bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of Human Clearance Based on Animal Data and Molecular Properties
Authors: Huang Wenkang , Geng Lv , Deng Rong , Lu Shaoyong , Ma Guangli , Yu Jianxiu , Zhang Jian , Liu Wei , Hou Tingjun , Lu Xuefeng 
Published: April 2015

Human clearance is often predicted prior to clinical study from in vivo preclinical data by virtue of interspecies allometric scaling methods. The aims of this study were to determine the important molecular descriptors for the extrapolation of animal data to human clearance and further to build a model to predict human clearance by combination of animal data and the selected molecular descriptors. These important molecular descriptors selected by genetic algorithm (GA) were from five classes: quantum mechanical, shadow indices, E‐state keys, molecular properties, and molecular property counts. Although the data set contained many outliers determined by the conventional Mahmood method, the variation of most outliers was reduced significantly by our final support vector machine (SVM) model. The values of cross‐validated correlation coefficient and root‐mean‐squared error (RMSE) for leave‐one‐out cross‐validation (LOOCV) of the final SVM model were 0.783 and 0.305, respectively. Meanwhile, the reliability and consistency of the final model were also validated by an external test set. In conclusion, the SVM model based on the molecular descriptors selected by GA and animal data achieved better prediction performance than the Mahmood method. This approach can be applied as an improved interspecies allometric scaling method in drug research and development.
Neuronal activity‐dependent regulation of retinal blood flow
Authors: Noonan Jonathan E , Lamoureux Ecosse L , Sarossy Marc 
Published: April 2015

AbstractBlood flow in the retina is intrinsically regulated to meet the metabolic demands of its constituent cells. Flickering light or stationary contrast reversals induce an increase in blood flow within seconds of the stimulus onset. This phenomenon is thought to compensate for an increase in ganglion cell activity and energy consumption. Ganglion cell activity is in turn dependent on signals from photoreceptors, bipolar cells, horizontal cells and amacrine cells. The physiological properties of these neurons determine how each type is affected by a particular light characteristic. Neuronal activity then triggers the release of signalling molecules that dilate local blood vessels and increase blood flow. Nitric oxide has been implicated as an important mediator, but metabolites of arachidonic acid may also be involved. Detailed elucidation of these mechanisms, together with advances in imaging technology, may facilitate the use of neurovascular tests to improve the detection of retinal damage in pathological conditions.
Treatment escalation options for patients with type 2 diabetes after failure of exenatide twice daily or glimepiride added to metformin: results from the prospective European Exenatide (EUREXA) study
Authors: Schernthaner G. , Rosas‐Guzmán J. , Dotta F. , Guerci B. , Simó R. , Festa A. , Kiljański J. , Zhou M. , Gallwitz B. 
Published: April 2015

AimsTo evaluate third‐line thiazolidinedione (TZD) or glimepiride therapy in patients inadequately controlled on metformin + exenatide twice daily, and third‐line exenatide twice daily in patients inadequately controlled on metformin + glimepiride.MethodsIn this randomized, open‐label, multicentre trial, 144 patients with type 2 diabetes inadequately controlled [glycated haemoglobin (HbA1c) >9% (75 mmol/mol) after 3 months' treatment or >7% (53 mmol/mol) at two consecutive visits 3 months apart, after 6 months' treatment] on metformin + exenatide twice daily were re‐randomized to add‐on TZD or glimepiride, and 166 patients inadequately controlled on metformin + glimepiride received add‐on exenatide twice daily. Changes in HbA1c, body mass index (BMI), lipids, hypoglycaemia and vital signs were evaluated.ResultsThe median duration of triple therapy was ∼2 years. In patients inadequately controlled on metformin + exenatide twice daily, add‐on TZD decreased HbA1c levels significantly better than add‐on glimepiride: 130‐week difference 0.48% [95% confidence interval (CI) 0.19–0.77] or 5.2 mmol/mol (95% CI 2.1–8.4; p = 0.001), but with significantly increased BMI and systolic blood pressure. The ratio of documented symptomatic (blood glucose ≤70 mg/dl [3.9 mmol/l]) hypoglycaemia rates for add‐on glimepiride to add‐on TZD was 8.48 (p < 0.0001). Add‐on exenatide twice daily after metformin + glimepiride significantly reduced HbA1c levels: mean [standard deviation (s.d.)] change from baseline −0.35 (0.89)% [−3.8 (9.7) mmol/mol] and BMI: mean (s.d.) change from baseline −0.82 (1.9) kg/m2 at 130 weeks, with a slightly increased rate of documented symptomatic hypoglycaemia from metformin + glimepiride (ratio 1.49).ConclusionsTZD, but not glimepiride, was an effective and well tolerated third‐line therapy in patients without glycaemic control after long‐term therapy with metformin + exenatide twice daily. Exenatide twice daily was an effective and well tolerated third‐line therapy in patients inadequately controlled on metformin + glimepiride.
Modulation of platelet and monocyte function by the chemokine fractalkine (CX3CL1) in cardiovascular disease
Authors: Flierl Ulrike , Bauersachs Johann , Schäfer Andreas 
Published: April 2015

AbstractBackgroundThe chemokine fractalkine, CX3CL1, bears unique features within the chemokine family: it exists in a membrane bound form acting as an adhesion molecule and surface receptor; however, when cleaved by ADAM 10, it functions as a soluble chemokine. Fractalkine and its chemokine receptor CX3CR1 are known to have multiple roles in diverse human diseases, for example inflammatory diseases, rheumatoid arthritis, renal diseases and atherosclerosis.Materials and methodsThis review is based on the material obtained via PubMed up to November 2014. The key search terms used were ‘fractalkine’, ‘CX3CL1’, ‘CX3CR1’, ‘cardiovascular disease’, ‘platelets’, ‘monocytes’ and ‘platelet–monocyte complexes’.ResultsAtherosclerosis is recognized as a highly inflammatory disease, and it has become increasingly evident that the immune system plays an important role in atherogenesis and atheroprogression. Two blood cell populations are crucially involved in the early development of atherosclerotic lesions: monocytes and platelets. They are detected at vascular sites of endothelial dysfunction and are involved in inflammatory immune responses. These cells directly interact with each other, forming platelet–monocyte complexes that are increased in cardiovascular diseases. During the development of atherosclerosis, fractalkine mediates leukocyte recruitment to the inflamed endothelium, which promotes early formation of lesions. This process only effectively works in the presence of activated platelets. It has been suggested that fractalkine and its receptor contribute to platelet–monocyte aggregate formation underlining the two important impacts of this chemokine for platelets as well as monocytes.ConclusionInteresting data hint at a role of fractalkine for platelet activation, adhesion and subsequent monocyte recruitment to activated endothelial cells in cardiovascular diseases. However, the exact mechanisms remain to become unravelled.
Heat waves imposed during early pod development in soybean (Glycine max) cause significant yield loss despite a rapid recovery from oxidative stress
Authors: Siebers Matthew H. , Yendrek Craig R. , Drag David , Locke Anna M. , Rios Acosta Lorena , Leakey Andrew D. B. , Ainsworth Elizabeth A. , Bernacchi Carl J. , Ort Donald R. 
Published: April 2015

AbstractHeat waves already have a large impact on crops and are predicted to become more intense and more frequent in the future. In this study, heat waves were imposed on soybean using infrared heating technology in a fully open‐air field experiment. Five separate heat waves were applied to field‐grown soybean (Glycine max) in central Illinois, three in 2010 and two in 2011. Thirty years of historical weather data from Illinois were analyzed to determine the length and intensity of a regionally realistic heat wave resulting in experimental heat wave treatments during which day and night canopy temperatures were elevated 6 °C above ambient for 3 days. Heat waves were applied during early or late reproductive stages to determine whether and when heat waves had an impact on carbon metabolism and seed yield. By the third day of each heat wave, net photosynthesis (A), specific leaf weight (SLW), and leaf total nonstructural carbohydrate concentration (TNC) were decreased, while leaf oxidative stress was increased. However, A, SLW, TNC, and measures of oxidative stress were no different than the control ca. 12 h after the heat waves ended, indicating rapid physiological recovery from the high‐temperature stress. That end of season seed yield was reduced (~10%) only when heat waves were applied during early pod developmental stages indicates the yield loss had more to do with direct impacts of the heat waves on reproductive process than on photosynthesis. Soybean was unable to mitigate yield loss after heat waves given during late reproductive stages. This study shows that short high‐temperature stress events that reduce photosynthesis and increase oxidative stress resulted in significant losses to soybean production in the Midwest, U.S. The study also suggests that to mitigate heat wave‐induced yield loss, soybean needs improved reproductive and photosynthetic tolerance to high but increasingly common temperatures.
Would protecting tropical forest fragments provide carbon and biodiversity cobenefits under REDD+?
Authors: Magnago Luiz Fernando S. , Magrach Ainhoa , Laurance William F. , Martins Sebastião V. , Meira‐Neto João Augusto A. , Simonelli Marcelo , Edwards David P. 
Published: April 2015

AbstractTropical forests store vast amounts of carbon and are the most biodiverse terrestrial habitats, yet they are being converted and degraded at alarming rates. Given global shortfalls in the budgets required to prevent carbon and biodiversity loss, we need to seek solutions that simultaneously address both issues. Of particular interest are carbon‐based payments under the Reducing Emissions from Deforestation and Forest Degradation (REDD+) mechanism to also conserve biodiversity at no additional cost. One potential is for REDD+ to protect forest fragments, especially within biomes where contiguous forest cover has diminished dramatically, but we require empirical tests of the strength of any carbon and biodiversity cobenefits in such fragmented systems. Using the globally threatened Atlantic Forest landscape, we measured above‐ground carbon stocks within forest fragments spanning 13 to 23 442 ha in area and with different degrees of isolation. We related these stocks to tree community structure and to the richness and abundance of endemic and IUCN Red‐listed species. We found that increasing fragment size has a positive relationship with above‐ground carbon stock and with abundance of IUCN Red‐listed species and tree community structure. We also found negative relationships between distance from large forest block and tree community structure, endemic species richness and abundance, and IUCN Red‐listed species abundance. These resulted in positive congruence between carbon stocks and Red‐listed species, and the abundance and richness of endemic species, demonstrating vital cobenefits. As such, protecting forest fragments in hotspots of biodiversity, particularly larger fragments and those closest to sources, offers important carbon and biodiversity cobenefits. More generally, our results suggest that macroscale models of cobenefits under REDD+ have likely overlooked key benefits at small scales, indicating the necessity to apply models that include finer‐grained assessments in fragmented landscapes rather than using averaged coarse‐grained cells.
The Prevalence of Mixed Helicobacter pylori Infections in Symptomatic and Asymptomatic Subjects in Dhaka, Bangladesh
Authors: Kibria Khandoker Mohammad K. , Hossain Md Enayet , Sultana Jinath , Sarker Shafiqul A. , Bardhan Pradip Kumar , Rahman Motiur , Nahar Shamsun 
Published: April 2015

AbstractBackgroundHelicobacter pylori is a highly genetically diverse bacterial species, which can persist in the gastric environment for decades. Recent studies have shown that single infections predominate in developed countries, whereas mixed infections are more prevalent in developing countries. Mixed infections of this bacterium may be important for adaptation to the hostile gastric environment and may facilitate dyspeptic symptoms.Materials and MethodsTo calculate the prevalence of mixed infections in symptomatic and asymptomatic subjects, 2010 H. pylori isolates collected from 83 symptomatic and 91 asymptomatic subjects from Dhaka, Bangladesh, were analyzed by (i) random amplified polymorphic DNA fingerprinting (RAPD) and (ii) multiplex PCR amplification for cagA and vacA virulence gene alleles.ResultsThe overall prevalence of mixed H. pylori infection was 60.15% (77/128), indicating substantial co‐colonization in this population. We additionally found that symptomatic subjects (53%) had a significantly higher rate of mixed infection than asymptomatic individuals (36.3%) (p = .016) and that the prevalence of the cagA and vacA and vacA m1/s1 and vacA m2/s1 alleles were higher in subjects with mixed infection.ConclusionOur findings suggest that an increased diversity of the H. pylori strains in the gastric environment may contribute to the development of disease symptoms.
Primary central nervous system diffuse large B‐cell lymphoma has poorer immune cell infiltration and prognosis than its peripheral counterpart
Authors: Chang Chen , Lin Ching‐Hung , Cheng Ann‐Lii , Medeiros L Jeffrey , Chang Kung‐Chao 
Published: April 2015

AimsPrimary central nervous system (CNS) diffuse large B‐cell lymphoma (PCNSL) is an ominous disease with a poor prognosis. The brain is an immune‐privileged sanctuary, and this may contribute to an ineffective host immune response and thus a poorer outcome. The aim of this study was therefore to study the difference in the immune composition inPCNSLand non‐CNSdiffuse large B‐cell lymphoma (DLBCL), and the role of the immune response inPCNSLprognosis.Methods and resultsThirty‐two biopsy specimens ofPCNSLand 30 specimens of low‐stage non‐CNS DLBCLfrom immunocompetent patients formed the study group. The density and distribution of immune cells, including dendritic cells (dendritic cell‐specific lysosomal‐associated membrane protein‐positive and S100‐positive), effector/memory T cells (CD45RO‐positive), and cytotoxic T cells (granzyme B‐positive), and the expression ofHLA‐DRby lymphoma cells, were evaluated immunohistochemically.PCNSLpatients showed poorer overall survival (P = 0.032). On comparison of thePCNSLandDLBCLbiopsy specimens, thePCNSLcells showed lessHLA‐DRexpression (P = 0.003), and there were fewer S100‐positive cells (P < 0.01), and effector T cells (P = 0.026) infiltratingPCNSLthan infiltratingDLBCL. ForPCNSLpatients, fewer cytotoxic T cells in the background constituted a poor prognostic factor (P = 0.004). Intratumoral S100‐positive cell infiltration was positively correlated with T‐cell infiltration, and a T‐cell rimming pattern.ConclusionsInPCNSL, the baseline antitumour immune response is less as compared with non‐CNS DLBCL, and this response may play a role in the poorer prognosis. Adjuvant dendritic cell and T‐cell immunotherapy may further boost treatment responses inPCNSLpatients.
International travel in the immunocompromised patient: a cross‐sectional survey of travel advice in 254 consecutive patients
Authors: Bialy C. , Horne K. , Dendle C. , Kanellis J. , Littlejohn G. , Ratnam I. , Woolley I. 
Published: April 2015

AbstractAimsOur primary aim was to determine the rate of overseas travel in immunocompromised individuals attending appropriate clinics at an Australian tertiary care hospital. We also aimed to characterise health‐seeking behaviour prior to travel and investigated sources of pre‐travel advice, compared travel patterns and activities between three specific immunosuppressed groups, and examined pre‐immunosuppression patient serology.MethodsWe implemented a cross‐sectional survey of patients between February and August 2012. This survey was implemented among three outpatient populations at Monash Medical Centre, an Australian tertiary care hospital.ResultsWe recruited 254 immunosuppressed adults from three patient populations: human immunodeficiency virus‐positive individuals, renal transplant patients and rheumatology patients requiring immunosuppressive therapy. No clinical intervention was performed. In the 10 years preceding the survey, 153 (60.2%) participants reported international travel. Of these, 105 (68.6%) were immunosuppressed at the time of travel. These patients were 47.6% male and 60% Australian born. Forty per cent were visiting friends and relatives as part of their travel. Fifty‐four per cent of those immunocompromised at the time of travel were going to high‐risk destinations. Pathology files indicated that serological screening was frequently not performed prior to immunosuppression in the renal transplant and rheumatology groups.ConclusionsImmunocompromised patients often travel to high‐risk destinations with limited or inadequate pre‐travel preparations. Doctors caring for the immunocompromised should be aware of travel risks, suitable vaccination protocols and when to refer to specialist travel clinics.
Nuclear medicine incident reporting in Australia: control charts and notification rates inform quality improvement
Authors: Larcos G. , Collins L. T. , Georgiou A. , Westbrook J. I. 
Published: April 2015

AbstractBackgroundAustralia has a statutory incident reporting system for radiopharmaceutical maladministrations, but additional research into registry data is required for the purpose of quality improvement in nuclear medicine.AimsWe (i) used control charts to identify factors contributing to special cause variation (indicating higher than expected rates) in maladministrations and (ii) evaluated the impact of heterogeneous notification criteria and extent of underreporting among jurisdictions and individual facilities, respectively.MethodsAnonymised summaries of Australian Radiation Incident Register reports permitted calculation of national monthly maladministration notification rates for 2007–2012 and preparation of control charts. Multivariate logistic regression assessed the association of population, insurance and regulatory characteristics with maladministration notifications in each Australian State and Territory. Maladministration notification rates from two facilities with familiarity of notification processes and commitment to radiation protection were compared with those elsewhere.ResultsSpecial cause variation occurred in only 3 months, but contributed to 21% of all incidents (42 of 197 patients), mainly because of ‘clusters’ of maladministrations (n = 24) arising from errors in bulk radiopharmaceutical dispensing. Maladministration notification rates varied significantly between jurisdictions (0 to 12.2 maladministrations per 100 000 procedures (P < 0.05)) and individual facilities (31.7 vs 5.8 per 100 000; χ2 = 40; 1 degree of freedom, P < 0.001).ConclusionsUnexpected increases in maladministration notifications predominantly relate to incident ‘clusters’ affecting multiple patients. The bulk preparation of radiopharmaceuticals is a vulnerable process and merits additional safeguards. Maladministration notification rates in Australia are heterogeneous. Adopting uniform maladministration notification criteria among States and Territories and methods to overcome underreporting are warranted.
Physiological roles of miR‐155
Authors: Mashima Ryuichi 
Published: April 2015

SummarymiR‐155 is involved in non‐coding microRNAs found in humans, mice and chickens of which the sequence is conserved. Historically, miR‐155 was identified as a B‐cell integration cluster (bic), which induces B‐cell leucosis in chickens, by its activation through viral promoter insertion. Subsequent studies have shown that transgenic mice expressing miR‐155 in B cells generated lymphoma, showing that miR‐155 is oncogenic. Biochemical investigation identifies many substrates of miR‐155, and one of them in B cells and macrophages is the SH2‐domain containing inositol‐5′‐phosphatase 1. A deficiency of miR‐155 in the immune system causes attenuated immune functions. Clinically, several types of malignancy including diffuse large B‐cell lymphoma have high miR‐155 expression levels.
Clinical differences between respiratory viral and bacterial mono‐ and dual pathogen detected among Singapore military servicemen with febrile respiratory illness
Authors: Ho Zheng Jie Marc , Zhao Xiahong , Cook Alex R. , Loh Jin Phang , Ng Sock Hoon , Tan Boon Huan , Lee Vernon J. 
Published: April 2015

BackgroundAlthough it is known that febrile respiratory illnesses (FRI) may be caused by multiple respiratory pathogens, there are no population‐level studies describing its impact on clinical disease.MethodsBetween May 2009 and October 2012, 7733 FRI patients and controls in the Singapore military had clinical data and nasal wash samples collected prospectively and sent for PCR testing. Patients with one pathogen detected (mono‐pathogen) were compared with those with two pathogens (dual pathogen) for differences in basic demographics and clinical presentation.ResultsIn total, 45.8% had one pathogen detected, 20.2% had two pathogens detected, 30.9% had no pathogens detected, and 3.1% had more than two pathogens. Multiple pathogens were associated with recruits, those with asthma and non‐smokers. Influenza A (80.0%), influenza B (73.0%) and mycoplasma (70.6%) were most commonly associated with mono‐infections, while adenovirus was most commonly associated with dual infections (62.9%). Influenza A paired with S. pneumoniae had higher proportions of chills and rigors than their respective mono‐pathogens (P = 0.03, P = 0.009). H. influenzae paired with either enterovirus or parainfluenzae had higher proportions of cough with phlegm than their respective mono‐pathogens. Although there were observed differences in mean proportions of body temperature, nasal symptoms, sore throat, body aches and joint pains between viral and bacterial mono‐pathogens, there were few differences between distinct dual‐pathogen pairs and their respective mono‐pathogen counterparts.ConclusionA substantial number of FRI patients have multiple pathogens detected. Observed clinical differences between patients of dual pathogen and mono‐pathogen indicate the likely presence of complex microbial interactions between the various pathogens.