bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of HER2-Positive Early Breast Cancer in Italy: A Maze Presenting Opportunities and Challenges
Authors: Stucci Luigia Stefania , Pisino Marco , D’Addario Claudia , Grassi Teresa , Toss Angela
Published: May 2022

The management of human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer (BC) has changed in recent years thanks to the introduction of anti-HER2 agents in clinical practice as standard of care in the neoadjuvant setting. In this scenario, we probed the issue of which HER2-positive BC patients are eligible for neoadjuvant or for adjuvant treatment, since these therapeutic strategies seem to be mutually exclusive in clinical practice according to an Italian drug surveillance system. We reviewed both alternatives to establish which is more suitable, considering the anti-HER2 drugs available in Italy. Randomized clinical trials demonstrated a similar clinical benefit for chemotherapy administered as neoadjuvant therapy or adjuvant therapy. A meta-analysis, including 11,955 patients treated with neoadjuvant therapy, demonstrated an improvement in event-free survival (EFS) and overall survival (OS). Moreover, the recent APHINITY trial, analyzed at 6 years follow-up, demonstrated the superiority of the combination pertuzumab–trastuzumab versus trastuzumab–placebo in previously untreated patients. A greater benefit was found in patients with positive lymph nodes treated in the adjuvant setting. Our analysis underlines the need for a therapeutic decision-making algorithm, which is still unavailable, to support clinicians in identifying patients suitable for neoadjuvant or adjuvant therapy. Further prospective clinical trials should be performed in collaboration with other Italian Breast Cancer Centers to establish the best strategy to be adopted in early HER2+ BC.
A Novel Affinity Engineered Anti-CD47 Antibody With Improved Therapeutic Index That Preserves Erythrocytes and Normal Immune Cells
Authors: Thaker Youg R. , Rivera Ianne , Pedros Christophe , Singh Alok R. , Rivero-Nava Laura , Zhou Heyue , Swanson Barbara A. , Kerwin Lisa , Zhang Yanliang , Gray J. Dixon , Kaufmann Gunnar F. , Ji Henry , Allen Robert D. , Bresson Damien
Published: May 2022

Therapeutic blockade of the CD47/SIRPα axis by small molecules or monoclonal antibodies (mAbs) is a proven strategy to enhance macrophages-mediated anti-tumor activity. However, this strategy has been hampered by elevated on-target toxicities and rapid clearance due to the extensive CD47 expression on normal cells (“antigen sink”) such as red blood cells (RBCs). To address these hurdles, we report on the development of STI-6643, an affinity-engineered fully human anti-CD47 IgG4 antibody with negligible binding to normal cells. STI-6643 exhibited no hemagglutination activity on human RBCs at concentrations up to 300 µg/mL yet specifically blocked the CD47/SIPRα interaction. Of particular interest, STI-6643 preserved T cell functionality in vitro and showed significantly lower immune cell depletion in vivo in contrast to three previously published competitor reference anti-CD47 clones Hu5F9, AO-176 and 13H3. In cynomolgus monkeys, STI-6643 was well-tolerated at the highest dose tested (300 mg/kg/week) and provided favorable clinical safety margins. Finally, STI-6643 displayed comparable anti-tumor activity to the high-affinity reference clone Hu5F9 in a RAJI-Fluc xenograft tumor model as monotherapy or in combination with anti-CD20 (rituximab) or anti-CD38 (daratumumab) mAbs. These data suggest that STI-6643 possesses the characteristics of an effective therapeutic candidate given its potent anti-tumor activity and low toxicity profile.
Research Advances in Genetic Mechanisms of Major Cucumber Diseases Resistance
Authors: He Yujin , Wei Mingming , Yan Yanyan , Yu Chao , Cheng Siqi , Sun Yihan , Zhu Xiangtao , Wei Lingling , Wang Huasen , Miao Li
Published: May 2022

Cucumber (Cucumis sativus L.) is an important economic vegetable crop worldwide that is susceptible to various common pathogens, including powdery mildew (PM), downy mildew (DM), and Fusarium wilt (FM). In cucumber breeding programs, identifying disease resistance and related molecular markers is generally a top priority. PM, DM, and FW are the major diseases of cucumber in China that cause severe yield losses and the genetic-based cucumber resistance against these diseases has been developed over the last decade. Still, the molecular mechanisms of cucumber disease resistance remain unclear. In this review, we summarize recent findings on the inheritance, molecular markers, and quantitative trait locus mapping of cucumber PM, DM, and FM resistance. In addition, several candidate genes, such as PM, DM, and FM resistance genes, with or without functional verification are reviewed. The data help to reveal the molecular mechanisms of cucumber disease resistance and provide exciting new opportunities for further resistance breeding.
GhHAI2, GhAHG3, and GhABI2 Negatively Regulate Osmotic Stress Tolerance via ABA-Dependent Pathway in Cotton (Gossypium hirsutum L.)
Authors: Shazadee Hamna , Khan Nadeem , Wang Lu , Wang Xinyu
Published: May 2022

The type 2C protein phosphatases (PP2Cs) are well known for their vital roles in plant drought stress responses, but their molecular mechanisms in cotton (Gossypium hirsutum L.) remain largely unknown. Here, we investigated the role of three clade A PP2C genes, namely, GhHAI2, GhAHG3, and GhABI2, in regulating the osmotic stress tolerance in cotton. The transcript levels of GhHAI2, GhAHG3, and GhABI2 were rapidly induced by exogenous abscisic acid (ABA) and polyethylene glycol (PEG) treatment. Silencing of GhHAI2, GhAHG3, and GhABI2 via virus-induced gene silencing (VIGS) improved osmotic tolerance in cotton due to decreased water loss, increase in both relative water content (RWC) and photosynthetic gas exchange, higher antioxidant enzyme activity, and lower malondialdehyde (MDA) content. The root analysis further showed that GhHAI2, GhAHG3, and GhABI2-silenced plants were more responsive to osmotic stress. Yeast two-hybrid (Y2H) and luciferase complementation imaging (LCI) assays further substantiated that GhHAI2, GhAHG3, and GhABI2 interact with the core receptors of ABA signaling, GhPYLs. The expression of several ABA-dependent stress-responsive genes was significantly upregulated in GhHAI2-, GhAHG3-, and GhABI2-silenced plants. Our findings suggest that GhHAI2, GhAHG3, and GhABI2 act as negative regulators in the osmotic stress response in cotton through ABA-mediated signaling.
Coping and Resilience Among Endurance Athletes During the COVID-19 Pandemic
Authors: Harman Brian , Dessart Grégory , Puke Liene , Philippe Roberta Antonini
Published: May 2022

COVID-19 lockdowns constrained the training opportunities of athletes resulting in physical and mental hardship. In this study, athletes involved in the outdoor endurance sports of running, cycling or swimming were recruited through Facebook groups and using online mailing lists. The final sample (n = 3,551) consisted of 576 female respondents (16.2%), and 2,975 male respondents (83.8%). The mean age of participants was 44.13  years (min = 16, max = 83, and SD = 9.84). An online survey was designed to measure variables relevant to athletes’ mental health; resilience and emotion regulation strategies; mobility restrictions; training routines; personal involvement in endurance sports; age; gender; and country of residence. Overall, the results of our study indicate that during lockdown, decreases in training volume, lower lockdown-specific resilience, and holding more negative perceptions about lockdown mobility restrictions (perceived strictness) all contributed to perceived barriers to training. In the analysis, athletes’ relative observance of mobility restrictions was controlled for. Athletes exhibiting high personal commitment to their sports displayed: greater lockdown resilience, a greater use of adaptive coping strategies, and lower levels of perceived barriers to training.
Benefits of Psychological Androgyny in Adolescence: The Role of Gender Role Self-Concept in School-Related Well-Being
Authors: Korlat Selma , Holzer Julia , Schultes Marie-Therese , Buerger Sarah , Schober Barbara , Spiel Christiane , Kollmayer Marlene
Published: May 2022

It has been repeatedly shown that the extent to which individuals adopt stereotypically masculine and feminine traits in their self-concept impacts their health and well-being. This is especially important in adolescence, when developmental changes and social pressures to conform to stereotypical gender roles can affect psychological functioning. However, previous studies investigating relationship between gender role self-concept and well-being in adolescents focused mostly on general well-being rather than well-being in specific contexts. Given that school is one of the most important contexts for adolescents’ development and well-being, the aim of this study was to investigate differences between adolescents with different gender role self-concepts (masculine, feminine, androgynous and undifferentiated) in school-related well-being. In line with the new conceptualization of well-being uniting hedonic (pleasure attainment and pain avoidance) and eudemonic (self-actualization and having meaningful purpose in one’s life) approaches, the present study used a measure of school-related well-being encompassing five domains suggested in the EPOCH (Engagement, Perseverance, Optimism, Connectedness and Happiness) model as well as a superordinate well-being factor. A total of 999 Austrian adolescents (52.2% girls, Mage = 13.79, SDage = 1.53) answered inventories assessing adolescents’ gender role self-concept (GRI-JUG) and school-related well-being (EPOCH-G-S). The results supported the androgyny model of well-being, showing clear advantages of having both positive masculine and feminine qualities in one’s self-concept for optimal levels of school-related well-being. In addition, our results indicated the strong importance of femininity in adolescence and the school context. Theoretical and practical implications are discussed.
Leisure Satisfaction, Personality, and Psychosexual Adjustment Among College Students: A Latent Profile Analysis
Authors: Xia Ximei , Wang Xiaotian , Wang Yuting
Published: May 2022

Although the factors influencing sexual health have been explored by researchers, the impact of leisure and personality on psychosexual adjustment and the interaction of these two factors remain unknown. This study investigated the relationship between leisure satisfaction and psychosexual adjustment based on the compensation theory and the social learning theory. The differences in psychosexual adjustment across different personality types were also explored. Finally, we examined the interaction between personality and leisure satisfaction based on the personal-environment fit models. The participants in this study were 1,161 college students. The results supported all the hypotheses proposed. There was a significant positive correlation between leisure satisfaction and psychosexual adjustment. Participants of four personality types (the overcontrolled, high-moderate, low-moderate, and resilient groups) had different performance in psychosexual adjustment. The resilient group had the highest scores, while the overcontrolled group had the lowest scores. The results suggest that there is an interaction between personality and leisure satisfaction. Our research could enrich the research contents of leisure and personality and provide a practical basis for the improvement of college students in psychosexual adjustment.
The Impact of Chinese EFL Teachers’ Emotion Regulation and Resilience on Their Success
Authors: Li Ling , Lv Lili
Published: May 2022

Success in EFL/ESL contexts by teachers requires developing some essential characteristics consisting of several interacting variables and underlying constructs. With the rise of positive psychology, the concepts of resilience and emotion regulation and their roles in the EFL/ESL milieu have caught attention. In this line, the present study aims to investigate whether there would be any relationship among EFL teachers’ resilience, emotion regulation, and their success in the Chinese context. In addition, we tried to examine the predictive power of EFL teachers’ resilience and emotion regulation toward their success. To that end, an online Likert scale questionnaire including items on teachers’ emotion regulation, teachers’ resilience, and teaching success was distributed to 323 Chinese EFL teachers. The participants were selected based on convenience sampling. Spearman Rho correlation index and multiple regression analysis along with ANOVA were used to analyze the collected data. The findings showed a direct and positive correlation among EFL teachers’ emotion regulation, resilience, and success. Furthermore, it was indicated that EFL teachers’ resilience was more powerful in terms of predicting success than their emotion regulation. Our findings imply that teacher education programs can enhance EFL teachers’ success through training resilience strategies and emotion regulation skills.
Regulatory and Educational Initiatives to Prevent Food Choking Injuries in Children: An Overview of the Current Approaches
Authors: Lorenzoni Giulia , Hochdorn Alexander , Beltrame Vriz Giulia , Francavilla Andrea , Valentini Romina , Baldas Solidea , Cuestas Giselle , Rodriguez Hugo , Gulati Achal , van As A. B. Sebastian , Gregori Dario
Published: May 2022

Choking injuries are one of the major causes of death among children ages 0–3, and most of these injuries are related to food. This work provides an overview of the current recommendations for food choking prevention and educational targets as a basis for developing a unified common set of knowledge for primary prevention policies development. Guidelines published by professional membership organizations and national governments in the English language were considered. All of these guidelines provide lists of hazardous food items and recommendations for food preparation to minimize choking hazard. Together with recommendations for food preparation, also recommendations aimed at stakeholders (food manufacturers, health care providers, and public authorities) are provided, underlining that this severe public health problem should be further addressed by adopting integrated public health interventions. Our overview stressed the importance of developing educational and primary prevention policies to sensitize adult supervisors and to regulate dangerous food products in the market.
Design of a Super Twisting Sliding Mode Controller for an MR Damper-Based Semi-Active Prosthetic Knee
Authors: Assfaw Dawit , Seid Solomon
Published: May 2022

A large number of transfemoral amputees living in low-income countries could not access a much-needed prosthesis. Hence, affordable semi-active prosthetic knees have been designed in recent years. As the swing phase of the gait cycle is unstable as compared to the stance phase, these designs could not perfectly mimic this phase of a healthy human being. In contribution toward such a gap, this study proposes the modeling and design of a robust controller for magnetorheological (MR) damper-based semi-active prosthetic knee. A dynamic model representation for the swing phase of the single-axis knee is derived first. Subsequently, an MR damper valve model is developed. Then, a higher-order sliding mode controller is designed and evaluated for its stability and performance. The numerical simulation results show that the super twisting sliding mode controller improves the semi-active prosthetic knee’s tracking efficiency. The design exhibited the finest performance, providing a low normalized mean square error as compared to previous designs. The variable speed performance and robustness evaluation for this controller also showed its ability to continue providing excellent performance in the presence of disturbances.
Storm the Capitol: Linking Offline Political Speech and Online Twitter Extra-Representational Participation on QAnon and the January 6 Insurrection
Authors: Lee Claire Seungeun , Merizalde Juan , Colautti John D. , An Jisun , Kwak Haewoon
Published: May 2022

The transfer of power stemming from the 2020 presidential election occurred during an unprecedented period in United States history. Uncertainty from the COVID-19 pandemic, ongoing societal tensions, and a fragile economy increased societal polarization, exacerbated by the outgoing president's offline rhetoric. As a result, online groups such as QAnon engaged in extra political participation beyond the traditional platforms. This research explores the link between offline political speech and online extra-representational participation by examining Twitter within the context of the January 6 insurrection. Using a mixed-methods approach of quantitative and qualitative thematic analyses, the study combines offline speech information with Twitter data during key speech addresses leading up to the date of the insurrection; exploring the link between Trump's offline speeches and QAnon's hashtags across a 3-day timeframe. We find that links between online extra-representational participation and offline political speech exist. This research illuminates this phenomenon and offers policy implications for the role of online messaging as a tool of political mobilization.
Early Mini-Invasive Treatment of Persistent Cervical Dysplasia: Clinical Outcome and Psycho-Relational Impact
Authors: Plotti Francesco , Rossini Gianmarco , Ficarola Fernando , De Cicco Nardone Carlo , Montera Roberto , Guzzo Federica , Luvero Daniela , Fabris Silvia , Angioli Roberto , Terranova Corrado
Published: May 2022

Introduction

After the diagnosis of L-SIL, 77. 3% had a persistent infection and anomalous Pap Test results. Many of these patients had highlighted psychological consequences such as anxiety, hypochondria, fear of cancer, and sexual problems. Several studies suggested that the clearance of HR-HPV infection could be accelerated by cervical excisional procedures, especially in L-SIL. In consideration of the psychological implications for HPV infection and related dysplasia in patients with CIN1 at PAP-smear and HR-HPV positivity at least for 6 months, we decided to plan a prospective study where we tried to anticipate excisional cervical using a minimally invasive treatment: thin loop electrosurgical excision procedure (t-LEEP). This study aims to analyze the clearance of HR-HPV after 6 and 12 months, clinical outcomes related to t-LEEP, and the psycho-relational impact at 12 months after t-LEEP.

Materials and Methods

We enrolled patients with the diagnosis of L-SIL at PAP-smear and HR-HPV positivity with a persistent CIN 1 (at least for 6 months), confirmed by cervical biopsy. All enrolled patients underwent t-LEEP. We followed prospectively and performed for all patients the HPV DNA test at 6 (T1) and 12 months (T2) and STAI-Y and FSFI scores at T0 and T2.

Results

We prospectively enrolled 158 patients, 22 are excluded for the established criteria. Patients with HR-HPV and CIN 1 lesions treated with t-LEEP had an overall clearance of 83.8% at T2. In subgroups analysis at T2, we had a regression: in smoker 71.8%, in contraceptive users 69.5%, in patients aged <25 years 100%, aged 25–30 years 85%, aged 30–35 years 94.4%, aged 35–40 years 92%, and aged ≥40 years 89.1%, in HPV-16 96.4%, in HPV-53 89.5%, in HPV-18 87.5%, in HPV-31 86.6%, and in coinfected 3.5%. STAI-Y and FSFI after t-LEEP (T2) were statistically significant, reducing anxiety status and improving sexual function.

Conclusion

Based on these results, the use of t-LEEP in patients with persistent CIN 1 and HPV-HR at least for 6 months could be useful for accelerating HPV-HR clearance, in particular, for a subpopulation patient with an increased risk of progression and/or patients with psychological and sexual consequences of carrying an HR-HPV infection.
Rethinking the Selection of Pathological T-Classification for Non-Small-Cell Lung Cancer in Varying Degrees of Visceral Pleural Invasion: A SEER-Based Study
Authors: Fang Pu , Cheng Jiayi , Lu Youjin , Fu Lin
Published: May 2022

Background

The T classification of non-small-cell lung cancer (NSCLC) was upgraded from T1 to T2 when accompanied by visceral pleural invasion (VPI). However, the association between VPI and prognostic outcomes was obscure in NSCLC patients with â‰¤3 cm tumor size (TS), which leaded the controversy of selection of T classification. The goal was to evaluate the effect of VPI on the prognosis of NSCLC with â‰¤ 3cm TS and present a modified T classification.

Methods

A total of 14,934 NSCLC patients without distant metastasis were recruited through a retrospective study in the SEER database. The effect of VPI on lung cancer specific survival (LCSS) was evaluated using survival curve and COX regression analysis in NSCLC patients with ≤3 cm TS.

Results

Although there was no difference of the LCSS of PL0 and PL1 patients with ≤2 cm TS in patients without lymph node (LN) metastasis, the LCSS was lower in PL2 patients than those in PL0 (T1a: p < 0.001; T1b: p = 0.001). Moreover, the LCSS was decreased in PL1 and PL2 patients with 2–3 cm TS compared with PL0 (T1c: PL1, p < 0.001; PL2, p = 0.009) of patients without LN metastasis. No difference of LCSS was observed in patients with LN metastasis between PL0 with PL1 and PL2.

Conclusion

In NSCLC patients without LN metastasis and TS ≤ 2 cm, tumor with PL1 should remain defined as T1, tumor with PL2 should be defined as T2. However, 2–3 cm TS patients with PL1 or PL2 should both defined as T2. Meanwhile, ≤3 cm TS patients with LN metastasis can be regarded as T1, whether NSCLC patients accompanied with PL1 or PL2.
Striving to Fill in Gaps between Clinical Practice and Standards: The Evolution of a Pan-Canadian Approach to Patient-Reported Outcomes Use
Authors: Caissie Amanda , Olson Robert , Barbera Lisa , O’Donnell Jennifer , Davis Carol-Anne , Croke Jennifer , Bird Louise , Kildea John , Brown Erika , Brundage Michael , Milosevic Michael
Published: May 2022

Despite the known importance and necessity of the standardized collection and use of patient-reported outcomes (PROs), there remain challenges to successful clinical implementation. Facilitated through a quality improvement initiative spearheaded by the Canadian Partnership for Quality Radiotherapy (CPQR), and now guided by the Canadian Association of Radiation Oncology (CARO)’s Quality and Standards Committee, patient representatives and early-adopter radiation treatment programs continue to champion the expansion of PROs initiatives across the country. The current review discusses the evolution of a pan-Canadian approach to PROs use, striving to fill in gaps between clinical practice and guideline recommendations through multi-centre and multidisciplinary collaboration.
Neoadjuvant Short-Course Radiotherapy Followed by Consolidation Chemotherapy before Surgery for Treating Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis
Authors: Liao Chun-Kai , Kuo Ya-Ting , Lin Yueh-Chen , Chern Yih-Jong , Hsu Yu-Jen , Yu Yen-Lin , Chiang Jy-Ming , Hsieh Pao-Shiu , Yeh Chien-Yuh , You Jeng-Fu
Published: May 2022

Neoadjuvant short course radiotherapy (SCRT) followed by consolidation chemotherapy (CCT) is an alternative treatment for locally advanced rectal cancer (LARC). We performed this systematic review and meta-analysis to explore the tumor response and oncological outcomes of this new approach compared to conventional chemoradiotherapy (CRT). An online search of the PubMed, Embase, and Cochrane Library databases was performed. This review included 7507 patients from 14 different cohorts. The pCR rate was higher with SCRT + CCT than that with CRT (RR: 1.60; 95% CI: 1.35–1.91; p < 0.01). SCRT + CCT provided a higher ypN0 response (RR: 1.06; 95% CI: 1.01–1.12; p = 0.02). There were no differences in R0 resection and positive CRM rates; however, more sphincter-preservation surgeries were performed in the SCRT + CCT arm (RR: 1.06; 95% CI: 1.01–1.11; p = 0.02). There was no difference in the OS and DFS between the SCRT + CCT and the CRT arms (OS: HR: 0.85, p = 0.07; DFS: HR: 0.88, p = 0.08). The compliance and toxicity were comparable between the SCRT and CRT groups. In the subgroup analysis, patients who underwent four or more cycles of CCT had better pCR and DFS events. Therefore, SCRT followed by consolidation chemotherapy might be an effective alternative treatment for LARC.
Exploiting the Moth–Flame Optimization Algorithm for Optimal Load Management of the University Campus: A Viable Approach in the Academia Sector
Authors: Ullah Ibrar , Hussain Irshad , Rehman Khalid , Wróblewski Piotr , Lewicki Wojciech , Kavin Balasubramanian Prabhu
Published: May 2022

Unbalanced load condition is one of the major issues of all commercial, industrial and residential sectors. Unbalanced load means that, when different loads are distributed on a three-phase four-wire system, unequal currents pass through the three phases. Due to it, a heavy current flows in the neutral wire, which not only adds the losses, but also puts constraints on three phases’ loads. In this paper, we have presented a practical approach for load balancing. First, we have considered the existing three-phase load system where the supply is a three-phase unbalanced supply. Before balancing the load, it is necessary to compensate the current in neutral wire. A nature-inspired moth–flame optimization (MFO) algorithm is used to propose a scheme for balancing of current in neutral wire. The information of a distributed single-phase load was used to balance the currents in a three-phase system. The feeder phase and load profiles of each single-phase load are used to reconfigure the network using an optimization process. By balancing the current of three phases, the current of the neutral conductor in substation transformers was reduced to almost zero.
Scenarios to Decarbonize Austria’s Energy Consumption and the Role of Underground Hydrogen Storage
Authors: Clemens Marcel , Clemens Torsten
Published: May 2022

The European Union is aiming at reaching greenhouse gas (GHG) emission neutrality in 2050. Austria’s current greenhouse gas emissions are 80 million t/year. Renewable Energy (REN) contributes 32% to Austria’s total energy consumption. To decarbonize energy consumption, a substantial increase in energy generation from renewable energy is required. This increase will add to the seasonality of energy supply and amplifies the seasonality in energy demand. In this paper, the seasonality of energy supply and demand in a Net-Zero Scenario are analyzed for Austria and requirements for hydrogen storage derived. We looked into the potential usage of hydrogen in Austria and the economics of hydrogen generation and technology and market developments to assess the Levelized Cost of Hydrogen (LCOH). Then, we cover the energy consumption in Austria followed by the REN potential. The results show that incremental potential of up to 140 TWh for hydropower, photovoltaic (PV), and wind exists in Austria. Hydropower generation and PV is higher in summer- than in wintertime, while wind energy leads to higher energy generation in wintertime. The largest incremental potential is PV, with agrivoltaic systems significantly increasing the area amenable for PV compared with PV usage only. Battery Electric Vehicles (BEV) and Fuel Cell Vehicles (FCV) use energy more efficiently than Internal Combustion Engine (ICE) cars; however, the use of hydrogen for electricity generation significantly decreases the efficiency due to electricity–hydrogen–electricity conversion. The increase in REN use and the higher demand for energy in Austria in wintertime require seasonal storage of energy. We developed three scenarios, Externally Dependent Scenario (EDS), Balanced Energy Scenario (BES) or Self-Sustained Scenario (SSS), for Austria. The EDS scenario assumes significant REN import to Austria, whereas the SSS scenario relies on REN generation within Austria. The required hydrogen storage would be 10.82 bn m3 for EDS, 13.34 bn m3 for BES, and 18.69 bn m3 for SSS. Gas and oil production in Austria and the presence of aquifers indicates that sufficient storage capacity might be available. Significant technology development is required to be able to implement hydrogen as an energy carrier and to balance seasonal energy demand and supply.
Numerical Simulation of Fluid Flow in Carbonate Rocks Based on Digital Rock Technology
Authors: Hu Yong , Wei Jiong , Li Tao , Zhu Weiwei , Gong Wenbo , Hui Dong , Wang Moran
Published: May 2022

Strong heterogeneity, low matrix permeability, and complex oil–water interaction make the fluid flow in carbonate rocks extremely complicated. In this study, we quantitatively characterize and simulate single-phase and multiphase flows with multiscale pore–vug–fracture structures involved in the carbonate reservoir developments. The main studies and conclusions include: (i) The CT technology is utilized to characterize the pores, fractures, and vugs of carbonate cores at multiple scales. It is found that even if the CT resolution reaches 0.5 μm, the pores of the core are still unconnected as a network, indicating that the carbonate matrix is particularly tight. The existence of fractures can increase the effective permeability, and even poorly connected fractures can significantly increase the permeability because it reduces the flow distance through the less permeable matrix. (ii) A numerical model of low-porosity strongly heterogeneous carbonate rocks was constructed based on digital image processing. Simulations of single-phase fluid flow under reservoir conditions were conducted, and the effects of surrounding pressure, pore pressure, and core size on the single-phase flow were investigated. Due to the strong heterogeneity of carbonate rocks, the pores, vugs, and fractures cause local preferential flow and disturbance within the core, which significantly affects the fluid flow path and the pressure distribution in the core. The overall permeability is a composite representation of the permeability of numerous microelements in the specimen. Permeability increases with an increasing pore pressure, and it decreases with increasing circumferential pressure. (iii) The gas–water two-phase flow model of a low-porosity strongly heterogeneous carbonate rock was established based on digital image processing. The variation law of the two-phase outlet flow velocity with the inlet gas pressure and the movement law of the two-phase interface of carbonate rock samples were obtained. Under certain surrounding pressure, the outlet gas velocity is larger than the outlet water velocity; with the increase of the inlet gas pressure, the pore space occupied by the gas phase in the rock becomes larger. With the increase of the surrounding pressure, the velocities of both outlet gas and water decrease. As the sample size decreases, the velocities of both outlet gas and water increase.
The Impact of Built Environment Factors on Elderly People’s Mobility Characteristics by Metro System Considering Spatial Heterogeneity
Authors: Yang Hong , Ruan Zehan , Li Wenshu , Zhu Huanjie , Zhao Jie , Peng Jiandong
Published: May 2022

This study used metro smart-card data from Wuhan, China, and explored the impact of the built environment on the metro ridership and station travel distance of elderly people using geographically weighted regression (GWR). First, our results show that elderly ridership at transfer stations is significantly higher than that at non-transfer stations. The building floor area ratio and the number of commercial facilities positively impact elderly ridership, while the number of road intersections and general hospitals has the opposite impact, of which factors show significant heterogeneity. Second, our results show that the average travel distance of terminal stations is significantly higher than that of non-terminal stations, and the average travel distance of non-transfer stations is higher than that of transfer stations. The distance of stations from the subcenter and building volume ratio have a positive effect, while station opening time and betweenness centrality have a negative effect. Our findings may provide insights for the optimization of land use in the built environment of age-friendly metros, help in the formulation of relevant policies to enhance elderly mobility, and provide a reference for other similar cities.
Sphingolipids at Plasmodesmata: Structural Components and Functional Modulators
Authors: Zhang Yingying , Wang Shuang , Wang Lu , Chang Xiaoyan , Fan Yongxiao , He Meiqing , Yan Dawei
Published: May 2022

Plasmodesmata (PD) are plant-specific channels connecting adjacent cells to mediate intercellular communication of molecules essential for plant development and defense. The typical PD are organized by the close apposition of the plasma membrane (PM), the desmotubule derived from the endoplasmic reticulum (ER), and spoke-like elements linking the two membranes. The plasmodesmal PM (PD-PM) is characterized by the formation of unique microdomains enriched with sphingolipids, sterols, and specific proteins, identified by lipidomics and proteomics. These components modulate PD to adapt to the dynamic changes of developmental processes and environmental stimuli. In this review, we focus on highlighting the functions of sphingolipid species in plasmodesmata, including membrane microdomain organization, architecture transformation, callose deposition and permeability control, and signaling regulation. We also briefly discuss the difference between sphingolipids and sterols, and we propose potential unresolved questions that are of help for further understanding the correspondence between plasmodesmal structure and function.
SK119, a Novel Shikonin Derivative, Leads to Apoptosis in Melanoma Cell Lines and Exhibits Synergistic Effects with Vemurafenib and Cobimetinib
Authors: Kretschmer Nadine , Durchschein Christin , Hufner Antje , Rinner Beate , Lohberger Birgit , Bauer Rudolf
Published: May 2022

Melanoma is a complex and heterogenous disease, displays the deadliest form of skin cancer, and accounts for approx. 80% of all skin cancer deaths. In this study, we reported on the synthesis and pharmacological effects of a novel shikonin derivative (SK119), which is active in a nano-molar range and exhibits several promising in vitro effects in different human melanoma cells. SK119 was synthesized from shikonin as part of our search for novel, promising shikonin derivatives. It was screened against a panel of melanoma and non-tumorigenic cell lines using XTT viability assays. Moreover, we studied its pharmacological effects using apoptosis and Western blot experiments. Finally, it was combined with current clinically used melanoma therapeutics. SK119 exhibited IC50 values in a nano-molar range, induced apoptosis and led to a dose-dependent increase in the expression and protein phosphorylation of HSP27 and HSP90 in WM9 and MUG-Mel 2 cells. Combinatorial treatment, which is highly recommended in melanoma, revealed the synergistic effects of SK119 with vemurafenib and cobimetinib. SK119 treatment changed the expression levels of apoptosis genes and death receptor expression and exhibited synergistic effects with vemurafenib and cobimetinib in human melanoma cells. Further research indicates a promising potential in melanoma therapy.
Regression Analysis of the Dielectric and Morphological Properties for Porous Nanohydroxyapatite/Starch Composites: A Correlative Study
Authors: Beh Chong You , Cheng Ee Meng , Mohd Nasir Nashrul Fazli , Abdul Majid Mohd Shukry , Khor Shing Fhan , Mohd Jamir Mohd Ridzuan , Mohd Tarmizi Emma Ziezie , Lee Kim Yee
Published: May 2022

This paper aims to investigate the dielectric properties, i.e., dielectric constant (ε′), dielectric loss factor (ε″), dielectric tangent loss (tan δ), electrical conductivity (σ), and penetration depth (Dp), of the porous nanohydroxyapatite/starch composites in the function of starch proportion, pore size, and porosity over a broad band frequency range of 5 MHz–12 GHz. The porous nanohydroxyapatite/starch composites were fabricated using different starch proportions ranging from 30 to 90 wt%. The results reveal that the dielectric properties and the microstructural features of the porous nanohydroxyapatite/starch composites can be enhanced by the increment in the starch proportion. Nevertheless, the composite with 80 wt% of starch proportion exhibit low dielectric properties (ε′, ε″, tan δ, and σ) and a high penetration depth because of its highly interconnected porous microstructures. The dielectric properties of the porous nanohydroxyapatite/starch composites are highly dependent on starch proportion, average pore size, and porosity. The regression models are developed to express the dielectric properties of the porous nanohydroxyapatite/starch composites (R2 > 0.96) in the function of starch proportion, pore size, and porosity from 1 to 11 GHz. This dielectric study can facilitate the assessment of bone scaffold design in bone tissue engineering applications.
An Experimental Study Reveals the Protective Effect of Autophagy against Realgar-Induced Liver Injury via Suppressing ROS-Mediated NLRP3 Inflammasome Pathway
Authors: Yang Jing , Li Jian , Guo Haoqi , Zhang Yuwei , Guo Ziwei , Liu Yu , Huo Taoguang
Published: May 2022

Realgar, a poisonous traditional Chinese medicine, has been shown to cause liver injury when used for long periods or overdoses. However, the underlying molecular mechanisms and therapeutic targets have not been fully elucidated. The aim of this study is to explore the role of autophagy in sub-chronic realgar exposure-induced liver injury. Here, the liver injury model was established by continuously administrating mice with 1.35 g/kg realgar for 8 weeks. 3-methyladenine (3-MA) and rapamycin (RAPA) were used to regulate autophagy. The results showed that realgar induced abnormal changes in liver function, pathological morphology, expression of inflammatory cytokines, and upregulated NLRP3 inflammasome pathway in mouse livers. RAPA treatment (an inducer of autophagy) significantly improved realgar-induced liver injury and NLRP3 inflammasome activation, while 3-MA (an inhibitor of autophagy) aggravated the realgar-induced liver injury and NLRP3 inflammasome activation. Furthermore, we found that realgar-induced NLRP3 inflammasome activation in mouse livers is mediated by ROS. RAPA eliminates excessive ROS, inhibits NF-κB nuclear translocation and down-regulates the TXNIP/NLRP3 axis, consequently suppressing ROS-mediated NLRP3 inflammasome activation, which may be the underlying mechanism of the protective effect of autophagy on realgar-induced liver injury. In conclusion, the results of this study suggest that autophagy alleviates realgar-induced liver injury by inhibiting ROS-mediated NLRP3 inflammasome activation. Autophagy may represent a therapeutic target in modulating realgar-induced liver injury.
Correction: Alfat et al. Phase Field Models for Thermal Fracturing and Their Variational Structures. Materials 2022, 15, 2571
Authors: Alfat Sayahdin , Kimura Masato , Maulana Alifian Mahardhika
Published: May 2022

The authors were not aware of typographical errors made in the writing phase, and, hence, wish to make the following corrections to the original paper [...]
Manipulation of the Phytochemical Profile of Tenderstem® Broccoli Florets by Short Duration, Pre-Harvest LED Lighting
Authors: Langston Faye M. A. , Monaghan James M. , Cousins Olivia , Nash Geoffrey R. , Bows John R. , Chope Gemma
Published: May 2022

Light quality has been reported to influence the phytochemical profile of broccoli sprouts/microgreens; however, few studies have researched the influence on mature broccoli. This is the first study to investigate how exposing a mature glasshouse grown vegetable brassica, Tenderstem® broccoli, to different light wavelengths before harvest influences the phytochemical content. Sixty broccoli plants were grown in a controlled environment glasshouse under ambient light until axial meristems reached >1 cm diameter, whereupon a third were placed under either green/red/far-red LED, blue LED, or remained in the original compartment. Primary and secondary spears were harvested after one and three weeks, respectively. Plant morphology, glucosinolate, carotenoid, tocopherol, and total polyphenol content were determined for each sample. Exposure to green/red/far-red light increased the total polyphenol content by up to 13% and maintained a comparable total glucosinolate content to the control. Blue light increased three of the four indole glucosinolates studied. The effect of light treatments on carotenoid and tocopherol content was inconclusive due to inconsistencies between trials, indicating that they are more sensitive to other environmental factors. These results have shown that by carefully selecting the wavelength, the nutritional content of mature broccoli prior to harvest could be manipulated according to demand.
Online In-Tube Solid-Phase Microextraction Coupled with Liquid Chromatography–Tandem Mass Spectrometry for Automated Analysis of Four Sulfated Steroid Metabolites in Saliva Samples
Authors: Kataoka Hiroyuki , Nakayama Daiki
Published: May 2022

Accurate measurement of sulfated steroid metabolite concentrations can not only enable the elucidation of the mechanisms regulating steroid metabolism, but also lead to the diagnosis of various related diseases. The present study describes a simple and sensitive method for the simultaneous determination of four sulfated steroid metabolites in saliva, pregnenolone sulfate (PREGS), dehydroepiandrosterone sulfate (DHEAS), cortisol sulfate (CRTS), and 17β-estradiol-3-sulfate (E2S), by online coupling of in-tube solid-phase microextraction (IT-SPME) and stable isotope dilution liquid chromatography–tandem mass spectrometry (LC–MS/MS). These compounds were extracted and concentrated on Supel-Q PLOT capillary tubes by IT-SPME and separated and detected within 6 min by LC–MS/MS using an InertSustain swift C18 column and negative ion mode multiple reaction monitoring systems. These operations were fully automated by an online program. Calibration curves using their stable isotope-labeled internal standards showed good linearity in the range of 0.01–2 ng mL−1 for PREGS, DHEAS, and CRTS and of 0.05–10 ng mL−1 for E2S. The limits of detection (S/N = 3) of PREGS, DHEAS, CRTS, and E2S were 0.59, 0.30, 0.80, and 3.20 pg mL−1, respectively. Moreover, intraday and interday variations were lower than 11.1% (n = 5). The recoveries of these compounds from saliva samples were in the range of 86.6–112.9%. The developed method is highly sensitive and specific and can easily measure sulfated steroid metabolite concentrations in 50 μL saliva samples.
Hydrolyzed Flavonoids from Cyrtosperma johnstonii with Superior Antioxidant, Antiproliferative, and Anti-Inflammatory Potential for Cancer Prevention
Authors: Naksuriya Ornchuma , Daowtak Krai , Tima Singkome , Okonogi Siriporn , Mueller Monika , Toegel Stefan , Khonkarn Ruttiros
Published: May 2022

Cyrtosperma johnstonii is one of the most interesting traditional medicines for cancer treatment. This study aimed to compare and combine the biological activities related to cancer prevention of the flavonoid glycosides rutin (RT) and isorhamnetin-3-o-rutinoside (IRR) and their hydrolysis products quercetin (QT) and isorhamnetin (IR) from C.johnstonii extract. ABTS and MTT assays were used to determine antioxidant activity and cytotoxicity against various cancer cells, as well as normal cells. Anti-inflammatory activities were measured by ELISA. The results showed that the antioxidant activities of the compounds decreased in the order of QT > IR > RT > IRR, while most leukemia cell lines were sensitive to QT and IR with low toxicity towards PBMCs. The reduction of IL-6 and IL-10 secretion by QT and IR was higher than that induced by RT and IRR. The combination of hydrolysis products (QT and IR) possessed a strong synergism in antioxidant, antiproliferative and anti-inflammatory effects, whereas the combination of flavonoid glycosides and their hydrolysis products revealed antagonism. These results suggest that the potential of the combination of hydrolyzed flavonoids from C. johnstonii can be considered as natural compounds for the prevention of cancer.
Co-Application of Statin and Flavonoids as an Effective Strategy to Reduce the Activity of Voltage-Gated Potassium Channels Kv1.3 and Induce Apoptosis in Human Leukemic T Cell Line Jurkat
Authors: Teisseyre Andrzej , Chmielarz Mateusz , Uryga Anna , Środa-Pomianek Kamila , Palko-Łabuz Anna
Published: May 2022

Voltage-gated potassium channels of the Kv1.3 type are considered a potential new molecular target in several pathologies, including some cancer disorders and COVID-19. Lipophilic non-toxic organic inhibitors of Kv1.3 channels, such as statins and flavonoids, may have clinical applications in supporting the therapy of some cancer diseases, such as breast, pancreas, and lung cancer; melanoma; or chronic lymphocytic leukemia. This study focuses on the influence of the co-application of statins—simvastatin (SIM) or mevastatin (MEV)—with flavonoids 8-prenylnaringenin (8-PN), 6-prenylnarigenin (6-PN), xanthohumol (XANT), acacetin (ACAC), or chrysin on the activity of Kv1.3 channels, viability, and the apoptosis of cancer cells in the human T cell line Jurkat. We showed that the inhibitory effect of co-application of the statins with flavonoids was significantly more potent than the effects exerted by each compound applied alone. Combinations of simvastatin with chrysin, as well as mevastatin with 8-prenylnaringenin, seem to be the most promising. We also found that these results correlate with an increased ability of the statin–flavonoid combination to reduce viability and induce apoptosis in cancer cells compared to single compounds. Our findings suggest that the co-application of statins and flavonoids at low concentrations may increase the effectiveness and safety of cancer therapy. Thus, the simultaneous application of statins and flavonoids may be a new and promising anticancer strategy.
Effect of Ionic and Non-Ionic Surfactant on Bovine Serum Albumin Encapsulation and Biological Properties of Emulsion-Electrospun Fibers
Authors: Kurpanik Roksana , Lechowska-Liszka Agnieszka , Mastalska-Popławska Joanna , Nocuń Marek , Rapacz-Kmita Alicja , Ścisłowska-Czarnecka Anna , Stodolak-Zych Ewa
Published: May 2022

Emulsion electrospinning is a method of modifying a fibers’ surface and functional properties by encapsulation of the bioactive molecules. In our studies, bovine serum albumin (BSA) played the role of the modifier, and to protect the protein during the electrospinning process, the W/O (water-in-oil) emulsions were prepared, consisting of polymer and micelles formed from BSA and anionic (sodium dodecyl sulfate–S) or nonionic (Tween 80–T) surfactant. It was found that the micelle size distribution was strongly dependent on the nature and the amount of the surfactant, indicating that a higher concentration of the surfactant results in a higher tendency to form smaller micelles (4–9 µm for S and 8–13 µm for T). The appearance of anionic surfactant micelles reduced the diameter of the fiber (100–700 nm) and the wettability of the nonwoven surface (up to 77°) compared to un-modified PCL polymer fibers (100–900 nm and 130°). The use of a non-ionic surfactant resulted in better loading efficiency of micelles with albumin (about 90%), lower wettability of the nonwoven fabric (about 25°) and the formation of larger fibers (100–1100 nm). X-ray photoelectron spectroscopy (XPS) was used to detect the presence of the protein, and UV-Vis spectrophotometry was used to determine the loading efficiency and the nature of the release. The results showed that the location of the micelles influenced the release profiles of the protein, and the materials modified with micelles with the nonionic surfactant showed no burst release. The release kinetics was characteristic of the zero-order release model compared to anionic surfactants. The selected surfactant concentrations did not adversely affect the biological properties of fibrous substrates, such as high viability and low cytotoxicity of RAW macrophages 264.7.