bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of prenatal diagnosis on the management and early outcome of critical duct-dependent cardiac lesions
Authors: Thakur Varsha , Dutil Nathalie , Schwartz Steven M. , Jaeggi Edgar 
Published: February 2018

AbstractObjectiveThe objective of this study was to compare the preoperative management and outcome of neonates with duct-dependent critical CHD with fetal versus postnatal diagnosis.MethodsPatients referred with CHD to our centre from January 1, 2009 to December 31, 2010 were enrolled prospectively. Live births with a critical form of CHD, a gestational age ⩾36 weeks and a weight ⩾2 kg at birth, and the intention-to-treat were included in this sub-study. Excluded were neonates with lethal non-cardiac and/or genetic anomalies.ResultsIn total, 129, 63 fetal and 66 postnatal, cases met the study inclusion criteria. All had received appropriate antenatal care, including a routine fetal anatomy scan. Both cohorts were comparable in weight, gestational age, and APGAR scores at birth. Unlike the postnatal cases, there were no deaths (0/63 versus 5/66; p=0.06) and no cardiac arrests (0/63 versus 9/63; p=0.003) before surgery or catheter intervention in those cases with a prenatal diagnosis of critical CHD. Moreover, newborns with fetal diagnoses were admitted earlier (median 0 (range 0–3) versus 2 (0–25) days; p<0.001) and were less likely to require preoperative ventilation (19/63 versus 31/61, p=0.03) and vasoactive medication (4/63 versus 15/61, p=0.006) than the postnatal cases.ConclusionsPrenatal diagnosis of critical CHD in this study was associated with significantly shorter time intervals from birth to neonatal admission and the absence of life-threatening or fatal preoperative cardiac events. Increased efforts should be made to improve rates of prenatal diagnosis.
Diagnostic errors in paediatric cardiac intensive care
Authors: Bhat Priya N. , Costello John M. , Aiyagari Ranjit , Sharek Paul J. , Algaze Claudia A. , Mazwi Mjaye L. , Roth Stephen J. , Shin Andrew Y. 
Published: February 2018

AbstractIntroductionDiagnostic errors cause significant patient harm and increase costs. Data characterising such errors in the paediatric cardiac intensive care population are limited. We sought to understand the perceived frequency and types of diagnostic errors in the paediatric cardiac ICU.MethodsPaediatric cardiac ICU practitioners including attending and trainee physicians, nurse practitioners, physician assistants, and registered nurses at three North American tertiary cardiac centres were surveyed between October 2014 and January 2015.ResultsThe response rate was 46% (N=200). Most respondents (81%) perceived that diagnostic errors harm patients more than five times per year. More than half (65%) reported that errors permanently harm patients, and up to 18% perceived that diagnostic errors contributed to death or severe permanent harm more than five times per year. Medication side effects and psychiatric conditions were thought to be most commonly misdiagnosed. Physician groups also ranked pulmonary overcirculation and viral illness to be commonly misdiagnosed as bacterial illness. Inadequate care coordination, data assessment, and high clinician workload were cited as contributory factors. Delayed diagnostic studies and interventions related to the severity of the patient’s condition were thought to be the most commonly reported process breakdowns. All surveyed groups ranked improving teamwork and feedback pathways as strategies to explore for preventing future diagnostic errors.ConclusionsPaediatric cardiac intensive care practitioners perceive that diagnostic errors causing permanent harm are common and associated more with systematic and process breakdowns than with cognitive limitations.
The nutritional content of supermarket beverages: a cross-sectional analysis of New Zealand, Australia, Canada and the UK
Authors: Chepulis Lynne , Mearns Gael , Hill Shaunie , Wu Jason HY , Crino Michelle , Alderton Sarah , Jenner Katharine 
Published: February 2018

AbstractObjectiveTo compare the nutritional content, serving size and taxation potential of supermarket beverages from four different Western countries.DesignCross-sectional analysis. Multivariate regression analysis and χ2 comparisons were used to detect differences between countries.SettingSupermarkets in New Zealand (NZ), Australia, Canada and the UK.SubjectsSupermarket beverages in the following categories: fruit juices, fruit-based drinks, carbonated soda, waters and sports/energy drinks.ResultsA total of 4157 products were analysed, including 749 from NZ, 1738 from Australia, 740 from Canada and 930 from the UK. NZ had the highest percentage of beverages with sugar added to them (52 %), while the UK had the lowest (9 %, P<0·001). Differences in energy, carbohydrate and sugar content were observed between countries and within categories, with UK products generally having the lowest energy and sugar content. Up to half of all products across categories/countries exceeded the US Food and Drug Administration’s reference single serving sizes, with fruit juices contributing the greatest number. Between 47 and 83 % of beverages in the different countries were eligible for sugar taxation, the UK having the lowest proportion of products in both the low tax (5–8 % sugar) and high tax (>8 % sugar) categories.ConclusionsThere is substantial difference between countries in the mean energy, serving size and proportion of products eligible for fiscal sugar taxation. Current self-regulatory approaches used in these countries may not be effective to reduce the availability, marketing and consumption of sugar-sweetened beverages and subsequent intake of free sugars.
Dignity in cancer patients with a life expectancy of a few weeks. Implementation of the factor structure of the Patient Dignity Inventory and dignity assessment for a patient-centered clinical intervention: A cross-sectional study
Authors: Bovero Andrea , Sedghi Nader Alessandro , Botto Rossana , Tosi Chiara , Ieraci Valentina , Torta Riccardo 
Published: February 2018

AbstractObjectiveHospice is a favored setting for dignity care. Studies on dignity dimension in end-of-life patients are growing. The Patient Dignity Inventory (PDI) is a tool that can lead to interesting information on dignity-related aspects of suffering. The study aimed to investigate dignity among end-of-life cancer patients, by examining the Italian version of the PDI factor structure and assessing the relationship between dignity and other patients’ psychosocial and spiritual variables to improve a patient-centered clinical practice.MethodThis is a cross-sectional study. Data were collected using a battery of self-administered validated rating scales. The sample included 127 hospice patients with a life expectancy of a few weeks and a Karnofsky Performance Status ≤40. Factor structure and concurrent validity of PDI and correlations between dignity and anxious and depressive symptomatology, quality of life, demoralization, personal coping styles, spiritual well-being, and spiritual daily experience were analyzed.ResultFactor analysis highlighted a five-factor solution, accounting for 60% of the overall variance. The factors were labeled Psychological Distress, Social Support, Physical Symptoms and Dependency, Existential Distress, and Loss of Purpose/Meaning. Dignity assessment evidenced that self-blame coping style, emotional and physical well-being, and depression were the loss of dignity significant predictors (R2 = 0.605; p < 0.01).Significance of resultsThe results point out the intercultural validity of the PDI and empower an accurate detection of dignity-related distress sources in the daily clinical practice. Personality traits seem to have an active role in the loss of dignity, whereas spirituality is confirmed to be positively involved in dignity enhancement.
Evaluation of autophagy inducers in epithelial cells carrying the ΔF508 mutation of the cystic fibrosis transmembrane conductance regulator CFTR
Authors: Zhang Shaoyi , Stoll Gautier , Pedro José Manuel Bravo San , Sica Valentina , Sauvat Allan , Obrist Florine , Kepp Oliver , Li Yousheng , Maiuri Luigi , Zamzami Naoufal , Kroemer Guido 
Published: February 2018

AbstractCystic Fibrosis (CF) due to the ΔF508 mutation of cystic fibrosis transmembrane conductance regulator (CFTR) can be treated with a combination of cysteamine and Epigallocatechin gallate (EGCG). Since ECGC is not a clinically approved drug, we attempted to identify other compounds that might favourably interact with cysteamine to induce autophagy and thus rescuing the function of ΔF508 CFTR as a chloride channel in the plasma membrane. For this, we screened a compound library composed by chemically diverse autophagy inducers for their ability to enhance autophagic flux in the presence of cysteamine. We identified the antiarrhythmic Ca2+ channel blocker amiodarone, as an FDA-approved drug having the property to cooperate with cysteamine to stimulate autophagy in an additive manner. Amiodarone promoted the re-expression of ΔF508 CFTR protein in the plasma membrane of respiratory epithelial cells. Hence, amiodarone might be yet another compound for the etiological therapy of CF in patients bearing the ΔF508 CFTR mutation.
ROS-independent ER stress-mediated NRF2 activation promotes warburg effect to maintain stemness-associated properties of cancer-initiating cells
Authors: Chang Ching-Wen , Chen Yu-Syuan , Tsay Yeou-Guang , Han Chia-Li , Chen Yu-Ju , Yang Cheng-Chieh , Hung Kai-Feng , Lin Chao-Hsiung , Huang Tsung-Yen , Kao Shou-Yen , Lee Te-Chang , Lo Jeng-Fan 
Published: February 2018

AbstractCancer-initiating cells (CICs) are responsible for tumor initiation, progression, and therapeutic resistance; moreover, redox homeostasis is important in regulating cancer stemness. Previously, we have identified that cancer cells containing low intracellular reactive oxygen species levels (ROSLow cells) display enhanced features of CICs. However, the specific metabolic signatures of CICs remain unclear and are required for further characterization by systemic screenings. Herein, we first showed CICs mainly relying on glycolysis that was important for the maintenance of stemness properties. Next, we revealed that NRF2, a master regulator of antioxidants, was able to maintain low intracellular ROS levels of CICs, even though in the absence of oxidative stress. We further characterized that NRF2 activation was required for the maintenance of CICs properties. Of ROSLow cells, NRF2 activation not only directly activates the transcription of genes encoding glycolytic enzymes but also inhibited the conversion of pyruvate to acetyl-CoA by directly activating pyruvate dehydrogenase kinase 1 (PDK1) to lead to inhibition of tricarboxylic acid (TCA) cycle; therefore, to promote Warburg effect. A positive regulatory ROS-independent ER stress pathway (GRP78/p-PERK/NRF2 signaling) was identified to mediate the metabolic shift (Warburg effect) and stemness of CICs. Lastly, co-expression of p-PERK and p-NRF2 was significantly associated with the clinical outcome. Our data show that NRF2 acting as a central node in the maintenance of low ROS levels and stemness associated properties of the CICs, which is significantly associated with the clinical outcome, but independent from ROS stress. Future treatments by inhibiting NRF2 activation may exhibit great potential in targeting CICs.
Neuroglobin boosts axon regeneration during ischemic reperfusion via p38 binding and activation depending on oxygen signal
Authors: Xiong Xin Xin , Pan Feng , Chen Ruo Qiao , Hu Dian Xing , Qiu Xin Yao , Li Chun Yang , Xie Xiao Qiang , Tian Bo , Chen Xiao Qian 
Published: February 2018

AbstractCerebral ischemia causes severe cell death or injury including axon breakdown or retraction in the brain. Axon regeneration is crucial for the functional recovery of injured neurons or brains after ischemia/reperfusion (I/R); however, this process has been proved extremely difficult in adult brains and there is still no effective therapy for it. Here we reported that neuroglobin (Ngb), a novel oxygen-binding or sensor protein existing predominantly in neurons or brains, functions as a driving factor for axon regeneration during I/R. Ngb was upregulated and accumulated in growth cones of ischemic neurons in primary cultures, rat, and human brains, correlating positively to the elevation of axon-regeneration markers GAP43, neurofilament-200, and Tau-1. Ngb overexpression promoted while Ngb knockdown suppressed axon regeneration as well as GAP43 expression in neurons during oxygen-glucose deprivation/reoxygenation (OGD/Re). By using specific pharmacological inhibitors, we identified p38 MAPK as the major downstream player of Ngb-induced axon regeneration during OGD/Re. Mechanistically, Ngb directly bound to and activated p38 in neurons upon OGD/Re. Serial truncation and point mutation of Ngb revealed that the 7–105 aa fragment of Ngb was required and the oxygen-binding site (His64) of Ngb was the major regulatory site for its p38 interaction/activation. Finally, administration of exogenous TAT-Ngb peptides significantly enhanced axon regeneration in cultured neurons upon OGD/Re. Taken together, Ngb promotes axon regeneration via O2-Ngb-p38-GAP43 signaling during I/R. This novel mechanism suggests potential therapeutic applications of Ngb for ischemic stroke and other related axonopathy.
Publisher Correction: A Co3O4-CDots-C3N4 three component electrocatalyst design concept for efficient and tunable CO2 reduction to syngas
Authors: Guo Sijie , Zhao Siqi , Wu Xiuqin , Li Hao , Zhou Yunjie , Zhu Cheng , Yang Nianjun , Jiang Xin , Gao Jin , Bai Liang , Liu Yang , Lifshitz Yeshayahu , Lee Shuit-Tong , Kang Zhenhui 
Published: February 2018

The original HTML version of this Article omitted to list Yeshayahu Lifshitz as a corresponding author and incorrectly listed Shuit-Tong Lee as a corresponding author.Correspondingly, the original PDF version of this Article incorrectly stated that “Correspondence and requests for materials should be addressed to X.J. (email: xin.jiang@uni-siegen.de), or to Y.L. (email: yangl@suda.edu.cn), or to S.-T.L. (email: shayli@technion.ac.il), or to Z.K. (email: zhkang@suda.edu.cn)”, instead of the correct “Correspondence and requests for materials should be addressed to X.J. (email: xin.jiang@uni-siegen.de), or to Y. Liu (email: yangl@suda.edu.cn), or to Y. Lifshitz (email: shayli@technion.ac.il), or to Z.K. (email: zhkang@suda.edu.cn)”.This has now been corrected in the PDF and HTML versions of the Article.
Neuropathic MORC2 mutations perturb GHKL ATPase dimerization dynamics and epigenetic silencing by multiple structural mechanisms
Authors: Douse Christopher H. , Bloor Stuart , Liu Yangci , Shamin Maria , Tchasovnikarova Iva A. , Timms Richard T. , Lehner Paul J. , Modis Yorgo 
Published: February 2018

AbstractMissense mutations in MORC2 cause neuropathies including spinal muscular atrophy and Charcot–Marie–Tooth disease. We recently identified MORC2 as an effector of epigenetic silencing by the human silencing hub (HUSH). Here we report the biochemical and cellular activities of MORC2 variants, alongside crystal structures of wild-type and neuropathic forms of a human MORC2 fragment comprising the GHKL-type ATPase module and CW-type zinc finger. This fragment dimerizes upon binding ATP and contains a hinged, functionally critical coiled-coil insertion absent in other GHKL ATPases. We find that dimerization and DNA binding of the MORC2 ATPase module transduce HUSH-dependent silencing. Disease mutations change the dynamics of dimerization by distinct structural mechanisms: destabilizing the ATPase-CW module, trapping the ATP lid, or perturbing the dimer interface. These defects lead to the modulation of HUSH function, thus providing a molecular basis for understanding MORC2-associated neuropathies.
Physician-initiated clinical study of limb ulcers treated with a functional peptide, SR-0379: from discovery to a randomized, double-blind, placebo-controlled trial
Authors: Nakagami Hironori , Sugimoto Ken , Ishikawa Takahiro , Fujimoto Taku , Yamaoka Toshifumi , Hayashi Misa , Kiyohara Eiji , Ando Hiroshi , Terabe Yuta , Takami Yoichi , Yamamoto Koichi , Takeya Yasushi , Takemoto Minoru , Koshizaka Masaya , Ebihara Tamotsu , Nakamura Ayumi , Nishikawa Mitsunori , Yao Xiang Jing , Hanaoka Hideki , Katayama Ichiro , Yokote Koutaro , Rakugi Hiromi 
Published: February 2018

AbstractSR-0379 is a functional peptide that has wound healing effect with anti-microbial action, making it an ideal drug to prevent infection. To evaluate the safety, efficacy, and pharmacokinetics of SR-0379 for the treatment of leg ulcers, a physician-initiated, phase I/IIa, first-in-patient clinical study was designed. A multi-center, double-blind, randomized clinical study was conducted from October 2015 to September 2016. The inclusion criteria for leg ulcers were (1) diabetes or critical limb ischemia and (2) wound size <6 cm in diameter. Twelve patients were randomized into four groups and administered 0.02%, 0.1%, or 0.5% SR-0379 or placebo treatment on skin ulcers once per day for 28 days. Efficiency was evaluated by determining the rate of wound size reduction as a primary endpoint at 4 weeks after the first treatment compared with the pre-treatment wound size. As a secondary endpoint, the DESIGN-R score index, time to wound closure, and the 50% wound size reduction ratio were also evaluated. The safety of SR-0379 was evaluated during the study period. In the evaluation of efficiency, the skin ulcer reduction rates at the last evaluation were 44.73% for the 0.02% SR-0379 group, 68.25% for the 0.1% group, and 71.61% for the 0.5% group, compared with 9.95% for the placebo group. Six adverse events were reported in four patients, of which one occurred in the placebo group, and causal relationships to study drugs were denied for all six events. Treatment with SR-0379 for chronic leg ulcers was safe, well tolerated, and effective.
Changed frontal pole gene expression suggest altered interplay between neurotransmitter, developmental, and inflammatory pathways in schizophrenia
Authors: Scarr Elizabeth , Udawela Madhara , Dean Brian 
Published: February 2018

AbstractSchizophrenia (Sz) probably occurs after genetically susceptible individuals encounter a deleterious environmental factor that triggers epigenetic mechanisms to change CNS gene expression. To determine if omnibus changes in CNS gene expression are present in Sz, we compared mRNA levels in the frontal pole (Brodmann’s area (BA) 10), the dorsolateral prefrontal cortex (BA 9) and cingulate cortex (BA 33) from 15 subjects with Sz and 15 controls using the Affymetrix™ Human Exon 1.0 ST Array. Differences in mRNA levels (±≥20%;p < 0.01) were identified (JMP Genomics 5.1) and used to predict pathways and gene x gene interactions that would be affected by the changes in gene expression using Ingenuity Pathway Analysis. There was significant variation in mRNA levels with diagnoses for 566 genes in BA 10, 65 genes in BA 9 and 40 genes in BA 33. In Sz, there was an over-representation of genes with changed expression involved in inflammation and development in BA 10, cell morphology in BA 9 and amino acid metabolism and small molecule biochemistry in BA 33. Using 94 genes with altered levels of expression in BA 10 from subjects with Sz, it was possible to construct an interactome of proven direct gene x gene interactions that was enriched for genes in inflammatory, developmental, oestrogen, serotonergic, cholinergic and NRG1 regulated pathways. Our data shows complex, regionally specific changes in cortical gene expression in Sz that are predicted to affect homeostasis between biochemical pathways already proposed to be important in the pathophysiology of the disorder.
Epithelial-mesenchymal transition (EMT) signature is inversely associated with T-cell infiltration in non-small cell lung cancer (NSCLC)
Authors: Chae Young Kwang , Chang Sangmin , Ko Taeyeong , Anker Jonathan , Agte Sarita , Iams Wade , Choi Wooyoung M. , Lee Kyoungmin , Cruz Marcelo 
Published: February 2018

AbstractEpithelial-mesenchymal transition (EMT) is able to drive metastasis during progression of multiple cancer types, including non-small cell lung cancer (NSCLC). As resistance to immunotherapy has been associated with EMT and immune exclusion in melanoma, it is important to understand alterations to T-cell infiltration and the tumor microenvironment during EMT in lung adenocarcinoma and squamous cell carcinoma. We conducted an integrated analysis of the immune landscape in NSCLCs through EMT scores derived from a previously established 16 gene signature of canonical EMT markers. EMT was associated with exclusion of immune cells critical in the immune response to cancer, with significantly lower infiltration of CD4 T-cells in lung adenocarcinoma and CD4/CD8 T-cells in squamous cell carcinoma. EMT was also associated with increased expression of multiple immunosuppressive cytokines, including IL-10 and TGF-β. Furthermore, overexpression of targetable immune checkpoints, such as CTLA-4 and TIM-3 were associated with EMT in both NSCLCs. An association may exist between immune exclusion and EMT in NSCLC. Further investigation is merited as its mechanism is not completely understood and a better understanding of this association could lead to the development of biomarkers that could accurately predict response to immunotherapy.
Gold nanoparticle-based rapid detection and isolation of cells using ligand-receptor chemistry
Authors: Rauta Pradipta Ranjan , Hallur Pavan M. , Chaubey Aditya 
Published: February 2018

AbstractIdentification and isolation of low-frequency cells of interest from a heterogeneous cell mixture is an important aspect of many diagnostic applications (including enumeration of circulating tumor cells) and is integral to various assays in (cancer) biology. Current techniques typically require expensive instrumentation and are not amenable to high throughput. Here, we demonstrate a simple and effective platform for cell detection and isolation using gold nanoparticles (Au NPs) conjugated with hyaluronic acid (HA) i.e. Au-PEG-HA NPs. The proposed platform exploits ligand-receptor chemistry to detect/isolate cells with high specificity and efficiency. When the Au-PEG-HA NPs come in contact with cells that express CD44 (the receptor for HA), a clear colorimetric change occurs (along with an accompanying SPR peak shift from 521 nm to 559 nm) in the solution due to NPs-cell interaction. This clearly discernible, colorimetric change can be leveraged by point-of-care devices employed in diagnostic applications. Finally, we show that we can successfully isolate viable cells from a heterogeneous cell population (including from human blood samples) with high specificity, which can be used in further downstream applications. The developed NPs-based platform can be a convenient and cost-efficient alternative for diagnostic applications and for cell isolation or sorting in research laboratories.