bluuebunny/crossref_metadata_2025_split huggingface dataset:
Closed Genome Sequence of Clostridium pasteurianum ATCC 6013
Authors: Rotta Carlo , Poehlein Anja , Schwarz Katrin , McClure Peter , Daniel Rolf , Minton Nigel P. 
Published: February 2015

ABSTRACT

We report here the closed genome of
Clostridium pasteurianum
ATCC 6013, a saccharolytic, nitrogen-fixing, and spore-forming Gram-positive obligate anaerobe. The organism is of biotechnological interest due to the production of solvents (butanol and 1,3-propanediol) but can be associated with food spoilage. The genome comprises a total of 4,351,223 bp.
Draft Genomes of Two Strains of Flavobacterium Isolated from Lake Washington Sediment
Authors: McTaggart Tami L. , Shapiro Nicole , Woyke Tanja , Chistoserdova Ludmila 
Published: February 2015

ABSTRACT

We report sequencing the genomes of two new Flavobacterium strains isolated from Lake Washington sediment. From genomic contents, versatile lifestyles were predicted but not
bona fide
methylotrophy. With the availability of their genomic sequences, the new Flavobacterium strains present prospective models for studying microbial communities in lake sediments.
Transmission of Ebola Viruses: What We Know and What We Do Not Know
Authors: Osterholm Michael T. , Moore Kristine A. , Kelley Nicholas S. , Brosseau Lisa M. , Wong Gary , Murphy Frederick A. , Peters Clarence J. , LeDuc James W. , Russell Phillip K. , Van Herp Michel , Kapetshi Jimmy , Muyembe Jean-Jacques T. , Ilunga Benoit Kebela , Strong James E. , Grolla Allen , Wolz Anja , Kargbo Brima , Kargbo David K. , Formenty Pierre , Sanders David Avram , Kobinger Gary P. 
Published: February 2015

ABSTRACT
Available evidence demonstrates that direct patient contact and contact with infectious body fluids are the primary modes for Ebola virus transmission, but this is based on a limited number of studies. Key areas requiring further study include (i) the role of aerosol transmission (either via large droplets or small particles in the vicinity of source patients), (ii) the role of environmental contamination and fomite transmission, (iii) the degree to which minimally or mildly ill persons transmit infection, (iv) how long clinically relevant infectiousness persists, (v) the role that “superspreading events” may play in driving transmission dynamics, (vi) whether strain differences or repeated serial passage in outbreak settings can impact virus transmission, and (vii) what role sylvatic or domestic animals could play in outbreak propagation, particularly during major epidemics such as the 2013–2015 West Africa situation. In this review, we address what we know and what we do not know about Ebola virus transmission. We also hypothesize that Ebola viruses have the potential to be respiratory pathogens with primary respiratory spread.
Elevated inflammatory biomarkers during unemployment: modification by age and country in the UK
Authors: Hughes Amanda , McMunn Anne , Bartley Mel , Kumari Meena 
Published: February 2015

BackgroundThere is raised risk of mortality following unemployment, and reviews have consistently found worse psychological health among the unemployed. Inflammation is increasingly implicated as a mediating factor relating stress to physical disease and is strongly linked to depression. Inflammation may, therefore, be implicated in processes associated with excess mortality and morbidity during unemployment. This study examined associations of unemployment with inflammatory markers among working-age men and women from England and Scotland.MethodsCross-sectional analyses using data from the Health Survey for England and the Scottish Health Survey collected between 1998 and 2010. Systemic inflammation was indexed by serum concentrations of C reactive protein (CRP) and fibrinogen, and compared between participants currently employed/self-employed, currently unemployed and other groups.ResultsCRP, fibrinogen and odds of CRP >3 mg/L were all significantly raised for the unemployed, as compared to the employed participants (eg, OR for CRP >3 mg/L=1.43, CI 1.15 to 1.78 N=23 025), following adjustment for age, gender, occupational social class, housing tenure, smoking, alcohol consumption, body mass index, long-term illness and depressive/anxiety symptoms. Strengths of associations varied considerably by both age and country/region, with effects mainly driven by participants aged ≥48 and participants from Scotland, which had comparatively high unemployment during this time.ConclusionsCurrent unemployment is associated with elevated inflammatory markers using data from two large-scale, nationally representative UK studies. Effect modification by age suggests inflammation may be particularly involved in processes leading to ill-health among the older unemployed. Country/regional effects may suggest the relationship of unemployment with inflammation is strongly influenced by contextual factors, and/or reflect life course accumulation processes.
Male involvement and maternal health outcomes: systematic review and meta-analysis
Authors: Yargawa Judith , Leonardi-Bee Jo 
Published: February 2015

BackgroundThe developing world accounts for 99% of global maternal deaths. Men in developing countries are the chief decision-makers, determining women's access to maternal health services and influencing their health outcomes. At present, it is unclear whether involving men in maternal health can improve maternal outcomes. This systematic review and meta-analysis aimed to investigate the impact of male involvement on maternal health outcomes of women in developing countries.MethodsFour electronic databases and grey literature sources were searched (up to May 2013), together with reference lists of included studies. Two reviewers independently screened and assessed the quality of studies based on prespecified criteria. Measures of effects were pooled and random effect meta-analysis was conducted, where possible.ResultsFourteen studies met the inclusion criteria. Male involvement was significantly associated with reduced odds of postpartum depression (OR=0.36, 95% CI 0.19 to 0.68 for male involvement during pregnancy; OR=0.34, 95% CI 0.19 to 0.62 for male involvement post partum), and also with improved utilisation of maternal health services (skilled birth attendance and postnatal care). Male involvement during pregnancy and at post partum appeared to have greater benefits than male involvement during delivery.ConclusionsMale involvement is associated with improved maternal health outcomes in developing countries. Contrary to reports from developed countries, there was little evidence of positive impacts of husbands’ presence in delivery rooms. However, more rigorous studies are needed to improve this area's evidence base.
Incarceration and perinatal smoking: a missed public health opportunity
Authors: Dumont Dora M , Parker Donna R , Viner-Brown Samara , Clarke Jennifer G 
Published: February 2015

BackgroundIncarceration is simultaneously a public health opportunity and a public health concern. We examined the association between maternal/partner incarceration in the year prior to birth and perinatal smoking.MethodsWe pooled 2006–2010 data from the Centers for Disease Control and Prevention's Pregnancy Risk Assessment and Monitoring System. Controlling for age, race/ethnicity, education, marital status and other stressors, we assessed prevalence and heaviness of perinatal smoking.FindingsWomen who reported incarceration of themselves or their partners in the year prior to delivery were more likely to smoke during the last trimester of pregnancy (adjusted OR (AOR) 1.51 (95% CI 1.36 to 1.67)), and they were more likely to smoke more than 10 cigarettes a day compared to smokers who did not report incarceration (AOR 1.35 (95% CI 1.10 to 1.65)). Patterns were similar for the 3 months prior to pregnancy and postbirth smoking.ConclusionsIncarceration of a parent in the 12 months before birth is associated with increased risk of fetal and newborn exposure to smoking. The criminal justice system can be utilised by public health practitioners to target perinatal smoking reduction interventions.
Relative deprivation in income and mortality by leading causes among older Japanese men and women: AGES cohort study
Authors: Kondo Naoki , Saito Masashige , Hikichi Hiroyuki , Aida Jun , Ojima Toshiyuki , Kondo Katsunori , Kawachi Ichiro 
Published: February 2015

BackgroundRelative deprivation of income is hypothesised to generate frustration and stress through upward social comparison with one's peers. If psychosocial stress is the mechanism, relative deprivation should be more strongly associated with specific health outcomes, such as cardiovascular disease (compared with other health outcomes, eg, non-tobacco-related cancer).MethodsWe evaluated the association between relative income deprivation and mortality by leading causes, using a cohort of 21 031 community-dwelling adults aged 65 years or older. A baseline mail-in survey was conducted in 2003. Information on cause-specific mortality was obtained from death certificates. Our relative deprivation measure was the Yitzhaki Index, derived from the aggregate income shortfall for each person, relative to individuals with higher incomes in that person's reference group. Reference groups were defined according to gender, age group and same municipality of residence.ResultsWe identified 1682 deaths during the 4.5 years of follow-up. A Cox regression demonstrated that, after controlling for demographic, health and socioeconomic factors including income, the HR for death from cardiovascular diseases per SD increase in relative deprivation was 1.50 (95% CI 1.09 to 2.08) in men, whereas HRs for mortality by cancer and other diseases were close to the null value. Additional adjustment for depressive symptoms and health behaviours (eg, smoking and preventive care utilisation) attenuated the excess risks for mortality from cardiovascular disease by 9%. Relative deprivation was not associated with mortality for women.ConclusionsThe results partially support our hypothesised mechanism: relative deprivation increases health risks via psychosocial stress among men.
Enrollment bias: frequency and impact on patient selection in endovascular stroke trials
Authors: Sheth Sunil A , Saver Jeffrey L , Starkman Sidney , Grunberg Ileana D , Guzy Judy , Ali Latisha K , Kim Doojin , Gonzalez Nestor R , Jahan Reza , Tateshima Satoshi , Duckwiler Gary , Liebeskind David S 
Published: February 2015

BackgroundSelection bias may have affected enrollment in first generation endovascular stroke trials. We investigate, evaluate, and quantify such bias for these trials at our institution.MethodsDemographic, clinical, imaging, and angiographic data were prospectively collected on a consecutive cohort of patients with acute ischemic stroke who were enrolled in formal trials of endovascular stroke therapy (EST) or received EST in clinical practice outside of a randomized trial for acute cerebral ischemia at a single tertiary referral center from September 2004 to December 2012.ResultsAmong patients considered appropriate for EST in practice, 47% were eligible for trials, with rates for individual trials ranging from 17% to 70%. Compared with trial ineligible patients treated with EST, trial eligible patients were younger (67 vs 74 years; p<0.05), more often treated with intravenous tissue plasminogen activator (53% vs 34%; p<0.01), and had shorter last known well to puncture times (328 vs 367 min; p<0.05). Focusing on the largest trial with a non-interventional control arm, compared with trial eligible patients treated with EST outside the trial, enrolled patients presented later (274 vs 163 min; p<0.001), had higher National Institutes of Health Stroke Scale scores (20 vs 17; p<0.05), and larger strokes (diffusion weighted imaging volumes 49 vs 18; p<0.001).ConclusionsThe majority of patients felt suitable for EST at our institution were excluded from recent trials. Formal entry criteria succeeded in selecting patients with better prognostic features, although many of these patients were treated outside of trials. Acknowledging and mitigating these biases will be crucial to ongoing investigations.
Implementation of NICE Clinical Guideline 95 for assessment of stable chest pain in a rapid access chest pain clinic reduces the mean number of investigations and cost per patient
Authors: Lee Alvin J X , Michail Michael , Quaderi Shumonta A , Richardson James A , Aggarwal Suneil K , Speechly-Dick M Elsya 
Published: February 2015

ObjectiveIn 2010, the National Institute for Health and Care Excellence (NICE) in the UK published Clinical Guideline 95 (CG95) advocating risk stratification of patients using ‘CADScore’ to guide appropriate cardiac investigations for chest pain of recent onset. Implementation of the guideline in the University College London Hospitals NHS Foundation Trust was evaluated to see if it led to a reduction in the average cost of the diagnostic journey per patient and fewer investigations per patient in order to confirm a diagnosis.MethodsThis was a single centre study at a Tertiary Centre in Central London. The investigative journey for each patient presenting to the Rapid Access Chest Pain Clinic (RACPC) at University College London Hospitals NHS Foundation Trust was recorded. Retrospective analysis on this data was performed.ResultsData for 4968 patients presenting to the RACPC from 2004 to 2012 was analysed and a size-matched cohort of 1503 patients preimplementation and postimplementation of the guidelines was compared. The mean cost of investigations postimplementation was £291.83 as compared to £319.54 preimplementation of the guidelines despite higher costs associated with some of the recommended initial investigations. The mean number of tests per patient postguidelines was 0.78 compared to 0.97 for preguidelines. An approximate twofold increase in patients not requiring tests was seen post-CG95 implementation (245 pre-CG95 vs 476 post-CG95).ConclusionsThe implementation of the NICE guidelines in our trust has reduced the average cost of the investigative journey and the number of investigations required per patient.
Bevacizumab Preconditioning Followed by Etoposide and Cisplatin Is Highly Effective in Treating Brain Metastases of Breast Cancer Progressing from Whole-Brain Radiotherapy
Authors: Lu Yen-Shen , Chen Tom Wei-Wu , Lin Ching-Hung , Yeh Dah-Cherng , Tseng Ling-Ming , Wu Pei-Fang , Rau Kun-Ming , Chen Bang-Bin , Chao Ta-Chung , Huang Shu-Min , Huang Chiun-Sheng , Shih Tiffany Ting-Fang , Cheng Ann-Lii 
Published: February 2015

AbstractPurpose: We hypothesized that a window period between bevacizumab and cytotoxic agents may enhance drug delivery into tumor tissue through bevacizumab-induced vascular normalization in patients with brain metastases of breast cancer (BMBC).Experimental Design: A single-arm phase II study was conducted in which BMBC patients refractory to whole-brain radiotherapy (WBRT) were enrolled. In a 21-day cycle, patients received bevacizumab (15 mg/kg) on day 1, which, with a 1-day window period, was followed by etoposide (70 mg/m2/day; days 2–4) and cisplatin (70 mg/m2; day 2; BEEP regimen). The BEEP regimen was administered for a maximum of 6 cycles. The primary endpoint was the central nervous system (CNS)–objective response rate according to volumetric response criteria.Results: A total of 35 patients were enrolled between January 2011 and January 2013. The median age was 54.3 years (range, 33–75); 19 patients (54.3%) had an Eastern Cooperative Oncology Group performance status of 2 or 3. Twenty-seven patients [77.1%; 95% confidence interval (CI), 59.9–89.6] achieved a CNS-objective response, including 13 patients (37.1%) with a ≥80% volumetric reduction of CNS lesions. With a median follow-up of 16.1 months, the median CNS progression-free survival and overall survival times were 7.3 months (95% CI, 6.5–8.1) and 10.5 months (95% CI, 7.8–13.2), respectively. Common grade 3 or 4 toxicities included neutropenia (30.8%) and infection (21.3%).Conclusions: By administering bevacizumab 1 day before etoposide and cisplatin, the BEEP regimen appeared highly effective in BMBC refractory to WBRT. Further study of vascular normalization window concept is warranted. Clin Cancer Res; 21(8); 1851–8. ©2015 AACR.
Obesity and Fatty Pancreatic Infiltration Are Risk Factors for Pancreatic Precancerous Lesions (PanIN)
Authors: Rebours Vinciane , Gaujoux Sébastien , d'Assignies Gaspard , Sauvanet Alain , Ruszniewski Philippe , Lévy Philippe , Paradis Valérie , Bedossa Pierre , Couvelard Anne 
Published: February 2015

Abstract
Purpose: The roles of intravisceral and subcutaneous fat are unknown, and the prevalence of precancerous lesions in obese patients was never evaluated. This study aims to assess the frequency and severity of pancreatic intraepithelial neoplasia (PanIN) and to correlate pathologic findings with metabolic abnormalities, type of fat, and fatty pancreatic infiltration.
Experimental Design: Normal pancreatic tissue from surgical specimens was analyzed. Fatty infiltration and fibrosis in intra- and extralobular locations and PanIN lesions were assessed. General characteristics were collected: body mass index (BMI), diabetes, and tobacco intake. Liver steatosis and subcutaneous and intravisceral fat were assessed by CT scan (ImageJ software).
Results: Of note, 110 patients were included [median age, 53.8 (17–85) years]. Arterial hypertension, diabetes, and tobacco intake were found in 19%, 9%, and 23%, respectively. Median BMI was 24 (16–37; BMI &lt; 25: 45%, 25 ≤ 30: 24%, ≥30: 11%). Overall, PanIN lesions were found in 65% (type I, II, and III PanIN in 62%, 38%, and 1%, respectively). Fibrosis and fatty pancreas (intra- and extralobular locations) were found in 1% and 24% and in 30% and 51%, respectively. A correlation was observed between PanIN lesions and fatty pancreas [extralobular (0.01) and intralobular (&lt;0.0001)], intralobular fibrosis (0.003), high BMI (P = 0.02), and subcutaneous (P = 0.02) and intravisceral fat (P = 0.02). The number of PanIN lesions was correlated with intravisceral fat (r = 0.22, P = 0.04), but not with subcutaneous fat (r = 0.14, P = 0.22). In multivariate analysis, PanIN lesions were associated with intralobular fibrosis [OR, 5.61; 95% confidence interval (CI), 1.18–42.99] and intralobular fat (OR, 17.86; 95% CI, 4.935–88.12).
Conclusions: Obesity (especially android obesity) and pancreatic fatty infiltration are risk factors for pancreatic precancerous lesions. Clin Cancer Res; 21(15); 3522–8. ©2015 AACR.
See related commentary by Wang et al., p. 3369
Trifluridine Induces p53-Dependent Sustained G2 Phase Arrest with Its Massive Misincorporation into DNA and Few DNA Strand Breaks
Authors: Matsuoka Kazuaki , Iimori Makoto , Niimi Shinichiro , Tsukihara Hiroshi , Watanabe Sugiko , Kiyonari Shinichi , Kiniwa Mamoru , Ando Koji , Tokunaga Eriko , Saeki Hiroshi , Oki Eiji , Maehara Yoshihiko , Kitao Hiroyuki 
Published: February 2015

Abstract
Trifluridine (FTD) is a key component of the novel oral antitumor drug TAS-102, which consists of FTD and a thymidine phosphorylase inhibitor. Like 5-fluoro-2′-deoxyuridine (FdUrd), a deoxynucleoside form of 5-fluorouracil metabolite, FTD is sequentially phosphorylated and not only inhibits thymidylate synthase activity, but is also incorporated into DNA. Although TAS-102 was effective for the treatment of refractory metastatic colorectal cancer in clinical trials, the mechanism of FTD-induced cytotoxicity is not completely understood. Here, we show that FTD as well as FdUrd induce transient phosphorylation of Chk1 at Ser345, and that this is followed by accumulation of p53 and p21 proteins in p53-proficient human cancer cell lines. In particular, FTD induced p53-dependent sustained arrest at G2 phase, which was associated with a proteasome-dependent decrease in the Cyclin B1 protein level and the suppression of CCNB1 and CDK1 gene expression. In addition, a p53-dependent increase in p21 protein was associated with an FTD-induced decrease in Cyclin B1 protein. Although numerous ssDNA and dsDNA breaks were induced by FdUrd, few DNA strand breaks were detected in FTD-treated HCT-116 cells despite massive FTD misincorporation into genomic DNA, suggesting that the antiproliferative effect of FTD is not due to the induction of DNA strand breaks. These distinctive effects of FTD provide insights into the cellular mechanism underlying its antitumor effect and may explain the clinical efficacy of TAS-102. Mol Cancer Ther; 14(4); 1004–13. ©2015 AACR.
P7170: A Novel Molecule with Unique Profile of mTORC1/C2 and Activin Receptor-like Kinase 1 Inhibition Leading to Antitumor and Antiangiogenic Activity
Authors: Jalota-Badhwar Archana , Bhatia Dimple R. , Boreddy Srinivas , Joshi Asavari , Venkatraman Magesh , Desai Nikesh , Chaudhari Sarika , Bose Julie , Kolla Lakshmi S. , Deore Vijaykumar , Yewalkar Nilambari , Kumar Sanjay , Sharma Rajiv , Damre Anagha , More Avinash , Sharma Somesh , Agarwal Veena R. 
Published: February 2015

Abstract
The mTOR pathway is often upregulated in cancer and thus intensively pursued as a target to design novel anticancer therapies. Approved and emerging drugs targeting the mTOR pathway have positively affected the clinical landscape. Recently, activin receptor-like kinase 1 (ALK1), belonging to the TGFβ receptor family, has been reported as an emerging target for antiangiogenic cancer therapy. Here, we describe a novel orally efficacious compound, P7170, that inhibits mTORC1/mTORC2/ALK1 activity with a potent cell growth inhibition. In cell-based assays, P7170 strongly inhibited (IC50 &lt; 10 nmol/L) the phosphorylation of p70S6K (T389) and pAKT (S473). In many cancer cell lines, such as prostate, ovarian, colon, and renal, P7170 treatment resulted in marked cell growth inhibition. Furthermore, it induced G1–S cell-cycle arrest and autophagy. In vitro HUVEC tube formation, in vivo Matrigel plug, and rat aorta ring assays demonstrated that P7170 exhibited significant antiangiogenic activity. In addition, ALK1 knockdown studies in HUVEC confirmed that the antiangiogenic activity of P7170 was primarily due to ALK1 inhibition. Strong inhibition of ALK1 in addition to mTORC1/mTORC2 differentiates P7170 in its mechanism of action in comparison with existing inhibitors. In vivo mouse xenograft studies revealed P7170 to exhibit a significant dose-dependent tumor growth inhibition in a broad range of human tumor types when administered orally at 10 to 20 mg/kg doses. The distinctive pharmacological profile with favorable pharmacokinetic parameters and in vivo efficacy makes P7170 an attractive candidate for clinical development. It is currently being tested in phase I clinical studies. Mol Cancer Ther; 14(5); 1095–106. ©2015 AACR.