced with DNA methyltransferases inhibitors decitabine, zebularine, and RG108, was impaired when comparing AF‐MSCs at p31/33 with p6. The expression of cardiomyocytes genes MYH6, TNNT2, DES together with ion channels genes of the heart (sodium, calcium, and potassium) decreased in p31/33 induced AF‐MSCs. AF‐MSCs have a great proliferative capacity and maintain most of the characteristics up to 33 passages; however, the cardiomyogenic differentiation capacity decreases to a certain extent during the long‐term cultivation. These results provide useful insights for the potential use of AF‐MSCs for biobanking and broad applications requiring high yield of cells or repeated infusions. Hence, it is vital to take into account the passage number of AF‐MSCs, cultivated in culture, when utilizing them in vivo or in clinical experiments.
Lnc‐MUC20‐9 binds to ROCK1 and functions as a tumor suppressor in bladder cancer
Authors: Dai Ranran , Zhou You , Chen Zhishan , Zou Zihao , Pan Zhaojun , Liu Ping , Gao Xingcheng
Published: January 2020

The study aimed to investigate the expression and function of bladder cancer (BC) long noncoding RNAs (lncRNAs) using a high‐throughput platform. High‐throughput sequencing was used to compare the expression profiles of lncRNA in BC and adjacent normal tissues. Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR), in situ hybridization, gene ontology, and Kyoto Encyclopedia of Genes and Genomes analysis were performed to verify differential expression of lncRNA. The effect of lncRNA overexpression on cellular proliferation, apoptosis, migration, and invasion was analyzed following the transfection of lncRNA overexpressing lentivirus into 5637 and T24 cell lines. The overexpressing cells were subcutaneously injected into nude mice to evaluate their effects on tumor growth. Tumor‐associated RNA‐binding proteins of lncRNA were analyzed by RNA pull‐down combined with mass spectrometry. A total of 93 lncRNA genes were upregulated and 352 lncRNA genes were downregulated in the tissues of patients with BC. Of which, we investigated the function of downregulated lnc‐MUC20‐9. Overexpression of lnc‐MUC20‐9 in 5637 and T24 cells resulted in decreased tumor cell viability and cell clones, decreased migration and invasion, and increased apoptosis. Similarly, nude mice bearing lnc‐MUC20‐9 overexpressing tumor cells exhibited smaller tumor size and volume than that of mice bearing control cells. Mass spectrometry analysis showed that lnc‐MUC20‐9 binds to ROCK1, an oncogene whose expression was decreased in lnc‐MUC20‐9 overexpressing cells. The study revealed that lnc‐MUC20‐9 has the function of inhibiting tumor growth, migration, and invasion. In BC cells, lnc‐MUC20‐9 binds to ROCK1 and may be involved in lnc‐MUC20‐9‐mediated tumor suppressor function, which might be potential therapeutic targets for BC.
Bio‐based benzoxazines synthesized in a deep eutectic solvent: A greener approach toward vesicular nanosystems
Authors: Behalo Mohamed S. , Bloise Ermelinda , Mele Giuseppe , Salomone Antonio , Messa Francesco , Carbone Luigi , Mazzetto Selma Elaine , Lomonaco Diego
Published: January 2020

A green synthesis of benzoxazines, based upon reaction of cardanol with formaldehyde and primary amines, is achieved in high yields using choline chloride‐urea mixture as deep eutectic solvent. Then, it is demonstrated how the cardanol‐based benxoxazines can be employed as only component for the preparation of a nanovesicular systems.
Administration of gamma‐hydroxybutyrate instead of beta‐hydroxybutyrate to a liver transplant recipient suffering from propionic acidemia and cardiomyopathy: A case report on a medication prescribing error
Authors: Tuchmann‐Durand Caroline , Thevenet Eloise , Moulin Florence , Lesage Fabrice , Bouchereau Juliette , Oualha Mehdi , Khraiche Diala , Brassier Anaïs , Wicker Camille , Gobin‐Limballe Stéphanie , Arnoux Jean‐Baptiste , Lacaille Florence , Wicart Clotilde , Coat Bruno , Schlattler Joel , Cisternino Salvatore , Renolleau Sylvain , Secretan Philippe‐Henri , De Lonlay Pascale
Published: January 2020

Beta‐hydroxybutyrate (BHB) is a synthetic ketone body used as an adjuvant energy substrate in the treatment of patients with metabolic cardiomyopathy. A medication prescribing error led to the administration of the general anesthetic sodium gamma‐hydroxybutyrate (GHB) instead of sodium BHB in a liver transplant recipient with propionic acidemia and cardiomyopathy, causing acute coma. A 15‐year‐old boy suffering from neonatal propionic acidemia underwent liver transplantation (LT) for metabolic decompensation and cardiomyopathy (treated with cardiotropic drugs and BHB) diagnosed a year previously. The patient had been rapidly extubated after LT, and was recovering well. Eight days after LT, the patient suddenly became comatose. No metabolic, immunological, hypertensive, or infectious complications were apparent. The brain magnetic resonance imaging and electroencephalography results were normal. The coma was soon attributed to a medication prescribing error: administration of GHB instead of BHB on day 8 post‐LT. The patient recovered fully within a few hours of GHB withdrawal. The computerized prescription system had automatically suggested the referenced anesthetic GHB (administered intravenously) instead of the non‐referenced ketone body BHB, triggering coma in our patient. A computerized prescription system generated a medication prescribing error for a rare disease, in which the general anesthetic GHB was mistaken for the nonreferenced energy substrate BHB.
The multi‐component Hekla Ö Tephra, Iceland: a complex widespread mid‐Holocene tephra layer
Authors: Jónsson Daníel Freyr , Gudmundsdóttir Esther Ruth , Larsen Gudrún , Óladóttir Bergrún Arna , Erlendsson Egill , Eddudóttir Sigrún Dögg , Sigmarsson Olgeir
Published: January 2020

Large Plinian eruptions from Hekla volcano, Iceland, produce compositionally zoned tephra used as key markers in tephrochronology. However, spatial variations in chemical composition of a tephra layer may complicate its identification. An example is the 5950–6180 cal a bp Hekla Ö tephra layer, which shows compositional spread from rhyolite, dacite and andesite to basalt. In soil sections north of Hekla, the SiO2 content of the tephra glass reaches 76 wt% in the lowest unit of the Hekla Ö deposit and decreases to 62–63 wt% in the uppermost unit. Intermingled within the whole deposit are basalt tephra grains having 46–47 wt% SiO2. The composition of the basalt glass includes primitive basalt and a more evolved basalt (MgO >6 and <6 wt%, respectively). Together with literature data, the Hekla Ö tephra and the so‐called T‐Tephra/Hekla‐T are most likely from contemporaneous eruptions of different vents on the Hekla volcanic system, forming a single important marker tephra (Hekla ÖT) deposited over 80% of Iceland. Identification is complicated by its spatial compositional heterogeneity, such as systematic decrease in SiO2 content from the east to the west of Hekla volcano. Consequently, an individual tephra layer from a large explosive eruption can have different composition at different locations. © 2020 John Wiley & Sons, Ltd.
Head‐attached live sperm cell for label‐free micro‐Raman evaluation of sperm DNA integrity: A preliminary study
Authors: Huang Zufang , Du ShengRong , Liang Xiaozhou , Sun Yan , Chen Xiwen , Lin Juqiang , Li Yongzeng , Chen Guannan , Feng Shangyuan
Published: January 2020

High‐quality spermatozoa are essential for intracytoplasmic sperm injection. However, there is still a lack of noninvasive, objective tools that provide biochemical characteristics to select high‐quality spermatozoa in clinical settings. In this work, a facile yet efficient approach was proposed, rendering the live sperm cell with its head being attached on the surface of a substrate, which allows the subsequent micro‐Raman‐based biochemical analysis and evaluation of sperm DNA integrity noninvasively and nondestructively. Moreover, our preliminary results show that Raman peaks at 1,050 and 1,095 cm−1, which are assigned to DNA backbone mode and whose spectral intensity ratio are suggested as a potential spectral biomarker for evaluation of sperm DNA integrity, can be clearly observed, thus implying our facile yet efficient technique for further potential DNA integrity assessment of live sperm cell.
Attenuation of immune‐mediated bone marrow damage in conventionally housed mice
Authors: Li Jun , Dubois Wendy , Thovarai Vishal , Wu Zhijie , Feng Xingmin , Peat Tyler , Zhang Shuling , Sen Shurjo K. , Trinchieri Giorgio , Chen Jichun , Mock Beverly A. , Young Neal S.
Published: January 2020

In humans, bone marrow (BM) failure syndromes, both constitutional and acquired, predispose to myeloid malignancies. We have modeled acquired immune aplastic anemia, the paradigmatic disease of these syndromes, in the mouse by infusing lymph node cells from specific pathogen‐free (SPF) CD45.1 congenic C57BL/6 (B6) donors into hybrid CByB6F1 recipients housed either in conventional (CVB) or SPF facilities. The severity of BM damage was reduced in CVB recipients; they also had reduced levels of CD44+CD62L− effector memory T cells, reduced numbers of donor‐type CD44+ T cells, and reduced expansion of donor‐type CD8 T cells carrying T‐cell receptor β‐variable regions 07, 11, and 17. Analyses of fecal samples through 16S ribosomal RNA amplicon sequencing revealed greater gut microbial alpha diversity in CVB mice relative to that of SPF mice. Thus, the presence of a broader spectrum of gut microorganisms in CVB‐housed CByB6F1 could have primed recipient animal's immune system leading to suppression of allogeneic donor T‐cell activation and expansion and attenuation of host BM destruction. These results suggest the potential benefit of diverse gut microbiota in patients receiving BM transplants.
Brain Mitochondrial Impairment in Early‐Onset Parkinson's Disease With or Without PINK1 Mutation
Authors: Rango Mario , Dossi Gabriele , Squarcina Letizia , Bonifati Cristiana
Published: January 2020

Background

PINK1 mutations are likely to affect mitochondrial function. The objective of this study was to study brain mitochondrial function in patients with early‐onset Parkinson's disease, with or without PINK1 mutations.

Methods

We investigated brain intracellular pH, mitochondrial activity, and energetics with functional magnetic resonance spectroscopy in patients with early‐onset Parkinson's disease with PINK1 mutations (n = 10), early‐onset Parkinson's disease without PINK1 mutations (n = 10), and healthy sex‐ and age‐matched subjects (n = 20). We measured peak areas of phosphocreatine and beta adenosine triphosphate.

Results

The EOPD‐ group had normal PCr + βATP contents at rest (P = NS) and under activation (P = NS), but reduced contents during recovery (P < 0.001). The EOPD+ group had abnormal PCr + βATP contents at rest (P < 0.001) and during activation (P < 0.001); during recovery, the contents only partially recovered (P < 0.001). Brain intracellular pH alterations were more severe with EOPD+ than with EOPD−.

Conclusions

Brain mitochondrial impairments were similar in early‐onset Parkinson's disease without PINK1 mutations and late‐onset Parkinson's disease. However, mitochondrial impairments were more severe in early‐onset Parkinson's disease with PINK1 mutations. © 2020 International Parkinson and Movement Disorder Society
Motion‐corrected MRI with DISORDER: Distributed and incoherent sample orders for reconstruction deblurring using encoding redundancy
Authors: Cordero‐Grande Lucilio , Ferrazzi Giulio , Teixeira Rui Pedro A. G. , O'Muircheartaigh Jonathan , Price Anthony N. , Hajnal Joseph V.
Published: January 2020

Purpose

To enable rigid body motion‐tolerant parallel volumetric magnetic resonance imaging by retrospective head motion correction on a variety of spatiotemporal scales and imaging sequences.

Theory and methods

Tolerance against rigid body motion is based on distributed and incoherent sampling orders for boosting a joint retrospective motion estimation and reconstruction framework. Motion resilience stems from the encoding redundancy in the data, as generally provided by the coil array. Hence, it does not require external sensors, navigators or training data, so the methodology is readily applicable to sequences using 3D encodings.

Results

Simulations are performed showing full inter‐shot corrections for usual levels of in vivo motion, large number of shots, standard levels of noise and moderate acceleration factors. Feasibility of inter‐ and intra‐shot corrections is shown under controlled motion in vivo. Practical efficacy is illustrated by high‐quality results in most corrupted of 208 volumes from a series of 26 clinical pediatric examinations collected using standard protocols.

Conclusions

The proposed framework addresses the rigid motion problem in volumetric anatomical brain scans with sufficient encoding redundancy which has enabled reliable pediatric examinations without sedation.
Exploring pelvic floor muscle activity in men with lower urinary tract symptoms
Authors: Vrolijks Ruben O. , Notenboom‐Nas Françoise J. M. , de Boer Deborah , Schouten Tamara , Timmerman Alice , Zijlstra Aylene , Witte Lambertus P. W. , Knol‐de Vries Grietje E. , Blanker Marco H.
Published: January 2020

Aim

We aimed to explore the utility of the Multiple Array Probe Leiden (MAPLe) device to assess pelvic floor muscle activity in men with lower urinary tract symptoms (LUTS).

Methods

This was an observational cohort study performed at the urology outpatient department of a large teaching hospital in the Netherlands between April and October 2018. We recruited male patients referred for the assessment of LUTS, without a history of prostate surgery, if they had an International Prostate Symptom Score greater than or equal to 8. The MAPLe device was then used to assess the puborectalis, pubococcygeus, iliococcygeus, urogenital diaphragm, and the internal and external anal sphincters during three tasks: a rest period (1 minute), five maximum voluntary contractions (held for 3 seconds each), and three maximal endurance contractions (held for 15 seconds each).

Results

In total, 57 patients were included, 5 of which had diabetes mellitus. Muscle activity at rest was significantly lower than during either contraction task and did not differ between the muscle groups. By contrast, the external anal sphincter had significantly less activity than any other muscle group during the endurance task, and the internal anal sphincter and puborectalis had significantly less activity during the maximum voluntary contraction task. No association was found between pelvic floor muscle activity and LUTS severity during any task.

Conclusion

Pelvic floor muscle activity and LUTS severity appear to be unrelated, but this does not completely exclude the possibility of muscle involvement in the development or experience of symptoms. Further research is needed.
Is there a link between back pain and urinary symptoms?
Authors: Welk Blayne , Baverstock Richard
Published: January 2020

Aims

To identify epidemiological studies of mechanical low back pain and urinary dysfunction, and to identify potential evidence supporting a mechanism for this relationship.

Methods

A systematic online search was conducted of EmBASE, Medline, CINAHL, and PEDro databases. We excluded studies where an obvious link between low back pain and urinary dysfunction exists (such as cauda equina syndrome). Two reviewers used inclusion/exclusion criteria to screen the articles. Data were extracted and summarised with a narrative review, and study quality was assessed.

Results

We included 22/930 studies. Twelve studies addressed the epidemiological link between low back pain and urinary symptoms. The studies all found a statistically significant association between the diagnosis of urinary incontinence or urinary symptoms and low back pain, (aOR's 1.1 to 3.1). Results were consistent when stratified by sex, age, and when adjusted for confounders. The study quality was good in 4/12. Eight studies reported on an assessment/intervention related to pelvic floor function, urinary symptoms and low back pain. Pelvic floor dysfunction was common in women with low back pain, however randomized studies and pre‐post studies reported mixed results for pelvic floor physiotherapy improving low back pain. The study quality was good in 3/8.

Conclusions

Low back pain and urinary incontinence are associated in large epidemiological studies, and the presence of one condition seems to predispose the development of the other. There is limited evidence to suggest pelvic floor interventions are useful for low back pain in this patient population, therefore the mechanism for this relationship is still unclear.