bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Intracellular Nanotrap Redirects Proteins and Organelles in Live Bacteria
Authors: Borg Sarah , Popp Felix , Hofmann Julia , Leonhardt Heinrich , Rothbauer Ulrich , Schüler Dirk 
Published: January 2015

ABSTRACT

Owing to their small size and enhanced stability, nanobodies derived from camelids have previously been used for the construction of intracellular “nanotraps,” which enable redirection and manipulation of green fluorescent protein (GFP)-tagged targets within living plant and animal cells. By taking advantage of intracellular compartmentalization in the magnetic bacterium
Magnetospirillum gryphiswaldense
, we demonstrate that proteins and even entire organelles can be retargeted also within prokaryotic cells by versatile nanotrap technology. Expression of multivalent GFP-binding nanobodies on magnetosomes ectopically recruited the chemotaxis protein CheW
1
-GFP from polar chemoreceptor clusters to the midcell, resulting in a gradual knockdown of aerotaxis. Conversely, entire magnetosome chains could be redirected from the midcell and tethered to one of the cell poles. Similar approaches could potentially be used for building synthetic cellular structures and targeted protein knockdowns in other bacteria.

IMPORTANCE
Intrabodies are commonly used in eukaryotic systems for intracellular analysis and manipulation of proteins within distinct subcellular compartments. In particular, so-called nanobodies have great potential for synthetic biology approaches because they can be expressed easily in heterologous hosts and actively interact with intracellular targets, for instance, by the construction of intracellular “nanotraps” in living animal and plant cells. Although prokaryotic cells also exhibit a considerable degree of intracellular organization, there are few tools available equivalent to the well-established methods used in eukaryotes. Here, we demonstrate the ectopic retargeting and depletion of polar membrane proteins and entire organelles to distinct compartments in a magnetotactic bacterium, resulting in a gradual knockdown of magneto-aerotaxis. This intracellular nanotrap approach has the potential to be applied in other bacteria for building synthetic cellular structures, manipulating protein function, and creating gradual targeted knockdowns. Our findings provide a proof of principle for the universal use of fluorescently tagged proteins as targets for nanotraps to fulfill these tasks.
Inactivation of a Foodborne Norovirus Outbreak Strain with Nonthermal Atmospheric Pressure Plasma
Authors: Ahlfeld Birte , Li Yangfang , Boulaaba Annika , Binder Alfred , Schotte Ulrich , Zimmermann Julia L. , Morfill Gregor , Klein Günter 
Published: January 2015

ABSTRACT

Human norovirus (NoV) is the most frequent cause of epidemic nonbacterial acute gastroenteritis worldwide. We investigated the impact of nonthermal or cold atmospheric pressure plasma (CAPP) on the inactivation of a clinical human outbreak NoV, GII.4. Three different dilutions of a NoV-positive stool sample were prepared and subsequently treated with CAPP for various lengths of time, up to 15 min. NoV viral loads were quantified by quantitative real-time reverse transcription PCR (RT-qPCR). Increased CAPP treatment time led to increased NoV reduction; samples treated for the longest time had the lowest viral load. From the initial starting quantity of 2.36 × 10
4
genomic equivalents/ml, sample exposure to CAPP reduced this value by 1.23 log
10
and 1.69 log
10
genomic equivalents/ml after 10 and 15 min, respectively (
P
< 0.01). CAPP treatment of surfaces carrying a lower viral load reduced NoV by at least 1 log
10
after CAPP exposure for 2 min (
P
< 0.05) and 1 min (
P
< 0.05), respectively. Our results suggest that NoV can be inactivated by CAPP treatment. The lack of cell culture assays prevents our ability to estimate infectivity. It is possible that some detectable, intact virus particles were rendered noninfectious. We conclude that CAPP treatment of surfaces may be a useful strategy to reduce the risk of NoV transmission in crowded environments.

IMPORTANCE
Human gastroenteritis is most frequently caused by noroviruses, which are spread person to person and via surfaces, often in facilities with crowds of people. Disinfection of surfaces that come into contact with infected humans is critical for the prevention of cross-contamination and further transmission of the virus. However, effective disinfection cannot be done easily in mass catering environments or health care facilities. We evaluated the efficacy of cold atmospheric pressure plasma, an innovative airborne disinfection method, on surfaces inoculated with norovirus. We used a clinically relevant strain of norovirus from an outbreak in Germany. Cold plasma was able to inactivate the virus on the tested surfaces, suggesting that this method could be used for continuous disinfection of contaminated surfaces. The use of a clinical strain of norovirus strengthens the reliability of our results as it is a strain relevant to outbreaks in humans.
Variation in local trust Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) policies: a review of 48 English healthcare trusts
Authors: Freeman Karoline , Field Richard A , Perkins Gavin D 
Published: January 2015

ObjectivesTo explore Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) policies from English acute, community and ambulance service Trusts for evidence of consistency and variation in implementation of national guidelines between healthcare organisations.SettingAcute, community or ambulance National Health Service (NHS) Trusts in England.Participants48 NHS Trusts.InterventionsFreedom of information requests for adult DNACPR policies were sent to a random sample of Trusts.OutcomesDNACPR policies were assessed on aspects identified from national guidelines including documentation, ethical and legal issues, decision-makers and involvement of others in DNACPR decisions as well as practical considerations such as validity, review and portability of decisions.ResultsPolicies from 26 acute, 12 community and 10 ambulance service Trusts were reviewed. There was variation in terminology used (85% described documents as policies, 6% procedures and 8% guidelines). Only one quarter of Trusts used the recommended Resuscitation Council (UK) record form (or a modification of the form). There was variation in the terminology used which included DNAR, DNACPR, Not for CPR and AND (allow natural death). Accountability for DNACPR decisions rested with consultants at all acute Trusts and the most senior clinician at community Trusts. Most Trusts (74%) recommended discussion of decisions with a multidisciplinary team. Compliance with guidance requiring clinical staff to assess the patient for capacity and when to consult a lasting power of attorney or independent mental capacity advocate occurred less commonly. There was wide variation in the duration of time over which a DNACPR decision was considered valid as well as in the Trusts’ approach to reviewing DNACPR decisions. The level of portability of DNACPR decisions between healthcare organisations was one of the greatest sources of variation.ConclusionsThere is significant variation in the translation of the national DNACPR guidelines into English healthcare Trusts’ DNACPR policies.
Does prewarming the i-gel supraglottic airway device fit the larynx better compared to keeping it at room temperature for non-paralysed, sedated patients: a randomised controlled trial
Authors: Komasawa Nobuyasu , Nishihara Isao , Tatsumi Shinichi , Minami Toshiaki 
Published: January 2015

ObjectiveThis study aimed to test the hypothesis that the i-gel supraglottic airway device would fit the larynx and provide better sealing pressure if prewarmed to 42°C relative to the device kept at room temperature in non-paralysed, sedated patients.MethodsA total of 74 adult patients were assigned to the warm (i-gel prewarmed to 42°C; W group; 37 patients) or the control (i-gel kept at room temperature; C group; 37 patients) groups. Anaesthesia was induced with propofol and fentanyl. The i-gel was prewarmed to 42°C for 30 min before insertion in the W group, but kept at room temperature (approximately 23°C) for the C group. The number of attempts made until successful insertion and sealing pressure were compared between the two groups.ResultsInsertion was successful with one attempt in 35 cases each for the W and C groups. Two attempts were needed in two cases for the W group and one case for the C group. There was one failed attempt in the C group, but none in the W group. None of the differences between the two groups were significant (p=0.51). Sealing pressure was slightly, but not significantly, higher in the W group than in the C group (W group 22.6±6.1 cm H2O; C group 20.7±6.1 cm H2O; p=0.15).ConclusionsPrewarming of the i-gel to 42°C did not increase the success rate of insertion, nor did it significantly increase sealing pressure in anaesthetised, non-paralysed patients. Our data suggest that we can keep the i-gel at room temperature for emergency airway management for non-paralysed, sedated patients.Trial registration numberUniversity Medical Information Network, Japan 000012287.
Prevalence and characteristics of tremor in the NARCOMS multiple sclerosis registry: a cross-sectional survey
Authors: Rinker John R , Salter Amber R , Walker Harrison , Amara Amy , Meador William , Cutter Gary R 
Published: January 2015

Objectives(1)To describe the prevalence and severity of tremor in patients with multiple sclerosis (MS) registered within a large North American MS registry; (2) to provide detailed descriptions on the characteristics and severity of tremor in a subset of registrants and (3) to compare several measures of tremor severity for strength of agreement.SettingThe North American Research Committee on MS (NARCOMS) registry.ParticipantsRegistrants of NARCOMS reporting mild or greater tremor severity.Outcome measuresWe determined the cross-sectional prevalence of tremor in the NARCOMS registry over three semiannual updates between fall 2010 and fall 2011. A subset of registrants (n=552) completed a supplemental survey providing detailed descriptions of their tremor. Outcomes included descriptive characteristics of their tremors and correlations between outcome measures to determine the strength of agreement in assessing tremor severity.ResultsThe estimated prevalence of tremor in NARCOMS ranged from 45% to 46.8%, with severe tremor affecting 5.5–5.9% of respondents. In the subset completing the supplemental survey, mild tremor severity was associated with younger age of MS diagnosis and tremor onset than those with moderate or severe tremor. However, tremor severity did not differ by duration of disease or tremor. Respondents provided descriptions of tremor symptoms on the Clinical Ataxia Rating Scale, which had a moderate to good (ρ=0.595) correlation with the Tremor Related Activities of Daily Living (TRADL) scale. Objectively scored Archimedes’ spirals had a weaker (ρ=0.358) correlation with the TRADL. Rates of unemployment, disability and symptomatic medication use increased with tremor severity, but were high even among those with mild tremor.ConclusionsTremor is common among NARCOMS registrants and severely disabling for some. Both ADL-based and symptom-descriptive measures of tremor severity can be used to stratify patients.
Salpingectomy as a Means to Reduce Ovarian Cancer Risk
Authors: Daly Mary B. , Dresher Charles W. , Yates Melinda S. , Jeter Joanne M. , Karlan Beth Y. , Alberts David S. , Lu Karen H. 
Published: January 2015

Abstract
Bilateral salpingo-oophorectomy (BSO) has become the standard-of-care for risk reduction in women at hereditary risk of ovarian cancer. Although this procedure significantly decreases both the incidence of and mortality from ovarian cancer, it affects quality of life, and the premature cessation of ovarian function may have long-term health hazards. Recent advances in our understanding of the molecular pathways of ovarian cancer point to the fallopian tube epithelium as the origin of most high-grade serous cancers (HGSC). This evolving appreciation of the role of the fallopian tube in HGSC has led to the consideration of salpingectomy alone as an option for risk management, especially in premenopausal women. In addition, it is postulated that bilateral salpingectomy with ovarian retention (BSOR), may have a public health benefit for women undergoing benign gynecologic surgery. In this review, we provide the rationale for salpingectomy as an ovarian cancer risk reduction strategy. Cancer Prev Res; 8(5); 342–8. ©2015 AACR.
See related commentary by Mark H. Greene, p. 339
Cigarette Smoking and Cardiovascular Events
Authors: McEvoy John W. , Blaha Michael J. , DeFilippis Andrew P. , Lima Joao A.C. , Bluemke David A. , Hundley W. Gregory , Min James K. , Shaw Leslee J. , Lloyd-Jones Donald M. , Barr R. Graham , Budoff Matthew J. , Blumenthal Roger S. , Nasir Khurram 
Published: January 2015

Objectives—
To examine the contemporary effect of smoking in a multiethnic sample, and to explore the respective contributions of inflammation and subclinical atherosclerosis to the cardiovascular consequences of smoking.

Approach and Results—

We studied 6814 participants free of cardiovascular disease and coronary heart disease (CHD) from the Multiethnic Study of Atherosclerosis. Smoking status and cumulative exposure were determined by self-report and confirmed by urinary cotinine. Multivariable Cox regression was used to estimate the association between smoking parameters and all-cause cardiovascular disease, all-cause CHD, and hard CHD events. We further adjusted for high-sensitivity C-reactive protein and coronary artery calcium (CAC) in hierarchical Cox models. We identified 3218 never smokers, 2607 former smokers, and 971 current smokers. Median follow-up was 10.2 years. Compared with never smokers, adjusted hazard ratios in current smokers were 1.7 (95% confidence interval, 1.3–2.2) for all-cause cardiovascular disease, 1.6 (1.1–2.1) for all-cause CHD, and 1.7 (1.2–2.4) for hard CHD. Similarly, among current smokers, hazard ratios were higher in the 4th versus 1st quartile of pack-years (eg, all-cause CHD hazard ratio=2.7 [1.1–6.6]). Both CAC>100 and high-sensitivity C-reactive protein ≥3 mg/L identified higher relative risk among current smokers (eg, all-cause CHD hazard ratio of 3.0 [1.5–6.0, compared with CAC=0] and 2.6 [1.4–4.8, compared with high-sensitivity C-reactive protein <2 mg/L], respectively). However, CAC was a stronger mediator of events and adversely modified the effect of smoking on events (eg,
P
-interaction=0.02 for hard CHD). Compared with never smokers, former smokers (median cessation interval=22 years) had similar adjusted hazard for events.

Conclusions—
In this multiethnic cohort, current smoking and cumulative exposure remain important modifiable determinants of cardiovascular disease. Both high-sensitivity C-reactive protein ≥3 mg/L and, particularly, CAC>100 identified high-risk smokers who may benefit from more intensive smoking-cessation efforts.
Cellular Postconditioning
Authors: Kanazawa Hideaki , Tseliou Eleni , Malliaras Konstantinos , Yee Kristine , Dawkins James F. , De Couto Geoffrey , Smith Rachel R. , Kreke Michelle , Seinfeld Jeffrey , Middleton Ryan C. , Gallet Romain , Cheng Ke , Luthringer Daniel , Valle Ileana , Chowdhury Supurna , Fukuda Keiichi , Makkar Raj R. , Marbán Linda , Marbán Eduardo 
Published: January 2015

Background—
Intracoronary delivery of cardiosphere-derived cells (CDCs) has been demonstrated to be safe and effective in porcine and human chronic myocardial infarction. However, intracoronary delivery of CDCs after reperfusion in acute myocardial infarction has never been assessed in a clinically-relevant large animal model. We tested CDCs as adjunctive therapy to reperfusion in a porcine model of myocardial infarction.

Methods and Results—
First, escalating doses (5, 7.5, and 10 million cells) of allogeneic CDCs were administered intracoronary 30 minutes after reperfusion. Forty-eight hours later, left ventriculography was performed and animals euthanized to measure area at risk, infarct size (IS), and microvascular obstruction. Second, identical end points were measured in a pivotal study of minipigs (n=14) that received 8.5 to 9 million allogeneic CDCs, placebo solution, or sham. Multiple indicators of cardioprotection were observed with 7.5 and 10 million allogeneic CDCs, but not 5 million CDCs, relative to control. In the pivotal study, IS, microvascular obstruction, cardiomyocyte apoptosis, and adverse left ventricular remodeling were all smaller in the CDC group than in sham or placebo groups. In addition, serum troponin I level at 24 hours was lower after CDC infusion than that in the placebo or sham groups, consistent with the histologically-demonstrated reduction in IS.

Conclusions—
Intracoronary delivery of allogeneic CDCs is safe, feasible, and effective in cardioprotection, reducing IS, preventing microvascular obstruction, and attenuating adverse acute remodeling. This novel cardioprotective effect, which we call cellular postconditioning, differs from previous strategies to reduce IS in that it works even when initiated with significant delay after reflow.
Hospital Variation in Quality of Discharge Summaries for Patients Hospitalized With Heart Failure Exacerbation
Authors: Al-Damluji Mohammed Salim , Dzara Kristina , Hodshon Beth , Punnanithinont Natdanai , Krumholz Harlan M. , Chaudhry Sarwat I. , Horwitz Leora I. 
Published: January 2015

Background—
Single-site studies have demonstrated inadequate quality of discharge summaries in timeliness, transmission, and content, potentially contributing to adverse outcomes. However, degree of hospital-level variation in discharge summary quality for patients hospitalized with heart failure (HF) is uncertain.

Methods and Results—

We analyzed discharge summaries of patients enrolled in the Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) study. We assessed hospital-level performance on timeliness (fraction of summaries completed on the day of discharge), documented transmission to the follow-up physician, and content (presence of components suggested by the Transitions of Care Consensus Conference). We obtained 1501 discharge summaries from 1640 (91.5%) patients discharged alive from 46 hospitals. Among hospitals contributing ≥10 summaries, the median hospital dictated 69.2% of discharge summaries on the day of discharge (range, 0.0%–98.0%;
P
<0.001); documented transmission of 33.3% of summaries to the follow-up physician (range, 0.0%–75.7%;
P
<0.001); and included 3.6 of 7 Transitions of Care Consensus Conference elements (range, 2.9–4.5;
P
<0.001). Hospital course was typically included (97.2%), but summaries were less likely to include discharge condition (30.7%), discharge volume status (16.0%), or discharge weight (15.7%). No discharge summary included all 7 Transitions of Care Consensus Conference–endorsed content elements, was dictated on the day of discharge, and was sent to a follow-up physician.

Conclusions—
Even at the highest performing hospital, discharge summary quality is insufficient in terms of timeliness, transmission, and content. Improvements in all aspects of discharge summary quality are necessary to enable the discharge summary to serve as an effective transitional care tool.
Predicting Graft Loss by 1 Year in Pediatric Heart Transplantation Candidates
Authors: Schumacher Kurt R. , Almond Christopher , Singh Tajinder P. , Kirk Richard , Spicer Robert , Hoffman Timothy M. , Hsu Daphne , Naftel David C. , Pruitt Elizabeth , Zamberlan Mary , Canter Charles E. , Gajarski Robert J. 
Published: January 2015

Background—
Pediatric data on the impact of pre–heart transplantation (HTx) risk factors on early post-HTx outcomes remain inconclusive. Thus, among patients with previous congenital heart disease or cardiomyopathy, disease-specific risk models for graft loss were developed with the use pre-HTx recipient and donor characteristics.

Methods and Results—
Patients enrolled in the Pediatric Heart Transplant Study (PHTS) from 1996 to 2006 were stratified by pre-HTx diagnosis into cardiomyopathy and congenital heart disease cohorts. Logistic regression identified independent, pre-HTx risk factors. Risk models were constructed for 1-year post-HTx graft loss. Donor factors were added for model refinement. The models were validated with the use of patients transplanted from 2007 to 2009. Risk factors for graft loss were identified in patients with cardiomyopathy (n=896) and congenital heart disease (n=965). For cardiomyopathy, independent risk factors were earlier year of transplantation, nonwhite race, female sex, diagnosis other than dilated cardiomyopathy, higher blood urea nitrogen, and panel reactive antibody >10%. The recipient characteristic risk model had good accuracy in the validation cohort, with predicted versus actual survival of 97.5% versus 95.3% (C statistic, 0.73). For patients with congenital heart disease, independent risk factors were nonwhite race, history of Fontan, ventilator dependence, higher blood urea nitrogen, panel reactive antibody >10%, and lower body surface area. The risk model was less accurate, with 86.6% predicted versus 92.4% actual survival, in the validation cohort (C statistic, 0.63). Donor characteristics did not enhance model precision.

Conclusions—
Risk factors for 1-year post-HTx graft loss differ on the basis of pre-HTx cardiac diagnosis. Modeling effectively stratifies the risk of graft loss in patients with cardiomyopathy and may be an adjunctive tool in allocation policies and center performance metrics.
Genes From a Translational Analysis Support a Multifactorial Nature of White Matter Hyperintensities
Authors: Lopez Lorna M. , Hill W. David , Harris Sarah E. , Valdes Hernandez Maria , Munoz Maniega Susana , Bastin Mark E. , Bailey Emma , Smith Colin , McBride Martin , McClure John , Graham Delyth , Dominiczak Anna , Yang Qiong , Fornage Myriam , Ikram M. Arfan , Debette Stephanie , Launer Lenore , Bis Joshua C. , Schmidt Reinhold , Seshadri Sudha , Porteous David J. , Starr John , Deary Ian J. , Wardlaw Joanna M. 
Published: January 2015

Background and Purpose—
White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative.

Methods—
We tested the associations between genes that were differentially expressed in brains of young spontaneously hypertensive stroke–prone rats and human WMH (using volume and visual score) in 621 subjects from the Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361 subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH associations found in subjects from CHARGE.

Results—

Of 126 spontaneously hypertensive stroke–prone rat genes, 10 were nominally associated with WMH volume or score in subjects from LBC1936, of which 5 (
AFP
,
ALB
,
GNAI1
,
RBM8a
, and
MRPL18
) were associated with both WMH volume and score (
P
<0.05); 2 of the 10 (
XPNPEP1
,
P
=6.7×10
−5
;
FARP1
,
P
=0.024) plus another spontaneously hypertensive stroke–prone rat gene (
USMG5
,
P
=0.00014), on chromosomes 10, 13, and 10 respectively, were associated with WMH in subjects from CHARGE. Gene set enrichment showed significant associations for downregulated spontaneously hypertensive stroke–prone rat genes with WMH in humans. In subjects from LBC1936, we replicated CHARGE’s genome-wide WMH associations on chromosomes 17 (
TRIM65
and
TRIM47
) and, for the first time, 1 (
PMF1
).

Conclusions—
Despite not passing multiple testing thresholds individually, these genes collectively are relevant to known WMH associations, proposed WMH mechanisms, or dementia: associations with Alzheimer's disease, late-life depression, ATP production, osmotic regulation, neurodevelopmental abnormalities, and cognitive impairment. If replicated further, they suggest a multifactorial nature for WMH and argue for more consideration of vascular contributions to dementia.