bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanopore lipid bilayer formed by self‐spreading method
Authors: Peng Zugui , Shimba Kenta , Miyamoto Yoshitaka , Yagi Tohru 
Published: December 2019

AbstractBlack lipid membrane suspending on a solid‐state nanopore (nano‐black lipid membranes; nano‐BLMs) is a functional application to detect single‐channel activities with a long lifetime. However, folding and painting techniques, which are traditionally used to form nano‐BLMs, only have a low success rate because of their complicated procedure. Herein, we report on the self‐spreading method on 50 nm pore size polycarbonate membrane filter to form nano‐BLMs by a simple procedure. Our results show that the nano‐BLMs have been successfully formed on the membrane filter. The spreading velocity of the nano‐BLMs exhibits a square root behavior, v ∼ t−1/2, which is in great agreement with the previous research. The experiments with fluorescence recovery after photobleaching show the recovery of a photobleached area in our nano‐BLMs. We also measure the elastic response of our nano‐BLMs by using an atomic force microscope, and our results demonstrate that the lipid bilayer is spanning on the pore of membrane filter. We also discuss the effect of temperature and the roughness of supporting surface on the spreading speed of lipid bilayer.
Manufacturing discontent: National institutions, multinational firm strategies, and anti‐globalization backlash in advanced economies
Authors: Butzbach Olivier , Fuller Douglas B. , Schnyder Gerhard 
Published: December 2019

AbstractResearch SummaryThere is mounting evidence of a widespread popular backlash against globalization in advanced economies, which can hurt multinational companies' (MNCs) interests. In this article, we argue that MNCs are both “culprits” and “victims” of backlash against globalization. Building on the comparative capitalism literature, we argue that national institutions influence the likelihood of a backlash by either encouraging MNCs to embrace a “labor arbitrage” strategy consisting in tapping into cheap labor markets overseas or preventing them from doing so. Where institutional constraints lead firms to adopt an “upgrading” route of using domestic workers, popular backlash is less likely. Such institutional factors help to explain variation in the likelihood of backlash across countries. We also discuss the strategic options available to firms facing backlash.Managerial SummaryMultinational companies are increasingly facing a backlash against globalization that, in some countries, may lead to policies that directly hurt their interests. Yet little is known about the link of this phenomenon with firm‐level strategies. In this article, we draw on comparative capitalism analysis to show that national institutions play a key role in determining the likelihood of backlash. They do so by inducing/discouraging MNCs to adopt certain strategies that expose non‐university‐educated workers to globalization pressures, influencing, in turn, the electorate's attitude toward globalization. We also present and discuss the strategic options available to firms facing backlash.
Follicular lymphoma: Update on management and emerging therapies at the dawn of the new decade
Authors: Apostolidis John , Mokhtar Nihad , Al Omari Rawan , Darweesh Mohammed , Al Hashmi Hani 
Published: December 2019

AbstractFollicular lymphoma is the most common indolent non‐Hodgkin lymphoma. Survival has improved over the last several decades, mainly because of the incorporation of the anti‐CD20 antibody rituximab into preexisting or rediscovered agents. The disease has a relapsing and remitting pattern, coupled with a risk of transformation into an aggressive lymphoma, and considered incurable for most patients. Next‐generation sequencing technologies have increased our understanding of the biology and genetic landscape of the disease, identifying potential druggable targets for treatment. Current prognostic models cannot accurately identify patients at risk of early progression and despite the availability of treatment options for relapsed/refractory disease, rational treatment selection balancing disease control, efficacy with toxicity, and quality of life remain unmet needs. This review provides an overview of biology, prognostication, treatment options, and emerging therapies that provide valid grounds for optimism.
The role of miR‐146a in viral infection
Authors: Nahand Javid Sadri , Karimzadeh Mohammad Reza , Nezamnia Maria , Fatemipour Maryam , Khatami Alireza , Jamshidi Sogol , Moghoofei Mohsen , Taghizadieh Mohammad , Hajighadimi Sarah , Shafiee Alimohammad , Sadeghian Mohammad , Bokharaei‐Salim Farah , Mirzaei Hamed 
Published: December 2019

AbstractCellular microRNAs (miRNAs) were identified as a key player in the posttranscriptional regulation of cellular‐genes regulatory pathways. They also emerged as a significant regulator of the immune response. In particular, miR‐146a acts as an importance modulator of function and differentiation cells of the innate and adaptive immunity. It has been associated with disorder including cancer and viral infections. Given its significance in the regulation of key cellular processes, it is not surprising which virus infection have found ways to dysregulation of miRNAs. miR‐146a has been identified in exosomes (exosomal miR‐146a). After the exosomes release from donor cells, they are taken up by the recipient cell and probably the exosomal miR‐146a is able to modulate the antiviral response in the recipient cell and result in making them more susceptible to virus infection. In this review, we discuss recent reports regarding miR‐146a expression levels, target genes, function, and contributing role in the pathogenesis of the viral infection and provide a clue to develop the new therapeutic and preventive strategies for viral disease in the future.
How to inform at‐risk relatives? Attitudes of 1379 Dutch patients, relatives, and members of the general population
Authors: Marleen van den Heuvel Lieke , Stemkens Daphne , van Zelst‐Stams Wendy A. G. , Willeboordse Floor , Christiaans Imke 
Published: December 2019

AbstractThe uptake of predictive DNA testing in families with a hereditary disease is <50%. Current practice often relies on the proband to inform relatives about the possibility of predictive DNA testing, but not all relatives are informed adequately. To enable informed decision‐making concerning predictive DNA testing, the approach used to inform at‐risk relatives needs to be optimized. This study investigated the preferences of patients, relatives, and the general population from the Netherlands on how to inform relatives at risk of autosomal dominant diseases. Online surveys were sent to people with autosomal dominant neuro‐, onco‐, or cardiogenetic diseases and their relatives via patient organizations (n = 379), and to members of the general population via a commercial panel (n = 1,000). Attitudes of the patient and population samples generally corresponded. A majority believed that initially only first‐degree relatives should be informed, following the principles of a cascade screening approach. Most participants also thought that probands and healthcare professionals (HCPs) should be involved in informing relatives, and a large proportion believed that HCPs should contact relatives directly in cases where patients are unwilling to inform, both for untreatable and treatable conditions. Participants from the patient sample were of the opinion that HCPs should actively offer support. Our findings show that both patients and HCPs should be involved in informing at‐risk relatives of autosomal dominant diseases and suggest that relatives' ‘right to know’ was considered a dominant issue by the majority of participants. Further research is needed on how to increase proactive support in informing of at‐risk relatives.
Clinical application of the new classification of periodontal diseases: Ground rules, clarifications and “gray zones”
Authors: Kornman Kenneth S. , Papapanou Panos N. 
Published: December 2019

AbstractBackgroundSuccessful dissemination of the new classification of periodontitis is facilitated by emphasis on the basic ground rules, clarification of ambiguities, and identification of “gray zones” where thoughtful application of the guidelines by an informed, experienced clinician is paramount to arrive at a correct Stage and Grade.MethodsHighlighted ground rules are (1) Stage is a patient‐based, not a tooth‐based concept, therefore, a single Stage is assigned per patient; (2) Stage can shift upward over time, if the periodontal status deteriorates, but the initially assigned Stage is retained even after improvement post‐therapy; (3) the complexity factors that determine Stage must be evaluated collectively, not in isolation, to arrive at a clinically meaningful assessment; (4) a single Grade is assigned to a patient based on a deliberate evaluation of the “biological fabric” of the case, in terms of history of/risk for further progression, interplay of risk factors, and the two‐way effects of periodontitis or its treatment on general health; (v) shift of Grade over time is possible towards either direction, after thorough, collective, evaluation of changes in the above parameters. Exemplified gray zones include a radiographically intact patient with minimal attachment loss in older age; presence of “frank” periodontitis affecting a single tooth; and assessment of factors that do/do not lead to increased complexity of therapy.ConclusionDifferentiating between Stage I/II versus Stage III/IV periodontitis is relatively uncomplicated; further distinction between Stages and correct assignment of Grade requires nuanced, thorough interpretation of a broad array of findings by a knowledgeable clinician.
miR‐636 represses cell survival by targeting CDK6/Bcl‐2 in cervical cancer
Authors: Hu Qing‐Lan , Xu Zun‐Peng , Lan Yun‐Fei , Li Bei 
Published: December 2019

AbstractCervical cancer is widely known as one of the most common types of cancer diagnosed in women, and microRNAs (miRNAs) has been characterized as an important regulator in tumor progression, such as cervical cancer. MiR‐636 was found to play a tumor suppressor role in hepatocellular carcinoma tumorigenesis. However, the tumorigenic mechanism of miR‐636 on cervical cancer has not yet been found. In the present study, we first found that miR‐636 was significantly downregulated in cervical cancer tissues and cell lines. in vitro gain‐ and loss‐of‐function assays revealed that overexpression of miR‐636 inhibited cell proliferation and induced cell apoptosis, while knockdown of miR‐636 reversed the effect on cervical tumorigenesis. Furthermore, cyclin‐dependent kinase 6 (CDK6) and B‐cell lymphoma 2 (Bcl‐2) were characterized as targets of miR‐636. Notably, overexpression of CDK6 or Bcl‐2 could reverse the inhibitory effect of miR‐636 on cervical cancer progression. Mechanistically, miR‐636 repressed cell survival by targeting CDK6/Bcl‐2 in cervical cancer, which may be the underlying mechanism of miR‐636‐inhibited cervical progression. In conclusion, our findings clarified the biologic significance of miR‐636/CDK6/Bcl‐2 axis in cervical cancer progression and suggested the potential therapeutic target ability of miR‐636 in treatment of cervical cancer.
Xanthophyll β‐Cryptoxanthin Inhibits Highly Refined Carbohydrate Diet–Promoted Hepatocellular Carcinoma Progression in Mice
Authors: Lim Ji Ye , Liu Chun , Hu Kang‐Quan , Smith Donald E. , Wu Dayong , Lamon‐Fava Stefania , Ausman Lynne M. , Wang Xiang‐Dong 
Published: December 2019

Scopeβ‐Cryptoxanthin (BCX) can be cleaved by both β‐carotene 15,15′‐oxygenase (BCO1) and β‐carotene 9′,10′‐oxygenase (BCO2), generating biological active vitamin A and apocarotenoids. We examined whether BCX feeding could inhibit diethylnitrosamine (DEN)‐initiated, highly refined carbohydrate diet (HRCD)‐promoted hepatocellular carcinoma (HCC) development, dependent or independent of BCO1/BCO2 activity.Methods and resultsTwo‐week‐old male wild‐type (WT) and BCO1−/−/BCO2−/− double knockout (DKO) mice are given a single intraperitoneal injection of DEN (25 mg kg−1 body weight) to initiate hepatic carcinogenesis. At 6 weeks of age, all animals are fed HRCD (66.5% of energy from carbohydrate) with or without BCX for 24 weeks. BCX feeding increases hepatic vitamin A levels in WT mice, but not in DKO mice that shows a significant accumulation of hepatic BCX. Compared to their respective HRCD littermates, both WT and DKO fed BCX have significantly lower HCC multiplicity, average tumor size, and total tumor volume, and the steatosis scores. The chemopreventive effects of BCX are associated with increased p53 protein acetylation and decreased protein levels of lactate dehydrogenase and hypoxia‐inducible factor‐1α in tumors.ConclusionThis study suggests that BCX feeding may alleviate HRCD‐promoted HCC progression by modulating the acetylation of p53, hypoxic tumor microenvironment, and glucose metabolism, independent of BCO1/BCO2.
Prospective Study of Long‐Term Interrelationships Among Adiposity‐Associated Biomarkers in Women
Authors: Baden Megu Y. , Hu Frank B. , Huang Tianyi 
Published: December 2019

ObjectiveThis study aimed to investigate the prospective interrelationships among biomarkers that may provide mechanistic insights into obesity‐related diseases.MethodsA total of 850 women in the Nurses’ Health Study II with two fasting blood measurements (1996‐1999 and 2010‐2011) of adiponectin, leptin, soluble leptin receptor, insulin, retinol‐binding protein 4, high‐sensitivity C‐reactive protein (hsCRP), and interleukin‐6 were included. Biomarker interrelationships were examined in the following three ways: (1) cross‐sectional associations at baseline and follow‐up, (2) longitudinal associations of concurrent biomarker changes, and (3) prospective associations of each baseline biomarker with other biomarker changes.ResultsIn cross‐sectional analyses, most biomarkers were correlated after multivariable adjustment including BMI, with the strongest correlations observed between leptin and insulin and between hsCRP and interleukin‐6. In longitudinal analyses, similar results were observed after multivariable adjustment including weight change. However, in prospective analyses, only three associations observed in cross‐sectional and longitudinal analyses were consistently significant (P < 0.05). Every doubling in baseline adiponectin was associated with −9.0% insulin change. The corresponding estimate was 9.3% for baseline leptin and hsCRP change and 3.1% for baseline hsCRP and leptin change.ConclusionsBaseline adiponectin concentrations were inversely associated with subsequent insulin change, whereas baseline leptin concentrations were positively associated with hsCRP change and vice versa.
Experimental Evidence on the Impacts of Need‐Based Financial Aid: Longitudinal Assessment of the Wisconsin Scholars Grant
Authors: Anderson Drew M. , Broton Katharine M. , Goldrick‐Rab Sara , Kelchen Robert 
Published: December 2019

AbstractWe conduct the first long‐term experimental evaluation of a need‐based financial aid program, the privately funded Wisconsin Scholars Grant. Over multiple cohorts, the program failed to increase degree completion and graduate school enrollment up to 10 years after matriculation. The program did reduce time‐to‐degree for some students and modestly increased the number of STEM degrees earned. The lack of robust effects raises important questions about the conditions necessary for financial aid to benefit students.
The regulation of ZCT1, a transcriptional repressor of monoterpenoid indole alkaloid biosynthetic genes in Catharanthus roseus
Authors: Mortensen Samuel , Weaver Jessica D. , Sathitloetsakun Suphinya , Cole Lauren F. , Rizvi Noreen F. , Cram Erin J. , Lee‐Parsons Carolyn W. T. 
Published: December 2019

AbstractCys2/His2‐type (C2H2) zinc finger proteins, such as ZCT1, are an important class of transcription factors involved in growth, development, and stress responses in plants. In the medicinal plant Catharanthus roseus, the zinc finger Catharanthus transcription factor (ZCT) family represses monoterpenoid indole alkaloid (MIA) biosynthetic gene expression. Here, we report the analysis of the ZCT1 promoter, which contains several hormone‐responsive elements. ZCT1 is responsive to not only jasmonate, as was previously known, but is also induced by the synthetic auxin, 1‐naphthalene acetic acid (1‐NAA). Through promoter deletion analysis, we show that an activation sequence‐1‐like (as‐1‐like)‐motif and other motifs contribute significantly to ZCT1 expression in seedlings. We also show that the activator ORCA3 does not transactivate the expression of ZCT1 in seedlings, but ZCT1 represses its own promoter, suggesting a feedback mechanism by which the expression of ZCT1 can be limited.
Structural characterization of aminoglycoside 4′‐O‐adenylyltransferase ANT(4′)‐IIb from Pseudomonas aeruginosa
Authors: Semper Cameron , Stogios Peter , Meziane‐Cherif Djalal , Evdokimova Elena , Courvalin Patrice , Savchenko Alexei 
Published: December 2019

AbstractAminoglycosides were one of the first classes of broad‐spectrum antibacterial drugs clinically used to effectively combat infections. The rise of resistance to these drugs, mediated by enzymatic modification, has since compromised their utility as a treatment option, prompting intensive research into the molecular function of resistance enzymes. Here, we report the crystal structure of aminoglycoside nucleotidyltransferase ANT(4′)‐IIb in apo and tobramycin‐bound forms at a resolution of 1.6 and 2.15 Å, respectively. ANT(4′)‐IIb was discovered in the opportunistic pathogen Pseudomonas aeruginosa and conferred resistance to amikacin and tobramycin. Analysis of the ANT(4′)‐IIb structures revealed a two‐domain organization featuring a mixed β‐sheet and an α‐helical bundle. ANT(4′)‐IIb monomers form a dimer required for its enzymatic activity, as coordination of the aminoglycoside substrate relies on residues contributed by both monomers. Despite harbouring appreciable primary sequence diversity compared to previously characterized homologues, the ANT(4′)‐IIb structure demonstrates a surprising level of structural conservation highlighting the high plasticity of this general protein fold. Site‐directed mutagenesis of active site residues and kinetic analysis provides support for a catalytic mechanism similar to those of other nucleotidyltransferases. Using the molecular insights provided into this ANT(4′)‐IIb‐represented enzymatic group, we provide a hypothesis for the potential evolutionary origin of these aminoglycoside resistance determinants.
Critical realism and complexity theory: Building a nonconstructivist systems research framework for effective governance analysis
Authors: Yang Yi 
Published: December 2019

AbstractComplexity theory (CT) intends to reveal public management's unpredictable side but its empirical applications are scarce due to prevailing constructivist approaches that collapse larger systematic outcomes into micro agent actions and conflate them into movements of co‐constitution and co‐evolution, precluding effective analysis. How can we capture emergent properties and outcomes if we cannot delineate objects and subjects? How can we attribute causes and effects without fixed, stable entities? To address this significant weakness of theorization for a more effective CT framework, Margaret Archer's critical realist model solves this constructivist conflation dilemma—agents and systems, though interrelated, are distinct and stable entities—public management and governance process is thus the result of emergence from a learning‐to‐control process for rule‐makers, with structurally unpredictable inputs from the ruled whereby systematic features predate and condition (Time 1) individual actions, which can maintain or reproduce them (Time 3) during agent–system interactive processes (Time 2).
Outcomes with respect to extent of surgical resection for pediatric atypical teratoid rhabdoid tumors
Authors: Richards Alexandra , Ved Ronak , Murphy Christopher , Hennigan Dawn , Kilday John-Paul , Kamaly-Asl Ian , Mallucci Conor , Bhatti Imran , Patel Chirag , Leach Paul 
Published: December 2019

Abstract
Purpose
To evaluate overall survival for atypical teratoid rhabdoid tumors (ATRTs) in relation to extent of surgical resection.

Methods
The neurosurgical tumor databases from three UK Pediatric centers (University Hospital of Wales, Alder Hey and Royal Manchester Children’s Hospital) were analyzed. Patients with a diagnosis of ATRT were identified between 2000 and 2018. Data was collected regarding demographics, extent of resection, complications, and overall survival.

Results
Twenty-four patients diagnosed with ATRT underwent thirty-eight operations. The age range was 20 days to 147 months (median 17.5 months). The most common location for the tumor was the posterior fossa (nine patients; 38%). Six patients (25%) underwent a complete total resection (CTR), seven (29%) underwent a near total resection (NTR), eight (33.3%) underwent a subtotal resection (STR), and three patients (12.5%) had biopsy only. Two-thirds of patients who underwent a CTR are still alive, as of March 2019, compared to 29% in the NTR and 12.5% in the STR groups. Out of the thirty-eight operations, there were a total of twenty-two complications, of which the most common was pseudomeningocele (27%). The extent of surgical resection (p = 0.021), age at surgery (p = 0.00015), and the presence of metastases at diagnosis (0.015) significantly affected overall survival.

Conclusions
Although these patients are a highly vulnerable group, maximal resection is recommended where possible, for the best chance of long-term survival. However, near total resections are likely beneficial when compared with subtotal resections and biopsy alone. Maximal surgical resection should be combined with adjuvant therapies for the best long-term outcomes.
Is the subtropical jet shifting poleward?
Authors: Maher Penelope , Kelleher Michael E. , Sansom Philip G. , Methven John 
Published: December 2019

AbstractThe tropics are expanding poleward at about $$0.5{^\circ }$$0.5∘ per decade in observations. This poleward expansion of the circulation is consistently reported using Hadley cell edge metrics and lower-atmospheric tropical edge metrics. However, some upper-atmospheric tropical metrics report smaller trends that are often not significant. One such upper-atmospheric metric is the subtropical jet latitude, which has smaller trends compared to the Hadley cell edge. In this study we investigate the robustness of the weak trends in the subtropical jet position by introducing a new method for locating the subtropical jet, and examining the trends and variability of the subtropical jet latitude. We introduce the tropopause gradient method based on the peak gradient in potential temperature along the dynamic tropopause. Using this method we find the trends in the subtropical jet latitude are indeed much smaller than $$0.5{^\circ }$$0.5∘ per decade, consistent with previous studies. We also find that natural variability within the subtropical jet latitude would not prevent trends from being detected if they were similar to the Hadley cell edge, as trends greater than 0.24$${^\circ }$$∘ per decade could reliably be detected using monthly data or 0.09$${^\circ }$$∘ per decade using daily data. Despite the poleward expansion of the tropics, there is no robust evidence to suggest the subtropical jet is shifting poleward in either hemisphere. Neither the current diagnostic methods nor natural variability can account for the small subtropical jet trends. The most likely explanation, which requires further investigation, is that the subtropical jet position is not tied dynamically to the Hadley cell edge.