bluuebunny/crossref_metadata_2025_split huggingface dataset:
l-Hydroxyproline andd-Proline Catabolism in Sinorhizobium meliloti
Authors: Chen Siyun , White Catharine E. , diCenzo George C. , Zhang Ye , Stogios Peter J. , Savchenko Alexei , Finan Turlough M. 
Published: February 2016

ABSTRACTSinorhizobium melilotiforms N2-fixing root nodules on alfalfa, and as a free-living bacterium, it can grow on a very broad range of substrates, includingl-proline and several related compounds, such as proline betaine,trans-4-hydroxy-l-proline (trans-4-l-Hyp), andcis-4-hydroxy-d-proline (cis-4-d-Hyp). Fourteenhypgenes are induced upon growth ofS. melilotiontrans-4-l-Hyp, and of those,hypMNPQencodes an ABC-typetrans-4-l-Hyp transporter andhypREencodes an epimerase that convertstrans-4-l-Hyp tocis-4-d-Hyp in the bacterial cytoplasm. Here, we present evidence that the HypO, HypD, and HypH proteins catalyze the remaining steps in whichcis-4-d-Hyp is converted to α-ketoglutarate. The HypO protein functions as ad-amino acid dehydrogenase, convertingcis-4-d-Hyp to Δ1-pyrroline-4-hydroxy-2-carboxylate, which is deaminated by HypD to α-ketoglutarate semialdehyde and then converted to α-ketoglutarate by HypH. The crystal structure of HypD revealed it to be a member of theN-acetylneuraminate lyase subfamily of the (α/β)8protein family and is consistent with the known enzymatic mechanism for other members of the group. It was also shown thatS. melilotican catabolized-proline as both a carbon and a nitrogen source, thatd-proline can complementl-proline auxotrophy, and that the catabolism ofd-proline is dependent on thehypcluster. Transport ofd-proline involves the HypMNPQ transporter, following whichd-proline is converted to Δ1-pyrroline-2-carboxylate (P2C) largely via HypO. The P2C is converted tol-proline through the NADPH-dependent reduction of P2C by the previously uncharacterized HypS protein. Thus, overall, we have now completed detailed genetic and/or biochemical characterization of 9 of the 14hypgenes.IMPORTANCEHydroxyproline is abundant in proteins in animal and plant tissues and serves as a carbon and a nitrogen source for bacteria in diverse environments, including the rhizosphere, compost, and the mammalian gut. While the main biochemical features of bacterial hydroxyproline catabolism were elucidated in the 1960s, the genetic and molecular details have only recently been determined. Elucidating the genetics of hydroxyproline catabolism will aid in the annotation of these genes in other genomes and metagenomic libraries. This will facilitate an improved understanding of the importance of this pathway and may assist in determining the prevalence of hydroxyproline in a particular environment.
Supporting breastfeeding In Local Communities (SILC) in Victoria, Australia: a cluster randomised controlled trial
Authors: McLachlan Helen L , Forster Della A , Amir Lisa H , Cullinane Meabh , Shafiei Touran , Watson Lyndsey F , Ridgway Lael , Cramer Rhian L , Small Rhonda 
Published: February 2016

ObjectivesBreastfeeding has significant health benefits for mothers and infants. Despite recommendations from the WHO, by 6 months of age 40% of Australian infants are receiving no breast milk. Increased early postpartum breastfeeding support may improve breastfeeding maintenance. 2 community-based interventions to increase breastfeeding duration in local government areas (LGAs) in Victoria, Australia, were implemented and evaluated.Design3-arm cluster randomised trial.SettingLGAs in Victoria, Australia.ParticipantsLGAs across Victoria with breastfeeding initiation rates below the state average and > 450 births/year were eligible for inclusion. The LGA was the unit of randomisation, and maternal and child health centres in the LGAs comprised the clusters.InterventionsEarly home-based breastfeeding support by a maternal and child health nurse (home visit, HV) with or without access to a community-based breastfeeding drop-in centre (HV+drop-in).Main outcome measuresThe proportion of infants receiving ‘any’ breast milk at 3, 4 and 6 months (women's self-report).Findings4 LGAs were randomised to the comparison arm and provided usual care (n=41 clusters; n=2414 women); 3 to HV (n=32 clusters; n=2281 women); and 3 to HV+drop-in (n=26 clusters; 2344 women). There was no difference in breastfeeding at 4 months in either HV (adjusted OR 1.04; 95% CI 0.84 to 1.29) or HV+drop-in (adjusted OR 0.92; 95% CI 0.78 to 1.08) compared with the comparison arm, no difference at 3 or 6 months, nor in any LGA in breastfeeding before and after the intervention. Some issues were experienced with intervention protocol fidelity.ConclusionsEarly home-based and community-based support proved difficult to implement. Interventions to increase breastfeeding in complex community settings require sufficient time and partnership building for successful implementation. We cannot conclude that additional community-based support is ineffective in improving breastfeeding maintenance given the level of adherence to the planned protocol.Trial registration numberACTRN12611000898954; Results.
Association of chronic insomnia symptoms and recurrent extreme sleep duration over 10 years with well-being in older adults: a cohort study
Authors: Abell Jessica G , Shipley Martin J , Ferrie Jane E , Kivimäki Mika , Kumari Meena 
Published: February 2016

ObjectivesThe extent to which aspects of sleep affect well-being in the long-term remains unclear. This longitudinal study examines the association between chronic insomnia symptoms, recurrent sleep duration and well-being at older ages.SettingA prospective cohort of UK civil servants (the Whitehall II study).Participants4491 women and men (25.2% women) with sleep measured 3 times over 10 years and well-being once at age 55–79 years. Insomnia symptoms and sleep duration were assessed through self-reports in 1997–1999, 2003–2004 and 2007–2009.Primary outcome measuresIndicators of well-being, measured in 2007–2009, were the Control, Autonomy, Self-realisation and Pleasure measure (CASP-19) of overall well-being (range 0–57) and the physical and mental well-being component scores (range 0–100) of the Short Form Health Survey (SF-36).ResultsIn maximally adjusted analyses, chronic insomnia symptoms were associated with poorer overall well-being (difference between insomnia at 3 assessments vs none −7.0 (SE=0.4) p<0.001), mental well-being (difference −6.9 (SE=0.4), p<0.001) and physical well-being (difference −2.8 (SE=0.4), p<0.001) independently of the other sleep measures. There was a suggestion of a dose–response pattern in these associations. In addition, recurrent short sleep (difference between ≤5 h sleep reported at 3 assessments vs none −1.7 (SE=0.7), p<0.05) and recurrent long sleep (difference between >9 h reported at 2 or 3 assessments vs none −3.5 (SE=0.9), p<0.001) were associated with poorer physical well-being.ConclusionsWe conclude that in older people, chronic insomnia symptoms are negatively associated with all aspects of well-being, whereas recurrent long and short sleep is only associated with reduced physical well-being.
Preferences for engagement in health technology assessment decision-making: a nominal group technique with members of the public
Authors: Wortley Sally , Tong Allison , Howard Kirsten 
Published: February 2016

ObjectiveTo identify characteristics (factors) about health technology assessment (HTA) decisions that are important to the public in determining whether public engagement should be undertaken and the reasons for these choices.DesignFocus groups using a nominal group technique to identify and rank factors relevant to public engagement in HTA decision-making. Thematic analysis was also undertaken to describe reasons underpinning participants’ choices and rankings.SettingMembers of the Australian general public.Participants58 people, aged 19–71 years participated in 6 focus groups.Results24 factors were identified by participants that were considered important in determining whether public engagement should be undertaken. These factors were individually ranked and grouped into 4 themes to interpret preferences for engagement. Members of the public were more likely to think public engagement was needed when trade-offs between benefits and costs were required to determine ‘value’, uncertainties in the evidence were present, and family members and/or carers were impacted. The role of public engagement was also seen as important if the existent system lacked transparency and did not provide a voice for patients, particularly for conditions less known in the community.ConclusionsMembers of the public considered value, impact, uncertainty, equity and transparency in determining when engagement should be undertaken. This indicates that the public's preferences on when to undertake engagement relate to both the content of the HTA itself as well as the processes in place to support HTA decision-making. By understanding these preferences, decision-makers can work towards more effective, meaningful public engagement by involving the public in issues that are important to them and/or improving the processes around decision-making.
ADding negative pRESSure to improve healING (the DRESSING trial): a RCT protocol
Authors: Gillespie Brigid M , Webster Joan , Ellwood David , Stapleton Helen , Whitty Jennifer A , Thalib Lukman , Cullum Nicky , Mahomed Kassam , Chaboyer Wendy 
Published: February 2016

IntroductionObese women are more likely to develop a surgical site infection (SSI) following caesarean section (CS) than non-obese women. Negative pressure wound therapy (NPWT) is increasingly being used to reduce SSI with limited evidence for its effectiveness.ObjectivesTo determine the clinical and cost-effectiveness of using NPWT in obese women having elective and semiurgent CS.Methods and analysisA multisite, superiority parallel pragmatic randomised controlled trial with an economic evaluation. Women with a body mass index (BMI) of ≥30, booked for elective and semiurgent CS at 4 Australian acute care hospitals will be targeted. A total of 2090 women will be enrolled. A centralised randomisation service will be used with participants block randomised to either NPWT or standard surgical dressings in a 1:1 ratio, stratified by hospital. The primary outcome is SSI; secondary outcomes include type of SSI, length of stay, readmission, wound complications and health-related quality of life. Economic outcomes include direct healthcare costs and cost-effectiveness, which will be evaluated using incremental cost per quality-adjusted life year gained. Data will be collected at baseline, and participants followed up on the second postoperative day and weekly from the day of surgery for 4 weeks. Outcome assessors will be masked to allocation. The primary statistical analysis will be based on intention-to-treat.Ethics and disseminationEthics approval has been obtained from the ethics committees of the participating hospitals and universities. The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations.Trial registration numberACTRN12615000286549; Pre-results.
Hybrid simulation compared to manikin alone in teaching pelvic examinations: a randomised control trial
Authors: Manley Kristyn , Edwards Sian , Mears Jane , Siassakos Dimitrios 
Published: February 2016

IntroductionPerforming a pelvic examination is a core skill for all medical undergraduates. The use of hybrid simulation, manikin with patient actress, to attain technical and communication skills competencies and to improve the quality of care we offer women, has not been compared to other teaching methods before. Outcome measures were technical skills, communication skills and confidence in completing a pelvic examination.MethodsA cluster randomised control trial was conducted over an academic year. Forty-eight medical students who completed an 8-week obstetrics and gynaecology attachment were recruited. Clusters were randomly assigned for initial training on hybrid or manikin only models and attended an end of attachment Objective Structured Clinical Assessment.ResultsOutcome data were received for 43/48 students (89.5%). Following the objectively structured clinical examination, the hybrid trained cohort had higher technical scores (mean 23 (95% CI 20.1 to 25.8) vs 16.7 (CI 14.7 to 18.6); mean difference 6.3, CI 3.0 to 9.6) and communication skills scores (mean 22.6 (CI 21.2 to 23.8) vs 15.9 (CI 14.4 to 17.3); mean difference 6.7, CI 4.8 to 8.5) compared to the manikin only trained participants. Confidence in undertaking future pelvic examinations were similar in the control and intervention groups; (p=0.10, r=0.18).ConclusionsThis study demonstrates the value of hybrid simulation compared to manikins alone in improving the short-term acquisition of competence in simulated pelvic examinations at an undergraduate level. Future research should focus on whether hybrid models lead to long-term acquisition of skill and comparison of these models with other innovative methods such as clinical teaching associates.
Association of diethylhexyl phthalate with obesity-related markers and body mass change from birth to 3 months of age
Authors: Kim Jin Hee , Park Hyunkyung , Lee Jangwoo , Cho Geumjoon , Choi Sooran , Choi Gyuyeon , Kim Su Young , Eun So-Hee , Suh Eunsook , Kim Sung Koo , Kim Hai-Joong , Kim Gun-Ha , Lee Jeong Jae , Kim Young Don , Eom Soyong , Kim Seunghyo , Moon Hyo-Bang , Park Jeongim , Choi Kyungho , Kim Sungjoo , Kim Sungkyoon 
Published: February 2016

BackgroundSeveral studies have suggested potential links of phthalates to obesity in children and adults. Limited evidence, however, has been available for the relations between diethylhexyl phthalate (DEHP) and obesity-related markers or body mass change in early life.Methods128 healthy pregnant women were recruited and, after delivery, their newborns’ first urine and umbilical cord blood samples were collected. We measured urinary levels of two DEHP metabolites, mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). We also measured the levels of leptin, total cholesterol and triglyceride (TG) in cord serum, and used them along with weight, length, head circumference and ponderal index (PI, 100 g/cm3) at birth, as obesity-related markers, and estimated the relations between DEHP metabolites and obesity-related markers using generalised linear models. For the evaluation of body mass increase by early life DEHP exposure, body mass index (BMI) z-score change during 3 months after birth by DEHP metabolites in the first urine samples of the newborns were evaluated using logistic regression.ResultsDEHP exposure was associated with decrease of PI and increase of TG (PI, β=−0.11, p=0.070 and TG, β=0.14, p=0.027), especially for boys (PI, β=−0.13, p=0.021; and TG, β=0.19, p=0.025). Moreover, DEHP exposure was positively associated with body mass increase during 3 months after birth (change of BMI z-scores, OR=4.35, p=0.025).ConclusionsOur findings suggest that DEHP exposure may affect body mass change in early life through changes of obesity-related markers.
Longer procedural times are independently associated with symptomatic intracranial hemorrhage in patients with large vessel occlusion stroke undergoing thrombectomy
Authors: Kass-Hout Tareq , Kass-Hout Omar , Sun Chung-Huan Johnny , Kass-Hout Taha A , Nogueira Raul , Gupta Rishi 
Published: February 2016

BackgroundTime to reperfusion is an essential factor in determination of outcomes in acute ischemic stroke (AIS).ObjectiveTo establish the effect of the procedural time on the clinical outcomes of patients with AIS.MethodsData from all consecutive patients who underwent mechanical thrombectomy between September 2010 and July 2012 were analysed retrospectively. The variable of interest was procedural time (defined as time from groin puncture to final recanalization time). Outcome measures included the rates of symptomatic intracranial hemorrhage (sICH, defined as any parenchymal hematoma—eg, PH-1/PH-2), final infarct volume, 90-day mortality, and independent functional outcomes (modified Rankin Scale 0–2) at 90 days.ResultsThe cohort included 242 patients with a mean age of 65.5±14.2 and median baseline National Institutes of Health Stroke Scale score 20. 51% of the patients were female. The mean procedure time was significantly shorter in patients with a good outcome (86.7 vs 73.1 min, respectively, p=0.0228). Patients with SICH had significantly higher mean procedure time than patients without SICH (79.67 vs 104.5 min, respectively; p=0.0319), which remained significant when controlling for the previous factors (OR=0.974, 95% CI 0.957 to 0.991). No correlation was found between the volume of infarction and the procedure time (r=0.10996, p=0.0984). No association was seen between procedure time and 90-day mortality (77.8 vs 88.2 min in survivals vs deaths, respectively; p=0.0958).ConclusionsOur data support an association between the risk of SICH and a longer procedure time, but no association between procedural times and the final infarction volume or long-term functional outcomes was found.
Social Role Participation Questionnaire for patients with ankylosing spondylitis: translation into Dutch, reliability and construct validity
Authors: van Genderen Simon , Plasqui Guy , Lacaille Diane , Arends Suzanne , van Gaalen Floris , van der Heijde Désirée , Heuft Liesbeth , Keszei András , Luime Jolanda , Spoorenberg Anneke , Landewé Robert , Gignac Monique , Boonen Annelies 
Published: February 2016

ObjectiveThe Social Role Participation Questionnaire (SRPQ) assesses the influence of health on participation in 11 specific and one general participation role across 4 participation dimensions: ‘importance’, ‘satisfaction with time’, ‘satisfaction with performance’ and ‘physical difficulty’. This study aimed to translate the SRPQ into Dutch, and assess the clinimetric properties and aspects of its validity among patients with ankylosing spondylitis (AS).MethodsTranslation was performed using the dual panel approach. For each participation dimension, internal consistency, test-retest reliability (n=31), and construct validity were assessed in 246 patients with AS.ResultsThe translation required only minor adaptations. Cronbach αs were α≥0.7. A strong correlation was present between satisfaction with ‘time’ and ‘performance’(r=0.85). Test-retest reliability was satisfactory (κ=0.79–0.95). Correlations with participation domains of the Short-Form Health Survey 36 (SF-36), the WHO Disease Assessment Score II, and generic as well as disease-specific health outcomes (Physical and Mental component scale of the SF-36, Satisfaction With Life Scale, Bath Ankylosing Spondylitis Disease Index (BASDAI), Bath Ankylosing Spondylitis Functioning Index (BASFI)) were at least moderate (r=−0.41 to 0.75) for all dimensions except for ‘role importance’ where correlations were weak (r≤40). Discriminative ability across 5 self-reported health states was good for all dimensions (p<0.01). The ‘general participation’ role showed similar reliability and validity for each dimension, as the average of the all 11 roles.ConclusionsThe Dutch version of the SRPQ is available to help understand social role participation of patients with AS. The dimension ‘role importance’ measures a distinct aspect of participation. The general participation item was a good global measure of participation.
The Ephrin-A1/EPHA2 Signaling Axis Regulates Glutamine Metabolism in HER2-Positive Breast Cancer
Authors: Youngblood Victoria M. , Kim Laura C. , Edwards Deanna N. , Hwang Yoonha , Santapuram Pranav R. , Stirdivant Steven M. , Lu Pengcheng , Ye Fei , Brantley-Sieders Dana M. , Chen Jin 
Published: February 2016

Abstract
Dysregulation of receptor tyrosine kinases (RTK) contributes to cellular transformation and cancer progression by disrupting key metabolic signaling pathways. The EPHA2 RTK is overexpressed in aggressive forms of breast cancer, including the HER2+ subtype, and correlates with poor prognosis. However, the role of EPHA2 in tumor metabolism remains unexplored. In this study, we used in vivo and in vitro models of HER2-overexpressing breast cancer to investigate the mechanisms by which EPHA2 ligand–independent signaling promotes tumorigenesis in the absence of its prototypic ligand, ephrin-A1. We demonstrate that ephrin-A1 loss leads to upregulated glutamine metabolism and lipid accumulation that enhanced tumor growth. Global metabolic profiling of ephrin-A1–null, HER2-overexpressing mammary tumors revealed a significant increase in glutaminolysis, a critical metabolic pathway that generates intermediates for lipogenesis. Pharmacologic inhibition of glutaminase activity reduced tumor growth in both ephrin-A1–depleted and EPHA2-overexpressing tumor allografts in vivo. Mechanistically, we show that the enhanced proliferation and glutaminolysis in the absence of ephrin-A1 were attributed to increased RhoA-dependent glutaminase activity. EPHA2 depletion or pharmacologic inhibition of Rho, glutaminase, or fatty acid synthase abrogated the increased lipid content and proliferative effects of ephrin-A1 knockdown. Together, these findings highlight a novel, unsuspected connection between the EPHA2/ephrin-A1 signaling axis and tumor metabolism, and suggest potential new therapeutic targets in cancer subtypes exhibiting glutamine dependency. Cancer Res; 76(7); 1825–36. ©2016 AACR.
Abscopal Benefits of Localized Radiotherapy Depend on Activated T-cell Trafficking and Distribution between Metastatic Lesions
Authors: Poleszczuk Jan T. , Luddy Kimberly A. , Prokopiou Sotiris , Robertson-Tessi Mark , Moros Eduardo G. , Fishman Mayer , Djeu Julie Y. , Finkelstein Steven E. , Enderling Heiko 
Published: February 2016

Abstract
It remains unclear how localized radiotherapy for cancer metastases can occasionally elicit a systemic antitumor effect, known as the abscopal effect, but historically, it has been speculated to reflect the generation of a host immunotherapeutic response. The ability to purposefully and reliably induce abscopal effects in metastatic tumors could meet many unmet clinical needs. Here, we describe a mathematical model that incorporates physiologic information about T-cell trafficking to estimate the distribution of focal therapy–activated T cells between metastatic lesions. We integrated a dynamic model of tumor–immune interactions with systemic T-cell trafficking patterns to simulate the development of metastases. In virtual case studies, we found that the dissemination of activated T cells among multiple metastatic sites is complex and not intuitively predictable. Furthermore, we show that not all metastatic sites participate in systemic immune surveillance equally, and therefore the success in triggering the abscopal effect depends, at least in part, on which metastatic site is selected for localized therapy. Moreover, simulations revealed that seeding new metastatic sites may accelerate the growth of the primary tumor, because T-cell responses are partially diverted to the developing metastases, but the removal of the primary tumor can also favor the rapid growth of preexisting metastatic lesions. Collectively, our work provides the framework to prospectively identify anatomically defined focal therapy targets that are most likely to trigger an immune-mediated abscopal response and therefore may inform personalized treatment strategies in patients with metastatic disease. Cancer Res; 76(5); 1009–18. ©2016 AACR.