bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methodology for Quantifying Fasting Glucose Homeostasis in Type 2 Diabetes: Observed Variability and Lability
Authors: Hill Nathan R. , Tsapas Apostolos , Hindmarsh Peter , Matthews David R. 
Published: January 2014

Background: Increased glycemic variability is associated with an increase risk of adverse clinical outcomes in diabetes. Central to the understanding of diabetes is glucose homeostasis. “Good” homeostasis is equated to low glycemic variability, and “poor” homeostasis is linked to greater glycemic variability. We have, therefore, developed a method with the aim to objectively quantify the domain of glucose-insulin homeostasis. We have termed this method as Observed Variability And Lability (OVAL). Method: Blood samples for the measurement of glucose and insulin concentrations were acquired every 2 min for 120 min from 12 patients with type 2 diabetes mellitus [T2DM; median (range) age 35 (25–47) years and duration of diabetes 7 (2–9) years receiving oral hypoglycemic treatment] and 27 controls [aged 38(30–53) years] with an equal split of genders and equal distribution of body mass indexes. The insulin-glucose time variant data form the boundaries of OVAL, defined as the ellipse enclosing the 95% confidence intervals of the insulin and glucose concentrations plotted on an x-y scatter graph and normalized to ensure equal weighting of insulin and glucose. Results: Less precise OVAL homeostasis was observed in subjects with T2DM, by a factor of 4, in comparison with controls [OVAL, T2DM 7.8(3.8) versus controls 1.9(1.0); p = .0003]. The assessment remained statistically robust ( p < .001) with increased sampling intervals up to 8 min. Conclusion: The OVAL model is a robust method for measuring glucose-insulin homeostasis in controls and T2DM subjects (available online at http://www.oval-calc.co.uk ). Deranged glucose-insulin homeostasis is the hallmark of diabetes and OVAL has the capacity to quantify in the fasting state.
Evaluation of a Minimally Invasive System for Measuring Glucose Area under the Curve during Oral Glucose Tolerance Tests: Usefulness of Sweat Monitoring for Precise Measurement
Authors: Sakaguchi Kazuhiko , Hirota Yushi , Hashimoto Naoko , Ogawa Wataru , Hamaguchi Tomoya , Matsuo Toshihiro , Miyagawa Jun-Ichiro , Namba Mitsuyoshi , Sato Toshiyuki , Okada Seiki , Tomita Koji , Matsuhisa Munehide , Kaneto Hideaki , Kosugi Keisuke , Maegawa Hiroshi , Nakajima Hiromu , Kashiwagi Atsunori 
Published: January 2014

Aims: We developed a system for measuring glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET). Sweat contamination during interstitial fluid glucose (IG) extraction affects the accuracy of glucose AUC measurement, because this technology uses extracted sodium ion levels as an internal standard. Therefore, we developed a sweat monitoring patch to reduce this effect and investigated its efficacy in volunteers undergoing oral glucose tolerance tests (OGTTs). Materials and Methods: Fifty diabetes mellitus inpatients and 10 healthy subjects undergoing the 75 g OGTT were included. Two sites on the forearm were pretreated with microneedle arrays, then hydrogels for interstitial fluid extraction were placed on the treated sites. Simultaneously, hydrogels for sweat monitoring were placed on untreated sites near the treated sites. Plasma glucose (PG) levels were measured every 30 min for 2 h to calculate reference AUC values. Using MIET, IG AUC was calculated from extracted glucose and sodium ion levels after attachment of the hydrogel for 2 h. Results: Good correlation between IG AUC measurements using MIET and reference AUCs measured using PG levels was confirmed over a wide AUC range (202–610 mg/h/dl) after correction for the sweat-induced error detected by the hydrogel patches on the nonpretreated skin. Strong correlation between IG AUC and peak glucose levels indicates that glucose spikes can be easily detected by this system. Conclusion: We confirmed the effectiveness of a sweat monitoring patch for precise AUC measurement using MIET. This novel, easy-to-use system has potential for glucose excursion evaluation in daily clinical practice.
Applicability Results of a Nonlinear Model-Based Robust Blood Glucose Control Algorithm
Authors: Kovács Levente , Szalay Péter , Almássy Zsuzsanna , Barkai László 
Published: January 2014

Introduction: Generating optimal control algorithms for an artificial pancreas is an intensively researched problem. The available models are all nonlinear and rather complex. Model predictive control or run-to-run-based methodologies have proven to be efficient solutions for individualized treatment of type 1 diabetes mellitus (T1DM). However, the controller has to ensure safety and stability under all circumstances. Robust control methods seek to provide this safety and guarantee to handle even the worst-case situations and, hence, to generalize and complement results obtained by individualized control algorithms. Methods: Modern robust (e.g., Hinf) control is a linear model-based methodology that we have combined with the nonlinear model-based linear parameter varying technique. The control algorithm was designed on the high-complexity modified nonlinear glucose-insulin model of Sorensen, and it was compared step-by-step with linear model-based Hinf control results published in the literature. The applicability of the developed algorithm was tested first on a control cohort of 10 healthy persons' oral glucose tolerance test results and then on a large meal absorption profile adapted from the literature. In the latter case, two preliminary virtual patients were generated based on 1–1 week real continuous glucose monitor measurements. Results: We have found that the algorithm avoids hypoglycemia (not caused by physical activity or stress) independently from the considered absorption profiles. Conclusion: Use of hard constraints proved their efficiency in fitting blood glucose level within a defined interval. However, in the future, more data of different T1DM patients will be collected and tested, including dynamic absorption model and in silico tests on validated simulators.
Outcomes of a 12-Month Technology-Based Intervention to Promote Weight Loss in Adolescents at Risk for Type 2 Diabetes
Authors: Patrick Kevin , Norman Gregory J. , Davila Evelyn P. , Calfas Karen J. , Raab Fred , Gottschalk Michael , Sallis James F. , Godbole Suni , Covin Jennifer R. 
Published: January 2014

Background: Obese adolescents are at risk for type 2 diabetes mellitus (T2DM). Obesity interventions delivered through media, such as the web and text messages [short message service (SMS)] may be beneficial when targeting obese adolescents. Methods: A randomized controlled trial, Pace-Internet for Diabetes Prevention Intervention (PACEi-DP), compared three forms of an obesity intervention to usual care (UC): (a) website only (W); (b) website, monthly group sessions, and follow-up calls (WG); and (c) website and SMS (WSMS). Participants were overweight or obese adolescents at risk for T2DM ( n = 101; age 12–16 years; mean body mass index (BMI) percentile = 97.6; 74.3% Hispanic). In addition to the website, WSMS participants received SMS supporting intervention goals and behavioral strategies and communicated via SMS with a case manager. WG participants had additional group activities related to weight loss and received follow-up calls from a health coach. UC participants were given printed materials and encouraged to attend three initial group sessions. Repeated measures mixed model regression analyses tested treatment effects for anthropometric, behavioral, and behavioral change strategy outcomes. Results: There were no treatment effects for BMI, adiposity, physical activity, or diet at 12 months. Treatment effects were observed for sedentary behavior, with the W arm having a greater decrease in sedentary behavior (4.9 to 2.8 h/day) than the UC arm ( p = .006). Conclusion: Although not sufficient to produce weight loss, the combination of web intervention and group sessions with telephone follow-up yielded improvements in sedentary behavior and in the use of behavior change strategies expected to lead to behavior change.
Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option: use of 96-well Optimul assay
Authors: Lordkipanidzé Marie , Lowe Gillian C. , Kirkby Nicholas S. , Chan Melissa V. , Lundberg Martina H. , Morgan Neil V. , Bem Danai , Nisar Shaista P. , Leo Vincenzo C. , Jones Matthew L. , Mundell Stuart J. , Daly Martina E. , Mumford Andrew D. , Warner Timothy D. , Watson Steve P. 
Published: January 2014

Key Points
The Optimul 96-well platelet aggregation assay has high levels of sensitivity and specificity for detecting platelet defects. The requirement for a small volume of blood, straightforward nature, and speed make Optimul a promising screening test in bleeding patients.
Analysis of TTG1 function in Arabis alpina
Authors: Chopra Divykriti , Wolff Heike , Span Johannes , Schellmann Swen , Coupland George , Albani Maria C , Schrader Andrea , Hülskamp Martin 
Published: January 2014

Abstract

Background
In Arabidopsis thaliana (A. thaliana) the WD40 protein TRANSPARENT TESTA GLABRA1 (TTG1) controls five traits relevant for the adaptation of plants to environmental changes including the production of proanthocyanidin, anthocyanidin, seed coat mucilage, trichomes and root hairs. The analysis of different Brassicaceae species suggests that the function of TTG1 is conserved within the family.

Results
In this work, we studied the function of TTG1 in Arabis alpina (A. alpina). A comparison of wild type and two Aattg1 alleles revealed that AaTTG1 is involved in the regulation of all five traits. A detailed analysis of the five traits showed striking phenotypic differences between A. alpina and A. thaliana such that trichome formation occurs also at later stages of leaf development and that root hairs form at non-root hair positions.

Conclusions
The evolutionary conservation of the regulation of the five traits by TTG1 on the one hand and the striking phenotypic differences make A. alpina a very interesting genetic model system to study the evolution of TTG1-dependent gene regulatory networks at a functional level.
Radiofrequency ablation following first-line transarterial chemoembolization for patients with unresectable hepatocellular carcinoma beyond the Milan criteria
Authors: Zhang Lan , Yin Xin , Gan Yu-hong , Zhang Bo-heng , Zhang Ju-bo , Chen Yi , Xie Xiao-ying , Ge Ning-lin , Wang Yan-hong , Ye Sheng-long , Ren Zheng-gang 
Published: January 2014

Abstract

Background
Recent studies suggest that a combination of radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) may have theoretical advantages over TACE alone for treatment of hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the effectiveness and safety of radiofrequency ablation following first-line TACE treatment in the management of HCC beyond the Milan Criteria.

Methods
Forty-five patients who consecutively underwent RFA following first-line TACE treatment for HCC beyond the Milan criteria were enrolled in this study. RFA was performed within 1–2 months after TACE treatment in patients who had incomplete necrotic tumor nodules. Primary effectiveness, complications, survival rates, and prognostic factors were evaluated retrospectively.

Results
Complete ablation was achieved in 76.2% of the lesions according to 1-month follow-up computed tomography/magnetic resonance imaging evaluation. The mean follow-up period was 30.9 months (range 3–94 months). There were no major complications after RFA therapy. The median overall survival was 29 months (range 20–38 months), with 1-, 2-, and 3-year survival of 89%, 61%, and 43%, respectively. Multivariate analysis revealed that tumor diameter (P = 0.045, hazard ratio [HR] = 0.228, 95% confidence interval [CI]: 0.054-0.968) and pretreatment serum alpha-fetoprotein level (P = 0.024, HR = 2.239, 95% CI: 1.114-4.500) were independent predictors for long-term survival.

Conclusions
HCC beyond the Milan criteria can be completely and safely ablated by radiofrequency ablation following first-line TACE treatment with a low rate of complications and favorable survival outcome. Further assessment of the survival benefits of combination treatment for HCCs beyond the Milan Criteria is warranted.
Rifampicin mono-resistant tuberculosis in France: a 2005–2010 retrospective cohort analysis
Authors: Meyssonnier Vanina , Bui Thuy Van , Veziris Nicolas , Jarlier Vincent , Robert Jérôme 
Published: January 2014

Abstract

Background
Rifampicin resistance is a risk factor for poor outcome in tuberculosis. Therefore, we sought to describe the characteristics and management of Rifampicin monoresistant (RMR) tuberculosis (TB) in France.

Methods
We conducted a retrospective cohort analysis in 2012 on RMR TB patients diagnosed in France between 2005 and 2010 by using a national laboratory network. A standardized questionnaire was used to collect basic demographic data, region of birth, history of TB, HIV-coinfection, alcohol use, and antituberculosis treatment. Outcome was assessed after at least 18 months of follow-up.

Results
A total of 39 patients with RMR TB were reported (0.12% of all TB cases). Overall, 19 (49%) had a previous history of treatment, 9 (23%) were HIV-coinfected, and 24 (62%) were smear-positive. Patient with secondary RMR were more likely to have alcohol abuse (P = 0.04) and HIV-coinfection (p = 0.04). Treatment outcome could be assessed for 30 patients, the nine others being dead or lost to follow-up. A total of 20 (67%) of the 30 assessed were cured, 3 (10%) died, 3 (10%) relapsed, and 4 (13%) were lost to follow up. Four (13%) received less than 6 months of treatment, 3 did not have any modification of the standardized regimen, 13 (43%) received fluoroquinolones, 4 (13%) aminoglycosides, and 8 (26%) a combination of both.

Conclusions
RMR TB is a rare disease in France, and its management was heterogeneous. The lack of treatment standardization may be a consequence of low expertise and may lead to the unsatisfactory low success rate.
The novel p.Cys65Tyr mutation in NR5A1gene in three 46,XY siblings with normal testosterone levels and their mother with primary ovarian insufficiency
Authors: Fabbri Helena Campos , de Andrade Juliana Gabriel Ribeiro , Soardi Fernanda Caroline , de Calais Flávia Leme , Petroli Reginaldo José , Maciel-Guerra Andréa Trevas , Guerra-Júnior Gil , de Mello Maricilda Palandi 
Published: January 2014

Abstract

Background
Disorders of sex development (DSD) is the term used for congenital conditions in which development of chromosomal, gonadal, or phenotypic sex is atypical. Nuclear receptor subfamily 5, group A, member 1 gene (NR5A1) encodes steroidogenic factor 1 (SF1), a transcription factor that is involved in gonadal development and regulates adrenal steroidogenesis. Mutations in the NR5A1 gene may lead to different 46,XX or 46,XY DSD phenotypes with or without adrenal failure. We report a Brazilian family with a novel NR5A1 mutation causing ambiguous genitalia in 46,XY affected individuals without Müllerian derivatives and apparently normal Leydig function after birth and at puberty, respectively. Their mother, who is also heterozygous for the mutation, presents evidence of primary ovarian insufficiency.

Case presentation
Three siblings with 46,XY DSD, ambiguous genitalia and normal testosterone production were included in the study. Molecular analyses for AR, SRD5A2 genes did not reveal any mutation. However, NR5A2 sequence analysis indicated that all three siblings were heterozygous for the p.Cys65Tyr mutation which was inherited from their mother. In silico analysis was carried out to elucidate the role of the amino acid change on the protein function. After the mutation was identified, all sibs and the mother had been reevaluated. Basal hormone concentrations were normal except that ACTH levels were slightly elevated. After 1 mcg ACTH stimulation test, only the older sib showed subnormal cortisol response.

Conclusion
The p.Cys65Tyr mutation located within the second zinc finger of DNA binding domain was considered deleterious upon analysis with predictive algorithms. The identification of heterozygous individuals with this novel mutation may bring additional knowledge on structural modifications that may influence NR5A1 DNA-binding ability, and may also contribute to genotype-phenotype correlations in DSD. The slightly elevated ACTH basal levels in all three patients with 46,XY DSD and the subnormal cortisol response after 1 mcg ACTH stimulation in the older sib indicate that a long-term follow-up for adrenal function is important for these patients. Our data reinforce that NR5A1 analysis must also be performed in 46,XY DSD patients with normal testosterone levels without AR mutations.
A European inventory of common electronic health record data elements for clinical trial feasibility
Authors: Doods Justin , Botteri Florence , Dugas Martin , Fritz Fleur 
Published: January 2014

Abstract

Background
Clinical studies are a necessity for new medications and therapies. Many studies, however, struggle to meet their recruitment numbers in time or have problems in meeting them at all. With increasing numbers of electronic health records (EHRs) in hospitals, huge databanks emerge that could be utilized to support research. The Innovative Medicine Initiative (IMI) funded project ‘Electronic Health Records for Clinical Research’ (EHR4CR) created a standardized and homogenous inventory of data elements to support research by utilizing EHRs. Our aim was to develop a Data Inventory that contains elements required for site feasibility analysis.

Methods
The Data Inventory was created in an iterative, consensus driven approach, by a group of up to 30 people consisting of pharmaceutical experts and informatics specialists. An initial list was subsequently expanded by data elements of simplified eligibility criteria from clinical trial protocols. Each element was manually reviewed by pharmaceutical experts and standard definitions were identified and added. To verify their availability, data exports of the source systems at eleven university hospitals throughout Europe were conducted and evaluated.

Results
The Data Inventory consists of 75 data elements that, on the one hand are frequently used in clinical studies, and on the other hand are available in European EHR systems. Rankings of data elements were created from the results of the data exports. In addition a sub-list was created with 21 data elements that were separated from the Data Inventory because of their low usage in routine documentation.

Conclusion
The data elements in the Data Inventory were identified with the knowledge of domain experts from pharmaceutical companies. Currently, not all information that is frequently used in site feasibility is documented in routine patient care.
VATS bullectomy and apical pleurectomy for spontaneous pneumothorax in a young patient with Swyer-James-Mc Leod syndrome: case report presentation and literature review focusing on surgically treated cases
Authors: Panagopoulos Nikolaos , Papavasileiou Gerasimos , Koletsis Efstratios , Kastanaki Myrto , Anastasiou Nikolaos 
Published: January 2014

AbstractBackgroundSwyer-James-McLeod Syndrome (SJMS) is an uncommon, emphysematous disease characterized by radiologic hyperlucency of pulmonary parenchyma due to loss of the pulmonary vascular structure and to alveolar overdistension.Case reportWe herein describe a 15-year-old Caucasian patient with well-established SJMS since childhood who presented with spontaneous pneumothorax. Video-assisted thoracoscopic bullectomy with apical pleurectomy was performed. Since SJMS is considered an on-going inflammatory process, the patient one year after surgery exhibits excellent quality of life with no pneumothorax recurrence.
Growth arrest lines and intra-epiphyseal silhouettes: a case series
Authors: Kennedy Ian W , Irwin Greg J , Huntley James S 
Published: January 2014

Abstract

Background
Growth arrest lines can develop within the skeleton after physiological stress or trauma. They are usually evident on radiographs as transverse lines in the metaphyses and have been used in fields from palaeontology to orthopaedics. This report consists of three cases, two of which describe growth arrest lines in an intra-epiphyseal site hitherto rarely documented, and a third demonstrating their clinical application.

Case presentation
Case 1 describes a 9-year-old who suffered a knee hyperflexion injury requiring anterior cruciate ligament and posterior cruciate ligament reattachments. She subsequently developed a marked distal femoral intra-epiphyseal arrest silhouette, as well as metaphyseal arrest lines in the femur, tibia and fibula. Case 2 describes an 8-year-old who sustained a tibial spine fracture and underwent open reduction and internal fixation. Subsequent imaging shows a further example of femoral intra-epiphyseal arrest silhouette as well as tibia and fibula metaphyseal arrest lines. Case 3 describes a 10-year-old who sustained a distal tibia fracture which was managed with open reduction and internal fixation. Subsequently the metaphyseal growth arrest line was parallel to the physis, suggesting no growth arrest (a danger with such a fracture).

Conclusion
This case series describes two examples of rarely described intra-epiphyseal growth arrest silhouettes and demonstrates the usefulness of arrest lines when assessing for growth plate damage.
IL-17E (IL-25) and IL-17RB promote respiratory syncytial virus-induced pulmonary disease
Authors: Petersen Bryan C , Dolgachev Vladislav , Rasky Andrew , Lukacs Nicholas W 
Published: January 2014

ABSTRACTOne of the most severe pathologic responses of RSV infection is associated with overproduction of cytokines and inflammation, leading to mucus hypersecretion. This study investigated the role of IL-25 in the development of RSV-associated immunopathology. IL-25 and its receptor IL-17RB were increased following RSV infection, and IL-25 blockade using neutralizing antibodies reduced RSV-associated pathology, AHR, and type 2 cytokine production. Likewise, IL-17RB−/− mice demonstrated a modified inflammatory response during RSV infection characterized by decreased Th2 and increased Th17 cytokine production. Additionally, the IL-17RB−/− mice demonstrated significantly reduced inflammation and cytokine production in a model of RSV-driven asthma exacerbation. These results indicate that IL-25 regulates the inflammatory response to RSV infection and that its inhibition may enable a reduction in the severity of RSV-associated pulmonary inflammation, including during viral-induced asthma exacerbation.
Instructional Materials for the Teacher to Hold Talks with Primary School Pupils on the Topic “Plants and Our Clothes”
Authors: Переверзева  , Pereverzeva E. 
Published: January 2014

Didactic materials are presented helpful for primary-school teachers to hold after-school extra-curricular talks
with pupils in order to enrich knowledge, received at the lessons on the subject “The World Around US”. Special attention
is given to cultivated textile plants native of the Old World and of the New World and introduced to the local soil. Such
information will give pupils general ideas about how technical plants have been cultivated and currently used to produce
fabrics, which form the basis for the modern textile industry.
Forms of Organization Suitable for the Process of Patriotic Up bringing at Primary School
Authors: Мусс  , Muss Galina 
Published: January 2014

Based on theoretical study, the author proves
the urgency of patriotic upbringing at the modern Russian
school. Patriotic upbringing is considered to be an integral
process of purposeful organization of activities,
communications and relationships between primary school
students. Special attention is given to different forms of
organization, facilitating the process of patriotic upbringing.