bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixed Method Research on Football Coaches’ Competitive Behavior
Authors: Rodrigues José , Rodrigues Filipe , Resende Rui , Espada Mário , Santos Fernando
Published: July 2021

Objective

The purpose of this study was to present the reliability of three validated measures, namely the System of Analysis of Instruction in Competition, the Questionnaire on Coach Instructional Behavior Expectations, and the Questionnaire on Coach Instructional Behavior Perception that could be used in a mix-method approach.

Methods

Three instruments underwent a robust process of construct and reliability analysis. Inter− and intra-observer reliability was tested for the observational instrument using Cohen’s k-agreement measure. Reliability values above 0.85 were considered as a good agreement between and within observers. To verify the internal consistency of the questionnaires, the correlation coefficients were considered.

Results

The results related to intra-observer and inter-observer reliability showed that intra-observer reliability k-agreement values ranged between 0.912 and 1 for observer 1, and 0.82 and 1 for observer 2. For inter-observer reliability, k-agreement values ranged between 0.885 and 1 between observers. Thus, values for reliability are above acceptable. The correlation coefficient values recorded for the questionnaires on instruction expectations in the competitive moment were above 0.82 and significant (p < 0.05), and for the questionnaire on instruction perception in competition above 0.88 and significant (p < 0.05). The pilot study showed some divergent results across expectations, behavior during competition, and perception about the instruction behavior.

Conclusion

The observational system and the expectations and perceptions questionnaires, used in a complementary way, can be considered as a mix-method approach for studies aiming to examine coaches’ competitive behavior.
Seeing the Window, Finding the Spider: Applying Critical Race Theory to Medical Education to Make Up Where Biomedical Models and Social Determinants of Health Curricula Fall Short
Authors: Tsai Jennifer , Lindo Edwin , Bridges Khiara
Published: July 2021

A professional and moral medical education should equip trainees with the knowledge and skills necessary to effectively advance health equity. In this Perspective, we argue that critical theoretical frameworks should be taught to physicians so they can interrogate structural sources of racial inequities and achieve this goal. We begin by elucidating the shortcomings in the pedagogic approaches contemporary Biomedical and Social Determinants of Health (SDOH) curricula use in their discussion of health disparities. In particular, current medical pedagogy lacks self-reflexivity; encodes social identities like race and gender as essential risk factors; neglects to examine root causes of health inequity; and fails to teach learners how to challenge injustice. In contrast, we argue that Critical Race Theory (CRT) is a theoretical framework uniquely adept at addressing these concerns. It offers needed interdisciplinary perspectives that teach learners how to abolish biological racism; leverage historical contexts of oppression to inform interventions; center the scholarship of the marginalized; and understand the institutional mechanisms and ubiquity of racism. In sum, CRT does what biomedical and SDOH curricula cannot: rigorously teach physician trainees how to combat health inequity. In this essay, we demonstrate how the theoretical paradigms operationalized in discussions of health injustice affect the ability of learners to confront health inequity. We expound on CRT tenets, discuss their application to medical pedagogy, and provide an in-depth case study to ground our major argument that theory matters. We introduce MedCRT: a CRT-based framework for medical education, and advocate for its implementation into physician training.
Development and Implementation of Couple-Based Collaborative Management Model of Type 2 Diabetes Mellitus for Community-Dwelling Chinese Older Adults: A Pilot Randomized Trial
Authors: Liu Yuyang , Xiao Xiaocun , Peng Chaonan , Zhao Tianyi , Wu Yanjuan , Yu Wanwen , Ou Liping , Chen Xiongfei , Wu Xueji , Xu Dong Roman , Liao Jing
Published: July 2021

Background: To mobilize family's positive involvement in improving and sustaining self-management activities of older adults with diabetes, we developed a couple-based collaborative management model (CCMM) for community-dwelling older Chinese.

Methods: The model was developed stepwise through applying theoretical models, interviewing older couples and community healthcare workers, as well as incorporating expert reviews. A 3-month pilot study was conducted to test the model's feasibility and its treatment effects by linear regression on 18 pairs of older couples aged 60 years+, who were equally divided into a couple-based intervention arm and a patient-only control arm.

Results: The developed CCMM covered four theory-driven intervention modules: dyadic assessment, dyadic education, dyadic behavior-change training, and dyadic monitoring. Each module was delivered by community healthcare workers and targeted at older couples as the management units. Based on interviews with older couples and healthcare workers, 4 weekly education and training group sessions and 2-month weekly behavior change booster calls were designed to address older adults' main management barriers. These modules and session contents were evaluated as essential and relevant by the expert panel. Furthermore, the CCMM showed good feasibility and acceptability in the pilot, with non-significant yet more positive changes in physiological outcomes of diabetic participants and couples' well-being and exercise levels of these in the intervention arm than their controlled counterparts.

Conclusion: We systematically developed a couple-based collaborative management model of diabetes, which was well-received by healthcare practitioners and highly feasible among older Chinese couples living in the community. The model's treatment effects need to be verified in fully powered randomized controlled trials.

Clinical Trial Registration:http://www.chictr.org.cn/showproj.aspx?proj=42964, identifier: ChiCTR1900027137.
ECO-CollecTF: A Corpus of Annotated Evidence-Based Assertions in Biomedical Manuscripts
Authors: Hobbs Elizabeth T. , Goralski Stephen M. , Mitchell Ashley , Simpson Andrew , Leka Dorjan , Kotey Emmanuel , Sekira Matt , Munro James B. , Nadendla Suvarna , Jackson Rebecca , Gonzalez-Aguirre Aitor , Krallinger Martin , Giglio Michelle , Erill Ivan
Published: July 2021

Analysis of high-throughput experiments in the life sciences frequently relies upon standardized information about genes, gene products, and other biological entities. To provide this information, expert curators are increasingly relying on text mining tools to identify, extract and harmonize statements from biomedical journal articles that discuss findings of interest. For determining reliability of the statements, curators need the evidence used by the authors to support their assertions. It is important to annotate the evidence directly used by authors to qualify their findings rather than simply annotating mentions of experimental methods without the context of what findings they support. Text mining tools require tuning and adaptation to achieve accurate performance. Many annotated corpora exist to enable developing and tuning text mining tools; however, none currently provides annotations of evidence based on the extensive and widely used Evidence and Conclusion Ontology. We present the ECO-CollecTF corpus, a novel, freely available, biomedical corpus of 84 documents that captures high-quality, evidence-based statements annotated with the Evidence and Conclusion Ontology.
Exploring Alternatives to the Hamiltonian Calculation of the Ashtekar-Olmedo-Singh Black Hole Solution
Authors: García-Quismondo Alejandro , Mena Marugán Guillermo A.
Published: July 2021

In this article, we reexamine the derivation of the dynamical equations of the Ashtekar-Olmedo-Singh black hole model in order to determine whether it is possible to construct a Hamiltonian formalism where the parameters that regulate the introduction of quantum geometry effects are treated as true constants of motion. After arguing that these parameters should capture contributions from two distinct sectors of the phase space that had been considered independent in previous analyses in the literature, we proceed to obtain the corresponding equations of motion and analyze the consequences of this more general choice. We restrict our discussion exclusively to these dynamical issues. We also investigate whether the proposed procedure can be reconciled with the results of Ashtekar, Olmedo, and Singh, at least in some appropriate limit.
Water Recognition on the Moon by Using THz Heterodyne-Spectrometer for Identifying the Appropriate Locations to Extract Water for Providing Oxygen for Breathing and Fuel for Spaceships’ Propulsion on the Moon with CubeSat
Authors: Rastinasab Vahid , Hu Weidong , Tahmasebi Mohammad Kazem
Published: July 2021

Asteroid mining offers vital sources for improving human lives and provides opportunities for interplanetary missions and space travel. There are many professional commercial space companies that are only investing billions of dollars on asteroids mining, but prior to that, one condition for asteroid mining could be planetary stations to refuel the pioneers’ spacecraft or human colonies on alien planets; hence, one of the vital sources for these purposes is water. Water can be harvested to split oxygen for breathing and hydrogen for refueling spaceships’ propulsions, and Earth-to-space water payload transporting is extremely expensive; therefore, discovering extraterrestrial water in outer space is economically beneficial. This paper presents a Lunar CubeSat Injector to deliver four 3U CubeSats into Low Lunar Orbit to make a constellation to identify locations of water sources on the Moon by using a THz heterodyne-spectrometer. In sum, this project can help scientists to recognize more water resources for those who will colonize the Moon and for those planning to go beyond it.
Genetic Dissection of Phosphorous Uptake and Utilization Efficiency Traits Using GWAS in Mungbean
Authors: Reddy Venkata Ravi Prakash , Das Shouvik , Dikshit Harsh Kumar , Mishra Gyan Prakash , Aski Muraleedhar S. , Singh Akanksha , Tripathi Kuldeep , Pandey Renu , Bansal Ruchi , Pal Singh Madan , Gore Padmavati Ganpat , P. B. Manjunatha , Kothari Deepali , Rai Neha , M. Nair RamaKrishnan
Published: July 2021

Mungbean (Vignaradiata L. Wilczek) is an early maturing legume grown predominantly in Asia for its protein-rich seeds. P deficiency can lead to several physiological disorders which ultimately result in a low grain yield in mungbean. The genetic dissection of PUpE (Puptake efficiency) and PUtE (P utilization efficiency) traits are essential for breeding mungbean varieties with a high P uptake and utilization efficiency. The study involves an association mapping panel consisting of 120 mungbean genotypes which were phenotyped for total dry weight, P concentration, total P uptake, and P utilization efficiency under low P (LP) and normal P (NP) conditions in a hydroponic system. A genotyping-by-sequencing (GBS) based genome-wide association study (GWAS) approach was employed to dissect the complexity of PUpE and PUtE traits at the genetic level in mungbean. This has identified 116 SNPs in 61 protein-coding genes and of these, 16 have been found to enhance phosphorous uptake and utilization efficiency in mungbeans. We identified six genes with a high expression (VRADI01G04370, VRADI05G20860, VRADI06G12490, VRADI08G20910, VRADI08G00070 and VRADI09G09030) in root, shoot apical meristem and leaf, indicating their role in the regulation of P uptake and utilization efficiency in mungbean. The SNPs present in three genes have also been validated using a Sanger sequencing approach.
The Effect of Mycorrhizal Fungi and PGPR on Tree Nutritional Status and Growth in Organic Apple Production
Authors: Przybyłko Sebastian , Kowalczyk Wojciech , Wrona Dariusz
Published: July 2021

The desire to reduce the negative impact of crops on the environment, as well as the growing concern for consumer health, is increasing interest in organic fruit production. In this context, the development of new environmentally friendly agrotechnical methods which allows for reducing the use of organic fertilizers by improving the nutrient use efficiency and consequently decreasing the leaching of them is a task of a great importance. The main purpose of this study was to evaluate the effect of mycorrhizal arbuscular fungi (AMF) combined with plant-growth-promoting rhizobacteria (PGPR) on growth and nutritional status of apple trees cultivated on a silty-loam, rich in clay minerals and humus soil under organic farming conditions. Thus, a trial was established in an experimental orchard in Wilanów in Central Poland with three cultivars (‘Topaz’, ‘Odra’, and ‘Chopin’) and a promising clone, U 8869. Trees were or were not inoculated with AMF + PGPR within a split-block experimental design with four replicates. According to the results, mycorrhizal frequency obtained in the inoculated tree roots was on average two-fold higher than in the roots of the control plants. After four years of AMF + PGPR inoculation, 24% higher trunk cross-section area (TCSA) was observed, with the nitrogen and magnesium concentrations in leaves increasing, on average, by 7.8% and 64.2%, and phosphorus and potassium content decreasing by 37.2% and 46.5%, respectively. This study shows that using AMF + PGPR inoculum supports tree roots colonization by AMF. As a result, better nitrogen nutrition status is observed that promote vigorous growth of trees and more efficient uptake of magnesium from the bulk soil. On the other hand, lower phosphorus content in inoculated tree leaves might be explained by a dilution effect, and potassium decrease could occur as a result of fungus–plant competition in conditions of this element deficiency in soil.
First Data on the Helminth Community of the Smallest Living Mammal on Earth, the Etruscan Pygmy Shrew, Suncus etruscus (Savi, 1822) (Eulipotyphla: Soricidae)
Authors: Galán-Puchades María Teresa , Mas-Coma Santiago , Valero María Adela , Fuentes Màrius V.
Published: July 2021

Suncus etruscus is the smallest living mammal on Earth by mass. Most adults weigh 1.8–3 g with a body length of 35–48 mm. Catching it in small mammal traps in nature is extremely difficult due to its minute size, and therefore special trapping methods must be used. We had the unique opportunity of studying, for the first time, the helminth parasites of 166 individuals of S. etruscus, part of the largest collection in the world, which belonged to the French scientist Dr Roger Fons (1942–2016). A total of 150 individuals were captured in the Banyuls-Cerbère area (France) and 16 in the island of Corsica (France). We found seven helminth species, specifically, the cestodes Joyeuxiella pasqualei larvae, Mesocestoides sp. larvae, Staphylocystis claudevaucheri, S. banyulsensis, S. cerberensis, and Pseudhymenolepis sp., and the nematodes Aonchotheca sp. and Nematoda gen. sp. larvae. Neither trematodes nor acanthocephalans were detected. We provide prevalences, infracommunity compositions, and helminth associations. The adult helminth community of S. etruscus seems to be highly specific, i.e., oioxenous, and linked to its insectivore diet. Due to its small size, S. etruscus has undergone numerous physiological adaptations that have probably influenced its helminth spectrum as well as its helminth specificity.
Hepcidin Protects Yellow Catfish (Pelteobagrus fulvidraco) against Aeromonas veronii-Induced Ascites Disease by Regulating Iron Metabolism
Authors: Fu Manquan , Kuang Rui , Wang Weicheng , Yu Yunzhen , Ai Taoshan , Liu Xiaoling , Su Jianguo , Yuan Gailing
Published: July 2021

Aeromonas veronii (A. veronii) is one of the main pathogens causing bacterial diseases in aquaculture. Although previous studies have shown that hepcidin as an antimicrobial peptide can promote fish resistance to pathogenic bacterial infections, but the mechanisms remain unclear. Here, we expressed and purified recombinant yellow catfish (Pelteobagrus fulvidraco) hepcidin protein (rPfHep). rPfHep can up-regulate the expression of ferritin and enhance the antibacterial activity in primary hepatocytes of yellow catfish. We employed berberine hydrochloride (BBR) and Fursultiamine (FSL) as agonists and antagonists for hepcidin, respectively. The results indicated that agonist BBR can inhibit the proliferation of pathogenic bacteria, and the antagonist FSL shows the opposite effect. After gavage administration, rPfHep and the agonist BBR can enhance the accumulation of iron in liver, which may hinder the iron transport and limit the amount of iron available to pathogenic bacteria. Moreover, rPfHep and the agonist BBR can also reduce the mortality rate, bacterial load and histological lesions in yellow catfish infected with A. veronii. Therefore, hepcidin is an important mediator of iron metabolism, and it can be used as a candidate target for prevent bacterial infections in yellow catfish. Hepcidin and BBR have potential application value in preventing anti-bacterial infection.
Effect of a Training Program on Hepatic Fat Content and Cardiometabolic Risk in Postmenopausal Women: The Randomized Controlled Trial
Authors: Reverter-Masia Joaquín , Pano-Rodriguez Alvaro , Beltran-Garrido Jose Vicente , Lecube Albert , Sánchez Enric , Hernández-González Vicenç
Published: July 2021

This 10-week randomized controlled trial investigates the effects of two different training modalities on hepatic fat content and cardiometabolic risk in sedentary postmenopausal women. Besides, alterations in physical fitness, hepatic fat content, and cardiometabolic risk will be associated with changes in those blood parameters that are usually modifiable by exercise training. Postmenopausal women (N = 32; ~61 years) were randomly assigned to one of the following treatment groups; (1) based on international exercise recommendations (EX group; n = 16), (2) exercise plus whole-body electromyostimulation (EX+EMS group; n = 16). Cardiometabolic risk score was calculated based on the international diabetes federation’s clinical criteria. Hepatic fat content was estimated using the fatty liver index. After the intervention, the cardiometabolic risk and the fatty liver index decreased, showing a higher impact on EX + WB-EMS. Physical fitness was assessed through aerobic and strength tests belonging to “Eurofit Testing Battery”. In all of them, significant differences were observed (p < 0.001), though EX+ EMS experienced better improvements (p < 0.05). In conclusion, a 10-week exercise training program, especially with WB-EMS, triggered improvements in physical fitness and reduced cardiometabolic risk and hepatic fat content in sedentary postmenopausal women.
Multipoint Detection Technique with the Best Clock Signal Closed-Loop Feedback to Prolong FPGA Performance
Authors: Jaafar Anuar , Soin Norhayati , Wan Muhamad Hatta Sharifah F. , Salim Sani Irwan , Zakaria Zahriladha
Published: July 2021

The degradation effect of a field-programmable gate array becomes a significant issue due to the high density of logic circuits inside the field-programmable gate array. The degradation effect occurs because of the rapid technology scaling process of the field-programmable gate array while sustaining its performance. One parameter that causes the degradation effect is the delay occurrence caused by the hot carrier injection and negative bias temperature instability. As such, this research proposed a multipoint detection technique that detects the delay occurrence caused by the hot carrier injection and negative bias temperature instability degradation effects. The multipoint detection technique also assisted in signaling the aging effect on the field-programmable gate array caused by the delay occurrence. The multipoint detection technique was also integrated with a method to optimize the performance of the field-programmable gate array via an automatic clock correction scheme, which could provide the best clock signal for prolonging the field-programmable gate array performance that degraded due to the degradation effect. The delay degradation effect ranged from 0° to 360° phase shifts that happened in the field-programmable gate array as an input feeder into the multipoint detection technique. With the ability to provide closed-loop feedback, the proposed multipoint detection technique offered the best clock signal to prolong the field-programmable gate array performance. The results obtained using the multipoint detection technique could detect the remaining lifetime of the field-programmable gate array and propose the best possible signal to prolong the field-programmable gate array’s performance. The validation showed that the multipoint detection technique could prolong the performance of the degraded field-programmable gate array by 13.89%. With the improvement shown using the multipoint detection technique, it was shown that compensating for the degradation effect of the field-programmable gate array with the best clock signal prolonged the performances.
Carbstone Pavers: A Sustainable Solution for the Urban Environment
Authors: Kazemi Kamyab Hadi , Nielsen Peter , Van Mierloo Peter , Horckmans Liesbeth
Published: July 2021

To reduce CO2 emissions from the building industry, one option is to replace cement in specific applications with alternative binders. The Carbstone technology is based on the reaction of calcium- and magnesium-containing minerals with CO2 to form carbonate binders. Mixes of carbon steel slag and stainless-steel slag, with tailored particle size distributions, were compacted with a vibro-press and subsequently carbonated in an autoclave to produce carbonated steel slag pavers. The carbonated materials sequester 100–150 g CO2/kg slag. Compressive and tensile splitting strength of the resulting pavers were determined, and the ratio was found to be comparable to that of concrete. The environmental performance of the Carbstone pavers, with an average tensile splitting strength of 3.6 MPa, was found to be in compliance with Belgian and Dutch leaching limit values for construction materials. In addition, leaching results for a concrete mix made with aggregates of crushed Carbstone pavers (simulating the so-called “second life” of pavers) demonstrate that the pavers can be recycled as aggregates in cement-bound products after their product lifetime.
Pullout Behavior of Nail Reinforcement in Nailed Soil Slope
Authors: Mohamed Mahmoud H. , Ahmed Mohd , Mallick Javed
Published: July 2021

The pullout resistance and displacement performance of reinforcement have significant effects on the safe and economic design of a reinforced-soil system. In this study, the nail pullout tests are conducted to assess the pullout behavior of soil nail reinforcement at different levels in the soil slope of granular materials. The similitude laboratory models of a reinforced soil system with a scale of 1:10 are prepared. The construction sequence used in a full scale slope was precisely followed in the laboratory model. The models consist of a Perspex wall box filled with sand and steel bars as a reinforcement. The models of sand beds are formed using an automatic sand raining system. Devices and instruments are installed to record the nails pullout resistance and displacement. The tests are carried out at variable footing pressures to get the pullout force of the nails based on a strain control technique. The finite element models of nailed soil slope are also analyzed to validate the laboratory model results. It infers from the numerical model results that the laboratory models underestimate the pullout behavior of nail reinforcement in nailed soil slope. The pull-out force in nail reinforcement increases as the displacement increases and then decreases slightly and becomes constant with an increase in displacement in the case of deeper placed nails, but it becomes constant immediately for upper nails.
Chlorobenzene Removal Using DBD Coupled with CuO/γ-Al2O3 Catalyst
Authors: Jin Xingpeng , Wang Guicheng , Lian Liping , Gao Fan , Zhang Renxi , Zhao Weixuan , Hou Jianyuan , Chen Shanping , Zhang Ruina
Published: July 2021

The removal of chlorobenzene using a dielectric barrier discharge (DBD) reactor coupled with CuO/γ-Al2O3 catalysts was investigated in this paper. The coupling of CuO enhanced the chlorobenzene degradation and complete oxidation ability of the DBD reactor, especially under low voltage conditions. The characterization of catalyst was carried out to understand the interaction between catalyst and plasma discharge. The effects of flow rate and discharge power on the degradation of chlorobenzene and the interaction between these parameters were analyzed using the response surface model (RSM). The analysis of variance was applied to evaluate the significance of the independent variables and their interactions. The results show that the interactions between flow rate and discharge power are not negligible for the degradation of chlorobenzene. Moreover, based on the analysis of byproducts, 4-chlorophenol was discriminated as the important intermediate of chlorobenzene degradation, and the speculative decomposition mechanism of chlorobenzene is explored.
Special Issue on Digital Twins in Industry
Authors: Nee A. Y. C. , Ong S. K.
Published: July 2021

Digital twin (DT) is an emerging and fast-growing technology which provides a promising way to connect and integrate physical and virtual spaces seamlessly [...]
The Inquiline Ant Myrmica karavajevi Uses Both Chemical and Vibroacoustic Deception Mechanisms to Integrate into Its Host Colonies
Authors: Casacci Luca Pietro , Barbero Francesca , Ślipiński Piotr , Witek Magdalena
Published: July 2021

Social parasitism represents a particular type of agonistic interaction in which a parasite exploits an entire society instead of a single organism. One fascinating form of social parasitism in ants is the “inquilinism”, in which a typically worker-less parasitic queen coexists with the resident queen in the host colony and produces sexual offspring. To bypass the recognition system of host colonies, inquilines have evolved a repertoire of deceiving strategies. We tested the level of integration of the inquiline Myrmica karavajevi within the host colonies of M. scabrinodis and we investigated the mechanisms of chemical and vibroacoustic deception used by the parasite. M. karavajevi is integrated into the ant colony to such an extent that, in rescue experiments, the parasite pupae were saved prior to the host’s brood. M. karavajevi gynes perfectly imitated the cuticular hydrocarbon profiles of M. scabrinodis queens and the parasite vibroacoustic signals resembled those emitted by the host queens eliciting the same levels of attention in the host workers during playback experiments. Our results suggest that M. karavajevi has evolved ultimate deception strategies to reach the highest social status in the colony hierarchy, encouraging the use of a combined molecular and behavioural approach when studying host–parasite interactions.
Vitamin D and Blood Parameters
Authors: Müller Thomas , Lohse Lutz , Blodau Andreas , Frommholz Katja
Published: July 2021

Background: Vitamin D has a steroid- and an anabolic-resembling chemical structure. Vitamin D is essential for many processes in the human body after hydroxylation. Aims of the Study: To investigate the impact of 25-hydroxy-vitamin D plasma concentrations on the blood parameters number of erythrocytes, hematocrit, mean corpuscular hemoglobin and mean corpuscular volume. Methods: Serial assessments were done in 290 patients with multiple sclerosis and repeated after a mean interval of 245 days. A recommendation for vitamin D supplementation was given in case of a concentration lower than 20 ng/mL combined with a prescription of a formulation containing vitamin D but not vitamin K. Results: There was a fall of vitamin D in 119 subjects and a rise in 164, while no change appeared in 7 participants. When vitamin D values went down between both assessments moments, the computed increase of mean corpuscular haemoglobin was significantly lower compared with the rise of mean corpuscular haemoglobin associated with a vitamin D elevation. When vitamin D declined, the computed fall of mean corpuscular volume fall was significantly lower compared with the decrease of mean corpuscular volume, when vitamin D rose. Positive correlations were found between differences of vitamin D and mean corpuscular haemoglobin, respectively mean corpuscular volume. Inverse relations appeared between disparities of vitamin D and erythrocytes, respectively haematocrit. Conclusions: The elevation of vitamin D plasma levels provides enhanced preconditions for a better tissue oxygenation on a cellular level.
A Novel Recombinant Fcγ Receptor-Targeted Survivin Combines with Chemotherapy for Efficient Cancer Treatment
Authors: Wu Chiao-Chieh , Chiang Chen-Yi , Liu Shih-Jen , Chen Hsin-Wei
Published: July 2021

Formyl peptide receptor-like 1 inhibitor (FLIPr), an Fcγ receptor (FcγR) antagonist, can be used as a carrier to guide antigen-FLIPr fusion protein to FcγR then enhances antigen-specific immune responses. Survivin, a tumor-associated antigen, is over-expressed in various types of human cancer. In this study, we demonstrate that recombinant survivin-FLIPr fusion protein (rSur-FLIPr) binds to FcγRs, and efficient uptake by dendritic cells in vivo. In addition, rSur-FLIPr alone stimulates survivin-specific immune responses, which effectively suppresses the tumor growth. The antitumor immunities are through TAP-mediated and CD8-dependent pathways. Furthermore, preexisting anti-FLIPr antibody does not abolish antitumor responses induced by rSur-FLIPr immunization. These results suggest that FLIPr is an effective antigen delivery vector and can be repeatedly used. Combination of chemotherapy with rSur-FLIPr treatment reveals a great benefit to tumor-bearing mice. Altogether, these findings suggest that rSur-FLIPr is a potential candidate for efficient cancer therapy.
Functional Connectivity-Derived Optimal Gestational-Age Cut Points for Fetal Brain Network Maturity
Authors: De Asis-Cruz Josepheen , Barnett Scott Douglas , Kim Jung-Hoon , Limperopoulos Catherine
Published: July 2021

The architecture of the human connectome changes with brain maturation. Pivotal to understanding these changes is defining developmental periods when transitions in network topology occur. Here, using 110 resting-state functional connectivity data sets from healthy fetuses between 19 and 40 gestational weeks, we estimated optimal gestational-age (GA) cut points for dichotomizing fetuses into ‘young’ and ‘old’ groups based on global network features. We computed the small-world index, normalized clustering and path length, global and local efficiency, and modularity from connectivity matrices comprised 200 regions and their corresponding pairwise connectivity. We modeled the effect of GA at scan on each metric using separate repeated-measures generalized estimating equations. Our modeling strategy involved stratifying fetuses into ‘young’ and ‘old’ based on the scan occurring before or after a selected GA (i.e., 28 to 33). We then used the quasi-likelihood independence criterion statistic to compare model fit between ‘old’ and ‘young’ cohorts and determine optimal cut points for each graph metric. Trends for all metrics, except for global efficiency, decreased with increasing gestational age. Optimal cut points fell within 30–31 weeks for all metrics coinciding with developmental events that include a shift from endogenous neuronal activity to sensory-driven cortical patterns.
Etiology and Outcomes of Hepatocellular Carcinoma in an Ethnically Diverse Population: The Multiethnic Cohort
Authors: Barzi Afsaneh , Zhou Kali , Wang Songren , Dodge Jennifer L. , El-Khoueiry Anthony , Setiawan Veronica Wendy
Published: July 2021

Backgrounds: HCC incidence varies by race/ethnicity. We characterized racial differences in underlying etiology, presentation, and survival in the linkage of Multiethnic Cohort Study with SEER and Medicare claims. Methods: HCC characteristics, treatment, and underlying etiology in participants were obtained. Deaths were ascertained using state death certificates and the National Death Index. Risk factors were collected via questionnaires. Cox models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for death. Results: Among 359 cases, the average age at diagnosis was 75.1. The most common etiology was hepatitis C (HCV) (33%), followed by nonalcoholic fatty liver disease (NAFLD) (31%), and different by ethnicity (p < 0.0001). African Americans (AA) (59.5%) and Latinos (40.6%) were more likely to be diagnosed with HCV-related HCC. In Japanese Americans (33.1%), Native Hawaiians (39.1%), and whites (34.8%), NAFLD was the most common etiology. Receipt of treatment varied across ethnic groups (p = 0.0005); AA had the highest proportion of no treatment (50.0%), followed by Latinos (45.3%), vs. whites (15.2%). HCC (72.2%) was the most common cause of death. In a multivariate analysis, AA (HR = 1.87; 95% CI: 1.06–3.28) had significantly higher mortality compared to whites. Conclusions: We found significant ethnic differences in HCC underlying etiology, receipt of treatment, and outcome. The findings are important for reducing disparities.
Improvement in the Assessment of Response to Preoperative Chemoradiotherapy for Rectal Cancer Using Magnetic Resonance Imaging and a Multigene Biomarker
Authors: Cho Eunhae , Jung Sung Woo , Park In Ja , Jang Jong Keon , Park Seong Ho , Hong Seung-Mo , Lee Jong Lyul , Kim Chan Wook , Yoon Yong Sik , Lim Seok-Byung , Yu Chang Sik , Kim Jin Cheon
Published: July 2021

The response to preoperative chemoradiotherapy (PCRT) is correlated with oncologic outcomes in patients with locally advanced rectal cancer. Accurate prediction of PCRT response before surgery can provide crucial information to aid clinicians in further treatment planning. This study aimed to develop an evaluation tool incorporating a genetic biomarker and magnetic resonance imaging (MRI) to improve the assessment of response in post-CRT patients with locally advanced rectal cancer. A total of 198 patients who underwent PCRT followed by surgical resection for locally advanced rectal cancer between 2010 and 2016 were included in this study. Each patient’s response prediction index (RPI) score, a multigene biomarker developed in our previous study, and magnetic resonance tumor regression grade (mrTRG) score were added to create a new predictive value for pathologic response after PCRT, called the combined radiation prediction value (cRPV). Based on the new value, 121 and 77 patients were predicted to be good and poor responders, respectively, showing significantly different cRPV values (p = 0.001). With an overall predictive accuracy of 84.8%, cRPV was superior to mrTRG and RPI for the prediction of pathologic chemoradiotherapy response (mrTRG, 69.2%; RPI, 77.3%). In multivariate analysis, cRPV was found to be the sole predictor of tumor response (odds ratio, 32.211; 95% confidence interval, 14.408–72.011; p = 0.001). With its good predictive value for final pathologic regression, cRPV may be a valuable tool for assessing the response to PCRT before surgery.
Sociodemographic Correlates of Human Papillomavirus Vaccine Uptake: Opportunistic and Catch-Up Vaccination in Norway
Authors: Dong Li , Nygård Mari , Hansen Bo T.
Published: July 2021

Achieving equity in human papillomavirus (HPV) vaccination has high priority. In this nationwide registry-based study, we aimed to investigate sociodemographic correlates of HPV vaccine uptake among women who were vaccinated opportunistically at their own initiative and cost during October 2006–June 2018, and among women who were vaccinated free-of-charge in a catch-up vaccination program during November 2016–June 2018. For 840,328 female residents born in Norway between 1975 and 1996, we retrieved HPV vaccination and sociodemographic data from national registries. We used separate models to analyze the sociodemographic correlates of the initiation and completion of HPV vaccination in opportunistic and catch-up vaccination settings. Overall initiation rate for opportunistic HPV vaccination was 2.2%. Uptake increased consistently with birth year, maternal education level, and household income. Having two immigrant parents or a mother working in a lower prestige occupation was strongly associated with low opportunistic vaccination uptake. Similar but weaker inequities were observed in catch-up HPV vaccination. Initiation rate during the first 20 months of the catch-up program was 46.2%. Completion rate was 72.1% and 73.0% for opportunistic or catch-up vaccination, respectively, with small inequities. In conclusion, HPV vaccine uptake was strongly associated with sociodemographic background both in opportunistic and catch-up vaccination settings, with particularly low uptake associated with having two immigrant parents and low household income.
Novel Prognostic Index of High-Risk Prostate Cancer Using Simple Summation of Very High-Risk Factors
Authors: Yamazaki Hideya , Suzuki Gen , Masui Koji , Aibe Norihiro , Shimizu Daisuke , Kimoto Takuya , Yamada Kei , Shiraishi Takumi , Fujihara Atsuko , Okihara Koji , Yoshida Ken , Nakamura Satoaki , Okabe Haruumi
Published: July 2021

This study aimed to examine the role of very high-risk (VHR) factors (T3b–4 and Gleason score 9–10) for prognosis of clinically localized high-risk prostate cancer. We reviewed multi-institutional retrospective data of 1413 patients treated with radiotherapy (558 patients treated with external beam radiotherapy (EBRT) and 855 patients treated with brachytherapy (BT) ± EBRT. We introduced an index by simple summation of the number of VHR factors—VHR-0, VHR-1, and VHR-2. With median follow-up of 69.6 months, the 5-year biochemical disease free survival rate (bDFS), prostate cancer-specific mortality (PCSM), and distant metastasis-free survival (DMSF) rates were 59.4%, 7.65%, and 83.2% for the VHR-2 group, respectively; 86.7%, 1.50%, and 95.4% for the VHR-1 group, respectively; and 93.1%, 0.12%, and 98.2% for the VHR-0 group, respectively. The VHR-2 group had significantly worse bDFS, PCSM, and DMSF than the VHR-0 (hazard ratios: 4.55, 9.607, and 7.904, respectively) and VHR-1 (hazard ratios: 1.723, 2.391, and 1.491, respectively) groups. The VHR-2 group could be identified as a super high-risk group compared with other groups, and could be a good candidate for clinical trials using multimodal intensified treatments. Simple summation of the number of VHR factors is an easy and useful predictive index for bDFS, PCSM, and DMSF.
Development of an Androgen Receptor Inhibitor Targeting the N-Terminal Domain of Androgen Receptor for Treatment of Castration Resistant Prostate Cancer
Authors: Ban Fuqiang , Leblanc Eric , Cavga Ayse Derya , Huang Chia-Chi Flora , Flory Mark R. , Zhang Fan , Chang Matthew E. K. , Morin Hélène , Lallous Nada , Singh Kriti , Gleave Martin E. , Mohammed Hisham , Rennie Paul S. , Lack Nathan A. , Cherkasov Artem
Published: July 2021

Prostate cancer patients undergoing androgen deprivation therapy almost invariably develop castration-resistant prostate cancer. Resistance can occur when mutations in the androgen receptor (AR) render anti-androgen drugs ineffective or through the expression of constitutively active splice variants lacking the androgen binding domain entirely (e.g., ARV7). In this study, we are reporting the discovery of a novel AR-NTD covalent inhibitor 1-chloro-3-[(5-([(2S)-3-chloro-2-hydroxypropyl]amino)naphthalen-1-yl)amino]propan-2-ol (VPC-220010) targeting the AR-N-terminal Domain (AR-NTD). VPC-220010 inhibits AR-mediated transcription of full length and truncated variant ARV7, downregulates AR response genes, and selectively reduces the growth of both full-length AR- and truncated AR-dependent prostate cancer cell lines. We show that VPC-220010 disrupts interactions between AR and known coactivators and coregulatory proteins, such as CHD4, FOXA1, ZMIZ1, and several SWI/SNF complex proteins. Taken together, our data suggest that VPC-220010 is a promising small molecule that can be further optimized into effective AR-NTD inhibitor for the treatment of CRPC.
Oral Metronomic Maintenance Therapy Can Improve Survival in High-Risk Neuroblastoma Patients Not Treated with ASCT or Anti-GD2 Antibodies
Authors: Sun Xiaofei , Zhen Zijun , Guo Ying , Gao Yuanhong , Wang Juan , Zhang Yu , Zhu Jia , Lu Suying , Sun Feifei , Huang Junting , Cai Ruiqing , Zhang Yizhuo , Liu Juncheng , Xiao Zizheng , Zeng Sihui , Liu Zhuowei
Published: July 2021

Despite aggressive treatment, the prognosis of high-risk NB patients is still poor. This retrospective study investigated the benefits of metronomic maintenance treatment (MT) in high-risk NB patients without ASCT or GD2 antibody therapy. Patients aged ≤ 21 years with newly diagnosed high-risk NB were included. Patients with complete/very good partial remission (CR/VGPR/PR) to conventional treatment received, or not, oral metronomic MT for 1 year. Two hundred and seventeen high-risk NB patients were enrolled. One hundred and eighty-five (85%) had a CR/VGPR/PR to conventional treatment, of the patients with stage 4, 106 receiving and 61 not receiving oral metronomic MT, and the 3-year event-free survival (EFS) rate was 42.5 ± 5.1% and 29.6 ± 6%, respectively (p = 0.017), and overall survival (OS) rate was 71.1 ± 4.7% and 59.4 ± 6.4%, respectively (p = 0.022). A total of 117 high-risk patients with oral metronomic MT had EFS rate of 42.7 ± 4.8%. The toxicity of MT was mild. For high-risk NB patients without ASCT or anti-GD2 antibody therapy, stage 4, MYCN amplication and patients with stage 4 not receiving oral metronomic MT after CR/VGPR/PR were independent adverse prognostic factors. Oral metronomic MT can improve survival in high-risk NB patients in CR/VGPR/PR without ASCT or anti-GD2 antibodies therapy.
Autophagy Inhibition in BRAF-Driven Cancers
Authors: Foth Mona , McMahon Martin
Published: July 2021

Several BRAF-driven cancers, including advanced BRAFV600E/K-driven melanoma, non-small-cell lung carcinoma, and thyroid cancer, are currently treated using first-line inhibitor combinations of BRAFV600E plus MEK1/2. However, despite the success of this vertical inhibition strategy, the durability of patient response is often limited by the phenomenon of primary or acquired drug resistance. It has recently been shown that autophagy, a conserved cellular recycling process, is increased in BRAF-driven melanoma upon inhibition of BRAFV600E signaling. Autophagy is believed to promote tumor progression of established tumors and also to protect cancer cells from the cytotoxic effects of chemotherapy. To this end, BRAF inhibitor (BRAFi)-resistant cells often display increased autophagy compared to responsive lines. Several mechanisms have been proposed for BRAFi-induced autophagy, such as activation of the endoplasmic reticulum (ER) stress gatekeeper GRP78, AMP-activated protein kinase, and transcriptional regulation of the autophagy regulating transcription factors TFEB and TFE3 via ERK1/2 or mTOR inhibition. This review describes the relationship between BRAF-targeted therapy and autophagy regulation, and discusses possible future treatment strategies of combined inhibition of oncogenic signaling plus autophagy for BRAF-driven cancers.
Disrupting Mitochondrial Electron Transfer Chain Complex I Decreases Immune Checkpoints in Murine and Human Acute Myeloid Leukemic Cells
Authors: Luna-Yolba Raquel , Marmoiton Justine , Gigo Véronique , Marechal Xavier , Boet Emeline , Sahal Ambrine , Alet Nathalie , Abramovich Ifat , Gottlieb Eyal , Visentin Virgile , Paillasse Michael R. , Sarry Jean-Emmanuel
Published: July 2021

Oxidative metabolism is crucial for leukemic stem cell (LSC) function and drug resistance in acute myeloid leukemia (AML). Mitochondrial metabolism also affects the immune system and therefore the anti-tumor response. The modulation of oxidative phosphorylation (OxPHOS) has emerged as a promising approach to improve the therapy outcome for AML patients. However, the effect of mitochondrial inhibitors on the immune compartment in the context of AML is yet to be explored. Immune checkpoints such as ectonucleotidase CD39 and programmed dead ligand 1 (PD-L1) have been reported to be expressed in AML and linked to chemo-resistance and a poor prognosis. In the present study, we first demonstrated that a novel selective electron transfer chain complex (ETC) I inhibitor, EVT-701, decreased the OxPHOS metabolism of murine and human cytarabine (AraC)-resistant leukemic cell lines. Furthermore, we showed that while AraC induced an immune response regulation by increasing CD39 expression and by reinforcing the interferon-γ/PD-L1 axis, EVT-701 reduced CD39 and PD-L1 expression in vitro in a panel of both murine and human AML cell lines, especially upon AraC treatment. Altogether, this work uncovers a non-canonical function of ETCI in controlling CD39 and PD-L1 immune checkpoints, thereby improving the anti-tumor response in AML.
Vasculogenic Mimicry in Breast Cancer: Clinical Relevance and Drivers
Authors: Morales-Guadarrama Gabriela , García-Becerra Rocío , Méndez-Pérez Edgar Armando , García-Quiroz Janice , Avila Euclides , Díaz Lorenza
Published: July 2021

In solid tumors, vasculogenic mimicry (VM) is the formation of vascular structures by cancer cells, allowing to generate a channel-network able to transport blood and tumor cells. While angiogenesis is undertaken by endothelial cells, VM is assumed by cancer cells. Besides the participation of VM in tumor neovascularization, the clinical relevance of this process resides in its ability to favor metastasis and to drive resistance to antiangiogenic therapy. VM occurs in many tumor types, including breast cancer, where it has been associated with a more malignant phenotype, such as triple-negative and HER2-positive tumors. The latter may be explained by known drivers of VM, like hypoxia, TGFB, TWIST1, EPHA2, VEGF, matrix metalloproteinases, and other tumor microenvironment-derived factors, which altogether induce the transformation of tumor cells to a mesenchymal phenotype with a high expression rate of stemness markers. This review analyzes the current literature in the field, including the participation of some microRNAs and long noncoding RNAs in VM-regulation and tumorigenesis of breast cancer. Considering the clinical relevance of VM and its association with the tumor phenotype and clinicopathological parameters, further studies are granted to target VM in the clinic.
Addendum: López-Vidal et al. Is Autophagy Involved in Pepper Fruit Ripening? Cells 2020, 9, 106
Authors: López-Vidal Omar , Olmedilla Adela , Sandalio Luisa María , Sevilla Francisca , Jiménez Ana
Published: July 2021

The authors would like to make an addendum to their published paper [...]
Optical pH Sensing in Milk: A Small Puzzle of Indicator Concentrations and the Best Detection Method
Authors: Voskoboynikova Olga , Sukhanov Aleksey , Duerkop Axel
Published: July 2021

Optical chemical sensors can yield distinctively different responses that are dependent on the method applied for readout and evaluation. We therefore present a comprehensive study on the pH determined non-continuously with optical sensors in real milk samples by either photometry or colorimetry (via the RGB-readout of digital images) compared to the pH values obtained electrochemically by potentiometry. Additionally, the photometric determination of pH was conducted with single-wavelength and a dual wavelength ratiometric evaluation of the absorbance. It was found that both the precision and accuracy of the pH determined by photometry benefit from lower concentrations of bromocresol purple, which served as the pH indicator inside the sensor membrane. A further improvement is obtained by the ratiometric evaluation of the photometric sensor response. The pH values obtained from the colorimetric evaluation, however, gain in precision and accuracy if a higher concentration of the indicator is immobilized inside the sensor membrane. This has a major impact on the future fabrication of optical pH sensor membranes because they can be better tuned to match to the most precise and accurate range of the planned detection method.