bluuebunny/crossref_metadata_2025_split huggingface dataset:
Set‐valued dynamic treatment regimes for competing outcomes
Authors: Laber Eric B. , Lizotte Daniel J. , Ferguson Bradley 
Published: January 2014

SummaryDynamic treatment regimes (DTRs) operationalize the clinical decision process as a sequence of functions, one for each clinical decision, where each function maps up‐to‐date patient information to a single recommended treatment. Current methods for estimating optimal DTRs, for example Q‐learning, require the specification of a single outcome by which the “goodness” of competing dynamic treatment regimes is measured. However, this is an over‐simplification of the goal of clinical decision making, which aims to balance several potentially competing outcomes, for example, symptom relief and side‐effect burden. When there are competing outcomes and patients do not know or cannot communicate their preferences, formation of a single composite outcome that correctly balances the competing outcomes is not possible. This problem also occurs when patient preferences evolve over time. We propose a method for constructing DTRs that accommodates competing outcomes by recommending sets of treatments at each decision point. Formally, we construct a sequence of set‐valued functions that take as input up‐to‐date patient information and give as output a recommended subset of the possible treatments. For a given patient history, the recommended set of treatments contains all treatments that produce non‐inferior outcome vectors. Constructing these set‐valued functions requires solving a non‐trivial enumeration problem. We offer an exact enumeration algorithm by recasting the problem as a linear mixed integer program. The proposed methods are illustrated using data from the CATIE schizophrenia study.
Obesity, sex and pubertal status affect appetite hormone responses to a mixed glucose and whey protein drink in adolescents
Authors: Patel Barkha P. , Anderson G. Harvey , Vien Shirley , Bellissimo Nick , McCrindle Brian W. , Hamilton Jill K. 
Published: January 2014

SummaryBackground and ObjectivesLittle information is available on how food intake regulatory hormones may be altered during pubertal development and across the weight spectrum in adolescents. Therefore, the effect of obesity, sex and pubertal status on subjective appetite and appetite hormones in response to a mixed glucose and whey protein drink was determined in 8–18 year old adolescents.Patients and MethodsA cross‐sectional cohort study was conducted at the Hospital for Sick Children, Toronto. After a 12 h fast, normal weight (n = 5 female, 4 male) and obese (n = 5 female, 4 male) adolescents (Experiment 1), and pre‐early pubertal (n = 10) and mid‐late pubertal (n = 10) obese male adolescents (Experiment 2) consumed a 250 ml glucose (30 g) and whey protein (30 g) beverage. Insulin, PYY, ghrelin and subjective appetite were measured over 120 min.ResultsObese adolescents (Experiment 1) have higher insulin, PYY and lower ghrelin (P < 0·006) than normal weight controls, with a more pronounced effect in males (P < 0·037). Puberty (Experiment 2) did not affect insulin (P = 0·305), but the change in PYY in response to the drink was greater (P = 0·032) and ghrelin was lower (P = 0·026) in mid‐late pubertal than pre‐early pubertal obese males. Average appetite 60 min post‐drink was higher in obese and mid‐late pubertal adolescents, but not related to hormone changes.ConclusionsObesity, sex and pubertal status affect macronutrient‐stimulated appetite hormone secretion and these factors may alter food intake in obese children during pubertal development.
The relative contributions of the abdominal visceral and subcutaneous fat depots to cardiometabolic risk in youth
Authors: Kelly A. S. , Dengel D. R. , Hodges J. , Zhang L. , Moran A. , Chow L. , Sinaiko A. R. , Steinberger J. 
Published: January 2014

SummaryThe aim of this study was to evaluate the association of abdominal visceral and subcutaneous fat, independent of total body fat, with cardiometabolic risk factors and insulin resistance among youth. Visceral and subcutaneous fat, percentage total body fat, insulin resistance (adjusted for lean body mass: Mlbm), blood pressure, glucose, insulin and lipids were obtained in 472 youth ages 6–18 years. Linear regression, adjusted for age, sex, race, Tanner stage and percentage total body fat, was used to evaluate associations of visceral and subcutaneous fat with cardiometabolic risk factors. Visceral fat was associated inversely with Mlbm (P = 0.003) and positively with fasting insulin (P = 0.002) and triglycerides (P = 0.002). Visceral fat levels above the mean were associated inversely with high‐density lipoprotein (HDL) cholesterol (P = 0.002), and positively with systolic blood pressure (P < 0.0001) and non‐HDL cholesterol (P < 0.0001). Subcutaneous fat was associated inversely with Mlbm (P = 0.003) and HDL cholesterol (P < 0.05), and positively with fasting glucose (P < 0.05), fasting insulin (P = 0.0003), systolic blood pressure (P = 0.005) and triglycerides (P = 0.003). Subcutaneous fat levels above the mean were associated with non‐HDL cholesterol (P = 0.0002). These findings suggest that there may be a threshold level of visceral and subcutaneous fat (regardless of total body fat), that when exceeded in childhood, is more likely to be associated with many cardiometabolic risk factors. Triglycerides and insulin resistance appear to be associated with these fat depots at even lower thresholds of abdominal adiposity.
Medical management of refractory epilepsy—Practical treatment with novel antiepileptic drugs
Authors: Ben‐Menachem Elinor 
Published: January 2014

SummaryThe ultimate treatment goal in epilepsy therapy is always freedom from seizures with as few treatment adverse effects as possible. If seizures persist with the first monotherapy, alternative monotherapy with another antiepileptic drug (AED) should be considered. Continuing seizures should lead to a reevaluation of differential diagnosis and adherence. Epilepsy surgery as an alternative therapy may be suitable in selected cases. If the diagnosis of epilepsy is established and epilepsy surgery is not appropriate, AED treatment should be optimized. Evidence for how to proceed is lacking. Concepts such as rational polytherapy have been advocated but remain speculative concerning better efficacy based on the use of AEDs with differing modes of action. A variety of new AEDs including rufinamide, lacosamide, vigabatrin, perampanel, and retigabine have been recently introduced in the United States. They are briefly characterized in this update review.
Developing DNA barcodes for species identification in Podophylloideae (Berberidaceae)
Authors: MAO Yun‐Rui , ZHANG Yong‐Hua , NAKAMURA Koh , GUAN Bi‐Cai , QIU Ying‐Xiong 
Published: January 2014

AbstractSpecies of Podophyllum, Dysosma, Sinopodophyllum, and Diphylleia, genera from Podophylloideae of Berberidaceae, have long been used in traditional herbal medicine in East Asia and/or North America. Accurate identification of the species of these four genera is crucial to their medicinal uses. In this study, we tested the utility of nine barcodes (matK, rbcL, atpH‐atpI, rpl32‐trnLUAG, rps18‐clpp, trnL‐trnF, trnL‐ndhJ, trnS‐trnfM, and internal transcribed spacer (ITS)) to discriminate different species of Podophylloideae. Thirty‐six individuals representing 12 species of Podophylloideae were collected from different locations in China, Japan, and North America. We assessed the feasibility of amplification and sequencing of all markers, examined the levels of the barcoding gap based on DNA sequence divergence between ranges of intra‐ and interspecific variation using pairwise distances, and further evaluated successful identifications using each barcode by similarity‐based and tree‐based methods. Results showed that nine barcodes, except rps18‐clpp, have a high level of primer universality and sequencing success. As a single barcode, ITS has the most variable sites, greater intra‐ and interspecific divergences, and the highest species discrimination rate (83%), followed by matK which has moderate variation and also high species discrimination rates. However, these species can also be discriminated by ITS alone, except Dysosma versipellis (Hance) M. Cheng ex T. S. Ying and D. pleiantha (Hance) Woodson. The combination of ITS + matK did not improve species resolution over ITS alone. Thus, we propose that ITS may be used as a sole region for identification of most species in Podophylloideae. The failure of ITS to distinguish D. versipellis and D. pleiantha is likely attributed to incomplete lineage sorting due to recent divergence of the two species.
Effect of Trilostane and Mitotane on Aldosterone Secretory Reserve in Dogs with Pituitary‐Dependent Hyperadrenocorticism
Authors: Reid L.E. , Behrend E.N. , Martin L.G. , Kemppainen R.J. , Ward C.R. , Lurye J.C. , Donovan T.C. , Lee H.P. 
Published: January 2014

BackgroundMaximal aldosterone secretion in healthy dogs occurs 30 minutes postadrenocorticotropin (ACTH; 5 μg/kg IV) stimulation. The effect of trilostane and mitotane on aldosterone at that time is unknown.ObjectivesTo assess the effect of trilostane and mitotane in dogs with pituitary‐dependent hyperadrenocorticism on aldosterone secretory reserve. To determine if aldosterone concentration correlates with electrolyte concentrations.AnimalsSerum collected from 79 client‐owned dogs and 33 stored samples.MethodsClient‐owned dogs hadACTHstimulation tests with cortisol concentrations measured at 0 and 60 minutes and aldosterone concentrations measured at 0, 30, and 60 minutes. Stored samples had aldosterone concentrations measured at 0 and 60 minutes. Ten historical clinically healthy controls were included. All had basal sodium and potassium concentrations measured.ResultsThe aldosterone concentrations in the mitotane‐ and trilostane‐treated dogs at 30 and 60 minutes post‐ACTHwere significantly lower than in clinically healthy dogs; no significant difference was detected in aldosterone concentration between 30 and 60 minutes in treated dogs. However, a significantly higher percentage of dogs had decreased aldosterone secretory reserve detected at 30 minutes than at 60 minutes. At 30 minutes, decreased secretory reserve was detected in 49% and 78% of trilostane‐ and mitotane‐treated dogs, respectively. No correlation was detected between aldosterone and serum electrolyte concentrations.Conclusions and Clinical ImportanceDecreased aldosterone secretory reserve is common in trilostane‐ and mitotane‐treated dogs; it cannot be predicted by measurement of serum electrolyte concentrations. Aldosterone concentration at 30 minutes post‐ACTHstimulation identifies more dogs with decreased aldosterone secretory reserve than conventional testing at 60 minutes.
Structural insights into the specific recognition of N‐heterocycle biodenitrogenation‐derived substrates by microbial amide hydrolases
Authors: Wu Geng , Chen Duoduo , Tang Hongzhi , Ren Yiling , Chen Qihua , Lv Yang , Zhang Zhenyi , Zhao Yi‐Lei , Yao Yuxiang , Xu Ping 
Published: January 2014

SummaryN‐heterocyclic compounds from industrial wastes, including nicotine, are environmental pollutants or toxicants responsible for a variety of health problems. Microbial biodegradation is an attractive strategy for the removal of N‐heterocyclic pollutants, during which carbon–nitrogen bonds in N‐heterocycles are converted to amide bonds and subsequently severed by amide hydrolases. Previous studies have failed to clarify the molecular mechanism through which amide hydrolases selectively recognize diverse amide substrates and complete the biodenitrogenation process. In this study, structural, computational and enzymatic analyses showed how the N‐formylmaleamate deformylase Nfo and the maleamate amidase Ami, two pivotal amide hydrolases in the nicotine catabolic pathway of Pseudomonas putida S16, specifically recognize their respective substrates. In addition, comparison of the α‐β‐α groups of amidases, which include Ami, pinpointed several subgroup‐characteristic residues differentiating the two classes of amide substrates as containing either carboxylate groups or aromatic rings. Furthermore, this study reveals the molecular mechanism through which the specially tailored active sites of deformylases and amidases selectively recognize their unique substrates. Our work thus provides a thorough elucidation of the molecular mechanism through which amide hydrolases accomplish substrate‐specific recognition in the microbial N‐heterocycles biodenitrogenation pathway.
Implications of the changes in serum neutrophil gelatinase‐associated lipocalin and cystatin C in patients with chronic kidney disease
Authors: Shen Shui‐Juan , Hu Zuo‐Xiang , Li Qing‐Hua , Wang Shi‐Min , Song Chun‐Jiao , Wu Dong‐Dong , He Jian‐Ling , Guan Ji‐Chao , Shan Juan‐Ping 
Published: January 2014

AbstractAimEarly intervention in patients with chronic kidney disease (CKD) significantly improves the prognosis. The present widely used markers of renal function, such as serum creatinine (sCr), fail to reflect early renal damage and predict the progression of disease. The authors aimed to evaluate whether neutrophil gelatinase‐associated lipocalin (NGAL), a novel specific biomarker of acute kidney injury, could predict the progression of CKD.MethodsWe identified 92 patients with stage 2–4 CKD caused by primary chronic glomerulonephritis. The patients were followed for 2 years, the changes in NGAL levels in the progressive and non‐progressive groups were compared.ResultsFirst, the serum NGAL levels of patients with stage 2–4 CKD were significantly increased compared with the control group. Second, based on Pearson correlation analysis, positive correlations existed between NGAL and cystatin C levels and between NGAL and sCr levels. Third, bounded by the progress of renal function, the area under the curve of serum NGAL was 0.872 (95% confidence interval, 0.786–0.933), which suggests a blood NGAL cut‐off level of 246 ng/mL (sensitivity 85.19%, specificity 81.54%). Fourth, Kaplan–Meier survival curve analysis showed that the serum NGAL level was closely related to the end‐point of renal function in patients with CKD. Fifth, Cox multivariate regression analysis showed that the estimated glomerular filtration rate and blood NGAL are associated with progression of CKD.ConclusionSerum NGAL is an effective biomarker for detecting early‐stage renal damage in CKD patients. Serum NGAL was significantly correlated with the severity of renal damage and the progression of renal function deterioration.
Short mandible – a possible risk factor for cleft palate with/without a cleft lip
Authors: Hermann N. V. , Darvann T. A. , Ersbøll B. K. , Kreiborg S. 
Published: January 2014

Structured AbstractObjectivesTo estimate the influence of a short mandible on the risk of developing a cleft palate with/without a cleft lip (CP).Setting and sample populationThe retrospective sample consisted of 115 2‐month‐old Danish infants with CP, and 70 control infants with unilateral incomplete cleft lip (UICL).Material and MethodsCephalometric X‐rays were obtained. Mandibular length (Lm) was measured and corrected for body length (Lb) to remove influence of varying body length in the sample. Logistic regression was applied to the corrected mandibular length (Lmc) to calculate the risk of having a cleft palate.ResultsThe mean mandibular length in the group with CP was about 4 mm shorter than in the control group. Odds ratio (OR) was calculated to be 0.58 (95% confidence interval 0.48–0.68), implying that an individual's risk of cleft palate with/without a cleft lip increases about 50% per mm decrease in mandibular length.ConclusionsA special facial type including a short mandible is a possible risk factor for cleft palate, and it was found that the risk of cleft palate increases 58% per mm decreases in mandibular length.
Genetic basis of coaggregation receptor polysaccharide biosynthesis in Streptococcus sanguinis and related species
Authors: Yang J. , Yoshida Y. , Cisar J.O. 
Published: January 2014

SummaryInterbacterial adhesion between streptococci and actinomyces promotes early dental plaque biofilm development. Recognition of coaggregation receptor polysaccharides (RPS) on strains of Streptococcus sanguinis, Streptococcus gordonii and Streptococcus oralis by Actinomyces spp. type 2 fimbriae is the principal mechanism of these interactions. Previous studies of genetic loci for synthesis of RPS (rps) and RPS precursors (rml, galE1 and galE2) in S. gordonii 38 and S. oralis 34 revealed differences between these strains. To determine whether these differences are strain‐specific or species‐specific, we identified and compared loci for polysaccharide biosynthesis in additional strains of these species and in several strains of the previously unstudied species, S. sanguinis. Genes for synthesis of RPS precursors distinguished the rps loci of different streptococci. Hence, rml genes for synthesis of TDP‐L‐Rha were in rps loci of S. oralis strains but at other loci in S. gordonii and S. sanguinis. Genes for two distinct galactose epimerases were also distributed differently. Hence, galE1 for epimerization of UDP‐Glc and UDP‐Gal was in galactose operons of S. gordonii and S. sanguinis strains but surprisingly, this gene was not present in S. oralis. Moreover, galE2 for epimerization of both UDP‐Glc and UDP‐Gal and UDP‐GlcNAc and UDP‐GalNAc was at a different locus in each species, including rps operons of S. sanguinis. The findings provide insight into cell surface properties that distinguish different RPS‐producing streptococci and open an approach for identifying these bacteria based on the arrangement of genes for synthesis of polysaccharide precursors.
Variability in the decision process leading to saccades: A specific marker for schizophrenia?
Authors: Theleritis Christos , Evdokimidis Ioannis , Smyrnis Nikolaos 
Published: January 2014

AbstractIn a previous study, deviance in the reaction time (RT) distribution of saccades for patients with schizophrenia was explained using an oculomotor decision model. Here, RTs of visually guided saccades in young healthy men, healthy children, older adults, patients with schizophrenia, and patients with obsessive compulsive disorder (OCD) were modeled to study the specificity of this decision process deviance for schizophrenia. The mean decision rate to saccade decreased with age in children and increased in older adults while the decision rate intrasubject variability (ISV) was not modulated by age. A significant increase in ISV of the decision rate was confirmed for patients with schizophrenia but not OCD compared to healthy controls. There was no effect of medication on model parameters in the OCD patient group. These results confirm the specificity of the deviance in a simple oculomotor decision process in schizophrenia.
Aggregate Degradation Characteristics of Stone Mastic Asphalt Mixtures
Authors: Hainin Mohd. Rosli , Mohd Akhir Norliza , Putra Jaya Ramadhansyah , Md. Yusoff Nur Izzi , Yaacob Haryati , Ismail Che Ros , Abdul Hassan Norhidayah 
Published: January 2014

Stone Mastic Asphalt (SMA) mixtures are designed to have a high coarse aggregate content and stone-on-stone contact, which results in more stress on the coarse aggregates during compaction and traffic loading. As a result, aggregates tend to break down more in SMA mixtures than in conventional dense graded mixtures. Aggregate degradation during compaction and traffic loading may cause changes in the original gradation and thus may also affect the volumetric parameters of SMA mixtures. Therefore, this study was conducted to determine the degree of aggregate degradation in SMA mixtures due to the compaction process. Aggregates of two Nominal Maximum Aggregates Sizes (NMAS), designated as SMA14 and SMA20, were compacted using 50 blows of the Marshall Hammer and 100 gyrations of the Superpave Gyratory Compactor (SGC). The verified samples were then prepared and extracted using the Centrifuge Method. The relationship between aggregate degradation and influencing factors, such as compaction effort and volumetric properties were investigated. Aggregate degradation by the Marshall Hammer was found to be significantly higher than degradation by the SGC. Voids in the mineral aggregate (VMA) of either compaction method decrease or are almost the same when aggregate degradation is not significant. SGC method can be selected to represent the field roller that results in a similar trend of aggregate degradation.
Offline multiple adaptive planning strategy for concurrent irradiation of the prostate and pelvic lymph nodes
Authors: Qi Peng , Pouliot Jean , Roach Mack , Xia Ping 
Published: January 2014

Purpose:Concurrent irradiation of the prostate and pelvic lymph nodes (PLNs) can be challenging due to the independent motion of the two target volumes. To address this challenge, the authors have proposed a strategy referred to as Multiple Adaptive Planning (MAP). To minimize the number of MAP plans, the authors’ previous work only considered the prostate motion in one major direction. After analyzing the pattern of the prostate motion, the authors investigated a practical number of intensity‐modulated radiotherapy (IMRT) plans needed to accommodate the prostate motion in two major directions simultaneously.Methods:Six patients, who received concurrent irradiation of the prostate and PLNs, were selected for this study. Nine MAP‐IMRT plans were created for each patient with nine prostate contours that represented the prostate at nine locations with respect to the PLNs, including the original prostate contour and eight contours shifted either 5 mm in a single anterior‐posterior (A‐P), or superior‐inferior (S‐I) direction, or 5 mm in both A‐P and S‐I directions simultaneously. From archived megavoltage cone beam CT (MV‐CBCT) and a dual imaging registration, 17 MV‐CBCTs from 33 available MV‐CBCT from these patients showed large prostate displacements (>3 mm in any direction) with respect to the pelvic bones. For each of these 17 fractions, one of nine MAP‐IMRT plans was retrospectively selected and applied to the MV‐CBCT for dose calculation. For comparison, a simulated isocenter‐shifting plan and a reoptimized plan were also created for each of these 17 fractions. The doses to 95% (D95) of the prostate and PLNs, and the doses to 5% (D5) of the rectum and bladder were calculated and analyzed.Results:For the prostate, D95 > 97% of the prescription dose was observed in 16, 16, and 17 of 17 fractions for the MAP, isocenter‐shifted, and reoptimized plans, respectively. For PLNs, D95 > 97% of the prescription doses was observed in 10, 3, and 17 of 17 fractions for the three types of verification plans, respectively. The D5 (mean ± SD) of the rectum was 45.78 ± 5.75, 45.44 ± 4.64, and 44.64 ± 2.71 Gy, and the D5 (mean ± SD) of the bladder was 45.18 ± 2.70, 46.91 ± 3.04, and 45.67 ± 3.61 Gy for three types of verification plans, respectively.Conclusions:The MAP strategy with nine IMRT plans to accommodate the prostate motions in two major directions achieved good dose coverage to the prostate and PLNs. The MAP approach can be immediately used in clinical practice without requiring extra hardware and software.