bluuebunny/crossref_metadata_2025_split huggingface dataset:
To Treat or Not to Treat, That Is the Question: The Role of Bone-Targeted Therapy in Metastatic Prostate Cancer
Authors: Higano Celestia S. 
Published: March 2014

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 62-year-old construction site manager experienced 6 weeks of back pain that was not responsive to over-the-counter nonsteroidal anti-inflammatory medications. He visited his wife's primary care physician for evaluation. He denied neurologic symptoms or worsening of pain while lying down. He smoked (30 pack-years, quit 4 years ago), and drinks 3 beers each evening and more on weekends (up to a six-pack). He has had two lower extremity fractures from falls at construction sites. At the time of the physical examination, he was 5 feet 11 inches tall and weighed 194 pounds. He was alert, oriented, and in mild distress. He had no percussion tenderness of his spine, and a neurologic examination was negative. A digital rectal examination revealed an enlarged prostate with an area of induration of the left, normal rectal tone, and guaiac-negative stool. Laboratory studies included normal blood counts, electrolytes, and renal and liver function tests (including lactic acid dehydrogenase and total protein). The prostate-specific antigen (PSA) was 114 ng/mL; he had no prior PSA test. A bone scan showed diffuse bony involvement including the T7 vertebral body and left pedicle, ribs, pelvis, and calvarium. Magnetic resonance imaging of his spine confirmed bone metastases but showed no evidence of extension into the epidural space or spinal cord compromise. A prostate biopsy revealed Gleason 4+4 adenocarcinoma of the prostate. Androgen deprivation therapy with leuprolide acetate was initiated, and the addition of a bone-targeted agent was considered.
Dendritic Tetrathiafulvalene Pentamers Linked by Methylenedithio Spacers
Authors: Kimura Haruka , Konishi Katsuya , Muraoka Shun-ya , Shirahata Takashi , Misaki Yohji 
Published: March 2014

Abstract
Dendritic tetrathiafulvalene (TTF) derivatives linked by methylenedithio groups 3 were synthesized. Cyclic voltammetry and spectroelectrochemistry analyses revealed the presence of considerable mutual interaction among multiple TTF units in the oxidation states.
Identification of Chromosomally Integrated Human Herpesvirus 6 by Droplet Digital PCR
Authors: Sedlak Ruth Hall , Cook Linda , Huang Meei-Li , Magaret Amalia , Zerr Danielle M , Boeckh Michael , Jerome Keith R 
Published: March 2014

Abstract

BACKGROUND
Human herpesvirus 6 (HHV-6) latently infects a majority of adults. In about 1% of the population HHV-6 exists in a chromosomally integrated form (ciHHV-6) that resides in every somatic and germ cell and can be transmitted through the germ line. Patients with ciHHV-6 have been misdiagnosed and unnecessarily treated for active HHV-6 infection, sometimes with important side effects, based on results from quantitative molecular HHV-6 tests.

METHODS
A droplet digital PCR (ddPCR) assay was developed to identify ciHHV-6 in cellular patient samples by precisely determining the ratio of HHV-6 to cellular DNA. We validated the assay on confirmed ciHHV-6 patient samples and a cell line derived from a ciHHV-6 patient, and we analyzed hematopoietic stem cell transplant patients suspected of having ciHHV-6. We additionally evaluated whether the assay could be applied to stored plasma samples from a study of clinical correlates of HHV-6.

RESULTS
The ddPCR assay accurately identified ciHHV-6 in cellular samples (buffy coat, peripheral blood mononuclear cells), giving a ratio very close to 1 HHV-6/cell [mean (SD), 1.02 (0.03)] in fluorescence in situ hybridization–confirmed sample). In stored plasma samples, the assay performance was set by design to have 100% sensitivity, which resulted in 82% specificity for ciHHV-6.

CONCLUSIONS
The possibility of ciHHV-6 is often overlooked in patients with detectable HHV-6 viral loads by quantitative PCR. Our ddPCR test provides rapid and accurate laboratory identification of ciHHV-6 from easily obtained cellular samples. In addition, the assay provides excellent sensitivity and specificity using stored plasma samples, facilitating retrospective analysis of the clinical significance of ciHHV-6.
Use of Observed Within-Person Variation of Cardiac Troponin in Emergency Department Patients for Determination of Biological Variation and Percentage and Absolute Reference Change Values
Authors: Simpson Aaron J , Potter Julia M , Koerbin Gus , Oakman Carmen , Cullen Louise , Wilkes Garry J , Scanlan Samuel L , Parsonage William , Hickman Peter E 
Published: March 2014

Abstract

BACKGROUND
Many patients presenting to the emergency department (ED) for assessment of possible acute coronary syndrome (ACS) have low cardiac troponin concentrations that change very little on repeat blood draw. It is unclear if a lack of change in cardiac troponin concentration can be used to identify acutely presenting patients at low risk of ACS.

METHODS
We used the hs-cTnI assay from Abbott Diagnostics, which can detect cTnI in the blood of nearly all people. We identified a population of ED patients being assessed for ACS with repeat cTnI measurement who ultimately were proven to have no acute cardiac disease at the time of presentation. We used data from the repeat sampling to calculate total within-person CV (CVT) and, knowing the assay analytical CV (CVA), we could calculate within-person biological variation (CVi), reference change values (RCVs), and absolute RCV delta cTnI concentrations.

RESULTS
We had data sets on 283 patients. Men and women had similar CVi values of approximately 14%, which was similar at all concentrations &lt;40 ng/L. The biological variation was not dependent on the time interval between sample collections (t = 1.5–17 h). The absolute delta critical reference change value was similar no matter what the initial cTnI concentration was. More than 90% of subjects had a critical reference change value &lt;5 ng/L, and 97% had values of &lt;10 ng/L.

CONCLUSIONS
With this hs-cTnI assay, delta cTnI seems to be a useful tool for rapidly identifying ED patients at low risk for possible ACS.
Analysis of the gene coding for steroidogenic factor 1 (SF1, NR5A1) in a cohort of 50 Egyptian patients with 46,XY disorders of sex development
Authors: Tantawy Sally , Mazen Inas , Soliman Hala , Anwar Ghada , Atef Abeer , El-Gammal Mona , El-Kotoury Ahmed , Mekkawy Mona , Torky Ahmad , Rudolf Agnes , Schrumpf Pamela , Grüters Annette , Krude Heiko , Dumargne Marie-Charlotte , Astudillo Rebekka , Bashamboo Anu , Biebermann Heike , Köhler Birgit 
Published: March 2014

ObjectiveSteroidogenic factor 1 (SF1, NR5A1) is a key transcriptional regulator of genes involved in the hypothalamic–pituitary–gonadal axis. Recently, SF1 mutations were found to be a frequent cause of 46,XY disorders of sex development (DSD) in humans. We investigate the frequency of NR5A1 mutations in an Egyptian cohort of XY DSD.DesignClinical assessment, endocrine evaluation and genetic analysis of 50 Egyptian XY DSD patients (without adrenal insufficiency) with a wide phenotypic spectrum.MethodsMolecular analysis of NR5A1 gene by direct sequencing followed by in vitro functional analysis of the two novel missense mutations detected.ResultsThree novel heterozygous mutations of the coding region in patients with hypospadias were detected. p.Glu121AlafsX25 results in severely truncated protein, p.Arg62Cys lies in DNA-binding zinc finger, whereas p.Ala154Thr lies in the hinge region of SF1 protein. Transactivation assays using reporter constructs carrying promoters of anti-Müllerian hormone (AMH), CYP11A1 and TESCO core enhancer of Sox9 showed that p.Ala154Thr and p.Arg62Cys mutations result in aberrant biological activity of NR5A1. A total of 17 patients (34%) harboured the p.Gly146Ala polymorphism.ConclusionWe identified two novel NR5A1 mutations showing impaired function in 23 Egyptian XY DSD patients with hypospadias (8.5%). This is the first study searching for NR5A1 mutations in oriental patients from the Middle East and Arab region with XY DSD and no adrenal insufficiency, revealing a frequency similar to that in European patients (6.5–15%). We recommend screening of NR5A1 in patients with hypospadias and gonadal dysgenesis. Yearly follow-ups of gonadal function and early cryoconservation of sperms should be performed in XY DSD patients with NR5A1 mutations given the risk of future fertility problems due to early gonadal failure.
Genome Sequence of Saccharomyces carlsbergensis, the World’s First Pure Culture Lager Yeast
Authors: Walther Andrea , Hesselbart Ana , Wendland Jürgen 
Published: March 2014

Abstract
Lager yeast beer production was revolutionized by the introduction of pure culture strains. The first established lager yeast strain is known as the bottom fermenting Saccharomyces carlsbergensis, which was originally termed Unterhefe No. 1 by Emil Chr. Hansen and has been used in production in since 1883. S. carlsbergensis belongs to group I/Saaz-type lager yeast strains and is better adapted to cold growth conditions than group II/Frohberg-type lager yeasts, e.g., the Weihenstephan strain WS34/70. Here, we sequenced S. carlsbergensis using next generation sequencing technologies. Lager yeasts are descendants from hybrids formed between a S. cerevisiae parent and a parent similar to S. eubayanus. Accordingly, the S. carlsbergensis 19.5-Mb genome is substantially larger than the 12-Mb S. cerevisiae genome. Based on the sequence scaffolds, synteny to the S. cerevisae genome, and by using directed polymerase chain reaction for gap closure, we generated a chromosomal map of S. carlsbergensis consisting of 29 unique chromosomes. We present evidence for genome and chromosome evolution within S. carlsbergensis via chromosome loss and loss of heterozygosity specifically of parts derived from the S. cerevisiae parent. Based on our sequence data and via fluorescence-activated cell-sorting analysis, we determined the ploidy of S. carlsbergensis. This inferred that this strain is basically triploid with a diploid S. eubayanus and haploid S. cerevisiae genome content. In contrast the Weihenstephan strain, which we resequenced, is essentially tetraploid composed of two diploid S. cerevisiae and S. eubayanus genomes. Based on conserved translocations between the parental genomes in S. carlsbergensis and the Weihenstephan strain we propose a joint evolutionary ancestry for lager yeast strains.
Health Assessment of Self‐employed Hairdressers in France
Authors: Deschamps Frederic , Langrand Jerome , Lesage Francois‐Xavier 
Published: March 2014

Health Assessment of Self‐employed Hairdressers in France: Frederic DESCHAMPS, et al. Occupational Disease Department University Hospital of Reims, France—ObjectiveHairdressers have a high incidence of occupational diseases, owing to excessive wet work and exposure to chemical substances. The objective of this study was to assess the prevalence of occupational diseases in a population of self‐employed hairdressers, matched for age and sex with a control group of wage‐earning hairdressers.MethodA health questionnaire was administered to both groups by an occupational health practitioner.ResultsIrritative skin diseases were reported by 1.5% of the self‐employed hairdressers versus 9.1% of the wage earners. Conversely, the rates of respiratory diseases and cumulative musculoskeletal injuries were much higher among self‐employed hairdressers.ConclusionsThis study shows that the overall health of self‐employed hairdressers is lower than that of their wage‐earning counterparts. This can be attributed to several aspects of work exposure, organization, including longer working hours, fewer protective measures and the absence of preventive medicine in the workplace.
Formation of the Nitrative DNA Lesion 8‐Nitroguanine is Associated with Asbestos Contents in Human Lung Tissues: A Pilot Study
Authors: Hiraku Yusuke , Sakai Kiyoshi , Shibata Eiji , Kamijima Michihiro , Hisanaga Naomi , Ma Ning , Kawanishi Shosuke , Murata Mariko 
Published: March 2014

Formation of the Nitrative DNA Lesion 8‐Nitroguanine is Associated with Asbestos Contents in Human Lung Tissues: A Pilot Study: Yusuke HIRAKU, et al. Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine—ObjectivesAsbestos causes lung cancer and malignant mesothelioma, and chronic inflammation is considered to participate in carcinogenesis. However, biomarkers to evaluate its carcinogenic risk have not been established. Reactive oxygen/nitrogen species are generated in biological systems under inflammatory conditions and may contribute to carcinogenesis by causing DNA damage. In this study, we examined the relationship between the formation of 8nitroguanine (8‐nitroG), a mutagenic DNA lesion formed during inflammation, and asbestos contents in human lung tissues.MethodsWe obtained non‐tumor lung tissues from patients with (n=15) and without mesothelioma (n=21). The expression of 8‐nitroG and related molecules was examined by immunohistochemistry, and their staining intensities were semiquantitatively evaluated. Asbestos contents in lung tissues were analyzed by analytical transmission electron microscopy.ResultsIn subjects without mesothelioma, staining intensities of 8‐nitroG and apurinic/apyrimidinic endonuclease 1 (APE1) were significantly correlated with total asbestos and amphibole contents (p<0.05), but not with chrysotile content. In mesothelioma patients, their staining intensities were not correlated with asbestos contents. The double immunofluorescence technique revealed that APE1 was expressed in 8‐nitroGpositive cells, suggesting that abasic sites were formed possibly due to the removal of 8‐nitroG. The staining intensities of 8‐oxo‐7,8‐dihydro‐2’‐deoxyguanosine, an oxidative DNA lesion, and its repair enzyme 8‐oxoguanine DNA‐glycosylase were correlated with age (p<0.05), but not with asbestos contents in subjects without mesothelioma.ConclusionsThis is the first study to demonstrate that 8‐nitroG formation is associated with asbestos contents in human lung tissues. This finding raises a possibility that 8‐nitroG serves as a biomarker that can be used to evaluate asbestos exposure and carcinogenic risk.
Economic Evaluation of the Routine Childhood Immunization Program in the United States, 2009
Authors: Zhou Fangjun , Shefer Abigail , Wenger Jay , Messonnier Mark , Wang Li Yan , Lopez Adriana , Moore Matthew , Murphy Trudy V. , Cortese Margaret , Rodewald Lance 
Published: March 2014

OBJECTIVES:To evaluate the economic impact of the 2009 routine US childhood immunization schedule, including diphtheria and tetanus toxoids and acellular pertussis, Haemophilus influenzae type b conjugate, inactivated poliovirus, measles/mumps/rubella, hepatitis B, varicella, 7-valent pneumococcal conjugate, hepatitis A, and rotavirus vaccines; influenza vaccine was not included.METHODS:Decision analysis was conducted using population-based vaccination coverage, published vaccine efficacies, historical data on disease incidence before vaccination, and disease incidence reported during 2005 to 2009. Costs were estimated using the direct cost and societal (direct and indirect costs) perspectives. Program costs included vaccine, administration, vaccine-associated adverse events, and parent travel and work time lost. All costs were inflated to 2009 dollars, and all costs and benefits in the future were discounted at a 3% annual rate. A hypothetical 2009 US birth cohort of 4 261 494 infants over their lifetime was followed up from birth through death. Net present value (net savings) and benefit-cost ratios of routine childhood immunization were calculated.RESULTS:Analyses showed that routine childhood immunization among members of the 2009 US birth cohort will prevent ∼42 000 early deaths and 20 million cases of disease, with net savings of $13.5 billion in direct costs and $68.8 billion in total societal costs, respectively. The direct and societal benefit-cost ratios for routine childhood vaccination with these 9 vaccines were 3.0 and 10.1.CONCLUSIONS:From both direct cost and societal perspectives, vaccinating children as recommended with these vaccines results in substantial cost savings.
Supplemental Nutrition Assistance Program Participation and Child Food Security
Authors: Mabli James , Worthington Julie 
Published: March 2014

OBJECTIVE:This article investigates the association between Supplemental Nutrition Assistance Program (SNAP) participation and child food security by using data from the largest national survey of the food security of SNAP participants to date.METHODS:The analysis used a survey of nearly 3000 households with children and a quasi-experimental research design that consisted of 2 sets of comparisons. Using a cross-sectional sample, we compared information collected from SNAP households within days of program entry with information collected from a contemporaneous sample of SNAP households that had participated for ∼6 months. Next, by using a longitudinal sample, we compared baseline information collected from new-entrant SNAP households with information from those same households 6 months later. Multivariate logistic regression analysis was used to estimate associations between SNAP and child food security.RESULTS:SNAP participation was associated with an approximately one-third decrease in the odds of children being food insecure in both samples. In the cross-sectional analysis only, SNAP was also associated with a decrease in the odds of children experiencing severe food insecurity (designated very low food security). Findings were qualitatively robust to different empirical specifications.CONCLUSIONS:After controlling for other possible confounders, we found children in households that had participated in SNAP for 6 months experienced improvements in food security. On the basis of these findings, we conclude SNAP serves a vital role in improving the health and well-being of low-income children by increasing food security. Future research is needed to determine whether specific groups of children experience differential improvements in food security.
Broad‐scale geographic variation in the organization of rocky intertidal communities in the Gulf of Maine
Authors: Bryson Elizabeth S. , Trussell Geoffrey C. , Ewanchuk Patrick J. 
Published: March 2014

A major challenge facing ecology is to better understand how large‐scale processes modify local‐scale processes to shape the organization of ecological communities. Although the results of ecological experiments are repeatable on local scales, different results often emerge across broad scales, which can hinder the development of general predictions that apply across the geographical range of a community. Numerous studies in the southern Gulf of Maine have shaped our understanding of community organization and dynamics on New England rocky intertidal shores, where consumers strongly control recovery from disturbance on sheltered shores, and high invertebrate recruitment and competition for space dictate recovery on wave‐exposed shores. It is unclear, however, whether the effects of consumers and recruitment variation on resulting community organization in this region apply more broadly to rocky intertidal habitats throughout the Gulf.We characterized variation in rocky intertidal community structure at 34 sites throughout the Gulf of Maine and experimentally examined the influence of consumers (present, absent) and wave energy (wave‐exposed, sheltered) on community recovery from disturbance in the northern and southern Gulf. Our results reinforced previous work in the southern Gulf, because consumers dictated the recovery of fucoid algae and mussels on sheltered shores, whereas high barnacle and mussel recruitment and competition for space shaped recovery on wave‐exposed shores. However, on sheltered shores in the northern Gulf, neither consumers nor barnacle and mussel recruitment impacted recovery, which was dominated by fucoid algae. Moreover, recovery on wave‐exposed shores in the northern Gulf was quite distinct from that observed in the southern Gulf; barnacle and mussel recruitment was negligible and fucoid algae dominated recovery, including the long‐term establishment of Ascophyllum nodosum, which is largely absent from wave‐exposed shores in the southern Gulf. Thus, distinct community types emerged in the northern and southern Gulf despite their sharing of many of the same species. These patterns likely emerged because of regional differences in coastal oceanography that modulate the recruitment of barnacles and mussels. Hence, increased attention to regional factors should provide key insight into how rocky‐shore communities are organized in the Gulf of Maine and elsewhere.
Agricultural practices indirectly influence plant productivity and ecosystem services through effects on soil biota
Authors: Köhl Luise , Oehl Fritz , van der Heijden Marcel G. A. 
Published: March 2014

It is well established that agricultural practices alter the composition and diversity of soil microbial communities. However, the impact of changing soil microbial communities on the functioning of the agroecosystems is still poorly understood. Earlier work showed that soil tillage drastically altered microbial community composition. Here we tested, using an experimental grassland (Lolium, Trifolium, Plantago) as a model system, whether soil microbial communities from conventionally tilled (CT) and non‐tilled (NT) soils have different influences on plant productivity and nutrient acquisition. We specifically focus on arbuscular mycorrhizal fungi (AMF), as they are a group of beneficial soil fungi that can promote plant productivity and ecosystem functioning and are also strongly affected by tillage management.Soil microbial communities from CT and NT soils varied greatly in their effects on the grassland communities. Communities from CT soil increased overall biomass production more than soil communities from NT soil. This effect was mainly due to a significant growth promotion of Trifolium by CT microorganisms. In contrast to CT soil inoculum, NT soil inoculum increased plant phosphorus concentration and total plant P content, demonstrating that the soil microbial communities from NT fields enhance P uptake. Differences in AM fungal community composition resulting, for instance, in twofold greater hyphal length in NT soil communities when compared to CT, are the most likely explanation for the different plant responses to CT and NT soil inocula.A range of field studies have shown that plant P uptake increases when farmers change to conservation tillage or direct seeding. Our results indicate that this enhanced P uptake results from enhanced hyphal length and an altered AM fungal community. Our results further demonstrate that agricultural management practices indirectly influence ecosystem services and plant community structure through effects on soil biota.