bluuebunny/crossref_metadata_2025 huggingface dataset:
A Convincing Finnish Move: Implications for State Identity of Persuading Sweden to Jointly Bid for NATO Membership
Authors:   Swedish Defence University, Lundqvist Stefan
Published: February 2023

This article examines the consequences for Sweden’s state identity by the decision of Finland and Sweden to apply for membership in NATO. Taking its starting point in Sweden’s shattering loss of its easternmost provinces in the 1809 Treaty of Fredrikshamn, it explores Sweden’s initial formulations of a policy of neutrality and its evolution until the end of the Cold War. The article then directs attention to how Social Democratic leaders managed to institutionalise a Swedish “active foreign policy”, exerting a lasting, formative infl uence on Sweden’s state identity. It also addresses the rapprochement of Finland and Sweden after the end of the Cold War and the consequences of the bilateral dynamics that characterised their EU-membership applications. The article critically discusses how Sweden reformulated its concept of neutrality into a nebulous concept of nonalignment and adopted a security policy rooted in a cooperative security approach. Based on key findings drawn from this historical account, this article addresses the processes that lead to Finland and Sweden unexpectedly deciding on jointly applying for NATO membership. It concludes with a forward-looking assessment of how a Swedish NATO membership will ultimately stabilise Sweden’s adaptable state identity and its implications for the Nordic countries’ regional military strategy.
Does ESG Improve Crisis Resilience? Empirical Evidence of Global Emerging Equity Markets during the Covid-19 Crisis
Authors: Naffa Helena , Dudás Fanni
Published: February 2023

We examine the role of Environmental, Social, and Governance (ESG) factors in explaining the crisis resilience of 1031 global emerging market (GEM) equities during the Covid-19 crisis downturn of Q1 2020. We use linear and quantile regressions (QR) and find a statistically significant negative relationship between a firm's ESG management score and crisis resilience as proxied by stock maximal drawdown. Our results suggest that companies with better ESG management were less crisis resilient, a finding consistent with agency-theory-based explanations found in the literature. Results are robust across all OLS and QR models.
Effects of Exogenous donor of nitric oxide - sodium nitroprusside on energy production of rat reticulocytes.
Authors: Maletić SD , Dragićević-Djoković LM , Ognjanović BI , Žikić RV , Štajn AŠ , Spasić MB
Published: February 2023

The effects of the sodium nitroprusside (SNP), a nitric oxide (NO) donor clinically used in the treatment of hypertensive emergencies on the energy production of rat reticulocytes were investigated. Rat reticulocyte-rich red blood cell suspensions were aerobically incubated without (control) or in the presence of different concentrations of SNP (0.1, 0.25, 0.5, 1.0 mM). SNP decreased total and coupled, but increased uncoupled oxygen consumption. This was accompanied by the stimulation of glycolysis, as measured by increased glucose consumption and lactate accumulation. Levels of all glycolytic intermediates indicate stimulation of hexokinase-phosphofructo kinase (HK-PFK), glyceraldehyde 3-phosphate dehydrogenase (GAPD) and pyruvate kinase (PK) activities in the presence of SNP. Due to the decrease of coupled oxygen consumption in the presence of SNP, ATP production via oxidative phosphorylation was significantly diminished. Simultaneous increase of glycolytic ATP production was not enough to provide constant ATP production. In addition, SNP significantly decreased ATP level, which was accompanied with increased ADP and AMP levels. However, the level of total adenine nucleotides was significantly lower, which was the consequence of increased catabolism of adenine nucleotides (increased hypoxanthine level). ATP/ADP ratio and adenylate energy charge level were significantly decreased. In conclusion, SNP induced inhibition of oxidative phosphorylation, stimulation of glycolysis, but depletion of total energy production in rat reticulocytes. These alterations were accompanied with instability of energy status.
Hippocampal afterdischarges in rats. I. Effects of antiepileptics.
Authors: Velíšek L , Mareš P
Published: February 2023

Hippocampal afterdischarges (ADs) are considered to be a model of complex partial seizures. To study the pharmacology of these ADs, stimulation electrodes were implanted into the dorsal hippocampus of 33 male Wistar rats. Stimulation (15-s series of monophasic rectangular pulses with a duration of 1 ms and frequency of 8 Hz) was applied four times with interstimulation intervals of 15 min. Drugs (carbamazepine 50 and 100 mg/kg; clonazepam 0.2 and 0.5 mg/kg; ethosuximide 125 and 250 mg/kg; phenobarbital 40 and 80 mg/kg) as well as solvent and isotonic saline were injected intraperitoneally 2 min after the cessation of the first AD. Duration of AD, of the latent period between AD and recurrent AD and duration of recurrent AD and the number of wet dog shakes were measured. ADs were markedly shortened by both doses of clonazepam and phenobarbital and by the higher dose of carbamazepine. The action of ethosuximide was negligible. Wet dog shakes were influenced in the same way as AD duration. Recurrent ADs were more sensitive to antiepileptics than ADs and wet dog shakes.
Changes in the development of uterine pinopodes in steroid hormone supplemented cycles.
Authors: Oborná I , Novotný R , Březinová J , Petrová P , Lichnovský V , Fingerová H
Published: February 2023

The endometrium acquires the ability to implant a hatched blastocyst only within a specific time termed the receptive phase. Ovarian steroid hormones are essential for structural and functional changes that prepare the endometrium to be receptive. Pinopodes have been suggested to be markers of uterine receptivity. The aim of this study was to compare the pinopode expression and serum levels of ovarian steroid hormones in the mid-luteal phase of the natural cycle and in a “mock” cycle in the same subject. Sequentional endometrial biopsies within 48 hours were obtained from women in the mid-luteal phase (ovulation +5, ovulation +7) of the natural cycle and in the “mock” cycle (progesterone supplementation +5 and +7). Biopsies were examined under a scanning electron microscope for pinopode detection. The expression of pinopodes was similar in both cycles, where pinopodes covered about 5 % of the endometrial surface. The developmental stages were also similar with a slight increase of fully developed pinopodes in both samples in the “mock” cycles. Our findings suggest that hormonal preparation of the endometrium do not change the timing of pinopode expression.
Analysis of The Potential of Subak as A Sustainable Tourism Attraction Based on Agro-Tourism In The Village of Jatiluwih
Authors: Amir Firlie Lanovia
Published: February 2023

Subak is an inseparable part of tourism in Bali. It is an organization that consists of paddy field owners and farmers that live around the subak area where they receive water from certain dams which are used by the members individually. Thus, an effort to preserve the existence of subak in the middle of modern global culture is needed by developing subak as sustainable tourism which is currently becoming a trend in the world of tourism. In this case, arts, cultures, and religion are potentials that must be owned by a sustainable tourism destination. The problem in developing a subak’s potential as a sustainable tourism destination is the lack of local people understanding in maximizing the potential of subak in Jatiluwih village as sustainable tourism. The purpose of this research is to identify the concept and the subak’s potential as a sustainable tourism destination in Jatiluwih village, Tabanan, Bali. This research can be categorized as a qualitative descriptive study that was carried out for one month and was located in Jatiluwih village, Tabanan, Bali. The data collection is done through non-participatory observation, an in-depth interview with three informants consisting of a local business actor, a pekseh (the leader of the subak), as well as a local public figure, and documentation studies towards relevant literature and related documents. The result of this research shows that subak still preserves the Tri Hita Karana concept in the system of implementing agricultural activities in Jatiluwih village. On the other hand, with the existence of subak people in Bali can be wiser in managing their natural resources and they can be used according to their needs so that the capacity of the natural resources will always be maintained and always be preserved it can be used by the next generation. Subak's potential development as a sustainable tourism destination can increase the local community commodities in driving sustainable tourism based on agro-tourism so that in the future, the preservation of their natural resources can always be maintained and can be enjoyed by the next generation.
A Positive-Psychology-based Multiple Regression model predicting Wellbeing in Chilean Youth
Authors: Pérez Díaz Pablo A. , Bachmann Vera Daniela , Wiium Nora
Published: February 2023

Positive Youth Development (PYD) addresses young people from their potential, strengths, and assets, in contrast to the deficit view that focuses on their weaknesses. The PYD model promotes constructive behaviours in youth by underscoring positive attributes usually found during the transition from childhood to adulthood in order to foster healthy development. In a nutshell, PYD comprises five key competence (5C), forty developmental assets, and the flourishing model. In the present study, 261 participants were approached by an online survey (nWomen= 189, nMen = 72, MeanAge= 22 years old), as part of the Cross-national project on PYD (CN-PYD), which included several measures, among which those included in the research were: The Developmental assets Scale, the Short-form of the Five Cs, and the Mental Health Continuum Short-Form (MHC-SF). Emotional, Social, Psychological and General Wellbeing scores were tested on the premise that females would score significantly lower than male participants (H1). In addition, two multiple regression models were tested with the first wave of the Chilean PYD project on the premise that Positive Identity, Confidence, Character, and Connection would predict the variance of General Wellbeing (H2), and Psychological Wellbeing (H3). The findings provided total support for H1 and H2, and partial support for H3. Overall, the research complements previous investigations conducted with Latin American and Chilean Youth, stressing the importance of researching Latin-American adolescents’ developmental assets, PYD competence, and the varieties of subjective wellbeing.
Urdu Translation and Adaptation of Interpersonal Rejection Sensitivity Scale
Authors: Sajid Bushra , Zeb Roomana , Riaz Mah Nazir
Published: February 2023

The aim of the study was to translate, adapt and validate the original 13-item English version of Interpersonal Rejection Sensitivity Scale (IRSS; Rohner et al., 2020) into Urdu language to facilitate administration on Pakistani adults. The study followed three stages: Translation and adaptation, linguistic equivalence with cross validation, and establishing psychometric properties of translated Urdu version of IRSS. The sample for stage II comprised of 100 adults above 18 years of age selected through convenience sampling technique. The results showed significant correlation (r = .84) between both English and Urdu versions of the IRSS. Similarly, inter-item correlation of English items and Urdu items showed significant correlations with an exception of only item 3 and item 12. Moreover, value of Cronbach's alpha (α = .72) illustrated the internal consistency of Urdu version of IRSS. In stage III of the study, Exploratory Factor Analysis run on a separate sample (N = 200) of adults indicated that the Urdu version of the IRSS is a standardized measure like the original English IRSS as all the items were significantly loaded; only items number 3 and 12 that did not load on the scale. Therefore, after excluding item number 3 and 12 with the permission of Rohner Research Publications, it is concluded that the 11-item Urdu translation of IRSS is a valid and reliable scale (α = .83) to measure interpersonal rejection-sensitivity among Pakistani population.
Attachment Styles and Nomophobia in Young Adults: The Mediating Role of Mindful Awareness
Authors: Gohar Areeb , Munir Mubeena
Published: February 2023

The present study investigated the relationships among attachment style, mindful awareness and nomophobia in university students. The study hypothesized that attachment style and mindful awareness are likely to predict nomophobia in university students; and mindful awareness is likely to mediate the relationship between attachment styles and nomophobia. With the help of cross-sectional research design and non-probability purposive sampling technique, a sample of 208 young adults was selected. Data was collected through Attachment Style Questionnaire (ASQ; Van Oudenhoven et al., 2003), Mindful Attention Awareness Scale (MASS; Brown & Ryan, 2003) and Nomophobia Questionnaire (NMP- Q; Yildirim & Correia, 2015). To analyze the data, SPSS and AMOS software were used. It was showed by Pearson Product Moment Correlation that secure attachment style had positive association with nomophobia and mindful awareness. Fearful and preoccupied attachment styles had negative association with mindful awareness and both are positively related to nomophobia. Analysis showed that secure, fearful, and preoccupied attachment styles were positively predicting nomophobia. Secure attachment style was positively predicting mindful awareness but fearful and preoccupied attachment styles were negatively predicting mindful awareness. Furthermore, mediation analysis showed that mindful awareness was significantly mediating the relationsship between attachment style and nomophobia. It was concluded that mindfulness could be helpful in the management of nomophobia.
Explaining Sense of Responsibility with Family Competence: Mediation by Family Conflict and Moderation by Gender
Authors: Zahra Syeda B. , Malik Jamil A.
Published: February 2023

This study investigated the role of family competence, with mediation by family conflict and moderation by gender, in determining sense of responsibility in young adults. The sample (N = 606) consisted of university students (men = 140, women = 433) with age ranging from 19-25 years (M = 20.70, SD = 1.90). Self- Report Family Inventory II (Beavers & Hampson, 2000) and Personal Responsibility Scale (Mergler, 2016) were used and results indicated a significantly negative relationship between family competence and sense of responsibility, contrary to our hypothesis. However, it was observed that conflict mediates between the effects of family competence on sense of responsibility, and that females score higher on sense of responsibility, both in line with the study’s hypotheses. Gender as a moderator for the effect of family conflict on sense of responsibility presented a significant relationship. Furthermore, the interaction between conflict and gender was significant. The regression model showed a significant direct conditional effect at low levels between competence and sense of responsibility, as well as a significant indirect effect at low and medium levels between competence and sense of responsibility, while a mediated effect at high level can also be observed. Findings can be used for parental awareness regarding the psychological needs of our target demographic.
Neuroticism and Psychosocial Stressors of Trauma in University Students: The Mediating Role of Self-Esteem and Self-Appraisal of Trauma
Authors: Rani Samia , Saleem Sadia , Zahra Sayyeda Taskeen
Published: February 2023

The current study aimed to find out the mediating role of anxious self-esteem and self-appraisal of trauma in the relationship of neuroticism and psycho-social stressors of trauma in a sample of 213 (men =31%, women = 68%) between the ages of 18 to 26 (M = 20.78, SD = 2.46). Participants were selected by using a purposive sampling strategy studying in private and government universities of Lahore, Pakistan. Neuroticism vs. Emotional Stability Scale (John et al., 1991), Anxious/ Withdrawn Self-esteem Scale for University Population (Zafar et al., 2012), Psychosocial Stressors of Trauma scale (PSST) (Rani et al., 2021), and Self-Appraisal Scale (Rani et al., 2021) were used to assess the neuroticism vs. emotional stability, anxious self-esteem, self-appraisal of trauma and psycho-social stressors of trauma in university students. Findings of correlation analysis depicted the interrelatedness of neuroticism, anxious self-esteem, self-appraisal of trauma, and psycho-social stressors. Mediation analysis suggested the serial mediating role of anxious self-esteem and self-appraisal of trauma in the association of neuroticism vs. emotional stability and PSST in university students. These findings might be used to overcome the adverse outcomes of trauma in University students.
Forgiveness and Empathy as Predictors of Psychological Wellbeing among Nurses
Authors: Khan Momina , Butt Sidra Farooq
Published: February 2023

The purpose of the study was to examine whether forgiveness and empathy have a significant correlation with psychological wellbeing among nurses. The present research will enable the theorist to develop measures that will cultivate empathy, forgiveness and psychological wellbeing in nurses. This was a correlational, survey based research. A sample of 151 nurses of age range 20-55 was selected via purposive sampling technique from Karachi, Pakistan. The participants were approached through online medium. The study variables were assessed through Toronto Empathy Questionnaire (Spreng et al., 2009), The Heartland Forgiveness scale (Thompson et al., 2005) and Ryff’s Psychological Well-Being Scales (Ryff, 1989). Statistical Package for Social Sciences (SPSS- Version 22) was used for analyzing the data, the results revealed that empathy and forgiveness are significant predictors of psychological wellbeing. Further findings of the research highlighted significant differences in empathy, forgiveness and psychological wellbeing with respect to nurse’s age, gender, education and family structure. The results of the present study could be useful for enhancing nurse’s psychological.
Construction and Validation of Organizational Conflict Types and Conflict Management Styles Inventories
Authors: Qayyum Shazia , Younas Faiz , Tariq Shahnila
Published: February 2023

Conflicts occupy a pertinent role in every aspect of human life and organizational settings are not an exception. In the absence of indigenous, comprehensive and latest assessment measures for organizational conflict types and management styles, the present study aimed to develop and validate inventories for both constructs by converging on the sociocultural context. Ensuing an exploratory sequential design, the investigation started with a qualitative study in which five focus group discussions (FGDs) were conducted with 30 professionals (including teachers, bankers, engineers, managers and doctors) who shared their experiences of organizational conflicts by highlighting types and management styles. From an initial pool of 137 items (65 & 72 items respectively), the subject matter experts finalized 55 items each for organizational conflict types and management style inventories. In study II, exploratory factor analysis was administered on a sample of 400 adult professionals resulting in a six-factor Qayyum-Younas Organizational Conflict Types Inventory (QY-OCTI) with 40 items. It was later confirmed by running a Confirmatory Factor Analysis on another sample of 400 professionals. In study III, EFA was conducted on a sample of 310 participants that revealed a six-factor model of the Qayyum-Younas Organizational Conflict Management Styles Inventory (QY-OCMSI) with 48 items and this model was later confirmed by running CFA on a sample of 490 participants. These scales have significant research, academic and organizational setting-based implications.
A hybrid individual-based mathematical model to study bladder infections
Authors: Lasri Doukkali Anas , Lorenzi Tommaso , Parcell Benjamin J. , Rohn Jennifer L. , Bowness Ruth
Published: February 2023

Introduction

Bladder infections are common, affecting millions each year, and are often recurrent problems.

Methods

We have developed a spatial mathematical framework consisting of a hybrid individual-based model to simulate these infections in order to understand more about the bacterial mechanisms and immune dynamics. We integrate a varying bacterial replication rate and model bacterial shedding as an immune mechanism.

Results

We investigate the effect that varying the initial bacterial load has on infection outcome, where we find that higher bacterial burden leads to poorer outcomes, but also find that only a single bacterium is needed to establish infection in some cases. We also simulate an immunocompromised environment, confirming the intuitive result that bacterial spread typically progresses at a higher rate.

Conclusions

With future model developments, this framework is capable of providing new clinical insight into bladder infections.
The carbon footprint of young-beef cattle finishing systems in the Eastern Plains of the Orinoco River Basin of Colombia
Authors: Ramírez-Restrepo Carlos A. , Vera-Infanzón Raul R. , Rao Idupulapati M.
Published: February 2023

Introduction

Previous research has shown increased productivity amongst sown grass pastures compared to native savanna pastures by year-round grazing for fattening of adult and young Brahman (Bos indicus)-bred cattle in the well-drained native savanna ecosystem of the Colombian Orinoquía. But there is limited information on the carbon footprint (CF) of commercial young-Brahman heifers and steers reared throughout life on well-managed Brachiaria decumbens Stapf pastures.

Methods

The present study characterized growth, lifetime enteric methane (CH4) emissions, carcass carbon dioxide equivalent (CO2-eq) CH4 efficiency intensities (i.e., emissions per kg of product), and estimated the overall CF of young cattle grazing B. decumbens pastures subject to a range of daily liveweight gains (DLWGs; 0.428 – 0.516 kg) and fattening framework (405 – 574 kg). Weaning data from seven consecutive calving seasons in a commercial Brahman breeding herd continuously grazed on B. decumbens were integrated with a Microsoft Excel® dynamic greenhouse gas emission (GHGE) simulation of stockers-yearlings, and seven fattening, and processing scenarios.

Results

The model predicted that heifers subject to low and high DLWGs (0.428 vs 0.516 kg) and steers (0.516 kg) may be successfully fattened without supplementation assuming that animals had access to a well-managed grass pasture. Depending on the fattening strategy, kg CO2-eq CH4/kg edible protein values ranged from 66.843 to 87.488 ± 0.497 for heifers and from 69.689 to 91.291 ± 0.446 for steers.

Discussion

Assuming that forage on offer is at least 1,500-2,000 kg of dry matter/ha during the rainy season, all the simulated systems showed potential for C neutrality and net-zero C emission when considering GHGEs from the soil, pasture, and animal components vs the estimated soil C capture over seven seasons. However, under a more optimistic scenario, these beef systems could accomplish substantial net gains of soil C, over the period for which field data are available. Overall, this study projects the positive impact of the design of plausible fattening strategies on grasslands for improving cattle productivity and reducing emission intensities with concomitant increases in technical efficiency.
Role of Streptococcus pneumoniae extracellular glycosidases in immune evasion
Authors: Mathew Bijina J. , Gupta Priyal , Naaz Tabassum , Rai Rupal , Gupta Sudheer , Gupta Sudipti , Chaurasiya Shivendra K. , Purwar Shashank , Biswas Debasis , Vyas Ashish Kumar , Singh Anirudh K.
Published: February 2023

Streptococcus pneumoniae (pneumococcus) typically colonizes the human upper airway asymptomatically but upon reaching other sites of the host body can cause an array of diseases such as pneumonia, bacteremia, otitis media, and meningitis. Be it colonization or progression to disease state, pneumococcus faces multiple challenges posed by host immunity ranging from complement mediated killing to inflammation driven recruitment of bactericidal cells for the containment of the pathogen. Pneumococcus has evolved several mechanisms to evade the host inflicted immune attack. The major pneumococcal virulence factor, the polysaccharide capsule helps protect the bacteria from complement mediated opsonophagocytic killing. Another important group of pneumococcal proteins which help bacteria to establish and thrive in the host environment is surface associated glycosidases. These enzymes can hydrolyze host glycans on glycoproteins, glycolipids, and glycosaminoglycans and consequently help bacteria acquire carbohydrates for growth. Many of these glycosidases directly or indirectly facilitate bacterial adherence and are known to modulate the function of host defense/immune proteins likely by removing glycans and thereby affecting their stability and/or function. Furthermore, these enzymes are known to contribute the formation of biofilms, the bacterial communities inherently resilient to antimicrobials and host immune attack. In this review, we summarize the role of these enzymes in host immune evasion.
Postbiotic gel relieves clinical symptoms of bacterial vaginitis by regulating the vaginal microbiota
Authors: Shen Xin , Xu Lin , Zhang Zhiquan , Yang Yitong , Li Pengxian , Ma Teng , Guo Shuai , Kwok Lai-Yu , Sun Zhihong
Published: February 2023

Vaginitis is the most common disease in gynecology. Vaginal dysbiosis is a main reason of bacteria vaginitis (BV), as the disrupted microecological environment facilitates the growth of various vaginal pathogens. The most dominant bacteria in the vaginal microbiota are lactic acid bacteria, which are important for maintaining vaginal health. At present, antibiotics and other drugs are often used in clinical treatment, but there are many adverse reactions and easy to relapse, and the intervention of probiotics can help restore vaginal microbiota and alleviate BV. This study is a human clinical trial of 50 patients with bacterial vaginitis (BV). The alleviation effect of applying a postbiotic gel for one week in BV was evaluated. Changes in patients’ clinical indicators of BV (properties of vaginal secretion) and the vaginal microbiota after using the postbiotic gel were monitored. Our results showed that apply the postbiotic gel improved the symptoms of BV, indicated by improvement in the abnormalities of patients’ vaginal secretions. After applying the gel, the relative abundance of vaginal lactobacilli increased compared to baseline. Significant negative correlations were found between lactobacilli and potential vaginal pathogens (including Gardnerella, Prevotella, and Atopobium), as well as the abnormalities of the vaginal secretion. Overall, our results showed that applying the postbiotic gel ameliorated BV, and the symptom improvement was accompanied by significant changes in the bacterial vaginal microbiota. Our study provides valuable clinical data in managing BV.
The role of overlayered nitride electro-materials for N2 reduction to ammonia
Authors: Abghoui Younes , Iqbal Atef , Skúlason Egill
Published: February 2023

Following our previous report on N2 reduction reaction (NRR) on the surface of nitrides, we investigated the influence of incorporation of titanium nitride as a stable and inactive-NRR material into the structure of DFT-predicted NRR-active surfaces of chromium, vanadium, niobium, and zirconium nitrides. The outcome of our density functional theory (DFT) based analyses suggests that combination of titanium nitride with vanadium nitride can enhance the potential-determining step of the reaction with up to 20% compared to pure vanadium nitride while maintaining similar number of proton-electron transfer steps for formation of two ammonia molecules. The influence of titanium nitride on chromium nitride is expected to be more pronounced as rate-determining step associated with nitrogen adsorption on the vacancy and regeneration of the catalyst improves by around 90% compared to the pure chromium nitride. This effect on niobium and zirconium nitride is, however, negative as the potential-determining step becomes larger for the case of niobium nitride, and the reaction pathway changes from nitrogen reduction to hydrogen evolution for the case of zirconium nitride. These results not only encourage experimentalists to explore these overlayered structures further in experiments, but it also opens up the avenue for considering the alloys and dopants of these nitrides via both density functional theory modelling and experiments.
Angiotensin receptor-neprilysin inhibitor improves coronary collateral perfusion
Authors: Li Kangbo , Kratzmann Victoria , Dai Mengjun , Gatzke Nora , Rocic Petra , Bramlage Peter , Grisk Olaf , Lubomirov Lubomir T. , Hoffmeister Meike , Lauxmann Martin A. , Ritter Oliver , Buschmann Eva , Bader Michael , Persson Anja Bondke , Buschmann Ivo , Hillmeister Philipp
Published: February 2023

Background

We investigated the pleiotropic effects of an angiotensin receptor-neprilysin inhibitor (ARNi) on collateral-dependent myocardial perfusion in a rat model of coronary arteriogenesis, and performed comprehensive analyses to uncover the underlying molecular mechanisms.

Methods

A rat model of coronary arteriogenesis was established by implanting an inflatable occluder on the left anterior descending coronary artery followed by a 7-day repetitive occlusion procedure (ROP). Coronary collateral perfusion was measured by using a myocardial particle infusion technique. The putative ARNi-induced pro-arteriogenic effects were further investigated and compared with an angiotensin-converting enzyme inhibitor (ACEi). Expression of the membrane receptors and key enzymes in the natriuretic peptide system (NPS), renin-angiotensin-aldosterone system (RAAS) and kallikrein-kinin system (KKS) were analyzed by quantitative polymerase chain reaction (qPCR) and immunoblot assay, respectively. Protein levels of pro-arteriogenic cytokines were measured by enzyme-linked immunosorbent assay, and mitochondrial DNA copy number was assessed by qPCR due to their roles in arteriogenesis. Furthermore, murine heart endothelial cells (MHEC5-T) were treated with a neprilysin inhibitor (NEPi) alone, or in combination with bradykinin receptor antagonists. MHEC5-T proliferation was analyzed by colorimetric assay.

Results

The in vivo study showed that ARNis markedly improved coronary collateral perfusion, regulated the gene expression of KKS, and increased the concentrations of relevant pro-arteriogenic cytokines. The in vitro study demonstrated that NEPis significantly promoted MHEC5-T proliferation, which was diminished by bradykinin receptor antagonists.

Conclusion

ARNis improve coronary collateral perfusion and exert pro-arteriogenic effects via the bradykinin receptor signaling pathway.
Prediction of compressive strength of recycled aggregate concrete using machine learning and Bayesian optimization methods
Authors: Zhang Xinyi , Dai Chengyuan , Li Weiyu , Chen Yang
Published: February 2023

With the sustainable development of the construction industry, recycled aggregate (RA) has been widely used in concrete preparation to reduce the environmental impact of construction waste. Compressive strength is an essential measure of the performance of recycled aggregate concrete (RAC). In order to understand the correspondence between relevant factors and the compressive strength of recycled concrete and accurately predict the compressive strength of RAC, this paper establishes a model for predicting the compressive strength of RAC using machine learning and hyperparameter optimization techniques. RAC experimental data from published literature as the dataset, extreme gradient boosting (XGBoost), random forest (RF), K-nearest neighbour (KNN), support vector machine regression Support Vector Regression (SVR), and gradient boosted decision tree (GBDT) RAC compressive strength prediction models were developed. The models were validated and compared using correlation coefficients (R2), Root Mean Square Error (RMSE), mean absolute error (MAE), and the gap between the experimental results of the predicted outcomes. In particular, The effects of different hyperparameter optimization techniques (Grid search, Random search, Bayesian optimization-Tree-structured Parzen Estimator, Bayesian optimization- Gaussian Process Regression) on model prediction efficiency and prediction accuracy were investigated. The results show that the optimal combination of hyperparameters can be searched in the shortest time using the Bayesian optimization algorithm based on TPE (Tree-structured Parzen Estimator); the BO-TPE-GBDT RAC compressive strength prediction model has higher prediction accuracy and generalisation ability. This high-performance compressive strength prediction model provides a basis for RAC’s research and practice and a new way to predict the performance of RAC.
Adjusting in a pandemic: Experiences of incoming international students
Authors: Tseu Anne , Ganesh Kirthana , Wirtz Derrick
Published: February 2023

Introduction

Over 4 million students travel outside their home countries to pursue tertiary education in the world, with over 600,000 students traveling to Canada alone. Adjustment to new cultures has often been shown to be stressful. The COVID-19 pandemic has been a significant global event that has affected all aspects of life in different ways. Although there is research showing the negative impact of the COVID-19 pandemic on international students globally, the study of the experiences of incoming cohorts of international students, particularly during the process of planning, traveling, and arriving at the host country, is still evolving.

Methods

Given that international students are sometimes at higher risk for mental health concerns, this qualitative study sought to explore the experiences of six incoming international graduate students, ages 18 to 32, through a semi-structured interview, as they moved from their home country to Canada. It explored their cultural adjustment in the context of the COVID-19 pandemic using a thematic analysis, through a descriptive phenomenological paradigm.

Results

Six themes emerged: choosing graduate programs; influence of pandemic on admission acceptance, moving to Canada, university experiences, adjustment; and adjustment as a student. Overall, international students appear to experience a “double dose” of stressors - the typical stressors of student hood, COVID-19 related challenges, as well as their unique manifestations in the context of being an international student.

Discussion

Limitations and implications of the study are discussed.
Teaching self-regulation through role modeling in K-12
Authors: Adıgüzel Tufan , Aşık Gürsu , Bulut Mehmet Akın , Kaya Mehmet Haldun , Özel Serkan
Published: February 2023

For K-12 teachers to develop effective teaching skills, integration of role modeling strategies into teaching and learning process as a dimension of selfregulated learning is of the foremost value. Role modeling strategy training through a hybrid professional development model bears the potential to serve as a facilitating component in promoting K-12 teachers’ instructional competence. Conducted within the self-regulated learning framework, this study suggested findings of a teacher professional development training aimed at role modeling strategy implementation at K-12 level. Pursuing a mixed-method model, the current research was performed with 16 teachers who were trained and supervised to integrate role-modeling strategies into their teaching context. In this study, the data sources were role-modeling- integrated lesson plans, trainers’ feedback on these lesson plans, and online student products. The data collection methods included lesson plan evaluation through a role-modeling rubric in a quantitative fashion, whereas content analysis of trainer feedback on lesson plans, latterly revised lesson plans and online student products composed the qualitative aspect. Results revealed that this professional development training achieved significantly positive changes in teachers’ role modeling strategy implementation skills, particularly in terms of teachers’ role as agents in students’ self-regulated learning skills, promotion of student-centered learning and overall improvement in students’ self-regulated learning skills. Further, the integration of education technology tools into lessons was observed to have a positive impact on enhancing students’ self-regulated learning skills. This study could offer major contributions to designing teacher professional development training for researchers, practitioners, and teacher trainers, particularly in role modeling dimension of self-regulated learning.
Development of a Syrian hamster anti-PD-L1 monoclonal antibody enables oncolytic adenoviral immunotherapy modelling in an immunocompetent virus replication permissive setting
Authors: Clubb James H. A. , Kudling Tatiana V. , Girych Mykhailo , Haybout Lyna , Pakola Santeri , Hamdan Firas , Cervera-Carrascon Víctor , Hemmes Annabrita , Grönberg-Vähä-Koskela Susanna , Santos João Manuel , Quixabeira Dafne C. A. , Basnet Saru , Heiniö Camilla , Arias Victor , Jirovec Elise , Kaptan Shreyas , Havunen Riikka , Sorsa Suvi , Erikat Abdullah , Schwartz Joel , Anttila Marjukka , Aro Katri , Viitala Tapani , Vattulainen Ilpo , Cerullo Vincenzo , Kanerva Anna , Hemminki Akseli
Published: February 2023

Introduction

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, but preclinical testing of hypotheses such as combination therapies has been complicated, in part due to species incompatibility issues. For example, one of few known permissive animal models for oncolytic adenoviruses is the Syrian hamster, for which an ICI, mainly an anti-PD-L1 monoclonal antibody (mAb) was not previously available. In this study, we developed an anti-Syrian hamster PD-L1 mAb to enable the evaluation of safety and efficacy, when combining anti-PD-L1 with an oncolytic adenovirus encoding tumour necrosis factor alpha (TNFα) and interleukin-2 (IL-2) (Ad5/3-E2F-D24-hTNFα-IRES-hIL-2 or TILT-123).

Methods

Recombinant Syrian hamster PD-L1 was expressed and mice immunized for mAb formation using hybridoma technology. Clonal selection through binding and functional studies in vitro, in silico and in vivo identified anti-PD-L1 clone 11B12-1 as the primary mAb candidate for immunotherapy modelling. The oncolytic virus (OV) and ICI combination approach was then evaluated using 11B12-1 and TILT-123 in a Syrian hamster model of pancreatic ductal adenocarcinoma (PDAC).

Results

Supernatants from hybridoma parent subclone 11B12B4 provided the highest positive PD-L1 signal, on Syrian hamster PBMCs and three cancer cell lines (HT100, HapT1 and HCPC1). In vitro co-cultures revealed superior immune modulated profiles of cell line matched HT100 tumour infiltrating lymphocytes when using subclones of 7G2, 11B12 and 12F1. Epitope binning and epitope prediction using AlphaFold2 and ColabFold revealed two distinct functional epitopes for clone 11B12-1 and 12F1-1. Treatment of Syrian hamsters bearing HapT1 tumours, with 11B12-1 induced significantly better (p<0.05) tumour growth control than isotype control by day 12. 12F1-1 did not induce significant tumour growth control. The combination of 11B12-1 with oncolytic adenovirus TILT-123 improved tumour growth control further, when compared to monotherapy (p<0.05) by day 26.

Conclusions

Novel Syrian hamster anti-PD-L1 clone 11B12-1 induces tumour growth control in a hamster model of PDAC. Combining 11B12-1 with oncolytic adenovirus TILT-123 improves tumour growth control further and demonstrates good safety and toxicity profiles.
The markers to delineate different phenotypes of macrophages related to metabolic disorders
Authors: Wei Quxing , Deng Yanyue , Yang Qianqian , Zhan Angyu , Wang Lexun
Published: February 2023

Macrophages have a wide variety of roles in physiological and pathological conditions, making them promising diagnostic and therapeutic targets in diseases, especially metabolic disorders, which have attracted considerable attention in recent years. Owing to their heterogeneity and polarization, the phenotypes and functions of macrophages related to metabolic disorders are diverse and complicated. In the past three decades, the rapid progress of macrophage research has benefited from the emergence of specific molecular markers to delineate different phenotypes of macrophages and elucidate their role in metabolic disorders. In this review, we analyze the functions and applications of commonly used and novel markers of macrophages related to metabolic disorders, facilitating the better use of these macrophage markers in metabolic disorder research.
Serum amyloid alpha 1-2 are not required for liver inflammation in the 4T1 murine breast cancer model
Authors: He Chenfeng , Konishi Riyo , Harata Ayano , Nakamura Yuki , Mizuno Rin , Yoda Mayuko , Toi Masakazu , Kawaguchi Kosuke , Kawaoka Shinpei
Published: February 2023

Cancers induce the production of acute phase proteins such as serum amyloid alpha (SAA) in the liver and cause inflammation in various host organs. Despite the well-known coincidence of acute phase response and inflammation, the direct roles of SAA proteins in inflammation in the cancer context remains incompletely characterized, particularly in vivo. Here, we investigate the in vivo significance of SAA proteins in liver inflammation in the 4T1 murine breast cancer model. 4T1 cancers elevate the expression of SAA1 and SAA2, the two major murine acute phase proteins in the liver. The elevation of Saa1-2 correlates with the up-regulation of immune cell-related genes including neutrophil markers. To examine this correlation in detail, we generate mice that lack Saa1-2 and investigate immune-cell phenotypes. RNA-seq experiments reveal that deletion of Saa1-2 does not strongly affect 4T1-induced activation of immune cell-related genes in the liver. Flow cytometry experiments demonstrate the dispensable roles of SAA1-2 in cancer-dependent neutrophil infiltration to the liver. Consistently, 4T1-induced gene expression changes in bone marrow do not require Saa1-2. This study clarifies the negligible contribution of SAA1-2 proteins in liver inflammation in the 4T1 breast cancer model.
Homologous booster immunization with an inactivated vaccine induced robust antibody response in healthcare workers: A retrospective study
Authors: Wen Gui-Ping , Zhu Min , Li Li-Rong , Li Xiu-Juan , Ye Hui-Ming , Zhou Yu-Lin
Published: February 2023

Coronavirus Disease 2019 (Covid-19) severely impacted the health, society, and economy around the world. With declining protective efficacy of primary vaccination and the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, a Covid-19 booster vaccination is being fully implemented globally. Many people received three doses of BBIBP-CorV inactivated vaccine in China and other developing countries. However, the antibody response and immune persistence of the homologous BBIBP-CorV booster vaccination is yet to be thoroughly evaluated, as previous studies focused within one month after the third dose. In this study, 97 participants were enrolled to analyze the antibody response and immune persistence within 6 months as well as the safety within 7 days after the third-dose of homologous BBIBP-CorV inactivated vaccine. The seroconversion rate for total antibody against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein were both 100% at month 1 and month 6 after the third dose. The IgG against the RBD of the SARS-CoV-2 S protein seroconversion rate increased from 42.27% before the third dose to 100% 1 month after the third dose and then slightly decreased to 98.97% 5 months later. Positive IgM against the RBD of the SARS-CoV-2 S protein was rare and was observed in only one participant at month 1 after the third dose. The neutralizing antibody levels at month 1 and month 6 after the third dose increased 63.32-fold and 13.16-fold compared with those before the third dose, and the positive rate for neutralizing antibody was still 100% at month 6 after the third dose. Importantly, the antibody responses induced by the vaccine and immune persistence were not affected by sex or age. No serious adverse reactions were reported. Total antibody and IgG against the RBD of the SARS-CoV-2 S protein were highly correlated with neutralizing antibody, suggesting that total antibody and IgG against the RBD of the SARS-CoV-2 S protein could be used as predictors for neutralizing antibody. In conclusion, the third dose of homologous BBIBP-CorV inactivated vaccine induced a robust antibody response and moderate immune persistence. These finding are of great significance for development future vaccination strategies.
Breaking down the cellular responses to type I interferon neurotoxicity in the brain
Authors: Viengkhou Barney , Hofer Markus J.
Published: February 2023

Since their original discovery, type I interferons (IFN-Is) have been closely associated with antiviral immune responses. However, their biological functions go far beyond this role, with balanced IFN-I activity being critical to maintain cellular and tissue homeostasis. Recent findings have uncovered a darker side of IFN-Is whereby chronically elevated levels induce devastating neuroinflammatory and neurodegenerative pathologies. The underlying causes of these ‘interferonopathies’ are diverse and include monogenetic syndromes, autoimmune disorders, as well as chronic infections. The prominent involvement of the CNS in these disorders indicates a particular susceptibility of brain cells to IFN-I toxicity. Here we will discuss the current knowledge of how IFN-Is mediate neurotoxicity in the brain by analyzing the cell-type specific responses to IFN-Is in the CNS, and secondly, by exploring the spectrum of neurological disorders arising from increased IFN-Is. Understanding the nature of IFN-I neurotoxicity is a crucial and fundamental step towards development of new therapeutic strategies for interferonopathies.