bluuebunny/crossref_metadata_2025_split huggingface dataset:
APOBEC3G and APOBEC3F Act in Concert To Extinguish HIV-1 Replication
Authors: Krisko John F. , Begum Nurjahan , Baker Caroline E. , Foster John L. , Garcia J. Victor 
Published: February 2016

ABSTRACT

The multifunctional HIV-1 accessory protein Vif counters the antiviral activities of APOBEC3G (A3G) and APOBEC3F (A3F), and some Vifs counter stable alleles of APOBEC3H (A3H). Studies in humanized mice have shown that HIV-1 lacking Vif expression is not viable. Here, we look at the relative contributions of the three APOBEC3s to viral extinction. Inoculation of bone marrow/liver/thymus (BLT) mice with CCR5-tropic HIV-1
JRCSF
(JRCSF) expressing a
vif
gene inactive for A3G but not A3F degradation activity (JRCSFvifH42/43D) displayed either no or delayed replication. JRCSF expressing a
vif
gene mutated to inactivate A3F degradation but not A3G degradation (JRCSFvifW79S) always replicated to high viral loads with variable delays. JRCSF with
vif
mutated to lack both A3G and A3F degradation activities (JRCSFvifH42/43DW79S) failed to replicate, mimicking JRCSF without Vif expression (JRCSFΔvif). JRCSF and JRCSFvifH42/43D, but not JRCSFvifW79S or JRCSFvifH42/43DW79S, degraded APOBEC3D. With one exception, JRCSFs expressing mutant Vifs that replicated acquired enforced
vif
mutations. These mutations partially restored A3G or A3F degradation activity and fully replaced JRCSFvifH42/43D or JRCSFvifW79S by 10 weeks. Surprisingly, induced mutations temporally lagged behind high levels of virus in blood. In the exceptional case, JRCSFvifH42/43D replicated after a prolonged delay with no mutations in
vif
but instead a V27I mutation in the RNase H coding sequence. JRCSFvifH42/43D infections exhibited massive GG/AG mutations in
pol
viral DNA, but in viral RNA, there were no fixed mutations in the Gag or reverse transcriptase coding sequence. A3H did not contribute to viral extinction but, in combination with A3F, could delay JRCSF replication. A3H was also found to hypermutate viral DNA.

IMPORTANCE
Vif degradation of A3G and A3F enhances viral fitness, as virus with even a partially restored capacity for degradation outgrows JRCSFvifH42/43D and JRCSFvifW79S. Unexpectedly, fixation of mutations that replaced H42/43D or W79S in viral RNA lagged behind the appearance of high viral loads. In one exceptional JRCSFvifH42/43D infection,
vif
was unchanged but replication proceeded after a long delay. These results suggest that Vif binds and inhibits the non-cytosine deaminase activities of intact A3G and intact A3F, allowing JRCSFvifH42/43D and JRCSFvifW79S to replicate with reduced fitness. Subsequently, enhanced Vif function is acquired by enforced mutations. In infected cells, JRCSFΔvif and JRCSFvifH42/43DW79S are exposed to active A3F and A3G and fail to replicate. JRCSFvifH42/43D Vif degrades A3F and, in some cases, overcomes A3G mutagenic activity to replicate. Vif may have evolved to inhibit A3F and A3G by stoichiometric binding and subsequently acquired the ability to target these proteins to proteasomes.
SGLT-2 receptor inhibitors for treating patients with type 2 diabetes mellitus: a systematic review and network meta-analysis
Authors: Shyangdan Deepson S , Uthman Olalekan A , Waugh Norman 
Published: February 2016

ObjectiveBecause of the lack of head-to-head trials, the aim was to indirectly compare sodium glucose transporter-2 (SGLT-2) inhibitors in the treatment of type 2 diabetes.DesignSystematic review and network meta-analysis.Data sourcesMEDLINE and EMBASE were searched from January 2005 to January 2015.Eligibility criteriaRandomised controlled trials assessing the efficacy of SGLT-2 inhibitors in patients with type 2 diabetes inadequately controlled with diet and exercise alone or metformin monotherapy. Minimum duration 24 weeks. Indirect comparison was undertaken using Bayesian methods.ResultsIn monotherapy, a greater proportion of patients achieved a glycated haemoglobin (HbA1c) level of <7% on canagliflozin 300 mg than on canagliflozin 100 mg (risk ratio (RR) 0.72%, 95% credible intervals (CrI) 0.59% to 0.87%) and dapagliflozin 10 mg (RR 0.63, 95% CrI 0.48 to 0.85) but there were no significant differences compared with either dose of empagliflozin. In monotherapy, canagliflozin 300 mg reduced HbA1c more than other SGLT-2 inhibitors (mean difference ranged from 0.20% to 0.64%). There were no significant differences in weight reduction. All the flozins reduced systolic blood pressure (SBP) more than placebo, ranging from a reduction of 6 mm Hg with canagliflozin 300–2.6 mm Hg with empagliflozin 10 mg. In dual therapy with metformin, all flozins were more effective than placebo for achieving HbA1c <7%, and reducing HbA1c, weight and SBP. The proportions achieving HbA1c level of <7% were mostly similar. Canagliflozin 300 mg reduced HbA1c more than the other drugs but this just reached statistical significance only against canagliflozin 100 mg (MD 0.15, CrI 0.04 to 0.26).ConclusionsThere were few differences among the SGLT-2 inhibitors, but in monotherapy, the glucose-lowering effect of canagliflozin 300 mg is slightly greater than most other SGLT-2 inhibitors.
Multilevel assessment of prenatal engagement in home visiting
Authors: Goyal Neera K , Folger Alonzo T , Hall Eric S , Teeters Angelique , Van Ginkel Judith B , Ammerman Robert T 
Published: February 2016

BackgroundLow engagement in prenatal home visiting may limit programme effectiveness to improve birth outcomes. Multiple factors may influence engagement.MethodsA retrospective cohort study of first-time mothers enrolled in home visiting prenatally in southwest Ohio from 2007 to 2010. The primary outcome was enrolment by 20weeks’ gestation; a secondary outcome included home visit frequency. Two multilevel assessments were conducted using random intercept multilevel modelling; maternal covariates were nested first within the home visiting agency and then within the ZIP code. In the first model, variations attributable to individual agency and agency volume were assessed. In the second model nested within the ZIP code, violence rates by ZIP code and interaction terms between violence rates and maternal factors were evaluated.ResultsOf 837 women, 25.3% enrolled ≤20 weeks and 7.4% enrolled early and received ≥75% of expected visits. The first model demonstrated a significant variation in early enrolment based on clustering by agency (p<0.001), however, agency volume was not a significant predictor. In the second model, violence rate was not associated with early enrolment (AOR 0.92, p=0.08), but an interaction term with maternal race was significant (p=0.02). The effect of increasing community violence disproportionately affected early enrolment among white women (AOR 0.80, p=0.005) compared with black women (AOR 0.95, p=0.30). In both the random intercept multilevel models, teenagers demonstrated a decreased likelihood of enrolling early (AOR 0.58, p=0.046 and AOR 0.49, p=0.004).ConclusionsPrenatal home visiting engagement is related to maternal, agency and community factors, presenting multiple opportunities to optimise programme implementation.
Outcrop analogues for hydrocarbon reservoirs in the Columbus Basin, offshore east Trinidad
Authors: Bowman Andrew 
Published: February 2016

Abstract
The Mayaro Formation, which is exposed in SE Trinidad, is the key outcrop analogue for prolific hydrocarbon reservoirs in the Columbus Basin, offshore east Trinidad, because it was deposited in the same basin setting by the same depositional system (the palaeo-Orinoco) as the offshore reservoirs. Sequence and parasequence stacking patterns affect the distribution of different types of reservoir sand bodies and heterogeneities, with the potential to influence fluid flow in subsurface hydrocarbon reservoirs. Spectacular outcrops of successions of storm-wave-influenced sand bodies, tens to hundreds of metres thick, deposited in axial and medial delta-lobe settings are characterized by high sand–shale ratios (0.7–>0.95), and are analogues for many producing reservoirs in the basin. Fluvial- and tide-influenced sand bodies deposited in distal distributary settings are also recognized in the outcrops, but may be difficult to distinguish from medial delta-lobe deposits in subsurface data. More complex, thinly bedded distal delta-lobe deposits, with subsurface reservoir potential, exhibit lower sand–shale ratios (0.3–0.6). Complex depositional architectures, with a high proportion of thinly bedded sandstones, also occur in association with delta-front deposits. The distal delta-lobe and delta-front deposits are analogous to some of the most challenging to develop reservoirs in the Columbus Basin.
Modification and Validation of Priestley–Taylor Model for Estimating Cotton Evapotranspiration under Plastic Mulch Condition
Authors: Ai Zhipin , Yang Yonghui 
Published: February 2016

AbstractCompared with more comprehensive physical algorithms such as the Penman–Monteith model, the Priestley–Taylor model is widely used in estimating evapotranspiration for its robust ability to capture evapotranspiration and simplicity of use. The key point in successfully using the Priestley–Taylor model is to find a proper Priestley–Taylor coefficient, which is variable under different environmental conditions. Based on evapotranspiration partition and plant physiological limitation, this study developed a new model for estimating the Priestley–Taylor coefficient incorporating the effects of three easily obtainable parameters such as leaf area index (LAI), air temperature, and mulch fraction. Meanwhile, the effects of plastic film on the estimation of net radiation and soil heat flux were fully considered. The reliability of the modified Priestley–Taylor model was testified using observed cotton evapotranspiration from eddy covariance in two growing seasons, with high coefficients of determination of 0.86 and 0.81 in 2013 and 2014, respectively. Then, the modified model was further validated by estimating cotton evapotranspiration under three fractions of mulch cover: 0%, 60%, and 100%. The estimated values agreed well with the measured values via water balance analysis. It can be found that seasonal variation of the modified Priestley–Taylor coefficient showed a more reasonable pattern compared with the original coefficient of 1.26. Sensitivity analysis showed that the modified Priestley–Taylor coefficient was more sensitive to LAI than to air temperature. Overall, the modified model has much higher accuracy and could be used for evapotranspiration estimation under plastic mulch condition.
The effect of pulsatile cardiopulmonary bypass on the need for haemofiltration in patients with renal dysfunction undergoing cardiac surgery
Authors: Farid Shakil , Povey Hannah , Anderson Simon , Nashef Samer A M , Abu-Omar Yasir 
Published: February 2016

Objectives: The aim of our study was to investigate the effects of pulsatile cardiopulmonary bypass (CPB) on renal function and the need for haemofiltration in patients with preoperative renal impairment undergoing cardiac surgery. Methods: Clinical data were collected prospectively for patients undergoing cardiac surgery with pulsatile CPB (Group A, n=66) and compared to matched patients with standard non-pulsatile CPB (Group B, n=66). Patients included in the study had mild renal impairment and at least moderate risk from surgery as defined by logistic EuroSCORE. Emergency operations were excluded. Results: Patients in Groups A and B had similar age (71 ± 10 versus 70 ± 10 years), sex distribution, mean preoperative renal function (creatinine clearance 63.9 ± 28 versus 67.7 ± 27.3 ml/min) and overall risk profile as predicted by the logistic EuroSCORE (8 ± 8.3 versus 11.05±13.3, p=0.122). Intraoperative variables were comparable with respect to bypass and cross-clamp times (96 ± 37 minutes and 64 ± 28 minutes versus 103 ± 40 minutes and 70 ± 33 minutes in Groups A and B, respectively). A smaller proportion of patients in Group A (4.5% versus 15%, p=0.076) required haemofiltration in the postoperative period. Postoperative mortality was low in both groups (Group A 1.54% versus Group B 3.03%, p=1.00). Conclusion: Within the limitations imposed by retrospective analyses, our study demonstrates that pulsatile CPB may confer a reno-protective effect in higher-risk patients with pre-existing mild renal dysfunction undergoing cardiac surgery.
The relation between clinical scores and quality-of-life in long-term follow-up
Authors: Catarinella Fabio S , Nieman Fred HM , Wittens Cees HA 
Published: February 2016

Introduction Quality-of-life and severity scores are both popular measures in medicine. For deep venous obstruction, the VEINES-QOL/Sym and venous clinical severity score (VCSS) are widely used. Combining a patient-reported outcome with a clinical severity score should give a more sensitive outcome for treatment results. To establish and compare their suitability for deep venous disease, we compared the outcomes of both scores in a group of patients who were interventionally treated for deep venous disease. Methods The venous clinical severity scores and VEINES-QOL/Sym scores of a group of patients who had received interventional treatment for deep venous obstruction more than 12 months ago were compared at T0 and T12. Results Both the Spearman’s rho and Pearson’s r show a very weak, negative correlation (statistically significant ( p ≤ 0.05)), between the venous clinical severity score and VEINES-QOL at T12 and between the venous clinical severity score and the VEINES-SYM at both T0 and T12. T0 VCSS-VSYM: rho = −0.219 ( p = 0.052), r = −0.236 ( p = 0.037), T12 VCSS-VQOL: rho = −0.459 ( p = 0.007), r = −0.379 ( p = 0.030), T12 VCSS-VSYM: rho = −0.463 ( p = 0.007), r = −0.432 ( p = 0.012). This negative correlation was not statistically ( p ≥ 0.05) confirmed for T0 VCSS-VSYM. Conclusion The physician-scored venous clinical severity score of patients treated for deep venous obstruction does not correlate well with their self-reported quality-of-life and symptom scores.
A prospective comparison of a new cyanoacrylate glue and laser ablation for the treatment of venous insufficiency
Authors: Bozkurt Ahmet Kürşat , Yılmaz Muhammet Fatih 
Published: February 2016

Introduction Cyanoacrylate ablation is the newest nonthermal vein ablation technique. The one-year results of a prospective comparative study of a new cyanoacrylate glue versus endovenous laser ablation for the treatment of venous insufficiency is presented. Material and methods A total of 310 adult subjects were treated with cyanoacrylate ablation or endovenous laser ablation. The primary endpoint of this study was complete occlusion of the great saphenous vein. Secondary endpoints were procedure time, procedural pain, ecchymosis at day 3, adverse events, changes from baseline in Venous Clinical Severity Score, and Aberdeen Varicose Vein Questionnaire. Results Operative time was shorter (15 ± 2.5 versus 33.2 ± 5.7, <0.001), and periprocedural pain was less (3.1 ± 1.6 versus 6.5 ± 2.3, <0.001) in cyanoacrylate ablation group compared to the endovenous laser ablation group. Ecchymosis at the third day was also significantly less in cyanoacrylate ablation group (<0.001). Temporary or permanent paresthesia developed in seven patients in endovenous laser ablation group and none in cyanoacrylate ablation group (p = 0.015). One, three, and 12 months closure rates were 87.1, 91.7, and 92.2% for endovenous laser ablation and 96.7, 96.6, and 95.8% for cyanoacrylate ablation groups. Closure rate at first month was significantly better in cyanoacrylate ablation group (<0.001). Although there is a trend of better closure rates in cyanoacrylate ablation patients, this difference did not reach to the statistical difference at sixth and 12th month (p = 0.127 and 0.138, respectively). Both groups had significant improvement in Venous Clinical Severity Score and Aberdeen Varicose Vein Questionnaire postoperatively (<0.001), but there was no significant difference in Venous Clinical Severity Score and Aberdeen Varicose Vein Questionnaire scores between the groups at first, sixth, and 12 months. Only a slightly better well-being trend was noted in cyanoacrylate ablation group in terms of Aberdeen Varicose Vein Questionnaire scores (p = 0.062). Conclusions The efficacy and safety analysis shows that cyanoacrylate ablation is a safe, simple method which can be recommended as an effective endovenous ablation technique. The follow-up data more than one year will clarify the future role of cyanoacrylate ablation for the treatment incompetent great saphenous veins.
The aging psychiatrist: lessons from our colleagues in surgery and anaesthesia
Authors: Waxman Bruce Philip 
Published: February 2016

Objectives: The Royal Australasian College of Surgeons (RACS) has been innovative in developing core competencies, which provide a framework for assessing performance and a ‘Code of Conduct’, for the lifelong journey of all surgeons. The older surgeon may face significant challenges, having passed their peak, with a lower volume of cases, and potentially increased complications. They also face the challenges of retiring from active clinical practice with its logistical and psychological dilemmas. The RACS has, therefore, put in place several initiatives to deal with these dilemmas. Conclusions: The Senior Surgeons’ Group, which conducts annual ‘Building Towards Retirement’ workshops, has been the driving force behind these initiatives. The group has a regular program in the RACS Annual Scientific Congress, including the multidisciplinary session ‘The ageing specialist - challenges for regulators: hypothetical’ which took place in 2014, and some of its members are part of a multidisciplinary team with an approach to adapting to ageing that encourages self-reflection and self-monitoring. It has also influenced the RACS Council to change the continuing professional development (CPD) regulations to include requirements for ageing surgeons regards health maintenance, peer reviews, and modified requirements to satisfy CPD completion. The RACS offers a variety of other opportunities for the ageing surgeon to remain active in college activities.
Flipped script for gefitinib: A reapproved tyrosine kinase inhibitor for first-line treatment of epidermal growth factor receptor mutation positive metastatic nonsmall cell lung cancer
Authors: Bogdanowicz Brian S , Hoch Matthew A , Hartranft Megan E 
Published: February 2016

Purpose The approval history, pharmacology, pharmacokinetics, clinical trials, efficacy, dosing recommendations, drug interactions, safety, place in therapy, and economic considerations of gefitinib are reviewed. Summary Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer death. Platinum-based chemotherapy and tyrosine kinase inhibitors, such as erlotinib and afatinib, are recommended therapies for nonsmall cell lung cancer. The European Medicines Association based their approval of gefitinib on the randomized, multicenter Iressa Pan-Asia Study (IPASS, NCT00322452) and a single-arm study showing effectiveness in Caucasians (IFUM, NCT01203917). Both studies were recently referenced by the United States Food & Drug Administration to reapprove gefitinib for the first-line treatment of advanced nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 substitution. Diarrhea, acneiform rash, and interstitial lung disease are known side effects of gefitinib. Conclusion Use of gefitinib for the first-line therapy of metastatic nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions (residues 747–750) or exon 21 substitution mutation (L858R) is well-documented and supported.
Expression of TGF-β Signaling Regulator RBPMS (RNA-Binding Protein With Multiple Splicing) Is Regulated by IL-1β and TGF-β Superfamily Members, and Decreased in Aged and Osteoarthritic Cartilage
Authors: Shanmugaapriya S. , van Caam A. , de Kroon L. , Vitters Elly L. , Walgreen B , van Beuningen H. , Davidson E. Blaney , van der Kraan Peter M. 
Published: February 2016

Objective RNA-binding protein with multiple splicing (RBPMS) has been shown to physically interact with Smads and enhance transforming growth factor-β (TGF-β)–mediated Smad2/3 transcriptional activity in mammalian cells. Objective of this study was to examine whether expression of RBPMS is regulated by interleukin-1β (IL)-1β and TGF-β superfamily growth factors and whether expression of RBPMS is altered during aging and experimental osteoarthritis. Methods Expression of RBPMS protein was investigated in chondrocyte cell lines of murine (H4) and human (G6) origin using Western blot analysis. Regulation of RBPMS expression in H4 chondrocytes at mRNA level was done by reverse transcriptase–quantitative polymerase chain reaction. Furthermore, characterization of Smad signaling pathways regulating RBPMS expression was performed by blocking studies using small molecule inhibitors or by transfection studies with adenoviral vector constructs (constitutive-active ALK1 and constitutive-active ALK5). Expression of RBPMS in cartilage of different age groups of C57BL/6N mice (6 months and 20 months) and in a surgically induced osteoarthritis (OA) mouse model was analyzed using immunohistochemistry. Results RBPMS was shown to be expressed in chondrocytes and cartilage of murine, human, and bovine origin. TGF-β inhibited RBPMS expression while BMP2 and IL-1β increased its expression. TGF-β-induced inhibition was blocked by ALK5 inhibitor. Overexpression of ca-ALK1 stimulated RBPMS expression. Moreover, RBPMS expression was found to be reduced with ageing and in OA pathogenesis. Conclusions Expression of RBPMS in chondrocytes is regulated by TGF-β superfamily members and IL-1β, indicating a counter-regulatory mechanism. Expression of RBPMS, in cartilage and its reduction during ageing and OA might suggest its potential role in the maintenance of normal articular cartilage.
A gain-of-function variant in DIAPH1 causes dominant macrothrombocytopenia and hearing loss
Authors: Stritt Simon , Nurden Paquita , Turro Ernest , Greene Daniel , Jansen Sjoert B. , Westbury Sarah K. , Petersen Romina , Astle William J. , Marlin Sandrine , Bariana Tadbir K. , Kostadima Myrto , Lentaigne Claire , Maiwald Stephanie , Papadia Sofia , Kelly Anne M. , Stephens Jonathan C. , Penkett Christopher J. , Ashford Sofie , Tuna Salih , Austin Steve , Bakchoul Tamam , Collins Peter , Favier Rémi , Lambert Michele P. , Mathias Mary , Millar Carolyn M. , Mapeta Rutendo , Perry David J. , Schulman Sol , Simeoni Ilenia , Thys Chantal ,   BRIDGE-BPD Consortium, Gomez Keith , Erber Wendy N. , Stirrups Kathleen , Rendon Augusto , Bradley John R. , van Geet Chris , Raymond F. Lucy , Laffan Michael A. , Nurden Alan T. , Nieswandt Bernhard , Richardson Sylvia , Freson Kathleen , Ouwehand Willem H. , Mumford Andrew D. 
Published: February 2016

Key PointsA gain-of-function variant in DIAPH1 causes macrothrombocytopenia and hearing loss and extends the spectrum of DIAPH1-related disease. Our findings of altered megakaryopoiesis and platelet cytoskeletal regulation highlight a critical role for DIAPH1 in platelet formation.