bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the enterprises competitive advantages on the basis of financial and economic activity indicators
Authors: Temchenko O. , Kryshtopa I. , Shevchuk N.
Published: November 2021

Object of the research is the level of competitiveness, competitive behavior and efficiency of making logistic decisions at PJSC «AVK» as key representative of national confectionery market. One of the most problematic aspects is the absence of mechanism of support of sustainable competitive status of domestic enterprises in conditions of crisis that requires daily and permanent monitoring and strategic assessment of the state of ensuring competitiveness and existing advantages, analyses of the key factors of leading competitors functioning at current confectionery market. The objective of this investigation is theoretical overview of the concepts of competitiveness and competitive behavior, analysis of competition in the domestic confectionery market in Ukraine in conditions of accelerating globalization and maintaining negative trends in the world economy, as well as identifying prospects for logistics in further development of domestic enterprises in conditions of crisis. In order to achieve this goal, the authors applied such research methods as: analysis and synthesis, comparison, method of classification and generalization, due to which the final conclusions are made. Also, economic and statistical methods are used in this paper, namely: horizontal analysis and index method for the determination of competition intensity in the market, traditional methods of statistical information processing, SWOT-analysis, methods of economic analyses, method of five forces of competition by M. Porter, method «Square of potential» to assess the effectiveness of making logistics decisions in the nearest future. The priority meaning of recommendations, proposed in the paper, is to form a set of organizational, managerial, financial, economic and logistical measures to increase the competitiveness of PJSC «AVK», which is implemented by means of management of key competitive advantages at tactical and strategic levels, and will have a positive impact on future results of production and economic activity of the enterprise and its financial indicators while maintaining negative trends in world and domestic economy. The authors proposed the set of organizational and economic measures based on systematization of sectoral peculiarities of financial and economic activities that will ensure stable competitive advantage of PJSC «AVK» and provides, first of all, introduction of new types of bar chocolate, and its further implementation will increase net income of the enterprise, performance, and accordingly – will allow to predict potential competitive advantages and improve the level of competitiveness of the enterprise as a whole in the domestic confectionery market.
Електромобіль з іноваційною життєзберігаючою автоматичною системою
Authors: Лорія М.Г. , Целіщев О.Б. , Миллер В.В.
Published: November 2021

В статті було запропоновано конструкцію електромобілю з покращеними характеристиками, удосконалено технологію виробництва та створено макет за допомогою якого можливо дослідити його роботу у реальних умовах для створення сучасного вітчизняного виробництва електромобілів. Проаналізовано технологію виробництва автомобілів с традиційним несучим кузовом, що дозволило виявити вагомі недоліки. Запропоновано замість традиційного несучого кузова зробити алюмінієву раму, за технологією frame-space, на якій будуть встановлені елементи кузова та інші компоненти. Елементи кузова пропонується виготовляти з полімерного матеріалу, який не вимагає лакування і не піддається корозії, за технологією вакуумної витяжки, це дозволяє суттєво, майже вдвічі, скоротити витрати на організацію виробництва та витрати на технічне обслуговування обладнання, що істотно впливає на кінцеву вартість електромобілю. Це дозволяє зменшити вагу автомобіля до 1100 кг. Виготовлення елементів кузова з полімерних матеріалів відкриває можливості рециклінгу матеріалів, що використовуються при виробництві. Запропоновано встановити сонячні батареї на кришу та капот електромобілю, які будуть підзаряджати основну батарею і забезпечувати додаткових 0-30 км в день, що в міських умовах істотно впливатиме на витрату батареї і збільшує її пробіг. Запропоновано забезпечити електромобіль додатковою батареєю, що стало можливим завдяки рамній конструкції. Це дозволить збільшить пробіг на одній зарядці до 500 км. Запропоновано унікальна система безпеки як для самого автомобіля так і для пішоходів, велосипедистів тощо. Ця технологія запатентована і вперше буде використана в автомобільному транспорті. Життєзберігаюча бамперна система електромобілю виконана з можливістю утримання удару при виникненні дорожньо-транспортної події щонайбільше при швидкості руху транспортного засобу 30 км/год без спрацювання подушки безпеки. Система виконана із можливістю визначення відстані до іншого транспортного засобу, перешкоди, пішохода на шляху транспортного засобу системи. Також система містить щонайменше один датчик удару, який підключено до системи керування.
Luova poikkitieteellinen yhteistyö ja oppiminen
Authors: Leiviskä Eija
Published: November 2021

Tutkimukseni tarkoituksena oli tutkia luovan poikkitieteellisen yhteistyön luonnetta ja sen merkitystä. Tutkimus tarjoaa tietoa poikkitieteellisen toiminnan ominaispiirteistä, lähestymistavan tuomista eduista sekä siihen liittyvistä konflikteista ja erityisvaatimuksista. Poikkitieteellisyyden, luovuuden, oppimisen ja yhteistyön teoriat ja käsitteelliset viitekehykset ovat ohjanneet tutkimustani.
 
Kirjoitus perustuu pääosaltaan lectio præcursoriaan, joka on esitetty Helsingin yliopiston kasvatustieteellisessä tiedekunnassa 9.3.2001 väitöskirjan ”Creative interdisciplinarity : engineering, business, and art & design students’ collaboration and learning in the International Design Business Management (IDBM) program” (ISBN 951-45-9834-2) tarkastuksessa. Vastaväittäjinä toimivat professori Pekka Pihlanto Turun kauppakorkeakoulusta ja professori Inkeri Sava Taideteollisesta korkeakoulusta.
PENINGKATAN KOMPETENSI GURU MA DARUR RIDHO AL-IRSYAD AL ISLAMIYYAH PADA PEMBELAJARAN DARING MELALUI MOODLE
Authors: Maskar Sugama , Dewi Putri Sukma
Published: November 2021

Pembelajaran dalam jaringan (daring) telah menjadi sesuatu yang baru namun menjadi keharusan di Indonesia. Pemanfaatan teknologi semakin kondusif semenjak dikeluarkannya SK Mendiknas 2001 tentang pendidikan jarak jauh. Perkembangan teknologi ini menghasilkan banyak aplikasi yang bisa mendukung pembelajaran di kelas sebut saja moodle dan geogebra.  Mitra dalam kegiatan pengabdian kepada masyarakat ini adalah MA Darur Ridho. Sekolah ini berada di desa Hanura Kecamatan Teluk Pandan Kabupaten Pesawaran. Jarak mitra dari Bandar Lampung adalah 40 km, sehingga dapat ditempuh dengan waktu 40 – 60 menit. MA Darur Ridho telah berdiri cukup lama, rata-rata guru di sekolah tersebut berusia di atas 40 tahun atau guru senior. Hal ini membuat mitra cukup sulit menerapkan pembelajaran dalam jaringan. salah satu solusi untuk mengatasi permasalahan tersebut adalah dengan cara meningkatkan kompetensi guru pada penggunaan e-learning dengan cara mengadakan pelatihan bagi guru-guru MA Darur Ridho mengenai penggunaan dan pemanfaatan e-learning sebagai salah satu media pembelajaran.  Tempat pelaksanaan pelatihan akan dilakukan di laboratorium komputer MA Darur Ridho dan juga dilaksanakan secara daring melalui aplikasi Zoom Meeting. Berdasarkan nilai tes awal dan tes akhir, sebelum dan sesudah kegiatan pelatihan, menunjukan bahwa guru-guru MA Darur Ridho menjadi lebih memahami dan dapat menggunakan moda aplikasi moodle melalui tautan  http://madarurridho.kelasdaring.net. Hasil analisis data dari nilai prestest dan postest instrumen tes menunjukkan bahwa rata-rata nilainya berturut-turut adalah 44,9 dan 91,3. Hal ini menunjukkan adanya peningkatan kemampuan awal dan kemampuan akhir peserta pelatihan. Standar deviasi juga menunjukkan penyebaran yang baik yaitu 8,1 dan 3,4.Kata Kunci: Pembelajaran Daring, Moodle, Pelatihan
Bio-Hydrogen Production Using Landfill Leachate Considering Different Photo-Fermentation Processes
Authors: Barghash Hind , Okedu Kenneth E. , Al Balushi Aisha
Published: November 2021

Recently, it has become imperative to find new sustainable and renewable sources of energy, in order to avoid dependence on non-renewable traditional energy resources. This would help to overcome the depleting of natural resources for energy production. Hydrogen gas production using biological processes is one of the most attractive solutions in this regard, due to its high energy content and ecofriendly nature. Production of hydrogen using single photo-fermentation process and landfill leachate as substrate was carried out in this paper, by utilizing batch bio-reactor and anaerobic conditions. The pH value and temperature, play an essential role in a bio-hydrogen production process. Thus, in this study, the pH values considered were 6, 6.5, and 7.2, respectively, at a controlled temperature of 37 ± 1°C. This study investigated various schemes that have the possibility of producing hydrogen using; landfill leachate alone, with leachate and addition of inoculum such as sewage sludge, and with substrate such as sucrose and glucose. All experiments were conducted with and without mixing, for effective comparative study. Heat and pH pretreatment were applied in each experiment with the objectives of decreasing the activities of methane-producing bacteria and enhancing the activities of hydrogen-producing bacteria. The hydraulic retention time used in this study was 48 h, in order to obtain optimal performance of the schemes employed. Analysis of liquid leachate was performed for each experiment, and based on the obtained results, the maximum yield of hydrogen produced was 5,754 ml H2/L, with a medium pH scale of 6.0, fermentation temperature of 37 ± 1°C and constant mixing speed of 100 rpm.
Two Complementary Signaling Pathways Depict Eukaryotic Chemotaxis: A Mechanochemical Coupling Model
Authors: Zhou Lüwen , Feng Shiliang , Li Long , Lü Shouqin , Zhang Yan , Long Mian
Published: November 2021

Many eukaryotic cells, including neutrophils and Dictyostelium cells, are able to undergo correlated random migration in the absence of directional cues while reacting to shallow gradients of chemoattractants with exquisite precision. Although progress has been made with regard to molecular identities, it remains elusive how molecular mechanics are integrated with cell mechanics to initiate and manipulate cell motility. Here, we propose a two dimensional (2D) cell migration model wherein a multilayered dynamic seesaw mechanism is accompanied by a mechanical strain-based inhibition mechanism. In biology, these two mechanisms can be mapped onto the biochemical feedback between phosphoinositides (PIs) and Rho GTPase and the mechanical interplay between filamin A (FLNa) and FilGAP. Cell migration and the accompanying morphological changes are demonstrated in numerical simulations using a particle-spring model, and the diffusion in the cell membrane are simulations using a one dimensional (1D) finite differences method (FDM). The fine balance established between endogenous signaling and a mechanically governed inactivation scheme ensures the endogenous cycle of self-organizing pseudopods, accounting for the correlated random migration. Furthermore, this model cell manifests directional and adaptable responses to shallow graded signaling, depending on the overwhelming effect of the graded stimuli guidance on strain-based inhibition. Finally, the model cell becomes trapped within an obstacle-ridden spatial region, manifesting a shuttle run for local explorations and can chemotactically “escape”, illustrating again the balance required in the complementary signaling pathways.
Leader-Following Multi-Agent Coordination Control Accompanied With Hierarchical Q(λ)-Learning for Pursuit
Authors: Zhu Zhe-Yang , Liu Cheng-Lin
Published: November 2021

In this paper, we investigate a pursuit problem with multi-pursuer and single evader in a two-dimensional grid space with obstacles. Taking a different approach to previous studies, this paper aims to address a pursuit problem in which only some pursuers can directly access the evader’s position. It also proposes using a hierarchical Q(λ)-learning with improved reward, with simulation results indicating that the proposed method outperforms Q-learning.
Associations of Serum Uromodulin and Its Genetic Variants With Blood Pressure and Hypertension in Chinese Adults
Authors: Wang Yang , Du Ming-Fei , Yao Shi , Zou Ting , Zhang Xiao-Yu , Hu Gui-Lin , Chu Chao , Liao Yue-Yuan , Chen Chen , Wang Dan , Ma Qiong , Wang Ke-Ke , Sun Yue , Niu Ze-Jiaxin , Yan Rui-Chen , Yan Yu , Zhou Hao-Wei , Jia Hao , Gao Wei-Hua , Li Hao , Li Chun-Hua , Chen Fang-Yao , Gao Ke , Zhang Jie , Safirstein Robert , Wang Feng , Yang Tie-Lin , Mu Jian-Jun
Published: November 2021

Background: Uromodulin, also named Tamm Horsfall protein, has been associated with renal function and regulation of sodium homeostasis. We aimed to examine the associations of serum uromodulin levels and its genetic variants with longitudinal blood pressure (BP) changes and hypertension incidence/risk.

Methods: A total of 514 participants from the original Baoji Salt-Sensitive Study cohort were genotyped to examine the associations of genetic variations in uromodulin gene with the longitudinal BP changes and the incidence of hypertension over 8 years of follow-up. In addition, 2,210 subjects from the cohort of Hanzhong Adolescent Hypertension Study were used to investigate the relationships between serum uromodulin levels and the risk of hypertension.

Results: SNPs rs12917707 and rs12708631 in the uromodulin gene were significantly associated with the longitudinal BP changes over 8 years of follow-up. SNP rs12708631 was significantly associated with the incidence of hypertension over 8 years. In addition, gene-based analyses supported the associations of uromodulin gene with the longitudinal BP changes and hypertension incidence in Baoji Salt-Sensitive Study cohort. Furthermore, serum uromodulin levels in the hypertensive subjects were lower than in the normotensive subjects (25.5 ± 1.1 vs. 34.7 ± 0.7 ng/mL). Serum uromodulin levels decreased gradually as BP levels increased (34.6, 33.2, 27.8, and 25.0 ng/mL for subjects with normotension, high-normal, grade 1 hypertension, and grade 2 hypertension, respectively). Serum uromodulin was significantly associated with the lower risk of hypertension [0.978 (0.972–0.984)] in Hanzhong Adolescent Hypertension Study cohort.

Conclusion: This study shows that uromodulin is associated with blood pressure progression and development of hypertension.
The Pivotal Role of Invasive Functional Assessment in Patients With Myocardial Infarction With Non-Obstructive Coronary Arteries (MINOCA)
Authors: Mangiacapra Fabio , Viscusi Michele Mattia , Paolucci Luca , Nusca Annunziata , Melfi Rosetta , Ussia Gian Paolo , Grigioni Francesco
Published: November 2021

Myocardial infarction with non-obstructive coronary arteries (MINOCA) encompasses several pathophysiological mechanisms not yet fully understood. Among the latter, vasomotion abnormalities and coronary microvascular dysfunction (CMD) play a major role for both epidemiological and prognostic reasons. Despite current guidelines do not recommend routine physiological assessment of both epicardial and microvascular coronary compartments within the context of an acute myocardial infarction, several recent evidence support the critical role of a comprehensive invasive functional assessment in order to identify the underlying pathophysiological mechanism and consequently to select an appropriate therapeutic strategy. Unfortunately, optimal medical therapy for these patients is not currently established due to the lack of dedicated trials evaluating clinical outcomes of commonly used medications for secondary prevention in MINOCA patients. For this reason, additional research is warranted to provide personalized treatments for patients affected by this puzzling clinical entity.
Study on the Mechanism of Baimai Ointment in the Treatment of Osteoarthritis Based on Network Pharmacology and Molecular Docking with Experimental Verification
Authors: Zhu Yingyin , Zhong Wanling , Peng Jing , Wu Huichao , Du Shouying
Published: November 2021

Purpose: The external preparation of the Tibetan medicine formula, Baimai ointment (BMO), has great therapeutic effects on osteoarthritis (OA). However, its molecular mechanism remains almost elusive. Here, a comprehensive strategy combining network pharmacology and molecular docking with pharmacological experiments was adopted to reveal the molecular mechanism of BMO against OA.

Methods: The traditional Chinese medicine for systems pharmacology (TCMSP) database and analysis platform, traditional Chinese medicine integrated database (TCMID), GeneCards database, and DisGeNET database were used to screen the active components and targets of BMO in treating OA. A component–target (C-T) network was built with the help of Cytoscape, and the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment through STRING. Autodock Tools which was used to dock the key components and key target proteins was analyzed. Animal experiments were performed to verify the key targets of BMO. Hematoxylin–eosin and toluidine blue staining were used to observe the pathology of joints. Protein expression was determined using enzyme-linked immunosorbent assay.

Results: Bioactive compounds and targets of BMO and OA were screened. The network analysis revealed that 17-β-estradiol, curcumin, licochalone A, quercetin, and glycyrrhizic acid were the candidate key components, and IL6, tumor necrosis factor (TNF), MAPK1, VEGFA, CXCL8, and IL1B were the candidate key targets in treating OA. The KEGG indicated that the TNF signaling pathway, NF-κB signaling pathway, and HIF-1 signaling pathway were the potential pathways. Molecular docking implied a strong combination between key components and key targets. The pathology and animal experiments showed BMO had great effects on OA via regulating IL6, TNF, MAPK1, VEGFA, CXCL8, and IL1B targets. These findings were consistent with the results obtained from the network pharmacology approach.

Conclusion: This study preliminarily illustrated the candidate key components, key targets, and potential pathways of BMO against OA. It also provided a promising method to study the Tibetan medicine formula or external preparations.
Fatigue-Related Effects in the Process of Task Interruption on Working Memory
Authors: Chen Yueyuan , Fang Weining , Guo Beiyuan , Bao Haifeng
Published: November 2021

Interruption generally has a negative effect on performance by affecting working memory (WM). However, the neural mechanism of interruption has yet to be understood clearly, and previous studies have largely ignored the role of fatigue state. To address these issues, the present study explores the behavioral and electrophysiological effects of interruption on WM performance using electroencephalography (EEG) data. The moderating effect of fatigue is also explored. The participants performed spatial 2-back tasks with math task interruption, suspension interruption, and non-interruption under different fatigue states. The results show that interruption led to increased alpha activity and P300 amplitude, indicating inhibitory control to interference from irrelevant information. Analysis of P200 amplitude revealed that interruption affected attentional reallocation when resuming the primary task. Increased theta power indicated an increased demand for information maintenance during the interruption. A speeding-up effect was discovered after interruption; however, fatigue impaired cognitive ability and further exacerbated the negative effects of interruption on WM and behavioral performance. These findings contribute to a better understanding of cognitive activity during the interruption and of the interaction with fatigue, and provide further support for the theory of memory for goals (MFG).
Hippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred Mice
Authors: Deng Tingzhi , Li Jingjing , Liu Jian , Xu Fuyi , Liu Xiaoya , Mi Jia , Bergquist Jonas , Wang Helen , Yang Chunhua , Lu Lu , Song Xicheng , Yao Cuifang , Tian Geng , Zheng Qing Yin
Published: November 2021

Age-related hearing loss (ARHL) is associated with cognitive dysfunction; however, the detailed underlying mechanisms remain unclear. The aim of this study is to investigate the potential underlying mechanism with a system genetics approach. A transcriptome-wide association study was performed on aged (12–32 months old) BXD mice strains. The hippocampus gene expression was obtained from 56 BXD strains, and the hearing acuity was assessed from 54 BXD strains. Further correlation analysis identified a total of 1,435 hearing-related genes in the hippocampus (p < 0.05). Pathway analysis of these genes indicated that the impaired glutamatergic synapse pathway is involved in ARHL (p = 0.0038). Further gene co-expression analysis showed that the expression level of glutamine synthetase (Gls), which is significantly correlated with ARHL (n = 26, r = −0.46, p = 0.0193), is a crucial regulator in glutamatergic synapse pathway and associated with learning and memory behavior. In this study, we present the first systematic evaluation of hippocampus gene expression pattern associated with ARHL, learning, and memory behavior. Our results provide novel potential molecular mechanisms involved in ARHL and cognitive dysfunction association.
Panoramic Uncertainty in Vertical Perception
Authors: Stapel Janny C. , Medendorp W. Pieter
Published: November 2021

Judgments of the orientation of a visual line with respect to earth vertical are affected by panoramic visual cues. This is illustrated by the rod-and-frame effect (RFE), the finding that the perceived orientation of a luminous rod is biased by the orientation of a surrounding squared frame. In this study, we tested how the uncertainty of frame orientation affects the RFE by asking upright or tilted participants to psychometrically judge the orientation of a briefly flashed rod contained within either a circular frame, a squared frame, or either of two intermediate frame forms, called squircles, presented in various orientations. Results showed a cyclical modulation of frame-induced bias across the range of the square and squircular frame orientations. The magnitude of this bias increased with increasing squaredness of the frame, as if the more unequivocal the orientation cues of the frame, the larger the reliance on them for rod orientation judgments. These findings are explained with a Bayesian optimal integration model in which participants flexibly weigh visual panoramic cues, depending on their orientation reliability, and non-visual cues in the perception of vertical.
Metabolomic Profiles of Plasma Retinol-Associated Dyslipidemia in Men and Women
Authors: Wang Ninglin , Ru Yuan , Yang Zhiying , Sun Changxuan , Li Shanshan , Min Yan , Zhao Xueyin , Lu Ying , Hsing Ann W. , Zhu Shankuan
Published: November 2021

Background and Aims: Studies of both animals and humans show that a high intake of vitamin A is associated with a lower risk of dyslipidemia. However, an association of plasma retinol levels with dyslipidemia is unclear. Therefore, the aim of this study is to investigate an association between plasma retinol and dyslipidemia and to identify related metabolites and pathways in the general population.

Methods: We included 250 participants aged 20–80 years from the Wellness Living Laboratory (WELL) China cohort. Associations between plasma retinol levels and dyslipidemia were analyzed using adjusted logistic models. Related metabolites were identified using ANCOVA, adjusted for the false discovery rate (FDR) and used for pathway analyses. Because there are sex differences in plasma retinol levels, all analyses were conducted separately by sex.

Results: Plasma retinol was significantly higher in men than in women. A positive association between plasma retinol and dyslipidemia was found in both sexes. In men, the 2nd and 3rd tertiles showed significantly higher proportions of dyslipidemia than the 1st tertile (1st tertile vs. 2nd tertile: p = 0.026; 1st tertile vs. 3rd tertile: p = 0.003). In women, the 3rd tertile showed a significantly higher proportion of dyslipidemia than the 1st and 2nd tertile (3rd tertile vs. 1st tertile: p = 0.002, 3rd tertile vs. 2nd tertile: p = 0.002). Overall, 75 and 30 metabolites were significantly associated with retinol levels in men and women, respectively. According to these metabolites, lipid metabolic pathways, including glycerophospholipid, arachidonic acid, linoleic acid, alpha-linolenic acid, and glycosylphosphatidylinositol (GPI), as well as steroid hormone biosynthesis pathways were found to overlap across the sexes. These pathways showed that elevated retinol levels might be associated with hormone metabolism and inflammation status.

Conclusions: We found a positive association between plasma retinol levels and dyslipidemia. Related metabolomic profiles and interrupted pathways showed that such an increase might be associated with steroid hormone synthesis and inflammation. In addition, large, population-based longitudinal studies and intervention studies are needed to confirm the role of retinol in lipid metabolism and the prevention of cardiovascular disease (CVD).
Anti-VEGF Therapy in Refractory Pituitary Adenomas and Pituitary Carcinomas: A Review
Authors: Dai Congxin , Liang Siyu , Sun Bowen , Li Yong , Kang Jun
Published: November 2021

Most pituitary tumors are considered benign adenomas, and only 0.1%–0.2% of them present metastasis and are defined as pituitary carcinomas (PCs). Refractory pituitary adenomas (PAs) lie between benign adenomas and true malignant PCs and are defined as aggressive-invasive PAs, characterized by a high Ki-67 index, rapid growth, frequent recurrence, and resistance to conventional treatments. Refractory PAs and PCs are notoriously difficult to manage because of limited therapeutic options. Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis not only during development but also during pathological processes in pituitary tumors. Recently, increasing numbers of preclinical studies and clinical research have demonstrated that anti-VEGF therapy plays an important role in pituitary tumors. The purpose of this review is to report the role of VEGF in the development and pathology of pituitary tumors and the progress of anti-VEGF therapy in pituitary tumors, including refractory PAs and PCs. Previous preclinical studies indicated that cyclin-dependent kinase 5 (CDK5)-mediated VEGF expression might play a crucial role in the development of PAs. Vascular endothelial growth inhibitors have been reported as independent predictors of invasion in human PAs and have been indicated as markers for poor outcome. Furthermore, several studies have reported that angiogenesis decreases tumor sizes in experimental animal models of pituitary tumors. The expression of VEGF is relatively high in PAs; therefore, anti-VEGF therapy has been used in some refractory PAs and PCs. To date, anti-VEGF has been reported as monotherapy, in combination with temozolomide (TMZ), TMZ and radiotherapy, and with pasireotide, which might be a promising alternative therapy for refractory PAs and PCs resistant to conventional treatments. However, the role of anti-VEGF therapy in pituitary tumors is still controversial due to a lack of large-scale clinical trials. In summary, the results from preclinical studies and clinical trials indicated that anti-VEGF therapy monotherapy or in combination with other treatments may be a promising alternative therapy for refractory PAs and PCs resistant to conventional treatments. More preclinical studies and clinical trials are needed to further evaluate the exact efficacy of anti-VEGF in refractory PAs and PCs.
Diagnosis of Breast Cancer Using Radiomics Models Built Based on Dynamic Contrast Enhanced MRI Combined With Mammography
Authors: Zhao You-Fan , Chen Zhongwei , Zhang Yang , Zhou Jiejie , Chen Jeon-Hor , Lee Kyoung Eun , Combs Freddie J. , Parajuli Ritesh , Mehta Rita S. , Wang Meihao , Su Min-Ying
Published: November 2021

Objective

To build radiomics models using features extracted from DCE-MRI and mammography for diagnosis of breast cancer.

Materials and Methods

266 patients receiving MRI and mammography, who had well-enhanced lesions on MRI and histologically confirmed diagnosis were analyzed. Training dataset had 146 malignant and 56 benign, and testing dataset had 48 malignant and 18 benign lesions. Fuzzy-C-means clustering algorithm was used to segment the enhanced lesion on subtraction MRI maps. Two radiologists manually outlined the corresponding lesion on mammography by consensus, with the guidance of MRI maximum intensity projection. Features were extracted using PyRadiomics from three DCE-MRI parametric maps, and from the lesion and a 2-cm bandshell margin on mammography. The support vector machine (SVM) was applied for feature selection and model building, using 5 datasets: DCE-MRI, mammography lesion-ROI, mammography margin-ROI, mammography lesion+margin, and all combined.

Results

In the training dataset evaluated using 10-fold cross-validation, the diagnostic accuracy of the individual model was 83.2% for DCE-MRI, 75.7% for mammography lesion, 64.4% for mammography margin, and 77.2% for lesion+margin. When all features were combined, the accuracy was improved to 89.6%. By adding mammography features to MRI, the specificity was significantly improved from 69.6% (39/56) to 82.1% (46/56), p<0.01. When the developed models were applied to the independent testing dataset, the accuracy was 78.8% for DCE-MRI and 83.3% for combined MRI+Mammography.

Conclusion

The radiomics model built from the combined MRI and mammography has the potential to provide a machine learning-based diagnostic tool and decrease the false positive diagnosis of contrast-enhanced benign lesions on MRI.
Dorsal Root Entry Zone Lesioning for Brachial Plexus Avulsion Injuries: Case Series and Literature Review
Authors: Chalil Alan , Wang Qian , Abbass Mohamad , Santyr Brendan G. , MacDougall Keith W. , Staudt Michael D.
Published: November 2021

Introduction: Brachial plexus avulsion (BPA) injuries commonly occur secondary to motor vehicle collisions, usually in the young adult population. These injuries are associated with significant morbidity, and up to 90% of patients suffer from deafferentation pain. Neuromodulation procedures can be efficacious in the treatment of refractory neuropathic pain, although the treatment of pain due to BPA can be challenging. Dorsal root entry zone (DREZ) lesioning is a classical and effective neurosurgical technique which has become underutilized in treating refractory root avulsion pain.

Methods: A systematic review of the different technical nuances, procedural efficacy, and complication profiles regarding DREZ lesioning for BPA injuries in the literature is included. We also present an institutional case series of 7 patients with BPA injuries who underwent DREZ lesioning.

Results: In the literature, 692 patients were identified to have undergone DREZ lesioning for pain related to BPA. In 567 patients, the surgery was successful in reducing pain intensity by over 50% in comparison to baseline (81.9%). Complications included transient motor deficits (11%) and transient sensory deficits (11%). Other complications including permanent disability, cardiovascular complications, infections, or death were rare (<1.9%). In our case series, all but one patient achieved >50% reduction in pain intensity, with the mean pre-operative pain of 7.9 ± 0.63 (visual analog scale) reduced to 2.1 ± 0.99 at last follow-up (p < 0.01).

Conclusion: Both the literature and the current case series demonstrate excellent pain severity reduction following DREZ ablation for deafferentation pain secondary to BPA.
Comparison of Five Prophylactically Intravenous Drugs in Preventing Opioid-Induced Cough: A Bayesian Network Meta-Analysis of Randomized Controlled Trials
Authors: Dong Yunxia , Chang Xiaohan
Published: November 2021

Background: Due to the absence of direct comparisons of different therapeutic drugs in preventing opioid-induced cough (OIC) during the induction of general anesthesia, clinicians often faced difficulties in choosing the optimal drug for these patients. Hence, this network meta-analysis was conducted to solve this problem.

Methods: Online databases, including Pubmed, Embase, Web of Science, Cochrane, and Google Scholar, were searched comprehensively to identify eligible randomized controlled trials (RCTs), up to March 15th, 2021. Within a Bayesian framework, network meta-analysis was performed by the “gemtc” version 0.8.2 package of R-3.4.0 software, and a pooled risk ratio (RR) associated with 95% credible interval (CrI) was calculated.

Results: A total of 20 RCTs were finally enrolled, and the overall heterogeneity for this study was low to moderate. Traditional pair-wise meta-analysis results indicated that all of the five drugs, namely, lidocaine, ketamine, dezocine, butorphanol, and dexmedetomidine could prevent OIC for four clinical outcomes, compared with the placebo (all p-values < 0.05). Moreover, dezocine had the best effect, compared with that of the other drugs (all p-values < 0.05). Network meta-analysis results suggested that the top three rank probabilities for four clinical outcomes from best to worst were dezocine, butorphanol, and ketamine based on individual/cumulative rank plots and surface under the cumulative ranking curve (SUCRA) probabilities. The node-splitting method indicated the consistency of the direct and indirect evidence.

Conclusions: Our results indicated that all of these five drugs could prevent OIC compared with the placebo. Moreover, the top three rank probabilities for four clinical outcomes from best to worst were dezocine, butorphanol, and ketamine. Our results were anticipated to provide references for guiding clinical research, and further high-quality RCTs were required to verify our findings.

Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021243358].
Knockout of AMPKα2 Blocked the Protection of Sestrin2 Overexpression Against Cardiac Hypertrophy Induced by Pressure Overload
Authors: Zhang Nan , Liao Hai-Han , Feng Hong , Mou Shan-Qi , Li Wen-Jing , Aiyasiding Xiahenazi , Lin Zheng , Ding Wen , Zhou Zi-Ying , Yan Han , Chen Si , Tang Qi-Zhu
Published: November 2021

Objectives: Sestrin2 (Sesn2) has been demonstrated to be a cysteine sulfinyl reductase and protects cells from multiple stress insults, including hypoxia, endoplasmic reticulum stress, and oxidative stress. However, the roles and mechanisms of Sesn2 in pressure overload-induced mouse cardiac hypertrophy have not been clearly clarified. This study intended to investigate whether sestrin2 (Sesn2) overexpression could prevent pressure overload-induced cardiac hypertrophy via an AMPKα2 dependent pathway through conditional knockout of AMPKα2.

Methods and results: Sesn2 expression was significantly increased in mice hearts at 2 and 4 weeks after aortic banding (AB) surgery, but decreased to 60–70% of the baseline at 8 weeks. Sesn2 overexpression (at 3, 6, and 9 folds) showed little cardiac genetic toxicity in transgenic mice. Cardiac dysfunctions induced by pressure overload were attenuated by cardiomyocyte-specific Sesn2 overexpression when measured by echocardiography and hemodynamic analysis. Results of HE and PSR staining showed that Sesn2 overexpression significantly alleviated cardiac hypertrophy and fibrosis in mice hearts induced by pressure overload. Meanwhile, adenovirus-mediated-Sesn2 overexpression markedly suppressed angiotensin II-induced neonatal rat cardiomyocyte hypertrophy in vitro. Mechanistically, Sesn2 overexpression increased AMPKα2 phosphorylation but inhibited mTORC1 phosphorylation. The cardiac protections of Sesn2 overexpression were also via regulating oxidative stress by enhancing Nrf2/HO-1 signaling, restoring SOD activity, and suppressing NADPH activity. Particularly, we first proved the vital role of AMPKα2 in the regulation of Sesn2 with AMPKα2 knockout (AMPKα2-/-) mice and Sesn2 transgenic mice crossed with AMPKα2-/-, since Sesn2 overexpression failed to improve cardiac function, inhibit cardiac hypertrophy and fibrosis, and attenuate oxidative stress after AMPKα2 knockout.

Conclusion: This study uniquely revealed that Sesn2 overexpression showed little genetic toxicity in mice hearts and inhibited mTORC1 activation and oxidative stress to protect against pressure overload-induced cardiac hypertrophy in an AMPKα2 dependent pathway. Thus, interventions through promoting Sesn2 expression might be a potential strategy for treating pathological cardiac hypertrophy and heart failure.
Game Analysis on Epidemic Prevention and Resuming Production: Based on China’s Experience With COVID-19
Authors: Zhuang Weiqing , Wu Qiong , Jiang Ming , Ichiro Nakamoto , Zhang Tingyi , Yu Xuelian
Published: November 2021

Since the outbreak of COVID-19, it became urgent to deal with the relationship between the prevention and control of the epidemic and the resumption of work and production. The purpose of this study is to observe and describe which approach seemed more important for the Chinese government and people, and how this trend evolved through time. To this end, a game model of resuming production and preventing the epidemic is constructed, using the evolutionary stable strategy (ESS). By combing China’s measures on epidemic prevention and resuming production during critical periods of epidemic outbreak, it is clarified that the present stage is considered a period of equal emphasis on both epidemic prevention and resuming production. Based on the dynamic between these two strategies and further theoretical research, present policies should equally focus on both preventive and controlling measures as well as on the socioeconomic development for most countries in the world.
Bibliometric Differences Between WEIRD and Non-WEIRD Countries in the Outcome Research on Solution-Focused Brief Therapy
Authors: Beyebach Mark , Neipp Marie-Carmen , Solanes-Puchol Ángel , Martín-del-Río Beatriz
Published: November 2021

Solution Focused Brief Therapy (SFBT) developed in parallel to Positive Psychology, as a type of intervention that also emphasizes the strengths and resources of clients. The aim of this study was to examine the development of outcome research on SFBT and to determine whether it is predominantly carried out in Western, Educated, Industrialized, Rich and Democratic (WEIRD) countries. A literature review was conducted using a bibliometric methodology, identifying: (a) authors and countries, (b) time trends, (c) language of publications; (d) and journals; (e) samples on which they were tested; (f) characteristics of interventions; and (g) main study designs. A total of 365 original outcome research articles published in scientific journals on solution-focused interventions were extracted. The results show that outcome research on SFBT has grown steadily over the last three decades. Although it started in WEIRD countries, the number of outcome research publications generated in non-WEIRD countries is now higher. There is little international collaboration and, although English is the main language of publication in WEIRD countries, English, Chinese and Parsi predominate in non-WEIRD countries. Productivity is low and most authors have only published one paper. The journals that have published the most papers have a very diverse visibility. The tested interventions are conducted both in clinical and non-clinical samples; mostly in individual and group format; face-to-face; and not only in the form of psychotherapy, but also as coaching and school interventions. Almost half of the publications are randomized controlled trials. The results confirm the wide applicability of SFBT as a single or main component of psychosocial interventions. They support the claim that solution-focused interventions are not a WEIRD practice, but a global practice.
The Implementation of a Primary Care-Based Integrated Mobile Health Intervention for Stroke Management in Rural China: Mixed-Methods Process Evaluation
Authors: Gong Enying , Sun Lixin , Long Qian , Xu Hanzhang , Gu Wanbing , Bettger Janet Prvu , Tan Jingru , Ma Jixiang , Jafar Tazeen Hasan , Oldenburg Brian , Yan Lijing L.
Published: November 2021

Background: There is a lack of evidence concerning the effective implementation of strategies for stroke prevention and management, particularly in resource-limited settings. A primary-care-based integrated mobile health intervention (SINEMA intervention) has been implemented and evaluated via a 1-year-long cluster-randomized controlled trial. This study reports the findings from the trial implementation and process evaluation that investigate the implementation of the intervention and inform factors that may influence the wider implementation of the intervention in the future.

Methods: We developed an evaluation framework by employing both the RE-AIM framework and the MRC process evaluation framework to describe the implementation indicators, related enablers and barriers, and illustrate some potential impact pathways that may influence the effectiveness of the intervention in the trial. Quantitative data were collected from surveys and extracted from digital health monitoring systems. In addition, we conducted quarterly in-depth interviews with stakeholders in order to understand barriers and enablers of program implementation and effectiveness. Quantitative data analysis and thematic qualitative data analysis were applied, and the findings were synthesized based on the evaluation framework.

Results: The SINEMA intervention was successfully implemented in 25 rural villages, reached 637 patients with stroke in rural Northern China during the 12 months of the trial. Almost 90% of the participants received all follow-up visits per protocol, and about half of the participants received daily voice messages. The majority of the intervention components were adopted by village doctors with some adaptation made. The interaction between human-delivered and technology-enabled components reinforced the program implementation and effectiveness. However, characteristics of the participants, doctor-patient relationships, and the healthcare system context attributed to the variation of program implementation and effectiveness.

Conclusion: A comprehensive evaluation of program implementation demonstrates that the SINEMA program was well implemented in rural China. Findings from this research provide additional information for program adaptation, which shed light on the future program scale-up. The study also demonstrates the feasibility of combining RE-AIM and MRC process evaluation frameworks in process and implementation evaluation in trials.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03185858.
Past, Present, and Future of the Scaling Relations of Galaxies and Active Galactic Nuclei
Authors: D’Onofrio Mauro , Marziani Paola , Chiosi Cesare
Published: November 2021

We review the properties of the established Scaling Relations (SRs) of galaxies and active galactic nuclei (AGN), focusing on their origin and expected evolution back in time, providing a short history of the most important progresses obtained up to now and discussing the possible future studies. We also try to connect the observed SRs with the physical mechanisms behind them, examining to what extent current models reproduce the observational data. The emerging picture clarifies the complexity intrinsic to the galaxy formation and evolution process as well as the basic uncertainties still affecting our knowledge of the AGN phenomenon. At the same time, however, it suggests that the detailed analysis of the SRs can profitably contribute to our understanding of galaxies and AGN.
Effect of Microvascular Invasion on the Prognosis in Hepatocellular Carcinoma and Analysis of Related Risk Factors: A Two-Center Study
Authors: Yanhan Wang , Lianfang Lu , Hao Liu , Yunfeng Ding , Nannan Song , Fanfan Lin , Chengzhan Zhu , Meilong Wu , Chuandong Sun
Published: November 2021

Objective: Microvascular invasion is considered to initiate intrahepatic metastasis and postoperative recurrence of hepatocellular carcinoma (HCC). We aimed to analyze the effect of MVI on the prognosis in HCC and identify related risk factors for microvascular invasion (MVI).

Methods: The clinical data of 553 HCC patients who underwent liver surgery at Qingdao University from January 2014 to December 2018 and 89 patients at Beijing Tsinghua Changgung Hospital treated between October 2014 and October 2019 were collected retrospectively. We explored the impact of MVI on the prognosis of patients with HCC using Kaplan-Meier analysis. We conducted logistic regression analysis to identify variables significantly related to MVI.

Results: Pathological examination confirmed the presence of MVI in 265 patients (41.3%). Six factors independently correlated with MVI were incorporated into the multivariate logistic regression analysis: Edmondson-Steiner grade [odds ratio (OR) = 3.244, 95%CI: 2.243–4.692; p < 0.001], liver capsule invasion (OR = 1.755; 95%CI: 1.215–2.535; p = 0.003), bile duct tumor thrombi (OR = 20.926; 95%CI: 2.552–171.553; p = 0.005), α-fetoprotein (> 400 vs. < 400 ng/ml; OR = 1.530; 95%CI: 1.017–2.303; p = 0.041), tumor size (OR = 1.095; 95%CI: 1.027–1.166; p = 0.005), and neutrophil-lymphocyte ratio (OR = 1.086; 95%CI: 1.016–1.162; p = 0.015). The area under the receiver operating characteristic curve (AUC) was 0.743 (95%CI: 0.704–0.781; p < 0.001), indicating that our logistic regression model had significant clinical usefulness.

Conclusions: We analyzed the effect of MVI on the prognosis in HCC and evaluated the risk factors for MVI, which could be helpful in making decisions regarding patients with a high risk of recurrence.
Reimagining the Power of Nucleic Acids as Therapeutic and Diagnostic Agents
Authors: Berdis Anthony
Published: November 2021

The central dogma of molecular biology proposes that in a typical cell, the flow of genetic information proceeds from DNA to RNA to polypeptide [...]
c-Met-Specific Chimeric Antigen Receptor T Cells Demonstrate Anti-Tumor Effect in c-Met Positive Gastric Cancer
Authors: Kang Chung Hyo , Kim Yeongrin , Lee Da Yeon , Choi Sang Un , Lee Heung Kyoung , Park Chi Hoon
Published: November 2021

Chimeric antigen receptor (CAR) technology has been highlighted in recent years as a new therapeutic approach for cancer treatment. Although the impressive efficacy of CAR-based T cell adoptive immunotherapy has been observed in hematologic cancers, limited effect has been reported on solid tumors. Approximately 20% of gastric cancer (GC) patients exhibit a high expression of c-Met. We have generated an anti c-Met CAR construct that is composed of a single-chain variable fragment (scFv) of c-Met antibody and signaling domains consisting of CD28 and CD3ζ. To test the CAR construct, we used two cell lines: the Jurkat and KHYG-1 cell lines. These are convenient cell lines, compared to primary T cells, to culture and to test CAR constructs. We transduced CAR constructs into Jurkat cells by electroporation. c-Met CAR Jurkat cells secreted interleukin-2 (IL-2) only when incubated with c-Met positive GC cells. To confirm the lytic function of CAR, the CAR construct was transduced into KHYG-1, a NK/T cell line, using lentiviral particles. c-Met CAR KHYG-1 showed cytotoxic effect on c-Met positive GC cells, while c-Met negative GC cell lines were not eradicated by c-Met CAR KHYG-1. Based on these data, we created c-Met CAR T cells from primary T cells, which showed high IL-2 and IFN-γ secretion when incubated with the c-Met positive cancer cell line. In an in vivo xenograft assay with NSG bearing MKN-45, a c-Met positive GC cell line, c-Met CAR T cells effectively inhibited the tumor growth of MKN-45. Our results show that the c-Met CAR T cell therapy can be effective on GC.