bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous EGFR and VEGF Alterations in Non-Small Cell Lung Carcinoma Based on Tissue Microarrays
Authors: Tsiambas Evangelos , Stamatelopoulos Athanasios , Karameris Andreas , Panagiotou Ioannis , Rigopoulos Dimitrios , Chatzimichalis Antonios , Bouros Demosthenes , Patsouris Efstratios 
Published: October 2017

BackgroundEpidermal growth factor receptor (EGFR) overexpression is observed in significant proportions of non-small cell lung carcinomas (NSCLC). Furthermore, overactivation of vascular endothelial growth factor (VEGF) leads to increased angiogenesis implicated as an important factor in vascularization of those tumors.Patients and MethodsUsing tissue microarray technology, forty-paraffin ( n = 40) embedded, histologically confirmed primary NSCLCs were cored and re-embedded into a recipient block. Immunohistochemistry was performed for the determination of EGFR and VEGF protein levels which were evaluated by the performance of computerized image analysis. EGFR gene amplification was studied by chromogenic in situ hybridization based on the use of EGFR gene and chromosome 7 centromeric probes.ResultsEGFR overexpression was observed in 23/40 (57.5%) cases and was correlated to the stage of the tumors ( p = 0.001), whereas VEGF was overexpressed in 35/40 (87.5%) cases and was correlated to the stage of the tumors ( p = 0.005) and to the smoking history of the patients ( p = 0.016). Statistical significance was assessed comparing the protein levels of EGFR and VEGF ( p = 0.043, k = 0.846). EGFR gene amplification was identified in 2/40 (5%) cases demonstrating no association to its overall protein levels ( p = 0.241), whereas chromosome 7 aneuploidy was detected in 7/40 (17.5%) cases correlating to smoking history of the patients ( p = 0.013).ConclusionsA significant subset of NSCLC is characterized by EGFR and VEGF simultaneous overexpression and maybe this is the eligible target group for the application of combined anti-EGFR/VEGF targeted therapies at the basis of genetic deregulation (especially gene amplification for EGFR).
GSMA: Gene Set Matrix Analysis, An Automated Method for Rapid Hypothesis Testing of Gene Expression Data
Authors: Cheadle Chris , Watkins Tonya , Fan Jinshui , Williams Marc A. , Georas Steven , Hall John , Rosen Antony , Barnes Kathleen C. 
Published: October 2017

Background Microarray technology has become highly valuable for identifying complex global changes in gene expression patterns. The assignment of functional information to these complex patterns remains a challenging task in effectively interpreting data and correlating results from across experiments, projects and laboratories. Methods which allow the rapid and robust evaluation of multiple functional hypotheses increase the power of individual researchers to data mine gene expression data more efficiently. Results We have developed (gene set matrix analysis) GSMA as a useful method for the rapid testing of group-wise up- or down-regulation of gene expression simultaneously for multiple lists of genes (gene sets) against entire distributions of gene expression changes (datasets) for single or multiple experiments. The utility of GSMA lies in its flexibility to rapidly poll gene sets related by known biological function or as designated solely by the end-user against large numbers of datasets simultaneously. Conclusions GSMA provides a simple and straightforward method for hypothesis testing in which genes are tested by groups across multiple datasets for patterns of expression enrichment.
Buprenorphine/Naloxone Maintenance Therapy: an Observational Retrospective Report on the Effect of Dose on 18 months Retention in an Office-Based Treatment Program
Authors: Parran Theodore V , Mace AG , Dahan Yael J , Adelman Christopher A , Kolganov Mykola 
Published: October 2017

Context and objective: Buprenorphine has been available with few reports of the dose range necessary to adequately maintain patients. We report on the effect of 8 mg/d versus 16 mg/d of buprenorphine on long-term patient retention in office-based opioid maintenance (OBOMT). Design, setting, and participants: Case series, at an urban hospital-based primary care clinic providing OBOMT to 157 opiate-dependent, low socioeconomic status, uninsured, nonhomeless patients. Intervention: The OBOMT program operated by a comprehensive sobriety treatment program experienced State funding cuts. Thus, after 2 years, the program was required by the State funder to decrease the buprenorphine maintenance dose from 16 to 8 mg/d for all new admissions. We report on patient retention before and after dose reduction. Main outcome measures: The primary outcomes of this study were to measure and compare patient retention in the 2 cohorts at each point of treatment transition over the 18 months following OBOMT initiation. Results: No significant differences in patient retention were observed between the 16 and 8 mg/d patient cohorts. Lower dose buprenorphine maintenance (8 mg/d) in uninsured patients enrolled in publicly funded long-term OBOMT combined with comprehensive sobriety counseling was as effective as higher dose therapy (16 mg/d) in promoting patient retention throughout the study period. This lower dose resulted in a substantial saving to the public funding agency. Conclusions: In an observational retrospective report, retention in treatment of opiate-addicted patients was the same at 8 and 16 mg/d buprenorphine doses after 18 months. These data have implications for public and managed care funding of OBOMT, for the general prescribing of buprenorphine in outpatient care, and may be instructive in the ongoing debate about the relationship between buprenorphine dose.
Pharmacokinetics of carfilzomib in patients with advanced malignancies and varying degrees of hepatic impairment: an open-label, single-arm, phase 1 study
Authors: Brown Jennifer , Plummer Ruth , Bauer Todd M. , Anthony Stephen , Sarantopoulos John , De Vos Filip , White Mike , Schupp Marco , Ou Ying , Vaishampayan Ulka 
Published: October 2017

Abstract
Background
Carfilzomib is approved in the United States and Europe for treatment of relapsed or refractory multiple myeloma (MM). This study evaluated pharmacokinetics (PK) and safety of carfilzomib in patients with relapsed or progressive advanced malignancies and varying degrees of impaired hepatic function.

Methods
Patients with normal hepatic function (normal) or hepatic impairment (mild, moderate, or severe) received carfilzomib infusion in 28-day cycles. The primary objective was to assess the influence of hepatic impairment on carfilzomib PK following 27 and 56 mg/m2 doses.

Results
The majority of patients enrolled in this study had solid tumors (n = 44) vs. MM (n = 2) since patients with multiple myeloma do not tend to have severe hepatic impairment in the same way as patients with solid tumors. A total of 11 normal and 17 mild, 14 moderate, and 4 severe hepatic impairment patients were enrolled. Compared with patients with normal hepatic function, patients with mild and moderate hepatic impairment had 44 and 26% higher carfilzomib AUC0–last, respectively (27 mg/m2 dose); increases at the 56 mg/m2 dose were 45 and 21%, respectively. Considerable PK variability (% coefficient of variation in AUC ≤100%) was discerned and no consistent trend of increasing exposure resulting from increasing hepatic impairment severity (moderate vs. mild) was seen. The observed adverse event (AE) profile in patients of mostly solid tumors was consistent with the known safety profile of carfilzomib, with the exception of an increased frequency of AEs consistent with hepatic function abnormalities.

Conclusions
In this population of primarily advanced solid tumor patients, patients with mild and moderate hepatic impairment had approximately 20–50% higher carfilzomib AUC vs. normal hepatic function patients. These increases are unlikely to be clinically significant, in light of the intrinsic PK variability and exposure–response relationship of carfilzomib.
Trial registrationhttp://clinicaltrials.gov NCT01949545; date of registration: September 6, 2013
Circulating microRNAs in patients with hormone receptor‐positive, metastatic breast cancer treated with dovitinib
Authors: Shivapurkar Narayan , Vietsch Eveline E. , Carney Erin , Isaacs Claudine , Wellstein Anton 
Published: October 2017

AbstractBackgroundSerial analysis of biomarkers in the circulation of patients undergoing treatment (“liquid biopsies”) can provide new insights into drug effects. In particular the analysis of cell‐free, circulating nucleic acids such as microRNAs (miRs) can reveal altered expression patterns indicative of mechanism of drug action, cancer growth, and tumor–stroma interactions.ResultsHere we analyzed plasma miRs in patients with hormone receptor positive, metastatic breast cancer with prior disease progression during aromatase inhibitor therapy (n = 8) in a phase I/II trial with the multiple tyrosine kinase inhibitor dovitinib (TKI258). Plasma miR levels were measured by quantitative RT‐qPCR before and after treatment with dovitinib. A candidate miR signature of drug response was established from a 379 miR screen for detectable plasma miRs as well as from the published literature. Changes in miR expression patterns and tumor sizes were compared. In this analysis we identified miR‐21‐5p, miR‐100‐5p, miR‐125b‐5p, miR‐126‐3p, miR‐375 and miR‐424‐5p as potential indicators of a response to dovitinib. The altered expression patterns observed for the six circulating miRs separated patients with resistant disease from those with drug responsive disease. There was no relationship between adverse effects of dovitinib treatment and identifiable changes in miR patterns.ConclusionWe conclude that changes in the expression patterns of circulating miRs can be indicators of drug responses that merit prospective studies for validation.
Virus interferes with host-seeking behaviour of mosquito
Authors: Vogels Chantal B. F. , Fros Jelke J. , Pijlman Gorben P. , van Loon Joop J. A. , Gort Gerrit , Koenraadt Constantianus J. M. 
Published: October 2017

ABSTRACT
Transmission of vector-borne pathogens is dependent on the host-seeking behaviour of their vector. Pathogen manipulation of the host-seeking behaviour of vectors towards susceptible hosts is supposedly beneficial for transmission. For West Nile virus (WNV), manipulation of the host-seeking behaviour of the main mosquito vector towards birds would be advantageous, because mammals are dead-end hosts. We hypothesised that WNV infection induces a stronger host-seeking response and a shift in host preference towards birds, to enhance its transmission by mosquitoes. However, here we show that WNV infection decreases the host-seeking response, and does not induce a shift in mosquito host preference. Other fitness-related traits are not affected by WNV infection. No effect of WNV infection was found on antennal electrophysiological responsiveness. Thus, the reduced host-seeking response is likely to result from interference in the mosquito's central nervous system. This is the first study that shows changes, specifically in the host-seeking behaviour induced by a pathogen, that do not favour transmission.
Case Report: Managing a giant, high-grade carotid body tumor in a resource-limited setting
Authors: Munakomi Sunil , Chaudhary Samrita , Cherian Iype 
Published: October 2017

Herein we report the management of a giant, high-grade and vascular carotid body tumor in a young woman. She presented with slowly progressive neck swelling. Vascular imaging revealed a left-sided, high-grade giant carotid body tumor (> 8cm). The tumor was completely excised by caudocranial subadventitial dissection. Histology of the tumor revealed a characteristic Zellballen pattern of the lesion, suggestive of a paraganglioma. The patient made an uneventful recovery. We also discuss newer insights regarding the management of such highly vascular lesions.
Managing real world venous leg ulcers with fetal bovine acellular dermal matrix: a single centre retrospective study
Authors: Paredes J.A. , Bhagwandin S. , T. Polanco , Lantis J.C. 
Published: October 2017

Objective: As compression treatment offers moderate improvement, especially to recurrent venous leg ulcers (VLUs), several alternative therapies using cellular based and/or tissue-derived products (CTPs) have emerged from bovine, porcine, and equine sources. Our aim was to look at the effect of a CTP in ‘real-life’ VLUs. Methods: This study looked at complex patients with chronic, large wounds in a single-centre retrospective review. All patients were treated with fetal bovine acellular dermal matrix (FBADM) for VLUs at our outpatient urban wound care programme. Results: A total of 40 wounds in 33 patients were analysed. At week four, 6% of wounds were closed; at week eight, 9% were closed; at week 12, 25% were closed; and at week 16, 38% of wounds were closed. The median time to wound closure was 67 days (range: 23–100 days) and the median percent wound closure through re-epithelialisation was 11% per week (range: 7–30% per week). At 4 weeks the median area reduction of all wounds was 23.5%, with 40% of VLUs having a ≥40% area reduction at the same point in time. Conclusion: There are limitations to any retrospective review; however; patients deemed to have a limited chance of closure at 4 months did better than expected, either healing or having a wound area reduction at 16 weeks, making their wound care much easier. Prospective studies should be conducted to optimise the treatment algorithm to determine if better clinical outcomes can be obtained for the ‘real-life’ VLU population.
GUIDELINES FOR THE ASSESSMENT OF DISEASE ACTIVITY AND FUNCTIONAL STATUS IN PATIENTS WITH ANKYLOSING SPONDYLITIS IN CLINICAL PRACTICE
Authors: Dubinina T. V. , Gaidukova I. Z. , Godzenko A. A. , Lapshina S. A. , Rebrov A. P. , Rumyantseva O. A. , Badokin V. V. , Bochkova A. G. , Bugrova O. V. , Dubikov A. I. , Ivanova O. N. , Korotaeva T. V. , Nesmeyanova O. B. , Nikishina I. P. , Otteva E. N. , Raskina T. A. , Smirnov A. V. , Sitalo A. V. , Erdes Sh. F. 
Published: September 2017

The paper gives the recommendations for the assessment of disease activity and functional status in patients with ankylosing spondylitis in clinical practice, which have been developed by experts, by taking into account international and Russian experience in managing these patients.
THE EFFICACY AND SAFETY OF RITUXIMAB BIOSIMILAR (ACELLBIA®) IN RHEUMATOID ARTHRITIS AS THE FIRST BIOLOGICAL AGENT: RESULTS OF PHASE III (ALTERRA) CLINICAL TRIAL
Authors: Nasonov E. L. , Mazurov V. I. , Zonova E. V. , Knyazeva L. A. , Marusenko I. M. , Nesmeyanova O. B. , Plaksina T. V. , Shapovalova Yu. S. , Ilivanova E. P. , Krechikova D. G. , Petrochenkova N. A. , Reshetko O. V. , Denisov L. N. , Gordeev I. G. , Davydova A. F. , Eremina N. A. , Zemerova E. V. , Ivanova T. B. , Kastanayan A. A. , Pokrovskaya T. G. , Smakotina S. A. , Smolyarchuk E. A. , Artemyeva A. V. , Ivanov R. A. , Usacheva Yu. V. , Chernyaeva E. V. 
Published: September 2017

The Russian biotechnological company «BIOCAD» has designed a chimeric monoclonal antibody against CD20 (BCD-020, Acellbia®) that is a biosimilar of rituximab (RTM; MabThera®, F. Hoffmann-La Roche Ltd., Switzerland). In recent years, there has been evidence that RTM can be used at lower doses than those given in the standard recommendations and instructions for the use of this drug. This serves as the basis for the BCD-020-4/ALTERRA (ALTErnative Rituximab regimen in Rheumatoid Arthritis) trial, the objective of which was to investigate the efficiency and safety of using Acellbia® (at a dose of 600 mg twice at a 2-week interval) as the first biological agent (BA) for methotrexate (MTX)-resistant active rheumatoid arthritis (RA). The investigation enrolled 159 patients aged 18 to 80 years with active RA. After 24 weeks 65.7 and 29.4% of patients achieved 20% improvement by the American College of Rheumatology (ACR) criteria in the Acellbia® + MTX and placebo (PL) + MTX groups, respectively (p<0.0001). The differences in the ACR20 response rate in the two groups were 36.3% (95% CI, 19.27–53.28%). There were significant differences between the groups in the ACR50 response rates: 28.4% and 5.9% (p=0.001) and in the ACR70 ones: 12.8% and only 2.0%, respectively (p=0.036). Analysis of all recorded adverse events (AE) frequency showed no significant differences between the patients in the study and control groups and demonstrates its equivalence with that of RTM (MabThera®); all the AE were expectable. It is noted that antibodies to RTM with binding and neutralizing activities had no impact on the efficiency and safety of therapy.
LINGUISTIC AND CULTURAL ADAPTATION AND VALIDATION OF THE KUJALA QUESTIONNAIRE AMONG PATIENTS WITH PAIN IN THE ANTERIOR PART OF KNEE JOINT
Authors: Kuznetsov I. A. , Maikov S. V , Salikhov M. R. , Shulepov D. A. , Avdeev A. I. 
Published: September 2017

Objective: to carry out linguistic and cultural adaptation and validation of the Kujala questionnaire that is today one of the most popular orthopedic tools used to evaluate the severity of pain in the anterior part of knee joint.Subjects and methods. In accordance with protocols on this type of investigations, the questionnaire was first translated directly and then back. Furthermore, an intermediate Russian-language version of the Kujala questionnaire was tested in 15 patients, followed by error correction and approval of its final Russian-language version. A study group included 50 patients who complained of obvious pain in the anterior part of knee joint and answered the questionnaire twice (for its test-retest reliability) every two or three days.Results and discussion. The intraclass correlation coefficient (ICC) equal to 0.948 (95% confidence interval, 0.025–0.967) indicated a high test-retest reliability of the Russian-language version of the Kujala questionnaire. Cronbach's alpha coefficient of 0.956 corresponded to a high level of internal consistency, which also suggested that the proposed version of the questionnaire had a high reliability. The criterion-related validity assessment, by calculating the Spearman correlation coefficient between the results of primary and repeated surveys using the Russian-language version of the Kujala questionnaire, as well as between the Russian- language versions of the Kujala questionnaire and the SF-36, showed their high correlation.Conclusion. The findings indicate that the Russian-language version of the Kujala questionnaire is a valid and reliable tool for subjective assessment of the severity of pain in the anterior part of knee joint.
INFLIXIMAB-INDUCED LUPUS-LIKE SYNDROME IN A FEMALE PATIENT WITH RHEUMATOID ARTHRITIS (A CASE REPORT): AN ACCIDENT OR REGULARITY?
Authors: Muravyev Yu. V. , Lebedeva V. V. , Alamankina S. Yu. 
Published: September 2017

The paper describes a case of infliximab-induced lupus-like syndrome in a female patient with rheumatoid arthritis and discusses the possible causes of this pathology.
Cortisol Levels and Autonomic Control of Heart Rate in Healthy Subjects
Authors: Santana Milana Drumond Ramos , Martiniano Eli Carlos , Monteiro Larissa Raylane Lucas , Oliveira Maria Do Socorro Santos De , Valenti Vitor E. , Garner David M. , Vanderlei Franciele Marques , Abreu Luiz Carlos De 
Published: October 2017

Abstract
Introduction: There is an increase in level of stress in the general population because of the social, personal and professional demands. Currently, there are only simple tools that can safely measure this stress such as levels of cortisol and heart rate variability (HRV). Objective: To analyze the relationship between salivary cortisol and the cardiac autonomic modulation. Methods: A total of fifty-one male and female subjects between 18 and 40 years old were evaluated. Saliva collection was achieved for the salivary cortisol dosage. The collection was performed through the SalivetteR tube. After this collection, the median cortisol levels (0.24 ug/dl) were analyzed and the volunteers were divided into two groups: i) cortisol below the mediane ii) cortisol above the median. After this division, each group consisted of 25 volunteers and then was verified the following information: age, gender, weight, height, body mass index (BMI), blood pressure. Shortly thereafter was assessment of cardiac autonomic modulation por meio da HRV. The Polar RS800cx heart rate receiver was placed on the chest of the volunteers, in the vicinity of the distal third of the sternum. The volunteers were instructed to remain in rest with spontaneous breathing in dorsal position for 20 minutes. HRV analysis included geometric, time and frequency domain indices. Results: There were no statistical differences for the two groups regarding systolic and diastolic blood pressure, heart rate, RR intervals or linear and frequency indices for the volunteers. In addition, also there was no correlation the cortisol with the analyzed variables (SAP, p=0.460; DAP, p = 0.270; HR, p = 0.360; RR, p = 0.380; SDNN, p = 0.510; rMSSD, p = 0.660; pNN50, p = 0.820; RRtri, p = 0.170; TINN, p = 0.470; SD1, p = 0.650; SD2, p = 0.500; LF [ms2], p = 0.880; LF [nu], p = 0.970; HF [ms2], p = 0.870; HF [nu], p = 0.960; LF/HF, p = 0.380 Conclusion: Heart rate variability autonomic control was unchanged in healthy subjects with physiological distribution of salivary cortisol levels. There was no association between normal salivary cortisol and resting autonomic regulation of heart rate.
Dual hesitant pythagorean fuzzy Hamacher aggregation operators in multiple attribute decision making
Authors: Wei Guiwu , Lu Mao 
Published: October 2017

AbstractIn this paper, we investigate the multiple attribute decision making (MADM) problem based on the Hamacher aggregation operators with dual Pythagorean hesitant fuzzy information. Then, motivated by the ideal of Hamacher operation, we have developed some Hamacher aggregation operators for aggregating dual hesitant Pythagorean fuzzy information. The prominent characteristic of these proposed operators are studied. Then, we have utilized these operators to develop some approaches to solve the dual hesitant Pythagorean fuzzy multiple attribute decision making problems. Finally, a practical example for supplier selection in supply chain management is given to verify the developed approach and to demonstrate its practicality and effectiveness.
Late Ordovician palaeogeography and the positions of the Kazakh terranes through analysis of their brachiopod faunas
Authors: Popov Leonid E. , Cocks Robin M. 
Published: October 2017

AbstractDetailed biogeographical and biofacies analyses of the Late Ordovician brachiopod faunas with 160 genera, grouped into 94 faunas from individual lithotectonic units within the Kazakh Orogen strongly support an archipelago model for that time in that area. The Kazakh island arcs and microcontinents within several separate clusters were located in the tropics on both sides of the Equator. Key units, from which the Late Ordovician faunas are now well known, include the Boshchekul, Chingiz-Tarbagatai, and Chu-Ili terranes. The development of brachiopod biogeography within the nearly ten million year time span of the Late Ordovician from about 458 to 443 Ma (Sandbian, Katian, and Hirnantian), is supported by much new data, including our revised identifications from the Kazakh Orogen and elsewhere. The Kazakh archipelago was west of the Australasian segment of the Gondwana Supercontinent, and relatively near the Tarim, South China and North China continents, apart from the Atashu-Zhamshi Microcontinent, which probably occupied a relatively isolated position on the south-western margin of the archipelago. Distinct faunal signatures indicate that the Kazakh terranes were far away from Baltica and Siberia throughout the Ordovician. Although some earlier terranes had joined each other before the Middle Ordovician, the amalgamation of Kazakh terranes into the single continent of Kazakhstania by the end of the Ordovician is very unlikely. The Late Ordovician brachiopods from the other continents are also compared with the Kazakh faunas and global provincialisation statistically determined.