bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia
Authors: Adhikari Bhim M. , Dukart Juergen , Hipp Joerg F. , Forsyth Anna , McMillan Rebecca , Muthukumaraswamy Suresh D. , Ryan Meghann C. , Hong L. Elliot , Eickhoff Simon B. , Jahandshad Neda , Thompson Paul M. , Rowland Laura M. , Kochunov Peter 
Published: October 2019

AbstractSubanesthetic administration of ketamine is a pharmacological model to elicit positive and negative symptoms of psychosis in healthy volunteers. We used resting‐state pharmacological functional MRI (rsPhfMRI) to identify cerebral networks affected by ketamine and compared them to the functional connectivity (FC) in schizophrenia. Ketamine can produce sedation and we contrasted its effects with the effects of the anxiolytic drug midazolam. Thirty healthy male volunteers (age = 19–37 years) underwent a randomized, three‐way, cross‐over study consisting of three imaging sessions, with 48 hr between sessions. A session consisted of a control period followed by infusion of placebo or ketamine or midazolam. The ENIGMA rsfMRI pipeline was used to derive two long‐distance (seed‐based and dual‐regression) and one local (regional homogeneity, ReHo) FC measures. Ketamine induced significant reductions in the connectivity of the salience network (Cohen's d: 1.13 ± 0.28, p = 4.0 × 10−3), auditory network (d: 0.67 ± 0.26, p = .04) and default mode network (DMN, d: 0.63 ± 0.26, p = .05). Midazolam significantly reduced connectivity in the DMN (d: 0.77 ± 0.27, p = .03). The effect sizes for ketamine for resting networks showed a positive correlation (r = .59, p = .07) with the effect sizes for schizophrenia‐related deficits derived from ENIGMA's study of 261 patients and 327 controls. Effect sizes for midazolam were not correlated with the schizophrenia pattern (r = −.17, p = .65). The subtraction of ketamine and midazolam patterns showed a significant positive correlation with the pattern of schizophrenia deficits (r = .68, p = .03). RsPhfMRI reliably detected the shared and divergent pharmacological actions of ketamine and midazolam on cerebral networks. The pattern of disconnectivity produced by ketamine was positively correlated with the pattern of connectivity deficits observed in schizophrenia, suggesting a brain functional basis for previously poorly understood effects of the drug.
Increased Affinity of 2′‐O‐(2‐Methoxyethyl)‐Modified Oligonucleotides to RNA through Conjugation of Spermine at Cytidines
Authors: Decuypere Elodie , Lepikhina Anastasia , Halloy François , Hall Jonathan 
Published: October 2019

AbstractStructural modification at the 2′‐O‐position of riboses in oligonucleotide therapeutics is of critical importance for their use as drugs. To date, the methoxyethyl (MOE) substituent is the most important and features in dozens of antisense oligonucleotides that have been tested in clinical trials. Yet, the search for new improved modifications continues in a quest for increased oligonucleotide potency, improved transport in vivo and favorable metabolism. Recently, we described how the conjugation of spermine groups to pyrimidines in oligonucleotides vastly increases their affinity for complementary RNAs through accelerated binding kinetics. Here we describe how spermines can be linked to the exocyclic amino groups of cytidines in MOE‐oligonucleotides employing a straightforward ‘convertible nucleoside approach’ during solid phase synthesis. Singly‐ or doubly‐modified oligonucleotides show greatly enhanced affinity for complementary RNA, with potential for a new generation of MOE‐based oligonucleotide drugs.
An update of a former FIGO Working Group Report on Management of Posterior Compartment Prolapse
Authors: Doumouchtsis Stergios K. , Raheem Ali Abdel , Milhem Haddad Jorge , Betschart Cornelia , Contreras Ortiz Oscar , Nygaard Christiana C. , Medina Carlos A. , La Torre Fillippo , Iancu George , Cervigni Mauro , Zanni Giuliano 
Published: October 2019

AbstractBackgroundThe FIGO Working Group (FWG) in Pelvic Floor Medicine and Reconstructive Surgery (2012–2015) established a consensus among international opinion leaders in evaluating current evidence and providing practice recommendations.ObjectivesTo provide an update of the previous clinical opinion report on conservative and surgical treatment of posterior compartment prolapse.Search strategySearch of evidence was performed using Pubmed, Embase, and Cochrane Library databases up to August 2018.Selection criteriaControlled trials on posterior colporrhaphy, site‐specific defect, transanal, abdominal, laparoscopic, and mesh repair.Data collection and analysisCollective consensus on surgical outcomes was based on a decision‐making process during meetings and multiple group consultations.Main resultsBasic evaluation and conservative treatment precede surgical management. Surgical techniques are performed by vaginal, transperineal, transanal, abdominal, or laparoscopic approach. The transvaginal surgical route without mesh appears superior to the transanal route. No conclusions can be drawn based on clinical studies or randomized controlled trials of posterior colporrhaphy and laparoscopic rectopexy.ConclusionsManagement of rectocele should include patients’ history, quality of life questionnaires, and, in case of complex anorectal symptoms, imaging and functional studies. Evidence on the best type of posterior vaginal wall repair is still scarce. Randomized controlled trials are needed to determine the best approach to achieve safe, effective, and long‐term anatomical and functional outcomes.
Prospective observational study of the efficacy of mixed methylene blue compound injection for treatment of vulvar non‐neoplastic epithelial disorders
Authors: Li Yanli , Shi Jie , Tan Wenfu , Ma Quanfu , Wu Xufeng , Gao Han 
Published: October 2019

AbstractObjectiveTo investigate the safety and efficacy of mixed methylene blue (MB) compound injection for treatment of vulvar non‐neoplastic epithelial disorders (NNEDs).MethodsA prospective observational study among 118 women with vulvar NNEDs treated with intradermal injection of mixed MB compound at a hospital in Wuhan, China, between 2013 and 2016. Itching score, skin hypopigmentation area percentage (SHAP), and recurrence were assessed by interview and physical examination before and after treatment. Adverse effects were recorded.ResultsBefore treatment, mean ± SD itching score was 7.78 ± 1.59. It decreased rapidly immediately after treatment and remained low thereafter (1.82 ± 2.31, 1.69 ± 2.39, 1.97 ± 2.73, 2.05 ± 2.72, and 2.19 ± 2.86 at 1, 3, 6, 12, and 24 months, respectively). Before treatment, mean ± SD SHAP was 28.01% ± 18.28%. SHAP decreased gradually and remained stably low 6 months later (26.28% ± 17.95%, 21.19% ± 18.42%, 19.19% ± 18.67%, 18.68% ± 18.91%, and 18.65% ± 19.20% at 1, 3, 6, 12, and 24 months, respectively). The recurrence rate in 2 years was 21.2% (25/118) with no major complications.ConclusionsIntradermal injection of mixed MB compound was found to be an effective and safe treatment for vulvar NNEDs.ClinicalTrials.gov: NCT03200808.
Phosphate glass fibers facilitate proliferation and osteogenesis through Runx2 transcription in murine osteoblastic cells
Authors: Lin Xiao , Chen Qiang , Xiao Yunyun , Gao Yongguang , Ahmed Ifty , Li Meng , Li Hui , Zhang Kewen , Qiu Wuxia , Liu Xianhu , Boccaccini Aldo R. , Qian Airong 
Published: October 2019

AbstractCell–material interactions and compatibility are important aspects of bioactive materials for bone tissue engineering. Phosphate glass fiber (PGF) is an attractive inorganic filler with fibrous structure and tunable composition, which has been widely investigated as a bioactive filler for bone repair applications. However, the interaction of osteoblasts with PGFs has not been widely investigated to elucidate the osteogenic mechanism of PGFs. In this study, different concentrations of short PGFs with interlaced oriented topography were cocultured with MC3T3‐E1 cells for different periods, and the synergistic effects of fiber topography and ionic product of PGFs on osteoblast responses including cell adhesion, spreading, proliferation, and osteogenic differentiation were investigated. It was found that osteoblasts were more prone to adhere on PGFs through Vinculin protein, leading to enhanced cell proliferation with polygonal cell shape and spreading cellular actin filaments. In addition, osteoblasts incubated on PGF meshes showed enhanced alkaline phosphatase activity, extracellular matrix mineralization, and increased expression of osteogenesis‐related marker genes, which could be attributed to the Wnt/β‐catenin/Runx2 signaling pathway. This study elucidated the possible mechanism of PGF on triggering specific osteoblast behavior, which would be highly beneficial for designing PGF‐based bone graft substitutes with excellent osteogenic functions.
Retracted: Long noncoding RNA MEG3 deteriorates inflammatory damage by downregulating microRNA‐101a
Authors: Tang Shouyi , Han Junxia , Jiao Hui , Si Jingna , Liu Yingying , Wang Jinlong 
Published: October 2019

AbstractValvulopathy is a familiar heart disease, which fearfully harms the health of the body. We studied the effects and mechanism of long noncoding RNA maternally expressed gene 3 (lncMEG3) on MVICs cell in inflammatory damage. Cell Counting Kit‐8 and flow cytometry were respectively used to detect the effect of tumor necrosis factor α (TNF‐α), MEG3 and microRNA (miR)‐101a on cell viability and apoptosis. Moreover, MEG3 and miR‐101a expression were changed by cell transfection and investigated by reverse transcription‐quantitative polymerase chain reaction. Furthermore, Western blot was used to investigate the levels of Bax, pro‐caspase‐3, cleaved‐caspase‐3, pro‐caspase‐9, cleaved‐caspase‐9, interleukin (IL)‐1β, IL‐6 and related‐proteins of cell pathways. Otherwise, the levels of IL‐1β and IL‐6 were also investigated by enzyme‐linked immunosorbent assay kit. Reactive oxygen species (ROS) was examined by ROS assay. We found TNF‐α caused inflammatory damage and upregulated MEG3. MEG3 was overexpressed and silenced in cells. Besides, MEG3 deteriorated inflammatory damage. Furthermore, MEG3 negatively regulated miR‐101a and miR‐101a mimic could reverse the effect of pc‐MEG3. Besides, MEG3 enhanced the JNK and NF‐κB pathways by downregulating miR‐101a. In conclusion, MEG3 deteriorated cell inflammatory damage by downregulating miR‐101a via JNK and NF‐κB pathways.
Development of a novel gene signature in patients without Helicobacter pylori infection gastric cancer
Authors: Lv Xuemei , Zhao Yanyun , Zhang Liwen , Zhou Shuqi , Zhang Bing , Zhang Qiang , Jiang Longyang , Li Xueping , Wu Huizhe , Zhao Lin , Wei Minjie , He Miao 
Published: October 2019

AbstractGastric cancer (GC) is one of the most fatal common cancers in worldwide. Helicobacter pylori (H. pylori) infection is closely related to the development of GC, although the mechanism is still unclear. In our study, we aim to develop a robust messenger RNA (mRNA) signature associated with H. pylori (‐) GC that can sensitively and efficiently predict the prognostic. The RNA‐seq expression profile and corresponding clinical data of 598 gastric cancer samples and 63 normal samples obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database. Using gene set enrichment analysis H. pylori (+) GC and H. pylori (‐) GC patients and normal samples to select certain genes for further analysis. Using univariate and multivariate Cox regression model to establish a gene signature for predicting the overall survival (OS). Finally, we identified G2/M related seven‐mRNA signature (TGFB1, EGF, MKI67, ILF3, INCENP, TNPO2, and CHAF1A) closely related to the prognosis of patients with H. pylori (‐) GC. The seven‐mRNA signature was identified to act as an independent prognostic biomarker by stratified analysis and multivariate Cox regression analysis. It was also validated on two test groups from TCGA and GSE15460 and shown that patients with high‐risk scores based on the expression of the seven mRNAs had significantly shorter survival times compared to patients with low‐risk scores (P < .0001).In this study, we developed a seven‐mRNA signature related to G2/M checkpoint from H. pylori (‐) GCs that as an independent biomarker potentially with a good performance in predicting OS and might be valuable for the clinical management for patients with GC.
Expression and clinical value of PD‐L1 which is regulated by BRD4 in tongue squamous cell carcinoma
Authors: Zhao Lu , Li Pengchong , Zhao Li , Wang Miao , Tong Dongdong , Meng Zilin , Zhang Qian , Li Qing , Zhang Fenghe 
Published: October 2019

AbstractThe programmed cell death‐ligand‐1 (PD‐L1) and bromodomain protein 4 (BRD4) are frequently overexpressed in cancer and have even been shown to act synergistically. The aim of this study was to determine their potential oncogenic role .in tongue squamous cell carcinoma (TSCC). We detected significantly higher expression levels of both PD‐L1 and BRD4 in TSCC tissues compared to normal tissues (P ≤ .05). In addition, the high levels of PD‐L1 were significantly associated with increased tumor lymphatic metastasis (P ≤ .05), tumor staging (P ≤ .01), as well as BRD4 expression (P ≤ .05). Genetic and pharmacological inhibition of BRD4 in TSCC cells not only reduced their growth rate but also PD‐L1 levels (P ≤ .05), while overexpression of BRD4 upregulated PD‐L1. Bioinformatics analysis showed that c‐MYC and CDK9 were interactive partners of both BRD4 and PD‐L1. While c‐MYC clearly modulated the expression of PD‐L1, as well as reversed the inhibitory effects of JQ1, no obvious association was observed between CDK9 and PD‐L1. We report a novel regulatory axis consisting of BRD4, PD‐L1, and c‐MYC that likely drives TSCC progression, and is a potential prognostic marker and/or therapeutic target for TSCC.
IL‐35, a double‐edged sword in cancer
Authors: Yazdani Zahra , Rafiei Alireza , Golpour Monireh , Zafari Parisa , Moonesi Mohammadreza , Ghaffari Sasan 
Published: October 2019

AbstractInterleukin 35 (IL‐35), a cytokine mainly produced by regulatory T cells (Treg cells), is composed of an Epstein‐Barr virus–induced gene 3 β‐chain and an IL‐12 p35 α‐chain. IL‐35 causes tumorigenicity in cancer, protects cancer cells against apoptosis, and facilitates cancer progression. However, a few reports have referred to its contradictory roles in cancer prevention. Therefore, the exact purpose of this cytokine in cancer development has become a fundamental question that needs to be answered. In this review, we explain the structure of IL‐35 and its receptors and their different signaling pathways. Finally, the function of IL‐35 in some cancers and the possible application of this cytokine in approaches for cancer therapy have been discussed.
Evaluation of a multiplex PCR assay for detection of respiratory viruses and Mycoplasma pneumoniae in oropharyngeal swab samples from outpatients
Authors: Zhang Ying , Cao Lan , Xu Zhi , Zhu Pingting , Huang Bing , Li Kuibiao , Xu Yang , Zhang Zhoubin , Wu Yong , Di Biao 
Published: October 2019

AbstractBackgroundRespiratory viruses, such as influenza viruses, initially infect the upper airways but can manifest as severe lower respiratory tract infections in high‐risk patients with significant morbidity and mortality. For syndromic diagnosis, several multiplex nucleic acid amplification tests have been developed for clinics, of which SureX 13 Respiratory Pathogen Multiplex Kit (ResP) can simultaneously detect 13 pathogens directly from airway secretion specimens. The organisms identified are influenza virus A, influenza virus A pdmH1N1 (2009), influenza virus A H3N2, influenza virus B, adenovirus, boca virus, rhinovirus, parainfluenza virus, coronavirus, respiratory syncytial virus, human metapneumovirus, Mycoplasma pneumoniae, and Chlamydia.MethodsThis study provides performance evaluation data of this assay by comparing with pathogen‐specific PCRs from oropharyngeal swab samples.ResultsTen pathogens were detected in this assay, of which rhinovirus, adenovirus, and influenza virus A pdmH1N1 (2009) were the most common. The overall agreement between the ResP and the comparator tests was 93.8%. The ResP demonstrated 86.5% agreement for positive results and 97.8% agreement for negative results.ConclusionThe ResP assay demonstrated a highly concordant performance comparing with pathogen‐specific PCRs for detection of respiratory pathogens in oropharyngeal swabs from outpatients and could aid in the diagnosis of respiratory infections in a variety of clinical scenarios.
The induced damage in the hepatopancreas of Orchestia species after exposure to a mixture of Cu/Zn—An ultrastructural study
Authors: Jelassi Raja , Khemaissia Hajer , Ghemari Chedliya , Raimond Maryline , Souty‐Grosset Catherine , Nasri‐Ammar Karima 
Published: October 2019

AbstractThe hepatopancreas of crustaceans species has been recognized as an essential target organ to assess trace elements' effects. Due to its dynamic and capability of detoxifying trace metal, this organ often indicates distinct pathological disturbances. In the present work, we intend to evaluate the bioaccumulation of trace metal in three Orchestia species (Orchestia montagui, Orchestia gammarellus, and Orchestia mediterranea) living in symmetry in the banks of Bizerte lagoon (37°13′8″N 09°55′1″E) after their exposure during 14 days to a mixture of copper and zinc, and to highlight the effect of these metals on their hepatopancreas ultrastructure using transmission electron microscopy. At the end of the experiment, results showed that the mortality and the body mass varied according to the used nominal concentrations. Significant alterations were noted in all the treatment groups. The degree of these alterations depends on the used concentration, and they are represented especially by the cells remoteness and the border lyses, the reduction of the nuclear volume, the increase in the cytoplasm density with the presence of trace metal in the nucleus as well as in the vacuole, the disorganization and the destruction of microvilli, the condensation of the majority of cellular organelles and mitochondria swelling. Through this study, Orchestia genus could be an attractive candidate for the biochemical study of trace metal toxicity in Tunisian wetlands.
Characterization of two‐dimensional materials from Raman spectral data
Authors: Mishra Preet , Narayan Tripathi Laxmi 
Published: October 2019

AbstractTwo‐dimensional materials like graphene and transition metal dichalcogenides materials such as WS2 and MoS2 are an attractive material platform for optoelectronics devices, photovoltaics, and strain‐induced deterministic single‐photon sources due to high carrier mobility, tunable band gap, and ease of transfer on the desired substrates. In many of these applications, knowing the number of layers is important; for example, only strained monolayer of WSe2 emits single photons at 4.5 K. Here, we present an analytical tool based on open‐source Python modules to determine the number of layers (accurately, up to five layers) by analyzing Raman spectral data. Using the data from spatially resolved Raman measurements on a two‐dimensional material and this tool, the sample morphology in terms of a number of layers can be preliminarily determined.
Polarization Gratings in Azobenzene‐Based Fully Liquid Crystalline Triblock Copolymer
Authors: Bugakov Miron , Sakhno Oksana , Boiko Natalia , Ryabchun Alexander 
Published: October 2019

AbstractPhotosensitive liquid crystalline (LC) block copolymers are a universal platform for designing functional materials for optics and photonics. Here, azobenzene LC ABA triblock copolymer containing mesogenic groups in each block is studied as a medium for the recording of polarization holographic gratings. The fast recording of polarization gratings is successfully performed with two orthogonally circularly polarized light beams of a 532‐nm laser. It is shown that annealing of the recorded polarization grating increases diffraction efficiency considerably, by a factor of 70, and provokes simultaneous erasing of the surface relief grating if it has been recorded. Holographic behavior of the triblock copolymer is compared with that of an azobenzene homopolymer and a random copolymer, which has the same monomer ratio as the triblock copolymer. The obtained results are expected to allow designing new materials for the polarization of optical elements and holographic data storage.
De novo splice site variant of ARID1B associated with pathogenesis of Coffin–Siris syndrome
Authors: Pranckėnienė Laura , Siavrienė Evelina , Gueneau Lucie , Preikšaitienė Eglė , Mikštienė Violeta , Reymond Alexandre , Kučinskas Vaidutis 
Published: October 2019

AbstractBackgroundCoffin–Siris syndrome is an extremely rare syndrome associated with developmental and congenital anomalies. It is caused by heterozygous pathogenic variants of ARID1A, ARID1B, SMARCA4, SMARCB1, SMARCE1, and SOX11.MethodsThis case study presents the whole exome sequencing of a patient with characteristic clinical features of Coffin–Siris syndrome. Analysis included Sanger sequencing of complementary DNA and bioinformatic analysis of the variant.ResultsAnalysis of cDNA Sanger sequencing data revealed that the donor splice site variant led to skipping of exon 19. Further, bioinformatic analysis predicted abnormal splicing in a translational frameshift of 11 amino acids and the creation of a premature termination codon. Results found a novel de novo splice site variant c.5025+2T>C in the ARID1B and truncated 1 633 amino acid protein NP_065783.3:p. (Thr1633Valfs*11).ConclusionTruncated ARID1B resulted in loss of the BAF250 domain, which is part of SWI/SNF‐like ATP‐dependent chromatin remodeling complex. The severe clinical manifestation presented by the proband was attributed to the disappearance of the BAF250 domain in the ARID1B protein. Our finding provides strong evidence that this pathogenic variant of exon 19 caused a frameshift mutation in the ARID1B at the terminal exon, resulting in the expression of a severe phenotype of CSS.