bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quorum Sensing Determines the Choice of Antiphage Defense Strategy in Vibrio anguillarum
Authors: Tan Demeng , Svenningsen Sine Lo , Middelboe Mathias 
Published: June 2015

ABSTRACTSelection for phage resistance is a key driver of bacterial diversity and evolution, and phage-host interactions may therefore have strong influence on the genetic and functional dynamics of bacterial communities. In this study, we found that an important, but so far largely overlooked, determinant of the outcome of phage-bacterial encounters in the fish pathogenVibrio anguillarumis bacterial cell-cell communication, known as quorum sensing. Specifically,V. anguillarumPF430-3 cells locked in the low-cell-density state (ΔvanTmutant) express high levels of the phage receptor OmpK, resulting in a high susceptibility to phage KVP40, but achieve protection from infection by enhanced biofilm formation. By contrast, cells locked in the high-cell-density state (ΔvanΟmutant) are almost completely unsusceptible due to quorum-sensing-mediated downregulation of OmpK expression. The phenotypes of the two quorum-sensing mutant strains are accurately reflected in the behavior of wild-typeV. anguillarum, which (i) displays increased OmpK expression in aggregated cells compared to free-living variants in the same culture, (ii) displays a clear inverse correlation betweenompKmRNA levels and the concentration ofN-acylhomoserine lactone quorum-sensing signals in the culture medium, and (iii) survives mainly by one of these two defense mechanisms, rather than by genetic mutation to phage resistance. Taken together, our results demonstrate thatV. anguillarumemploys quorum-sensing information to choose between two complementary antiphage defense strategies. Further, the prevalence of nonmutational defense mechanisms in strain PF430-3 suggests highly flexible adaptations to KVP40 phage infection pressure, possibly allowing the long-term coexistence of phage and host.IMPORTANCEComprehensive knowledge on bacterial antiphage strategies and their regulation is essential for understanding the role of phages as drivers of bacterial evolution and diversity. In an applied context, development of successful phage-based control of bacterial pathogens also requires detailed understanding of the mechanisms of phage protection in pathogenic bacteria. Here, we demonstrate for the first time the presence of quorum-sensing-regulated phage defense mechanisms in the fish pathogenVibrio anguillarumand provide evidence that quorum-sensing regulation allowsV. anguillarumto alternate between different phage protection mechanisms depending on population cell density. Further, our results demonstrate the prevalence of nonmutational defense mechanisms in the investigatedV. anguillarumstrain, which allow flexible adaptations to a dynamic phage infection pressure.
The temporal association of excessive health expenditure with suicidal ideation among primary income earners: a cross-sectional design using the Korean Welfare Panel Survey (KoWePS)
Authors: Shin Jaeyong , Choi Jae Woo , Jang Sung-in , Choi Young , Lee Sang Gyu , Ihm Tae Hwan , Park Eun-Cheol 
Published: June 2015

ObjectiveExcessive health expenditure (EHE) is a global issue for households suffering from high-cost medical conditions, low incomes and limited insurance coverage. After the international financial crisis of 2008, EHE became a social problem in developed countries. Such economic crisis might induce severe mental stress, resulting in suicidal ideation.MethodsWe used the Korean Welfare Panel Study (KoWePS) from 2011 to 2013 and selected primary income earners, who were defined as practical and economic representatives of households; the total number of analysed samples was 4247 of 5717 households in the database. We only included households that had never experienced EHE before 2011. To examine the temporal relationship between EHE and suicidal ideation, we conducted a logistic regression analysis.ResultsAmong 4247 participants, 146 (3.4%) experienced suicidal ideation, whereas 4101 (96.6%) did not. One scale of depression score (OR=1.28, CI 1.23 to 1.34, p<0.001) was associated with increased suicidal ideation. Such ideation was influenced to a greater extent by a recent EHE above 10% of disposable income (OR=1.91, CI 1.16 to 3.15, p=0.012) than by either a remote EHE (OR=1.29, CI 0.71 to 2.32) or one in 2011 and 2012 (OR=1.67, CI 1.01 to 2.78, p=0.048).ConclusionsIn this study, more recent EHE resulted in more suicidal ideation. In conclusion, we suggest that recent household EHE might be considered as an important factor to prevent suicidal ideation and to improve the mental health of individuals.
Understanding paratyphoid infection: study protocol for the development of a human model ofSalmonella entericaserovar Paratyphi A challenge in healthy adult volunteers
Authors: McCullagh David , Dobinson Hazel C , Darton Thomas , Campbell Danielle , Jones Claire , Snape Matthew , Stevens Zoe , Plested Emma , Voysey Merryn , Kerridge Simon , Martin Laura B , Angus Brian , Pollard Andrew J 
Published: June 2015

IntroductionThis study will develop the first human challenge model of paratyphoid infection which may then be taken forward to evaluate paratyphoid vaccine candidates.SalmonellaParatyphi A is believed to cause a quarter of the estimated 20 million cases of enteric fever annually. Epidemiological evidence also suggests that an increasing proportion of the enteric fever burden is attributable toS. Paratyphi infection meriting further attention and interest in vaccine development. Assessment of paratyphoid vaccine efficacy in preclinical studies is complicated by the lack of a small animal model and the human-restricted nature of the infection. The use of experimental human infection in healthy volunteers provides an opportunity to address these problems in a cost-effective manner.Methods and analysisVolunteers will ingest virulentS. Paratyphi A bacteria (NVGH308 strain) with a bicarbonate buffer solution to establish the infectious dose resulting in an ‘attack rate’ of 60–75%. Using an a priori decision-making algorithm, the challenge dose will be escalated or de-escalated to achieve the target attack rate, with the aim of reaching the study end point while exposing as few individuals as possible to infection. The attack rate will be determined by the proportion of paratyphoid infection in groups of 20 healthy adult volunteers, with infection being defined by one or more positive blood cultures (microbiological end point) and/or fever, defined as an oral temperature exceeding 38°C sustained for at least 12 h (clinical end point); 20–80 participants will be required. Challenge participants will start a 2-week course of an oral antibiotic on diagnosis of infection, or after 14 days follow-up.Ethics and disseminationThe strict eligibility criterion aims to minimise risk to participants and their close contacts. Ethical approval has been obtained. The results will be disseminated in a peer-reviewed journal and presented at international congresses.Trial registration numberNCT02100397.
A Resolution of the Paradox of Enrichment
Authors: Feng Z. C. , Li Y. Charles 
Published: June 2015

The paradox of enrichment was observed by Rosenzweig [1971] in a class of predator–prey models. Two of the parameters in the models are crucial for the paradox. These two parameters are the prey's carrying capacity and prey's half-saturation for predation. Intuitively, increasing the carrying capacity due to enrichment of the prey's environment should lead to a more stable predator–prey system. Analytically, it turns out that increasing the carrying capacity always leads to an unstable predator–prey system that is susceptible to extinction from environmental random perturbations. This is the so-called paradox of enrichment. Our resolution here rests upon a closer investigation on a dimensionless number H formed from the carrying capacity and the prey's half-saturation. By recasting the models into dimensionless forms, the models are in fact governed by a few dimensionless numbers including H. The effects of the two parameters: carrying capacity and half-saturation are incorporated into the number H. In fact, increasing the carrying capacity is equivalent (i.e. has the same effect on H) to decreasing the half-saturation which implies more aggressive predation. Since there is no paradox between more aggressive predation and instability of the predator–prey system, the paradox of enrichment is resolved. The so-called instability of the predator–prey system is characterized by the existence of a stable limit cycle in the phase plane, which gets closer and closer to the predator axis and prey axis. Due to random environmental perturbations, this can lead to extinction. We also further explore spatially dependent models for which the phase space is infinite-dimensional. The spatially independent limit cycle which is generated by a Hopf bifurcation from an unstable steady state, is linearly stable in the infinite-dimensional phase space. Numerical simulations indicate that the basin of attraction of the limit cycle is riddled. This shows that spatial perturbations can sometimes (neither always nor never) remove the paradox of enrichment near the limit cycle!
Colorectal Cancer Risk Following Adenoma Removal: A Large Prospective Population-Based Cohort Study
Authors: Coleman Helen G. , Loughrey Maurice B. , Murray Liam J. , Johnston Brian T. , Gavin Anna T. , Shrubsole Martha J. , Bhat Shivaram K. , Allen Patrick B. , McConnell Vivienne , Cantwell Marie M. 
Published: June 2015

Abstract
Background: Randomized controlled trials have demonstrated significant reductions in colorectal cancer incidence and mortality associated with polypectomy. However, little is known about whether polypectomy is effective at reducing colorectal cancer risk in routine clinical practice. The aim of this investigation was to quantify colorectal cancer risk following polypectomy in a large prospective population-based cohort study.
Methods: Patients with incident colorectal polyps between 2000 and 2005 in Northern Ireland were identified via electronic pathology reports received to the Northern Ireland Cancer Registry. Patients were matched to the Northern Ireland Cancer Registry to detect colorectal cancer and deaths up to December 31, 2010. Colorectal cancer standardized incidence ratios (SIR) were calculated and Cox proportional hazards modeling applied to determine colorectal cancer risk.
Results: During 44,724 person-years of follow-up, 193 colorectal cancer cases were diagnosed among 6,972 adenoma patients, representing an annual progression rate of 0.43%. Colorectal cancer risk was significantly elevated in patients who had an adenoma removed (SIR, 2.85; 95% CI, 2.61–3.25) compared with the general population. Male sex, older age, rectal site, and villous architecture were associated with an increased colorectal cancer risk in adenoma patients. Further analysis suggested that not having a full colonoscopy performed at, or following, incident polypectomy contributed to the excess colorectal cancer risk.
Conclusions: Colorectal cancer risk was elevated in individuals following polypectomy for adenoma, outside of screening programs.
Impact: This finding emphasizes the need for full colonoscopy and adenoma clearance, and appropriate surveillance, after endoscopic diagnosis of adenoma. Cancer Epidemiol Biomarkers Prev; 24(9); 1373–80. ©2015 AACR.
Disruption of Proline Synthesis in Melanoma Inhibits Protein Production Mediated by the GCN2 Pathway
Authors: Kardos Gregory R. , Wastyk Hannah C. , Robertson Gavin P. 
Published: June 2015

Abstract
Many processes are deregulated in melanoma cells and one of those is protein production. Although much is known about protein synthesis in cancer cells, effective ways of therapeutically targeting this process remain an understudied area of research. A process that is upregulated in melanoma compared with normal melanocytes is proline biosynthesis, which has been linked to both oncogene and tumor suppressor pathways, suggesting an important convergent point for therapeutic intervention. Therefore, an RNAi screen of a kinase library was undertaken, identifying aldehyde dehydrogenase 18 family, member A1 (ALDH18A1) as a critically important gene in regulating melanoma cell growth through proline biosynthesis. Inhibition of ALDH18A1, the gene encoding pyrroline-5-carboxylate synthase (P5CS), significantly decreased cultured melanoma cell viability and tumor growth. Knockdown of P5CS using siRNA had no effect on apoptosis, autophagy, or the cell cycle but cell-doubling time increased dramatically suggesting that there was a general slowdown in cellular metabolism. Mechanistically, targeting ALDH18A1 activated the serine/threonine protein kinase GCN2 (general control nonderepressible 2) to inhibit protein synthesis, which could be reversed with proline supplementation. Thus, targeting ALDH18A1 in melanoma can be used to disrupt proline biosynthesis to limit cell metabolism thereby increasing the cellular doubling time mediated through the GCN2 pathway.
Implications: This study demonstrates that melanoma cells are sensitive to disruption of proline synthesis and provides a proof-of-concept that the proline synthesis pathway can be therapeutically targeted in melanoma tumors for tumor inhibitory efficacy. Mol Cancer Res; 13(10); 1408–20. ©2015 AACR.
Cerebral Microbleeds Predict Intracerebral Hemorrhage in Hemodialysis Patients
Authors: Naganuma Toshihide , Takemoto Yoshiaki , Shoji Tetsuo , Ishimura Eiji , Okamura Mikio , Nakatani Tatsuya 
Published: June 2015

Background and Purpose—
In hemodialysis patients, previous reports have described a high prevalence of cerebral microbleeds (CMBs), but no longitudinal studies have been performed to determine the clinical significance of CMBs in these patients. In this study, we investigated whether the presence of CMBs was a predictor of future strokes in hemodialysis patients.

Methods—
Cranial MRI, including T2*-weighted magnetic resonance imaging, was performed on 179 hemodialysis patients with no past history of cerebrovascular events. The patients were followed prospectively until death or renal transplantation. We used the Cox proportional hazards model with inverse probability of treatment weighting using the propensity score to compare the event-free survivals of patients with/without CMBs. For sensitivity analyses, stratification by propensity score quintile and regression adjustment were used.

Results—
CMBs were detected in 45 of the 179 patients. During a median follow-up period of 5.0 years, stroke occurred in 24 patients, including 12 with intracerebral hemorrhage and 12 with cerebral infarctions. Cox proportional hazards analysis with inverse probability of treatment weighting using the propensity score revealed that the presence of CMBs was a strong and significant predictor of intracerebral hemorrhage (hazard ratio, 26.53; 95% confidence interval, 2.88–244.90) but not cerebral infarction (hazard ratio, 0.91; 95% confidence interval, 0.25–3.34). Sensitivity analyses yielded similar results.

Conclusions—
This study showed that the presence of CMBs was an independent and strong predictor of intracerebral hemorrhage in stroke-free hemodialysis patients, indicating that hemodialysis patients with CMBs should be carefully monitored for future onset of intracerebral hemorrhage.
Pediatric Idiopathic Intracranial Hypertension Presenting With Sensorineural Hearing Loss
Authors: Reitsma Sietze , Stokroos Robert , Weber Jacobiene W. , van Tongeren Joost 
Published: June 2015

Objective: To present the rare case of a young boy with idiopathic intracranial hypertension presenting with bilateral sensorineural hearing loss developing over several months. This was accompanied by headaches, otalgia, tinnitus, and vertigo. Furthermore, we aim to provide a concise review on this matter, as this report represents the second case in literature of pediatric idiopathic intracranial hypertension presenting with hearing loss. Methods: Workup of a 9-year-old boy with bilateral sensorineural hearing loss, including (among others) physical examination, audiometry, diagnostic imaging, and lumbar puncture. Results: Physical examination including fundoscopy as well as imaging showed no abnormalities. At presentation, pure tone audiometry revealed bone conduction thresholds of about 30 dB HL in both ears. Two months later, this declined to about 35 dB HL in both ears. Lumbar puncture revealed an increased intracranial pressure. The boy was thus diagnosed with idiopathic intracranial hypertension. After the lumbar puncture, the otological complaints gradually resolved, and the hearing normalized (bone conduction thresholds of 0-5 dB HL). Conclusion: Although rare, sensorineural hearing loss in the pediatric population together with otalgia, tinnitus, and vertigo can be due to idiopathic intracranial hypertension and as such can be reversible.
Decisional Conflict in Parents Considering Bone-Anchored Hearing Devices in Children With Unilateral Aural Atresia
Authors: Graham M. Elise , Haworth Rebecca , Chorney Jill , Bance Manohar , Hong Paul 
Published: June 2015

Objective: The benefits of bone-anchored hearing devices (BAHD) in children with unilateral aural atresia are controversial. We sought to determine whether there is parental decisional conflict surrounding elective placement of BAHD for this indication. Methods: Caregivers of pediatric patients with unilateral aural atresia and normal contralateral ear undergoing percutaneous BAHD consultation were enrolled. All consultations were carried out by one pediatric otolaryngologist in a consistent manner. After consultation, the participants completed a demographics form and the Decisional Conflict Scale (DCS) questionnaire. Results: Twenty-three caregivers of 15 male (65.2%) and 8 female (34.8%) children (mean age 5.65 years) participated. The overall median DCS score was 15.63 (standard error = 4.21). Significant decisional conflict (DCS score ≥ 25) was found in 10 participants (43.5%). The median DCS score in the group choosing surgery was 5.47, and it was 23.44 in those who did not choose surgery (Mann–Whitney U = 39, Z = −1.391, P = .164). The median DCS score for mothers and fathers was 25 and 3.91, respectively. Conclusion: Many parents experienced significant decisional conflict when considering percutaneous BAHD surgery in children with unilateral aural atresia in our study population. Future research should explore the impact of decisional conflict on health outcomes.
Symbol and Image Worship in Jainism
Authors: Kishore Kanika 
Published: June 2015

The history of Jainism in Mathura has been reconstructed largely on the basis of donative inscriptions and the remains of temples, stūpas and tīrthaṅkara images unearthed in this area. The āyāgapaṭas—an integral part of Mathura art and extremely important for the understanding of Jaina art and religious practice—have been relatively neglected. The āyāgapaṭas reflect the simultaneous existence of symbol and image worship in Jainism. The practice of donating these carved slabs started in the first century BCE and continued till the third century CE. The āyāgapaṭas were intended for worship as the inscriptions specify that they were set up for the worship of arhats ( tīrthaṅkaras).  This article aims to understand the āyāgapaṭa inscriptions in the context of their relief carvings. The religious imagery on these slabs represents various foci of Jaina worship, namely the stūpa, the dharmacakra and the Jina image. The evidence of the Jina image carved on the āyāgapaṭas as early as the first century BCE, points towards the prevalence of image worship in Jainism even before the first century CE. The analysis of the āyāgapaṭa inscriptions highlights the varied occupational background of donors and the active role played by women donors. The article explores the probable reasons for the discontinuation of āyāgapaṭas after the third century CE at Mathura. Finally, it clearly establishes that āyāgapaṭas were installed in temples and monasteries and were objects of worship and an important component of Jaina religious practice.
Refuse derived fuel (RDF) plasma torch gasification as a feasible route to produce low environmental impact syngas for the cement industry
Authors: López-Sabirón Ana M , Fleiger Kristina , Schäfer Stefan , Antoñanzas Javier , Irazustabarrena Ane , Aranda-Usón Alfonso , Ferreira Germán A 
Published: June 2015

Plasma torch gasification (PTG) is currently researched as a technology for solid waste recovery. However, scientific studies based on evaluating its environmental implications considering the life cycle assessment (LCA) methodology are lacking. Therefore, this work is focused on comparing the environmental effect of the emissions of syngas combustion produced by refuse derived fuel (RDF) and PTG as alternative fuels, with that related to fossil fuel combustion in the cement industry. To obtain real data, a semi-industrial scale pilot plant was used to perform experimental trials on RDF-PTG. The results highlight that PTG for waste to energy recovery in the cement industry is environmentally feasible considering its current state of development. A reduction in every impact category was found when a total or partial substitution of alternative fuel for conventional fuel in the calciner firing (60 % of total thermal energy input) was performed. Furthermore, the results revealed that electrical energy consumption in PTG is also an important parameter from the LCA approach.
Vancomycin pharmacokinetics and predicted dosage requirements in pediatric cancer patients
Authors: Abdel Hadi Ola , Al Omar Suha , Nazer Lama H , Mubarak Sawsan , Le Jennifer 
Published: June 2015

Purpose To determine the pharmacokinetic parameters and compare pharmacodynamic target attainment at different dosing strategies of vancomycin in pediatric cancer patients. Methods Pediatric patients who received vancomycin and had at least two steady-state concentrations taken within the same dosing interval were identified. Vancomycin minimum inhibitory concentrations (MICs) for methicillin resistant staphylococcus aureus (MRSA) isolates from our institution were determined using E-test. The population-based pharmacokinetic modeling was performed using NONMEM 7.2. A one-compartment model with first-order kinetics was used to estimate clearance (CL) and volume of distribution (Vd). Monte Carlo simulations ( N = 9800) were performed to compare area-under-the-curve over 24 h (AUC24)/MIC and trough concentration at different doses. Results Forty-nine patients, with 120 vancomcyin serum concentrations, were included in the analysis, mean age was 6 ± 2.5 (SD) years, mean weight was 19.6 ± 6.9(SD) kg, mean baseline serum creatinine was 0.4 ± 0.11(SD) mg/dl, and mean initial vancomycin dose was 205 mg/day (range 100–460). Final model pharmacokinetic parameters were: CL (L/h) = 0.381 × weight0.75 and Vd (L) = 0.663 × weight. Mean baseline (±SD) vancomycin CL was 0.20 ± 0.07 L/h/kg and Vd 0.66 ± 0.001 L/kg. . Renal function, sex, age, stay in the intensive care unit, and co-administration of nephrotoxic medications did not have an effect on the calculated parameters. Using Monte Carlo simulation with reported MICs, a dose of 60 mg/kg/day achieved AUC24/MIC ≥400 and trough concentration ≥15 mcg/mL in only 21.5% and 11% of virtual subjects, respectively. Conclusions Higher than usual vancomycin doses may be required to treat serious MRSA infections in pediatric patients. The currently recommended dose of 60 mg/kg/day is unlikely to achieve the targets in most subjects. The optimal vancomycin dosing in pediatric cancer patients requires further investigations.