bluuebunny/crossref_metadata_2025 huggingface dataset:
Textural and sensory characteristics of sugar‐free biscuit formulated with quinoa flour, isomalt, and maltodextrin
Authors: Nadian Narges , Azizi Mohammad Hossain , Abbastabar Ahangar Hossein , Aarabi Aazam
Published: September 2021

A low‐calorie biscuit formulation containing quinoa flour (cultivars TTKK), isomalt, and maltodextrin was optimized using response surface methodology. Optimized samples were evaluated in terms of total phenolic compounds (TPC), sensory properties, and nutritional value while samples containing only wheat flour (Pishgam var.) and sucrose were used as control. Morphology of isolated starch from quinoa was also investigated. The results showed that with increasing amounts of quinoa, isomalt, and maltodextrin ΔE and Browning index increased, whereas hardness and L values decreased. The formulation containing 25% quinoa flour, 3.5% maltodextrin, and 10% isomalt was found to be optimal with an overall desirability value of 0.95. The sensory evaluation showed that replacement of wheat flour with 25 g/100 g quinoa flour in biscuits was acceptable. TPC of the optimal biscuit (1,180.34 ± 0.02 μg GAE/g) was higher than that of the control sample (729.95 ± 0.007 μg GAE/g). In addition, the optimized biscuit had more protein (8.36 ± 0.035%) and dietary fiber (2.14 ± 0.035%) content compared with the control sample (7.01 ± 0.007% and 1.66 ± 0.028%, respectively). The consumption of 100 g of optimized quinoa biscuits supplies the daily requirement of Fe, Mg, Ca, and Zn at 2.43%, 44.81%, 19.46% and 1.12%, respectively.
Aberrant DNA methylation patterns in microsatellite stable human colorectal cancers define a new marker panel for the CpG island methylator phenotype
Authors: Gebhard Claudia , Mulet‐Lazaro Roger , Glatz Dagmar , Schwarzfischer‐Pfeilschifter Lucia , Schirmacher Peter , Gaedcke Jochen , Weichert Wilko , Reuschel Edith , Dietmaier Wolfgang , Rehli Michael
Published: September 2021

A distinct group of colorectal carcinomas (CRCs) referred to as the “CpG island methylator phenotype” (CIMP) shows an extremely high incidence of de novo DNA methylation and may share common pathological, clinical or molecular features. However, there is limited consensus about which CpG islands (CGIs) define a CIMP, particularly in microsatellite stable (MSS) carcinomas. To study this phenotype in a systematic manner, we analyzed genome‐wide CGI DNA methylation profiles of 19 MSS CRC using methyl‐CpG immunoprecipitation (MCIp) and hybridization on 244K CGI oligonucleotide microarrays, determined KRAS and BRAF mutation status and compared disease‐related DNA methylation changes to chromosomal instability as detected by microarray‐based comparative genomic hybridization. Results were validated using mass spectrometry analysis of bisulfite‐converted DNA at a subset of 76 individual CGIs in 120 CRC and 43 matched normal tissue samples. Both genome‐wide profiling and CpG methylation fine mapping segregated a group of CRC showing pronounced and frequent de novo DNA methylation of a distinct group of CGIs that only partially overlapped with previously established classifiers. The CIMP group defined in our study revealed significant association with colon localization, either KRAS or BRAF mutation, and mostly minor chromosomal losses but no association with known histopathological features. Our data provide a basis for defining novel marker panels that may enable a more reliable classification of CIMP in all CRCs, independently of the MS status.
Comparative analysis of the potential of the secretomes of cardiac resident stromal cells and fibroblasts
Authors: Lino Jhonatan Basso , Robert Anny Waloski , Stimamiglio Marco Augusto , de Aguiar Alessandra Melo
Published: September 2021

The secretome of different cell types has been applied on in vitro and in vivo assays, indicating considerable therapeutic potential. However, the choice of the ideal cell type and culture conditions for obtaining the best set of soluble factors, as well as the assays to assess specific effects, remain subjects of vigorous debate. In this study, we used mass spectrometry to characterize the secretomes of ventricle derived‐cardiac resident stromal cells (vCRSC) and human dermal fibroblasts (HDFs) and evaluate them in an effort to understand the niche specificity of biological responses toward different cellular behaviors, such as cell proliferation, adhesion, migration, and differentiation. It was interesting to note that the HDF and vCRSC secretomes were both able to induce proliferation and cardiac differentiation of H9c2 cells, as well as to increase the adhesion activity of H9c2 cells and human umbilical vein endothelial cells. Analysis of the secretome composition showed that the vCRSCs derived from different donors secreted a similar set of proteins. Despite the differences, almost half of the proteins identified in conditioned medium were common to both HDF and vCRSC. Consequently, a high number of common biological processes were identified in the secretomes of the two cell types, which could help to explain the similar results observed in the in vitro assays. We show that soluble factors secreted by both HDF and vCRSC are able to promote proliferation and differentiation of cardiomyoblasts in vitro. Our study indicates the possible use of vCRSC or HDF secretomes in acellular therapies for regenerative medicine.
SHP2: The protein tyrosine phosphatase involved in chronic pulmonary inflammation and fibrosis
Authors: Chang Chun‐Jung , Lin Chiou‐Feng , Chen Bing‐Chang , Lin Pei‐Yun , Chen Chia‐Ling
Published: September 2021

Chronic respiratory diseases (CRDs), including pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), lung cancer, and asthma, are significant global health problems due to their prevalence and rising incidence. The roles of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) in controlling tyrosine phosphorylation of targeting proteins modulate multiple physiological cellular responses and contribute to the pathogenesis of CRDs. Src homology‐2 domain‐containing PTP2 (SHP2) plays a pivotal role in modulating downstream growth factor receptor signaling and cytoplasmic PTKs, including MAPK/ERK, PI3K/AKT, and JAK/STAT pathways, to regulate cell survival and proliferation. In addition, SHP2 mutation and activation are commonly implicated in tumorigenesis. However, little is known about SHP2 in chronic pulmonary inflammation and fibrosis. This review discusses the potential involvement of SHP2 deregulation in chronic pulmonary inflammation and fibrosis, as well as the therapeutic effects of targeting SHP2 in CRDs.
The inhibitory mechanisms of losartan and vitamin D on amiodarone‐induced lung inflammation in rats: Role of mitogen‐activated protein kinases/activator protein‐1
Authors: Al‐Hassan Sara , Attia Hala , Alomar Hatun , Arafa Maha , Ali Rehab A.
Published: September 2021

Amiodarone (AMD), an antiarrhythmic drug, is used cautiously due to its lung toxicity that is characterized by alveolar inflammation followed by fatal fibrosis. AMD induces lung inflammation via increasing the alveolar macrophages and disturbing the balance of T‐helper‐1 (Th1) and Th2 cells cytokines. In this study, the role of the mitogen‐activated protein kinases (MAPKs)/activator protein‐1 (AP‐1) pathway in AMD‐induced lung inflammation was evaluated. Also, the anti‐inflammatory and antifibrotic effects of losartan and/or vitamin D were investigated following 7, 14, and 28 days of AMD administration. AMD resulted in lung injury, inflammatory infiltration, and increased pulmonary levels of inflammatory cytokines starting from Week 1 of exposure. A significant increase in serum levels of interleukin‐4 along with a significant reduction of interferon‐gamma, in addition to strong expression of CD68, were reported after 14 and 28 days of AMD administration reflecting Th1/Th2 cytokines imbalance and the accumulation of alveolar macrophages, respectively. The phosphorylation of MAPKs (ERK1/2, JNK, p38) and AP‐1 was significantly enhanced starting from Week 1 of exposure. Marked expression of transforming growth factor beta‐1 and massive deposition of collagen were detected after 28 days reflecting late fibrosis. All these abnormalities were significantly mitigated by vitamin D and its combination with losartan. Losartan alone has less prominent anti‐inflammatory effects particularly after 28 days; however, it efficiently prevented late fibrosis. This study concludes that MAPKs/AP‐1 pathway is involved in AMD‐induced lung inflammation and that vitamin D and/or losartan could be used as a prophylactic agent to prevent AMD‐induced lung toxicity.
Magnetization‐prepared spoiled gradient‐echo snapshot imaging for efficient measurement of R2‐R1ρ in knee cartilage
Authors: Han Misung , Tibrewala Radhika , Bahroos Emma , Pedoia Valentina , Majumdar Sharmila
Published: September 2021

Purpose

To validate the potential of quantifying R2‐R1ρ using one pair of signals with T1ρ preparation and T2 preparation incorporated to magnetization‐prepared angle‐modulated partitioned k‐space spoiled gradient‐echo snapshots (MAPSS) acquisition and to find an optimal preparation time (Tprep) for in vivo knee MRI.

Methods

Bloch equation simulations were first performed to assess the accuracy of quantifying R2‐R1ρ using T1ρ‐ and T2‐prepared signals with an equivalent Tprep. For validation of this technique in comparison to the conventional approach that calculates R2‐R1ρ after estimating both T2 and T1ρ, phantom experiments and in vivo validation with five healthy subjects and five osteoarthritis patients were performed at a clinical 3T scanner.

Results

Bloch equation simulations demonstrated that the accuracy of this efficient R2‐R1ρ quantification method and the optimal Tprep can be affected by image signal‐to‐noise ratio (SNR) and tissue relaxation times, but quantification can be closest to the reference with an around 25 ms Tprep for knee cartilage. Phantom experiments demonstrated that the proposed method can depict R2‐R1ρ changes with agarose gel concentration. With in vivo data, significant correlation was observed between cartilage R2‐R1ρ measured from the conventional and the proposed methods, and a Tprep of 25.6 ms provided the most agreement by Bland‐Altman analysis. R2‐R1ρ was significantly lower in patients than in healthy subjects for most cartilage compartments.

Conclusion

As a potential biomarker to indicate cartilage degeneration, R2‐R1ρ can be efficiently measured using one pair of T1ρ‐prepared and T2‐prepared signals with an optimal Tprep considering cartilage relaxation times and image SNR.
Demonstration of fast multi‐slice quasi‐steady‐state chemical exchange saturation transfer (QUASS CEST) human brain imaging at 3T
Authors: Kim Hahnsung , Krishnamurthy Lisa C. , Sun Phillip Zhe
Published: September 2021

Purpose

To combine multi‐slice chemical exchange saturation transfer (CEST) imaging with quasi‐steady‐state (QUASS) processing and demonstrate the feasibility of fast QUASS CEST MRI at 3T.

Methods

Fast multi‐slice echo planar imaging (EPI) CEST imaging was developed with concatenated slice acquisition after single radiofrequency irradiation. The multi‐slice CEST signal evolution was described by the spin‐lock relaxation during saturation duration (Ts) and longitudinal relaxation during the relaxation delay time (Td) and post‐label delay (PLD), from which the QUASS CEST was generalized to fast multi‐slice acquisition. In addition, numerical simulations, phantom, and normal human subjects scans were performed to compare the conventional apparent and QUASS CEST measurements with different Ts, Td, and PLD.

Results

The numerical simulation showed that the apparent CEST effect strongly depends on Ts, Td, and PLD, while the QUASS CEST algorithm minimizes such dependences. In the L‐carnosine gel phantom, the proposed QUASS CEST effects (2.68 ± 0.12% [mean ± SD]) were higher than the apparent CEST effects (1.85 ± 0.26%, p < 5e‐4). In the human brain imaging, Bland‐Altman analysis bias of the proposed QUASS CEST effects was much smaller than the PLD‐corrected apparent CEST effects (0.03% vs. −0.54%), indicating the proposed fast multi‐slice CEST imaging is robust and accurate.

Conclusions

The QUASS processing enables fast multi‐slice CEST imaging with minimal loss in the measurement of the CEST effect.
Prozesstechnik: Ein potenzieller Polymerbaustein
Authors: Schmiedl Detlef , Kunkel Robin , Schmidt Volkmar M.
Published: September 2021

Vanillin ist nicht nur für die Lebensmittel‐ und Kosmetikindustrie interessant. Die aromatische Verbindung aus fossilen oder nachwachsenden Rohstoffen ist auch Intermediat in der Pharmaindustrie und in der Erforschung von Kunststoffsynthesen: Rohstoffquellen, Herstellungsprozesse und Synthesewege.
Materialien: Magnetische Marker
Authors: Müssig Stephan , Mandel Karl
Published: September 2021

Mit einem eingearbeiteten Pass aus klugem Rost lassen sich Gegenstände nachverfolgen. Er ist klein und lässt sich nicht nur außen an einem Produkt, sondern auch im Inneren anbringen.
Blickpunkt Anorganik: Fließender Übergang
Authors: Hanf Schirin
Published: September 2021

Phosphanliganden sind in ihren sterischen und elektronischen Eigenschaften vielfältig. Daher sind sie sowohl aus der homogenen als auch der heterogenen Katalyse nicht mehr wegzudenken, wo sie beispielsweise Nanopartikel modifizieren.
Cardiovascular status of breast cancer patients before and after receiving anthracycline chemotherapy regimen
Authors: Dong Zhaoying , Liu Zhaojun , Chen Siyu , Zhang Changhong , Xiao Jun , Zhou Xiaoli
Published: September 2021

Aim

To explore the effect of TEC chemotherapy regimen (Docetaxel + Epirubicin + Cyclophosphamide) on traditional cardiovascular risk factors, atherosclerotic cardiovascular disease and cardiac electrical activity.

Design

243 patients with first initially diagnosed breast cancer were collected who receiving TEC chemotherapy.

Methods

Univariate analysis, multivariate analysis, binary logistic regression analysis and statistical description were used to analyse the data.

Results

Among the first diagnosed patients, prevalence of hypertension and overweight/obesity in postmenopausal patients were significantly higher than premenopausal group. Compared with initially diagnosed state, incidence of hyperlipidaemia increased significantly after TEC chemotherapy, blood glucose level was remarkably increased, and prevalence of hyperuricaemia was significantly increased, changes of blood pressure level and prevalence rate of hypertension were not significant, and there was no statistical difference. Different menopause status showed the same trend. Atherosclerotic cardiovascular disease risk stratification showed after chemotherapy low‐risk patients decrease, medium‐risk and high‐risk people increased. Grouped by menstrual status, after chemotherapy, both groups showed the same trend. The independent influencing factors of increased heart rate after chemotherapy were postmenopausal status. Postmenopausal patients had more cardiovascular risk factors than premenopausal patients. After receiving chemotherapy, levels of cardiovascular risk factors in both groups mostly changed to the direction of disease. Chemotherapy drugs increase the risk of atherosclerotic cardiovascular disease in breast cancer patients. It is necessary to strengthen interdisciplinary cooperation to dynamic assess the cardiovascular health of patients of breast cancer patients.
Targeted liquid chromatography‐tandem mass spectrometry analysis of proteins: Basic principles, applications, and perspectives
Authors: Kulyyassov Arman , Fresnais Margaux , Longuespée Rémi
Published: September 2021

Liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS) is now the main analytical method for the identification and quantification of peptides and proteins in biological samples. In modern research, identification of biomarkers and their quantitative comparison between samples are becoming increasingly important for discovery, validation, and monitoring. Such data can be obtained following specific signals after fragmentation of peptides using multiple reaction monitoring (MRM) and parallel reaction monitoring (PRM) methods, with high specificity, accuracy, and reproducibility. In addition, these methods allow measurement of the amount of post‐translationally modified forms and isoforms of proteins. This review article describes the basic principles of MRM assays, guidelines for sample preparation, recent advanced MRM‐based strategies, applications and illustrative perspectives of MRM/PRM methods in clinical research and molecular biology.
Dynamical propagation and growth mechanisms for convectively coupled equatorial Kelvin waves over the Indian Ocean
Authors: Matthews Adrian J.
Published: September 2021

Convectively coupled equatorial Kelvin waves (CCKWs) are high‐impact tropical weather systems that can lead to severe flooding over the Maritime Continent. Here, a vorticity budget for CCKWs over the Indian Ocean is constructed using reanalysis data, to identify the basic mechanisms of eastward propagation and growth. The budget is reasonably well closed, with a small residual/subgrid‐scale term. In the lower troposphere, CCKWs behave like strongly modified theoretical equatorial Kelvin waves. Vortex stretching, from the divergence of the Kelvin wave acting on planetary vorticity (the term), is the sole mechanism by which the vorticity structure of a theoretical Kelvin wave propagates eastward. In the lower and middle troposphere, this term is also the key mechanism for the eastward propagation of CCKWs but, due to subtleties in its structure and phasing linked to a combination of modal structures, it also contributes to growth. Unlike in the theoretical Kelvin wave, other vorticity source terms also play a role in the propagation and growth of CCKWs. In particular, vortex stretching from relative vorticity (the term) is the largest source term, and this leads strongly to growth, through interactions between the background and perturbation vorticity and divergence. Horizontal vorticity advection by the background flow contributes to propagation, and also acts to retard the growth of the CCKW. The sum of the source terms in this complex vorticity budget leads to eastward propagation and growth of CCKWs. The structure and vorticity budget of CCKWs in the upper troposphere is quite unlike that of a Kelvin wave, and appears to arise as a forced response to the lower‐tropospheric structure. The implications for numerical weather prediction and climate simulations are discussed.
Command filtered fixed‐time control for a class of multi‐agent systems with sensor faults
Authors: Dong Guowei , Li Xiao‐Meng , Yao Deyin , Li Hongyi , Lu Renquan
Published: September 2021

In this article, the command filtered fixed‐time fault‐tolerant control (FTC) problem is investigated for multi‐agent systems (MASs). The considered MASs with nonstrict feedback form are affected by unknown nonlinear functions and sensor faults, which are solved by using the properties of neural networks (NNs). In the design process, in order to avoid the “singularity” and “explosion of complexity” problems, an adaptive command filtered fixed‐time NN fault‐tolerant controller is devised. Based on the Lyapunov stability theory, all output signals of leader and followers in the closed‐loop system are synchronized within fixed time. Finally, the effectiveness of the proposed control scheme is verified by simulation experiments.
Engineering the synergistic effect of carbon dots‐stabilized atomic and subnanometric ruthenium as highly efficient electrocatalysts for robust hydrogen evolution
Authors: Liu Yuan , Chen Ning , Li Weidong , Sun Mingzi , Wu Tong , Huang Bolong , Yong Xue , Zhang Qinghua , Gu Lin , Song Haoqiang , Bauer Robert , Tse John S. , Zang Shuang‐Quan , Yang Bai , Lu Siyu
Published: September 2021

Currently, the most efficient electrocatalyst for the hydrogen evolution reaction (HER) in water dissociation is Pt‐based catalyst. Unfortunately, the high cost and less than perfect efficiency hinder wide‐range industrial/technological applications. Here, by controlling the treatment temperature of tris (2,2‐bipyridine) ruthenium dichloride hexahydrate, synthesis of compounds with novel ruthenium single/dual atoms (Ru S/DAs) mixed with Ru nanoclusters (Ru S/DAs + Ru NCs) and supported by carbon dots is demonstrated. These compounds are shown to be highly efficient and competitive catalysts for hydrogen evolution. Ru S/DAs + Ru NCs exhibit very high activity, with overpotentials of 15 and 40 mV at a current density of 10 mA/cm2 in 1.0 mol/L KOH and 0.5 mol/L H2SO4, respectively. Furthermore, the composites are found to possess outstanding stability and rapid HER kinetics. X ray absorption fine structure analysis, supported by density functional theory calculations, shows charge rearrangement in single‐atomic Ru, and the Ru dual sites promote active hydrogen adsorption and recombination. Ru S/DAs and Ru NCs demonstrate high electroactivity due to the electroactive Ru 4d orbitals. The introduction of Ru NCs activates the carbon support, providing a high electronic conductivity to transfer electrons from Ru NCs to Ru S/DAs, and facilitates water dissociation for the HER process.
Building Criteria for Energy Labeling of Photovoltaic Modules and Small Systems
Authors: Polverini Davide , Amillo Ana Gracia , Taylor Nigel , Sample Tony , Salis Elena , Dunlop Ewan D.
Published: September 2021

As part of the Ecodesign framework, the European Union's energy‐labeling scheme has proved to be a powerful tool to communicate with consumers regarding the energy use of products. With sales of photovoltaic (PV) modules and small systems set to expand rapidly for the European Union to meet its commitments on CO2 reduction, ensuring that newly installed PV products in the European Union are environmentally friendly and do not create future burdens on the environment is of primary importance. Herein, an innovative methodology in support of a potential energy‐labeling scheme for both PV modules and PV systems (installations) is proposed. The estimated annual and lifetime yields for a PV module and system respectively are used as parameters for classification from A (best) to G (worst) in the proposed scheme. How to “translate” the methodology into a practical energy‐labeling scheme, i.e., for use in EU policy implementing measures, is also discussed. The conceptual challenges of proposing an energy label for energy‐generating products, i.e., PV modules and systems, are also discussed.
Cysteamine administration in lambs grazing on mountain pastures: Effects on the body weight, antioxidant capacity, thyroid hormones and growth hormone secretion
Authors: Shokrollahi Borhan , Fazli Abdullah , Morammazi Salim , Saadati Nazila , Ahmad Hafiz Ishfaq , Hassan Faiz‐ul
Published: September 2021

This study aimed to evaluate the effects of intravenous injection of cysteamine (CS) on body weight (BW), growth hormone (GH), thyroid hormones (TH) secretion, and antioxidant status of growing lambs grazing on mountain pastures. Fifteen lambs (3–4 months of age) were randomly allocated into three experimental groups which received different dosages of CS: 0, 20, and 50 mg/kg BW−1. The CS was injected on the 1st, 10th, and 20th days of the experiment to the lambs through the jugular vein. Assessment of plasma concentration of GH and TH hormones was carried out at days 0 (a day before the start of CS injections), 15, and 30 of the experiment. The antioxidant enzymes were measured at the end of the experiment. Lambs were weighed at days 0, 10, 20, and 30 of the experiment. The results showed that treatment and time affected the BW, GH, triiodothyronine (T3), and tetraiodothyronine (T4) secretion. The intravenous injection of CS increased the BW of growing lambs (p < 0.01) and increased the plasma concentration of GH, T3, and T4 (p < 0.01). The treatment also enhanced glutathione peroxidase (GSH‐Px; p < 0.05) and reduced malondialdehyde concentrations (MDA; p < 0.01). Total antioxidant capacity (T‐AOC) level reduced in CS‐1 treatment compared to GC and CS‐2 treatments (p < 0.01). The levels of superoxide dismutase (SOD) and catalase (CAT) were not affected by CS. In conclusion, intravenous injection of CS improved BW, GH, and TH concentrations and antioxidant capacity in growing lambs grazing on mountain pastures.
A New Approach to School Development
Authors: Ylimaki Rose M. , Brunderman Lynnette A.
Published: September 2021

In this chapter, we further explore and contextualize school development amidst the tensions between contemporary policies and the educational needs of students. We conceptualize school development as a process that mediates among tensions that result in a Zone of Uncertainty. We then describe our application of school development in the Arizona Initiative for Leadership Development and Research (AZiLDR). Content was initially drawn from findings from the International Successful School Principalship Project (ISSPP) exploring leadership in high-needs, culturally diverse schools and related leadership studies. Our approach differs from other school development models in at least four ways. First, the approach is grounded in education theory as explicated by John Dewey and others. Closely related, our approach attempts to balance evidence-based values with humanistic values. Third, our approach is grounded in our empirical research and related studies of leadership in culturally diverse schools and communities. Fourth, our approach is process oriented and contextually sensitive for schools as they are situated in the larger community and serving culturally diverse populations. Finally, we develop leadership through a collaborative approach in that we work with school teams as a unit.
Strength-Based Approaches to Meeting Culturally Diverse Student Needs
Authors: Ylimaki Rose M. , Brunderman Lynnette A.
Published: September 2021

A strengths-based approach to education is essential for successful school development in culturally diverse schools. Chapter 7 reflects that education lies in the pedagogical relations and provocations into the self-realizations and growth of young people. In this arena, provocation refers to intentions to provoke thoughts, ideas, and actions that help students to learn and grow. A provocation should be grounded in the child’s cultural background strengths. We explicitly worked with school teams to recognize the equal value of different cultures in their students’ ethnic and linguistic backgrounds and to lead in culturally responsive ways with regards to pedagogy, curriculum, data-analysis, education and community engagement. We drew on research to include positive perspectives of parents and families, communication of high expectations, learning within the context of culture, student-centered and culturally mediated instruction, reshaping the curriculum, and teacher as facilitator. Thus, culturally relevant teaching requires teachers to embrace diversity, build on strengths, and recognize that students learn in a variety of ways. It is the job of the leader to help teachers gain an understanding of those cultures, and how to incorporate that into their classrooms. Sample activities and case studies expand the concepts.
The Swedish Context Bringing Support Structures to Scale: The Role of the State and School Districts
Authors: Johansson Olof , Ärlestig Helene
Published: September 2021

This chapter explores the “theory of action” underlying the Swedish government’s national school improvement program called Cooperation for Better Schools. We discuss particularly the assumptions about the roles and responsibilities of key stakeholders, including schools, school districts, and universities. Our analysis focuses on the issue of institutional capacity for sustained system improvement. In this regard, our approach draws on the perspectives associated with contemporary policy analysis, which includes greater attention to qualitative and interpretive methods to understand the complexity of policy-induced change in contemporary society. We start by describing the project structure and our method. Thereafter, we analyze the government’s understanding and arguments for why it is important to help underperforming schools, before we give examples about how involved actors define problems and solutions in project documents. In the conclusion, we highlight strengths and deficits in the improvement process.
Isomorphism, ‘Cultural Spheres’, and Education Systems: A Brief Summary and Concluding Remarks
Authors: Windzio Michael , Martens Kerstin
Published: September 2021

In Chap.11, Michael Windzio and Kerstin Martens evaluate the theoretical framework presented in the introductory chapter in light of the empirical findings of the individual chapters. The chapter also points to avenues for further research as a result of this volume.
Holographic correlators with multi-particle states
Authors: Čeplak Nejc , Giusto Stefano , Hughes Marcel R. R. , Russo Rodolfo
Published: September 2021

Abstract

We derive the connected tree-level part of 4-point holographic correlators in AdS3 × S3 × $$ \mathcal{M} $$
M
(where $$ \mathcal{M} $$
M
is T4 or K3) involving two multi-trace and two single-trace operators. These connected correlators are obtained by studying a heavy-heavy-light-light correlation function in the formal limit where the heavy operators become light. These results provide a window into higher-point holographic correlators of single-particle operators. We find that the correlators involving multi-trace operators are compactly written in terms of Bloch-Wigner-Ramakrishnan functions — particular linear combinations of higher-order polylogarithm functions. Several consistency checks of the derived expressions are performed in various OPE channels. We also extract the anomalous dimensions and 3-point couplings of the non-BPS double-trace operators of lowest twist at order 1/c and find some positive anomalous dimensions at spin zero and two in the K3 case.
Association of interleukin 6 -174 G/C polymorphism with coronary artery disease and circulating IL-6 levels: a systematic review and meta-analysis
Authors: Rai Himanshu , Colleran Roisin , Cassese Salvatore , Joner Michael , Kastrati Adnan , Byrne Robert A.
Published: September 2021

Introduction

Circulating IL-6 levels and at least one polymorphic form of IL6 gene (IL6 -174 G/C, rs1800795) have been shown to be independently associated with coronary artery disease (CAD) by several investigators. Despite more than 12 published meta-analyses on this subject, association of -174 G/C with CAD, especially amongst distinct ancestral population groups remain unclear. We, therefore, conducted a systematic review and an updated meta-analysis to comprehensively ascertain the association of IL6 -174 G/C with CAD and circulating IL-6 levels.

Materials and methods

Relevant case–control/cohort studies investigating association of -174 G/C with CAD and circulating IL-6 levels were identified following a comprehensive online search. Association status for CAD was determined for the pooled sample, as well as separately for major ancestral subgroups. Association status for circulating IL-6 levels was assessed for the pooled sample, as well as separately for CAD cases and CAD free controls. Study-level odds ratios (OR) and 95% confidence intervals (CI) were pooled using random/fixed-effects model.

Results

Quantitative synthesis for the CAD endpoint was performed using 55 separate qualifying studies with a collective sample size of 51,213 (19,160 cases/32,053 controls). Pooled association of -174 G/C with CAD was found to be statistically significant through dominant (OR 1.15; 95% CI 1.05–1.25, p = 0.002) as well as allelic genetic model comparisons (OR 1.13, 95% CI 1.06–1.21, p = 0.0003). This effect was largely driven by Asian and Asian Indian ancestral subgroups, which also showed significant association with CAD in both genetic model comparisons (OR range 1.29–1.53, p value range ≤ 0.02). Other ancestral subgroups failed to show any meaningful association.

Circulating IL-6 levels were found to be significantly higher amongst the ‘C’ allele carriers in the pooled sample (Standard mean difference, SMD 0.11, 95% CI 0.01–0.22 pg/ml, p = 0.009) as well as in the CAD free control subgroup (SMD 0.10, 95% CI 0.02–0.17 pg/ml, p = 0.009), though not in the CAD case subgroup (SMD 0.17, 95% CI = − 0.02 to 0.37, p = 0.12).

Conclusions

The present systematic review and meta-analysis demonstrate an overall association between IL6 -174 G/C polymorphism and CAD, which seems to be mainly driven by Asian and Asian Indian ancestral subgroups. Upregulation of plasma IL-6 levels in the ‘C’ allele carriers seems to be at least partly responsible for this observed association. This warrants further investigations with large, structured case–control studies especially amongst Asian and Asian Indian ancestral groups.
Revidierte Diagnosekriterien für die Neurofibromatose Typ 1 (NF1) ermöglichen eine frühe präzise differenzialdiagnostische Abgrenzung zu anderen RASopathien und erleichtern die Diagnose
Authors: Kehrer-Sawatzki H. , Farschtschi S. , Mautner V.-F.
Published: September 2021

Hintergrund

Die Neurofibromatose Typ 1 (NF1) ist eines der häufigsten erblichen Tumorprädispositionssyndrome und zählt zu den RASopathien, einer Gruppe von Erkrankungen mit überlappender Symptomatik, die durch Störungen des RAS-vermittelten Signaltransduktionsweges entstehen. Die diagnostischen Kriterien für NF1 sind 1988 definiert worden. Neue klinische und genetische Erkenntnisse erforderten eine Revision dieser Kriterien. Besonders im frühen Kindesalter ermöglichen die NF1-Diagnosekriterien von 1988 häufig noch keine Diagnose der NF1 und keine differenzialdiagnostische Abgrenzung zu anderen RASopathien wie dem Legius-Syndrom.

Methoden

Es erfolgte eine selektive Literaturrecherche zu Genetik und Symptomatik der NF1. Die Autoren nahmen an einer Delphi-Methode zur Revision der NF1-Diagnosekriterien durch ein internationales Expertengremium teil. Es wurden hierbei auch erstmalig die Diagnosekriterien für das Legius-Syndrom sowie für Mosaikformen beider Erkrankungen erstellt.

Ergebnisse

Die NF1-Diagnosekriterien wurden überarbeitet; dabei wurden neue klinische Merkmale wie choroidale Anomalien aufgenommen, aber auch genetische Befunde wie der Nachweis pathogener NF1-Genvarianten.

Diskussion

Mit den revidierten NF1-Diagnosekriterien und den neu erstellten Diagnosekriterien für das Legius-Syndrom ist es nun möglich, auch bei Kindern die Diagnose einer NF1 mit hoher Sensitivität und Spezifität frühzeitig zu stellen. Diese Diagnosekriterien ermöglichen eine genaue differenzialdiagnostische Abgrenzung von anderen Erkrankungen mit phänotypischen Überlappungen zur NF1, was eine frühe Risikostratifizierung und somit eine zielgerichtete Behandlung und Betreuung der Patienten ermöglicht.
The importance of increasing population diversity in genetic studies of type 2 diabetes and related glycaemic traits
Authors: Barroso Inês
Published: September 2021

Type 2 diabetes has a global prevalence, with epidemiological data suggesting that some populations have a higher risk of developing this disease. However, to date, most genetic studies of type 2 diabetes and related glycaemic traits have been performed in individuals of European ancestry. The same is true for most other complex diseases, largely due to use of ‘convenience samples’. Rapid genotyping of large population cohorts and case–control studies from existing collections was performed when the genome-wide association study (GWAS) ‘revolution’ began, back in 2005. Although global representation has increased in the intervening 15 years, further expansion and inclusion of diverse populations in genetic and genomic studies is still needed. In this review, I discuss the progress made in incorporating multi-ancestry participants in genetic analyses of type 2 diabetes and related glycaemic traits, and associated opportunities and challenges. I also discuss how increased representation of global diversity in genetic and genomic studies is required to fulfil the promise of precision medicine for all.

Graphical abstract
Effectiveness of a polyphenolic extract (Lippia citriodora and Hibiscus sabdariffa) on appetite regulation in overweight and obese grade I population: an 8-week randomized, double-blind, cross-over, placebo-controlled trial
Authors: Serna Ana , Marhuenda Javier , Arcusa Raúl , Pérez-Piñero Silvia , Sánchez-Macarro Maravillas , García-Muñoz Ana María , Victoria-Montesinos Desirée , Cánovas Fernando , López-Román F. Javier
Published: September 2021

Introduction

Polyphenols have shown capacity to improve appetite sensation, leading to enhanced control of body weight. However, despite being related with hunger-related hormones, metabolic and mechanism are not well known.

Methods

The effectiveness of a nutraceutical composed of extract toLippia citriodoraandHibiscus sabdarrifa(Lc-Hs) for controlling satiety and hunger was analyzed in a cross-over, placebo-controlled (Pla) clinical intervention. The study was divided in two 60-day periods separated by 30-day length wash-out period. At the end of each period, overweight and obese subjects (n = 33; age = 33.76 ± 12.23; BMI = 28.20 kg/m2 ± 2.47; fat mass 30.65 ± 8.39%; both sexes were proposed to eat an ad-libitum meal. Meanwhile, appetite sensation was determined by visual analog scales at different times. Moreover, blood extraction was performed to determine biochemical parameters (lipid and glucidic profile and safety parameters) and to evaluate hunger-related hormones (insulin, leptin, ghrelin, adiponectin, GLP-1 and peptide YY).

Results

A decrease in appetite sensation was observed in Lc-Hs treatment, showing higher satiety quotient (Pla = 3.36 ± 2.33%mm/kcal; Lc-Hs = 5.53 ± 2.91%mm/kcal;p < 0.0001). Area under the curve was higher in Pla compared to Lc-Hs during the test, from baseline to minute 240 (240 (Pla 9136.65 ± 2261.46%xmin−1; Lc-Hs 8279.73 ± 2745.71%xmin−1;p < 0.014). Energy consumption was lower for subjects treated with Lc-Hs (774.44 ± 247.77 kcal) compared to those treated with Pla (849.52 ± 246.54 kcal) (p < 0.004). Leptin values varied from baseline (Pla 12.36 ± 1.98 ng/mL; Lc-Hs 13.13 ± 1.99 ng/mL) to the end of the study (Pla 12.60 ± 2.02 ng/mL; Lc-Hs 12.06 ± 2.05 ng/mL;p < 0.047). GLP-1 values varied (p < 0.001) in Lc-Hs treatment from baseline (4.34 ± 0.49 ng/mL) to the end of the study (3.23 ± 0.52 ng/mL).

Conclusion

The supplementation with the Lc-Hs extract decreases appetite sensation in overweight and obese population, reducing calorie intake after an ad-libitum meal. Due to variation on hunger-related hormones and the relationship between satiety feeling, it would be interesting to develop future research focused on the variation of the hormones themselves.
Joint optic disc and cup segmentation based on multi-scale feature analysis and attention pyramid architecture for glaucoma screening
Authors: Sun Guangmin , Zhang Zhongxiang , Zhang Junjie , Zhu Meilong , Zhu Xiao-rong , Yang Jin-Kui , Li Yu
Published: September 2021

Automatic segmentation of optic disc (OD) and optic cup (OC) is an essential task for analysing colour fundus images. In clinical practice, accurate OD and OC segmentation assist ophthalmologists in diagnosing glaucoma. In this paper, we propose a unified convolutional neural network, named ResFPN-Net, which learns the boundary feature and the inner relation between OD and OC for automatic segmentation. The proposed ResFPN-Net is mainly composed of multi-scale feature extractor, multi-scale segmentation transition and attention pyramid architecture. The multi-scale feature extractor achieved the feature encoding of fundus images and captured the boundary representations. The multi-scale segmentation transition is employed to retain the features of different scales. Moreover, an attention pyramid architecture is proposed to learn rich representations and the mutual connection in the OD and OC. To verify the effectiveness of the proposed method, we conducted extensive experiments on two public datasets. On the Drishti-GS database, we achieved a Dice coefficient of 97.59%, 89.87%, the accuracy of 99.21%, 98.77%, and the Averaged Hausdorff distance of 0.099, 0.882 on the OD and OC segmentation, respectively. We achieved a Dice coefficient of 96.41%, 83.91%, the accuracy of 99.30%, 99.24%, and the Averaged Hausdorff distance of 0.166, 1.210 on the RIM-ONE database for OD and OC segmentation, respectively. Comprehensive results show that the proposed method outperforms other competitive OD and OC segmentation methods and appears more adaptable in cross-dataset scenarios. The introduced multi-scale loss function achieved significantly lower training loss and higher accuracy compared with other loss functions. Furthermore, the proposed method is further validated in OC to OD ratio calculation task and achieved the best MAE of 0.0499 and 0.0630 on the Drishti-GS and RIM-ONE datasets, respectively. Finally, we evaluated the effectiveness of the glaucoma screening on Drishti-GS and RIM-ONE datasets, achieving the AUC of 0.8947 and 0.7964. These results proved that the proposed ResFPN-Net is effective in analysing fundus images for glaucoma screening and can be applied in other relative biomedical image segmentation applications.
Second-line pembrolizumab versus chemotherapy in Japanese patients with advanced esophageal cancer: subgroup analysis from KEYNOTE-181
Authors: Muro Kei , Kojima Takashi , Moriwaki Toshikazu , Kato Ken , Nagashima Fumio , Kawakami Hisato , Ishihara Ryu , Ogata Takashi , Satoh Taroh , Iwakami Keiichi , Han Shirong , Yatsuzuka Naoyoshi , Takami Tomoko , Bhagia Pooja , Doi Toshihiko
Published: September 2021

Background

Safe and effective treatments for advanced esophageal cancer are an unmet need in Japan. We report results of a subgroup analysis of Japanese patients enrolled in KEYNOTE-181, a randomized, open-label, phase 3 study of pembrolizumab versus chemotherapy as second-line therapy for patients with advanced or metastatic esophageal cancer whose disease progressed after standard first-line therapy.

Methods

Patients were randomly assigned 1:1 to receive pembrolizumab 200 mg every 3 weeks or investigator’s choice of paclitaxel, docetaxel, or irinotecan. Efficacy was evaluated in all Japanese patients and in those with programmed death ligand 1 combined positive score ≥ 10.

Results

Of the 152 Japanese patients enrolled (pembrolizumab, n = 77; chemotherapy, n = 75), 150 (98.7%) had squamous cell carcinoma and 79 (52.0%) had combined positive score ≥ 10. At the final analysis, median overall survival was improved among all patients (12.4 vs 8.2 months with pembrolizumab and chemotherapy, respectively; hazard ratio, 0.68; 95% CI 0.48–0.97) and patients with combined positive score ≥ 10 (12.6 vs 8.4 months; hazard ratio, 0.68; 95% CI 0.42–1.10). Fewer patients had any-grade (74.0% vs 95.9%) or grade 3–5 (16.9 vs 50.0%) treatment-related adverse events with pembrolizumab than with chemotherapy.

Conclusion

Consistent with the global trial results, second-line pembrolizumab therapy showed a survival benefit and a favorable safety profile compared with chemotherapy in Japanese patients with advanced esophageal cancer.
Sacred natural sites and biodiversity conservation: a systematic review
Authors: Zannini Piero , Frascaroli Fabrizio , Nascimbene Juri , Persico Angela , Halley John Maxwell , Stara Kalliopi , Midolo Gabriele , Chiarucci Alessandro
Published: September 2021

Sacred natural sites (SNS) have gained recognition from conservationists, and are regarded as the oldest form of habitat protection in human history. Many case studies and literature reviews have been published on the subject. However, an updated and global-level synthesis on the effect of SNS on biodiversity conservation is still lacking. Here, we provide the first systematic review on SNS and biodiversity conservation, aiming to evaluate the effect of SNS across different: (i) continents; (ii) taxa; (iii) metrics. We checked 2750 papers and by applying inclusion criteria we selected 27 relevant papers. From these, we extracted descriptive data and 131 comparisons between SNS and Reference Sites. We applied vote-counting, multinomial and binomial post-hoc tests to the 131 comparisons. We found strong evidence that SNS have a positive effect on biodiversity, but also strong geographical and taxonomical biases, with most research focusing on Asia and Africa and on plants. We found that SNS have mainly positive effects on taxonomical diversity, vegetation structure and cultural uses of biodiversity. Our results strongly support the view that SNS have positive effects on biodiversity across continents and geographical settings, as found in a number of local studies and earlier overviews. These effects should be given official recognition in appropriate conservation frameworks, together with the specific forms of governance and management that characterize SNS. At the same time, further efforts are also required to fill the geographical and taxonomical gaps here highlighted, and to advancing our knowledge of SNS through more systematic research.
Role of non-coding RNAs in tumor progression and metastasis in pancreatic cancer
Authors: Sempere Lorenzo F. , Powell Katherine , Rana Jatin , Brock Andrew A. , Schmittgen Thomas D.
Published: September 2021

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer with an overall 5-year survival rate of less than 10%. The 1-year survival rate of patients with locally advanced or metastatic disease is abysmal. The aggressive nature of cancer cells, hypovascularization, extensive desmoplastic stroma, and immunosuppressive tumor microenvironment (TME) endows PDAC tumors with multiple mechanisms of drug resistance. With no obvious genetic mutation(s) driving tumor progression or metastatic transition, the challenges for understanding the biological mechanism(s) of these processes are paramount. A better understanding of the molecular and cellular mechanisms of these processes could lead to new diagnostic tools for patient management and new targets for therapeutic intervention. microRNAs (miRNAs) are an evolutionarily conserved gene class of short non-coding regulatory RNAs. miRNAs are an extensive regulatory layer that controls gene expression at the posttranscriptional level. This review focuses on preclinical models that functionally dissect miRNA activity in tumor progression or metastatic processes in PDAC. Collectively, these studies suggest an influence of miRNAs and RNA-RNA networks in the processes of epithelial to mesenchymal cell transition and cancer cell stemness. At a cell-type level, some miRNAs mainly influence cancer cell–intrinsic processes and pathways, whereas other miRNAs predominantly act in distinct cellular compartments of the TME to regulate fibroblast and immune cell functions and/or influence other cell types’ function via cell-to-cell communications by transfer of extracellular vesicles. At a molecular level, the influence of miRNA-mediated regulation often converges in core signaling pathways, including TGF-β, JAK/STAT, PI3K/AKT, and NF-κB.