bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased Acute Otitis Media With Treatment Failure After Introduction of the Ten-valent Pneumococcal Haemophilus influenzae Protein D Conjugate Vaccine
Authors: Eythorsson Elias , Hrafnkelsson Birgir , Erlendsdóttir Helga , Gudmundsson Sigmar Atli , Kristinsson Karl G. , Haraldsson Ásgeir 
Published: December 2017

Background:
Acute otitis media (AOM) nonresponsive to antibiotics is most commonly caused by antibiotic-resistant Streptococcus pneumoniae and Haemophilus influenzae. A strategy for treating these infections with parenteral ceftriaxone was adopted at the Children’s Hospital Iceland. The 10-valent pneumococcal H. influenzae protein D-conjugate vaccine was introduced into the vaccination program in Iceland in 2011. The aim was to study its effect on the incidence of AOM with treatment failure.

Methods:
This retrospective observational study included children who visited the Children’s Hospital Iceland because of AOM or received ceftriaxone, regardless of indication from 2008–2015. Incidence rate was calculated for prevaccine (2008–2011) and postvaccine (2012–2015) periods using person-years at risk within the hospital’s referral region. Incidence rate ratio of ceftriaxone treatment episodes of AOM was calculated using the Mantel–Haenzel method adjusting for age. Incidence risk ratio of ceftriaxone treatment if presenting to the hospital with AOM was calculated to adjust for rate of AOM visits.

Results:
Visits for AOM decreased from 47.5 to 33.9 visits per 1000 person-years, incidence rate ratio (IRR) 0.86 (95% confidence interval [CI]: 0.81–0.91), P < 0.001. Fewer AOM episodes were treated with ceftriaxone, decreasing from 6.49 to 2.96 treatment episodes per 1000 person-years, with an overall Mantel–Haenzel adjusted IRR 0.45 (95% CI: 0.37–0.54; P < 0.001). This remained significant after adjusting for the decrease in AOM visits, IRR 0.53 (95% CI: 0.44–0.63; P < 0.001).

Conclusions:
Visits for AOM and ceftriaxone use decreased significantly after H. influenzae protein D-conjugate vaccine introduction. The observed decrease in ceftriaxone use is presumed to represent a decline in AOM with treatment failure, secondary to a decrease in resistant infections.
Depth of Cervical Intraepithelial Neoplasia Grade 3 in Peruvian Women: Implications for Therapeutic Depth of Necrosis
Authors: Taxa Luis , Jeronimo Jose , Alonzo Todd A. , Gage Julia , Castle Philip E. , Cremer Miriam L. , Felix Juan C. 
Published: December 2017

Objective
To determine the involvement of cervical intraepithelial neoplasia grade 3 (CIN3) in a population of women in a lower-resource setting.

Methods
One hundred twelve consecutive cone excision specimens with histological diagnosis of CIN3 were retrieved from the National Institute of Neoplastic Diseases in Lima Peru. Two pathologists independently evaluated each specimen microscopically and confirmed 107 cases that could be measured by optical micrometry. Depth and breadth of the lesions were measured microscopically.

Results
The mean maximal depth of cervical involvement by CIN3 was 2 ± 0.13 mm; depth was less than 3.5 mm in 89.7% of cases and less than 5 mm in 93.5%. Mean breadth of CIN3 was 7.3 ± 4.4 mm; breadth was less than 15.9 mm in 95% of cases and less than 20.5 mm in 99.7%. The correlation coefficient between breadth and depth of CIN3 was 0.61. No significant correlation was found between age and depth.

Conclusions
Depth of CIN3 involvement in a developing country is significantly deeper than that reported in the United States. Treatment selection for women with CIN3 and risk of treatment failure may vary between developing and developed countries because of the difference in the depth of lesions. Countries with underscreened populations need to consider the increased disease severity in devising treatment strategies.
Impact of Trainee Involvement in Cervical Excision Procedures: Does Trainee Involvement Impact Quality?
Authors: Sullivan Stephanie A. , Clark Leslie H. , West Lindsay M. , Myrick Katie S. , Tran Arthur-Quan , Soper John T. , Rahangdale Lisa 
Published: December 2017

Objective
Cervical excision procedures are essential to the care of cervical dysplasia and malignancy. We sought to determine whether learner involvement in cervical excision procedures affects the quality of excision specimen.

Materials and Methods
A retrospective cohort study of cervical cancer patients diagnosed from July 1, 2000, to July 1, 2015, was performed. We included patients who had (1) a cervical excision procedure, either loop electrosurgical excision procedure or cold knife cone, and (2) pathologic information available. Primary outcome was the margin status of the specimen; secondary outcome was the size of the excision specimen including both width and depth. The exposure of interest was trainee participation, defined as resident physicians under the supervision of either a gynecologist or gynecologic oncologist. Descriptive statistics and general linear models were used for analysis.

Results
Ninety-four patients were identified. Overall, 58% (n = 54) of procedures were performed with trainee involvement. There was no difference in age, body mass index, or specimen width between trainee-performed and nontrainee-performed excisions. There was no significant difference in the status of margins with or without a trainee [44/57 (77%) and 29/37 (78%), respectively, p = .89]. There was a statistically significant difference in median specimen depth between trainee-performed and nontrainee-performed cases (15.4 mm vs 12 mm, p < .02). When adjusting for age, body mass index, excision type, indication, presence of trainee, and type of supervising physician, only the indication and type of excision were associated with greater depth of excision, (p < .01).

Conclusions
Trainee involvement in cervical excision procedures does not alter the quality of excision specimen.
The diversification of inequality
Authors: Brynin Malcolm , Longhi Simonetta , Zwysen Wouter 
Published: December 2017

AbstractWe examine intersectionality on the basis of increasingly complex interactions between gender and ethnic groups, which we argue derive from the growing diversity of these groups. While we critique the concept of superdiversity, we suggest that increased diversity leads to a ‘diversification of inequality’. This is characterised by an increasing incidence of inequality through the growth in migration and of the size and variety of ethnic minorities, and by a weakening of specific inequalities. We demonstrate this using the Labour Force Survey and conclude that there is a clear diversification of inequality but also that ethnicity is a more potent source of inequality than gender. Diversity also increases the reach of inequality through producing and increasing the number of intersections.
Intracoronary Thrombus Formation Following Carbon Monoxide Poisoning
Authors: Caron‐Cantin Marilou , Abbott Marcia , Brooks‐Lim Elizabeth , Adeagbo Bamidele 
Published: December 2017

AbstractThromboembolic events in the context of carbon monoxide (CO) exposure have been well described in the literature. Six cases of clinically significant coronary thrombosis following CO exposure were previously reported. However, factors affecting the development of coronary thrombus in CO exposure are poorly understood, and the significance of this finding in a forensic context is not clear. This article discusses a case of coronary thrombosis found at autopsy following a death in which CO poisoning was suspected. A 67‐year‐old man was found dead in his garage with four vehicles with their ignition in the “on” position and their tanks empty. At autopsy, severe coronary atherosclerosis and an acute nonocclusive coronary thrombus were found. Given the dissimilarities among cases and the presence of CO exposure, it was suggested that the coronary artery thrombosis is likely due to the inherent prothrombotic mechanism of CO, the only common denominator in all the cases.
Comparative efficacy of antiepileptic drugs in children and adolescents: A network meta‐analysis
Authors: Rosati Anna , Ilvento Lucrezia , Lucenteforte Ersilia , Pugi Alessandra , Crescioli Giada , McGreevy Kathleen S. , Virgili Gianni , Mugelli Alessandro , De Masi Salvatore , Guerrini Renzo 
Published: December 2017

SummaryObjectiveTo estimate the comparative efficacy among antiepileptic drugs in the pediatric population (0‐18 years).MethodsUsing the Embase and MEDLINE databases, we updated to February 2017 the search strategy of the National Institute for Health and Care Excellence guidelines for epilepsy. We only included randomized clinical trials conducted in children and mixed‐age populations. According to the PRISMA network meta‐analysis guideline, the study‐level quality assessment was made with the Cochrane risk‐of‐bias tool. Three investigators independently selected articles. The efficacy outcome was considered to be seizure freedom or ≥50% seizure reduction.ResultsWe selected 46 randomized clinical trials. A total of 5652 individuals were randomized to 22 antiepileptic drugs and placebo. The point estimates of carbamazepine and lamotrigine efficacy showed their superiority with respect to all comparator antiepileptic drugs for the treatment of newly diagnosed focal epilepsy. In refractory focal epilepsy, levetiracetam (odds ratio [OR] = 3.3, 95% credible interval [CrI] = 1.3‐7.6) and perampanel (OR = 2.5, 95% CrI = 1.1‐5.8) were more effective compared to placebo. Ethosuximide and valproic acid were both superior to lamotrigine against absence seizures. The OR point estimate showed the superiority of adrenocorticotropic hormone over all comparators in infantile spasms. A wide heterogeneity in the length of follow‐up was observed among the studies.SignificanceThis network meta‐analysis suggests that the quality of studies should be improved through the use of comparative designs, relevant outcomes, appropriate follow‐up length, and more reliable inclusion criteria.
Folliculotropism in pigmented facial macules: Differential diagnosis with reflectance confocal microscopy
Authors: Persechino Flavia , De Carvalho Nathalie , Ciardo Silvana , De Pace Barbara , Casari Alice , Chester Johanna , Kaleci Shaniko , Stanganelli Ignazio , Longo Caterina , Farnetani Francesca , Pellacani Giovanni 
Published: December 2017

AbstractPigmented facial macules are common on sun damage skin. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging. Reflectance confocal microscopy (RCM) has been proven to increase diagnostic accuracy of facial lesions. A total of 154 pigmented facial macules, retrospectively collected, were evaluated for the presence of already‐described RCM features and new parameters depicting aspects of the follicle. Melanocytic nests, roundish pagetoid cells, follicular infiltration, bulgings from the follicles and many bright dendrites and infiltration of the hair follicle (ie, folliculotropism) were found to be indicative of LM/LMM compared to non‐melanocytic skin neoplasms (NMSNs), with an overall sensitivity of 96% and specificity of 83%. Concerning NMSNs, solar lentigo and lichen planus‐like keratosis resulted better distinguishable from LM/LMM because usually lacking malignant features and presenting characteristic diagnostic parameters, such as epidermal cobblestone pattern and polycyclic papillary contours. On the other hand, distinction of pigmented actinic keratosis (PAK) resulted more difficult, and needing evaluation of hair follicle infiltration and bulging structures, due to the frequent observation of few bright dendrites in the epidermis, but predominantly not infiltrating the hair follicle (estimated specificity for PAK 53%). A detailed evaluation of the components of the folliculotropism may help to improve the diagnostic accuracy. The classification of the type, distribution and amount of cells, and the presence of bulging around the follicles seem to represent important tools for the differentiation between PAK and LM/LMM at RCM analysis.
Impact of Local Groundwater Flow Model Errors on Transport and a Practical Solution for the Issue
Authors: Panday Sorab , Bedekar Vivek , Langevin Christian D. 
Published: December 2017

AbstractA groundwater flow model is typically used to provide the flow field for conducting groundwater solute transport simulations. The advection term of the mass conserved formulation for groundwater transport assumes that the flow field is perfectly balanced and that all water flowing into a numerical grid cell is exactly balanced by outflows after accounting for sources/sinks or internal storage. However, in many complicated regional or site‐scale models, there may be localized flow balance errors that may be difficult to eliminate through tighter flow convergence tolerances due to simulation time constraints or numerical limits on convergence tolerances. Thus, if water is erroneously gained or lost within a grid cell during the flow computation, the solutes within it will also be numerically affected in the associated transport simulation. Transport solutions neglect this error in groundwater flow as the transport equations that are solved assume no error in flow. This flow imbalance error can however have consequences on the transport solution ranging from unnoticeable errors in the resulting concentrations to spurious oscillations that can grow in time and hinder further solution. An approach has been suggested here, to explicitly handle these flow imbalances during mass conserved advective transport computations and report them in the corresponding transport mass balance output, as corrections that are needed to handle errors originating in the flow solution. Example problems are provided to explain the concepts and demonstrate the impacts.
Circulating levels of miR‐122 and nonalcoholic fatty liver disease in pre‐pubertal obese children
Authors: Brandt S. , Roos J. , Inzaghi E. , Kotnik P. , Kovac J. , Battelino T. , Cianfarani S. , Nobili V. , Colajacomo M. , Kratzer W. , Denzer C. , Fischer‐Posovszky P. , Wabitsch M. 
Published: December 2017

SummaryObjectivesThe liver‐specific miR‐122 was proposed as biomarker for NAFLD in adults. Here, we investigated the relationship between miR‐122 levels, parameters of liver metabolism and NAFLD in pre‐pubertal obese children.MethodsParameters of liver metabolism (ALT, AST and GGT) of three European cohorts were included (German cohort [n = 71; age: 11.53 ± 1.29 years; BMI z‐score: 2.96 ± 0.64], Italian cohort [n = 45; age: 9.60 ± 2.11 years; BMI z‐score: 3.57 ± 1.16], Slovenian cohort [n = 31; age: 7.53 ± 1.47 years; BMI z‐score: 3.66 ± 0.88]). MiR‐122 levels and CK18 concentrations were measured in fasting blood samples. In the German and Italian cohort, the diagnosis of NAFLD and grading of NAFLD was assessed by ultrasound.ResultsNAFLD was diagnosed in n = 50 patients of the German cohort (29.6%) and in n = 29 patients (72.5%) of the Italian cohort. In all three cohorts, miR‐122 was positively correlated with ALT and AST as well as with CK18 concentrations. MiR‐122 levels were higher in children with NAFLD compared with healthy controls.ConclusionsMiR‐122 levels in pre‐pubertal obese children could be a potential biomarker for paediatric NAFLD.
GIMDA: Graphlet interaction‐based MiRNA‐disease association prediction
Authors: Chen Xing , Guan Na‐Na , Li Jian‐Qiang , Yan Gui‐Ying 
Published: December 2017

AbstractMicroRNAs (miRNAs) have been confirmed to be closely related to various human complex diseases by many experimental studies. It is necessary and valuable to develop powerful and effective computational models to predict potential associations between miRNAs and diseases. In this work, we presented a prediction model of Graphlet Interaction for MiRNA‐Disease Association prediction (GIMDA) by integrating the disease semantic similarity, miRNA functional similarity, Gaussian interaction profile kernel similarity and the experimentally confirmed miRNA‐disease associations. The related score of a miRNA to a disease was calculated by measuring the graphlet interactions between two miRNAs or two diseases. The novelty of GIMDA lies in that we used graphlet interaction to analyse the complex relationships between two nodes in a graph. The AUCs of GIMDA in global and local leave‐one‐out cross‐validation (LOOCV) turned out to be 0.9006 and 0.8455, respectively. The average result of five‐fold cross‐validation reached to 0.8927 ± 0.0012. In case study for colon neoplasms, kidney neoplasms and prostate neoplasms based on the database of HMDD V2.0, 45, 45, 41 of the top 50 potential miRNAs predicted by GIMDA were validated by dbDEMC and miR2Disease. Additionally, in the case study of new diseases without any known associated miRNAs and the case study of predicting potential miRNA‐disease associations using HMDD V1.0, there were also high percentages of top 50 miRNAs verified by the experimental literatures.
Proinflammatory cytokines as serum biomarker in oral carcinoma—A prospective multi‐biomarker approach
Authors: Schiegnitz Eik , Kämmerer Peer W. , Schön Holger , Blatt Sebastian , Berres Manfred , Sagheb Keyvan , Al‐Nawas Bilal 
Published: December 2017

BackgroundInflammation and cell‐mediated immunity have a key role in different stages of carcinogenesis. The aim of this prospective study was to assess serum levels of proinflammatory cytokines interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), soluble interleukin‐2 receptor (sIL‐2R), tumor necrosis factor alpha (TNF‐α), and MHC class I polypeptide‐related sequence B (MICB) in patients with oral premalignant lesion (OPL), oral squamous cell carcinoma (OSCC), and healthy controls in a multi‐biomarker approach as a potential diagnostic and prognostic tool for OSCC.Material and MethodsA total of 205 patients (81 with OSCC, 75 with OPL, and 49 healthy controls) were included in this prospective study. Cytokine concentrations were measured by commercial enzyme linked immunoassay and chemiluminescence immunoassay.ResultsIL‐6, IL‐8, and sIL‐2R were significantly elevated in OSCC patients compared to healthy controls and to OPL patients. Higher T‐Grade (>T2) and positive lymph node involvement resulted in significantly higher IL‐6 values (P < .001 and P = .037). IL‐6 serum values ≥5 pg/mL (n = 45) and sIL‐2R serum values ≥623 U/mL (n = 19) indicated a significant lower survival rate compared to OSCC patients with low IL‐6 (n = 36) and sIL‐2R values (n = 62, P = .023 and P = .026). ROC and classification tree analyses identified the combination of IL‐6 and IL‐8 as diagnostic markers with good diagnostic accuracy.ConclusionIn conclusion, IL‐6, IL‐8, and sIL‐2R are strongly associated with OSCC oncogenesis and IL‐6 and sIL‐2R seem to be promising and potent biomarkers for evaluating patients' prognosis.
Increased recurrence rates of hepatocellular carcinoma after DAA therapy in a hepatitis C‐infected Egyptian cohort: A comparative analysis
Authors: El Kassas M. , Funk A. L. , Salaheldin M. , Shimakawa Y. , Eltabbakh M. , Jean K. , El Tahan A. , Sweedy A. T. , Afify S. , Youssef N. F. , Esmat G. , Fontanet A. 
Published: December 2017

SummaryIn Egypt, hepatocellular carcinoma (HCC) is the most common form of cancer and direct‐acting antivirals (DAA) are administered on a large scale to patients with chronic HCV infection to reduce the risk. In this unique setting, we aimed to determine the association of DAA exposure with early‐phase HCC recurrence in patients with a history of HCV‐related liver cancer. This was a prospective cohort study of an HCV‐infected population from one Egyptian specialized HCC management centre starting from the time of successful HCC intervention. The incidence rates of HCC recurrence between DAA‐exposed and nonexposed patients were compared, starting from date of HCC complete radiological response and censoring after 2 years. DAA exposure was treated as time varying. Two Poisson regressions models were used to control for potential differences in the exposed and nonexposed group; multivariable adjustment and balancing using inverse probability of treatment weighting (IPTW). We included 116 patients: 53 treated with DAAs and 63 not treated with DAAs. There was 37.7% and 25.4% recurrence in each group after a median of 16.0 and 23.0 months of follow‐up, respectively. Poisson regression using IPTW demonstrated an association between DAAs and HCC recurrence with an incidence rate ratio of 3.83 (95% CI: 2.02‐7.25), which was similar in the multivariable‐adjusted model and various sensitivity analyses. These results add important evidence towards the possible role of DAAs in HCC recurrence and stress the need for further mechanistic studies and clinical trials to accurately confirm this role and to identify patient characteristics that may be associated with this event.
Conjugative transposition of the vancomycin resistance carrying Tn1549: enzymatic requirements and target site preferences
Authors: Lambertsen Lotte , Rubio‐Cosials Anna , Patil Kiran Raosaheb , Barabas Orsolya 
Published: December 2017

SummaryRapid spread of resistance to vancomycin has generated difficult to treat bacterial pathogens worldwide. Though vancomycin resistance is often conferred by the conjugative transposon Tn1549, it is yet unclear whether Tn1549 moves actively between bacteria. Here we demonstrate, through development of an in vivo assay system, that a mini‐Tn1549 can transpose in E. coli away from its natural Gram‐positive host. We find the transposon‐encoded INT enzyme and its catalytic tyrosine Y380 to be essential for transposition. A second Tn1549 protein, XIS is important for efficient and accurate transposition. We further show that DNA flanking the left transposon end is critical for excision, with changes to nucleotides 7 and 9 impairing movement. These mutations could be partially compensated for by changing the final nucleotide of the right transposon end, implying concerted excision of the two ends. With changes in these essential DNA sequences, or without XIS, a large amount of flanking DNA transposes with Tn1549. This rescues mobility and allows the transposon to capture and transfer flanking genomic DNA. We further identify the transposon integration target sites as TTTT‐N6‐AAAA. Overall, our results provide molecular insights into conjugative transposition and the adaptability of Tn1549 for efficient antibiotic resistance transfer.
Genome‐wide association mapping in Arabidopsis identifies novel genes underlying quantitative disease resistance to Alternaria brassicae
Authors: Rajarammohan Sivasubramanian , Pradhan Akshay Kumar , Pental Deepak , Kaur Jagreet 
Published: December 2017

SummaryQuantitative disease resistance (QDR) is the predominant form of resistance against necrotrophic pathogens. The genes and mechanisms underlying QDR are not well known. In the current study, the Arabidopsis–Alternaria brassicae pathosystem was used to uncover the genetic architecture underlying resistance to A. brassicae in a set of geographically diverse Arabidopsis accessions. Arabidopsis accessions revealed a rich variation in the host responses to the pathogen, varying from complete resistance to high susceptibility. Genome‐wide association (GWA) mapping revealed multiple regions to be associated with disease resistance. A subset of genes prioritized on the basis of gene annotations and evidence of transcriptional regulation in other biotic stresses was analysed using a reverse genetics approach employing T‐DNA insertion mutants. The mutants of three genes, namely At1g06990 (GDSL‐motif lipase), At3g25180 (CYP82G1) and At5g37500 (GORK), displayed an enhanced susceptibility relative to the wild‐type. These genes are involved in the development of morphological phenotypes (stomatal aperture) and secondary metabolite synthesis, thus defining some of the diverse facets of quantitative resistance against A. brassicae.