bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral Epitranscriptomics
Authors: Kennedy Edward M. , Courtney David G. , Tsai Kevin , Cullen Bryan R. 
Published: March 2017

ABSTRACT

Although it has been known for over 40 years that eukaryotic mRNAs bear internal base modifications, it is only in the last 5 years that the importance of these modifications has begun to come into focus. The most common mRNA modification, the addition of a methyl group to the
N
6
position of adenosine (m
6
A), has been shown to affect splicing, translation, and stability, and m
6
A is also essential for embryonic development in organisms ranging from plants to mice. While all viral transcripts examined so far have been found to be extensively m
6
A modified, the role, if any, of m
6
A in regulating viral gene expression and replication was previously unknown. However, recent data generated using HIV-1 as a model system strongly suggest that sites of m
6
A addition not only are evolutionarily conserved but also enhance virus replication. It is therefore likely that the field of viral epitranscriptomics, which can be defined as the study of functionally relevant posttranscriptional modifications of viral RNA transcripts that do not change the nucleotide sequence of that RNA, is poised for a major expansion in scientific interest and may well fundamentally change our understanding of how viral replication is regulated.
The ND10 Component Promyelocytic Leukemia Protein Acts as an E3 Ligase for SUMOylation of the Major Immediate Early Protein IE1 of Human Cytomegalovirus
Authors: Reuter Nina , Schilling Eva-Maria , Scherer Myriam , Müller Regina , Stamminger Thomas 
Published: March 2017

ABSTRACT

Previous studies identified the nuclear domain 10 (ND10) components promyelocytic leukemia protein (PML), hDaxx, and Sp100 as factors of an intrinsic immune response against human cytomegalovirus (HCMV). This antiviral function of ND10, however, is antagonized by viral effector proteins like IE1p72, which induces dispersal of ND10. Furthermore, we have shown that both major immediate early proteins of HCMV, IE1p72 and IE2p86, transiently colocalize with ND10 subnuclear structures and undergo modification by the covalent attachment of SUMO. Since recent reports indicate that PML acts as a SUMO E3 ligase, we asked whether the SUMOylation of IE1p72 and IE2p86 is regulated by PML. To address this, PML-depleted fibroblasts, as well as cells overexpressing individual PML isoforms, were infected with HCMV. Western blot experiments revealed a clear correlation between the degree of IE1p72 SUMO conjugation and the abundance of PML. On the other hand, the SUMOylation of IE2p86 was not affected by PML. By performing
in vitro
SUMOylation assays, we were able to provide direct evidence that IE1p72 is a substrate for PML-mediated SUMOylation. Interestingly, disruption of the RING finger domain of PML, which is proposed to confer SUMO E3 ligase activity, abolished PML-induced SUMOylation of IE1p72. In contrast, IE1p72 was still efficiently SUMO modified by a SUMOylation-defective PML mutant, indicating that intact ND10 bodies are not necessary for this effect. Thus, this is the first report that the E3 ligase PML is capable of stimulating the SUMOylation of a viral protein which is supposed to serve as a cellular mechanism to compromise specific functions of IE1p72.

IMPORTANCE
The major immediate early proteins of human cytomegalovirus, termed IE1p72 and IE2p86, have previously been shown to undergo posttranslational modification by covalent coupling to SUMO moieties at specific lysine residues. However, the enzymatic activities that are responsible for this modification have not been identified. Here, we demonstrate that the PML protein, which mediates an intrinsic immune response against HCMV, specifically serves as an E3 ligase for SUMO modification of IE1p72. Since SUMO modification of IE1p72 has previously been shown to interfere with STAT factor binding, thus compromising the interferon-antagonistic function of this viral effector protein, our finding highlights an additional mechanism through which PML is able to restrict viral infections.
Early rehabilitation for the prevention of postintensive care syndrome in critically ill patients: a study protocol for a systematic review and meta-analysis
Authors: Kondo Yutaka , Fuke Ryota , Hifumi Toru , Hatakeyama Junji , Takei Tetsuhiro , Yamakawa Kazuma , Inoue Shigeaki , Nishida Osamu 
Published: March 2017

IntroductionPostintensive care syndrome (PICS) is defined as a new or worsening impairment in cognition, mental health and physical function after critical illness. There is little evidence regarding treatment of patients with PICS; new directions for effective treatment strategies are urgently needed. Early physiotherapy may prevent or reverse some physical impairments in patients with PICS, but no systematic reviews have investigated the effectiveness of early rehabilitation on PICS-related outcomes. The purpose of this systematic review is to evaluate whether early rehabilitative interventions in critically ill patients can prevent PICS and decrease mortality.MethodsWe will conduct a systematic review and meta-analysis of early rehabilitation for the prevention of PICS in critically ill adults. We will search PubMed, EMBASE and the Cochrane Central Register of Controlled Trials for published randomised controlled trials. We will screen search results and assess study selection, data extraction and risk of bias in duplicate, resolving disagreements by consensus. We will pool data from clinically homogeneous studies using a random-effects meta-analysis; assess heterogeneity of effects using the χ2test of homogeneity; and quantify any observed heterogeneity using the I2statistic. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to rate the quality of evidence.DiscussionThis systematic review will present evidence on the prevention of PICS in critically ill patients with early rehabilitation.EthicsEthics approval is not required.DisseminationThe results will be disseminated via peer-reviewed journal publication, conference presentation(s) and publications for patient information.Trial registration numberCRD42016039759.
Healthier central England or North–South divide? Analysis of national survey data on smoking and high-risk drinking
Authors: Beard Emma , Brown Jamie , West Robert , Angus Colin , Kaner Eileen , Michie Susan 
Published: March 2017

ObjectivesThis paper compares patterns of smoking and high-risk alcohol use across regions in England, and assesses the impact on these of adjusting for sociodemographic characteristics.DesignPopulation survey of 53 922 adults in England aged 16+ taking part in the Alcohol and Smoking Toolkit Studies.MeasuresParticipants answered questions regarding their socioeconomic status (SES), gender, age, ethnicity, Government Office Region, smoking status and completed the Alcohol Use Disorders Identification Test (AUDIT). High-risk drinkers were defined as those with a score of 8 or more (7 or more for women) on the AUDIT.ResultsIn unadjusted analyses, relative to the South West, those in the North of England were more likely to smoke, while those from the East of England, South East and London were less likely. After adjustment for sociodemographics, smoking prevalence was no higher in North East (RR 0.97, p>0.05), North West (RR 0.98, p>0.05) or Yorkshire and the Humber (RR 1.03, p>0.05) but was less common in the East and West Midlands (RR 0.86, p<0.001; RR 0.91, p<0.05), East of England (RR 0.86, p<0.001), South East (RR 0.92, p<0.05) and London (RR 0.85, p<0.001). High-risk drinking was more common in the North but was less common in the Midlands, London and East of England. Adjustment for sociodemographics had little effect. There was a higher prevalence in the North East (RR 1.67, p<0.001), North West (RR 1.42, p<0.001) and Yorkshire and the Humber (RR 1.35, p<0.001); lower prevalence in the East Midlands (RR 0.69, p<0.001), West Midlands (RR 0.77, p<0.001), East of England (RR 0.72, p<0.001) and London (RR 0.71, p<0.001); and a similar prevalence in the South East (RR 1.10, p>0.05)ConclusionsIn adjusted analyses, smoking and high-risk drinking appear less common in ‘central England’ than in the rest of the country. Regional differences in smoking, but not those in high-risk drinking, appear to be explained to some extent by sociodemographic disparities.
Remifentanil for procedural sedation: a systematic review of the literature
Authors: Kisilewicz Magdalena , Rosenberg Hans , Vaillancourt Christian 
Published: March 2017

ObjectiveWe sought to determine the performance characteristics of remifentanil as an agent of procedural sedation and analgesia (PSA) for adult and paediatric patients undergoing procedures similar to those executed in the ED.MethodsWe systematically reviewed electronically published literature, grey literature, conference proceedings and trial registries from 1946 to 2015. Outcome measures included PSA effectiveness, recovery time, patient safety and resource management. We performed narrative summary analyses. Heterogeneity among selected studies precluded meta-analysis.ResultsWe found 1525 citations, reviewed 34 full manuscripts (kappa=0.64) and included 10 studies (kappa=0.71). Seven were randomised controlled trials and three studies took place in the ED. Included procedures were lumbar puncture (80), cardioversion (66), orthopaedic manipulation (63), incision and drainage (15), thoracostomy (8) and nasal packing (2). There was extensive variation in remifentanil dosing (0.15– 1.5 μg/kg), administration protocols and use of additional PSA drugs. All studies noted superior or equivalent sedation effectiveness compared withcontrols. Several studies, including all those performed in the ED, noted faster procedure completion or patient recovery with remifentanil compared with control groups. The most commonly reported adverse event was respiratory depression, especially in paediatric patients. All studies were found to carry significant risk of bias.ConclusionsThere is currently a lack of high-quality data on the use of remifentanil in the ED. Physicians should exert caution when using remifentanil in the absence of published standardised dosing protocols in light of frequently reported paediatric respiratory depression. However, PSA efficacy combined with faster recovery times merit ongoing investigations into its use.
Proof of some congruences conjectured by Z.-W. Sun
Authors: Mao Guo-Shuai 
Published: March 2017

In this paper, we show that for any prime [Formula: see text], [Formula: see text] and [Formula: see text] where [Formula: see text] denotes the Bernoulli polynomial of degree [Formula: see text]. And we prove that [Formula: see text] and [Formula: see text] where [Formula: see text] stands for the [Formula: see text]th Bernoulli number. This confirms several conjectures of Z.-W. Sun.
The brittle and ductile components of displacement along fault zones
Authors: Homberg C. , Schnyder J. , Roche V. , Leonardi V. , Benzaggagh M. 
Published: March 2017

Abstract
The total offset across a fault zone may include offsets by discontinuous faulting as well as continuous deformation, including fault-related folding. This study investigates the relationships between these two components during fault growth. We established conceptual models for the distributions of displacement due to faulting (i.e. brittle component or near-field displacement), to folding (i.e. ductile component) and to the sum of both (i.e. far-field displacement) for different mechanisms of fault-related folding. We then compared these theoretical displacement profiles with those measured along mesoscale normal faults cutting carbonate-rich sequences in the Southeast Mesozoic sedimentary basin of France. The near-field and far-field displacement profiles follow either a flat-topped or a triangular shape. Several fold mechanisms were recognized, sometimes occurring together along the same fault and represent either fault-propagation folds, shear folds or coherent drag folds. In the last case, local deficit in the fault slip is balanced by folding so that the brittle and ductile components compose together a coherent fault zone. Common characteristics of these faults are a high folding component that can reach up to 75% of the total fault throw, a high displacement gradient (up to 0.5) and a strong fault sinuosity.
Lipocalin-2 Promotes Pancreatic Ductal Adenocarcinoma by Regulating Inflammation in the Tumor Microenvironment
Authors: Gomez-Chou Sobeyda B. , Swidnicka-Siergiejko Agnieszka Katarzyna , Badi Niharika , Chavez-Tomar Myrriah , Lesinski Gregory B. , Bekaii-Saab Tanios , Farren Matthew R. , Mace Thomas A. , Schmidt Carl , Liu Yan , Deng Defeng , Hwang Rosa F. , Zhou Liran , Moore Todd , Chatterjee Deyali , Wang Huamin , Leng Xiaohong , Arlinghaus Ralph B. , Logsdon Craig D. , Cruz-Monserrate Zobeida 
Published: March 2017

Abstract
Lipocalin-2 (LCN2) promotes malignant development in many cancer types. LCN2 is upregulated in patients with pancreatic ductal adenocarcinoma (PDAC) and in obese individuals, but whether it contributes to PDAC development is unclear. In this study, we investigated the effects of Lcn2 depletion on diet-induced obesity, inflammation, and PDAC development. Mice with acinar cell–specific expression of KrasG12D were crossed with Lcn2-depleted animals and fed isocaloric diets with varying amounts of fat content. Pancreas were collected and analyzed for inflammation, pancreatic intraepithelial neoplasia (PanIN), and PDAC. We also used a syngeneic orthotopic PDAC mouse model to study tumor growth in the presence or absence of Lcn2 expression. In addition, to understand the mechanistic role of how LCN2 could be mediating PDAC, we studied LCN2 and its specific receptor solute carrier family 22 member 17 (SLC22A17) in human pancreatic cancer stellate cells (PSC), key mediators of the PDAC stroma. Depletion of Lcn2 diminished extracellular matrix deposition, immune cell infiltration, PanIN formation, and tumor growth. Notably, it also increased survival in both obesity-driven and syngeneic orthotopic PDAC mouse models. LCN2 modulated the secretion of proinflammatory cytokines in PSC of the PDAC tumor microenvironment, whereas downregulation of LCN2-specific receptor SLC22A17 blocked these effects. Our results reveal how LCN2 acts in the tumor microenvironment links obesity, inflammation, and PDAC development. Cancer Res; 77(10); 2647–60. ©2017 AACR
Decision Support and Navigation to Increase Colorectal Cancer Screening among Hispanic Primary Care Patients
Authors: Myers RE , Stello B , Daskalakis C , Sifri R , DiCarlo M , Johnson M , Gonzalez E , Hegarty S , Rivera A , Gordis-Molina L , Shaak K , Quinn A , Careyva B , Anderson-Ortiz R 
Published: March 2017

Abstract
The study compared the impact of a novel decision support and navigation intervention (DSNI) to a mailed standard intervention (SI) on colorectal cancer (CRC) screening among Hispanic patients from 5 primary care practices in the Lehigh Valley Health Network (LVHN). Methods. We randomized surveyed and consented patients who were 50 to 75 years of age and were eligible for CRC screening either to an SI Group (n = 200) or a DSNI Group (n = 200). Following randomization, SI Group participants were mailed a set of standard materials (i.e., a letter from the participant's primary care practice encouraging selection and performance of either colonoscopy screening or a stool blood test (SBT) screening, a SBT kit, and instructions for arranging a colonoscopy appointment. Print materials were provided in English and Spanish. DSNI Group participants were also mailed the standard materials. In addition, DSNI participants received a telephone call from a bilingual patient navigator who reviewed the screening materials and verified the participant's preferred CRC screening test. During the call, the patient navigator used an online Decision Counseling Program© (DCP) to determine the participant's likelihood of test performance and to develop a personalized test preference- and likelihood-based screening plan. The plan was mailed to the participant and his/her primary care practice; and a participant screening status report was sent to the practice at 6 months. Finally, a 6-month survey was targeted to participants in both study groups. Results. Based on 6-month survey and medical records data, we found that CRC screening adherence was significantly higher (OR = 3.48, CI: 2.29, 5.29, P &lt; 0.001) in the DSNI Group (73%) versus the SI Group (44%). Conclusions. A decision support and navigation intervention significantly increased CRC screening adherence among Hispanic primary care patients.
Health System-Based HPV Vaccine Reminders: Randomized Trial Results
Authors: Henrikson N , Zhu W , Nguyen M , Baba L , Berthoud H , Hofstetter A 
Published: March 2017

Abstract
Purpose: Evaluate the impact of health system-based outreach and reminders on human papillomavirus (HPV) vaccine series initiation and completion. Methods: We conducted a 12-month randomized trial at an integrated care system in the Pacific Northwest in 2015–2016. Parents of 10–12 year olds who had not received any doses of HPV vaccine were randomized to an intervention group (mailed letter and brochure followed by an interactive voice recognition (IVR) reminder call encouraging HPV vaccine initiation) or usual care control group. Parents could opt in to receive future messages via SMS text message on all calls. Parents of intervention group children who initiated vaccination were re-randomized to receive either no further reminders or reminders for doses 2/3. We interviewed a subset of 50 parents to assess acceptability of the program. Outcomes were HPV vaccine initiation (within 12 months or 120 days of the initial letter), on-time series completion (within 210 days of initiation), and time to vaccination, assessed with Kaplan-Meier survival analyses. Results: 1624 children were eligible for randomization (46% age 10, 32.9% age 11, 20.4% age 12). The sample was 48.3% female and 64.6% white. Rates of overall HPV vaccine initiation were similar between the intervention and control groups (49.0% and 45.8%, P = 0.26), but initiation within 120 days of outreach was higher in the intervention group (23.6% and 18.8%, P = 0.04). This effect continued through to completion within 12 months (10.3% vs. 6.8%, P = 0.04). Opt-in rates to SMS were low: 24 people completed the opt-in process. Rates of on-time series completion were similar in those who received dose 1 reminders only compared to those who received reminders for all vaccine doses (12.1% and 19.7%, P = 0.10); time-to-completion results were similar. Parent interviews suggested reminders were acceptable and useful. Conclusion: Reminder calls after an outreach letter led to more timely vaccine initiation and overall completion. Reminders beyond the initial letter and reminder call did not appear to impact vaccine series completion. The program was acceptable to parents, though there was low uptake of SMS reminders.
Development and Validation of a Bilingual Stroke Preparedness Assessment Instrument
Authors: Skolarus Lesli E. , Mazor Kathleen M. , Sánchez Brisa N. , Dome Mackenzie , Biller José , Morgenstern Lewis B. 
Published: March 2017

Background and Purpose—
Stroke preparedness interventions are limited by the lack of psychometrically sound intermediate end points. We sought to develop and assess the reliability and validity of the video-Stroke Action Test (video-STAT) an English and a Spanish video-based test to assess people’s ability to recognize and react to stroke signs.

Methods—
Video-STAT development and testing was divided into 4 phases: (1) video development and community-generated response options, (2) pilot testing in community health centers, (3) administration in a national sample, bilingual sample, and neurologist sample, and (4) administration before and after a stroke preparedness intervention.

Results—

The final version of the video-STAT included 8 videos: 4 acute stroke/emergency, 2 prior stroke/nonemergency, 1 nonstroke/emergency, and 1 nonstroke/nonemergency. Acute stroke recognition and action response were queried after each vignette. Video-STAT scoring was based on the acute stroke vignettes only (score range 0–12 best). The national sample consisted of 598 participants, 438 who took the video-STAT in English and 160 who took the video-STAT in Spanish. There was adequate internal consistency (Cronbach α=0.72). The average video-STAT score was 5.6 (SD=3.6), whereas the average neurologist score was 11.4 (SD=1.3). There was no difference in video-STAT scores between the 116 bilingual video-STAT participants who took the video-STAT in English or Spanish. Compared with baseline scores, the video-STAT scores increased after a stroke preparedness intervention (6.2 versus 8.9,
P
<0.01) among a sample of 101 black adults and youth.

Conclusions—
The video-STAT yields reliable scores that seem to be valid measures of stroke preparedness.
Neuronal Death After Hemorrhagic Stroke In Vitro and In Vivo Shares Features of Ferroptosis and Necroptosis
Authors: Zille Marietta , Karuppagounder Saravanan S. , Chen Yingxin , Gough Peter J. , Bertin John , Finger Joshua , Milner Teresa A. , Jonas Elizabeth A. , Ratan Rajiv R. 
Published: March 2017

Background and Purpose—
Intracerebral hemorrhage leads to disability or death with few established treatments. Adverse outcomes after intracerebral hemorrhage result from irreversible damage to neurons resulting from primary and secondary injury. Secondary injury has been attributed to hemoglobin and its oxidized product hemin from lysed red blood cells. The aim of this study was to identify the underlying cell death mechanisms attributable to secondary injury by hemoglobin and hemin to broaden treatment options.

Methods—
We investigated cell death mechanisms in cultured neurons exposed to hemoglobin or hemin. Chemical inhibitors implicated in all known cell death pathways were used. Identified cell death mechanisms were confirmed using molecular markers and electron microscopy.

Results—
Chemical inhibitors of ferroptosis and necroptosis protected against hemoglobin- and hemin-induced toxicity. By contrast, inhibitors of caspase-dependent apoptosis, protein or mRNA synthesis, autophagy, mitophagy, or parthanatos had no effect. Accordingly, molecular markers of ferroptosis and necroptosis were increased after intracerebral hemorrhage in vitro and in vivo. Electron microscopy showed that hemin induced a necrotic phenotype. Necroptosis and ferroptosis inhibitors each abrogated death by >80% and had similar therapeutic windows in vitro.

Conclusions—
Experimental intracerebral hemorrhage shares features of ferroptotic and necroptotic cell death, but not caspase-dependent apoptosis or autophagy. We propose that ferroptosis or necroptotic signaling induced by lysed blood is sufficient to reach a threshold of death that leads to neuronal necrosis and that inhibition of either of these pathways can bring cells below that threshold to survival.