bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspirin ameliorates lung cancer by targeting the miR‐98/WNT1 axis
Authors: Gan Huizhu , Lin Lin , Hu Nanjun , Yang Yang , Gao Yu , Pei Yu , Chen Kang , Sun Butong
Published: February 2019

Background

Aspirin, an anti‐inflammatory drug, has been widely investigated in the treatment of many cancer types, including colorectal, ovarian, breast, and prostate cancers. MicroRNAs (miRNAs) are the most well studied noncoding RNAs in cancers. In the current study, we were interested in defining the function of aspirin in lung cancer treatment and the related noncoding RNAs involved in this process.

Methods

The function of aspirin in lung cancer growth was evaluated by cell viability and colony formation assays. Screening of miRNAs affected by aspirin was performed through quantitative real‐time PCR. Prediction of miR‐98 targeting WNT1 was performed using online bioinformatics software and was further confirmed by luciferase reporter gene analysis. The levels of miR‐98 and WNT1 were tested through immunoblotting and quantitative real‐time PCR analysis in lung cancer cells under aspirin treatment.

Results

Cell viability was sharply suppressed in lung cancer cells with an increasing dose of aspirin. Aspirin markedly weakened the malignant colony formation ability of lung cancer cells. One out of six tumor suppressor miRNAs could be obviously regulated by aspirin in lung cancer cells. The inhibition of miR‐98 on the luciferase activities of wild‐type 3' untranslated region vectors of WNT1 was clearly revealed in lung cancer cells. Meanwhile, the inhibitor of miR‐98 increased the luciferase activities of wild‐type 3' untranslated region vectors of WNT1. After treatment with aspirin the expression of miR‐98 was induced and then its target gene, WNT1, was depressed in the cells.

Conclusion

Aspirin targets the miR‐98/WNT1 axis to ameliorate lung cancer development.
Comorbidity of bipolar I disorder and conduct disorder: a familial risk analysis
Authors: Wozniak J. , Wilens T. , DiSalvo M. , Farrell A. , Wolenski R. , Faraone S. V. , Biederman J.
Published: February 2019

Objective

To investigate the association between pediatric bipolar I (BP‐I) disorder and conduct disorder (CD) using familial risk analysis.

Method

We compared diagnoses in relatives of youth in four proband groups defined by the presence or absence of BP‐I and CD: (1) probands with neither CD nor BP‐I (probands: N = 550; relatives: N = 1656), (2) probands with CD and without BP‐I (probands: N = 40; relatives: N = 127), (3) probands with BP‐I and without CD (probands: N = 197; relatives: N = 579), and (4) probands with both CD and BP‐I (probands: N = 176; relatives: N = 488). All subjects were evaluated with structured diagnostic interviews, and diagnoses of relatives were made blind to the diagnoses of probands.

Results

Relatives of probands with BP‐I disorder had high rates of BP‐I, and relatives of probands with CD had high rates of CD irrespective of the comorbidity with the other disorder. Relatives of probands with the combined condition of CD and BP‐I had high rates of the combined condition.

Conclusion

The finding of cosegregation between BP‐I disorder and CD is consistent with the hypothesis that the combined condition represents a distinct subtype of either disorder.
First‐line therapy for metastatic colorectal cancer: Current perspectives and future directions
Authors: Burge Matthew , Price Timothy , Karapetis Christos S.
Published: February 2019

The prognosis for patients with newly diagnosed inoperable metastatic colorectal cancer has steadily improved over the past two decades as new agents have been introduced into clinical practice and many new biomarkers have been discovered. In parallel with this progress, clinicians face increasingly complex treatment decisions. This review summarizes recent progress, with a historical perspective, which should help guide the clinician in decision making and optimal therapy selection. This review not only focuses on important and readily identifiable subsets, including primary tumor side and v‐RAF murine sarcoma viral oncogene homologue B (BRAF) mutations, but also discusses rarer molecular subgroups that may be important for determining treatment in the future.
Biomarkers of ovarian reserve in childhood and adolescence: A systematic review
Authors: Bhide Priya , Pundir Jyotsna , Homburg Roy , Acharya Ganesh
Published: February 2019

Introduction

Certain medical disorders as well as their management may affect gonadal function. Recent advances in the management of these conditions accompanied by the availability and success of methods of fertility preservation has highlighted the need for assessment of ovarian reserve in childhood and adolescence. Serum anti‐Mullerian hormone (AMH) and antral follicle count are well established markers of ovarian reserve and serum inhibin has also been used. However, literature on reference ranges for ovarian reserve markers in this age‐group is relatively scarce. Thus, our aim was to evaluate published data to estimate reference values of ovarian reserve makers in childhood and adolescence.

Material and methods

We performed a systematic review of the literature reporting ovarian reserve markers in childhood and adolescence. We included only those studies examining markers of ovarian reserve in the normal healthy population between the ages of 0 and 19 years. PROSPERO registration: CRD42018119064.

Results

Serum AMH emerged as the most common biomarker assessed. Serum AMH was detectable at birth and, after a transient increase in infancy, increased steadily in childhood. Following a slight decrease at puberty, levels were constant throughout adolescence with a peak in adolescence or early adulthood. The mean serum AMH values during infancy, childhood and adolescence were 10.55, 22.32 and 31.84 pmol/L, respectively. The corresponding median values were 9.85, 24.49 and 26.32 pmol/L. It was not possible to construct age‐specific reference intervals because of methodological heterogeneity, variations in the assay used to measure AMH and differing interval width for age used in included studies. Serum inhibin showed an increase from childhood to adolescence, with median serum inhibin values of 53.86 pg/mL in adolescence. Antral follicle count showed a significant positive correlation with serum AMH and a median value of 30.52 in adolescence.

Conclusions

We summarize the trends and levels of biomarkers of ovarian reserve from birth until young adulthood. Peak levels of serum AMH are reported in adolescence or early adulthood. We have reported median/mean values for serum AMH in different age‐groups based on data pooled from several studies, which may be used as a reference when evaluating ovarian reserve in childhood and adolescence especially when considering fertility preservation.
Cognitive diagnosis models for multiple strategies
Authors: Ma Wenchao , Guo Wenjing
Published: February 2019

Cognitive diagnosis models (CDMs) have been used as psychometric tools in educational assessments to estimate students’ proficiency profiles. However, most CDMs assume that all students adopt the same strategy when approaching problems in an assessment, which may not be the case in practice. This study develops a generalized multiple‐strategy CDM for dichotomous response data. The proposed model provides a unified framework to accommodate various condensation rules (e.g., conjunctive, disjunctive, and additive) and different strategy selection approaches (i.e., probability‐matching, over‐matching, and maximizing). Model parameters are estimated using the marginal maximum likelihood estimation via expectation‐maximization algorithm. Simulation studies showed that the parameters of the proposed model can be adequately recovered and that the proposed model was relatively robust to some types of model misspecifications. A set of real data was analysed as well to illustrate the use of the proposed model in practice.
Impact of recycling and lateral sediment input on grain size fining trends—Implications for reconstructing tectonic and climate forcings in ancient sedimentary systems
Authors: Harries Rebekah M. , Kirstein Linda A. , Whittaker Alex C. , Attal Mikael , Main Ian
Published: February 2019

Grain size trends in basin stratigraphy are thought to preserve a rich record of the climatic and tectonic controls on landscape evolution. Stratigraphic models assume that over geological timescales, the downstream profile of sediment deposition is in dynamic equilibrium with the spatial distribution of tectonic subsidence in the basin, sea level and the flux and calibre of sediment supplied from mountain catchments. Here, we demonstrate that this approach in modelling stratigraphic responses to environmental change is missing a key ingredient: the dynamic geomorphology of the sediment routing system. For three large alluvial fans in the Iglesia basin, Argentine Andes we measured the grain size of modern river sediment from fan apex to toe and characterise the spatial distribution of differential subsidence for each fan by constructing a 3D model of basin stratigraphy from seismic data. We find, using a self‐similar grain size fining model, that the profile of grain size fining on all three fans cannot be reproduced given the subsidence profile measured and for any sediment supply scenario. However, by adapting the self‐similar model, we demonstrate that the grain size trends on each fan can be effectively reproduced when sediment is not only sourced from a single catchment at the apex of the system, but also laterally, from tributary catchments and through fan surface recycling. Without constraint on the dynamic geomorphology of these large alluvial systems, signals of tectonic and climate forcing in grain size data are masked and would be indecipherable in the geological record. This has significant implications for our ability to make sensitive, quantitative reconstructions of external boundary conditions from the sedimentary record.
FASTC: a file format for multi‐character sequence data
Authors: Wheeler Ward C. , Washburn Alexander J.
Published: February 2019

Here, we define a sequence file format that allows for multi‐character elements (FASTC). The format is derived from the FASTA format and the custom alphabet format of POY4/5. The format is more general than either of these formats and can represent a broad variety of sequence‐type data. This format should be useful for analyses involving datasets encoded as linear streams such as gene synteny, comparative linguistics, temporal gene expression and development, complex animal behaviours, and general biological time‐series data.
Military training areas facilitate the recolonization of wolves in Germany
Authors: Reinhardt Ilka , Kluth Gesa , Nowak Carsten , Szentiks Claudia A. , Krone Oliver , Ansorge Hermann , Mueller Thomas
Published: February 2019

Wolves (Canis lupus) are currently showing a remarkable comeback in the highly fragmented cultural landscapes of Germany. We here show that wolf numbers increased exponentially between 2000 and 2015 with an annual increase of about 36%. We demonstrate that the first territories in each newly colonized region were established over long distances from the nearest known reproducing pack on active military training areas (MTAs). We show that MTAs, rather than protected areas, served as stepping‐stones for the recolonization of Germany facilitating subsequent spreading of wolf territories in the surrounding landscape. We did not find any significant difference between MTAs and protected areas with regard to habitat. One possible reason for the importance of MTAs may be their lower anthropogenic mortality rates compared to protected and other areas. To our knowledge, this is the first documented case where MTAs facilitate the recolonization of an endangered species across large areas.
Organizational discretion, board control, and shareholder wealth: A contingency perspective
Authors: Ponomareva Yuliya , Shen Wei , Umans Timurs
Published: February 2019

Research Question/Issue

How does organizational context influence the impact of board control over managerial decisions on shareholder wealth?

Research Findings/Insights

We introduce a new theoretical concept—organizational discretion—to characterize the upper limit of managers' latitude of actions presented by their organizational context and propose that it moderates the impact of board control on shareholder wealth. Specifically, we first argue that strategic control by boards over managerial decisions reduces managers' latitude of actions and leads to trade‐offs between the containment of managerial opportunism and the pursuit of strategic opportunities, which consequently influence the relationship between strategic control and shareholder wealth. We then suggest that the trade‐offs incurred by strategic control over managerial decisions are more prominent in firms with high organizational discretion. Because of the trade‐offs, we propose that boards are likely to decide whether to rely more on strategic control or financial control in internal corporate governance based on their firms' level of organizational discretion.

Theoretical/Academic Implications

By introducing the concept of organizational discretion and highlighting the trade‐offs caused by boards' strategic control over managerial decisions, we advance a contingency perspective to enhance the understanding about the impact of board control on shareholder wealth. It also bridges the strategic management and corporate governance research on managerial discretion that has largely evolved separately in the literature.

Practitioner/Policy Implications

Boards should attend to the trade‐offs between the containment of managerial opportunism and the pursuit of strategic opportunities when exercising strategic control over managerial decisions. Moreover, considering the trade‐offs involved, boards should carefully design and implement internal corporate governance mechanisms based on their firms' level of organizational discretion.
Relative contribution of basal and postprandial hyperglycaemia stratified by HbA1c categories before and after treatment intensification with dulaglutide
Authors: Umpierrez Guillermo , Pantalone Kevin M. , Atisso Charles M. , Landó Laura Fernández , Patel Hiren
Published: February 2019

Aim

To assess the effect of dulaglutide on the relative contribution of basal hyperglycaemia (BHG) and postprandial hyperglycaemia (PPHG) to overall hyperglycaemia across HbA1c categories in patients with type 2 diabetes.

Methods

Data from five phase 3 studies (N = 673) were pooled to assess the change in relative contributions of BHG and PPHG to overall hyperglycaemia across different HbA1c categories after 6 months of treatment intensification with dulaglutide 1.5 mg as monotherapy or with 1 or 2 oral medication(s) in patients with type 2 diabetes. BHG and PPHG were calculated using the area under the curve (AUC) of 7‐point self‐monitored plasma glucose concentration profiles. As a secondary objective, relative contribution of BHG and PPHG for dulaglutide versus liraglutide, exenatide BID and insulin glargine was assessed by individual studies at 6 months.

Results

In pooled data, after 6 months of treatment intensification with dulaglutide 1.5 mg, there was a significant reduction from baseline in overall hyperglycaemia (AUCoverall) [(mean ± SE) ‐466.31 ± 18.32 mg*h/dL (P < 0.001)], BHG (AUCbasal) [(mean ± SE) ‐371.46 ± 16.36 mg*h/dL (P < 0.001)] and PPHG (AUCpostprandial) [(mean ± SE) ‐94.84 ± 7.97 mg*h/dL (P < 0.001)]. At baseline, relative contributions of BHG increased and PPHG decreased with increasing HbA1c levels. This pattern was maintained at 6 months, even as overall glycaemia improved with decreasing HbA1c values.

Conclusions

In patients with type 2 diabetes, dulaglutide reduces HbA1c by lowering both basal and postprandial hyperglycaemia across various HbA1c levels.
Access to health care after dental trauma in children: A quantitative and qualitative evaluation
Authors: Kayıllıoğlu Zencircioğlu Özlem , Eden Ece , Öcek Zeliha Aslı
Published: February 2019

Background/Aims

The aim of this study was to evaluate the accessibility of proper and on‐time treatment after dental trauma in children and to explore the affecting factors via parents’ and health professionals’ perspectives. The study is important to understand how to improve access to dental treatment after trauma.

Materials and Method

The method included quantitative and qualitative parts. For the quantitative method, parents of dental trauma patients who applied to Ege University, Department of Pedodontics during January 2015‐June 2016 were the target group. One hundred and forty parents answered the questionnaire on trauma experiences. The participation rate was 62.78%. Questions covered variables such as first admitted health institution, time to go there, access to diagnostics, treatment methods, referral from institution, and sociodemographic characteristics of the family. On‐time and proper treatment access was defined using an algorithm for treatment priority of the case, total time to reach treatment, and the correct intervention. For the qualitative method, ten parents and thirty health professionals were interviewed in‐depth using a semi‐structured question guide. Thematic analysis was applied to the interview texts.

Results

The percentage of patients who accessed on‐time and proper treatment was 19.29%. Logistic regression analysis showed that admission to the university clinic first increased the access to treatment by 14.135 times. For the qualitative evaluation, treatment access was summarized into three main themes: (a) physical accessibility of dental health services, (b) a quality dental health service as an outcome, and (c) communication among parties.

Conclusion

The level of accessing proper and on‐time treatment was quite inadequate. It is suggested that distribution of dental care centers should be increased and dental centers where competent dentists work should be established. Performance‐based payment should be reorganized and cooperation between medical and dental institutions should be encouraged.
Does fMRI repetition suppression reveal mirror neuron activity in the human brain? Insights from univariate and multivariate analysis
Authors: Fuelscher Ian , Caeyenberghs Karen , Enticott Peter Gregory , Kirkovski Melissa , Farquharson Shawna , Lum Jarrad , Hyde Christian
Published: February 2019

Mirror neurons (MN) have been proposed as the neural substrate for a wide range of clinical, social and cognitive phenomena. Over the last decade, a commonly used tool for investigating MN activity in the human brain has been functional magnetic resonance (fMRI) repetition suppression (RS) paradigms. However, the available evidence is mixed, largely owing to inconsistent application of the methodological criteria necessary to infer MN properties. This raises concerns about the degree to which one can infer the presence (or absence) of MN activity from earlier accounts that adopted RS paradigms. We aimed to clarify this issue using a well‐validated fMRI RS paradigm and tested for mirror properties by rigorously applying the widely accepted criteria necessary to demonstrate MN activity using traditional univariate techniques and Multivariate Pattern Analysis (MVPA). While univariate whole brain analysis in healthy adults showed uni‐modal RS effects within the supplementary motor area, no evidence for cross‐modal RS effects consistent with mirror neuron activity was found. MVPA on the other hand revealed a region along the anterior intraparietal sulcus that met the criteria for MN activity. Taken together, these results clarify disparate evidence from earlier RS studies, highlighting that traditional univariate analysis of RS data may not be sensitive for detecting MN activity when rigorously applying the requisite criteria. In light of these findings, we recommend that short of increasing sample sizes substantially, future studies using RS paradigms to investigate MNs across the human brain consider the use of MVPA.
Give them credit‐the greenhouse gas performance of regional biogas systems
Authors: O'Keeffe Sinéad , Franko Uwe , Oehmichen Katja , Daniel‐Gromke Jaqueline , Thrän Daniela
Published: February 2019

Anaerobic digestion to produce biogas is an important decentralised renewable energy technology. Production varies extensively between different countries and within countries, as biogas production is heavily dependent on local and regional feedstocks. In Germany, distinct regional differences can be observed. Therefore, understanding the kinds of biogas systems operating within a region is crucial to determine their greenhouse gas (GHG) mitigation potential and carbon neutrality. This is the first study to conduct an integrated life cycle assessment of biogas configurations in the landscape (biogas plants and their biomass catchments) for an entire region. RELCA a ‘REgional Life Cycle inventory Assessment’ approach was used to model the GHG mitigation potential of 425 biogas plants in the region of Central Germany (CG), aggregated to nine biogas clusters, based on feedstock mix (e.g. animal manures and energy crops) and installed capacity. GHG emission profiles were generated to compare and to identify the role of GHG credits and size of installed capacity on the mitigation performance of the regional biogas clusters. We found that smaller scaled slurry dominant clusters had significantly better GHG mitigation performance (−0.1 to −0.2 kg CO2eq kWhel−1), than larger energy crop dominant (ECdom) clusters (0.04–0.16 kg CO2eq kWhel−1), due to lower cultivation emissions and larger credits for avoided slurry storage. Thus, for the CG region larger ECdom clusters should be targeted first, to support GHG mitigation improvements to the overall future electricity supplied by the regional biogas systems. With the addition of GHG credits, the CG region is producing biogas with GHG savings (−0.15 kg CO2eq kWhel−1, interquartile range: 0.095 kg CO2eq kWhel−1). This infers that biogas production, as a waste management strategy for animal manures, could have important ramifications for future policy setting and national inventory accounting.
Exome‐wide association of deltamethrin resistance in Aedes aegypti from Mexico
Authors: Saavedra‐Rodriguez K. , Campbell C. L. , Lenhart A. , Penilla P. , Lozano‐Fuentes S. , Black W. C.
Published: February 2019

Aedes aegypti is the major vector of a number of arboviruses that cause disease in humans. Without vaccines or pharmaceuticals, pyrethroid insecticides remain the major tool for public health protection. Pyrethroid resistance is now widespread. Replacement substitutions in the voltage‐gated sodium channel (vgsc) that reduce the stability of pyrethroid binding account for most of the resistance, but metabolic mechanisms also inactivate pyrethroids. High‐throughput sequencing and the A. aegypti L5 annotated physical map has allowed interrogation of the exome for genes and single‐nucleotide polymorphisms associated with pyrethroid resistance. We exposed females of A. aegypti from Mexico to a deltamethrin discriminating dose to designate them as resistant (active after 1 h) or susceptible (knocked down with no recovery after 4 h). The vgsc on chromosome 3 had the highest association, followed by genes proximal to vgsc. We identified potential detoxification genes located singly (eg HPX8C) or within clusters in chromosome 2 [three esterase clusters, two of cytochrome P450 monooxygenases (CYP)] and chromosome 3 (one cluster of 16 CYP325 and seven CYP9 genes). Deltamethrin resistance in A. aegypti is associated with mutations in the vgsc gene and a large assortment of genes.
La Grippe or Russian influenza: Mortality statistics during the 1890 Epidemic in Indiana
Authors: Ewing E. Thomas
Published: February 2019

Background

The Russian influenza, which began in late 1889, has long been recognized as a major global epidemic yet available statistical evidence for morbidity and mortality has not been fully examined using historical and epidemiological tools. This study of cases and deaths in Indiana during the extended time period associated with the Russian influenza is the first scholarly effort to determine the number of victims from this influenza outbreak across a broad regional case study in the US.

Methods

The sources for this study include historical records from the US Census, Annual Reports from the Indiana State Board of Health, and death notices published in newspapers. The available evidence is analyzed using historical and epidemiological methods to determine the consistency of reporting categories, the accuracy of death records, and the applicability of contemporary categories for measuring mortality.

Results

In the 3 years during and following the outbreak of “Russian influenza” in January 1890 in the state of Indiana, approximately 3200 died specifically of this disease while a total of 11 700 died of influenza and other respiratory diseases. These results confirm that extremely widespread influenza contributed to higher than normal death rates by causing additional deaths in related categories, especially pneumonia and other respiratory diseases.

Conclusions

More reliable and thorough analysis of morbidity and mortality during the Russian influenza based on systematic and critical review of local, regional, and national statistics can inform contemporary understanding of the long‐term history of influenza epidemics.
Identification of dysregulation of atrial proteins in rats with chronic obstructive apnea using two‐dimensional polyacrylamide gel electrophoresis and mass spectrometry
Authors: Lux Jacob C. , Channaveerappa Devika , Aslebagh Roshanak , Heintz Timothy A. , McLerie Meredith , Panama Brian K. , Darie Costel C.
Published: February 2019

Obstructive sleep apnea (OSA) affects an estimated 20% of adults worldwide and has been associated with electrical and structural abnormalities of the atria, although the molecular mechanisms are not well understood. Here, we used two‐dimensional polyacrylamide gel electrophoresis (2D PAGE) coupled with nanoliquid chromatography‐tandem mass spectrometry (nanoLC‐MS/MS) to investigate the proteins that are dysregulated in the atria from severe and moderate apnea when compared to control. We found enzymes involved in the glycolysis, beta‐oxidation, electron transport chain and Krebs cycle to be down‐regulated. The data suggested that the dysregulated proteins may play a role in atrial pathology developing via chronic obstructive apnea and hypoxia. Our results are consistent with our previous 1D‐PAGE and nanoLC‐MS/MS study (Channaveerappa et al, J Cell Mol Med. 2017), where we found that some aerobic and anaerobic glycolytic and Krebs cycle enzymes were down‐regulated, suggesting that apnea may be a result of paucity of oxygen and production of ATP and reducing equivalents (NADH). The 2D‐PAGE study not only complements our current study, but also advances our understanding of the OSA. The complete mass spectrometry data are available via ProteomeXchange with identifier PXD011181.
Treatment of intrabony periodontal defects using rhFGF‐2 in combination with deproteinized bovine bone mineral or rhFGF‐2 alone: A 6‐month randomized controlled trial
Authors: Saito Atsushi , Bizenjima Takahiro , Takeuchi Takahiro , Suzuki Eiichi , Sato Masahiro , Yoshikawa Kouki , Kitamura Yurie , Matsugami Daisuke , Aoki Hideto , Kita Daichi , Imamura Kentaro , Irokawa Daisuke , Seshima Fumi , Tomita Sachiyo
Published: February 2019

Aim

To evaluate the use of recombinant human fibroblast growth factor (rhFGF)‐2 in combination with deproteinized bovine bone mineral (DBBM) compared with rhFGF‐2 alone, in the treatment of intrabony periodontal defects.

Materials and Methods

Patients with periodontitis who had received initial periodontal therapy and had intrabony defects of ≥ 3 mm in depth were enrolled. Sites were randomly assigned to receive a commercial formulation of 0.3% rhFGF‐2 + DBBM (test) or rhFGF‐2 alone (control). Clinical parameters and a patient‐reported outcome measure (PROM) were evaluated at baseline and at 3 and 6 months postoperatively.

Results

Twenty‐two sites in each group were evaluated. A significant improvement in clinical attachment level (CAL) from baseline was observed in both groups at 6 months postoperatively. CAL gain was 3.16 ± 1.45 mm in the test group and 2.77 ± 1.15 mm in the control group, showing no significant difference between groups. Radiographic bone fill was significantly greater in the test group (47.2%) than in the control group (29.3%). No significant difference in PROM between groups was observed.

Conclusions

At 6 months, no significant difference in CAL gain or PROM between the two treatments was observed, although combination therapy yielded an enhanced radiographic outcome.
Association between income levels and irregular physician visits after a health checkup, and its consequent effect on glycemic control among employees: A retrospective propensity score‐matched cohort study
Authors: Nishi Takumi , Babazono Akira , Maeda Toshiki
Published: February 2019

Aims/Introduction

The present study aimed to evaluate the effects of income levels on physician visit patterns and to quantify the consequent impact of irregular physician visits on glycemic control among employees’ health insurance beneficiaries in Japan.

Materials and Methods

We obtained specific health checkup data of untreated diabetes patients from the Fukuoka branch of the Japanese Health Insurance Association. We selected 2,981 insurance beneficiaries and classified 650 and 2,331 patients into, respectively, the regular visit and irregular visit group. We implemented propensity score matching to select an adequate control group.

Results

Compared with those with a standard monthly income <$2,000 (US$1 = ¥100), those with a higher monthly income were less likely to have irregular visits; $2,000–2,999: odds ratio 0.74 (95% confidence interval 0.56–0.98), $3,000–3,999: odds ratio 0.63 (95% confidence interval 0.46–0.87) and ≥$5,000: odds ratio 0.58 (95% confidence interval 0.39–0.86). After propensity score matching and adjusting for covariates, the irregular visit group tended to have poor glycemic control; increased glycated hemoglobin ≥0.5: odds ratio 1.90 (95% confidence interval 1.30–2.77), ≥1.0: odds ratio 2.75 (95% confidence interval 1.56–4.82) and ≥20% relatively: odds ratio 3.18 (95% confidence interval 1.46–6.92).

Conclusions

We clarified that there was a significant relationship between income and irregular visits, and this consequently resulted in poor glycemic control. These findings would be useful for more effective disease management.
Non‐invasive structure–function assessment of the liver by 2D time‐harmonic elastography and the dynamic Liver MAximum capacity (LiMAx) test
Authors: Heucke Niklas , Wuensch Tilo , Mohr Julia , Kaffarnik Magnus , Arsenic Ruza , Sinn Bruno , Müller Tobias , Pratschke Johann , Stockmann Martin , Sack Ingolf , Tzschätzsch Heiko
Published: February 2019

Background and Aim

Accurate assessment of structural and functional characteristics of the liver could improve the diagnosis and the clinical management of patients with chronic liver diseases. However, the structure–function relationship in the progression of chronic liver disease remains elusive. The aim of this study is the combined measurement of liver function by the 13C‐methacetin Liver MAximum capacity (LiMAx) test and tissue‐structure related stiffness by 2D time‐harmonic elastography for the assessment of liver disease progression.

Methods

LiMAx test and time‐harmonic elastography were applied, and the serological scores fibrosis 4 index and aspartate aminotransferase to platelet ratio index were calculated in patients with chronic liver diseases (n = 75) and healthy control subjects (n = 22). In 47 patients who underwent surgery, fibrosis was graded by histological examination of the resected liver tissue.

Results

LiMAx values correlated negatively with liver stiffness (r = −0.747), aminotransferase to platelet ratio index (r = −0.604), and fibrosis 4 (r = −0.573). Median (interquartile range) LiMAx values decreased with fibrosis progression from 395 μg/kg/h (371–460 μg/kg/h) in participants with no fibrosis to 173 μg/kg/h (126–309 μg/kg/h) in patients with severe fibrosis. Median liver stiffness increased progressively with the stage of fibrosis from no fibrosis (1.56 m/s [1.52–1.63 m/s]) to moderate fibrosis (1.60 m/s [1.54–1.67 m/s]) to severe fibrosis (1.85 m/s [1.76–1.92 m/s]).

Conclusion

Our findings show that structural changes in the liver due to progressing liver diseases and reflected by increased tissue stiffness correlate with a functional decline of the organ as reflected by a decreased metabolic capacity of the liver.
An anticlockwise P–T–t path at high‐pressure, high‐temperature conditions for a migmatitic gneiss from the island of Fjørtoft, Western Gneiss Region, Norway, indicates two burial events during the Caledonian orogeny
Authors: Liu Penglei , Massonne Hans‐Joachim
Published: February 2019

The Blåhø Nappe on the island of Fjørtoft, which represents an isolated portion of the Seve Nappe Complex in the Western Gneiss Region, Norway, has been suggested to have experienced two deep burial cycles during the Caledonian orogeny. However, evidence on this multiple burial process by the derivation of a pressure–temperature–time (P–T–t) path has never been given in the literature. In this study, the ‘diamondiferous’ kyanite–garnet gneiss from the Blåhø Nappe on Fjørtoft was revisited to determine if such a process was correct. Two types of garnet, porphyroblastic garnet‐1 and fine‐grained garnet‐2, were recognized in the gneiss. The core of garnet‐1 is poor in Ca and documents P–T conditions of 1.2–1.3 GPa at c. 880°C based on pseudosection modelling. The inner rims of garnet‐1 and the core of garnet‐2 are both richer in Ca, recording P–T conditions of 1.35–1.45 GPa and 770–820°C. Application of conventional geothermobarometry on the outer rim of garnet‐1 and the rim of garnet‐2 yielded retrograde P–T conditions of 0.75–0.90 GPa and 610–685°C. These estimates define an anticlockwise P–T path at pressures below 1.5 GPa. Accessory monazite was dated with the electron microscope. Relicts of detrital monazite in the gneiss point to Sveconorwegian and possibly also Cryogenian provenance for the detritus of the sedimentary protolith. Metamorphic monazite in the gneiss records a wide age range from 460 to 380 Ma, with a peak c. 435 Ma and a shoulder at 395 Ma. These data suggest that the original (Ediacaran?) Baltica margin sediment (gneiss protolith) was transported to the base of an overlying plate during the early Caledonian (pre‐Scandian) orogeny. A long residence time of the metasedimentary rock at this base caused its heating to 880°C and homogenization of the early garnet chemistry. The late Caledonian (Scandian) collision between Baltica and Laurentia led to further burial, during which the studied gneiss was close to the former surface of the downgoing continental plate and, thus, cooled. The reconstructed P–T–t path confirms the multiple burial history of the Blåhø Nappe but contradicts previous ideas of deep burial of the Fjørtoft gneiss to more than 100 km.
Integrated garnet and zircon–titanite geochronology constrains the evolution of ultra‐high–pressure terranes: An example from the Sulu orogen
Authors: Wang Da , Vervoort Jeffrey D. , Fisher Christopher M. , Cao Hui , Li Guangxu
Published: February 2019

Dating ultra‐high–pressure (UHP) metamorphic rocks provides important timing constraints on deep subduction zone processes. Eclogites, deeply subducted rocks now exposed at the surface, undergo a wide range of metamorphic conditions (i.e. deep subduction and exhumation) and their mineralogy can preserve a detailed record of chronologic information of these dynamic processes. Here, we present an approach that integrates multiple radiogenic isotope systems in the same sample to provide a more complete timeline for the subduction–collision–exhumation processes, based on eclogites from the Dabie–Sulu orogenic belt in eastern China, one of the largest UHP terranes on Earth. In this study, we integrate garnet Lu–Hf and Sm–Nd ages with zircon and titanite U–Pb ages for three eclogite samples from the Sulu UHP terrane. We combine this age information with Zr‐in‐rutile temperature estimates, and relate these multiple chronometers to different P–T conditions. Two types of rutile, one present as inclusions in garnet and the other in the matrix, record the temperatures of UHP conditions and a hotter stage, subsequent to the peak pressure (‘hot exhumation') respectively. Garnet Lu–Hf ages (c. 238–235 Ma) record the initial prograde growth of garnet, while coupled Sm–Nd ages (c. 219–213 Ma) reflect cooling following hot exhumation. The maximum duration of UHP conditions is constrained by the age difference of these two systems in garnet (c. 235–220 Ma). Complementary zircon and titanite U–Pb ages of c. 235–230 Ma and c. 216–206 Ma provide further constraints on the timing of prograde metamorphism and the ‘cold exhumation' respectively. We demonstrate that timing of various metamorphic stages can thus be determined by employing complementary chronometers from the same samples. These age results, combined with published data from adjacent areas, show lateral diachroneity in the Dabie–Sulu orogeny. Three sub‐blocks are thus defined by progressively younger garnet ages: western Dabie (243–238 Ma), eastern Dabie–northern Sulu (238–235 Ma) and southern Sulu terranes (225–220 Ma), which possibly correlate to different crustal slices in the recently proposed subduction channel model. These observed lateral chronologic variations in a large UHP terrane can possibly be extended to other suture zones.
Randomized, single‐blinded, crossover study of a novel wound dressing vs current clinical practice after percutaneous collagen induction therapy
Authors: Gold Michael H. , Biron Julie , RN Brynne Thompson
Published: February 2019

Introduction

Skin rejuvenation procedures have become common with sophisticated technologies with reduced downtime and related risks. Recently, microneedling has been paired with radiofrequency to create Fractional Radiofrequency Microneedling (FRFM) to induce neocollagenesis. Frequently, topical products are applied immediately after the needling. This procedure is known as percutaneous collagen induction therapy (PCIT). Postoperative topical wound care is critical for prompt rapid and safe healing, with moist wound healing deemed of primary importance for fast and correct scarring process. An ideal dressing enables a moist environment while reducing postprocedural inflammatory responses in the first stages of wound healing.

Objective

To evaluate whether an innovative silicone‐based wound dressing is superior than standard of care therapy in decreasing severity and duration of treatment‐site acute inflammatory reactions post PCIT.

Materials and Methods

Endymed PRO Intensif Handpiece (Endymed, Israel) was used for the full‐face FRFM procedure. Subjects (n = 20) applied treatment (Stratacel®—Stratpharma SG, Switzerland) and control (Aquaphor®—Beiersdorf Inc, USA) immediately after the procedure and daily; they were evaluated immediately postprocedure (baseline assessment), at 2, 3 and 7 days postprocedure. Digital and 3D pictures (Antera 3D Camera for Skin Analysis—Miravex, Ireland) were taken at each assessment.

Results

All patients healed properly without reporting adverse reactions to any of the studied products. Erythema at each study visit was significantly reduced with the use of the novel wound dressing (P < 0.001). A statistically significant difference in favor of the innovative wound dressing also emerged with respect to the patient‐rated product properties (P = 0.008), such as feel on skin, drying time and stickiness.

Conclusions

The novel wound dressing reduced signs of acute inflammation following PCIT when compared to standard of care, without reporting adverse events and resulting in a more favorable outcome from a patient perspective.
Insulin action is severely impaired in adipocytes of apparently healthy overweight and obese subjects
Authors: Rydén M. , Petrus P. , Andersson D. P. , Medina‐Gómez G. , Escasany E. , Corrales Cordón P. , Dahlman I. , Kulyté A. , Arner P.
Published: February 2019

Objective

Many overweight/obese subjects appear metabolically healthy with normal in vivo insulin sensitivity. Still, they have increased long‐term risk of developing type 2 diabetes. We hypothesized that adipose tissue dysfunction involving decreased insulin action in adipocytes is present in apparently healthy overweight/obese subjects.

Design/Methods

Subjects with normal metabolic health according to Adult Treatment Panel‐III or Framingham risk score criteria were subdivided into 67 lean, 32 overweight and 37 obese according to body mass index. They were compared with 200 obese individuals with metabolic syndrome. Insulin sensitivity and maximum action on inhibition of lipolysis and stimulation of lipogenesis was determined in subcutaneous adipocytes. Gene expression was determined by micro‐array and qPCR. DNA methylation was assessed by array, pyrosequencing and reporter assays.

Results

Compared with lean, adipocytes in overweight/obese displayed marked reductions in insulin sensitivity in both antilipolysis and lipogenesis as well as an attenuated maximum lipogenic response. Among these, only antilipolysis sensitivity correlated with whole‐body insulin sensitivity. These differences were already evident in the overweight state, were only slightly worse in the unhealthy obese state and were not related to fat cell size. Adipose tissue analyses linked this to reduced expression of the insulin signalling protein AKT2, which associated with increased methylation at regulatory sites in the AKT2 promoter.

Conclusions

Apparently healthy subjects have severely disturbed adipocyte insulin signalling already in the overweight state which involves epigenetic dysregulation of AKT2. This may constitute an early defect in insulin action that appears even upon modest increases in fat mass.
Risk factors forCandidaurinary tract infections in dogs and cats
Authors: Reagan Krystle L. , Dear Jonathan D. , Kass Philip H. , Sykes Jane E.
Published: February 2019

Background

Candidaurinary tract infections occur in both dogs in cats but there is limited data about risk factors.

Objective

To identify risk factors for candiduria in dogs in cats.

Animals

Eighteen dogs and 8 cats with candiduria.

Methods

A retrospective case‐control study, using univariate exact logistic regression. Medical records were searched for a diagnosis ofCandidaand animals with culture‐confirmed candiduria were enrolled. Controls had bacterial cystitis (dogs and cats) or cutaneousMalasseziainfection (dogs only).

Results

Administration of antibacterial drugs in the 30 days before diagnosis was associated with candiduria in dogs compared to controls with bacterial cystitis (OR 14.5; 95% CI 3.1‐66.9) or withMalasseziainfection (OR 26.4; 95% CI 3.4‐206.7). Antecedent antibacterial drug administration was associated with candiduria in cats (OR 15.7; 95% CI 1.9‐132.3). Immunosuppression was associated with candiduria in dogs when compared to controls withMalasseziainfection (OR 4.2, 95% CI 1.4‐12.8), but not significantly when compared to dogs with bacterial cystitis (OR 2.7, 95% CI 0.9‐8.0). Lower urinary tract diseases other than infection were associated with candiduria in cats (OR 6.7, 95% CI 1.6‐27.9), but not significantly in dogs (OR 2.5, 95% CI 0.7‐8.7). Neither diabetes mellitus nor history of hospitalization was significantly associated with candiduria in either species.

Conclusions and clinical importance

The recent administration of antibacterial drug therapy is a potential risk factor for development of candiduria in dogs and cats. Judicious use of antibacterial drugs might help to prevent candiduria.
Food and feeding habits of Octopus insularis in the Veracruz Reef System National Park and confirmation of its presence in the southwest Gulf of Mexico
Authors: Rosas‐Luis Rigoberto , Jiménez Badillo María de Lourdes , Montoliu‐Elena Lucia , Morillo‐Velarde Piedad S.
Published: February 2019

Octopuses are active predators that feed on a wide range of prey including crustaceans, fishes, and mollusks. They are important components of coral reef systems and support local and artisanal fisheries in the Gulf of México. Octopus insularis has been found to be one of the most relevant components in catches from the coral reef system of Veracruz in the southwestern Gulf of Mexico, and its role in the ecosystem requires assessment. To corroborate the morphological identification of O. insularis, six octopuses were identified by genetic methods. And to understand the trophic relationships between this octopus species and its prey, 394 octopuses caught during 2016 and 2017 by an artisanal fleet were sampled and their stomach contents analyzed. Results showed that crustaceans are the most frequently consumed group, with the genera Mithraculus and Etisus being the most important in the diet. Fishes, bivalves, and gastropods were identified as uncommon prey items in the diet. Their presence in the stomachs could be related to the movement of this octopus outside of the coral reef. Considering that our samples were of medium‐ and large‐sized individuals, cannibalism could be discarded for O. insularis in this size range in the Veracruz reef system. These findings suggest a generalist and opportunistic predation of O. insularis on the most abundant and available prey in the study area, namely the crustaceans. These represents an effective transfer of biomass from the low trophic levels to top predators in the coral reef system.
Retinal microvascular changes in microvascular angina: Findings from the Australian Heart Eye Study
Authors: Liew Gerald , Mitchell Paul , Chiha Joseph , Plant Adam J. H. , White Andrew , Joachim Nichole , Wang Sarah , Burlutsky George , Kovoor Pramesh , Thiagalingam Aravinda , Gopinath Bamini
Published: February 2019

Objective

Microvascular changes in microvascular angina are poorly understood due to difficulties in imaging the coronary microcirculation in vivo. The retinal microvasculature may reflect changes in coronary microcirculation. We assessed microvascular changes in the retina in patients with microvascular angina and compared them with patients with angiographically proven coronary artery disease.

Methods

We performed retinal photography and coronary angiography on 915 patients. Retinal vessel calibers were measured using a validated computer‐assisted method; coronary artery disease was graded from coronary angiograms. Microvascular angina was defined as angina with <25% stenosis in all coronary epicardial arteries.

Results

A total of 139 patients (15.2%) had microvascular angina, while 776 (84.8%) had coronary artery disease. Participants with microvascular angina and coronary artery disease had similar retinal arteriolar and venular calibers. After adjustment for age, ethnicity, mean arterial pressure, diabetes, current smoking, body mass index, and fellow vessel caliber, women with smaller venules were threefold more likely to have microvascular angina than women with larger venules (multivariable‐adjusted odds ratio 3.54, 95% confidence interval 1.35 to 9.24, P < 0.01). This difference was not observed in men.

Conclusions

Microvascular angina in women was associated with microvascular changes distinct from those in coronary artery disease.
First‐in‐human retrieval of chronically implanted Micra transcatheter pacing system
Authors: Curnis Antonio , Cerini Manuel , Mariggiò Davide , Mitacchione Gianfranco , Giacopelli Daniele , Inama Lorenza , Bontempi Luca
Published: February 2019

We report the first‐in‐human retrieval of a chronically implanted Micra transcatheter pacing system (TPS; Medtronic, Minneapolis, MN, USA). A 41‐year‐old woman suffering from third‐degree atrioventricular block was successfully implanted with a TPS in the low septum of the right ventricle. After 29 months, due to an increased electrical threshold and 100% pacing percentage, the device showed low battery voltage. Despite the long implant duration, the attempt of device retrieval using a snare loop inserted in the delivery system of a TPS was successful. In the same procedure, a new leadless pacemaker was implanted in the high right ventricular septum with optimal pacing threshold.