bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin lispro low mixture twice daily versus basal insulin glargine once daily and prandial insulin lispro once daily in patients with type 2 diabetes requiring insulin intensification: a randomized phase IV trial
Authors: Tinahones F. J. , Gross J. L. , Onaca A. , Cleall S. , Rodríguez A. 
Published: April 2014

AimsTo compare the efficacy and safety of two insulin intensification strategies in patients with type 2 diabetes inadequately controlled on basal insulin glargine with metformin and/or pioglitazone.MethodsA multinational, randomized, open‐label trial that compared insulin lispro low mixture (LM25; n = 236) twice daily with a basal–prandial regimen of insulin glargine once daily and insulin lispro once daily (IGL; n = 240) over 24 weeks in patients with HbA1c 7.5–10.5% and fasting plasma glucose ≤6.7 mmol/l. The primary objective was to assess non‐inferiority [per‐protocol (PP) population], and then superiority [intention‐to‐treat (ITT) population], of LM25 versus IGL according to change in HbA1c after 24 weeks (non‐inferiority margin 0.4%, two‐sided significance level 0.05).ResultsEstimated change [least squares (LS) mean (95% CI)] in HbA1c after 24 weeks: −1.30 (−1.44, −1.16)% with LM25 and −1.08 (−1.22, −0.94)% with IGL. Non‐inferiority was shown [LS mean (95% CI) HbA1c treatment difference −0.21 (−0.38, −0.04) (PP population)]; gated superiority assessment showed a statistically significant advantage for LM25 (p = 0.010; ITT population). Mean blood glucose, glycaemic variability, overall tolerability and hypoglycaemic episodes per patient‐year did not show significant differences between treatments during the study.ConclusionsIn patients with type 2 diabetes inadequately controlled on once‐daily basal insulin glargine and metformin and/or pioglitazone, intensification with LM25 was superior to a basal–prandial approach in terms of reduction in HbA1c after 24 weeks and did not increase hypoglycaemia episodes.
Plant traits mediate effects of predators across pepper (Capsicum annuum) varieties
Authors: ABDALA‐ROBERTS LUIS , BERNY‐MIER Y TERÁN JORGE C. , MOONEY KAILEN A. , MOGUEL‐ORDONEZ YOLANDA B. , TUT‐PECH FELIPE 
Published: April 2014

The magnitude of plant intra‐specific variation for indirect defence and the underlying plant traits influencing predators remain relatively unstudied, particularly in cultivated plants.We tested whether differences in flower number, pollen production, and leaf trichome density among 17 pepper (Capsicum annuumLinnaeus) varieties influenced the abundance and predation intensity by the omnivorous miteAmblyseius swirskiiAthias‐Henriot.A greenhouse experiment was conducted where pepper plants were infested with thrips (Frankliniella cephalicaCrawford DL) and subsequently exposed toA. swirskii. We estimated thrips and mite density based on arthropod counts conducted over a 4‐week period, and also performed flower and trichome counts, and estimated pollen production per anther.Significant differences were found among varieties for all three traits, as well as mite and thrips density. After accounting for all traits in a multiple regression model, we found that flower and trichome number had significant positive effects on mite density (by providing food and shelter, respectively). Increased mite density was in turn associated with a decrease in thrips density, presumably as a result of mite predation. Moreover, we found that flower number (but not trichome density) increased the strength of thrips suppression and that such an effect was mediated by mite density.These findings suggest that genetic variation for plant traits may indirectly influence herbivore suppression in peppers (although traits may vary in the strength or direction of their effects), and underscore the evolutionary potential and importance of selection not only for direct but also indirect resistance in crops.
Red cell distribution width as a potential index to assess the severity of hepatitis B virus‐related liver diseases
Authors: Huang Rui , Yang Chenchen , Wu Kangkang , Cao Shufeng , Liu Yong , Su Ran , Xiong Yali , Huang Aijun , Wu Chao 
Published: April 2014

AimTo investigate the association between red cell distribution width (RDW) and the severity of hepatitis B virus (HBV)‐related liver diseases.MethodsSixty‐nine patients with chronic hepatitis B (CHB) and 61 patients with HBV‐related liver cirrhosis were enrolled in the present study. Forty‐one healthy individuals were included as controls. Hematological parameters, hepatitis B e‐antigen (HBeAg) status, HBV DNA levels and liver biochemistry were analyzed. Child–Pugh scores and Model for End‐Stage Liver Disease (MELD) scores of the patients with HBV‐related liver cirrhosis were calculated.ResultsThe RDW was significantly higher in patients with HBV‐related liver cirrhosis as compared with CHB patients and healthy controls. RDW was slightly higher in CHB patients as compared with healthy controls. An increasing correlation of RDW with Child–Pugh grades was found. RDW was positively correlated with Child–Pugh scores and MELD scores. In patients with HBV‐related liver cirrhosis, RDW was also positively correlated with total bilirubin and negatively correlated with hemoglobin and serum albumin concentration. However, no significant difference was found between HBeAg positive and negative patients and no significant correlation between RDW and HBV DNA levels was found.ConclusionThe RDW was elevated in CHB patients and patients with HBV‐related liver cirrhosis and was positively correlated with the severity of HBV‐related liver cirrhosis. RDW is a potential index to assess the severity of HBV‐related liver diseases.
Assessment of seasonality of influenza in swine using field submissions to a diagnostic laboratory in Ontario between 2007 and 2012
Authors: Poljak Zvonimir , Carman Susy , McEwen Beverly 
Published: April 2014

BackgroundSeasonality of any infectious disease is important for its control and monitoring. While influenza seasonality in people has been evaluated extensively, this question has not been studied well in swine populations.ObjectiveThe goal of this study was to investigate seasonality of influenza in swine, using diagnostic submissions to a diagnostic laboratory.MethodsTwo thousand seven hundred and eleven virological tests within 685 submissions and 5471 serological tests within 193 submissions in Ontario swine between 2007 and 2012 were included in the study and converted to total monthly number of virological and serological submissions, and the number of positive submissions. Data were analyzed by time‐series decomposition, fixed‐effect Poisson, random‐effect Poisson regression with month as uncorrelated and correlated random effects.ResultsAll approaches identified seasonality in virological submissions (P < 0·02) with peak in January and April, and a trough in July, but were not able to detect seasonality of influenza‐positive virological submissions (P > 0·13). Seasonality of positive serological submissions was identified only if independence between months was assumed (P < 0·03). Almost 50% of serological submissions had evidence of exposure to H3N2 and H1N1.ConclusionsThus, this study identified evidence of seasonality in influenza‐like disease in swine herds, but not in circulation of influenza virus. Evidence of seasonality in exposure to influenza was dependent on assumptions of between‐month correlation. High exposure to H3N2 and H1N1 subtypes warrants more detailed investigation of within‐herd influenza virus circulation. The study provides initial insight into seasonality of influenza in swine and should be followed with herd‐level studies.
Prevalence of psychiatric disorders among heroin users who received methadone maintenance therapy in Taiwan
Authors: Fan Chiung‐Yueh , Tan Happy Kuy‐Lok , Chien I‐Chia , Chou Sun‐Yuan 
Published: April 2014

BackgroundMany patients under methadone maintenance treatment are present with comorbid psychiatric symptoms.ObjectiveWe wish to examine the prevalence of psychiatric disorders among heroin users who received methadone maintenance therapy (MMT) in Taiwan.MethodsBy combining the National Health Insurance Research database and Center for Disease Control database, 18,271 heroin users who received MMT were defined as the subject group and after matching age and sex, 73,084 patients were randomly selected as the control group.ResultsThe 1 year prevalence of any psychiatric disorder, any psychotic disorder, neurotic and other nonpsychotic disorder among MMT patients and control group were 13.14% versus 2.50% (OR 5.89, CI 5.53–6.27), 4.21% versus 1.29% (OR 3.38, CI 3.07–3.72), and 9.89% versus 1.31% (OR 8.25, CI 7.62–8.94), respectively.ConclusionThe prevalence of any co‐morbid psychiatric disorder among MMT patients is almost six times higher than the control group.Scientific SignificanceA thorough psychiatric screening and appropriate aggressive intervention should be incorporated into an effective methadone treatment program. (Am J Addict 2014;23:249–256)
Predictors of drinking and functional outcomes for men and women following inpatient alcohol treatment
Authors: Sugarman Dawn E. , Kaufman Julia S. , Trucco Elisa M. , Brown Jodi C. , Greenfield Shelly F. 
Published: April 2014

Background and ObjectivesThis prospective study uses path analytic models to examine baseline characteristics associated with both functioning and drinking outcomes 12 months after inpatient alcohol treatment.MethodsAlcohol‐dependent participants (N = 101) were recruited during inpatient alcohol treatment and assessed monthly 1 year after discharge.ResultsAlcohol severity was negatively associated with education and self‐efficacy; marital status was positively associated with self‐efficacy; and education and self‐efficacy were negatively associated with drinking outcomes. Low alcohol severity, not having a depression diagnosis, and being married were associated with less social support impairment, which was in turn associated with better drinking outcomes. Having a history of sexual abuse did not influence drinking outcomes. However, having a history of sexual abuse was negatively associated with global functioning.Conclusions and Scientific SignificanceDrinking outcomes were associated with education, self‐efficacy, social support, and diagnosis of depression at baseline; however, global functioning 1 year following treatment was primarily and negatively associated with sexual abuse history. Future treatment research should include measures of both functioning and drinking behavior outcomes. (Am J Addict 2014;23:226–233)
Pharmacogenetics of naltrexone and disulfiram in alcohol dependent, dually diagnosed veterans
Authors: Arias Albert J. , Gelernter Joel , Gueorguieva Ralitza , Ralevski Elizabeth , Petrakis Ismene L. 
Published: April 2014

BackgroundDisulfiram and naltrexone were evaluated in treatment of individuals with co‐occurring alcohol dependence and other Axis I disorders (e.g., Major Depression). We explored pharmacogenetic interactions in genotyped subjects.MethodsAlcohol dependent (AD) subjects received naltrexone alone, placebo alone, disulfiram with placebo or disulfiram with naltrexone. They were genotyped for OPRM1 rs1799971 (Asn40Asp), and DBH rs1611115 (C‐1021T). N = 107 male European‐American subjects were included.ResultsThere were no significant interactions with OPRM1. DBH interacted with naltrexone on the primary outcome of abstinence from heavy drinking (χ2(1) = 5.23, p = .02). “T” allele carriers on naltrexone had more abstinence compared to “CC” subjects on naltrexone (FET, p = .01). “T” allele carriers on naltrexone had the highest overall rates of abstinence from heavy drinking (>90%). Also, DBH genotype interacted with disulfram (F(1,17) = 7.52, p = .01) on drinks per drinking day with less drinking for subjects with the “CC” genotype than for T allele carriers on disulfiram.ConclusionsDBH*rs1611115*T associated with better response to naltrexone, while for those on disulfiram that drank, “CC” subjects drank less than T carriers. For rs1799971*G, we did not replicate findings from previous studies showing a more favorable response to NTX, possibly due to the small available sample.Scientific SignificanceGenotyping rs1611115 may be useful in understanding inter‐individual differences in AD treatment response.Future DirectionsFurther study of rs1611115 pharmacogenetics is warranted. (Am J Addict 2014;23:288–293)
High‐Density Epicardial Activation Mapping to Optimize the Site for Video‐Thoracoscopic Left Ventricular Lead Implant
Authors: POLASEK ROSTISLAV , SKALSKY IVO , WICHTERLE DAN , MARTINCA TOMAS , HANULIAKOVA JANA , ROUBICEK TOMAS , BAHNIK JAN , JANSOVA HELENA , PIRK JAN , KAUTZNER JOSEF 
Published: April 2014

Optimization of Left Ventricular Lead PositionBackgroundThe left ventricular (LV) lead local electrogram (EGM) delay from the beginning of the QRS complex (QLV) is considered a strong predictor of response to cardiac resynchronization therapy. We have developed a method for fast epicardial QLV mapping during video‐thoracoscopic surgery to guide LV lead placement.MethodsA three‐port, video‐thoracoscopic approach was used for LV free wall epicardial mapping and lead implantation. A decapolar electrophysiological catheter was introduced through one port and systematically attached to multiple accessible LV sites. The pacing lead was targeted to the site with maximum QLV. The LV free wall activation pattern was analyzed in 16 pre‐specified anatomical segments.ResultsWe implanted LV leads in 13 patients with LBBB or IVCD. The procedural and mapping times were 142 ± 39 minutes and 20 ± 9 minutes, respectively. A total of 15.0 ± 2.2 LV segments were mappable with variable spatial distribution of QLV‐optimum. The QLV ratio (QLV/QRSd) at the optimum segment was significantly higher (by 0.17 ± 0.08, p < 0.00001) as compared to an empirical midventricular lateral segment. The LV lead was implanted at the optimum segment in 11 patients (at an adjacent segment in 2 patients) achieving a QLV ratio of 0.82 ± 0.09 (range 0.63–0.93) and 99.5 ± 0.6% match with intraprocedural mapping.ConclusionVideo‐thoracoscopic LV lead implantation can be effectively and safely guided by epicardial QLV mapping. This strategy was highly successful in targeting the selected LV segment and resulted in significantly higher QLV ratios compared to an empirical midventricular lateral segment.
Dietary Sodium and Potassium Intake Is Not Associated With Elevated Blood Pressure in US Adults With No Prior History of Hypertension
Authors: Sharma Shailendra , McFann Kim , Chonchol Michel , Kendrick Jessica 
Published: April 2014

The relationship between dietary sodium and potassium intake with elevated blood pressure (BP) levels is unclear. The authors examined the association between dietary sodium and potassium intake and BP levels in 6985 adults aged 18 years and older with no prior history of hypertension who participated in the National Health and Nutrition Examination Survey (2001–2006). After adjustment for age, sex, race, body mass index, diabetes, and estimated glomerular filtration rate, there was no association between higher quartiles of sodium or potassium intake with the risk of a BP >140/90 mm Hg or >130/80 mm Hg. There was also no relationship between dietary sodium and potassium intake with BP when systolic and diastolic BP were measured as continuous outcomes (P=.68 and P=.74, respectively). Furthermore, no association was found between combinations of sodium and potassium intake with elevated BP. In the US adult population without hypertension, increased dietary sodium or low potassium intake was not associated with elevated BP levels.
Comprehensive characterization of immunoglobulin gene rearrangements in patients with chronic lymphocytic leukaemia
Authors: René Céline , Prat Nathalie , Thuizat Audrey , Broctawik Mélanie , Avinens Odile , Eliaou Jean‐François 
Published: April 2014

AbstractPrevious studies have suggested a geographical pattern of immunoglobulin rearrangement in chronic lymphocytic leukaemia (CLL), which could be as a result of a genetic background or an environmental antigen. However, the characteristics of Ig rearrangements in the population from the South of France have not yet been established. Here, we studied CLL B‐cell repertoire and mutational pattern in a Southern French cohort of patients using an in‐house protocol for whole sequencing of the rearranged immunoglobulin heavy‐chain genes. Described biased usage of variable, diversity and joining genes between the mutated and unmutated groups was found in our population. However, variable gene frequencies are more in accordance with those observed in the Mediterranean patients. We found that the third complementary‐determining region (CDR) length was higher in unmutated sequences, because of bias in the diversity and joining genes usage and not due to the N diversity. Mutations found in CLL followed the features of canonical somatic hypermutation mechanism: preference of targeting for activation‐induced cytidine deaminase and polymerase motifs, base change bias for transitions and more replacement mutations occurring in CDRs than in framework regions. Surprisingly, localization of activation‐induced cytidine deaminase motifs onto the variable gene showed a preference for framework regions. The study of the characteristics at the age of diagnosis showed no difference in clinical outcome, but suggested a tendency of increased replacement and transition‐over‐transversion mutations and a longer third CDR length in older patients.
Growth/differentiation factor‐5: pre‐clinical and clinical evaluations of periodontal regeneration and alveolar augmentation – review
Authors: Lee Jaebum , Wikesjö Ulf M.E. 
Published: April 2014

Abstract: Aim: Growth/differentiation factor‐5 (GDF‐5) plays critical roles in mesenchymal cell differentiation and stimulates human periodontal ligament cell proliferation. Potentially, GDF‐5 may also play roles in wound healing including periodontal regeneration and alveolar augmentation. The objective of this review was to provide up‐to‐date information from pre‐clinical/clinical studies evaluating GDF‐5 for these indications.Methods: A comprehensive search using PubMed and Google search engines was conducted to identify reports on GDF‐5 applied to periodontal and alveolar indications. Two reviewers independently screened the titles and abstracts from a total of 479 reports. Full‐length articles of 17 pre‐clinical and four clinical studies were selected and reviewed.Results: Canine‐, porcine‐ and non‐human primate‐based models as well as human clinical trials were used in the evaluation of GDF‐5 in support of periodontal regeneration and alveolar augmentation. An absorbable collagen sponge (ACS), β‐tricalcium phosphate (β‐TCP) and a poly(lactic‐co‐glycolic) acid (PLGA) were evaluated as candidate carriers for GDF‐5 using various dose and healing intervals demonstrating significantly enhanced periodontal regeneration/alveolar augmentation including cementum, periodontal ligament and alveolar bone with limited, if any, adverse effects.Conclusion: Growth/differentiation factor‐5 supports periodontal regeneration/alveolar augmentation without aberrant healing events documented in qualified pre‐clinical models and clinical pilot studies. In perspective, GDF‐5 appears a promising technology for periodontal regeneration/alveolar augmentation.
Fitness landscapes emerging from pharmacodynamic functions in the evolution of multidrug resistance
Authors: Engelstädter J. 
Published: April 2014

AbstractAdaptive evolution often involves beneficial mutations at more than one locus. In this case, the trajectory and rate of adaptation is determined by the underlying fitness landscape, that is, the fitness values and mutational connectivity of all genotypes under consideration. Drug resistance, especially resistance to multiple drugs simultaneously, is also often conferred by mutations at several loci so that the concept of fitness landscapes becomes important. However, fitness landscapes underlying drug resistance are not static but dependent on drug concentrations, which means they are influenced by the pharmacodynamics of the drugs administered. Here, I present a mathematical framework for fitness landscapes of multidrug resistance based on Hill functions describing how drug concentrations affect fitness. I demonstrate that these ‘pharmacodynamic fitness landscapes’ are characterized by pervasive epistasis that arises through (i) fitness costs of resistance (even when these costs are additive), (ii) nonspecificity of resistance mutations to drugs, in particular cross‐resistance, and (iii) drug interactions (both synergistic and antagonistic). In the latter case, reciprocal drug suppression may even lead to reciprocal sign epistasis, so that the doubly resistant genotype occupies a local fitness peak that may be difficult to access by evolution. Simulations exploring the evolutionary dynamics on some pharmacodynamic fitness landscapes with both constant and changing drug concentrations confirm the crucial role of epistasis in determining the rate of multidrug resistance evolution.
Serum 25‐hydroxy vitamin D concentrations are more deficient/insufficient in peritoneal dialysis than haemodialysis patients in a sunny climate
Authors: Hanna K. , Fassett R. G. , Gill E. , Healy H. , Kimlin M. , Ross L. , Ash S. 
Published: April 2014

AbstractBackgroundResearch has identified associations between serum 25(OH)D and a range of clinical outcomes in chronic kidney disease and wider populations. The present study aimed to investigate vitamin D deficiency/insufficiency in dialysis patients and the relationship with vitamin D intake and sun exposure.MethodsA cross‐sectional study was used. Participants included 30 peritoneal dialysis (PD) (43.3% male; 56.87 ± 16.16 years) and 26 haemodialysis (HD) (80.8% male; 63.58 ± 15.09 years) patients attending a department of renal medicine. Explanatory variables were usual vitamin D intake from diet/supplements (IU day−1) and sun exposure (min day−1). Vitamin D intake, sun exposure and ethnic background were assessed by questionnaire. Weight, malnutrition status and routine biochemistry were also assessed. Data were collected during usual department visits. The main outcome measure was serum 25(OH)D (nm).ResultsPrevalence of inadequate/insufficient vitamin D intake differed between dialysis modality, with 31% and 43% found to be insufficient (<50 nm) and 4% and 33% found to be deficient (<25 nm) in HD and PD patients, respectively (P < 0.001). In HD patients, there was a correlation between diet and supplemental vitamin D intake and 25(OH)D (ρ = 0.84, P < 0.001) and average sun exposure and 25(OH)D (ρ = 0.50, P < 0.02). There were no associations in PD patients. The results remained significant for vitamin D intake after multiple regression, adjusting for age, gender and sun exposure.ConclusionsThe results highlight a strong association between vitamin D intake and 25(OH)D in HD but not PD patients, with implications for replacement recommendations. The findings indicate that, even in a sunny climate, many dialysis patients are vitamin D deficient, highlighting the need for exploration of determinants and consequences.