bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta‐analysis
Authors: Liakos A. , Karagiannis T. , Athanasiadou E. , Sarigianni M. , Mainou M. , Papatheodorou K. , Bekiari E. , Tsapas A. 
Published: April 2014

AimTo assess the efficacy and safety of the novel sodium‐glucose cotransporter 2 (SGLT2) inhibitor empagliflozin compared with placebo or other antidiabetic agents in patients with type 2 diabetes.MethodsWe conducted a systematic review and meta‐analysis of randomized controlled trials. We searched Medline, Embase and the Cochrane Library through December 2013 and grey literature. Two reviewers working independently extracted relevant data and carried out risk‐of‐bias assessments. We synthesized results using random‐effects models and computed weighted mean differences (WMDs) and odds ratios (ORs).ResultsWe included 10 studies with 6203 participants. Compared with placebo, mean changes in haemoglobin A1c were −0.62% [95% confidence interval (CI) −0.68 to −0.57%] for empagliflozin 10 mg and −0.66% (−0.76 to −0.57%) for empagliflozin 25 mg. Empagliflozin 25 mg daily had glycaemic efficacy similar to metformin or sitagliptin (WMD −0.11%; 95% CI −0.25 to 0.03%), without increasing risk for hypoglycaemia. It was also associated with body weight loss (WMD −1.84; 95% CI −2.30 to −1.38 kg vs. placebo) and had a favourable effect on blood pressure. Incidence of hypoglycaemia with empagliflozin was similar to placebo (OR 1.10; 95% CI 0.87 to 1.39); nevertheless we noted an increased risk for genital tract infections (OR 3.31; 95% CI 1.55 to 7.09). Findings were similar for the 10‐mg dosing regimen.ConclusionsEmpagliflozin effectively lowers blood glucose and provides additional clinical benefits including body weight and blood pressure reduction. Ongoing trials will elucidate the long‐term safety and effect of empagliflozin on cardiovascular outcomes.
Increased atmospheric carbon dioxide concentration: effects on eucalypt rust (Puccinia psidii), C:N ratio and essential oils in eucalypt clonal plantlets
Authors: Ghini R. , Leod R. E. de O. Mac , Torre Neto A. , Cardoso D. C. , Bettiol W. , de Morais L. A. S. , Vique B. 
Published: April 2014

SummaryEvaluation of impacts of high CO2 atmospheric concentration is strategically important for the development of adaptation measures and sustainable crop management. The objective of this study was to evaluate the effects of increased atmospheric CO2 concentration on eucalypt rust (Puccinia psidii), C:N ratio, yield and chemical composition of essential oils and growth of eucalypt clonal plantlets. Two clones with different levels of rust resistance were studied: a Eucalyptus urophylla × E. camaldulensis hybrid (VM 01) and an E. urophylla (clone MN 463). The experiments were performed in open‐top chambers (OTCs) with CO2 mean concentrations (μmol mol−1) of 399 (unenclosed control), 412 (OTCs with ambient CO2 concentration) and 508 (OTCs with high CO2 concentration) and in closed chambers (CCs) with CO2 mean concentrations of 390, 405, 520 and 700. Increased atmospheric CO2 concentrations resulted in a decrease in rust pustules per leaf, uredinia per leaf area, spores per uredinia and area under the disease progress curve in VM 01 (hybrid) clonal plantlets. The disease did not occur in MN 463 clonal plantlets, which demonstrated that high CO2 concentrations did not change the level of rust resistance. Plant growth of the two clones was stimulated by up to 23% in height and 26% in stem diameter in OTCs and by 18% for both clones in CCs. An increased C:N ratio in leaves, stems and roots was observed only for the VM 01 clonal plantlets. Essential oils produced by VM 01 (2.8 g 100 g−1) and MN 463 (1.4 g 100 g−1), as well as the major essential oil compounds (80% 1.8‐cineole for VM 01; 50% 1.8‐cineole and 32% α‐pinene for MN 463), were not altered. In this study, increased concentrations of atmospheric CO2 favourably impacted eucalypt growth and reduced rust severity, while not influencing the production of essential oils.
Aspirin inhibits proliferation and induces apoptosis of multiple myeloma cells through regulation of Bcl‐2 and Bax and suppression of VEGF
Authors: Ding Jiang‐hua , Yuan Li‐ya , Huang Rui‐Bin , Chen Guo‐an 
Published: April 2014

AbstractObjectivesAspirin (ASA) has been frequently used for thromboprophylaxis in patients with multiple myeloma (MM) when treated with thalidomide or lenalidomide. Despite the well‐recognized chemopreventive role of ASA in some solid tumors particularly for colon cancer, whether ASA displays the antimyeloma activity remains unclear.MethodsMM1.S and RPMI‐8226 cell lines harboring K‐Ras and N‐Ras mutation, respectively, were treated with various concentrations of ASA for different hours. The cell proliferation and apoptosis were performed to explore the effects of ASA on myeloma. Then, the exact mechanisms governing ASA's antimyeloma were explored by qRT‐PCR and Western blot. Also, the effect of ASA on tumor growth was observed in NOD/SCID mice bearing myeloma xenografts.ResultsASA of 0–10 mm concentration inhibits proliferation MM1.S and RPMI‐8226 cells in time‐ and dose‐dependent manner. The myeloma cells exposed to ASA treatment displayed concentration‐dependent apoptosis, which was closely associated with activation of caspases, upregulation of Bax, and downregulation of Bcl‐2 and VEGF. Study in vivo revealed that ASA administration retarded the tumor growth accompanying the survival time of mice bearing myeloma xenografts.ConclusionsASA exerted antiproliferative and pro‐apoptotic action in myeloma cells in vitro and delayed the growth of human myeloma cells in vivo. The underlying mechanisms were ascribed to regulation of Bcl‐2 and Bax and suppression of VEGF.
Should the cut‐off values of the lymphocyte to monocyte ratio for prediction of prognosis in diffuse large B‐cell lymphoma be changed in elderly patients?
Authors: Koh Young Wha , Park Chan‐Sik , Yoon Dok Hyun , Suh Cheolwon , Huh Jooryung 
Published: April 2014

AbstractObjectivesA recent study suggested a prognostic role for the peripheral blood absolute lymphocyte/monocyte ratio (LMR) at diagnosis of diffuse large B‐cell lymphoma (DLBCL). Here, we investigated the significance of LMR in DLBCL patients in relation to advanced age.MethodsWe examined the prognostic impact of LMR in 603 DLBCL treated with rituximab plus CHOP, using the receiver operating characteristic curve analysis for optimal cut‐off values, and performed a subgroup analysis according to age.ResultsIn elderly groups (age ≥ 70), absolute monocyte count was significantly increased, whereas LMR was significantly decreased compared to younger groups. Patients under 70 yr of age with LMR <3.04 had significantly lower overall survival (OS) and progression‐free survival (PFS) compared to those with LMR ≥3.04 (P < 0.001 for both). However, in elderly patients (age ≥ 70), there was no significant difference in OS between patients' LMR levels using the 3.04 cut‐off value (P = 0.059). Therefore, a new LMR cut‐off value of 2.36 was selected in elderly patients, having observed that elderly patients with LMR <2.36 had significantly lower OS compared to those with LMR ≥2.36 (P = 0.021). In multivariate analysis, LMR remained a significant prognostic factor for OS (P = 0.004) or PFS (P < 0.001).ConclusionsWe suggest the use of a different cut‐off value of LMR in elderly patients to distinguish high‐risk from low‐risk groups.
Impact of risk score calculations in choosing front‐line tyrosine kinase inhibitors for patients with newly diagnosed chronic myeloid leukemia in the chronic phase
Authors: Hu Bei , Savani Bipin N. 
Published: April 2014

AbstractThe approval of multiple tyrosine kinase inhibitors targeting BCR‐ABL has broadened the number of available therapeutic options for chronic myeloid leukemia in the chronic phase (CML‐CP). This provides an impetus for optimizing prognostic risk score systems that can guide treatment decisions. Presently, three risk scores—the Sokal, Hasford, and European Treatment and Outcome Study (EUTOS) metrics—have been implemented clinically in CML‐CP. While these three formulations all endeavor to gauge likely disease course, they differ from one another in several important respects, with potential implications for prognosis and therapy. Here, we review these risk scores and propose how prognostic systems in CML‐CP might be refined to direct patients to optimally effective therapies as efficiently and accurately as possible.
Atypical presentation of ‘acalculous cholecystitis’ with marked isolated hyperbilirubinaemia in patients treated for haematological malignancies
Authors: Berrevoets Marvin A.H. , Hermans John J. , Wanten Geert J.A. , van der Velden Walter J.F.M. 
Published: April 2014

AbstractFour patients diagnosed with haematological malignancies developed an isolated hyperbilirubinaemia following cytarabine‐ and anthracycline‐based chemotherapy. The clinical picture was consistent with acalculous cholecystitis, but ultrasonography did not show the typical gallbladder wall thickening. All patients suffered from severe mucositis with neutropenic enterocolitis. We hypothesise that damage of the mucosa of the gallbladder induced by chemotherapy results in hyperpermeability of the mucosal barrier with bile leakage and isolated hyperbilirubinaemia.
Clinical activity of ponatinib in one patient with chronic myeloid leukemia in chronic phase with e19a2 transcript and T315I mutation
Authors: Ferri Cristian A. , Bianchini Michele , Bengió Raquel M. , Moiraghi Elena B. , Gonzalez Mariana S. , Noriega María F. , Larripa Irene B. 
Published: April 2014

AbstractBackgroundChronic myeloid leukemia (CML) is a hematological disorder that in rare cases, mainly in CML neutrophilic, presents the e19a2 rearrangement. The encoded product is a 230‐KDa protein. Despite the remarkable responses to treatment of most patients, a small but significant fraction of them develop clinical resistance to the tyrosine kinase inhibitors (TKIs). The most common mechanism of resistance is point mutations in the ABL1 kinase domain. The recently approved third‐generation TKI ponatinib demonstrated remarkable activity in patients with multi‐TKI‐resistant disease. Particularly impressive was its efficacy in patients with T315I mutation that is resistant to all other TKIs.MethodsQualitative PCR was carried out by multiplex approach. Relative transcripts quantification was performed by one‐step real‐time PCR, with a specific Taqman probe and primers for the e19a2 rearrangement. We carried out a mutational screening by high‐resolution melting, and the mutation was identified by Sanger method. The mutation burden was quantified by quantitative PCR using allele‐specific primers.ResultsIn a patient with CML, we identified a PCR product corresponding to e19a2 rearrangement harboring T315I mutation. At the time of mutational analysis, during dasatinib treatment, the T315I clone was 100% and the quantification of BCR‐ABL1 was 18%. After ponatinib therapy, the T315I mutation burden decreased down to undetectable levels and the BCR‐ABL1 transcripts showed a very low value (0.011%).ConclusionsHere, we report the hematological, cytogenetic, and molecular response of a patient with refractory CML in chronic phase with e19a2 transcripts, carrying T315I mutation that was successfully treated with ponatinib.
Experimental slab salvage and reinstatement after pipeline construction in a threatened grassland community
Authors: Jellie Zoe V. , Wills Timothy J. , Kutt Alex S. , Hemming Victoria L. , King Drew J. , McKenzie Vanessa J. , Retallick Richard W. R. , Timewell Christopher A. , van Eeden Lily 
Published: April 2014

SummaryThe protection and management of grasslands is a priority to conserve biodiversity, particularly in fragmented landscapes subject to human‐induced disturbance. We examined the success of salvage and reinstatement of multiple 90 m2slabs of modified temperate grassland in a pipeline construction corridor in south‐eastern Australia and compared it with a reinstated topsoil treatment (i.e. standard pipeline reinstatement practice) and an undisturbed control. Thirty‐six plots (each 9 × 10 m) representing the three treatments were monitored across six locations, pre‐ and postconstruction every 3 months for 2 years. We sampled 18 vegetation/habitat variables to examine the effect of treatments over time. Introduced grass cover was consistently higher than native grasses for both treatments, and the cover of introduced grasses increased over time in both treatments. Conversely, control plots had considerably higher native grass cover than the slab and reinstated topsoil treatments. Native species richness was not negatively affected by the slab reinstatement process. Our results suggest that in this instance, slab replacement was an ineffective way to reinstate native grasslands, as it appeared to confer minimal benefit when compared to the standard practice of reinstating topsoil. This was most likely due to the high degree of disturbance to slabs during the reinstatement process.
Population differentiation of zander (Sander lucioperca) across native and newly colonized ranges suggests increasing admixture in the course of an invasion
Authors: Eschbach Erik , Nolte Arne W. , Kohlmann Klaus , Kersten Petra , Kail Jochem , Arlinghaus Robert 
Published: April 2014

AbstractIn addition to ecological factors, evolutionary processes can determine the invasion success of a species. In particular, genetic admixture has the potential to induce rapid evolutionary change, which can result from natural or human‐assisted secondary contact between differentiated populations. We studied the recent range expansion of zander in Germany focusing on the interplay between invasion and genetic admixture. Historically, the rivers Elbe and Danube harboured the most north‐western source populations from which a north‐westward range expansion occurred. This was initiated by introducing zander outside its native range into rivers and lakes, and was fostered by migration through artificial canals and stocking from various sources. We analysed zander populations of the native and invaded ranges using nuclear and mitochondrial genetic markers. Three genetic lineages were identified, which were traced to ancestral ranges. Increased genetic diversity and admixture in the invaded region highlighted asymmetric gene flow towards this area. We suppose that the adaptive potential of the invading populations was promoted by genetic admixture, whereas competitive exclusion in the native areas provided a buffer against introgression by novel genotypes. These explanations would be in line with evidence that hybridization can drive evolutionary change under conditions when new niches can be exploited.
A comparison of three doses of omeprazole in the treatment of equine gastric ulcer syndrome: A blinded, randomised, dose–response clinical trial
Authors: Sykes B. W. , Sykes K. M. , Hallowell G. D. 
Published: April 2014

SummaryReasons for performing the studyA previous study demonstrated that a dose effect between 1.6 and 4.0 mg/kg bwt of omeprazoleper oss.i.d. is present in the treatment of equine gastric ulceration. In the same study, healing of glandular ulceration appeared inferior to healing of squamous ulceration. However, several limitations were recognised in that study and further investigation is warranted.ObjectivesTo further investigate the presence of a dose relationship in the treatment of gastric ulceration under conditions that may favour omeprazole efficacy such as administration prior to exercise and after a brief fast, and potential differences between the response of squamous and glandular ulceration to omeprazole therapy.Study designA blinded, randomised, dose–response clinical trial.MethodsSixtyThoroughbred racehorses withgrade≥2/4squamous and/or glandular ulceration were identified by gastroscopy. Horses were randomly assigned to receive either 1.0, 2.0 or 4.0 mg/kg bwt of enteric coated omeprazoleper oss.i.d. 1–4 h prior to exercise. Gastroscopy was repeated at approximately 28 days.ResultsThe lower doses studied (1.0 and 2.0 mg/kg bwt) were noninferior to the reference dose (4.0 mg/kg bwt) in the treatment of squamous ulceration. Healing was greater in squamous ulceration than glandular ulceration (86% vs. 14%; P<0.0001). Improvement in ulcer grade was more likely in squamous lesions than glandular lesions (96% vs. 34%; P<0.0001). Worsening of the glandular ulcer grade was observed in 36% of horses.ConclusionsThe results of this study suggest that, under the conditions studied, where omeprazole is administered before exercise and following a brief fast, doses of omeprazole as low as 1 mg/kg bwtper oss.i.d. may be as effective as higher doses. The proportion of glandular ulceration that heals with 28 days of omeprazole therapy is less than that of squamous ulceration.
Quantifying fish species richness and abundance in Amazonian streams: assessment of a multiple gear method suitable for Terra firme stream fish assemblages
Authors: Mojica J. I. , Lobón‐Cerviá J. , Castellanos C. 
Published: April 2014

AbstractA multigear sampling method to quantify fish richness and abundance in Amazonian Terra firme streams was assessed. This method is based on the four‐pass removal method using the combined application of different nets. The efficiency of the method was explored over 10 replicated sites along three streams over day, night and seasons. Use of four successive passes allowed both abundant and rare species to be collected and the abundance of common species to be estimated. On average, a high proportion (41%) of rare species was collected per sample (only one or two individuals) after four fishing passes. The efficiency of the sampling method to detect species richness per sample between successive passes was estimated using an autosimilarity approach. Although species richness and abundance increased with successive passes, no major differences were obtained between the third and fourth pass. A single pass considerably underestimated the richness and abundance of species in these type of streams, and night sampling also increased beta‐diversity by at least 20%. Abundance estimates demonstrated high efficiency with an overall sampling error of only 8 and 11% for samples and single species, respectively. Capture efficiency differed among fish species exhibiting different ecological traits and showed significant differences among seasons for total samples. Results supported the robustness of the method and its suitability to quantify fish richness and abundance in small, wadeable Amazonian Terra firme streams inhabited by highly diverse fish assemblages.
Epidemiological aspects of inhibitor development redefine the clinical importance of inhibitors
Authors: van den Berg H. M. 
Published: April 2014

SummaryInhibitor development is a serious complication of treatment with coagulation products. Presently, 25–30% of all newly diagnosed patients with severe haemophilia A are diagnosed with inhibitors. An increasing number of genetic and non‐genetic risk factors have been reported to be involved, although the impact of them in understanding the aetiology is still limited. Much attention has been focused on factor VIII products, but more recent studies show very little, if any, difference between class plasma and recombinant factor VIII products. More intensive treatment and higher dosing are probably more important factors. More than 10% of the inhibitors diagnosed in the last decade are of low titre. A first goal should be to understand their importance. It is argued that the impact of different risk factors should be studied in high‐titre inhibitors to prevent dilution by non‐significant low‐titre inhibitors.
Laboratory testing for factor inhibitors
Authors: Favaloro E. J. , Verbruggen B. , Miller C. H. 
Published: April 2014

SummaryInhibitor assays are performed when patients present with unexplained prolonged routine coagulation test times and unexpected and/or unusual bleeding (potential for acquired haemophilia) as well as being a part of normal congenital haemophilia management and monitoring, particularly when bleeding occurs on therapy, or when increments in factor levels post‐factor replacement remain lower than expected. In this article, we will describe the assays used, as well as their development, pitfalls in testing such as inter‐laboratory variability and false negative/positive results, as well as some strategies for overcoming these pitfalls and potential alternative test approaches. The inter‐laboratory coefficient of variation often approaches (and sometimes exceeds) 50%, as evidenced by various external quality assessment groups, and this variability has not improved over recent years. Additional important considerations include appropriate interpretation of test results, repeat testing for confirmation, and assessment of recovery as part of the diagnostic process.
Laboratory aspects of von Willebrand disease: test repertoire and options for activity assays and genetic analysis
Authors: Castaman G. , Hillarp A. , Goodeve A. 
Published: April 2014

SummaryThe deficiency or abnormal function of von Willebrand factor (VWF) causes von Willebrand disease (VWD), the most frequent inherited bleeding disorder. The laboratory diagnosis of VWD can be difficult as the disease is heterogeneous and an array of assays is required to describe the phenotype. Basic classification of quantitative (type 1 and 3) and qualitative (type 2) VWD variants requires determination of VWF antigenic (VWF:Ag) levels and assaying of VWF ristocetin cofactor (VWF:RCo) activity, determining the capacity of VWF to interact with the platelet GPIb‐receptor. Knowing the VWF:RCo activity is essential for identifying, subtyping and monitoring VWD, but the assay is poorly standardized and many protocols do not fulfil the clinical need in all situations. This has led to the development of novel activity assays, independent of ristocetin, with enhanced assay characteristics. Results from the first independent clinical evaluations are promising, showing that they are reliable and suitable for VWD diagnosis. The qualitative type 2 VWF deficiency can be further divided into four different subtypes (A, B, M and N) using specific assays that explore other activities or the size distribution of VWF multimers. These methods are discussed herein. However, in a number of patients it may be difficult to correctly classify the VWD phenotype and genetic analysis may provide the best option to clarify the disorder, through mutation identification.
von Willebrand disease and platelet disorders
Authors: Favaloro E. J. , Bodó I. , Israels S. J. , Brown S. A. 
Published: April 2014

SummaryThe diagnosis and management of bleeding disorders is made difficult by the complexity and variety of disorders, clinical symptoms and bleeding type and severity. von Willebrand disease (VWD) and platelet disorders are disorders of primary haemostasis and together represent the most common inherited bleeding disorders. In this article, we describe the diagnosis of VWD and platelet disorders and the treatment options for VWD.