bluuebunny/crossref_metadata_2025_split huggingface dataset:
In long bacterial cells, the Min system can act off‐center
Authors: MacCready Joshua S. , Vecchiarelli Anthony G. 
Published: June 2018

SummaryIn many rod‐shaped bacteria, the Min system is well‐known for generating a cell‐pole to cell‐pole standing wave oscillation with a single node at mid‐cell to align cell division. In filamentous E. coli cells, the single‐node standing wave transitions into a multi‐nodal oscillation. These multi‐nodal dynamics have largely been treated simply as an interesting byproduct of artificially elongated cells. However, a recent in vivo study by Muraleedharan et al. shows how multi‐nodal Min dynamics are used to align non‐mid‐cell divisions in the elongated swarmer cells of Vibrio parahaemolyticus. The authors propose a model where the combined actions of cell‐length dependent Min dynamics, in concert with nucleoid occlusion along the cell length and regulation of FtsZ levels ensures Z ring formation and complete chromosome segregation at a single off‐center position. By limiting the number of cell division events to one per cell at an off‐center position, long swarmer cells are preserved within a multiplying population. The findings unveil an elegant mechanism of cell‐division regulation by the Min system that allows long swarmer cells to divide without the need to ‘dedifferentiate’.
Ancient association of cyanobacterial multicellularity with the regulator HetR and an RGSGR pentapeptide‐containing protein (PatX)
Authors: Elhai Jeff , Khudyakov Ivan 
Published: June 2018

SummaryOne simple model to explain biological pattern postulates the existence of a stationary regulator of differentiation that positively affects its own expression, coupled with a diffusible suppressor of differentiation that inhibits the regulator’s expression. The first has been identified in the filamentous, heterocyst‐forming cyanobacterium, Anabaena PCC 7120 as the transcriptional regulator, HetR and the second as the small protein, PatS, which contains a critical RGSGR motif that binds to HetR. HetR is present in almost all filamentous cyanobacteria, but only a subset of heterocyst‐forming strains carry proteins similar to PatS. We identified a third protein, PatX that also carries the RGSGR motif and is coextensive with HetR. Amino acid sequences of PatX contain two conserved regions: the RGSGR motif and a hydrophobic N‐terminus. Within 69 nt upstream from all instances of the gene is a DIF1 motif correlated in Anabaena with promoter induction in developing heterocysts, preceded in heterocyst‐forming strains by an apparent NtcA‐binding site, associated with regulation by nitrogen‐status. Consistent with a role in the simple model, PatX is expressed dependent on HetR and acts to inhibit differentiation. The acquisition of the PatX/HetR pair preceded the appearance of both PatS and heterocysts, dating back to the beginnings of multicellularity.
Factors associated with immune hemolytic anemia after pediatric liver transplantation
Authors: Rock Nathalie , Ansari Marc , Villard Jean , Ferrari‐Lacraz Sylvie , Waldvogel Sophie , McLin Valérie Anne 
Published: June 2018

AbstractImmune‐mediated hemolytic anemia following SOT is a rare disorder, the risk factors for which are unknown. Our purpose was to analyze a seemingly increased incidence in our center with the aim to identify predisposing factors. This recipients single‐center retrospective study reviewed the medical records of 96 pediatric LT between 2000 and 2013. IHA was defined as acute anemia with a positive direct antiglobulin test. Seven cases of immune‐mediated hemolytic anemia were identified (incidence 8.5%). Three cases presented during the first 3 months following LT (early IHA), and 4 presented later (late IHA). All patients with late IHA required rituximab. Using univariate analysis, the following factors were associated with IHA onset: BA (P = .04), younger age (P = .04), and the use of IGL‐1 preservation solution (P = .05). Late IHA was associated with viral infections occurring beyond 3 months following LT, younger age, and BA (P = .01). Overall, CMV infection was associated with the development of both early and late IHA: CMV‐negative recipients who received an organ from a CMV‐positive donor were more likely to develop IHA (P = .035), and de novo CMV infection during the first year post‐LT was associated with late IHA (P = .03). IHA is a rare complication following pediatric LT, occurring more frequently in younger patients and patients with an initial diagnosis of BA. CMV‐negative recipients and patients who experience a de novo CMV infection in the first year following LT seem particularly vulnerable. IGL‐1 preservation solution may be associated with an increased likelihood of developing IHA, a novel finding which warrants further investigation.
Cwp19 Is a Novel Lytic Transglycosylase Involved in Stationary-Phase Autolysis Resulting in Toxin Release in
Clostridium difficile
Authors: Wydau-Dematteis Sandra , El Meouche Imane , Courtin Pascal , Hamiot Audrey , Lai-Kuen René , Saubaméa Bruno , Fenaille François , Butel Marie-José , Pons Jean-Louis , Dupuy Bruno , Chapot-Chartier Marie-Pierre , Peltier Johann 
Published: June 2018

ABSTRACT

Clostridium difficile
is the major etiologic agent of antibiotic-associated intestinal disease. Pathogenesis of
C. difficile
is mainly attributed to the production and secretion of toxins A and B. Unlike most clostridial toxins, toxins A and B have no signal peptide, and they are therefore secreted by unusual mechanisms involving the holin-like TcdE protein and/or autolysis. In this study, we characterized the cell surface protein Cwp19, a newly identified peptidoglycan-degrading enzyme containing a novel catalytic domain. We purified a recombinant His
6
-tagged Cwp19 protein and showed that it has lytic transglycosylase activity. Moreover, we observed that Cwp19 is involved in cell autolysis and that a
C. difficile
cwp19
mutant exhibited delayed autolysis in stationary phase compared to the wild type when bacteria were grown in brain heart infusion (BHI) medium. Wild-type cell autolysis is correlated to strong alterations of cell wall thickness and integrity and to release of cytoplasmic material. Furthermore, we demonstrated that toxins were released into the extracellular medium as a result of Cwp19-induced autolysis when cells were grown in BHI medium. In contrast, Cwp19 did not induce autolysis or toxin release when cells were grown in tryptone-yeast extract (TY) medium. These data provide evidence for the first time that TcdE and bacteriolysis are coexisting mechanisms for toxin release, with their relative contributions
in vitro
depending on growth conditions. Thus, Cwp19 is an important surface protein involved in autolysis of vegetative cells of
C. difficile
that mediates the release of the toxins from the cell cytosol in response to specific environment conditions.

IMPORTANCE
Clostridium difficile
-associated disease is mainly known as a health care-associated infection. It represents the most problematic hospital-acquired infection in North America and Europe and exerts significant economic pressure on health care systems. Virulent strains of
C. difficile
generally produce two toxins that have been identified as the major virulence factors. The mechanism for release of these toxins from bacterial cells is not yet fully understood but is thought to be partly mediated by bacteriolysis. Here we identify a novel peptidoglycan hydrolase in
C. difficile
, Cwp19, exhibiting lytic transglycosylase activity. We show that Cwp19 contributes to
C. difficile
cell autolysis in the stationary phase and, consequently, to toxin release, most probably as a response to environmental conditions such as nutritional signals. These data highlight that Cwp19 constitutes a promising target for the development of new preventive and curative strategies.
Suture snare technique for scleral fixation of intraocular lenses and capsular tension devices
Authors: Chee Soon-Phaik , Chan Nicole Shu-Wen 
Published: June 2018

Polytetrafluoroethylene (Gore-Tex) suture is preferred for scleral fixation of intraocular lenses or capsular tension devices as it is more resilient to breakage than polypropylene 10–0. However, manipulation of the thick calibre and overcurved configuration of the Gore-Tex needle within the eye poses a risk of damage to the intraocular structures. Existing techniques that overcome the problem of needles within the anterior chamber involve special instruments to retrieve the suture. We describe a technique that creates a suture snare from a short segment of the Gore-Tex suture borne on a 26-gauge needle, which is used to retrieve the Gore-Tex suture safely at the scleral fixation site. The suture is threaded into the bore of the needle leaving a short length extending from the hub which is secured by inserting a 1 cc syringe acting as a handle. The needle is inserted at the scleral fixation site, and the suture trailing from the needle tip forms a loop which is externalised at the main incision. This suture snare is used to retrieve the end of the Gore-Tex suture bearing the device to the scleral fixation site when the needle and the loop of the suture are withdrawn from the eye. This technique eliminates the inappropriate needle and the need for a large sclerostomy, and is cost-effective and can also be used in combination with the conjunctival-sparing Hoffman corneoscleral pocket.
Study to determine the likely accuracy of pH testing to confirm nasogastric tube placement
Authors: Rowat Anne M , Graham Catriona , Dennis Martin 
Published: June 2018

ObjectiveTo establish the likely accuracy of pH testing to identify gastric aspirates at different pH cut-offs to confirm nasogastric tube placement.MethodsThis prospective observational study included a convenience sample of adult patients who had two (one fresh and one frozen) gastric and oesophageal samples taken during gastroscopy or two bronchial and saliva samples taken during bronchoscopy. The degree of observer agreement for the pH of fresh and frozen samples was indicted by kappa (k) statistics. The sensitivities and specificities at pH ≤5.5 and the area under the receiver operating characteristics (ROC) curve at different pH cut-offs were calculated to identify gastric and non-gastric aspirates.ResultsNinety-seven patients had a gastroscopy, 106 a bronchoscopy. There was complete agreement between observers in 57/92 (62%) of the paired fresh and frozen gastric samples (k=0.496, 95% CI 0.364 to 0.627). The sensitivity of a pH ≤5.5 to correctly identify gastric samples was 68% (95% CI 57 to 77) and the specificity was 79% (95% CI 74 to 84). The overall accuracy to correctly classify samples was between 76% and 77%, regardless of whether patients were taking antacids or not. The area under the ROC curve at different pH cut-offs was 0.74.ConclusionThe diagnostic accuracy of pH ≤5.5 to differentiate gastric from non-gastric samples was low, regardless of whether patients were taking antacids or not. Due to the limited accuracy of the pH sticks and the operators’ ability to differentiate colorimetric results, there is an urgent need to identify more accurate and safer methods to confirm correct placement of nasogastric tubes.
Cohort profile: the Geoscience and Health Cohort Consortium (GECCO) in the Netherlands
Authors: Timmermans Erik J , Lakerveld Jeroen , Beulens Joline W J , Boomsma Dorret I , Kramer Sophia E , Oosterman Mirjam , Willemsen Gonneke , Stam Mariska , Nijpels Giel , Schuengel Carlo , Smit Jan H , Brunekreef Bert , Dekkers Jasper E C , Deeg Dorly J H , Penninx Brenda W J H , Huisman Martijn 
Published: June 2018

PurposeIn the Netherlands, a great variety of objectively measured geo-data is available, but these data are scattered and measured at varying spatial and temporal scales. The centralisation of these geo-data and the linkage of these data to individual-level data from longitudinal cohort studies enable large-scale epidemiological research on the impact of the environment on public health in the Netherlands. In the Geoscience and Health Cohort Consortium (GECCO), six large-scale and ongoing cohort studies have been enriched with a variety of existing geo-data. Here, we introduce GECCO by describing: (1) the phenotypes of the involved cohort studies, (2) the collected geo-data and their sources, (3) the methodology that was used to link the collected geo-data to individual cohort studies, (4) the similarity of commonly used geo-data between our consortium and the nationwide situation in the Netherlands and (5) the distribution of geo-data within our consortium.ParticipantsGECCO includes participants from six prospective cohort studies (eg, 44 657 respondents (18–100 years) in 2006) and it covers all municipalities in the Netherlands. Using postal code information of the participants, geo-data on the address-level, postal code-level as well as neighbourhood-level could be linked to individual-level cohort data.Findings to dateThe geo-data could be successfully linked to almost all respondents of all cohort studies, with successful data-linkage rates ranging from 97.1% to 100.0% between cohort studies. The results show variability in geo-data within and across cohorts. GECCO increases power of analyses, provides opportunities for cross-checking and replication, ensures sufficient geographical variation in environmental determinants and allows for nuanced analyses on specific subgroups.Future plansGECCO offers unique opportunities for (longitudinal) studies on the complex relationships between the environment and health outcomes. For example, GECCO will be used for further research on environmental determinants of physical/psychosocial functioning and lifestyle behaviours.
Children’s views on research without prior consent in emergency situations: a UK qualitative study
Authors: Roper Louise , Sherratt Frances C , Young Bridget , McNamara Paul , Dawson Angus , Appleton Richard , Crawley Esther , Frith Lucy , Gamble Carrol , Woolfall Kerry 
Published: June 2018

ObjectivesWe explored children’s views on research without prior consent (RWPC) and sought to identify ways of involving children in research discussions.DesignQualitative interview study.SettingParticipants were recruited through a UK children’s hospital and online advertising.Participants16 children aged 7–15 years with a diagnosis of asthma (n=14) or anaphylaxis (n=2) with recent (<12 months) experience of emergency care.ResultsChildren were keen to be included in medical research and viewed RWPC as acceptable in emergency situations if trial interventions were judged safe. Children trusted that doctors would know about their trial participation and act in their best interests. All felt that children should be informed about the research following their recovery and involved in discussions with a clinician or their parent(s) about the use of data already collected as well as continued participation in the trial (if applicable). Participants suggested methods to inform children about their trial participation including an animation.ConclusionsChildren supported, and were keen to be involved in, clinical trials in emergency situations. We present guidance and an animation that practitioners and parents might use to involve children in trial discussions following their recovery.
Accuracy, reproducibility and costs of different laboratory assays for the monitoring of unfractionated heparin in clinical practice: a prospective evaluation study and survey among Swiss institutions
Authors: Bürki Susanne , Brand Béatrice , Escher Robert , Wuillemin Walter A , Nagler Michael 
Published: June 2018

ObjectivesTo investigate the accuracy, reproducibility and costs of different laboratory assays for the monitoring of unfractionated heparin (UFH) in clinical practice and to study test utilisation in Switzerland.DesignProspective evaluation study and survey among Swiss hospitals and laboratories.SettingSecondary care hospital in rural Switzerland (evaluation study); all Swiss hospitals and laboratories (survey).ParticipantsAll consecutive patients, monitored for treatment with UFH during two time periods, were included (May to July 2014 and January to February 2015; n=254).Outcome measuresResults of activated partial thromboplastin time (aPTT), thrombin time (TT), prothrombinase-induced clotting time (PiCT) and anti-Xa activity with respect to UFH concentrationResultsSpearman’s correlation coefficient (rs) with regard to anti-Xa activity was 0.68 (95% CI 0.60 to 0.75) for aPTT, 0.79 (0.69 to 0.86) for TT and 0.94 (0.93 to 0.95) for PiCT. The correlation (rs) between anti-Xa activity and heparin concentration as determined by spiking plasma samples was 1.0 (1.0 to 1.0). The coefficient of variation was at most 5% for PiCT and anti-Xa activity (within-run as well as day-to-day variability). The total costs per test in Swiss Francs (SFr) were SFr23.40 for aPTT, SFr33.30 for TT, SFr15.70 for PiCT and SFr24.15 for anti-Xa activity. The various tests were employed in Swiss institutions with the following frequencies: aPTT 53.2%, TT 21.6%, anti-Xa activity 7.2%, PiCT 1.4%; 16.6% of hospitals performed more than one test.ConclusionsThe accuracy and reproducibility of PiCT and anti-Xa activity for monitoring of UFH was superior, and analytical costs were equivalent to or lower than aPTT and TT.
Anti-PSMA/CD3 Bispecific Antibody Delivery and Antitumor Activity Using a Polymeric Depot Formulation
Authors: Leconet Wilhem , Liu He , Guo Ming , Le Lamer-Déchamps Sophie , Molinier Charlotte , Kim Sae , Vrlinic Tjasa , Oster Murielle , Liu Fang , Navarro Vicente , Batra Jaspreet S. , Noriega Adolfo Lopez , Grizot Sylvestre , Bander Neil H. 
Published: June 2018

Abstract
Small therapeutic proteins represent a promising novel approach to treat cancer. Nevertheless, their clinical application is often adversely impacted by their short plasma half-life. Controlled long-term delivery of small biologicals has become a challenge because of their hydrophilic properties and in some cases their limited stability. Here, an in situ forming depot-injectable polymeric system was used to deliver BiJ591, a bispecific T-cell engager (BiTE) targeting both prostate-specific membrane antigen (PSMA) and the CD3 T-cell receptor in prostate cancer. BiJ591 induced T-cell activation, prostate cancer–directed cell lysis, and tumor growth inhibition. The use of diblock (DB) and triblock (TB) biodegradable polyethylene glycol–poly(lactic acid; PEG-PLA) copolymers solubilized in tripropionin, a small-chain triglyceride, allowed maintenance of BiJ591 stability and functionality in the formed depot and controlled its release. In mice, after a single subcutaneous injection, one of the polymeric candidates, TB1/DB4, provided the most sustained release of BiJ591 for up to 21 days. Moreover, the use of BiJ591-TB1/DB4 formulation in prostate cancer xenograft models showed significant therapeutic activity in both low and high PSMA–expressing tumors, whereas daily intravenous administration of BiJ591 was less efficient. Collectively, these data provide new insights into the development of controlled delivery of small therapeutic proteins in cancer. Mol Cancer Ther; 17(9); 1927–40. ©2018 AACR.
Expression and Implication of Clusterin in Left Ventricular Remodeling After Myocardial Infarction
Authors: Turkieh Annie , Fertin Marie , Bouvet Marion , Mulder Paul , Drobecq Hervé , Lemesle Gilles , Lamblin Nicolas , de Groote Pascal , Porouchani Sina , Chwastyniak Maggy , Beseme Olivia , Amouyel Philippe , Mouquet Frédéric , Balligand Jean-Luc , Richard Vincent , Bauters Christophe , Pinet Florence 
Published: June 2018

Background:
Left ventricular remodeling (LVR) after myocardial infarction is associated with an increased risk of heart failure and death. In spite of a modern therapeutic approach, LVR remains relatively frequent and difficult to predict in clinical practice. Our aim was to identify new biomarkers of LVR and understand their involvement in its development.

Methods and Results:
Proteomic analysis of plasma from the REVE-2 study (Remodelage Ventriculaire)—a study dedicated to the analysis of LVR which included 246 patients after a first anterior myocardial infarction—identified increased plasma levels of CLU (clusterin) in patients with high LVR. We used a rat model of myocardial infarction to analyze CLU expression in the LV and found a significant increase that was correlated with LVR parameters. We found increased CLU expression and secretion in primary cultures of rat neonate cardiomyocytes hypertrophied by isoproterenol. Silencing of CLU in hypertrophied neonate cardiomyocytes induced a significant decrease in cell size, ANP (atrial natriuretic peptide), and BNP (B-type natriuretic peptide) expression, associated with a decreased ERK (extracellular signal-regulated kinase) 1/2 activity, suggesting a prohypertrophic role of CLU. We then confirmed a significant increase of both intracellular p-CLU (precursor form of CLU) and m-CLU (mature form of CLU) in failing human hearts. Finally, the circulating levels of CLU (secreted form) were increased in patients with chronic heart failure who died from cardiovascular cause during a 3-year follow-up (n=99) compared with survivors (n=99).

Conclusions:
Our results show for the first time that plasma CLU levels are associated with LVR post–myocardial infarction, have in part a cardiac origin, and are a predictor of early death in heart failure patients.
Open Repair of Mycotic Abdominal Aortic Aneurysms With Biological Grafts: An International Multicenter Study
Authors: Heinola Ivika , Sörelius Karl , Wyss Thomas R. , Eldrup Nikolaj , Settembre Nicla , Setacci Carlo , Mani Kevin , Kantonen Ilkka , Venermo Maarit 
Published: June 2018

Background
The treatment of mycotic abdominal aortic aneurysm requires surgery and antimicrobial therapy. Since prosthetic reconstructions carry a considerable risk of reinfection, biological grafts are noteworthy alternatives. The current study evaluated the durability, infection resistance, and midterm outcome of biological grafts in treatment of mycotic abdominal aortic aneurysm.

Methods and Results
All patients treated with biological graft in 6 countries between 2006 and 2016 were included. Primary outcome measures were 30‐ and 90‐day survival, treatment‐related mortality, and reinfection rate. Secondary outcome measures were overall mortality and graft patency. Fifty‐six patients (46 males) with median age of 69 years (range 35–85) were included. Sixteen patients were immunocompromised (29%), 24 (43%) had concomitant infection, and 12 (21%) presented with rupture. Bacterial culture was isolated from 43 (77%). In‐situ aortic reconstruction was performed using autologous femoral veins in 30 patients (54%), xenopericardial tube‐grafts in 12 (21%), cryopreserved arterial/venous allografts in 9 (16%), and fresh arterial allografts in 5 (9%) patients. During a median follow‐up of 26 months (range 3 weeks–172 months) there were no reinfections and only 3 patients (5%) required assistance with graft patency. Thirty‐day survival was 95% (n=53) and 90‐day survival was 91% (n=51). Treatment‐related mortality was 9% (n=5). Kaplan–Meier estimation of survival at 1 year was 83% (95% confidence interval, 73%–94%) and at 5 years was 71% (52%–89%).

Conclusions
Mycotic abdominal aortic aneurysm repair with biological grafts is a durable option for patients fit for surgery presenting an excellent infection resistance and good overall survival.