bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment‐naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II)
Authors: Zeuzem S. , Flisiak R. , Vierling J. M. , Mazur W. , Mazzella G. , Thongsawat S. , Abdurakhmanov D. , Van Kính N. , Calistru P. , Heo J. , Stanciu C. , Gould M. , Makara M. , Hsu S.‐J. , Buggisch P. , Samuel D. , Mutimer D. , Nault B. , Merz M. , Bao W. , Griffel L. H. , Brass C. , Naoumov N. V. ,   the ESSENTIAL II Study Group
Published: August 2015

SummaryBackgroundAlisporivir (ALV) is an oral, host‐targeting agent with pangenotypic anti‐hepatitis C virus (HCV) activity and a high barrier to resistance.AimTo evaluate efficacy and safety of ALV plus peginterferon‐α2a and ribavirin (PR) in treatment‐naïve patients with chronic HCV genotype 1 infection.MethodsDouble‐blind, randomised, placebo‐controlled, Phase 3 study evaluating ALV 600 mg once daily [response‐guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy.ResultsA total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose‐dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension.ConclusionsAlisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment‐naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon‐free combination regimens.
Screening and Identification of Inhibitors of Trypanosoma brucei Cathepsin L with Antitrypanosomal Activity
Authors: Jefferson Tierra , McShan Danielle , Warfield Jasmine , Ogungbe Ifedayo Victor 
Published: August 2015

Current treatment options for human African trypanosomiasis (HAT) are ineffective, and they have several well‐known clinical limitations. In our continued efforts to identify chemotypes that can be developed into clinically useful drugs, we screened a targeted compound library against the major cathepsin L (rhodesain) in T. brucei. We report the antirhodesain activity and antitrypanosomal activity of the compounds in this letter. The identified compounds can serve as starting points for structure‐ and/or phenotype‐based lead optimization strategy against Trypanosoma brucei.
A Prospective Longitudinal Study on Implant Prosthetic Rehabilitation in Controlled HIV‐Positive Patients with 1‐Year Follow‐Up: The Role of CD4+ Level, Smoking Habits, and Oral Hygiene
Authors: Gherlone Enrico F. , Capparé Paolo , Tecco Simona , Polizzi Elisabetta , Pantaleo Giuseppe , Gastaldi Giorgio , Grusovin Maria Gabriella 
Published: August 2015

AbstractBackgroundA recent study showed that implant‐prosthetic rehabilitation in well‐controlled HIV patients gave slightly worse results than in an healthy population, and failures were all linked to infection.PurposeThe aim of this study was to examine the associations between the success of implant‐prosthetic treatment and systemic CD4+ level, smoking habits, and oral hygiene.Materials and MethodsThis mono‐centric study included HIV patients with a stable disease and good oral hygiene requiring implant rehabilitation. Each patient received at least one dental implant. Prosthesis were delivered after 90 days in the upper jaw and 60 days in the lower jaw. Primary outcome measures were prosthetic failures, implant failures, peri‐implant marginal bone level changes, and biological complications (peri‐implantitis, pus, pain, paresthesia). The possible association with CD4 count, smoking habits, and oral hygiene was analyzed.ResultsSixty‐eight patients received 194 implants, and 66 patients (190 implants) were followed for 1 year. No significant associations were found between CD4+ count, oral hygiene‐associated variables, and any of the outcome measures. If compared with nonsmoking/light smoking patients, patients who smoked >10 cigarettes/day suffered a statistically significant greater number of implant failures (p ≤ .005), presented a comparatively higher number of peri‐implantitis (p < .001), as well as a higher frequency of pus (p ≤ .007), and reported pain (p ≤ .009).ConclusionWithin the limitation of the present study, placement of dental implants in HIV‐positive patients with stable disease seems a reasonable treatment option, regardless of CD4+ cell count, provided that they are in a normal range. Oral hygiene variables were not influent in this group of patient following recall appointments, while HIV‐positive heavy smokers (>10 cigarettes/day) demonstrated an increased risk of early implant failure, peri‐implantitis, episodes of pus, and self‐reported pain.
Conservation threats and the phylogenetic utility of IUCN Red List rankings inInciliustoads
Authors: Schachat Sandra R. , Mulcahy Daniel G. , Mendelson Joseph R. 
Published: August 2015

AbstractPhylogenetic analysis of extinction threat is an emerging tool in the field of conservation. However, there are problems with the methods and data as commonly used. Phylogenetic sampling usually extends to the level of family or genus, but International Union for Conservation of Nature (IUCN) rankings are available only for individual species, and, although different species within a taxonomic group may have the same IUCN rank, the species may have been ranked as such for different reasons. Therefore, IUCN rank may not reflect evolutionary history and thus may not be appropriate for use in a phylogenetic context. To be used appropriately, threat‐risk data should reflect the cause of extinction threat rather than the IUCN threat ranking. In a case study of the toad genus Incilius, with phylogenetic sampling at the species level (so that the resolution of the phylogeny matches character data from the IUCN Red List), we analyzed causes of decline and IUCN threat rankings by calculating metrics of phylogenetic signal (such as Fritz and Purvis’ D). We also analyzed the extent to which cause of decline and threat ranking overlap by calculating phylogenetic correlation between these 2 types of character data. Incilius species varied greatly in both threat ranking and cause of decline; this variability would be lost at a coarser taxonomic resolution. We found far more phylogenetic signal, likely correlated with evolutionary history, for causes of decline than for IUCN threat ranking. Individual causes of decline and IUCN threat rankings were largely uncorrelated on the phylogeny. Our results demonstrate the importance of character selection and taxonomic resolution when extinction threat is analyzed in a phylogenetic context.
Inappropriate drug use in elderly patients is associated with prolonged hospital stay and increased postoperative mortality after colorectal cancer surgery: a population‐based study
Authors: Samuelsson K. S. , Egenvall M. , Klarin I. , Lökk J. , Gunnarsson U. 
Published: August 2015

AbstractAimThe study aimed to investigate whether continuing potentially inappropriate medication (PIM) is associated with length of hospital stay (LOS) and postoperative mortality in elderly people undergoing colorectal cancer surgery.MethodThe Swedish National Colorectal Cancer Register and the Swedish Prescribed Drug Register provided matched data on 7279 patients aged 75 years or more who had undergone bowel resection for colorectal cancer between 2007 and 2010. Patients were divided into two groups depending on whether or not they were taking PIM at the time of surgery. The primary efficacy variables were the LOS and 30‐day postoperative mortality.ResultsOf the 7279 patients, 22.5% (1641) of the patients were exposed to at least one PIM and the total number of drugs taken in this group was six, compared with three in the non‐PIM group (P < 0.001). Postoperative mortality was higher in the PIM group (7.1% vs 4.5%, P < 0.001), and LOS was longer (10 days vs 9, P = 0.001). When adjusted for independent predictors, the differences in LOS (odds ratio 1.14; 95% confidence interval 1.00–1.29, P = 0.046) and postoperative mortality (odds ratio 1.43; 95% confidence interval 1.11–1.85, P = 0.006) remained significant.ConclusionThe use of PIM prior to surgery is associated with increased postoperative mortality and prolonged hospital stay. Although no causal relationship is proved, the results add a further aspect to preoperative optimization of elderly patients about to have major colorectal surgery.
Poor positive predictive value of influenza‐like illness criteria in adult transplant patients: a case for multiplex respiratory virus PCR testing
Authors: Claus Jonathan A. , Hodowanec Aimee C. , Singh Kamaljit 
Published: August 2015

AbstractBackgroundRespiratory viral infections (RVIs) are a significant cause of morbidity and mortality among transplant patients. The CDC's influenza‐like illness (ILI) criteria (fever ≥100°F with cough and/or sore throat) are a screening tool for influenza with unknown applicability to the transplant population.MethodsWe reviewed all respiratory virus PCR tests performed on adult patients with a history of solid organ (SOT) or stem cell transplantation (HSCT) during the 2012–2013 influenza season. The positive (PPV) and negative predictive values (NPV) of ILI criteria were calculated.ResultsOf 126 transplant patients (66 HSCT, 60 SOT), 54 (42.8%) tested positive for an RVI by PCR: 24 influenza and 30 non‐influenza. Of 30 patients who met ILI criteria, 12 (40%) were positive for influenza. The PPV and NPV of ILI for influenza were 50% and 82.4%, respectively. Mortality was low (3.7%), but morbidity was high (14.8% required ICU stay) among transplant patients diagnosed with RVI.ConclusionsInfluenza and non‐influenza RVIs are associated with significant morbidity among transplant patients. CDC ILI criteria correlate poorly with PCR‐positive cases of influenza in transplant patients, but may be useful in excluding the diagnosis. Routine RVI PCR testing is recommended for better diagnosis and improved antiviral use in transplant patients with suspected RVI.
Human activities and climate variability drive fast‐paced change across the world's estuarine–coastal ecosystems
Authors: Cloern James E. , Abreu Paulo C. , Carstensen Jacob , Chauvaud Laurent , Elmgren Ragnar , Grall Jacques , Greening Holly , Johansson John Olov Roger , Kahru Mati , Sherwood Edward T. , Xu Jie , Yin Kedong 
Published: August 2015

AbstractTime series of environmental measurements are essential for detecting, measuring and understanding changes in the Earth system and its biological communities. Observational series have accumulated over the past 2–5 decades from measurements across the world's estuaries, bays, lagoons, inland seas and shelf waters influenced by runoff. We synthesize information contained in these time series to develop a global view of changes occurring in marine systems influenced by connectivity to land. Our review is organized around four themes: (i) human activities as drivers of change; (ii) variability of the climate system as a driver of change; (iii) successes, disappointments and challenges of managing change at the sea‐land interface; and (iv) discoveries made from observations over time. Multidecadal time series reveal that many of the world's estuarine–coastal ecosystems are in a continuing state of change, and the pace of change is faster than we could have imagined a decade ago. Some have been transformed into novel ecosystems with habitats, biogeochemistry and biological communities outside the natural range of variability. Change takes many forms including linear and nonlinear trends, abrupt state changes and oscillations. The challenge of managing change is daunting in the coastal zone where diverse human pressures are concentrated and intersect with different responses to climate variability over land and over ocean basins. The pace of change in estuarine–coastal ecosystems will likely accelerate as the human population and economies continue to grow and as global climate change accelerates. Wise stewardship of the resources upon which we depend is critically dependent upon a continuing flow of information from observations to measure, understand and anticipate future changes along the world's coastlines.
Topical steroid therapy induces pro‐tolerogenic changes in Langerhans cells in human skin
Authors: Alhadj Ali Mohammad , Thrower Sally L. , Hanna Stephanie J. , Coulman Sion A. , Birchall James C. , Wong F Susan , Dayan Colin Mark , Tatovic Danijela 
Published: August 2015

SummaryWe have investigated the efficacy of conditioning skin Langerhans cells (LCs) with agents to promote tolerance and reduce inflammation, with the goal of improving the outcomes of antigen‐specific immunotherapy. Topical treatments were assessed ex vivo, using excised human breast skin maintained in organ bath cultures, and in vivo in healthy volunteers by analysing skin biopsies and epidermal blister roof samples. Following topical treatment with a corticosteroid, tumour necrosis factor‐α levels were reduced in skin biopsy studies and blister fluid samples. Blister fluid concentrations of monocyte chemoattractant protein‐1, macrophage inflammatory proteins ‐1α and 1β and interferon‐γ inducible protein‐10 were also reduced, while preserving levels of interleukin‐1α (IL‐1α), IL‐6, IL‐8 and IL‐10. Steroid pre‐treatment of the skin reduced the ability of LCs to induce proliferation, while supernatants showed an increase in the IL‐10/interferon‐γ ratio. Phenotypic changes following topical steroid treatment were also observed, including reduced expression of CD83 and CD86 in blister‐derived LCs, but preservation of the tolerogenic signalling molecules immunoglobulin‐like transcript 3 and programmed death‐1. Reduced expression of HLA‐DR, CD80 and CD86 were also apparent in LCs derived from excised human skin. Topical therapy with a vitamin D analogue (calcipotriol) and steroid, calcipotriol alone or vitamin A elicited no significant changes in the parameters studied. These experiments suggest that pre‐conditioning the skin with topical corticosteroid can modulate LCs by blunting their pro‐inflammatory signals and potentially enhancing tolerance. We suggest that such modulation before antigen‐specific immunotherapy might provide an inexpensive and safe adjunct to current approaches to treat autoimmune diseases.
The Canadian Hedge Fund Industry: Performance and Market Timing
Authors: Klein Peter , Purdy Daryl , Schweigert Isaac , Vedrashko Alexander 
Published: August 2015

AbstractWe analyze the risk and return characteristics of Canadian hedge funds based on a comprehensive database we compiled. We find that Canadian hedge funds have higher risk‐adjusted performance and different distributional characteristics relative to the global hedge fund indices. We investigate market timing by Canadian hedge funds and find that they do not time the Canadian or global stock and bond markets, but hedge funds in the Managed Futures strategy group time the commodity market. These results are robust to parameter instability and structural changes in the model. We also illustrate the impact of using local and global risk factors to analyze the performance of local investment firms.
Static and Dynamic Views of European Integration
Authors: Rose Richard , Borz Gabriela 
Published: August 2015

AbstractThere is a theoretical and empirical need to distinguish between static support for the EU as it now is and dynamic support for further integration. Although most Europeans endorse the EU as a good thing today, the European Election Study finds no popular majority for an ever closer union, the commitment of EU institutions. Less than one‐third endorses further integration and less than one‐third thinks integration has gone too far. The largest group favours keeping the EU as it is. Their outlook reflects ambivalence; they see the EU as having both strengths and weaknesses. It does not reflect lack of EU knowledge or of socio‐economic resources, as is the case with ‘don't knows’. While eurozone institutions are committed to further integration, most EU citizens are not. Likewise, there is no majority supporting eurosceptic demands for returning powers to national governments.
Elasticity of the tibial nerve assessed by sonoelastography was reduced before the development of neuropathy and further deterioration associated with the severity of neuropathy in patients with type 2 diabetes
Authors: Ishibashi Fukashi , Taniguchi Miki , Kojima Rie , Kawasaki Asami , Kosaka Aiko , Uetake Harumi 
Published: August 2015

AbstractAims/IntroductionTo measure the elasticity of the tibial nerve using sonoelastography, and to associate it with diabetic neuropathy severity, the cross‐sectional area of the tibial nerve and neurophysiological findings in type 2 diabetic patients.Materials and MethodsThe elasticity of the tibial nerve was measured as the tibial nerve:acoustic coupler strain ratio using high‐resolution ultrasonography in 198 type 2 diabetic patients stratified into subgroups by neuropathy severity, and 29 control participants whose age and sex did not differ from the diabetic subgroups.ResultsThe elasticity of the tibial nerve in patients without neuropathy (P < 0.001) was reduced compared with controls (0.76 ± 0.023), further decreasing (0.655 ± 0.014 to 0.414 ± 0.018) after developing neuropathy. The cut‐off value of elasticity of the tibial nerve that suggested the presence of neuropathy was 0.558. The area under the curve (0.829) was greater than that for the cross‐sectional area (0.612). The cross‐sectional area of the tibial nerve in diabetic patients without neuropathy (6.11 ± 0.13 mm2) was larger than that in controls (4.84 ± 0.16 mm2), and increased relative to neuropathy severity (P < 0.0001). The elasticity of the tibial nerve was negatively associated with neuropathy severity (P < 0.0001), cross‐sectional area (P = 0.002) and 2000 Hz current perception threshold (P = 0.011), and positively associated with nerve conduction velocities (P < 0.0001).ConclusionsDetermining the elasticity of the tibial nerve in type 2 diabetic patients could reveal early biomechanical changes that were likely caused by thickened fibrous sheaths of peripheral nerves, and might be a novel tool for characterizing diabetic neuropathy.
State‐dependent cooperation in burying beetles: parents adjust their contribution towards care based on both their own and their partner's size
Authors: Pilakouta N. , Richardson J. , Smiseth P. T. 
Published: August 2015

AbstractHandicapping experiments on species with biparental care show that a focal parent increases its contribution when its partner is handicapped. Such results are interpreted as evidence for negotiation, whereby each parent adjusts its amount of care to that of its partner. However, it is currently unclear whether the focal parent responds to a change in its handicapped partner's behaviour or state. To address this gap, we conducted an experiment on the burying beetle Nicrophorus vespilloides where we first generated different‐sized males and females by varying the duration of larval development. We then used a 2 × 2 factorial design in which a small or large male was paired with a small or large female. Small females provided less direct care (food provisioning and interactions with larvae) than large females, and both males and females provided less direct care when paired with a small partner. Thus, the focal parent adjusted its contribution towards care based on both its own state and that of its partner. There was also evidence for negotiation between the two parents as the focal parent adjusted its contribution based on the amount of care by its partner. However, there was no evidence that negotiation accounted for how the focal parent responded to its partner's size. Our results have important implications for our understanding of biparental cooperation as they show that each parent adjusts its contribution not only based on the amount of care provided by its partner but also based on its own state and its partner's state.
Association of factor V Leiden, Janus kinase 2, prothrombin, and MTHFR mutations with primary Budd–Chiari syndrome in Egyptian patients
Authors: El Sebay Hatem M , Safan Manal A , Daoud Ashraf A , Tayel Safaa I , A Nouh Mohamed , El Shafie Shymaa 
Published: August 2015

AbstractBackground and AimBudd–Chiari syndrome (BCS) is defined as obstruction of hepatic venous outflow anywhere from the small hepatic veins to the suprahepatic inferior vena cava. The pathogenesis of BCS is still not fully understood. This study aimed to evaluate the association of factor V Leiden (FVL), Janus kinase 2 (JAK2), prothrombin, and methylene tetrahydrofolate reductase (MTHFR) mutations with primary BCS.MethodsThe study was carried out on 35 patients with primary BCS and 15 age and gender matched healthy individuals as a control group. Genotyping of FVL, prothrombin, and MTHFR mutations was determined by GENEQUALITY AB‐THROMBO TYPE kit based on the reverse hybridization principle. JAK2 mutation was determined by polymerase chain reaction‐restriction fragment length polymorphism.ResultsThere was a statistically significant difference between patients and controls regarding FVL, MTHFR C677T, and MTHFR A1298C mutations with odds ratio of 1.83, 2.0, and 1.79, respectively. Hetero MTHFR C677T, hetero FVL, and hetero MTHFR A1298C were the most common etiological factors being responsible for 57.1, 42.9, and 42.9% of primary BCS cases, respectively.ConclusionIt could be concluded that BCS is a multifactorial disease; in the current study, MTHFR C677T mutation was the most common cause of disease. Identification of one cause of BCS should not eliminate investigations for detection of other etiological factors.