bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Cell-Free Assembly System for Generating Infectious Human Papillomavirus 16 Capsids Implicates a Size Discrimination Mechanism for Preferential Viral Genome Packaging
Authors: Cerqueira Carla , Pang Yuk-Ying S. , Day Patricia M. , Thompson Cynthia D. , Buck Christopher B. , Lowy Douglas R. , Schiller John T. 
Published: November 2015

ABSTRACT

We have established a cell-free
in vitro
system to study human papillomavirus type 16 (HPV16) assembly, a poorly understood process. L1/L2 capsomers, obtained from the disassembly of virus-like particles (VLPs), were incubated with nuclear extracts to provide access to the range of cellular proteins that would be available during assembly within the host cell. Incorporation of a reporter plasmid “pseudogenome” was dependent on the presence of both nuclear extract and ATP. Unexpectedly, L1/L2 VLPs that were not disassembled prior to incubation with a reassembly mixture containing nuclear extract also encapsidated a reporter plasmid. As with HPV pseudoviruses (PsV) generated intracellularly, infection by cell-free particles assembled
in vitro
required the presence of L2 and was susceptible to the same biochemical inhibitors, implying the cell-free assembled particles use the infectious pathway previously described for HPV16 produced in cell culture. Using biochemical and electron microscopy analyses, we observed that, in the presence of nuclear extract, intact VLPs partially disassemble, providing a mechanistic explanation to how the exogenous plasmid was packaged by these particles. Further, we provide evidence that capsids containing an <8-kb pseudogenome are resistant to the disassembly/reassembly reaction. Our results suggest a novel size discrimination mechanism for papillomavirus genome packaging in which particles undergo iterative rounds of disassembly/reassembly, seemingly sampling DNA until a suitably sized DNA is encountered, resulting in the formation of a stable virion structure.

IMPORTANCE
Little is known about papillomavirus assembly biology due to the difficulties in propagating virus
in vitro
. The cell-free assembly method established in this paper reveals a new mechanism for viral genome packaging and will provide a tractable system for further dissecting papillomavirus assembly. The knowledge gained will increase our understanding of virus-host interactions, help to identify new targets for antiviral therapy, and allow for the development of new gene delivery systems based on
in vitro
-generated papillomavirus vectors.
Minor Contribution of Chimeric Host-HIV Readthrough Transcripts to the Level of HIV Cell-Associated
gag
RNA
Authors: Pasternak Alexander O. , DeMaster Laura K. , Kootstra Neeltje A. , Reiss Peter , O'Doherty Una , Berkhout Ben 
Published: November 2015

ABSTRACT

Cell-associated HIV unspliced RNA is an important marker of the viral reservoir. HIV
gag
RNA-specific assays are frequently used to monitor reservoir activation. Because HIV preferentially integrates into actively transcribed genes, some of the transcripts detected by these assays may not represent genuine HIV RNA but rather chimeric host-HIV readthrough transcripts. Here, we demonstrate that in HIV-infected patients on suppressive combination antiretroviral therapy, such host-derived transcripts do not significantly contribute to the HIV
gag
RNA level.
Occupancy of RNA Polymerase II Phosphorylated on Serine 5 (RNAP S5
P
) and RNAP S2
P
on Varicella-Zoster Virus Genes 9, 51, and 66 Is Independent of Transcript Abundance and Polymerase Location within the Gene
Authors: Henderson Heather H. , Timberlake Kensey B. , Austin Zoe A. , Badani Hussain , Sanford Bridget , Tremblay Keriann , Baird Nicholas L. , Jones Kenneth , Rovnak Joel , Frietze Seth , Gilden Don , Cohrs Randall J. 
Published: November 2015

ABSTRACT

Regulation of gene transcription in varicella-zoster virus (VZV), a ubiquitous human neurotropic alphaherpesvirus, requires coordinated binding of multiple host and virus proteins onto specific regions of the virus genome. Chromatin immunoprecipitation (ChIP) is widely used to determine the location of specific proteins along a genomic region. Since the size range of sheared virus DNA fragments governs the limit of accurate protein localization, particularly for compact herpesvirus genomes, we used a quantitative PCR (qPCR)-based assay to determine the efficiency of VZV DNA shearing before ChIP, after which the assay was used to determine the relationship between transcript abundance and the occupancy of phosphorylated RNA polymerase II (RNAP) on the gene promoter, body, and terminus of VZV genes 9, 51, and 66. The abundance of VZV gene 9, 51, and 66 transcripts in VZV-infected human fetal lung fibroblasts was determined by reverse transcription-linked quantitative PCR. Our results showed that the C-terminal domain of RNAP is hyperphosphorylated at serine 5 (S5
P
) on VZV genes 9, 51, and 66 independently of transcript abundance and the location within the virus gene at both 1 and 3 days postinfection (dpi). In contrast, phosphorylated serine 2 (S2
P
)-modified RNAP was not detected at any virus gene location at 3 dpi and was detected at levels only slightly above background levels at 1 dpi.

IMPORTANCE
Regulation of herpesvirus gene transcription is an elaborate choreography between proteins and DNA that is revealed by chromatin immunoprecipitation (ChIP). We used a quantitative PCR-based assay to determine fragment size after DNA shearing, a critical parameter in ChIP assays, and exposed a basic difference in the mechanism of transcription between mammalian cells and VZV. We found that hyperphosphorylation at serine 5 of the C-terminal domain of RNAP along the lengths of VZV genes (the promoter, body, and transcription termination site) was independent of mRNA abundance. In contrast, little to no enrichment of serine 3 phosphorylation of RNAP was detected at these virus gene regions. This is distinct from the findings for RNAP at highly regulated host genes, where RNAP S5
P
occupancy decreased and S2
P
levels increased as the polymerase transited through the gene. Overall, these results suggest that RNAP associates with human and virus transcriptional units through different mechanisms.
The Effect and Mechanism of Electroacupuncture at Li11 and St37 on Constipation in a Rat Model
Authors: Zhu Xianwei , Liu Zhibin , Qu Hongyan , Niu Wenmin , Gao Li , Wang Yuan , Zhang Aimin , Bai Lu 
Published: November 2015

Background Electroacupuncture (EA) is used clinically for the treatment of constipation. Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in colonic motility; however it is unknown whether alterations in colonic 5-HT are associated with EA. In this study, the effect and mechanism of EA at acupuncture points LI11 and ST37 were examined using a cold saline-induced rat model of constipation. Methods A rat constipation model was induced by cold saline gavage in 24 Sprague-Dawley rats. A further six rats were included as a Control group. The constipated rats were divided into four groups (n=6 each): a Constipation group that remained untreated; a Constipation+LI11 group that received EA at LI11; a Constipation+ST37 groups that received EA at ST37; and a Constipation+LI11+ST37 group that received EA at both LI11 and ST37. After EA treatment, faecal water content, defaecation frequency, and gastrointestinal (GI) transit were measured, as well as the expression of tryptophan hydroxylase (TPH) in colonic tissues (by Western blot analysis) and 5-HT in both faeces and colonic tissues (by ELISA). Results All three EA-treated groups demonstrated significant improvements in faecal water content, defaecation frequency and GI transit (p<0.05). In addition, TPH and 5-HT expression were both increased by EA at LI11 and/or ST37 (p<0.05). There were no significant differences between the three EA groups for any outcomes. Conclusions EA at LI11 and/or ST37 had a positive effect on objective markers of constipation in a rat model. In addition, EA increased 5-HT and TPH in the colonic tissues.
Evidence used in model-based economic evaluations for evaluating pharmacogenetic and pharmacogenomic tests: a systematic review protocol
Authors: Peters Jaime L , Cooper Chris , Buchanan James 
Published: November 2015

IntroductionDecision models can be used to conduct economic evaluations of new pharmacogenetic and pharmacogenomic tests to ensure they offer value for money to healthcare systems. These models require a great deal of evidence, yet research suggests the evidence used is diverse and of uncertain quality. By conducting a systematic review, we aim to investigate the test-related evidence used to inform decision models developed for the economic evaluation of genetic tests.Methods and analysisWe will search electronic databases including MEDLINE, EMBASE and NHS EEDs to identify model-based economic evaluations of pharmacogenetic and pharmacogenomic tests. The search will not be limited by language or date. Title and abstract screening will be conducted independently by 2 reviewers, with screening of full texts and data extraction conducted by 1 reviewer, and checked by another. Characteristics of the decision problem, the decision model and the test evidence used to inform the model will be extracted. Specifically, we will identify the reported evidence sources for the test-related evidence used, describe the study design and how the evidence was identified. A checklist developed specifically for decision analytic models will be used to critically appraise the models described in these studies. Variations in the test evidence used in the decision models will be explored across the included studies, and we will identify gaps in the evidence in terms of both quantity and quality.DisseminationThe findings of this work will be disseminated via a peer-reviewed journal publication and at national and international conferences.
Defining venous thromboembolism and measuring its incidence using Swedish health registries: a nationwide pregnancy cohort study
Authors: Abdul Sultan Alyshah , West Joe , Stephansson Olof , Grainge Matthew J , Tata Laila J , Fleming Kate M , Humes David , Ludvigsson Jonas F 
Published: November 2015

ObjectiveTo accurately define venous thromboembolism (VTE) in the routinely collected Swedish health registers and quantify its incidence in and around pregnancy.Study designCohort study using data from the Swedish Medical Birth Registry (MBR) linked to the National Patient Registry (NPR) and the Swedish Prescribed Drug Register (PDR).SettingSecondary care centres, Sweden.Participant509 198 women aged 15–44 years who had one or more pregnancies resulting in a live birth or stillbirth between 2005 and 2011.Main outcome measureTo estimate the incidence rate (IR) of VTE in and around pregnancy using various VTE definitions allowing direct comparison with other countries.ResultsThe rate of VTE varied based on the VTE definition. We found that 43% of cases first recorded as outpatient were not accompanied by anticoagulant prescriptions, whereas this proportion was much lower than those cases first recorded in the inpatient register (9%). Using our most inclusive VTE definition, we observed higher rates of VTE compared with previously published data using similar methodology. These reduced by 31% (IR=142/100 000 person-years; 95% CI 132 to 153) and 22% (IR=331/100 000 person-years; 95% CI 304 to 361) during the antepartum and postpartum periods, respectively, using a restrictive VTE definition that required anticoagulant prescriptions associated with diagnosis, which were more in line with the existing literature.ConclusionsWe found that including VTE codes without treatment confirmation risks the inclusion of false-positive cases. When defining VTE using the NPR, anticoagulant prescription information should therefore be considered particularly for cases recorded in an outpatient setting.
Half-life of a printed handoff document
Authors: Rosenbluth Glenn , Jacolbia Ronald , Milev Dimiter , Auerbach Andrew D 
Published: November 2015

BackgroundPrinted handoff documents are nearly universally present in the pockets of providers taking inhouse call. They are frequently used to answer clinical questions. However, the static nature of printed documents makes it likely that information will quickly become inaccurate as a result of ongoing management. This increases the potential for medical errors, especially in clinical services which rely heavily on printed documents for ongoing patient management.ObjectiveTo measure the average time to potential inaccuracy, represented as the ‘half-life’ of printed handoff documents.Design, setting, participantsCross-sectional analysis of 100 adult inpatients during a single 24 h period at an academic medical centre in 2014.Main outcome and measureThe half-life was defined as the time at which half of the patients would be expected to have inaccurate information on a printed handoff document, based on review of orders which populate data fields on these printed handoff documents.ResultsIn our sample, the half-life was 6 h on the 12 h night shift and 3.3 h on the day shift. We identified at least on change within the 24 h period for 92% of patients. Most changes (90% n=1411) were medication-related, but the overall distribution of order types was significantly different between day and night (p=0.002).Conclusions and relevanceThe accuracy of printed handoff documents quickly deteriorated over the course of a physician shift. Based on this decay rate, a typical physician getting sign-out on 20 patients overnight can safely assume that the data for 10 of them will be inaccurate or outdated in 6 h and that it will be inaccurate on another two by the morning.
Coaching for recovery: a quality improvement project in mental healthcare
Authors: Burhouse Anna , Rowland Madeleine , Marie Niman Heather , Abraham Daisy , Collins Elizabeth , Matthews Helen , Denney Joanna , Ryland Howard 
Published: November 2015

AbstractApproximately one in four adults in the UK will experience a mental health difficulty at some point in their life. This figure is approximately 400 million people worldwide.[1] Depression alone is currently estimated to cost the UK 1.7% of GDP and is one of the largest causes of ill health in the world.[2] For conditions like psychosis, evidence tells us that people have poorer quality of life outcomes, are more likely to die early, become obese, smoke, be unemployed, and have long term physical conditions than average.[3] People’s social situation is also likely to be more complex, with housing needs, social isolation, stigma, and poverty.[4] All of these factors can make it hard for a person with a long-term mental health condition, or those supporting them, to hold onto a sense of hope that positive change is possible or that "recovery" towards a life that holds optimum meaning to them is achievable.An innovative "pop up" Recovery College model was co-produced, delivered, and evaluated by a team of people with lived experience of mental health difficulties, known as peer trainers. The Recovery College offered courses containing the best evidence-based knowledge about recovery in mental health, self-care and self-management. Each learning session included theory, personal testament from peer trainers, and volunteers and demonstrations of practical self-care skills and techniques.The courses were open to people experiencing mental health difficulties, their families, friends, and professionals. After the college course finished each student was offered up to three individual coaching sessions to help support putting the lessons learnt from the college into practice.The project aimed to test whether this innovative educational and coaching model could offer hope, knowledge and practical skills in self-management to support resilience and recovery. The project was underpinned by quality improvement methodologies to develop, deliver, and refine the model.
Getting Access to Toxbase for Doctors in the Avon and Wiltshire Partnership
Authors: Coombs Catherine , Ewins Liz 
Published: November 2015

AbstractDoctors working in mental health often review patients who have taken an overdose. Having an evidence based resource which has information regarding the toxic doses of the drug taken enables informed discussions with senior doctors and decision making about whether to admit the patient to hospital. No site across the Avon and Wiltshire Partnership (AWP) Trust had access to TOXBASE, the Public Health England drug Toxicology database.A primary questionnaire (N= 39) found 97% of doctors thought that TOXBASE would be useful and 84.5% could not think of a better alternative.Through a series of Plan, Do, Study, Act cycles, TOXBASE access was gained for one site (Imber ward, Devizes) and following successful implementation this could be rolled out across all sites in the Trust. Doctors were surveyed and one month after the first site gained access, two out of seven doctors had used TOXBASE and found it useful. Further questionnaires were distributed following three months at three sites and then at six months to everyone. The final questionnaire showed that one third knew they had access and five doctors had used it in clinical context. Action was then taken by creating a TOXBASE on the Intranet site which directed doctors to their local inpatient unit for login details. By the end of the project access to TOXBASE was successfully gained at six out of the seven sites in the Trust. The surveys showed that access to the resource was highly regarded by doctors, and that it had enabled informed discussions with medical colleagues leading to reduced potentially lengthy transfers of patients to medical units. This has high cost implications of the transport of mental health patients, as well as reducing the distress caused to patients.
Utilisation of a trauma meeting handover proforma to improve trauma patient pathway
Authors: Smyth Rachel , Parton Felicity , Trikha Paul 
Published: November 2015

AbstractDecision making within orthopaedic centres predominantly occurs at the trauma meeting, where all decisions are made as a part of the multidisciplinary process. This is an essential handover process.Difficulties occur when teaching and detailed case discussions detract from the actual decision making process, leading to failure in documentation and implementing treatment plans.An audit was carried out in a busy district general hospital (DGH), assessing the quality of trauma meeting documentation in patient records, and assessing whether the introduction of a proforma document would improve this.Prospective clinical reviews were performed on all patients discussed in the trauma meeting over a one month period. Following the initial audit cycle a proforma was introduced, and the audit process was repeated at a two month and six month interval.The quality of the entries were assessed and compared to the Academy of Medical Royal Colleges Standards for the clinical structure and content of patient records, and The Royal College of Surgeons (RCS) of England Guidelines for Clinicians on Medical Records and Notes.Sixty three patient records during a one month period from 1 August 2014 found that only 16% had any documentation of the trauma meeting, none of which met the standard set at the beginning of the audit. Following the introduction of the proforma, 102 patient records were reviewed from October 2014, showing 70% had documentation of the trauma meeting. This improved further to 84% in February 2015.The proforma has provided an effective means of documenting and communicating management plans, and in turn also improved the trauma patient pathway to theatre or discharge.
Postoperative analgesia for Enhanced recovery in Joint replacement: Audit of a new electronic prescribing order set
Authors: Wright Jonathan , Cullinger Benjamin , Bacarese-Hamilton Ian 
Published: November 2015

AbstractEnhanced recovery in joint replacement has been shown to reduce length of inpatient stay, reduce re-admission rates, and can improve early functional recovery. Postoperative analgesia is an important component of the group of interventions required to form a holistic enhanced recovery protocol. The introduction of electronic prescribing provides the opportunity to introduce some standardisation, where clinically appropriate, in the prescription of an evidence based postoperative analgesia protocol.Enhanced recovery following joint replacement has been used at this institution since 2011. An order set for the postoperative analgesia protocol was introduced to the in house electronic prescribing system in August 2014 (JAC Medicines Management; JAC Computer Services Ltd., Basildon, UK). An audit was performed to follow the effect of the new system on compliance with the postoperative analgesia guidelines.Improvements were seen following introduction of the electronic prescribing protocol in all criteria of the guideline with a demonstrated improvement in overall compliance from 0% to 35% in the first loop, with subsequent audit showing further improvement to 59% compliance.Use of an embedded order set within an electronic prescribing system has demonstrated improved compliance with an enhanced recovery protocol. This ensures that the correct evidence based protocol is available to guide the junior clinician at the point of care, when the medication is being prescribed.
Potential underestimation of pesticide suicide and its impact on secular trends in South Korea, 1991–2012
Authors: Cha Eun Shil , Chang Shu-Sen , Lee Won Jin 
Published: November 2015

BackgroundPesticide ingestion is among the most commonly used suicide methods globally. Underestimation of deaths by pesticide self-poisoning is thought to be common but under-researched. We investigated potential misclassification and underestimation of suicide by pesticide poisoning and their impact on trends in pesticide suicide in South Korea.MethodsWe compared sociodemographic profiles between deaths certified as suicide, undetermined deaths and injuries by poisoning using pesticides, unspecified chemicals and medicines/alcohol in South Korea (1991–2012), and calculated similarity scores. Joinpoint regression analysis was used to examine time trends.ResultsThe profiles of deaths classified as pesticide suicides showed generally similar patterns to those for undetermined deaths/injuries by poisoning using pesticides and suicides/undetermined deaths/injuries by poisoning using unspecified chemicals. Over the study period, the number of pesticide suicides (on average 2033 per year; range 623–3530) would increase by 15%, 23% and 31%, when assuming that 20%, 30% and 40% of deaths in alternative cause-of-death categories were misclassified pesticide suicides respectively. Age-standardised rates of pesticide suicide increased more than four times in 1991–2003 but fell by around 50% in 2003–2012. This trend did not change when the assumed proportion of misclassification was 20%, whereas the rapid increase in 2000–2003 would be lessened if misclassification occurred by 30% or more.ConclusionsPesticide suicides may be underestimated in South Korea as some are possibly misclassified as deaths due to other causes; however, such underestimation would not substantially affect estimated secular trends.