bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Distribution of Infectious F-Specific RNA Phage Genotypes in Surface Waters
Authors: Hata Akihiko , Hanamoto Seiya , Shirasaka Yuya , Yamashita Naoyuki , Tanaka Hiroaki 
Published: May 2016

ABSTRACT
F-specific RNA phages (FRNAPHs) are considered potential viral indicators of water pollution due to their occurrence and stability in water environments. However, their suitability as viral indicators is not fully elucidated because the characteristics of FRNAPHs are variable depending on the genotype. In this study, for the characterization of infectious FRNAPH genotypes, integrated culture reverse transcription-PCR coupled with the most probable number approach was applied to surface water samples. Further, to recover low concentrations of FRNAPH genotypes, an FRNAPH recovery method was developed. The novel FRNAPH recovery method using a noncharged microfiltration membrane could effectively recover FRNAPH strains without inactivation, while a method using an electronegative microfiltration membrane resulted in the inactivation of some strains. Infectious FRNAPH genotypes in surface water samples were successfully quantified with an efficiency comparable to that of the conventional plaque assay. Genotype I (GI) and GII FRNAPHs tended to be predominant at locations impacted by treated and untreated municipal wastewater, respectively. The numbers and proportions of infectious FRNAPHs tended to be higher during the winter season when water temperature decreased.

IMPORTANCE
Properties of FRNAPHs are highly variable depending on their genotypes. Previous typing methods for FRNAPHs are not quantitative and/or are based on molecular assays, which cannot differentiate infective strains from inactive strains. Due to the reasons mentioned above, the utility of FRNAPHs as viral indicators of water pollution has not been fully validated. In this study, a quantitative genotyping method for infectious FRNAPHs was developed and applied to surface water samples. The method enabled characterization of infectious FRNAPH genotypes in terms of their occurrence and seasonality. Moreover, comparison of the method to a conventional molecular assay (reverse transcription-quantitative PCR) enabled characterization of their stability. Our approach can provide novel findings for further validation of FRNAPHs as viral indicators of water pollution.
In Situ
Hydrogen Dynamics in a Hot Spring Microbial Mat during a Diel Cycle
Authors: Revsbech Niels Peter , Trampe Erik , Lichtenberg Mads , Ward David M. , Kühl Michael 
Published: May 2016

ABSTRACT

Microbes can produce molecular hydrogen (H
2
) via fermentation, dinitrogen fixation, or direct photolysis, yet the H
2
dynamics in cyanobacterial communities has only been explored in a few natural systems and mostly in the laboratory. In this study, we investigated the diel
in situ
H
2
dynamics in a hot spring microbial mat, where various ecotypes of unicellular cyanobacteria (
Synechococcus
sp.) are the only oxygenic phototrophs. In the evening, H
2
accumulated rapidly after the onset of darkness, reaching peak values of up to 30 μmol H
2
liter
−1
at about 1-mm depth below the mat surface, slowly decreasing to about 11 μmol H
2
liter
−1
just before sunrise. Another pulse of H
2
production, reaching a peak concentration of 46 μmol H
2
liter
−1
, was found in the early morning under dim light conditions too low to induce accumulation of O
2
in the mat. The light stimulation of H
2
accumulation indicated that nitrogenase activity was an important source of H
2
during the morning. This is in accordance with earlier findings of a distinct early morning peak in N
2
fixation and expression of
Synechococcus
nitrogenase genes in mat samples from the same location. Fermentation might have contributed to the formation of H
2
during the night, where accumulation of other fermentation products lowered the pH in the mat to less than pH 6 compared to a spring source pH of 8.3.

IMPORTANCE
Hydrogen is a key intermediate in anaerobic metabolism, and with the development of a sulfide-insensitive microsensor for H
2
, it is now possible to study the microdistribution of H
2
in stratified microbial communities such as the photosynthetic microbial mat investigated here. The ability to measure H
2
profiles within the mat compared to previous measurements of H
2
emission gives much more detailed information about the sources and sinks of H
2
in such communities, and it was demonstrated that the high rates of H
2
formation in the early morning when the mat was exposed to low light intensities might be explained by nitrogen fixation, where H
2
is formed as a by-product.
Regulation of Polyhydroxybutyrate Synthesis in the Soil Bacterium Bradyrhizobium diazoefficiens
Authors: Quelas J. I. , Mesa S. , Mongiardini E. J. , Jendrossek D. , Lodeiro A. R. 
Published: May 2016

ABSTRACT

Polyhydroxybutyrate (PHB) is a carbon and energy reserve polymer in various prokaryotic species. We determined that, when grown with mannitol as the sole carbon source,
Bradyrhizobium diazoefficiens
produces a homopolymer composed only of 3-hydroxybutyrate units (PHB). Conditions of oxygen limitation (such as microoxia, oxic stationary phase, and bacteroids inside legume nodules) were permissive for the synthesis of PHB, which was observed as cytoplasmic granules. To study the regulation of PHB synthesis, we generated mutations in the regulator gene
phaR
and the phasin genes
phaP1
and
phaP4
. Under permissive conditions, mutation of
phaR
impaired PHB accumulation, and a
phaP1 phaP4
double mutant produced more PHB than the wild type, which was accumulated in a single, large cytoplasmic granule. Moreover, PhaR negatively regulated the expression of
phaP1
and
phaP4
as well as the expression of
phaA1
and
phaA2
(encoding a 3-ketoacyl coenzyme A [CoA] thiolases),
phaC1
and
phaC2
(encoding PHB synthases), and
fixK
2
(encoding a cyclic AMP receptor protein [CRP]/fumarate and nitrate reductase regulator [FNR]-type transcription factor of genes for microoxic lifestyle). In addition to the depressed PHB cycling,
phaR
mutants accumulated more extracellular polysaccharides and promoted higher plant shoot dry weight and competitiveness for nodulation than the wild type, in contrast to the
phaC1
mutant strain, which is defective in PHB synthesis. These results suggest that
phaR
not only regulates PHB granule formation by controlling the expression of phasins and biosynthetic enzymes but also acts as a global regulator of excess carbon allocation and symbiosis by controlling
fixK
2
.

IMPORTANCE
In this work, we investigated the regulation of polyhydroxybutyrate synthesis in the soybean-nodulating bacterium
Bradyrhizobium diazoefficiens
and its influence in bacterial free-living and symbiotic lifestyles. We uncovered a new interplay between the synthesis of this carbon reserve polymer and the network responsible for microoxic metabolism through the interaction between the gene regulators
phaR
and
fixK
2
. These results contribute to the understanding of the physiological conditions required for polyhydroxybutyrate biosynthesis. The interaction between these two main metabolic pathways is also reflected in the symbiotic phenotypes of soybeans inoculated with
phaR
mutants, which were more competitive for nodulation and enhanced dry matter production by the plants. Therefore, this knowledge may be applied to the development of superior strains to be used as improved inoculants for soybean crops.
Educational differences in sickness absence trends among young employees from 2002 to 2013 in Helsinki, Finland
Authors: Sumanen Hilla , Lahelma Eero , Lahti Jouni , Pietiläinen Olli , Rahkonen Ossi 
Published: May 2016

ObjectiveSocioeconomic differences in sickness absence (SA) are well established among older employees but poorly understood among the young. Our aim was to examine 12-year trends in educational differences in SA among young female and male employees, and to assess the magnitude of the differences.DesignWe examined annual SA spells. The data were obtained from the employer's registers and linked to Statistics Finland's register data on completed education and qualifications. Education was classified into four hierarchical groups. Joinpoint regression models were used to identify turning points in SA trends. The magnitude of the relative educational differences was estimated in accordance with the relative index of inequality for 2002, 2008 and 2013.SettingEmployees of the City of Helsinki, Finland, in 2002–2013.ParticipantsThe analyses covered female and male employees aged 25–34 years: employees aged 35–54 years were used as a reference group.OutcomeSA spells.ResultsAn educational gradient emerged among younger and older women and men. SA spells increased in the early 2000s, and downward turning points were located in 2007–2010 in all educational groups among women and in most groups among men. The magnitude of the differences remained broadly stable among younger women from 2002 to 2013, and decreased slightly among older women and more strongly among younger and older men. The educational differences were greater among men than women in the early 2000s, but similar among both at the end of the study period.ConclusionsThe changes in SA spells may reflect the economic downturn started in 2008 and resulting job insecurity. Early preventive measures aimed at reducing educational differences in SA should be focused at an early stage on those with low levels of education in particular.
Does a strategy to promote shared decision-making reduce medical practice variation in the choice of either single or double embryo transfer after in vitro fertilisation? A secondary analysis of a randomised controlled trial
Authors: Brabers Anne E M , van Dijk Liset , Groenewegen Peter P , van Peperstraten Arno M , de Jong Judith D 
Published: May 2016

ObjectivesThe hypothesis that shared decision-making (SDM) reduces medical practice variations is increasingly common, but no evidence is available. We aimed to elaborate further on this, and to perform a first exploratory analysis to examine this hypothesis. This analysis, based on a limited data set, examined how SDM is associated with variation in the choice of single embryo transfer (SET) or double embryo transfer (DET) after in vitro fertilisation (IVF). We examined variation between and within hospitals.DesignA secondary analysis of a randomised controlled trial.Setting5 hospitals in the Netherlands.Participants222 couples (woman aged <40 years) on a waiting list for a first IVF cycle, who could choose between SET and DET (ie, ≥2 embryos available).InterventionSDM via a multifaceted strategy aimed to empower couples in deciding how many embryos should be transferred. The strategy consisted of decision aid, support of IVF nurse and the offer of reimbursement for an extra treatment cycle. Control group received standard IVF care.Outcome measureDifference in variation due to SDM in the choice of SET or DET, both between and within hospitals.ResultsThere was large variation in the choice of SET or DET between hospitals in the control group. Lower variation between hospitals was observed in the group with SDM. Within most hospitals, variation in the choice of SET or DET appeared to increase due to SDM. Variation particularly increased in hospitals where mainly DET was chosen in the control group.ConclusionsAlthough based on a limited data set, our study gives a first insight that including patients’ preferences through SDM results in less variation between hospitals, and indicates another pattern of variation within hospitals. Variation that results from patient preferences could be potentially named the informed patient rate. Our results provide the starting point for further research.Trial registration numberNCT00315029; Post-results.
From QASC to QASCIP: successful Australian translational scale-up and spread of a proven intervention in acute stroke using a prospective pre-test/post-test study design
Authors: Middleton Sandy , Lydtin Anna , Comerford Daniel , Cadilhac Dominique A , McElduff Patrick , Dale Simeon , Hill Kelvin , Longworth Mark , Ward Jeanette , Cheung N Wah , D'Este Cate 
Published: May 2016

ObjectivesTo embed an evidence-based intervention to manageFEver, hyperglycaemia (Sugar) andSwallowing (the FeSS protocols) in stroke, previously demonstrated in the Quality in Acute Stroke Care (QASC) trial to decrease 90-day death and dependency, into all stroke services in New South Wales (NSW), Australia's most populous state.DesignPre-test/post-test prospective study.Setting36 NSW stroke services.MethodsOur clinical translational initiative, the QASC Implementation Project (QASCIP), targeted stroke services to embed 3 nurse-led clinical protocols (the FeSS protocols) into routine practice. Clinical champions attended a 1-day multidisciplinary training workshop and received standardised educational resources and ongoing support. Using the National Stroke Foundation audit collection tool and processes, patient data from retrospective medical record self-reported audits for 40 consecutive patients with stroke per site pre-QASCIP (1 July 2012 to 31 December 2012) were compared with prospective self-reported data from 40 consecutive patients with stroke per site post-QASCIP (1 November 2013 to 28 February 2014). Inter-rater reliability was substantial for 10 of 12 variables.Primary outcome measuresProportion of patients receiving care according to the FeSS protocols pre-QASCIP to post-QASCIP.ResultsAll 36 (100%) NSW stroke services participated, nominating 100 site champions who attended our educational workshops. The time from start of intervention to completion of post-QASCIP data collection was 8 months. All (n=36, 100%) sites provided medical record audit data for 2144 patients (n=1062 pre-QASCIP; n=1082 post-QASCIP). Pre-QASCIP to post-QASCIP, proportions of patients receiving the 3 targeted clinical behaviours increased significantly: management of fever (pre: 69%; post: 78%; p=0.003), hyperglycaemia (pre: 23%; post: 34%; p=0.0085) and swallowing (pre: 42%; post: 51%; p=0.033).ConclusionsWe obtained unprecedented statewide scale-up and spread to all NSW stroke services of a nurse-led intervention previously proven to improve long-term patient outcomes. As clinical leaders search for strategies to improve quality of care, our initiative is replicable and feasible in other acute care settings.
Opportunities to improve clinical summaries for patients at hospital discharge
Authors: Sarzynski Erin , Hashmi Hamza , Subramanian Jeevarathna , Fitzpatrick Laurie , Polverento Molly , Simmons Michael , Brooks Kevin , Given Charles 
Published: May 2016

BackgroundClinical summaries are electronic health record (EHR)-generated documents given to hospitalised patients during the discharge process to review their hospital stays and inform postdischarge care. Presently, it is unclear whether clinical summaries include relevant content or whether healthcare organisations configure their EHRs to generate content in a way that promotes patient self-management after hospital discharge. We assessed clinical summaries in three relevant domains: (1) content; (2) organisation; and (3) readability, understandability and actionability.MethodsTwo authors performed independent retrospective chart reviews of 100 clinical summaries generated at two Michigan hospitals using different EHR vendors for patients discharged 1 April –30 June 2014. We developed an audit tool based on the Meaningful Use view-download-transmit objective and the Society of Hospital Medicine Discharge Checklist (content); the Institute of Medicine recommendations for distributing easy-to-understand print material (organisation); and five readability formulas and the Patient Education Materials Assessment Tool (readability, understandability and actionability).ResultsClinical summaries averaged six pages (range 3–12). Several content elements were universally auto-populated into clinical summaries (eg, medication lists); others were not (eg, care team). Eighty-five per cent of clinical summaries contained discharge instructions, more often generated from third-party sources than manually entered by clinicians. Clinical summaries contained an average of 14 unique messages, including non-clinical elements irrelevant to postdischarge care. Medication list organisation reflected reconciliation mandates, and dosing charts, when present, did not carry column headings over to subsequent pages. Summaries were written at the 8th–12th grade reading level and scored poorly on assessments of understandability and actionability. Inter-rater reliability was strong for most elements in our audit tool.ConclusionsOur study highlights opportunities to improve clinical summaries for guiding patients' postdischarge care.
Artemisinins as potential anticancer agents: uptake detection in erythrocytes using Fourier transform infrared spectroscopy and cytotoxicity against bladder cancer cells
Authors: Humphreys Charlotte , Cooper Alan J , Barbu Eugen , Birch Brian R , Lwaleed Bashir A 
Published: May 2016

AimsSemisynthetic derivatives of the antimalarial drug artemisinin may also possess anticancer properties. The ability to detect artemisinin uptake and distribution in cells would facilitate live cell imaging without labelling. This study describes mid-range infrared absorption spectra for three artemisinin variants and attempts to detect their presence in a simple cell model (erythrocytes). Cytotoxicity assays assess potential anticancer properties against bladder cancer cells.MethodsMid-range Fourier transform infrared spectra were obtained from dry preparations of dihydroartemisinin (DHA), artesunate (ART) and artemether (ARTE). Erythrocytes were prepared from normal blood and incubated for 30 min at 37°C with the three artemisinin derivatives. Cytospin preparations were prepared on aluminium foil for spectroscopy. Potential for growth inhibition in the RT112 bladder carcinoma cell line was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide residual viable biomass method.ResultsSpectra were obtained from the three native compounds. Repeat scans after 8 weeks showed ART and ARTE to be stable, stored under manufacturer's recommendations. DHA exhibited marked changes over the same period. It was possible by subtraction to detect DHA in cytospins, but not ART or ARTE. The fit between the subtraction spectrum and that of the native compound was >80%. DHA and ART showed strong cytotoxic potential against RT112 cells.ConclusionsThe artemisinin derivatives tested exhibit unique mid-range infrared absorption spectra which can be used to monitor degradation and, for DHA, can be detected by subtraction in loaded erythrocytes rendering future imaging studies feasible. Its cytotoxic efficacy against RT112 cells suggests bladder cancer as a possible target disease.
Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk: Evidence from the Ovarian Cancer Association Consortium
Authors: Cannioto Rikki , LaMonte Michael J. , Risch Harvey A. , Hong Chi-Chen , Sucheston-Campbell Lara E. , Eng Kevin H. , Brian Szender J. , Chang-Claude Jenny , Schmalfeldt Barbara , Klapdor Ruediger , Gower Emily , Minlikeeva Albina N. , Zirpoli Gary R. , Bandera Elisa V. , Berchuck Andrew , Cramer Daniel , Doherty Jennifer A. , Edwards Robert P. , Fridley Brooke L. , Goode Ellen L. , Goodman Marc T. , Hogdall Estrid , Hosono Satoyo , Jensen Allan , Jordan Susan ,   on behalf of The Australian Ovarian Cancer Study Group, Kjaer Susanne K. , Matsuo Keitaro , Ness Roberta B. , Olsen Catherine M. , Olson Sara H. , Leigh Pearce Celeste , Pike Malcolm C. , Anne Rossing Mary , Szamreta Elizabeth A. , Thompson Pamela J. , Tseng Chiu-Chen , Vierkant Robert A. , Webb Penelope M. , Wentzensen Nicolas , Wicklund Kristine G. , Winham Stacey J. , Wu Anna H. , Modugno Francesmary , Schildkraut Joellen M. , Terry Kathryn L. , Kelemen Linda E. , Moysich Kirsten B. 
Published: May 2016

Abstract
Background: Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC risk. We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium to investigate the association between chronic recreational physical inactivity and EOC risk.
Methods: In accordance with the 2008 Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the ORs and 95% confidence intervals (CI) for the association between inactivity and EOC risk overall and by subgroups based upon histotype, menopausal status, race, and body mass index.
Results: The current analysis included data from 8,309 EOC patients and 12,612 controls. We observed a significant positive association between inactivity and EOC risk (OR = 1.34; 95% CI, 1.14–1.57), and similar associations were observed for each histotype.
Conclusions: In this large pooled analysis examining the association between recreational physical inactivity and EOC risk, we observed consistent evidence of an association between chronic inactivity and all EOC histotypes.
Impact: These data add to the growing body of evidence suggesting that inactivity is an independent risk factor for cancer. If the apparent association between inactivity and EOC risk is substantiated, additional work via targeted interventions should be pursued to characterize the dose of activity required to mitigate the risk of this highly fatal disease. Cancer Epidemiol Biomarkers Prev; 25(7); 1114–24. ©2016 AACR.
ASH1L Links Histone H3 Lysine 36 Dimethylation to MLL Leukemia
Authors: Zhu Li , Li Qin , Wong Stephen H.K. , Huang Min , Klein Brianna J. , Shen Jinfeng , Ikenouye Larissa , Onishi Masayuki , Schneidawind Dominik , Buechele Corina , Hansen Loren , Duque-Afonso Jesús , Zhu Fangfang , Martin Gloria Mas , Gozani Or , Majeti Ravindra , Kutateladze Tatiana G. , Cleary Michael L. 
Published: May 2016

Abstract
Numerous studies in multiple systems support that histone H3 lysine 36 dimethylation (H3K36me2) is associated with transcriptional activation; however, the underlying mechanisms are not well defined. Here, we show that the H3K36me2 chromatin mark written by the ASH1L histone methyltransferase is preferentially bound in vivo by LEDGF, a mixed-lineage leukemia (MLL)–associated protein that colocalizes with MLL, ASH1L, and H3K36me2 on chromatin genome wide. Furthermore, ASH1L facilitates recruitment of LEDGF and wild-type MLL proteins to chromatin at key leukemia target genes and is a crucial regulator of MLL-dependent transcription and leukemic transformation. Conversely, KDM2A, an H3K36me2 demethylase and Polycomb group silencing protein, antagonizes MLL-associated leukemogenesis. Our studies are the first to provide a basic mechanistic insight into epigenetic interactions wherein placement, interpretation, and removal of H3K36me2 contribute to the regulation of gene expression and MLL leukemia, and suggest ASH1L as a novel target for therapeutic intervention.
Significance: Epigenetic regulators play vital roles in cancer pathogenesis and represent a new frontier in therapeutic targeting. Our studies provide basic mechanistic insight into the role of H3K36me2 in transcription activation and MLL leukemia pathogenesis and implicate ASH1L histone methyltransferase as a promising target for novel molecular therapy. Cancer Discov; 6(7); 770–83. ©2016 AACR.
See related commentary by Balbach and Orkin, p. 700.
This article is highlighted in the In This Issue feature, p. 681