bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma and Joint Fluid Glypican-3 Are Inversely Correlated with the Severity of Knee Osteoarthritis
Authors: Udomsinprasert Wanvisa , McConachie Ellie , Ngarmukos Srihatach , Theerawattanapong Nipaporn , Tanavalee Aree , Honsawek Sittisak
Published: April 2019

Objective

Glypican-3 possesses a possible action in regulation of bone growth and development implicated in osteoarthritis (OA) pathology. Therefore, this study aimed to investigate glypican-3 in plasma and synovial fluid of knee OA patients and to determine the possible association between glypican-3 levels and radiographic severity.

Design

A total of 80 knee OA patients and 80 healthy controls were recruited. Glypican-3 levels in plasma and synovial fluid were measured using enzyme-linked immunosorbent assay. The severity of knee OA was assessed by radiographic grading according to the Kellgren-Lawrence classification. Relative mRNA expression of glypican-3 in 10 inflamed synovial tissues from OA patients and 10 noninflamed synovial controls was quantified using real-time polymerase chain reaction.

Results

Plasma glypican-3 levels were significantly lower in OA patients than in healthy controls ( P = 0.03), whereas synovial fluid glypican-3 levels were remarkably greater than in paired plasma samples of OA patients ( P < 0.001). Subsequent analysis demonstrated that plasma and synovial fluid glypican-3 levels were inversely associated with the radiographic severity of knee OA ( r = −0.691, P < 0.001; r = −0.646, P < 0.001, respectively). Furthermore, there was a positive relationship between plasma and synovial fluid glypican-3 levels in knee OA patients ( r = 0.515, P < 0.001). Additionally, overexpression of glypican-3 mRNA was observed in inflamed synovium of OA patients ( P = 0.021).

Conclusions

The present study revealed that plasma and synovial glypican-3 levels were negatively associated with radiographic severity of knee OA. Glypican-3 could emerge as a potential biomarker for reflecting the severity of knee OA and might play a plausible role in the pathophysiology of degenerative joint disease.
Recent developments in EU legislation on anti-money laundering and terrorist financing
Authors: Silva Patrícia Godinho
Published: April 2019

Money laundering and terrorist financing pose a clear risk to the integrity, proper functioning, reputation and stability of society, especially regarding the financial system. Accordingly, there must be effective measures to address these risks and threats, which are of a cross-border nature. The European Commission has been doing a relevant work in this field but it is important not to rush things, in order to ensure that, in close cooperation with the Member States and all the actors involved, the new legislative measures and initiatives will be properly implemented, in order to achieve a harmonized framework and to avoid unnecessary overlapping and redundancies with real impact on the fight against money laundering and terrorist financing. Moreover, it is necessary to ensure that the effectiveness of the anti-money laundering and counter-terrorist financing (AML/CFT) policies does not impinge upon human rights in an impermissible manner. In particular, as regards the processing and access to personal data involved in beneficial ownership information, the amendments to the 4th AML Directive might arguably not be in full compliance with the principle of proportionality.
Effects of attitudes towards ambiguity on subclinical depression and anxiety in healthy individuals
Authors: Enoki Hiroyuki , Koda Munenaga , Nishimura Sayako , Kondo Tsuyoshi
Published: April 2019

This study aims to examine the effects of multidimensional attitudes towards ambiguity on subclinical depression and anxiety in healthy individuals. Attitudes Towards Ambiguity Scale, consisting of four clusters (enjoyment, anxiety, exclusion, and noninterference), Self-Rating Depression Scale, and State-Trait Anxiety Inventory–trait version were administered to 1019 Japanese volunteers. The result of a regression analysis suggested that the score of Attitudes Towards Ambiguity Scale–enjoyment factor significantly contributed to the Self-Rating Depression Scale score while that of Attitudes Towards Ambiguity Scale–anxiety factor significantly contributed to the State-Trait Anxiety Inventory–trait score. Among attitudes toward ambiguity, enjoyment may have protective effects against subclinical depression whereas anxiety can enhance anxiety-trait in nonclinical individuals.
A comparison study on hindfoot correction, Achilles tendon length and thickness between clubfoot patients treated with percutaneous Achilles tendon tenotomy versus casting alone using Ponseti method
Authors: Chandirasegaran Saturveithan , Gunalan Roshan , Aik Saw , Kaur Shaleen
Published: April 2019

Purpose:

To compare the hindfoot correction using clinical and ultrasonography assessment in clubfoot patients undergoing Achilles tendon tenotomy with patients corrected with casting alone.

Method:

A prospective observational study on idiopathic clubfoot patients less than 3 months old. Clinical assessment was done using hindfoot Pirani score and measurement of ankle dorsiflexion. Serial ultrasonography was done to measure the length and thickness of the Achilles tendon pre-hindfoot correction, 3 and 6 weeks post-hindfoot correction. Independent t-test was used to analyse the increase in ankle dorsiflexion, improvement in length and thickness of Achilles tendon between the two groups. Mann–Whitney U test was used to analyse the improvement in hindfoot Pirani score. Pearson correlation test was used for correlation in between clinical severity and ultrasonography assessment.

Results:

Twenty-three patients with bilateral clubfoot and four with unilateral clubfoot were recruited with a total of 50 clubfeet. Each group consists of 25 feet with a mean age of 2 months. Marked improvement in hindfoot correction was noted in tenotomy group compared to non-tenotomy group as evidenced by significant increase in Achilles tendon length, ankle dorsiflexion and improvement of hindfoot Pirani score. No significant difference in Achilles tendon thickness was noted between the two groups. Positive correlation was demonstrated between increase in Achilles tendon length and increase in ankle dorsiflexion as well as improvement in hindfoot Pirani score.

Conclusion:

We would like to propose Achilles tendon tenotomy in all clubfoot patients as it is concretely evident that superior hindfoot correction was achieved in tenotomy group.
Acquired Factor X Deficiency in Patients With Primary Light Chain Amyloidosis
Authors: Dejhansathit Siroj , Suvannasankha Attaya
Published: April 2019

Acquired factor X (FX) deficiency is a rare but serious complication of primary amyloidosis, presumably caused by the binding of amyloid proteins to the clotting factors. The prolonged prothrombin time, partial thromboplastin time, and low FX level, which are correctable by mixing study, are the disease hallmarks. An immediate goal of care is to stop bleeding. Clotting factor replacement requires close monitoring of coagulogram and FX levels due to varying FX clearance among patients. High-purity FX is currently approved for hereditary FX deficiency and has been successfully used in some acquired FX deficiency cases. Ongoing bleeding risk complicates the treatment decision. Novel therapies yielding rapid and deep response reduce amyloid protein production and improve long-term outcome.
Thymoquinone-Induced Reactivation of Tumor Suppressor Genes in Cancer Cells Involves Epigenetic Mechanisms
Authors: Qadi Shahad A , Hassan Mohammed A , Sheikh Ryan A , Baothman Othman AS , Zamzami Mazin A , Choudhry Hani , Al-Malki Abdulrahman Labeed , Albukhari Ashwag , Alhosin Mahmoud
Published: April 2019

The epigenetic silencing of tumor suppressor genes (TSGs) is a common finding in several solid and hematological tumors involving various epigenetic readers and writers leading to enhanced cell proliferation and defective apoptosis. Thymoquinone (TQ), the major biologically active compound of black seed oil, has demonstrated anticancer activities in various tumors by targeting several pathways. However, its effects on the epigenetic code of cancer cells are largely unknown. In the present study, we performed RNA sequencing to investigate the anticancer mechanisms of TQ-treated T-cell acute lymphoblastic leukemia cell line (Jurkat cells) and examined gene expression using different tools. We found that many key epigenetic players, including ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 ( UHRF1), DNMT1,3A,3B, G9A, HDAC1,4,9, KDM1B, and KMT2A,B,C,D,E, were downregulated in TQ-treated Jurkat cells. Interestingly, several TSGs, such as DLC1, PPARG, ST7, FOXO6, TET2, CYP1B1, SALL4, and DDIT3, known to be epigenetically silenced in various tumors, including acute leukemia, were upregulated, along with the upregulation of several downstream pro-apoptotic genes, such as RASL11B, RASD1, GNG3, BAD, and BIK. Data obtained from RNA sequencing were confirmed using quantitative reverse transcription polymerase chain reaction (RT-qPCR) in Jurkat cells, as well as in a human breast cancer cell line (MDA-MB-468 cells). We found that the decrease in cell proliferation and in the expression of UHRF1, DNMT1, G9a, and HDAC1 genes in both cancer cell (Jurkat cells and MDA-MB-468 cells) lines depends on the TQ dose. Our results indicate that the use of TQ as an epigenetic drug represents a promising strategy for epigenetic therapy for both solid and blood tumors by targeting both DNA methylation and histone post-translational modifications.
Inhibition of platelet GPVI induces intratumor hemorrhage and increases efficacy of chemotherapy in mice
Authors: Volz Julia , Mammadova-Bach Elmina , Gil-Pulido Jesus , Nandigama Rajender , Remer Katharina , Sorokin Lydia , Zernecke Alma , Abrams Scott I. , Ergün Süleyman , Henke Erik , Nieswandt Bernhard
Published: April 2019

Maintenance of tumor vasculature integrity is indispensable for tumor growth and thus affects tumor progression. Previous studies have identified platelets as major regulators of tumor vascular integrity, as their depletion selectively rendered tumor vessels highly permeable and caused massive intratumoral hemorrhage. While these results established platelets as potential targets for antitumor therapy, their depletion is not a treatment option due to their essential role in hemostasis. Thus, a detailed understanding of how platelets safeguard vascular integrity in tumors is urgently demanded. Here, we show for the first time that functional inhibition of glycoprotein VI (GPVI) on the platelet surface with an antibody (JAQ1) F(ab)2 fragment rapidly induces tumor hemorrhage and diminishes tumor growth similar to complete platelet depletion while not inducing systemic bleeding complications. The intratumor bleeding and tumor growth arrest could be reverted by depletion of Ly6G+ cells, confirming them to be responsible for the induction of bleeding and necrosis within the tumor. In addition, JAQ1 F(ab)2–mediated GPVI inhibition increased intratumoral accumulation of coadministered chemotherapeutic agents, such as Doxil and paclitaxel, thereby resulting in a profound antitumor effect. In summary, our findings identify platelet GPVI as a key regulator of vascular integrity specifically in growing tumors and could serve as a basis for the development of antitumor strategies based on the interference with platelet function.
Identification of a novel enhancer of CEBPE essential for granulocytic differentiation
Authors: Shyamsunder Pavithra , Shanmugasundaram Mahalakshmi , Mayakonda Anand , Dakle Pushkar , Teoh Weoi Woon , Han Lin , Kanojia Deepika , Lim Mei Chee , Fullwood Melissa , An Omer , Yang Henry , Shi Jizhong , Hossain Mohammad Zakir , Madan Vikas , Koeffler H. Phillip
Published: April 2019

CCAAT/enhancer binding protein ε (CEBPE) is an essential transcription factor for granulocytic differentiation. Mutations of CEBPE occur in individuals with neutrophil-specific granule deficiency (SGD), which is characterized by defects in neutrophil maturation. Cebpe-knockout mice also exhibit defects in terminal differentiation of granulocytes, a phenotype reminiscent of SGD. Analysis of DNase I hypersensitive sites sequencing data revealed an open chromatin region 6 kb downstream of the transcriptional start site of Cebpe in murine myeloid cells. We identified an interaction between this +6-kb region and the core promoter of Cebpe using circular chromosome conformation capture sequencing (4C-seq). To understand the role of this putative enhancer in transcriptional regulation of Cebpe, we targeted it using catalytically inactive Cas9 fused to Krüppel-associated box (KRAB) domain and observed a significant downregulation of transcript and protein levels of CEBPE in cells expressing guide RNA targeting the +6-kb region. To further investigate the role of this novel enhancer further in myelopoiesis, we generated mice with deletion of this region using CRISPR/Cas9 technology. Germline deletion of the +6-kb enhancer resulted in reduced levels of CEBPE and its target genes and caused a severe block in granulocytic differentiation. We also identified binding of CEBPA and CEBPE to the +6-kb enhancer, which suggests their role in regulating the expression of Cebpe. In summary, we have identified a novel enhancer crucial for regulating expression of Cebpe and required for normal granulocytic differentiation.
PD-1 blockade with pembrolizumab for classical Hodgkin lymphoma after autologous stem cell transplantation
Authors: Armand Philippe , Chen Yi-Bin , Redd Robert A. , Joyce Robin M. , Bsat Jad , Jeter Erin , Merryman Reid W. , Coleman Kimberly C. , Dahi Parastoo B. , Nieto Yago , LaCasce Ann S. , Fisher David C. , Ng Samuel Y. , Odejide Oreofe O. , Freedman Arnold S. , Kim Austin I. , Crombie Jennifer L. , Jacobson Caron A. , Jacobsen Eric D. , Wong Jeffrey L. , Patel Sanjay S. , Ritz Jerome , Rodig Scott J. , Shipp Margaret A. , Herrera Alex F.
Published: April 2019

Autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL) who respond to salvage chemotherapy. However, relapse after ASCT remains a frequent cause of treatment failure, with poor subsequent prognosis. Because cHL is uniquely vulnerable to programmed cell death-1 (PD-1) blockade, PD-1 blockade given as consolidation after ASCT could improve ASCT outcomes. We therefore conducted a multicohort phase 2 study of pembrolizumab in patients with RR cHL after ASCT, hypothesizing that it would improve the progression-free survival (PFS) at 18 months after ASCT (primary end point) from 60% to 80%. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles, starting within 21 days of post-ASCT discharge. Thirty patients were treated on this study. The median age was 33 years, and 90% were high-risk by clinical criteria. Seventy-seven percent completed all 8 cycles. Toxicity was manageable, with 30% of patients experiencing at least 1 grade 3 or higher adverse event (AE), and 40% at least 1 grade 2 or higher immune-related AE. Two patients were lost to follow-up in complete remission at 12 months. The PFS at 18 months for the 28 evaluable patients was 82%, meeting the primary end point. The 18-month overall survival was 100%. In conclusion, pembrolizumab was successfully administered as post-ASCT consolidation in patients with RR cHL, and resulted in a promising PFS in a high-risk patient cohort, supporting the testing of this strategy in a randomized trial. This trial was registered at www.clinicaltrials.gov as #NCT02362997.
Red blood cells modulate structure and dynamics of venous clot formation in sickle cell disease
Authors: Faes Camille , Ilich Anton , Sotiaux Amandine , Sparkenbaugh Erica M. , Henderson Michael W. , Buczek Laura , Beckman Joan D. , Ellsworth Patrick , Noubouossie Denis F. , Bhoopat Lantarima , Piegore Mark , Renoux Céline , Bergmeier Wolfgang , Park Yara , Ataga Kenneth I. , Cooley Brian , Wolberg Alisa S. , Key Nigel S. , Pawlinski Rafal
Published: April 2019

Sickle cell disease (SCD) is associated with chronic activation of coagulation and an increased risk of venous thromboembolism. Erythrocyte sickling, the primary pathologic event in SCD, results in dramatic morphological changes in red blood cells (RBCs) because of polymerization of the abnormal hemoglobin. We used a mouse model of SCD and blood samples from sickle patients to determine if these changes affect the structure, properties, and dynamics of sickle clot formation. Sickling of RBCs and a significant increase in fibrin deposition were observed in venous thrombi formed in sickle mice. During ex vivo clot contraction, the number of RBCs extruded from sickle whole blood clots was significantly reduced compared with the number released from sickle cell trait and nonsickle clots in both mice and humans. Entrapment of sickled RBCs was largely factor XIIIa–independent and entirely mediated by the platelet-free cellular fraction of sickle blood. Inhibition of phosphatidylserine, but not administration of antisickling compounds, increased the number of RBCs released from sickle clots. Interestingly, whole blood, but not plasma clots from SCD patients, was more resistant to fibrinolysis, indicating that the cellular fraction of blood mediates resistance to tissue plasminogen activator. Sickle trait whole blood clots demonstrated an intermediate phenotype in response to tissue plasminogen activator. RBC exchange in SCD patients had a long-lasting effect on normalizing whole blood clot contraction. Furthermore, RBC exchange transiently reversed resistance of whole blood sickle clots to fibrinolysis, in part by decreasing platelet-derived PAI-1. These properties of sickle clots may explain the increased risk of venous thromboembolism observed in SCD.
Long non-coding RNA GBCDRlnc1 induces chemoresistance of gallbladder cancer cells by activating autophagy
Authors: Cai Qiang , Wang Shouhua , Jin Longyang , Weng Mingzhe , Zhou Di , Wang Jiandong , Tang Zhaohui , Quan Zhiwei
Published: April 2019

Background

Gallbladder cancer is the most common biliary tract malignancy and not sensitive to chemotherapy. Autophagy is an important factor prolonging the survival of cancer cells under chemotherapeutic stress. We aimed to investigate the role of long non-coding RNAs (lncRNAs) in autophagy and chemoresistance of gallbladder cancer cells.

Methods

We established doxorubicin (Dox)-resistant gallbladder cancer cells and used microarray analysis to compare the expression profiles of lncRNAs in Dox-resistant gallbladder cancer cells and their parental cells. Knockdown or exogenous expression of lncRNA combined with in vitro and in vivo assays were performed to prove the functional significance of lncRNA. The effects of lncRNA on autophagy were assessed by stubRFP-sensGFP-LC3 and western blot. We used RNA pull-down and mass spectrometry analysis to identify the target proteins of lncRNA.

Results

The drug-resistant property of gallbladder cancer cells is related to their enhanced autophagic activity. And we found a lncRNA ENST00000425894 termed gallbladder cancer drug resistance-associated lncRNA1 (GBCDRlnc1) that serves as a critical regulator in gallbladder cancer chemoresistance. Furthermore, we discovered that GBCDRlnc1 is upregulated in gallbladder cancer tissues. Knockdown of GBCDRlnc1, via inhibiting autophagy at initial stage, enhanced the sensitivity of Dox-resistant gallbladder cancer cells to Dox in vitro and in vivo. Mechanically, we identified that GBCDRlnc1 interacts with phosphoglycerate kinase 1 and inhibits its ubiquitination in Dox-resistant gallbladder cancer cells, which leads to the down-regulation of autophagy initiator ATG5-ATG12 conjugate.

Conclusions

Our findings established that the chemoresistant driver GBCDRlnc1 might be a candidate therapeutic target for the treatment of advanced gallbladder cancer.
Diagnosing and tracing the pathogens of infantile infectious diarrhea by amplicon sequencing
Authors: Liu Haiyan , Guo Mingzhang , Jiang Yuanchunzi , Cao Yanhua , Qian Qingzeng , He Xiaoyun , Huang Kunlun , Zhang Jianwei , Xu Wentao
Published: April 2019

Background

Metagenomic methods have been widely applied to study the relationship between gut microbiota and human health. To test whether metagenomic amplicon sequencing could be an effective method to diagnose and trace the pathogens of infantile infectious diarrhea, the fecal samples of 20 diarrheic and 13 healthy infants were collected. After 16S rDNA amplicon sequencing, diversity analyses were carried out. The relationship between the pathogens of the gut microbiota and geography of patients was analyzed.

Results

The diversity of the gut microbiota in diarrheic infants was significantly lower than that of the gut microbiota in healthy ones and that, the composition of gut microbiota in the diarrheic group was significantly different than that of the gut microbiota in the healthy group. The results also indicated that in some of the patients, the amounts of Escherichia coli were significantly increased in the diarrheic infants, which was in agreement with the result of the qPCR analysis. Using a geographical map, we found some patterns between pathogen source and geographical location. This is helpful for an early warning of the disease.

Conclusions

The method of using high-throughput DNA sequencing and a comprehensive and deep data analysis can be a new strategy to detect and trace pathogens in infantile infectious diarrhea.

Trial registration Diagnosing and tracing the pathogens of infantile infectious diarrhea by amplicon sequencing, ChiCTR-DDD-1701088, Registered 16 March 2017-Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=18477
Regularized full-waveform inversion with automated salt flooding
Authors: Kalita Mahesh , Kazei Vladimir , Choi Yunseok , Alkhalifah Tariq
Published: April 2019

Full-waveform inversion (FWI) attempts to resolve an ill-posed nonlinear optimization problem to retrieve the unknown subsurface model parameters from seismic data. In general, FWI fails to obtain an adequate representation of models with large high-velocity structures over a wide region, such as salt bodies and the sediments beneath them, in the absence of low frequencies in the recorded seismic signal, due to nonlinearity and nonuniqueness. We alleviate the ill posedness of FWI associated with data sets affected by salt bodies using model regularization. We have split the optimization problem into two parts: First, we minimize the data misfit and the total variation in the model, seeking to achieve an inverted model with sharp interfaces; and second, we minimize sharp velocity drops with depth in the model. Unlike conventional industrial salt flooding, our technique requires minimal human intervention and no information about the top of the salt. Those features are demonstrated on data sets of the BP 2004 and Sigsbee2A models, synthesized from a Ricker wavelet of dominant frequency 5.5 Hz and minimum frequency 3 Hz. We initiate the inversion process with a simple model in which the velocity increases linearly with depth. The model is well-retrieved when the same constant density acoustic code is used to simulate the observed data, which is still one of the most common FWI tests. Moreover, our technique allows us to reconstruct a reasonable depiction of the salt structure from the data synthesized independently with the BP 2004 model with variable density. In the Sigsbee2A model, we manage to even capture some of the fine layering beneath the salt. In addition, we evaluate the versatility of our method on a field data set from the Gulf of Mexico.
Valproate in dementia: time to move on?
Authors: Dhindsa Amreek
Published: April 2019

Baillonet al’s Cochrane review included 430 participants with agitation in dementia from five randomised controlled trials. Overall, the reviewers found that valproate was no better than placebo for the treatment of agitation in people with dementia; however, the quality of the studies included was very variable. Adverse effects and events were higher in the treatment group compared with the controls, although these finding were largely based on low-quality data with incomplete reporting; thus, valproate's safety profile is of concern. This review demonstrates that there is insufficient evidence to change current treatment guidelines.

DECLARATION OF INTEREST

None.
Understanding psychiatrists' knowledge, attitudes and experiences in identifying and supporting their patients on the autism spectrum: online survey
Authors: Crane Laura , Davidson Ian , Prosser Rachel , Pellicano Elizabeth
Published: April 2019

Background

Psychiatrists play a critical role in identifying and supporting their patients on the autism spectrum in the UK, yet little is known about their knowledge, attitudes and experiences in this regard.

Aims

To understand psychiatrists' experiences of working with autistic individuals, their confidence in making diagnostic/management decisions and the factors that affect such decisions.

Method

A total of 172 psychiatrists took part in an online self-report survey.

Results

Most psychiatrists reported receiving useful training on autism and were knowledgeable about the condition, particularly those with a personal connection to autism. Higher confidence in working with autistic patients was linked to greater levels of autism knowledge, experience and training. Several systemic and autism-specific factors were highlighted by psychiatrists, which were felt to challenge their ability to provide effective care and support for their patients on the autism spectrum.

Conclusions

Psychiatrists' views corroborated previous research with the autism community, highlighting the need to co-design services that are accessible, respectful and person-centred.

Declaration of interest

I.D. is the Royal College of Psychiatrists' Autism Champion.
Phosphorylation of Forkhead Protein FoxO1 at S253 Regulates Glucose Homeostasis in Mice
Authors: Zhang Kebin , Guo Xiaoqin , Yan Hui , Wu Yuxin , Pan Quan , Shen James Zheng , Li Xiaopeng , Chen Yunmei , Li Ling , Qi Yajuan , Xu Zihui , Xie Wei , Zhang Weiping , Threadgill David , He Ling , Villarreal Daniel , Sun Yuxiang , White Morris F , Zheng Hongting , Guo Shaodong
Published: April 2019

The transcription factor forkhead box O1 (FoxO1) is a key mediator in the insulin signaling pathway and controls multiple physiological functions, including hepatic glucose production (HGP) and pancreatic β-cell function. We previously demonstrated that S256 in human FOXO1 (FOXO1-S256), equivalent to S253 in mouse FoxO1 (FoxO1-S253), is a key phosphorylation site mediating the effect of insulin as a target of protein kinase B on suppression of FOXO1 activity and expression of target genes responsible for gluconeogenesis. Here, we investigated the role of FoxO1-S253 phosphorylation in control of glucose homeostasis in vivo by generating global FoxO1-S253A/A knockin mice, in which FoxO1-S253 alleles were replaced with alanine (A substitution) blocking FoxO1-S253 phosphorylation. FoxO1-S253A/A mice displayed mild increases in feeding blood glucose and insulin levels but decreases in fasting blood glucose and glucagon concentrations, as well as a reduction in the ratio of pancreatic α-cells/β-cells per islet. FoxO1-S253A/A mice exhibited a slight increase in energy expenditure but barely altered food intake and glucose uptake among tissues. Further analyses revealed that FoxO1-S253A/A enhances FoxO1 nuclear localization and promotes the effect of glucagon on HGP. We conclude that dephosphorylation of S253 in FoxO1 may reflect a molecular basis of pancreatic plasticity during the development of insulin resistance.
Diagnostic value of urea, creatinine and blood parameters in patients with pneumonia diagnosed with chronic obstructive pulmonary disease
Authors: Akduman Seha
Published: April 2019

Background: This study aimed to investigate the diagnostic value of urea, creatinine and other blood parameters in patients with pneumonia diagnosed with chronic obstructive pulmonary disease (COPD) for the first time.

Methods: In this retrospective study, patients who had been diagnosed with COPD for the first time and were diagnosed with pneumonia were included. A total of 193 patients were divided into three groups as COPD + pneumonia (n=123), COPD (n=36) and pneumonia (n=34).

Results: In total, 59 women (48.0%) and 64 men (52.0%) from the COPD + pneumonia group, 13 women (36.1%) and 23 men (63.9%) from the COPD group, 21 women (61.8%) and 13 men (38.2%) from the pneumonia group were assessed. The mean age of the COPD + pneumonia group was 69.58±13.62, 66.28±12.55 for the COPD group and 53.97±19.72 for the pneumonia group. The highest values of C-reactive protein (CRP), urea, creatinine, white blood cells (WBC), neutrophils, eosinophils and hemoglobin were the highest in COPD + pneumonia group. CRP levels were significantly different between COPD + pneumonia group (p<0.05). The parameters urea, WBC and neutrophils were significantly different between COPD + pneumonia group and pneumonia group (p<0.05). There was a statistically significant difference between COPD and pneumonia groups in terms of neutrophils and eosinophils values (p<0.05). According to the results of receiver operating characteristic analysis, the diagnostic value of the urea parameter in determining the COPD + pneumonia group was not statistically significant (p>0.05). On the other hand, the diagnostic value of CRP, WBC and neutrophils values were statistically significant (p<0.05).

Conclusions: Elevation in WBC and neutrophil values in patients diagnosed with pneumonia have an important role in diagnosis of COPD.
Practice Summary: Managing Capacity at the University of Mary Washington’s College of Business
Authors: Garcia Christopher
Published: April 2019

To manage growth as the university approaches capacity, the author modeled the problem as a multiobjective max-flow system with pooled resources and developed a spreadsheet model to determine the optimal allocation of resources across the university’s programs.
On the Profitability of Stacked Discounts: Identifying Revenue and Cost Effects of Discount Framing
Authors: Ertekin Necati , Shulman Jeffrey D. , Chen Haipeng (Allan)
Published: April 2019

A multimethod investigation of how stacked discounts (e.g., “25% off, plus an extra 20% off”) affect initial sales and product returns.
The nursing aspects of a transcatheter aortic valve implantation patient's pathway
Authors: Carpenter Sadie
Published: April 2019

Globally, symptomatic aortic stenosis is becoming a more prevalent medical condition as a result of an ageing population. Transcatheter aortic valve implantation is an alternative treatment for elderly patients with multiple comorbidities who are not suitable for surgery. Following multiple tests, patients are discussed at a heart valve specialist multidisciplinary team meeting to determine whether they are suitable for a transcatheter aortic valve implantation procedure. Understanding the pathophysiology of aortic stenosis and function of the native aortic valve is imperative to understand how a replacement prosthetic valve can treat aortic stenosis. This article outlines how patients are managed and explores future considerations for nursing practice.
Managing the patient with heel pain
Authors: Bhatty Usman N , Khan Shah HM , Zubairy Aamir I
Published: April 2019

Heel pain presents frequently to primary care, commonly affecting athletic and elderly patients. Its presentation can be a common source of confusion for clinicians given the wide variety of differential diagnoses and the similarities in presenting symptoms and signs. This review classifies heel pain according to site of pain and explores the common pathologies clinicians may encounter. A brief summary of common imaging modalities used is provided. The literature is reviewed to guide evidence-based practice and to provide a framework to help clinicians investigate and manage heel pain before onward referral for specialist intervention. A linked article detailing the imaging of heel pain is included in this issue ( https://doi.org/10.12968/hmed.2019.80.4.192 ).
Radiotherapy in the control of bleeding from primary and secondary lung tumours
Authors: Gaito Simona , Hughes Christopher , Woolf David , Radhakrishna Ganesh
Published: April 2019

This literature review clarifies the role of radiotherapy in the management of low-volume haemoptysis. Embase and Medline were interrogated, and PRISMA guidelines were then used to select relevant articles. Seventy-eight articles were considered relevant and manually reviewed.

The evidence suggests that external beam radiotherapy is more effective than endobronchial brachytherapy at controlling low-volume haemoptysis. There is no evidence to recommend a combination of the two techniques. Different doses and fractionations appear equally effective, with a potential survival advantage of higher dose regimens for fitter patients.

Palliative radiotherapy is effective at controlling low-volume haemoptysis. External beam radiotherapy is the first-line treatment, with endobronchial brachytherapy recommended following external beam radiotherapy failure. Choice of dose and fractionation should take into account the patient's performance status.
Models to support whole-school planning
Authors: Burnage Steve
Published: April 2019

Effective long-term, strategic planning is at the very heart of the outstanding school. Steve Burnage looks at how two popular models for whole-school planning work in practice
Effects of Quality and Sensory Characteristics of Yogurt Added with Tagatose
Authors: Sung Dong-Eun , Lim Seung-Yong
Published: April 2019

To investigate the effects of tagatose added to yogurt fermented with Streptococcus thermophiles (ST) or Lactobacillus delbrueckii subsp. Bulgaricus (LB), pH, titratable acidity (TA), sugar content, color value, viable cell number, and sensory evaluation were determined on yogurts added with 7% sucrose, tagatose, or a mixture of sucrose and tagatose in triplicate. After 24 h, pH and sugar content of sucrose-added yogurt reached nearly 4.5 and 4.2 respectively, and were lower than those of yogurt with tagatose (above 5.6 and 8.6, respectively). Also, TA of sucroseadded yogurt (1.51%) was much higher than that of yogurt with tagatose (0.59%). There were no significant differences in color value and viable cell count after 24 h. However, the addition of tagatose seems to slow the growth rate of LB more than that of ST. Sensory preference revealed that mixture-added yogurts scored significantly higher in taste (5.90), texture (5.86), and overall acceptability (6.16) than yogurts with tagatose (5.20, 5.02, and 5.36, respectively), but there was no significant difference from the sucrose-added yogurts. In conclusion, tagatose inhibited the fermentation rate, but the mixture of tagatose and sucrose could be used for yogurts with lower calories and glucose index (GI) without a sensory difference from sucrose-added yogurt.
Preparation of Carbon Source for Modified MRS Medium and Antibacterial Activity of Bacteriocin from L. plantarum
Authors: Yu DaJung , Park GwiGun
Published: April 2019

β-mannanase from Trichoderma reesei was purified by DEAE Sephadex A-50 ion exchange chromatography and Sephadex G-100 gel chromatography. The molecular weight was determined to be 54 kDa by tricine SDS-PAGE. Trigonella foenum-graecum galactomannan was hydrolyzed by the purified β-mannanase, and then the hydrolysates were separated by Bio-Gel P2 chromatography. The main hydrolysates were composed of D.P. (degree of polymerization) 2, 3, and 4, 6 galactomanno-oligosaccharides. To investigate the effects of Trigonella foenum-graecum galactomanno- oligosaccharides on in vitro growth of L. plantarum, were cultivated individually on a modified-MRS medium containing carbon sources such as low- and high-molecular-weight galactomanno-oligosaccharide. Lactobacillus plantarum grew 1.8-fold after treatment with high- and low-molecular-weight galactomanno-oligosaccharides, compared to 1.3-fold for those with standard MRS medium. Bacteriocin was purified by Sephadex G-100 gel chromatography and determined to be 122 kDa by tricine SDS-PAGE. The bacteriocin activated doubly more effectively after treatment with galactosmanno-oligosaccharides compared to those with standard MRS medium. Bacteriocin showed antimicrobial activity against Staphylococcus aureus. The inhibitory compound lost activity when heated to temperatures greater than 30°C and when inhibited to pH changes that lowered the pH below 4 or raised it above 5. Furthermore, its effects were inhibited by treatment with proteolytic enzymes.
fLEX: Flexioa eta LEXikoa aztertzeko test eleanitza (5-10 urteko hamar haur euskaldunen emaitzen azterketa).
Authors: Pourquié Marie
Published: April 2019

Artikulu honen helburua da fLEX aplikazio eleanitzaren motibazioa, egitura, eta funtzionamendua aurkeztea eta, horretan oinarrituta, hamar haur euskaldunengandik bildutako datuak aztertzea. Ahozko bost probak eta orotara 160 estimuluk osatzen dute fLEX, prozesaketa lexikala zein flexionala, ekoizpena eta ulermenean aztertzeko: gauzak eta ekintzak izendatzea; esaldiak ekoiztea eta ulertzea; kasu eta posposizio sintagmak ekoiztea. Aurreikusten zen proba hauek egiteko zailtasunik ez agertzea bost urtetik gorako haurrentzat. 5-10 urte tarteko hamar haur euskaldunek parte hartu dute ikerketan. Emaitzek erakusten dute esaldiak ekoiztea dela emaitza ahulenak dakartzan proba; «ditu» eta «die» aditz laguntzaileak ekoizteko emaitzak apalak direla forma horiek ulertzeko arazo handirik ez den arren; ergatiboa, destinatiboa eta lekuzko genitiboa ekoizteko, beste kasu eta posposizioak ekoizteko baino huts gehiago agertzen dira. Datuen kantitatezko eta kalitatezko deskribapena egiten da, prozesaketa flexionalean eta lexikalean puntu ahulak erakutsiz. Haurren garapen tipikoaren ahuleziak definitzea ezinbestekoa da hizkuntza-arazoak diagnostikatzeko garaian. Psikohizkuntzalaritzaren ikuspegitik corpus baliagarri bat eskaintzeaz gain, euskaraz hizkuntza aztertzeko tresnak garatzeko beharra azpimarratzen da.
Nőtt az egyetemi tanulmányaikat kezdő diákok tanulási potenciálja és problémamegoldó képessége: években mérhető különbségek a diákok között
Authors: Molnár Gyöngyvér
Published: April 2019

Az értékesnek számító tudás változásával, a gondolkodási és tanulási képességek szerepének felértékelődésével megjelent az igény olyan felsőoktatásban is könnyen alkalmazható tesztek, tesztrendszerek kidolgozására, amelyek túllépnek a hagyományos tudásszintmérő teszteken és szélesebb skálán jellemzik a diákok kognitív fejlődését. Miután a dinamikus problémamegoldó képesség jól jellemzi a diákok tanulási potenciálját és a frissen tanultak alkalmazási képességét, egy potenciális mérési területévé vált egy, a fenti igényeket kielégítő, a Szegedi Tudományegyetemen 2015 óta működtetett mérési rendszernek. A négy évet átfogó kutatási eredmények alapján megállapítható, hogy stabilan és megbízhatóan működtethető egy olyan értékelési rendszer, amely túllép a tudásszintmérő tesztek világán és azonnali visszacsatolás mellett alkalmas annak megállapítására, hogy a hallgatók milyen tanulási potenciállal és problémamegoldó képességgel kezdik meg egyetemi tanulmányaikat. A közel 7000 diák részvételével végzett mérés alapján megállapítható, hogy 2015 óta jelentős mértékben nőtt az egyetemre frissen felvett diákok tanulási potenciálja és problémamegoldó képessége. Mindemellett a diákok közötti különbség meglehetősen nagy, több éves fejlődésnek felel meg. Vannak olyan hallgatók, akik átlagos képességszintje egy általános iskolás diákénak felel meg. Az egyetemi bemeneti kompetenciamérés eredményei 2018-ban már negyedik alkalommal bizonyították, hogy az érettségi eredmények nem jelzik kellő biztonsággal az egyetemi tanulmányokra való alkalmasságot. A közép és emelt szintű vizsgák és a teszteredmények közötti összefüggés tantárgyanként és évenként is különböző erősségű. A különböző szinteken nyújtott teljesítmények nem hasonlíthatóak össze egymással és az érettségi által jellemzett tudásszint évenként változik.
Continuing Medical Education Questions: April 2019
Authors: Ho Edith Y.
Published: April 2019

To receive CME/MOC credit for this activity, please go to: http://acgjournalcme.gi.org/

Article Title: Diagnosis and Treatment of Rumination Syndrome: A Critical Review
Benchmark Nachhaltigkeit: Sustainability Zeroline
Authors: Dahm J. Daniel
Published: April 2019

Die »Sustainability Zeroline« ist die erste scharfe Benchmark für Nachhaltigkeit. Sie setzt einen klaren Impuls, Zukunftsfähigkeit konsequent neu, lebensdienlich, zu denken und ökonomisch zu realisieren. Aus der Analyse der ökologischen und sozioökonomischen Effekte einer lebensverzehrenden Wirtschaft folgt die Notwendigkeit zur Neukultivierung des Wechselspiels von Menschheit und Natur. Praktisch wirksam wird das Dilemma von Expansionsdenken und ökologischen Grenzen im Konflikt zwischen Privatgütern und Commons. Im weit gespannten Bogen lässt der Geograph J. Daniel Dahm aus dem planetaren Biogeosystem die Anthroposphäre aufsteigen. Bildhaft mit zahlreichen Beispielen, entfaltet sich aus dem Kosmos menschlicher Vorstellungen und Traditionen ein neuer Blick auf das Mensch-Natur-Verhältnis, und mündet in eine neue, normative Orientierung für unsere Zukunft und als Handlungsnorm für Politik und Ökonomie. Für alle, die sich ernsthaft mit Nachhaltigkeit befassen, ob als interessierte Bürger*innen, ob aus Politik und Wirtschaft oder als Journalist*innen, ist der Band eine Pflichtlektüre.
Inklusives Theater
Authors: Henneberger Susanne , Sihler Jürgen
Published: April 2019

Susanne Henneberger und Jürgen Sihler führen anhand der Entwicklung des gemeinnützigen Vereins WERKRAUM: Karlsruhe aus, wie sich über die Jahre immer stärker eine inklusive Orientierung der theaterpädagogischen Praxis herausbildete. Anhand konkreter Episoden aus der Probenarbeit lassen die Autorin und der Autor die unmittelbaren biographischen Auswirkungen sichtbar werden, die kulturell-künstlerische Praxis auf Menschen in besonderen Lebenslagen haben kann.
Ritual und Shared Intentionality in der musikalischen Praxis
Authors: Gerland Juliane
Published: April 2019

Juliane Gerland trifft als Ausgangspunkt ihres Beitrags die Feststellung, dass der Begriff Inklusion mit einer hohen normativen Aufladung versehen ist. Neben den notwendigen gesetzlichen, strukturellen und systematischen Veränderungen ist aber letztlich entscheidend, ob das individuelle Erleben von zwischenmenschlicher Interaktion als gelungen beziehungsweise gelingend betrachtet wird, um die Ziele des inklusiven Gedankens erreichen zu können. Der Beitrag legt den Fokus auf die Mikroebene des gesamtgesellschaftlichen Inklusionsprozesses. Es wird ein theoretischer Rahmen entwickelt, innerhalb dessen beschreibbar ist, wie sich Inklusion im künstlerischen Handeln vollziehen kann.
Inklusive kulturelle Bildungsangebote in Baden-Württemberg
Authors: Schult Johannes , Henning Ina
Published: April 2019

Johannes Schult und Ina Henning berichten Befunde einer detaillierten Erhebung zum Umfang und Inhalt von inklusiven kulturellen Bildungsangeboten an Schulen in Baden-Württemberg. Am häufigsten sind Aktivitäten im Bereich Musik vertreten, gefolgt von Bewegungsangeboten und künstlerischen Partizipationsmöglichkeiten. Die meisten Angebote finden sich an Gemeinschaftsschulen, einer Schulart, die als Ort des gemeinsamen Lernens für heterogene Lerngruppen und auch Inklusion konzipiert wurde. Allerdings fehlen an zehn Prozent der Schulen jegliche inklusiven kulturellen Bildungsangebote. Insgesamt zeigte sich in den Rückmeldungen, dass die kulturelle Bildungslandschaft vielfältig ist, nicht zuletzt dank engagierter Lehrkräfte und Helfer*innen, ohne die diese Angebote oft nicht (mehr) möglich sind.
Games and Bereavement
Authors: Harrer Sabine
Published: April 2019

How can videogames portray love and loss? Games and Bereavement answers this question by looking at five videogames and carrying out a participatory design study with grievers. Sabine Harrer highlights possible connections between grief and videogames, arguing that game design may help make difficult personal feelings tangible. After a brief literary review of grief concepts and videogame theory, the book deep-dives into examples of tragic inter-character relationships from videogame history. Building on these examples, the book presents a case study on pregnancy loss as a potential grief experience that can be validated through game design dialogue.
Genealogie der Selbstführung
Authors: Senne Stefan , Hesse Alexander
Published: April 2019

Ob Flexibilisierungsprozesse in der Wirtschaft oder Ökonomisierungsprozesse in Schule und Medizin - überall da, wo die Rufe nach Selbstbestimmung und Entscheidungsfreiheit, aber auch nach Eigenverantwortung das kritische Forschungsinteresse weckten, geriet in den letzten Jahren auch zunehmend das Thema »Selbstführung« in den Fokus. Eine entscheidende Frage blieb dabei jedoch bisher unbeantwortet: Woher kommt dieses Konzept überhaupt? Stefan Senne und Alexander Hesse schließen diese Lücke, indem sie dem Aufruf zur Selbstführung genealogisch nachgehen und mit einem gouvernementalitätstheoretisch informierten Blick nach konkreten historischen Formationen fragen. Als Quellen dienen hierbei Lebensratgeber zur Idealisierung am Subjekt aus verschiedenen Jahrzehnten. Diese historische Perspektive lässt drei verschiedene Regime für das 20. Jahrhundert erkennen und rückt die aktuelle Debatte in ein neues Licht.
Interdisziplinäre Teams in inklusiven Schulen
Authors: Labhart David
Published: April 2019

David Labhart analysiert in Form einer ethnografischen Studie Fallbesprechungen in multiprofessionell zusammengesetzten Gruppen in der inklusiven Schule. Dabei bedient er sich der Akteur-Netzwerk-Theorie und zeigt am Beispiel des Kantons Zürich, wie das »Interdisziplinäre Team« in der Praxis agiert: Welche Aufgaben werden bearbeitet, wie werden Probleme verortet und welches Wissen wird integriert?
Wykorzystanie duoetnografii jako innowacyjnego podejścia w rozwijaniu refleksji przyszłych nauczycieli języka obcego
Authors: Werbińska Dorota
Published: April 2019

Duo-ethnography is a research methodology, through which people of  difference reconceptualise their histories of a particular phenomenon in juxtaposition with one another. Although initiated by researchers, duo- ethnographies can also be used as an innovative pedagogic tool that develops deep reflection in teacher candidates. After discussing the efficacy of duo-ethnography, a onesemester-long duo-ethnographic study is escribed, which was conducted by the author with six preservice English teachers. In the study, the participants worked in pairs (duo) and reflected on their own understandings of language teaching and learning (stage one), themselves as learners and future language teachers on the basis of the data from stage one (stage two), their conversational partners as learners and teachers on the basis of the data from stage one (stage three) and, finally, on the value of the duo-ethnographic project in language teacher preparation courses from their own perspective (stage four). The presentation ends with the author’s remarks about the project as a learning tool that undoubtedly encourages students to reflect but, on the other hand, has limitations that have to be acknowledged if duo- ethnography is employed as a pedagogic instrument in the classroom context.