bluuebunny/crossref_metadata_2025 huggingface dataset:
The Regulation of the Concentrations of Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha and Sirtuin 1 Protein in the Soleus Muscle by Aerobic Exercise Training in Obese Wistar Rats
Authors: Hejazi Keyvan , Attarzadeh Hosseini Seyyed Reza , Fathi Mehrdad , Mosaferi Ziaaldini Mohammad
Published: November 2020

Background: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) and Sirtuin 1 (SIRT1) are significant indicators of obesity and other metabolic disorders. Objectives: The present study aimed to investigate the regulation of the concentrations of PGC-1a and SIRT1 protein in the soleus muscle by aerobic exercise training in obese Wistar rats. Methods: This study was conducted on 24 obese male rats, which were randomly categorized into three groups of control, medium-intensity training (28 m/min), and high-intensity training (34 m/min) after obesity induction through a high-fat diet. A series of aerobic trainings in five sessions of 60-minute aerobic training per week was performed for eight weeks. Data analysis was performed using one-way ANOVA to examine the mean differences between the groups. In addition, Tukey’s post-hoc test was used for the paired comparisons of the groups. Results: Significant differences were observed in the concentrations of the PGC-1a (P < 0.001) and SIRT1 proteins between the study groups (P < 0.001). Tukey’s post-hoc test revealed a significant difference between the moderate-intensity aerobic exercise and control groups (P < 0.01) regarding their mean concentration of the PGC-1a protein. However, the high- and moderate-intensity groups showed no difference in this regard (P < 0.028). Moreover, there was a significant difference in the concentration of the SIRT1 protein between the moderate-intensity aerobic exercise and control groups (P < 0.02), and the high-intensity training and control groups (P < 0.005). Conclusions: According to the results, aerobic exercise training could activate SIRT1 and PGC-1a and might enhance mitochondrial biogenesis in the subcutaneous fat. Therefore, aerobic training is recommended as a therapeutic approach to obesity and several other metabolic diseases.
Comparing the Effectiveness of Flipped and Traditional Teaching Methods in Problem-solving Learning and Self-determination Among University Students
Authors: Khayat Mahnaz , Hafezi Fariba , Asgari Parviz , Talebzadeh Shoushtari Marzieh
Published: November 2020

Background: The flipped classroom model provides an ideal ground to convert a traditional classroom into an interactive environment based on problem-solving learning with a focus on university students’ self-determination. Objectives: The present study aimed to investigate the effectiveness of flipped and traditional teaching methods in problem-solving learning and self-determination among university students. Methods: The research method was experimental with a pretest-posttest design and a control group. The statistical population included all female students of Farhangian University in Ahvaz city in the academic year 2019. Using a purposive sampling method, 36 students were selected and randomly divided into experimental and control groups (n = 18 per group). The research instrument included the Problem-Solving Inventory (PSI) and the Basic Psychological Need Satisfaction scale. The experimental group received the flipped teaching program during eight 120-min sessions once a week; however, the control group received the traditional teaching method. multivariate analysis of covariance (MANCOVA), univariate analysis of covariance (ANCOVA), and Bonferroni post hoc tests were used to analyze the data. Results: The posttest scores (mean ± SD) of problem-solving learning and self-determination were 83.77 ± 14.17 and 119.33 ± 13.79, respectively, in the experimental group, which were significantly different from the scores of the control group. The flipped classroom promoted problem-solving learning and components of self-determination among university students in the experimental group when compared to the control group (P = 0.01). The flipped teaching method was more effective than the traditional method in increasing problem-solving learning and self-determination among university students. Conclusions: According to the findings, the flipped teaching method had greater impacts on students’ problem-solving and self-determination than had the traditional method.
Apperception and Pre-Reflective Self-Consciousness in Kant
Authors: Forgione Luca ,   Philosophy Documentation Center
Published: November 2020

Kant points to two forms of self-consciousness: the inner sense (empirical apperception) grounded in a sensory form of self-awareness and transcendental apperception. The aim of this paper is to show that a sophisticated notion of basic self-consciousness, which contains a pre-reflective self-consciousness as its first level, is provided by the notion of transcendental apperception. The necessity for a pre-reflective self-consciousness has been pointed out in phenomenological literature. According to this account, every self-ascription of any property implies a more fundamental form of self-consciousness, i.e., a kind of immediate familiarity with oneself. This pre-reflective self-consciousness is a non-relational and non-identificational form of self-consciousness and concerns an immediate acquaintance of the subject with itself. In the specific terms of transcendentalism every thought contains an implicit reference to a first-personal “givenness” or a sense of “mineness” that articulates a non-relational and non-identificational form of a pre-reflective model of self-consciousness.
The Right Stuff
Authors: Barker Michael ,   Philosophy Documentation Center
Published: November 2020

I consider Kant’s theory of matter, examine his distinction between “formal” and “material” purposiveness, review the related secondary literature, and interpret the role of the stuff of which organs consist in his conception of the special characteristics of organisms. As organisms ingest or absorb compounds, they induce chemical changes among those materials to grow and repair organs. Those organs have their functions with respect to each other in part on account of the materials of which they are composed. A Kantian biological law, I argue, is a coordinated system of lower-order chemical and mechanical regularities that an organism instantiates in the relations that its organs have to each other. I interpret Kant’s contention that organisms resist cognition as claiming that a “discursive understanding” can have no conception of why a particular biological law instantiates whichever lower-order mechanical and chemical regularities it does.
Selected Presentations from the Network of Early Career Researchers in Old Norse (2017-2019)
Authors: Kapitan Katarzyna Anna , Leslie-Jacobsen Helen F. , Murphy Luke John , Nygaard Simon , Rogers Beth
Published: November 2020

This is a selection of posters and presentations as well as introductions to the Network of Early Career Researchers in Old Norse and the meetings in Copenhagen in 2017 and Bergen in 2019.
Patient Characteristics Related to Phlebitis in the East Coast of Peninsular Malaysia Hospital
Authors: Daud Azlina , Mohamad Fatimah
Published: November 2020

The insertion of peripheral intravenous catheters (PIVCs) is common for treatment among hospitalized patients. However, this procedure usually fails before the end of therapy because of several complications, including phlebitis. Therefore, this study aimed to determine the incidence and associated factors of phlebitis among patients with PIVC. A prospective cohort study was conducted in one of the hospitals located in East Coast Malaysia. The presence of phlebitis was assessed using the visual infusion phlebitis score checklist. The patients were followed until PIVC removal. A total of 321 data were collected among patients who received a new PIVC in the medical, gynecology, and orthopedic wards. The incidence of phlebitis was 36.1% (n = 116), and 96.6% of which were grade II. Patients aged 60 years (51.5%), men (42.2%), no known phlebitis history (47.4%), and with chronic disease record (46.8%) were determined as the highest percentage with phlebitis. This study demonstrated that age, gender, and chronic diseases were risk factors of developing phlebitis.  Abstrak Karakteristik Pasien yang Berhubungan dengan Flebitis di Rumah Sakit Pantai Timur Semenanjung Malayía. Di antara pasien yang dirawat di rumah sakit, penyisipan kateter intravena perifer (PIVC) umum untuk pengobatan. Namun, prosedur ini seringkali gagal sebelum terapi selesai karena beberapa komplikasi. Salah satu komplikasi yang terjadi adalah flebitis. Oleh karena itu, penelitian ini bertujuan untuk menentukan kejadian dan faktor-faktor terkait flebitis di antara pasien dengan PIVC. Sebuah studi kohort prospektif dilakukan di salah satu rumah sakit yang berlokasi di Pantai Timur Malaysia. Kejadian flebitis dinilai menggunakan daftar periksa skor Visual Infusion Phlebitis (VIP). Para pasien ditindaklanjuti sampai pengangkatan PIVC. Terdapat 321 data yang dikumpulkan di antara pasien yang menerima PIVC baru di bangsal medis, ginekologi, dan ortopedi. Insiden flebitis ditemukan 36,1% (n = 116), 96,6% di antaranya adalah grade II. Pasien berusia 60 tahun (51,5%), pria (42,2%), pasien tidak memiliki riwayat flebitis (47,4%) dan pasien dengan catatan penyakit kronis (46,8%) tercatat sebagai persentase tertinggi dengan flebitis. Studi ini menunjukkan bahwa usia, jenis kelamin, dan pasien dengan penyakit kronis kemungkinan besar mengalami flebitis.Kata Kunci: flebitis, kateter intravena peripheral, pasien dewasa.
Pensando un horizonte democrático, pluralista e intercultural para el reconocimiento de los pueblos indígenas en América Latina, desde una relectura crítica a Laclau y Mouffe
Authors: Faundes Peñafiel Juan Jorge
Published: November 2020

Desarrollamos la propuesta de un horizonte democrático, pluralista e intercultural que corresponde a una visión de la democracia sostenida en articulaciones democráticas, propias de un orden social nunca del todo alcanzable y presupuesto necesario del reconocimiento de la identidad cultural de los pueblos indígenas latinoamericanos, como sujetos constituyentes de los procesos de reconstitución de sus estados.Como punto de partida, revisamos el pluralismo agonístico de Laclau y Mouffe, releyéndolo crítica e interculturalmente, sosteniendo que el reconocimiento de la identidad cultural de los pueblos indígenas en América Latina supone la existencia de una relación dual y paradójica, entre conflicto y diálogo, que redefine el consenso racional comunicativo, desplaza la matriz liberal “igualdad-libertad” por una matriz “intercultural” que articula la diversidad como un nuevo imaginario democrático y marco institucional.
El procedimiento monitorio civil en la Reforma Procesal Civil: ¿puro o documental?
Authors: Delgado Castro Jordi
Published: November 2020

El presente trabajo trata acerca de la definición del modelo de procedimiento monitorio civil en Chile. El legislador ha terminado confundiendo el procedimiento monitorio puro y el documental y su establecimiento, lejos de resultar una opción baladí, ha de determinar un funcionamiento diferente en cada caso. Nuestros jueces civiles deben tener claridad, para evitar que se pierda el objetivo principal, cual es la obtención de un título ejecutivo en el menor tiempo posible.
Paz en la Araucanía: observaciones a su diagnóstico y propuesta
Authors: Painecura Medina Lincoyan
Published: November 2020

El presente artículo es un análisis teórico del diagnóstico y propuesta de Paz en la Araucanía, movimiento creado entre los agricultores y trasportistas que sufren violencia en el denominado conflicto mapuche, a causa de la tenencia legal de terrenos en conflicto. Los propietarios legales dicen no ser un actor del conflicto, pero sí víctimas de la dinámica inconclusa entre el Estado y las comunidades mapuche. Señalan que una minoría mapuche ejerce el terrorismo en la Región de la Araucanía y que el Estado no ha sido capaz de aplicar las respectivas sanciones. Sin embargo, éstos no identifican una causa histórica de esta situación en su relato, racializando la violencia en el conflicto y no asumiéndose como un tercer actor dentro de éste. Para demostrar lo anterior, este artículo problematiza sobre el concepto de paz en base a la discusión entre Johan Galtung y Kenneth E. Boulding, sistematiza el discurso de Paz en la Araucanía y lo estudia en relación a los conceptos teóricos mencionados en su discurso. Los resultados apuntan a que los propietarios ofrecen una propuesta minimalista de paz, enfocada en el concepto de paz negativa, sin buscar una solución definitiva al conflicto e invalidando la demanda mapuche.
Editorial
Authors: Olivares Alberto
Published: November 2020

Editorial
Munc13 binds and recruits SNAP25 to chaperone SNARE complex assembly
Authors: Kalyana Sundaram Ramalingam Venkat , Jin Huaizhou , Li Feng , Shu Tong , Coleman Jeff , Yang Jie , Pincet Frederic , Zhang Yongli , Rothman James E. , Krishnakumar Shyam S.
Published: November 2020

Synaptic vesicle fusion is mediated by SNARE proteins—VAMP2 on the vesicle and Syntaxin‐1/SNAP25 on the presynaptic membrane. Chaperones Munc18‐1 and Munc13‐1 cooperatively catalyze SNARE assembly via an intermediate ‘template’ complex containing Syntaxin‐1 and VAMP2. How SNAP25 enters this reaction remains a mystery. Here, we report that Munc13‐1 recruits SNAP25 to initiate the ternary SNARE complex assembly by direct binding, as judged by bulk FRET spectroscopy and single‐molecule optical tweezer studies. Detailed structure–function analyses show that the binding is mediated by the Munc13‐1 MUN domain and is specific for the SNAP25 ‘linker’ region that connects the two SNARE motifs. Consequently, freely diffusing SNAP25 molecules on phospholipid bilayers are concentrated and bound in ~ 1 : 1 stoichiometry by the self‐assembled Munc13‐1 nanoclusters.
LIMEs and LEMONs: Critically Examining the Effect of a Blog Post on Junior Faculty Learners
Authors: Messman Anne M. , Ehrman Robert R. , Gruppen Larry D.
Published: November 2020

Introduction

The usage of asynchronous resources such as blogs and podcasts is pervasive in academic medicine, despite little understanding of their actual effect on learner knowledge acquisition. This study sought to examine the objective effect of a blog post on knowledge acquisition and application among junior faculty in emergency medicine (EM) via randomized controlled study.

Methods

All accredited EM residency programs in the United States and Canada were contacted to identify assistant and associate program directors and medical education fellows for recruitment into this study. Upon enrollment, participants were randomized as to whether they received access to a supplemental blog post prior to listening to a podcast episode. After listening to the podcast episode, all participants completed an assessment that included a test of knowledge application and knowledge acquisition; demographic information was also obtained.

Results

Ultimately, 103 participants completed the study; the study closed for enrollment in July 2019. Data were nonnormally distributed and groups were compared using the Wilcoxon rank‐sum test. There were no significant differences between the demographics of the two groups nor was there a significant difference in knowledge between the two groups.

Conclusion

The addition of a supplementary blog post did not increase junior faculty knowledge of a podcast episode.
Sex‐specific risk profiles for substance use among college students
Authors: Martin Caitlin E. , Ksinan Albert J. , Moeller Frederick Gerard , Dick Danielle ,   Spit for Science Working Group
Published: November 2020

Introduction

Growing evidence indicates sex and gender differences exist in substance use. Framed by a lifecourse perspective, we explored prospectively by sex the effects of distal and proximal factors on the initiation of drug use in college.

Methods

College students without prior drug use (n = 5,120 females; n = 2,951 males) were followed longitudinally across 4 years. Analyses were estimated as a multigroup survival analysis separately by sex within a latent variable SEM framework with illicit drug use (6 or more times in past year) as the latent factor.

Results

More males initiated drug use (8.5%) than females (6.4%, χ2 (1) = 10.351, p = .001), but less so for Black males (AOR 0.33, 95% CI [0.18, 0.60]) and females (0.35 [0.23, 0.54]). Students initiating drug use more likely included students smoking cigarettes at baseline (males 1.40 [1.23, 1.59]; females 1.43 [1.24, 1.64]), using alcohol (males 1.04 [1.02, 1.06]; females 1.04 [1.02, 1.06]), or having cannabis using peers (males 1.79 [1.52, 2.11]; females 1.70 [1.49, 1.93]). Impulsivity domain associations differed by sex [negative urgency: females (1.23 [1.02, 1.49) and sensation seeking: males (1.33 [1.01, 1.75])]. History of unwanted/uncomfortable sexual experience predicted drug use for males (1.60 [1.09, 2.35]) and females (1.95 [1.45, 2.62]) but physical assault only for females (1.45 [1.08, 1.94]). Mood symptoms predicted drug use only for males [depression (0.73 [0.56, 0.95]); anxiety (1.40 [1.04, 1.89])].

Conclusions

Risk factors for initiating drug use during college differ by sex. As substance use during early age predisposes one for addiction, sex‐ and gender‐informed interventions for young adults are needed.
Microbiological survey of equipment and wheat‐milled fractions of a milling operation
Authors: Sabillón Luis , Stratton Jayne , Rose Devin , Bianchini Andréia
Published: November 2020

Background and objectives

As wheat is milled into flour, there is a substantial risk of cross‐contamination by microorganisms potentially inhabiting the milling equipment. The objectives of this study were designed (a) to assess the levels of microbial contamination associated with the milling equipment and the wheat as it is processed from grain to packaged flour, and (b) to identify equipment that could serve as a source of contamination during processing.

Findings

Equipment used to clean and temper wheat grain was found to harbor substantial populations of aerobic mesophilic bacteria, Enterobacteriaceae, and molds. Generic E. coli was found in 2 instances on cleaning equipment at an average of 0.4 log CFU/10 cm2. Coliform counts increased markedly in wheat kernels and milled fractions after passing through the different milling steps.

Conclusions

These data demonstrate that microorganisms, including fecal indicators, were common colonizers of milling equipment and that a consistent cross‐contamination risk existed throughout the processing line. Cleaning and sanitation efforts should focus especially on tempering equipment and prompt removal of buildup of grain/flour residues within the milling equipment.

Significance and novelty

This study identified critical control areas and equipment where cross‐contamination is likely to occur during milling. Appropriate sanitary measures should, therefore, be implemented in the mill to minimize the risk of microbial contamination during wheat milling.
Nutritional and cooking quality improvement of brown rice noodles prepared with extruded rice bran
Authors: Wu Na‐Na , Ma Zhan‐Qian , Li Huan‐Huan , Tian Xiao‐Hong , Fang Yong , Tan Bin
Published: November 2020

Background and objectives

Wholegrain foods have gained great attention due to their benefits on health. However, the texture, taste, and cooking quality of wholegrain foods are not good because of the bran in wholegrain. The objectives of this study were to improve the quality of brown rice noodles with rice bran that was treated by extrusion cooking. In this study, brown rice noodles with extruded rice bran (BRN‐ERB) were prepared to improve their quality compared to white rice noodles (WRN) and brown rice noodles with un‐extruded rice bran (BRN).

Findings

The total phenolic, flavonoid, anthocyanin, and dietary fiber contents in BRN‐ERB were 44.87 mg GAE, 36.15 mg RE, 0.11 mg Cy‐3‐O‐G, and 4.48 g per 100 g, respectively, significantly higher than those in BRN and WRN. The BRN‐ERB had the highest antioxidant activities of DPPH, ABTS, and T‐AOC, the highest resistant starch content, and the lowest starch hydrolysis rate among the three types of rice noodles. Seven phenolics, six flavonoids, and three anthocyanins were individually detected in these rice noodles, and BRN‐ERB exhibited higher contents of protocatechuic acid, p‐coumaric acid, ferulic acid, and daidzein than BRN and WRN did. The cooking and textural qualities of BRN‐ERB were improved with lower optimum cooking time and cooking loss, and higher hardness, tensile strength, and elasticity compared to BRN.

Conclusions

The brown rice noodles with extruded rice bran had higher contents of nutritional components than brown rice noodles with un‐extruded rice bran and white rice noodles, and better cooking and textural properties than brown rice noodles with un‐extruded rice bran.

Significance and novelty

The results provided the evidences that brown rice noodles prepared with extruded rice bran might become functional foods from the sources of staple rice products.
Adenoid cystic carcinoma of buccal mucosa: A report of two rare cases and review of literature
Authors: Karimi Abbas , Parhiz Alireza , Eslamiamirabadi Negin , Moradzadeh Khiavi Monir , Derakhshan Samira
Published: November 2020

In the oral cavity, adenoid cystic carcinomas of the buccal mucosa are extremely rare. Minor salivary grand adenoid cystic carcinoma should receive aggressive treatment to achieve negative surgical margins to inhibit recurrence.
Faggot cells in therapy‐related acute myeloid leukemia with inv(16)
Authors: Vega González de Viñaspre Ana , De Miguel Sánchez Carlos , Robles De Castro Diego , Roldán Galiacho Verónica , Mendizabal Abad Arantza , Guinea De Castro José María
Published: November 2020

Faggot cells are an uncommon finding in nonacute promyelocytic leukemia, even rarer when observed in mature granulocytic cells. Inv(16) should be dismissed when pre‐eosinophilic granulation and faggot neutrophils are observed.
Without a silhouette
Authors: Sazumi Yosuke , Tokumasu Kazuki , Hagiya Hideharu , Otsuka Fumio
Published: November 2020

Primary effusion lymphoma (PEL) is a kind of malignant lymphoma that develops without a tumor mass. A fluid smear is of no use for the diagnosis of miscellaneous condition. Repeated cell‐block smear with immunostaining is useful for the diagnosis of PEL.
Ectopic parathyroid gland within carotid sheath
Authors: Poh Benjamin Ruimin , Nagadia Rahul Harshad , Tay Gerald Ci‐An
Published: November 2020

During operative exploration of the neck for parathyroid surgery, the surgeon should always consider possible ectopic locations of the glands and have a reasonable surgical strategy for locating these ectopic glands.
Upper gastrointestinal ischemia as a rare complication of paroxysmal nocturnal hemoglobinuria
Authors: Ueno Masayuki , Shimodate Yuichi , Okada Kazuya , Takaya Ryosuke , Yamamoto Hiroshi , Mizuno Motowo
Published: November 2020

When patients with PNH present with abdominal symptoms, thrombosis‐induced gastrointestinal injury should be considered; computed tomography and esophagogastroduodenoscopy may help make the diagnosis of this potentially serious complication.
Association of polycythemia vera with positive JAK2V617F mutation and myasthenia gravis: A report of two cases
Authors: Sasi Sreethish , Yassin Mohamed A. , Kamran Sadat , Mnatsakanyan Vazgen
Published: November 2020

Screening for MG in patients with PV positive for JAK2V617F mutation can help in early diagnosis and treatment, resulting in a significant reduction in morbidity and mortality.
A weighted local steady‐state determination approach based on the globally optimal economic steady‐states
Authors: Liu Jianbang , Sun Haojie , Lu Yunsong , Hu Jingtao , Zou Tao
Published: November 2020

Steady‐state incremental constraints of manipulated variables play a vital role in making given steady‐states satisfy physical limitations and avoiding drastic set‐point changes. Nevertheless, some research reveals that the steady‐state incremental constraints will make the given locally optimal economic steady‐states diverge from the globally optimal economic steady‐states. Therefore, a novel weighted local steady‐state determination approach based on the globally optimal economic steady‐states is presented in this paper. Firstly, the globally and locally optimal economic steady‐states are both evaluated through considering and not considering steady‐state incremental constraints. Then, the angle between them is evaluated and the closest local steady‐state from the globally optimal economic steady‐state is calculated. Subsequently, a new weighted local steady‐state is evaluated by combining the locally optimal economic steady‐state and the closest local steady‐state, in which the weighting coefficient is carefully tuned based on the above‐calculated angle. Finally, several simulations verify that the proposed method could effectively shorten the settling time of controlled systems and improve their economic performance.
Effects of high oil viscosity on oil‐gas downward flow in deviated pipes. Part 1: Experimental setup and flow pattern transitions
Authors: Soto‐Cortes Gabriel , Pereyra Eduardo , Sarica Cem , Rivera‐Trejo Fabian , Torres Carlos
Published: November 2020

This work provides new experimental data on high viscosity oil‐gas flow. A set of 170 downward flow experiments were carried out using a mixture of air and mineral oil (213 mPa · s, 50.8 mm internal diameter, 21.5 m long) for five different elevations: −45°, −60°, −70°, −80°, and −85°. Superficial liquid and gas velocities varied from 0.05 m/s to 0.7 m/s and 0.7 m/s to 7 m/s, respectively. Flow pattern transitions were identified and analyzed. The results helped to evaluate the effects of pipe inclination and liquid viscosity on the stratified‐annular transition, as well as the characterization of subclasses of annular flow pattern, named falling film, liquid slip, and wavy annular. Based on the experimental evidence, the study proposes a constant liquid‐fraction value as a transition between liquid slip and wavy annular flow patterns. A comparison of the present data with the flow pattern predictions of the available models were made. Results show disagreements, which justifies the need for a detailed study of the effects of viscosity and the inclination of the pipe in liquid‐gas downward flow mixtures.
Metal‐Free Catalyzed Cyclization of N‐Methoxybenzamides to Construct Quaternary Carbon‐Containing Isoindolinones
Authors: Zhang Lin‐Bao , Wang Zi‐Chen , Sun Sheng‐Zheng , Ni Shao‐Fei , Wen Li‐Rong , Li Ming
Published: November 2020

Main observation and conclusion

Through the intramolecular cyclization of N‐methoxybenzamides, a simple and efficient method for constructing valuable isoindolinones under metal‐free conditions was developed. The reaction was featured by employing low‐cost catalyst, simple operation, 100% atomic economy and excellent regioselectivity. Moreover, a detailed computational study on the reaction system has been performed to clarify the mechanism. This protocol tolerated a variety of functional groups and provided a metal‐free protocol for the synthesis of chromane‐ or tetrahydroquinoline‐fused isoindolinones in good yields.
Tumor cell invasiveness in the initial stages of bladder cancer development ‐ A computational study
Authors: Carvalho Joao , Lopes Valeria , Travasso Rui
Published: November 2020

Bladder cancer is one of the most common types of cancer, being the sixth more frequent in men, and one with higher recurrence rates and overall treatment costs. We introduce an agent‐based computational model of the urothelium, adopting a Cellular Potts Model (CPM) approach to describe both a healthy urothelium and the development of bladder cancer. We focus on the identification of the conditions in which cancer cells cross, by mechanical means, the basement membrane and invade the bladder lamina propria. When within the urothelium the tumor grows in a very constrained environment. These tight conditions imply that the urothelium layer where the tumor initiates greatly determines tumor growth and invasiveness. Moreover, we demonstrate how specific mechanical properties of the cancer cells, as their stiffness or the adhesion to neighboring cells, heavily modulate the critical initial moments of tumor development. We propose that these characteristics should be considered as therapeutic targets to control tumor growth.
A novel algorithm to resolve lack of convergence and checkerboard instability in bone adaptation simulations using non‐local averaging
Authors: Calvo‐Gallego José Luis , Pivonka Peter , García‐Aznar José Manuel , Martínez‐Reina Javier
Published: November 2020

Checkerboard is a typical instability in finite element (FE) simulations of bone adaptation and topology optimization in general. It consists in a patchwork pattern with elements of alternating stiffness, producing lack of convergence and instabilities in the predicted bone density. Averaging techniques have been proposed to solve this problem. One of the most acknowledged techniques (node based formulation) has severe drawbacks such as: high sensitivity to mesh density and type of element integration (full vs reduced) and, more importantly, oscillatory solutions also leading to lack of convergence. We propose a new solution consisting in a non‐local smoothing technique. It defines, as the mechanical stimulus governing bone adaptation in a certain integration point of the mesh, the average of the stimuli obtained in the neighbour integration points. That average is weighted with a decay function of the distance to the centre of the neighbourhood. The new technique has been shown to overcome all the referred problems and perform in a robust way. It was tested on a hollow cylinder, resembling the diaphysis of a long bone, subjected to bending or torsion. Checkerboard instability was eliminated and local convergence of bone adaptation was achieved rapidly, in contrast to the other averaging technique and to the model without control of checkerboard instability. The new algorithm was also tested with good results on the same geometry but in a model containing a void, which produces a stress concentration that usually leads to checkerboard instability, like in other applications such as simulations of bone‐implant interfaces.
Increasing comparability among coral bleaching experiments
Authors: Grottoli A. G. , Toonen R. J. , van Woesik R. , Vega Thurber R. , Warner M. E. , McLachlan R. H. , Price J. T. , Bahr K. D. , Baums I. B. , Castillo K. D. , Coffroth M. A. , Cunning R. , Dobson K. L. , Donahue M. J. , Hench J. L. , Iglesias‐Prieto R. , Kemp D. W. , Kenkel C. D. , Kline D. I. , Kuffner I. B. , Matthews J. L. , Mayfield A. B. , Padilla‐Gamiño J. L. , Palumbi S. , Voolstra C. R. , Weis V. M. , Wu H. C.
Published: November 2020

Coral bleaching is the single largest global threat to coral reefs worldwide. Integrating the diverse body of work on coral bleaching is critical to understanding and combating this global problem. Yet investigating the drivers, patterns, and processes of coral bleaching poses a major challenge. A recent review of published experiments revealed a wide range of experimental variables used across studies. Such a wide range of approaches enhances discovery, but without full transparency in the experimental and analytical methods used, can also make comparisons among studies challenging. To increase comparability but not stifle innovation, we propose a common framework for coral bleaching experiments that includes consideration of coral provenance, experimental conditions, and husbandry. For example, reporting the number of genets used, collection site conditions, the experimental temperature offset(s) from the maximum monthly mean (MMM) of the collection site, experimental light conditions, flow, and the feeding regime will greatly facilitate comparability across studies. Similarly, quantifying common response variables of endosymbiont (Symbiodiniaceae) and holobiont phenotypes (i.e., color, chlorophyll, endosymbiont cell density, mortality, and skeletal growth) could further facilitate cross‐study comparisons. While no single bleaching experiment can provide the data necessary to determine global coral responses of all corals to current and future ocean warming, linking studies through a common framework as outlined here, would help increase comparability among experiments, facilitate synthetic insights into the causes and underlying mechanisms of coral bleaching, and reveal unique bleaching responses among genets, species, and regions. Such a collaborative framework that fosters transparency in methods used would strengthen comparisons among studies that can help inform coral reef management and facilitate conservation strategies to mitigate coral bleaching worldwide.
The curious case of IL‐33 in homeostasis and infection
Authors: Nadafi Reza , Arens Ramon
Published: November 2020

The importance of interleukin (IL)‐33 in promoting effective antiviral immune responses is evident, yet the critical cellular sources of IL‐33 in homeostasis and infection are largely unknown. In this issue of the European Journal of Immunology, Aparicio‐Domingo et al. [Eur. J. Immunol. 2021. 51: 76–90] explore the main source of IL‐33 expression in lymph nodes (LNs) and dissect its role in LN homeostasis and antiviral adaptive immune response. The authors reveal that fibroblastic reticular cells and lymphatic endothelial cells are both producing IL‐33 in steady‐state LNs. Remarkably, however, by using cell‐type specific deletion approaches, the authors demonstrate that exclusively fibroblastic reticular cells, and not lymphatic endothelial cells, are the critical cellular source for promoting antiviral CD8+ T‐cell responses upon infection. These findings provide an important insight into the role of specific LN stromal cell subsets as potent modulators of antiviral immunity.
Low‐Field High‐Resolution PFG‐NMR to Predict the Size Distribution of Inner Droplets in Double Emulsions
Authors: Khadem Behnam , Parrott Andrew , Nordon Alison , Sheibat‐Othman Nida
Published: November 2020

In double emulsions, the inner and outer droplet size distribution (DSD) determines the quality of the double emulsion and is therefore essential to be measured. Low‐field high‐resolution pulsed‐field gradient nuclear magnetic resonance is used to measure the inner DSD in water‐in‐oil‐in‐water double emulsions. The Gaussian phase distribution approach is employed with a mixture of two normal distributions to predict bimodal inner droplets. This approach allows the prediction of the swelling of inner droplet during storage of double emulsions, and thus to validate a phenomenological population balance model estimating inner droplet swelling. Only a fraction of the inner droplets are found to swell during storage, due to differences in the Laplace pressure, thus leading to the formation of a bimodal size distribution of the inner droplets.

Practical Applications: This methodology is useful to predict the evolution of double emulsions during storage, in a wide range of applications, such as food and pharmaceutical products.
Ultra‐orthodoxy and selective voluntarism: How did the Orbán regime react to the first wave of the pandemic?
Authors: Ádám Zoltán
Published: November 2020

Viktor Orbán's regime in Hungary is a prime example of authoritarian populism in a relatively developed country that has been part of the European Union since 2004. The paper argues that in response to the pandemic, the Orbán government pursued a set of selectively voluntarist policies that have been informed by an ultra‐orthodox, state‐centered worldview that sought to minimize the regime's democratic accountability and to reduce the counter‐mobilization ability of the opposition. These policies had been associated with comparatively low infection and death rates in the first wave of the pandemic, hence enabling high approval ratings for the government despite generating considerable human and economic costs. In light of rising infection and death rates from September 2020, however, it is yet to be seen whether the COVID‐19 crisis, in balance, will reinforce or undermine popular support to the regime.
Clinical and genomic analysis of a large Chinese family with familial cortical myoclonic tremor with epilepsy and SAMD12 intronic repeat expansion
Authors: Zhou Yongxing , Sood Raman , Wang Qun , Carrington Blake , Park Morgan , Young Alice C. , Birnbaum Daniel , Liu Zhao , Ashizawa Tetsuo , Mullikin James C. , Koubeissi Mohamad Z. , Liu Paul
Published: November 2020

Objective

Our goal was to perform detailed clinical and genomic analysis of a large multigenerational Chinese family with 21 individuals showing symptoms of Familial Cortical Myoclonic Tremor with Epilepsy (FCMTE) that we have followed for over 20 years.

Methods

Patients were subjected to clinical evaluation, routine EEG, and structural magnetic resonance imaging. Whole exome sequencing, repeat‐primed PCR, long‐range PCR, and PacBio sequencing were performed to characterize the disease‐causing mutation in this family.

Results

All evaluated patients manifested adult‐onset seizures and presented with progressive myoclonic postural tremors starting after the third or fourth decade of life. Seizures typically diminished markedly in frequency with implementation of antiseizure medications but did not completely cease. The electroencephalogram of affected individuals showed generalized or multifocal spikes and slow wave complexes. An expansion of TTTTA motifs with addition of TTTCA motifs in intron 4 of SAMD12 was identified to segregate with the disease phenotype in this family. Furthermore, we found that the mutant allele is unstable and can undergo both contraction and expansion by changes in the number of repeat motifs each time it is passed to the next generation. The size of mutant allele varied from 5 to 5.5 kb with 549‐603 copies of TTTTA and 287‐343 copies of TTTCA repeat motifs in this family.

Significance

Our study provides a detailed description of clinical progression of FCMTE symptoms and its management with antiseizure medications. Our method of repeat analysis by PacBio sequencing of long‐range PCR products does not require high‐quality DNA and hence can be easily applied to other families to elucidate any correlation between the repeat size and phenotypic variables, such as, age of onset, and severity of symptoms.
Operation optimization of integrated energy systems based on heat storage characteristics of heating network
Authors: Pan Ersheng , Li Hui , Wang Zhidong , Peng Dong , Zhao Lang , Fan Lisha , Wang Yongli , Huang Feifei , Ma Yang , Liu Lin
Published: November 2020

With the development of multi‐energy technology, the electric‐heat integrated energy system has become an important research direction for multi‐energy joint supply. The dynamic characteristics and energy storage capacity of heat supply network provide potential for joint dispatching of electric heating energy system. Aiming at the problem of electric‐heat joint dispatching, this paper presents an operation optimization model of electric‐heat integrated energy system considering the virtual energy storage characteristics of heat supply network. Firstly, according to the characteristics of transmission delay and user temperature fuzzy, the virtual energy storage characteristics of heat supply network are studied, and a model of the dynamic transfer of energy in the heat system was built. Then, the operation optimization model of the electric‐heat integrated energy system is established to minimize the operation cost. In order to improve the robustness of scheduling optimization results, the Monte Carlo Simulation embedded Quantum Particle Swarm Optimization algorithm is proposed to solve the model. In order to prove the validity of the proposed model, this paper selects a park (a 36 node thermal system) in the northwest region of China as a simulation case. The results show that the operation optimization method considering the virtual energy storage of heat supply network will greatly enhance the complementary potential of the electric‐heat integrated energy system and reduce the operation cost of the system.
Synergistic flame retardancy of bis(1‐methoxy‐2,2,6,6‐tetramethylpiperidin‐4‐yl)sebacate and aluminium hypophosphite/melamine hydrobromide in PP
Authors: Qiu Yanyan , Sun Mingmei , Wu Hongzhi , Tang Min , Yan Bo , Tang Linsheng
Published: November 2020

Synergistic flame retardancy of bis(1‐methoxy‐2,2,6,6‐tetramethylpiperidin‐4‐yl)sebacate (NORSM) and aluminium hypophosphite (ALHP)/melamine hydrobromide (MHB) in polypropylene (PP) was studied by limiting oxygen index (LOI) determination, UL‐94 test and cone calorimetry test. The results reveal that NORSM, together with ALHP/MHB, has an exceptional synergistic flame retardant effect in PP. For the FR‐PP containing 1.0 wt% of ALHP and 1.5 wt% of MHB, combining NORSM in 0.30 wt% concentration can make its LOI increases from 19.0% to 26.3%, the flame retardant effectivity increases from 0.48 to 3.04, the synergistic effectivity is as high as 2.03, the UL‐94 rating is improved from none to V‐2, the fire performance index increases from 58.7 to 91.3, various heat release parameter values are reduced obviously. It is confirmed that NORSM plays the role of synergism with ALHP/MHB mainly through the following mechanisms: the active radicals such as methyl radicals, methoxy radicals, nitro radicals, and aminyl radicals produced by the pyrolysis of NORSM, together with PH3 and HBr, quench active free radical such as ·OH, so the chain reaction of combustion is interrupted and results in a more efficient flame retardant effect in gaseous phase.
Fluid–fluid interactions in pseudopotential lattice Boltzmann models: Effects of model schemes and fluid properties
Authors: Pasieczynski Kamil , Chen Baixin
Published: November 2020

This article demonstrates the characteristics of interparticle forces and forcing schemes in pseudopotential lattice Boltzmann simulations. The Yuan–Schaefer (YS), multipseudopotential interaction (MPI), and piecewise linear methods are examined as techniques of equation of state (EOS) inclusion in pseudopotential models. It is suggested here that it is important to have an understanding of the interparticle forces generated by the models in order to obtain good quality results. Poor choice of parameters can lead to generation of unphysical interactions. The piecewise linear method is found to perform well and to decouple parameters. It decouples the density ratio from the surface tension and from the collision operator relaxation rates. It is proposed that the decoupling occurs due to generation of lower values of high‐order error terms in the interfacial region by the piecewise linear EOS. In general, the multiple‐relaxation‐time (MRT) collision operator should be combined with the Huang–Wu forcing scheme for simulating high values of surface tension and with the Li–Luo method for simulating low values of surface tension. It is found that reducing kinematic viscosity is more detrimental to the stability of the simulations than increasing the density ratio. Introducing a kinematic viscosity ratio between the phases practically eliminates the influence of density ratio on spurious velocities. The factors affecting stability of dynamic simulations are examined. It is found that they have the following hierarchy from the greatest impact to the least: kinematic viscosity ratio between the phases, bulk viscosity, method of EOS inclusion, and reduced temperature/density ratio.
Dual Targeting of G9a and DNA Methyltransferase‐1 for the Treatment of Experimental Cholangiocarcinoma
Authors: Colyn Leticia , Bárcena‐Varela Marina , Álvarez‐Sola Gloria , Latasa M. Ujue , Uriarte Iker , Santamaría Eva , Herranz Jose M. , Santos‐Laso Alvaro , Arechederra Maria , Ruiz de Gauna Mikel , Aspichueta Patricia , Canale Matteo , Casadei‐Gardini Andrea , Francesconi Maria , Carotti Simone , Morini Sergio , Nelson Leonard J. , Iraburu Maria J. , Chen Chaobo , Sangro Bruno , Marin Jose J.G. , Martinez‐Chantar Maria L. , Banales Jesus M. , Arnes‐Benito Robert , Huch Meritxell , Patino John M. , Dar Altaf A. , Nosrati Mehdi , Oyarzábal Julen , Prósper Felipe , Urman Jesus , Cubero Francisco Javier , Trautwein Christian , Berasain Carmen , Fernandez‐Barrena Maite G. , Avila Matias A.
Published: November 2020

Background and Aims

Cholangiocarcinoma (CCA) is a devastating disease often detected at advanced stages when surgery cannot be performed. Conventional and targeted systemic therapies perform poorly, and therefore effective drugs are urgently needed. Different epigenetic modifications occur in CCA and contribute to malignancy. Targeting epigenetic mechanisms may thus open therapeutic opportunities. However, modifications such as DNA and histone methylation often coexist and cooperate in carcinogenesis. We tested the therapeutic efficacy and mechanism of action of a class of dual G9a histone‐methyltransferase and DNA‐methyltransferase 1 (DNMT1) inhibitors.

Approach and Results

Expression of G9a, DNMT1, and their molecular adaptor, ubiquitin‐like with PHD and RING finger domains‐1 (UHRF1), was determined in human CCA. We evaluated the effect of individual and combined pharmacological inhibition of G9a and DNMT1 on CCA cell growth. Our lead G9a/DNMT1 inhibitor, CM272, was tested in human CCA cells, patient‐derived tumoroids and xenograft, and a mouse model of cholangiocarcinogenesis with hepatocellular deletion of c‐Jun‐N‐terminal‐kinase (Jnk)‐1/2 and diethyl‐nitrosamine (DEN) plus CCl4 treatment (JnkΔhepa + DEN + CCl4 mice). We found an increased and correlative expression of G9a, DNMT1, and UHRF1 in CCAs. Cotreatment with independent pharmacological inhibitors G9a and DNMT1 synergistically inhibited CCA cell growth. CM272 markedly reduced CCA cell proliferation and synergized with Cisplatin and the ERBB‐targeted inhibitor, Lapatinib. CM272 inhibited CCA tumoroids and xenograft growth and significantly antagonized CCA progression in JnkΔhepa + DEN + CCl4 mice without apparent toxicity. Mechanistically, CM272 reprogrammed the tumoral metabolic transcriptome and phenotype toward a differentiated and quiescent status.

Conclusions

Dual targeting of G9a and DNMT1 with epigenetic small molecule inhibitors such as CM272 is a potential strategy to treat CCA and/or enhance the efficacy of other systemic therapies.
Targeting the Four Pillars of Enterohepatic Bile Salt Cycling; Lessons From Genetics and Pharmacology
Authors: Kunst Roni F. , Verkade Henkjan J. , Oude Elferink Ronald P.J. , van de Graaf Stan F.J.
Published: November 2020

Bile salts play a pivotal role in lipid homeostasis, are sensed by specialized receptors, and have been implicated in various disorders affecting the gut or liver. They may play a role either as culprit or as potential panacea. Four very efficient transporters mediate most of the hepatic and intestinal bile salt uptake and efflux, and are each essential for the efficient enterohepatic circulation of bile salts. Starting from the intestinal lumen, conjugated bile salts cross the otherwise impermeable lipid bilayer of (primarily terminal ileal) enterocytes through the apical sodium–dependent bile acid transporter (gene SLC10A2) and leave the enterocyte through the basolateral heteromeric organic solute transporter, which consists of an alpha and beta subunit (encoded by SLC51A and SLC51B). The Na+‐taurocholate cotransporting polypeptide (gene SLC10A1) efficiently clears the portal circulation of bile salts, and the apical bile salt export pump (gene ABCB11) pumps the bile salts out of the hepatocyte into primary bile, against a very steep concentration gradient. Recently, individuals lacking either functional Na+‐taurocholate cotransporting polypeptide or organic solute transporter have been described, completing the quartet of bile acid transport deficiencies, as apical sodium–dependent bile acid transporter and bile salt export pump deficiencies were already known for years. Novel pathophysiological insights have been obtained from knockout mice lacking functional expression of these genes and from pharmacological transporter inhibition in mice or humans. Conclusion: We provide a concise overview of the four main bile salt transport pathways and of their status as possible targets of interventions in cholestatic or metabolic disorders.