bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abiotic Stress and Phyllosphere Bacteria Influence the Survival of Human Norovirus and Its Surrogates on Preharvest Leafy Greens
Authors: Esseili Malak A. , Gao Xiang , Tegtmeier Sarah , Saif Linda J. , Wang Qiuhong 
Published: October 2015

ABSTRACT
Foodborne outbreaks of human noroviruses (HuNoVs) are frequently associated with leafy greens. Because there is no effective method to eliminate HuNoV from postharvest leafy greens, understanding virus survival under preharvest conditions is crucial. The objective of this study was to evaluate the survival of HuNoV and its surrogate viruses, murine norovirus (MNV), porcine sapovirus (SaV), and Tulane virus (TV), on preharvest lettuce and spinach that were subjected to abiotic stress (physical damage, heat, or flood). We also examined the bacteria culturable from the phyllosphere in response to abiotic stress and in relation to viral persistence. Mature plants were subjected to stressors 2 days prior to inoculation of the viruses on leaves. We quantified the viral RNA, determined the infectivity of the surrogates, and performed bacterial counts on postinoculation days (PIDs) 0, 1, 7, and 14. For both plant types, time exerted significant effects on HuNoV, MNV, SaV, and TV RNA titers, with greater effects being seen for the surrogates. Infectious surrogate viruses were undetectable on PID 14. Only physical damage on PID 14 significantly enhanced HuNoV RNA persistence on lettuce, while the three stressors differentially enhanced the persistence of MNV and TV RNA. Bacterial counts were significantly affected by time and plant type but not by the stressors. However, bacterial counts correlated significantly with HuNoV RNA titers on spinach and with the presence of surrogate viruses on both plant types under various conditions. In conclusion, abiotic stressors and phyllosphere bacterial density may differentially influence the survival of HuNoV and its surrogates on lettuce and spinach, emphasizing the need for the use of preventive measures at the preharvest stage.
Influence of Salmonella enterica Serovar Typhimurium
ssrB
on Colonization of Eastern Oysters (Crassostrea virginica) as Revealed by a Promoter Probe Screen
Authors: Cox Clayton E. , Wright Anita C. , McClelland Michael , Teplitski Max 
Published: October 2015

ABSTRACT

Although
Salmonella
has been isolated from 7.4 to 8.6% of domestic raw oysters, representing a significant risk for food-borne illness, little is known about the factors that influence their initial colonization by
Salmonella
. This study tested the hypothesis that specific regulatory changes enable a portion of the invading
Salmonella
population to colonize oysters. An
in vivo
promoter probe library screen identified 19 unique regions as regulated during colonization. The mutants in the nearest corresponding downstream genes were tested for colonization defects in oysters. Only one mutation, in
ssrB
, resulted in a significantly reduced ability to colonize oysters compared to that of wild-type
Salmonella
. Because
ssrB
regulates
Salmonella
pathogenicity island 2 (SPI-2)-dependent infections in vertebrate macrophages, the possibility that
ssrB
mediated colonization of oyster hemocytes in a similar manner was examined. However, no difference in hemocyte colonization was observed. The complementary hypothesis that signal exchange between
Salmonella
and the oyster's native microbial community aids colonization was also tested. Signals that triggered responses in quorum sensing (QS) reporters were shown to be produced by oyster-associated bacteria and present in oyster tissue. However, no evidence for signal exchange was observed
in vivo
. The
sdiA
reporter responded to salinity, suggesting that SdiA may also have a role in environmental sensing. Overall, this study suggests the initial colonization of live oysters by
Salmonella
is controlled by a limited number of regulators, including
ssrB
.
Inhibitory Role of Greatwall-Like Protein Kinase Rim15p in Alcoholic Fermentation via Upregulating the UDP-Glucose Synthesis Pathway in Saccharomyces cerevisiae
Authors: Watanabe Daisuke , Zhou Yan , Hirata Aiko , Sugimoto Yukiko , Takagi Kenichi , Akao Takeshi , Ohya Yoshikazu , Takagi Hiroshi , Shimoi Hitoshi 
Published: October 2015

ABSTRACT

The high fermentation rate of
Saccharomyces cerevisiae
sake yeast strains is attributable to a loss-of-function mutation in the
RIM15
gene, which encodes a Greatwall-family protein kinase that is conserved among eukaryotes. In the present study, we performed intracellular metabolic profiling analysis and revealed that deletion of the
RIM15
gene in a laboratory strain impaired glucose-anabolic pathways through the synthesis of UDP-glucose (UDPG). Although Rim15p is required for the synthesis of trehalose and glycogen from UDPG upon entry of cells into the quiescent state, we found that Rim15p is also essential for the accumulation of cell wall β-glucans, which are also anabolic products of UDPG. Furthermore, the impairment of UDPG or 1,3-β-glucan synthesis contributed to an increase in the fermentation rate. Transcriptional induction of
PGM2
(phosphoglucomutase) and
UGP1
(UDPG pyrophosphorylase) was impaired in Rim15p-deficient cells in the early stage of fermentation. These findings demonstrate that the decreased anabolism of glucose into UDPG and 1,3-β-glucan triggered by a defect in the Rim15p-mediated upregulation of
PGM2
and
UGP1
redirects the glucose flux into glycolysis. Consistent with this, sake yeast strains with defective Rim15p exhibited impaired expression of
PGM2
and
UGP1
and decreased levels of β-glucans, trehalose, and glycogen during sake fermentation. We also identified a sake yeast-specific mutation in the glycogen synthesis-associated glycogenin gene
GLG2
, supporting the conclusion that the glucose-anabolic pathway is impaired in sake yeast. These findings demonstrate that downregulation of the UDPG synthesis pathway is a key mechanism accelerating alcoholic fermentation in industrially utilized
S. cerevisiae
sake strains.
The CreC Regulator of Escherichia coli, a New Target for Metabolic Manipulations
Authors: Godoy Manuel S. , Nikel Pablo I. , Cabrera Gomez José G. , Pettinari M. Julia 
Published: October 2015

ABSTRACT

The CreBC (
c
arbon source-
re
sponsive) two-component regulation system of
Escherichia coli
affects a number of functions, including intermediary carbon catabolism. The impacts of different
creC
mutations (a Δ
creC
mutant and a mutant carrying the constitutive
creC510
allele) on bacterial physiology were analyzed in glucose cultures under three oxygen availability conditions. Differences in the amounts of extracellular metabolites produced were observed in the null mutant compared to the wild-type strain and the mutant carrying
creC510
and shown to be affected by oxygen availability. The Δ
creC
strain secreted more formate, succinate, and acetate but less lactate under low aeration. These metabolic changes were associated with differences in AckA and LdhA activities, both of which were affected by CreC. Measurement of the NAD(P)H/NAD(P)
+
ratios showed that the
creC510
strain had a more reduced intracellular redox state, while the opposite was observed for the Δ
creC
mutant, particularly under intermediate oxygen availability conditions, indicating that CreC affects redox balance. The null mutant formed more succinate than the wild-type strain under both low aeration and no aeration. Overexpression of the genes encoding phosphoenolpyruvate carboxylase from
E. coli
and a NADH-forming formate dehydrogenase from
Candida boidinii
in the Δ
creC
mutant further increased the yield of succinate on glucose. Interestingly, the elimination of
ackA
and
adhE
did not significantly improve the production of succinate. The diverse metabolic effects of this regulator on the central biochemical network of
E. coli
make it a good candidate for metabolic-engineering manipulations to enhance the formation of bioproducts, such as succinate.
Leisure time physical activity and cancer risk: evaluation of the WHO's recommendation based on 126 high-quality epidemiological studies
Authors: Liu Li , Shi Yun , Li Tingting , Qin Qin , Yin Jieyun , Pang Shuo , Nie Shaofa , Wei Sheng 
Published: October 2015

BackgroundThe WHO has concluded that physical activity reduces the risk of numerous diseases. However, few systemic reviews have been performed to assess the role of leisure time physical activity (LTPA) in lowering the risk of cancer in a dose-dependent manner and furthermore the suitability of recommendation of physical activity by the WHO.MethodsA systematic review and meta-analysis was designed to estimate cancer risk by LTPA in binary comparison and in a dose-dependent manner. MEDLINE and Web of Science were searched up to 30 December 2014 without language restrictions. Reference lists were reviewed for potential articles.ResultsA total of 126 studies were recruited into the meta-analysis. Overall, the total cancer risk was reduced by 10% in people who undertook the most LTPA as compared with those who did the least. Dose–response meta-analysis indicated that the current WHO recommendation (equal to an average of 10 metabolic equivalents of energy hours per week) induced a 7% (95% CI 5% to 9%) cancer reduction. Moreover, the protective role of LTPA against cancer becomes saturated at 20 metabolic equivalents of energy hours per week, with a relative risk of 0.91 (95% CI 0.88 to 0.93). Subanalyses results based on cancer types showed that LTPA only exhibited significant protection against breast cancer and colorectal cancer.ConclusionsOur meta-analysis indicates that the current WHO recommendation of physical activity can result in a 7% reduction in cancer risk, which is mainly attributed to its protective role against breast cancer and colorectal cancer. Furthermore, two-fold of current recommendation level is considered to give its saturated protection against cancer.
Improving handover of acute orthopaedic admissions
Authors: Karayiannis Paul , Warnock Jonathan 
Published: October 2015

AbstractHandover is a crucial part of patient care and is a well recognized cause of patient harm if not performed well. The introduction of full shift working for doctors has placed even more emphasis on this area of patient care. We identified handover of orthopaedic admissions in our unit was substandard. A prospective audit over a one week period including the weekend was undertaken. The Royal College of Surgeons of England guidance on handovers was used as minimum criteria and we also included criteria essential for handover of orthopaedic patients. This initial audit revealed a poor standard of handover. 21 patients were included and in particular patient location (57%), responsible consultant (14%), and pending investigations (29%) were poorly performed. In addition two patient safety incidents were noted, including one admission that was not handed over. To improve the handover we created a trauma specific handover proforma. We then conducted a re-audit again over a one week period including the weekend with the proforma in use. There was a notable improvement, 17 patients were included and only 3 criteria fell below 80%. We presented our findings at the local audit meeting where the results were discussed with all members of the trauma team. We suggested that an electronic proforma, accessible from multiple computers within the hospital may improve handover further. This was created in conjunction with the IT department. Once again we reaudited handover over a one week period including the weekend with the electronic proforma in use. 23 patients were included and a further improvement was noted; only one criterion fell below 95%. In conclusion handover of acute fracture admissions within the unit has undoubtedly improved. The electronic proforma tool was a simple, cost effective, and accurate method of improving handover.
An evaluation study of a pilot group education programme for inflammatory bowel disease
Authors: Sephton Mark , Kemp Karen , Ridgway Victoria 
Published: October 2015

Background and aimsThe emphasis for healthcare clinicians to provide adequate disease-related education is increasing. Yet little is known about the effect of providing disease-related education within inflammatory bowel disease (IBD). Previous studies have demonstrated increased levels of knowledge and satisfaction, but failed to capture any positive effects on the psychosocial elements of living with IBD. The aim of this qualitative study was to evaluate the impact of providing a group patient education programme on the psychosocial elements of living with IBD.MethodsThe data were obtained through eight semistructured qualitative interviews. Participants were recruited at the education programme using purposive sampling. All the interviews were digital recorded and transcribed. Thematic analysis was used by two independent researchers to analyse the transcripts and agreed emerging themes.ResultsA global theme of ‘mastery’ was evident within the transcripts. This was underpinned with two core themes of enablement and cooperative learning. The education programme ‘enabled’ the participants in a variety of ways: increased confidence, control, courage and power over their disease. An unexpected core theme of cooperative learning was also identified, with participants describing the overwhelming benefit of interaction with other people who also had IBD.ConclusionsThis is the first qualitative study to report on the effects of providing a group patient education within IBD. The results identify new and interesting psychosocial elements that existing quantitative studies have failed to identify.
Alcohol, drug and other prior crimes and risk of arrest in handgun purchasers: protocol for a controlled observational study
Authors: Wintemute Garen J , Kass Philip H , Stewart Susan L , Cerdá Magdalena , Gruenewald Paul J 
Published: October 2015

Background and objectiveAlcohol abuse is common in the USA and is a well-established risk factor for violence. Other drug use and criminal activity are risk factors as well and frequently occur together with alcohol abuse. Firearm ownership is also common; there are >50 million firearm owners in the USA. This study assesses the relationships between alcohol and drug abuse and future violence among firearm owners, which no prior research has done.Design and study populationThis records-based retrospective cohort study will involve all persons who legally purchased handguns in California in 2001—approximately 116 000 individuals—with follow-up through the end of 2013.MethodsThe principal exposures include prior convictions for alcohol-related and drug-related offenses. The primary outcome measure is an arrest following handgun purchase for a violent Crime Index offense: homicide, rape, robbery or aggravated assault. Subjects will be considered at risk for outcome events for only as long as their residence in California can be established independently of outcome events. Covariates include individual characteristics (eg, age, sex, criminal history, firearm purchase history) and community characteristics (eg, demographics, socioeconomic measures, firearm ownership and alcohol outlet density). We will employ survival analytic methods, expressing effects as HRs.DiscussionThe results of this large-scale study are likely to be generalisable and to have important implications for violence prevention policies and programmes.
Comprehensive genomic profiling of extrahepatic cholangiocarcinoma reveals a long tail of therapeutic targets
Authors: Lee Hwajeong , Wang Kai , Johnson Adrienne , Jones David M , Ali Siraj M , Elvin Julia A , Yelensky Roman , Lipson Doron , Miller Vincent A , Stephens Philip J , Javle Milind , Ross Jeffrey S 
Published: October 2015

AimWe queried whether extrahepatic cholangiocarcinoma featured clinically relevant genomic alterations that could lead to targeted therapy.MethodsComprehensive genomic profiling by hybridisation capture of up to 315 genes was performed on 99 clinically advanced extrahepatic cholangiocarcinoma.ResultsThere were 60 male and 39 female patients with a median age of 60.5 years. A total of 400 alterations were identified (mean 4.0; range 0–13) in 84 genes. Eighty-two (83%) of extrahepatic cholangiocarcinoma patients featured at least one clinically relevant genomic alterations includingKRAS(43%);ERBB2(9%),PTEN(7%);ATMandNF1(6%) andCCND1,FBXW7,GNAS,MDM2andNRAS(all at 5%).BRAF, BRCA2,CDK4,CDK6,FGFR1,FGFR3,PTCH1,RAF1and STK11were each altered in a single patient. NoIDH1/2mutations orFGFR2gene fusions were identified.ConclusionsComprehensive genomic profiling of extrahepatic cholangiocarcinoma differs significantly from intrahepatic cholangiocarcinoma and pancreatic adenocarcinoma, and reveals diverse opportunities for the use of targeted therapies.
Vaccination with LAG-3Ig (IMP321) and Peptides Induces Specific CD4 and CD8 T-Cell Responses in Metastatic Melanoma Patients—Report of a Phase I/IIa Clinical Trial
Authors: Legat Amandine , Maby-El Hajjami Hélène , Baumgaertner Petra , Cagnon Laurène , Abed Maillard Samia , Geldhof Christine , Iancu Emanuela M. , Lebon Luc , Guillaume Philippe , Dojcinovic Danijel , Michielin Olivier , Romano Emanuela , Berthod Grégoire , Rimoldi Donata , Triebel Frédéric , Luescher Immanuel , Rufer Nathalie , Speiser Daniel E. 
Published: October 2015

Abstract
Purpose: Cancer vaccines aim to generate and maintain antitumor immune responses. We designed a phase I/IIa clinical trial to test a vaccine formulation composed of Montanide ISA-51 (Incomplete Freund's Adjuvant), LAG-3Ig (IMP321, a non-Toll like Receptor agonist with adjuvant properties), and five synthetic peptides derived from tumor-associated antigens (four short 9/10-mers targeting CD8 T-cells, and one longer 15-mer targeting CD4 T-cells). Primary endpoints were safety and T-cell responses.
Experimental Design: Sixteen metastatic melanoma patients received serial vaccinations. Up to nine injections were subcutaneously administered in three cycles, each with three vaccinations every 3 weeks, with 6 to 14 weeks interval between cycles. Blood samples were collected at baseline, 1-week after the third, sixth and ninth vaccination, and 6 months after the last vaccination. Circulating T-cells were monitored by tetramer staining directly ex vivo, and by combinatorial tetramer and cytokine staining on in vitro stimulated cells.
Results: Side effects were mild to moderate, comparable to vaccines with Montanide alone. Specific CD8 T-cell responses to at least one peptide formulated in the vaccine preparation were found in 13 of 16 patients. However, two of the four short peptides of the vaccine formulation did not elicit CD8 T-cell responses. Specific CD4 T-cell responses were found in all 16 patients.
Conclusions: We conclude that vaccination with IMP321 is a promising and safe strategy for inducing sustained immune responses, encouraging further development for cancer vaccines as components of combination therapies. Clin Cancer Res; 22(6); 1330–40. ©2015 AACR.
Safety and Pharmacokinetics of Lenvatinib in Patients with Advanced Hepatocellular Carcinoma
Authors: Ikeda Masafumi , Okusaka Takuji , Mitsunaga Shuichi , Ueno Hideki , Tamai Toshiyuki , Suzuki Takuya , Hayato Seiichi , Kadowaki Tadashi , Okita Kiwamu , Kumada Hiromitsu 
Published: October 2015

AbstractPurpose: To determine the maximum tolerable dose (MTD), safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of lenvatinib in patients with advanced hepatocellular carcinoma (HCC).Experimental Design: This multicenter, open-label, phase I, dose-escalation study included patients aged 20 to 80 years, refractory to standard therapy, and stratified by hepatic function measured using Child–Pugh (CP) scores: CP-A (score, 5–6) and CP-B (score, 7–8). Lenvatinib was administered continually once daily for 4-week cycles. MTD was defined as the maximum dose associated with ≤ 1 dose-limiting toxicity (DLT) occurring in cycle 1 among 6 patients.Results: In total, 20 patients (9 in CP-A and 11 in CP-B) were enrolled. The MTD was 12 and 8 mg once daily in CP-A and CP-B, respectively; DLTs included proteinuria, hepatic encephalopathy, and hyperbilirubinemia. The most common grade 3 toxicities included hypertension in CP-A and hyperbilirubinemia in CP-B. Lenvatinib plasma concentration at 24 hours after administration (C24 h) for 12 mg once daily was higher in patients with HCC than in patients with other solid tumors shown in a previous phase I study, but C24 h for 25 mg once daily lenvatinib was comparable. After lenvatinib treatment, the number of circulating endothelial and c-Kit+ cells decreased and the levels of interleukin (IL)-6, IL10, granulocyte-colony stimulating factor, and vascular endothelial growth factor increased (P &lt; 0.05). Partial responses were observed in 3 patients and tumor shrinkage occurred in 14 patients.Conclusions: Lenvatinib (12 mg once daily) demonstrated preliminary efficacy with manageable toxicity and is the recommended dose for phase II studies in patients with HCC and CP-A. Clin Cancer Res; 22(6); 1385–94. ©2015 AACR.
Sensitive Detection of Mono- and Polyclonal ESR1 Mutations in Primary Tumors, Metastatic Lesions, and Cell-Free DNA of Breast Cancer Patients
Authors: Wang Peilu , Bahreini Amir , Gyanchandani Rekha , Lucas Peter C. , Hartmaier Ryan J. , Watters Rebecca J. , Jonnalagadda Amruth R. , Trejo Bittar Humberto E. , Berg Aaron , Hamilton Ronald L. , Kurland Brenda F. , Weiss Kurt R. , Mathew Aju , Leone Jose Pablo , Davidson Nancy E. , Nikiforova Marina N. , Brufsky Adam M. , Ambros Tadeu F. , Stern Andrew M. , Puhalla Shannon L. , Lee Adrian V. , Oesterreich Steffi 
Published: October 2015

Abstract
Purpose: Given the clinical relevance of ESR1 mutations as potential drivers of resistance to endocrine therapy, this study used sensitive detection methods to determine the frequency of ESR1 mutations in primary and metastatic breast cancer, and in cell-free DNA (cfDNA).
Experimental Design: Six ESR1 mutations (K303R, S463P, Y537C, Y537N, Y537S, D538G) were assessed by digital droplet PCR (ddPCR), with lower limits of detection of 0.05% to 0.16%, in primary tumors (n = 43), bone (n = 12) and brain metastases (n = 38), and cfDNA (n = 29). Correlations between ESR1 mutations in metastatic lesions and single (1 patient) or serial blood draws (4 patients) were assessed.
Results: ESR1 mutations were detected for D538G (n = 13), Y537S (n = 3), and Y537C (n = 1), and not for K303R, S463P, or Y537N. Mutation rates were 7.0% (3/43 primary tumors), 9.1% (1/11 bone metastases), 12.5% (3/24 brain metastases), and 24.1% (7/29 cfDNA). Two patients showed polyclonal disease with more than one ESR1 mutation. Mutation allele frequencies were 0.07% to 0.2% in primary tumors, 1.4% in bone metastases, 34.3% to 44.9% in brain metastases, and 0.2% to 13.7% in cfDNA. In cases with both cfDNA and metastatic samples (n = 5), mutations were detected in both (n = 3) or in cfDNA only (n = 2). Treatment was associated with changes in ESR1 mutation detection and allele frequency.
Conclusions: ESR1 mutations were detected at very low allele frequencies in some primary breast cancers, and at high allele frequency in metastases, suggesting that in some tumors rare ESR1-mutant clones are enriched by endocrine therapy. Further studies should address whether sensitive detection of ESR1 mutations in primary breast cancer and in serial blood draws may be predictive for development of resistant disease. Clin Cancer Res; 22(5); 1130–7. ©2015 AACR.
See related commentary by Gu and Fuqua, p. 1034