bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Our Natural Food Our Homeostasis? Array of a Thousand Effect-Directed Profiles of 68 Herbs and Spices
Authors: Schreiner Tamara , Sauter Dorena , Friz Maren , Heil Julia , Morlock Gertrud Elisabeth
Published: December 2021

The beneficial effects of plant-rich diets and traditional medicines are increasingly recognized in the treatment of civilization diseases due to the abundance and diversity of bioactive substances therein. However, the important active portion of natural food or plant-based medicine is presently not under control. Hence, a paradigm shift from quality control based on marker compounds to effect-directed profiling is postulated. We investigated 68 powdered plant extracts (botanicals) which are added to food products in food industry. Among them are many plants that are used as traditional medicines, herbs and spices. A generic strategy was developed to evaluate the bioactivity profile of each botanical as completely as possible and to straightforwardly assign the most potent bioactive compounds. It is an 8-dimensional hyphenation of normal-phase high-performance thin-layer chromatography with multi-imaging by ultraviolet, visible and fluorescence light detection as well as effect-directed assay and heart-cut of the bioactive zone to orthogonal reversed-phase high-performance liquid chromato-graphy−photodiode array detection−heated electrospray ionization mass spectrometry. In the non-target, effect-directed screening via 16 different on-surface assays, we tentatively assigned more than 60 important bioactive compounds in the studied botanicals. These were antibacterials, estrogens, antiestrogens, androgens, and antiandrogens, as well as acetylcholinesterase, butyrylcholinesterase, α-amylase, α-glucosidase, β-glucosidase, β-glucuronidase, and tyrosinase inhibitors, which were on-surface heart-cut eluted from the bioautogram or enzyme inhibition autogram to the next dimension for further targeted characterization. This biological-physicochemical hyphenation is able to detect and control active mechanisms of traditional medicines or botanicals as well as the essentials of plant-based food. The array of 1,292 profiles (68 samples × 19 detections) showed the versatile bioactivity potential of natural food. It reveals how efficiently and powerful our natural food contributes to our homeostasis.
Metabolomic Profiling Identifies Exogenous and Microbiota-Derived Metabolites as Markers of Methotrexate Efficacy in Juvenile Idiopathic Arthritis
Authors: Funk Ryan Sol , Becker Mara L.
Published: December 2021

Variability in methotrexate (MTX) efficacy represents a barrier to early and effective disease control in the treatment of juvenile idiopathic arthritis (JIA). This work seeks to understand the impact of MTX on the plasma metabolome and to identify metabolic biomarkers of MTX efficacy in a prospective cohort of children with JIA. Plasma samples from a cohort of children with JIA (n = 30) collected prior to the initiation of MTX and after 3 months of therapy were analyzed using a semi-targeted global metabolomic platform detecting 673 metabolites across a diversity of biochemical classes. Disease activity was measured using the 71-joint count juvenile arthritis disease activity score (JADAS-71) and clinical response to MTX was based on achievement of ACR Pedi 70 response. Metabolomic analysis identified 50 metabolites from diverse biochemical classes that were altered following the initiation of MTX (p < 0.05) with 15 metabolites reaching a false-discovery rate adjusted p-value (q-value) of less than 0.05. Enrichment analysis identified a class-wide reduction in unsaturated triglycerides following initiation of MTX (q = 0.0009). Twelve of the identified metabolites were significantly associated with disease activity by JADAS-71. Reductions in three metabolites were found to be associated with clinical response by ACR Pedi 70 response criteria and represented several microbiota and exogenously derived metabolites including: dehydrocholic acid, biotin, and 4-picoline. These findings support diverse metabolic changes following initiation of MTX in children with JIA and identify metabolites associated with microbial metabolism and exogenous sources associated with MTX efficacy.
A Bimodal Pattern and Age-Related Growth of Intra-Annual Wood Cell Development of Chinese Fir in Subtropical China
Authors: Jiang Yanyan , Zhang Xiongqing , Chhin Sophan , Zhang Jianguo
Published: December 2021

Age plays an important role in regulating the intra-annual changes in wood cell development. Investigating the effect of age on intra-annual wood cell development would help to understand cambial phenology and xylem formation dynamics of trees and predict the growth of trees accurately. Five intermediate trees in each stand (total of 5 stands) in five age groupings of Chinese fir (Cunninghamia lanceolataHook.) plantations in subtropical China were monitored on micro-cores collected weekly or biweekly from January to December in 2019. We modeled the dynamics of wood cell development with a mixed effects model, analyzed the age effect on intra-annual wood cell development, and explored the contribution of rate and duration of wood cell development on intra-annual wood cell development. We found a bimodal pattern of wood cell development in all age classes, and no matter the date of peak or the maximal number of cells the bimodal patterns were similar in all age classes. In addition, compared with the older trees, the younger trees had the longest duration of wood cell development because of the later end of wood cell development and a larger number of wood cells. The younger trees had the faster growth rate than the older trees, but the date of the maximal growth rate in older trees was earlier than younger trees, which led to the production of more wood cells in the younger trees. Moreover, we found that the number of cells in wood cell formation was mostly affected by the rate (92%) rather than the duration (8%) of wood cell formation.
What Influences People’s Tradeoff Decisions Between CO2 Emissions and Travel Time? An Experiment With Anchors and Normative Messages
Authors: Andersson Hanna , Ahonen-Jonnarth Ulla , Holmgren Mattias , Marsh John E. , Wallhagen Marita , Bökman Fredrik
Published: December 2021

One of the today’s greatest challenges is to adjust our behavior so that we can avoid a major climate disaster. To do so, we must make sacrifices for the sake of the environment. The study reported here investigates how anchors (extrinsic motivational-free information) and normative messages (extrinsic motivational information) influence people’s tradeoffs between travel time and carbon dioxide (CO2) emissions in the context of car travel and whether any interactions with environmental concern (an intrinsic motivational factor) can be observed. In this study, people received either a CO2, health or no normative message together with either a high anchor, a low anchor, or no anchor. People that received both a high anchor and a CO2 emission normative message were willing to travel for a longer time than those that only received a high anchor. If a low anchor was presented, no differences in willingness to travel for a longer time were found between the three different conditions of normative message groups, i.e., CO2 normative message, health normative message, or no normative message. People with higher concern for the environment were found to be willing to travel for a longer time than those with lower concern for the environment. Further, this effect was strongest when a high anchor was presented. These results suggest that anchors and normative messages are among the many factors that can influence people’s tradeoffs between CO2 emission and travel time, and that various factors may have to be combined to increase their influence over pro-environmental behavior and decisions.
Do Emotions Benefit Investment Decisions? Anticipatory Emotion and Investment Decisions in Non-professional Investors
Authors: Hinvest Neal S. , Alsharman Muhamed , Roell Margot , Fairchild Richard
Published: December 2021

Increasing financial trading performance is big business. A lingering question within academia and industry concerns whether emotions improve or degrade trading performance. In this study, 30 participants distributed hypothetical wealth between a share (a risk) and the bank (paying a small, sure, gain) within four trading games. Skin Conductance Response was measured while playing the games to measure anticipatory emotion, a covert emotion signal that impacts decision-making. Anticipatory emotion was significantly associated with trading performance but the direction of the correlation was dependent upon the share’s movement. Thus, anticipatory emotion is neither wholly “good” nor “bad” for trading; instead, the relationship is context-dependent. This is one of the first studies exploring the association between anticipatory emotion and trading behaviour using trading games within an experimentally rigorous environment. Our findings elucidate the relationship between anticipatory emotion and financial decision-making and have applications for improving trading performance in novice and expert traders.
The Future of Positive Psychology and Disability
Authors: Wehmeyer Michael L.
Published: December 2021

For much of the history of the application of psychology to disability, the research and clinical focus of the field was deficits-oriented: documenting what people with disability could not do, proposing theories of why they could not do these things, creating measures to assess this incapacity and incompetence, and building interventions and treatments predicated on disease and pathology. It has been only in the last few decades that conceptualizations of disability allowed for consideration of strengths and positive attributes along with the presence of disability and only in the past two decades that a positive psychology of disability has emerged. This article will briefly summarize the factors that led to the emergence of a focus on the positive psychology of disability and a strength-based approach in the field, examine the state of knowledge and practice as it pertains to the positive psychology of disability, and will examine challenges that serve as barriers to progress in this area and opportunities for advancement. Among these is examining how “optimal human functioning” can be understood in ways that includes, and not excludes, people with disability. The importance of shifting the disability research and practice focus to emphasize flourishing, well-being, and self-determination of and for people with disability will be discussed, as well as the necessity for the field of positive psychology to more aggressively reach out to include people with disability among those populations whom the field values and includes.
Innovation Orientation in the Non-profit Sector: Analysis of Its Impact on the Performance of Spanish Non-governmental Development Organizations
Authors: Valero-Amaro Víctor , Galera-Casquet Clementina , Barroso-Méndez María Jesús
Published: December 2021

Since 2015, the approval of the 2030 Agenda and of the 17 Sustainable Development Goals (SDGs) has led to a notable reshaping and expansion of the architecture of the international cooperation system. The SDGs mark a new path for the planning processes of the different actors working for development, expanding their goals, proposing an update of the roles they must play, and defining new frameworks for relationships and spaces for action. Non-governmental development organizations (NGDOs), whose traditional mission focused on reducing the poverty gap, defending human rights, or promoting environmental protection, must be able to respond satisfactorily to these new challenges, pass beyond their classic positions, and adapt to an increasingly complex and turbulent global context. Achieving high impact in the SDGs requires development organizations to be more agile and innovative. With the intention of bringing visibility to the importance that innovation can play in the success and results achieved by development cooperation organizations, the main objective of this study was to validate, through a sample of Spanish NGDOs, a causal model that represents the positive contribution which innovation orientation generates in the result of the activity of these entities. This research concludes by confirming that innovation orientation favors the attainment of a higher degree of success in the projects and actions carried out by non-profit entities which promote the SDGs, which has a direct and positive impact on the performance they achieve.
Service Characteristics and Geographical Variation in Compulsory Hospitalisation: An Exploratory Random Effects Within–Between Analysis of Norwegian Municipalities, 2015–2018
Authors: Hofstad Tore , Rugkåsa Jorun , Ose Solveig Osborg , Nyttingnes Olav , Kjus Solveig Helene Høymork , Husum Tonje Lossius
Published: December 2021

Background: Compulsory hospitalisation in mental healthcare is contested. For ethical and legal reasons, it should only be used as a last resort. Geographical variation could indicate that some areas employ compulsory hospitalisation more frequently than is strictly necessary. Explaining variation in compulsory hospitalisation might contribute to reducing overuse, but research on associations with service characteristics remains patchy.

Objectives: We aimed to investigate the associations between the levels of compulsory hospitalisation and the characteristics of primary mental health services in Norway between 2015 and 2018 and the amount of variance explained by groups of explanatory variables.

Methods: We applied random-effects within–between Poisson regression of 461 municipalities/city districts, nested within 72 community mental health centre catchment areas (N = 1,828 municipality-years).

Results: More general practitioners, mental health nurses, and the total labour-years in municipal mental health and addiction services per population are associated with lower levels of compulsory hospitalisations within the same areas, as measured by both persons (inpatients) and events (hospitalisations). Areas that, on average, have more general practitioners and public housing per population have lower levels of compulsory hospitalisation, while higher levels of compulsory hospitalisation are seen in areas with a longer history of supported employment and the systematic gathering of service users' experiences. In combination, all the variables, including the control variables, could account for 39–40% of the variation, with 5–6% related to municipal health services.

Conclusion: Strengthening primary mental healthcare by increasing the number of general practitioners and mental health workers can reduce the use of compulsory hospitalisation and improve the quality of health services.
Mental Disorders in Individuals With Exercise Addiction—A Cross-Sectional Study
Authors: Meyer Maximilian , Sattler Isabel , Schilling Hanna , Lang Undine E. , Schmidt André , Colledge Flora , Walter Marc
Published: December 2021

Background and Aims: Exercise addiction has not yet been designated as an addictive disorder in the DSM-5 due to a lack of detailed research. In particular, associations with other psychiatric diagnoses have received little attention. In this study, individuals with a possible exercise addiction are clinically assessed, in order to establish a profile of co-occurring psychiatric disorders in individuals with exercise addiction.

Methods: One hundred and fifty-six individuals who reported exercising more than 10 h a week, and continued to do so despite illness or injury, were recruited for the study. Those who met the cut-off of the Exercise Dependence Scale (n = 32) were invited to participate in a screening with the Structured Clinical Interview for DSM-5 (SCID-5-CV) and personality disorders (SCID-5-PD). Additionally, an interview based on the DSM-5 criteria of non-substance-related addictive disorders was conducted to explore the severity of exercise addiction symptoms.

Results: 75% of participants fulfilled the criteria for at least one psychiatric disorder. Depressive disorders (56.3%), personality disorders (46.9%) and obsessive-compulsive disorders (31.3%) were the most common disorders. Moreover, there was a significant positive correlation between the number of psychiatric disorders and the severity of exercise addiction (r = 0.549, p = 0.002).

Discussion: The results showed a variety of mental disorders in individuals with exercise addiction and a correlation between the co-occurrence of mental disorders and the severity of exercise addiction. Exercise addiction differs from other addictive und substance use disorders, as obsessive-compulsive (Cluster C), rather than impulsive (Cluster B) personality traits were most commonly identified.

Conclusions: Our results underscore the importance of clinical diagnostics, and indicate that treatment options for individuals with exercise addiction are required. However, the natural history and specific challenges of exercise addiction must be studied in more detail.
Construction and Analysis of a Diagnostic Model Based on Differential Expression Genes in Patients With Major Depressive Disorder
Authors: Long Qing , Wang Rui , Feng Maoyang , Zhao Xinling , Liu Yilin , Ma Xiao , Yu Lei , Li Shujun , Guo Zeyi , Zhu Yun , Teng Zhaowei , Zeng Yong
Published: December 2021

Background: Major depressive disorder (MDD) is a common and severe psychiatric disorder with a heavy burden on the individual and society. However, the prevalence varies significantly owing to the lack of auxiliary diagnostic biomarkers. To identify the shared differential expression genes (DEGs) with potential diagnostic value in both the hippocampus and whole blood, a systematic and integrated bioinformatics analysis was carried out.

Methods: Two datasets from the Gene Expression Omnibus database (GSE53987 and GSE98793) were downloaded and analyzed separately. A weighted gene co-expression network analysis was performed to construct the co-expression gene network of DEGs from GSE53987, and the most disease-related module was extracted. The shared DEGs from the module and GSE98793 were identified using a Venn diagram. Functional pathway prediction was used to identify the most disease-related DEGs. Finally, several DEGs were chosen, and their potential diagnostic value was determined by receiver operating characteristic curve analysis.

Results: After weighted gene co-expression network analysis, the most MDD-related module (MEgrey) was identified, and 623 DEGs were extracted from this module. The intersection between MEgrey and GSE98793 was calculated, and 163 common DEGs were identified. The co-expression network of 163 DEGs from these was then reconstructed. All hub genes were identified based on the connective degree of the reconstructed co-expression network. Based on the results of functional pathway enrichment, 17 candidate hub genes were identified. Finally, logistic regression and receiver operating characteristic curves showed that three candidate hub genes (CEP350, SMAD5, and HSPG2) had relatively high auxiliary value in the diagnosis of MDD.

Conclusion: Our results showed that the combination of CEP350, SMAD5, and HSPG2 has a relatively high diagnostic value for MDD. Pathway enrichment analysis also showed that these genes may play an important role in the pathogenesis of MDD. These results suggest a potentially important role for this gene combination in clinical practice.
Solidarity and HIV Testing Willingness During the COVID-19 Epidemic: A Study Among Men Who Have Sex With Men in China
Authors: Lyu Hang , Zhou Yi , Dai Wencan , Zhen Shihan , Huang Shanzi , Zhou Lanlan , Huang Liqun , Tang Weiming
Published: December 2021

Background: Solidarity, such as community connectedness and social cohesion, may be useful in improving HIV testing uptake among men who have sex with men (MSM). This study aimed to evaluate the impact of solidarity on HIV testing before the coronavirus disease 2019 (COVID-19) and HIV testing willingness during COVID-19 among MSM in China.

Materials and Methods: An online survey was conducted to collect sociodemographic, sexual behavioral, and solidarity items' information from the participants. We first used factor analysis to reveal the principal component of the solidarity items and then used logistic regression to study the impact of solidarity on HIV testing, by adjusting the possible confounding factors, such as age and education.

Results: Social cohesion and community connectedness were revealed by the factor analysis. MSM with high community connectedness were more willing to undergo HIV testing before the epidemic adjusted by age [odds ratio (OR): 1.07, 95% CI: 1.01–1.13]. The community connectedness was also related to the willingness of HIV testing during the epidemic, with adjustments of 1.09 (95% CI: 1.03–1.15). People who did not test for HIV before the COVID-19 epidemic were more willing to have the HIV test during the epidemic, which was correlated with the community connectedness, and the OR value was 1.14 (95%: 1.03–1.25).

Conclusion: A high level of community connectedness helped to increase the HIV testing rate before COVID-19 and the willingness of HIV testing during the epidemic among MSM. Strategies can strengthen the role of the community in the management and service of MSM.
Connecting Medical Personnel to Dentists via Teledentistry in a Children's Hospital System: A Pilot Study
Authors: Hammersmith Kimberly J. , Thiel Macaire C. , Messina Matthew J. , Casamassimo Paul S. , Townsend Janice A.
Published: December 2021

Investigators evaluated feasibility, acceptability, and sustainability of a teledentistry pilot program within a children's hospital network between March, 2018, and April, 2019. The program connected dentists to medical personnel and patients being treated in urgent care clinics, a primary care clinic, and a freestanding emergency department via synchronous video consultation. Three separate but parallel questionnaires evaluated caregiver, medical personnel, and dentist perspectives on the experience. Utilization of teledentistry was very low (2%, 14/826 opportunities), but attitudes regarding this service were largely positive among all groups involved and across all survey domains. Uptake of new technology has barriers but teledentistry may be an acceptable service, especially in the case of dental trauma.
What Is Genetic Diversity and Why Does it Matter?
Authors: Minter Melissa , Nielsen Erica S. , Blyth Colette , Bertola Laura D. , Kantar Michael Benjamin , Morales Hernán E. , Orland Chloé , Segelbacher Gernot , Leigh Deborah M.
Published: December 2021

All living things on Earth contain a unique code within them, called DNA. DNA is organised into genes, similar to the way letters are organised into words. Genes give our bodies instructions on how to function. However, the exact DNA code is different even between individuals within the same species. We call this genetic diversity. Genetic diversity causes differences in the shape of bird beaks, in the flavours of tomatoes, and even in the colour of your hair! Genetic diversity is important because it gives species a better chance of survival. However, genetic diversity can be lost when populations get smaller and isolated, which decreases a species’ ability to adapt and survive. In this article, we explore the importance of genetic diversity, discuss how it is formed and maintained in wild populations, how it is lost and why that is dangerous, and what we can do to conserve it.
Secondary Magnetic Reconnection at Earth’s Flank Magnetopause
Authors: Tang B. B. , Li W. Y. , Wang C. , Khotyaintsev Yu. V. , Graham D. B. , Zhang Q. H. , Sun T. R. , Li H. , Wang X. Y. , Trattner K. J. , Giles B. L. , Lindqvist P. A. , Ergun R. E. , Burch J. L.
Published: December 2021

We report local secondary magnetic reconnection at Earth’s flank magnetopause by using the Magnetospheric Multiscale observations. This reconnection is found at the magnetopause boundary with a large magnetic shear between closed magnetospheric field lines and the open field lines generated by the primary magnetopause reconnection at large scales. Evidence of this secondary reconnection are presented, which include a secondary ion jet and the encounter of the electron diffusion region. Thus the observed secondary reconnection indicates a cross-scale process from a global scale to an electron scale. As the aurora brightening is also observed at the morning ionosphere, the present secondary reconnection suggests a new pathway for the entry of the solar wind into geospace, providing an important modification to the classic Dungey cycle.
The Problematic Experience of Players' Mutations Between Clubs: Discovering the Social Adaptability Skills Required
Authors: Owiti Samuel , Hauw Denis
Published: December 2021

Objective:During their career, most players working in professional team sports move from club to club. These transitions are not always completely successful and could highly impact the route of the players' development. However, there is a lack of knowledge on the psychological processes involved when players encounter problems in adapting from one club to another. Thus, it was the aim of this study to identify the most difficult aspects of these transitions, as experienced by team sports players and the psychological skills that contribute to successful outcomes.

Design and Method:The present study included twenty professional basketball players (aged between 20 and 36 years old; Mean = 26.05, SD = 4.12), who had played under different coaches (coach range 4–15; Mean = 8.65, SD = 2.92), and also played for different clubs (range 3–10; Mean = 5.35, SD = 2.08). They took part in retrospective interviews regarding their embedded experiences during club to club transitions. A situated E-approach was used to identify their problematic experiences, the adaptability skills and how they are applied during club mutations.

Results and Conclusions:The identification of problematic experiences revealed seven components in relation to coaching (e.g., obeying orders, reduced play time), three components with teammates (e.g., respect), two components with the club (e.g., lack of support), and three components with family/friends (e.g., geographical constraints). Additionally, results indicated that the adaptability skills used during mutation are related to three groups namely mental skills, learning methods, and interpersonal skills. The results provide coaches, players, sports psychologists, and national sport organizations a set of issues for understanding the challenges players encounter when they move from one club to another.
Longer Neurophysiological vs. Clinical Recovery Following Sport Concussion
Authors: Ntikas Michail , Hunter Angus M. , Gallagher Iain J. , Di Virgilio Thomas G.
Published: December 2021

Objectives:The objective of this study was to assess if injury-related alterations in the Sport Concussion Assessment Tool-5 (SCAT5) are matched by changes in transcranial magnetic stimulation-derived intracortical inhibition. We hypothesised that neurophysiological measures would take longer to return to normal than recovery assessed by the SCAT5 following sport related concussion (SRC).

Methods:Thirteen male contact sport athletes (20.5 ± 4.5 years), who reported a concussion were recruited from local Rugby and American football clubs. Participants were tested at 4 timepoints throughout the concussion recovery period: within 24 h of concussion (day 0), and at 7, 9, and 11 days after concussion. All participants completed the SCAT5 and underwent TMS to assess cortical silent period duration (CSp), a measure of intracortical inhibition.

Results:After concussion CSp significantly declined from day 0 (122 ± 28 ms) to day 11 (106 ± 15 ms) [F(3, 33)= 7.80,p< 0.001]. SCAT5 measures of symptom number and severity were significantly decreased [symptom number:χ(3)2= 30.44,p< 0.01; symptom severity:χ(3)2= 25.75,p< 0.001] between the day 0 timepoint and each of the other timepoints. SCAT5 balance errors (mBESS) decreased significantly [F(3, 33)= 19.55,p< 0.001] between the day 0 timepoint and each of the other timepoints. CSp and SCAT5 recovery patterns were different. SCAT5 domains recovered faster showing no further significant changes after day 7, whilst CSp was still decreasing between days 7 and 9. Due to the small sample size we also used a Bayesian linear model to investigate the recovery of CSp and mBESS. The posterior distribution of our Bayesian model provided evidence that CSp decreased at day 7 and it continued to decrease at day 9, unlike mBESS which decreased at day 7 and then reached a plateau.

Conclusion:There are clinically important discrepancies between clinical and neurophysiological measures of concussion recovery. This finding has important implications for return to play (RTP) protocols and the prevention of complications after sport concussion.
Organoids in Lung Cancer Management
Authors: Li Yushi , Chan Joyce W. Y. , Lau Rainbow W. H. , Cheung Winnie W. Y. , Wong Alissa Michelle , Wong Aikha M. , Wong Nathalie , Ng Calvin Sze Hang
Published: December 2021

Lung cancer is a complex milieu of genomically altered cancer cells, a diverse collection of differentiated cells and nonneoplastic stroma. Lung cancer organoids is a three-dimensional structure grown from patient cancer tissue that could mimic in vivo complex behavior and cellular architecture of the cancer. Furthermore, the genomic alterations of the primary lung tumor is captured ex vivo. Lung cancer organoids have become an important preclinical model for oncology studies in recent years. It could be used to model the development of lung cancer, investigate the process of tumorigenesis, and also study the signaling pathways. The organoids could also be a platform to perform drug screening and biomarker validation of lung cancer, providing a promising prediction of patient-specific drug response. In this review, we described how lung cancer organoids have opened new avenues for translating basic cancer research into clinical therapy and discussed the latest and future developments in organoid technology, which could be further applied in lung cancer organoids research.
Targeting Myeloid-Derived Suppressor Cells Derived From Surgical Stress: The Key to Prevent Post-surgical Metastasis
Authors: Zhu Sha , Zhao Yunuo , Quan Yuxin , Ma Xuelei
Published: December 2021

Myeloid-derived suppressor cells (MDSCs) are known to play an essential part in tumor progression under chronic stress settings through their manipulation of adaptive and innate immune systems. Previous researches mainly focus on MDSC's role in the chronic tumor immune environment. In addition, surgery can also serve as a form of acute stress within the patient's internal environment. Nevertheless, the part that MDSCs play in post-surgical tumor development has not gained enough attention yet. Although surgery is known to be an effective definite treatment for most localized solid tumors, there are still plenty of cancer patients who experience recurrence or metastasis after radical resection of the primary tumor. It is believed that surgery has the paradoxical capability to enhance tumor growth. Many possible mechanisms exist for explaining post-surgical metastasis. We hypothesize that surgical resection of the primary tumor can also facilitate the expansion of MDSCs and their pro-tumor role since these surgery-induced MDSCs can prepare the pre-metastatic niche (the “soil”) and at the same time interact with circulating tumor cells (the “seeds”). This vicious, reciprocal mechanism is a crucial point in the emergence of post-surgical metastasis. According to our hypothesis, MDSCs can be the precise target to prevent cancer patients from post-surgical recurrence and metastasis during the perioperative phase to break the wretched cycle and provide better long-term survival for these patients. Future studies are needed to validate this hypothesis.
Owner's Perception of Seizure Detection Devices in Idiopathic Epileptic Dogs
Authors: Bongers Jos , Gutierrez-Quintana Rodrigo , Stalin Catherine Elizabeth
Published: December 2021

Accurate knowledge of seizure frequency is key to optimising treatment. New methods for detecting epileptic seizures are currently investigated in humans, which rely on changes in biomarkers, also called seizure detection devices. Critical to device development, is understanding user needs and requirements. No information on this subject has been published in veterinary medicine. Many dog health collars are currently on the market, but none has proved to be a promising seizure detector. An online survey was created and consisted of 27 open, closed, and scaled questions divided over two parts: part one focused on general questions related to signalment and seizure semiology, the second part focused specifically on the use of seizure detection devices. Two hundred and thirty-one participants caring for a dog with idiopathic epilepsy, were included in the study. Open questions were coded using descriptive coding by two of the authors independently. Data was analysed using descriptive statistics and binary logistic regression. Our results showed that the unpredictability of seizures plays a major part in the management of canine epilepsy and dog owners have a strong desire to know when a seizure occurs. Nearly all dog owners made changes in their daily life, mainly focusing on intensifying supervision. Owners believed seizure detection devices would improve their dog's seizure management, including a better accuracy of seizure frequency and the ability to administer emergency drugs more readily. Owners that were already keeping track of their dog's seizures were 4.2 times more likely to show confidence in using seizure detection devices to manage their pet's seizures, highlighting the need for better monitoring systems. Our results show that there is a receptive market for wearable technology as a new management strategy in canine epilepsy and this topic should be further explored.
Using Patient-Derived Xenografts to Explore the Efficacy of Treating Head-and-Neck Squamous Cell Carcinoma With Anlotinib
Authors: Hu Fangling , Guo Liang , Yu Jieqing , Dai Daofeng , Xiong Yuanping , He Yuanqiao , Zhou Wensheng
Published: December 2021

Objective: The efficacy of anlotinib as a treatment for head-and-neck squamous cell carcinoma (HNSCC) has been little explored. Here, we used patient-derived xenografts (PDXs) to this end.

Methods: Fresh tumor tissues of HNSCC patients were screened in terms of in vitro drug sensitivity using the MTT assay. Patient PDXs were used to confirm the anti-tumor effects of anlotinib in vivo. After the medication regimen was complete, the tumor volume changes in mice were calculated. Apoptosis was measured using the TUNEL assay. The cell proliferation and apoptosis levels of PDXs yielded data on the utility of anlotinib treatment in vivo.

Results: Anlotinib suppressed the in vitro proliferation of nine tumor tissues by an average of 51.05 ± 13.74%. Anlotinib also significantly inhibited the growth of three PDXs in mice (tumor growth inhibition 79.02%). The expression levels of Ki-67 and proliferating cell nuclear antigen after anlotinib treatment were significantly lower than those in the controls. The negative and positive controls exhibited no and some apoptosis, respectively, whereas the anlotinib group evidenced extensive apoptosis.

Conclusion: Anlotinib suppressed HNSCC growth in vitro and in vivo (by inhibiting cell proliferation and promoting apoptosis), suggesting that anlotinib can potentially treat HNSCC.
Bölcsességfogak koronektómiája és annak szövődményei
Authors: Körmöczi Kinga , Bogdán Sándor , Joób-Fancsaly Árpád
Published: December 2021

Az alsó impaktált bölcsességfogak sebészi ellátása a beavatkozások buktatói és lehetséges szövődményei miatt komoly kihívást jelenthetnek a szájsebészek, fogorvosok számára. A szövődmények elkerülése érdekében alapos anatómiai, műtéttechnikai ismeretekre, korszerű diagnosztikai módszerekre van szükségünk. Az egyik legrettegettebb szövődmény a nervus alveolaris inferior sérülése, az érintett ajakfél átmeneti vagy maradandó paraesthesiája. Ennek elkerülése érdekében alkalmazható alternatív módszer a bölcsességfogak koronektómiája. Közleményünkben klinikai eseteinken keresztül tekintjük át a koronektómia lehetőségeit, annak lehetséges buktatóit.
A fogászati implantátumok felületmorfológiájának befolyása a csontintegrációra
Authors: Koppány Ferenc
Published: December 2021

A dentális implantátumok felületi morfológiájának fontosságát már Bränemark is hangsúlyozta a nyolcvanas években megfogalmazott csontintegráció folyamatának alapjaként. Az elmúlt pár évtizedben – mint sok más területen – az orális implantológián belül is jelentős változások történtek. A felületi morfológia jelenleg is az egyik legintenzívebb alapkutatási terület. Az internetes keresőportálok szerint napi egy-két tudományos publikáció jelenik meg ebben a témában. A hazai kutások is jelentősek. Több tudományos műhelyben – kooperálva a műszaki területen tevékenykedő kollégákkal – vizsgálatok sora zajlik most is. Számtalan publikáció, előadás, PhD munka született az implantátumok felületének vizsgálati anyagából. A szerző célja az volt, hogy összefoglalja a múlt és jelen állását a témából és irányvonalakat mutassona jövőbeli kutatások tárgyából is.
Mouse Models of Frequently Mutated Genes in Acute Myeloid Leukemia
Authors: Mohanty Sagarajit , Heuser Michael
Published: December 2021

Acute myeloid leukemia is a clinically and biologically heterogeneous blood cancer with variable prognosis and response to conventional therapies. Comprehensive sequencing enabled the discovery of recurrent mutations and chromosomal aberrations in AML. Mouse models are essential to study the biological function of these genes and to identify relevant drug targets. This comprehensive review describes the evidence currently available from mouse models for the leukemogenic function of mutations in seven functional gene groups: cell signaling genes, epigenetic modifier genes, nucleophosmin 1 (NPM1), transcription factors, tumor suppressors, spliceosome genes, and cohesin complex genes. Additionally, we provide a synergy map of frequently cooperating mutations in AML development and correlate prognosis of these mutations with leukemogenicity in mouse models to better understand the co-dependence of mutations in AML.
The Role of Chaperone-Mediated Autophagy in Bortezomib Resistant Multiple Myeloma
Authors: Nikesitch Nicholas , Rebeiro Patricia , Ho Lye Lin , Pothula Srinivasa , Wang Xin Maggie , Khong Tiffany , Quek Hazel , Spencer Andrew , Lee Cheok Soon , Roberts Tara L. , Ling Silvia C. W.
Published: December 2021

Background: Multiple myeloma (MM) remains incurable despite high-dose chemotherapy, autologous stem cell transplants and novel agents. Even with the improved survival of MM patients treated with novel agents, including bortezomib (Bz), the therapeutic options in relapsed/refractory MM remain limited. The majority of MM patients eventually develop resistance to Bz, although the mechanisms of the resistance are poorly understood. Methods: Lysosomal associated membrane protein 2A (LAMP2A) mRNA and protein expression levels were assessed in ex vivo patient samples and a Bz-resistant MM cell line model by in real-rime PCR, western blotting and immunohistochemistry. In vitro modelling of chaperone-mediated autophagy (CMA) activity in response to ER stress were assessed by western blotting and confocal microscopy. The effects of CMA inhibition on MM cell viability and Bz sensitivity in MM cells were assessed by Annexin V/7AAD apoptosis assays using flow cytometry. Results: In this study, there is evidence that CMA, a chaperone-mediated protein degradation pathway, is upregulated in Bz-resistant MM and the inhibition of CMA sensitises resistant cells to Bz. The protein levels of LAMP2A, the rate-limiting factor of the CMA pathway, are significantly increased in MM patients resistant to Bz and within our Bz-resistant cell line model. Bz-resistant cell lines also possessed higher basal CMA activity than the Bz-sensitive parent cell line. In MM cell lines, CMA activity was upregulated in response to ER stress induced by Bz. The inhibition of CMA sensitises Bz-resistant cells to Bz and the combination of CMA inhibition and Bz in vitro had a more cytotoxic effect on myeloma cells than Bz alone. Conclusion: In summary, the upregulation of CMA is a potential mechanism of resistance to Bz and a novel target to overcome Bz-resistant MM.
Killing by Degradation: Regulation of Apoptosis by the Ubiquitin-Proteasome-System
Authors: Abbas Ruqaia , Larisch Sarit
Published: December 2021

Apoptosis is a cell suicide process that is essential for development, tissue homeostasis and human health. Impaired apoptosis is associated with a variety of human diseases, including neurodegenerative disorders, autoimmunity and cancer. As the levels of pro- and anti-apoptotic proteins can determine the life or death of cells, tight regulation of these proteins is critical. The ubiquitin proteasome system (UPS) is essential for maintaining protein turnover, which can either trigger or inhibit apoptosis. In this review, we will describe the E3 ligases that regulate the levels of pro- and anti-apoptotic proteins and assisting proteins that regulate the levels of these E3 ligases. We will provide examples of apoptotic cell death modulations using the UPS, determined by positive and negative feedback loop reactions. Specifically, we will review how the stability of p53, Bcl-2 family members and IAPs (Inhibitor of Apoptosis proteins) are regulated upon initiation of apoptosis. As increased levels of oncogenes and decreased levels of tumor suppressor proteins can promote tumorigenesis, targeting these pathways offers opportunities to develop novel anti-cancer therapies, which act by recruiting the UPS for the effective and selective killing of cancer cells.
Sol–Gel Approach for Design of Pt/Al2O3-TiO2 System—Synthesis and Catalytic Tests
Authors: Dobrosielska Marta , Zieliński Michał , Frydrych Miłosz , Pietrowski Mariusz , Marciniak Piotr , Martyła Agnieszka , Sztorch Bogna , Przekop Robert E.
Published: December 2021

Al2O3-TiO2 systems with Ti:Al 0.1, 0.5 and 1.0 molar ratio obtained by the sol–gel method have been used as a platinum support. As a precursor of alumina gel, aluminum isopropoxide has been chosen. Titanium tert-butoxylate was applied to obtain titania gel and hexachloroplatinic acid was applied as a source of platinum. The systems have been characterized by the following methods: thermogravimetric analysis (TGA), Fourier transformation infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD), low-temperature nitrogen adsorption–desorption isotherms (BET, BJH), temperature-programmed reduction with hydrogen (TPR-H2) and hydrogen chemisorption. Reactions of toluene to methylcyclohexane and selective o-chloronitrobenzene (o-CNB) to o-chloroaniline (o-CAN) hydrogenation were used as the tests of systems’ catalytic activity. The application of Al2O3-TiO2 as a support has enabled the obtaining of platinum catalysts showing high activities for hydrogenation of toluene and selective hydrogenation of o-chloronitrobenzene to o-chloroaniline in the liquid phase. The highest activity in both reactions has been found for Pt/Al2O3-0.5TiO2 catalyst and the highest selectivity for Pt/Al2O3-. The activity of Pt/Al2O3-TiO2 catalysts was higher than that of alumina-supported ones.
Cardiotoxicity and Chemotherapy—The Role of Precision Medicine
Authors: Viswanathan Thyla , Lang Chim C. , Petty Russell D. , Baxter Mark A.
Published: December 2021

Cancer and cardiovascular disease are the leading causes of death in the United Kingdom. Many systemic anticancer treatments are associated with short- and long-term cardiotoxicity. With improving cancer survival and an ageing population, identifying those patients at the greatest risk of cardiotoxicity from their cancer treatment is becoming a research priority and has led to a new subspecialty: cardio-oncology. In this concise review article, we discuss cardiotoxicity and systemic anticancer therapy, with a focus on chemotherapy. We also discuss the challenge of identifying those at risk and the role of precision medicine as we strive for a personalised approach to this clinical scenario.
Management of Voltage Flexibility from Inverter-Based Distributed Generation Using Multi-Agent Reinforcement Learning
Authors: Tomin Nikita , Voropai Nikolai , Kurbatsky Victor , Rehtanz Christian
Published: December 2021

The increase in the use of converter-interfaced generators (CIGs) in today’s electrical grids will require these generators both to supply power and participate in voltage control and provision of grid stability. At the same time, new possibilities of secondary QU droop control in power grids with a large proportion of CIGs (PV panels, wind generators, micro-turbines, fuel cells, and others) open new ways for DSO to increase energy flexibility and maximize hosting capacity. This study extends the existing secondary QU droop control models to enhance the efficiency of CIG integration into electrical networks. The paper presents an approach to decentralized control of secondary voltage through converters based on a multi-agent reinforcement learning (MARL) algorithm. A procedure is also proposed for analyzing hosting capacity and voltage flexibility in a power grid in terms of secondary voltage control. The effectiveness of the proposed static MARL control is demonstrated by the example of a modified IEEE 34-bus test feeder containing CIGs. Experiments have shown that the decentralized approach at issue is effective in stabilizing nodal voltage and preventing overcurrent in lines under various heavy load conditions often caused by active power injections from CIGs themselves and power exchange processes within the TSO/DSO market interaction.
Key Factors Which Contribute to the Participation of Consumers in Demand Response Programs and Enable the Proliferation of Renewable Energy Sources
Authors: Tantau Adrian , Puskás-Tompos András , Stanciu Costel , Fratila Laurentiu , Curmei Catalin
Published: December 2021

Consumer behaviour in the energy field is playing a more important role in the new approach dominated by the proliferation of renewable energy sources. In this new context, the grid has to balance the intermittent and uncertain renewable energy generated, and find solutions, also, on the consumer side for increasing the stability and reliability of the energy system. The main de-mand response solutions are price and incentive based, but there is a need to identify the main factors which can influence their efficiency due to the fact that there is a lack of knowledge about the preferences of consumers. The main goal of this article is to identify the main demand response solutions and the related key factors which influence the participation of consumers in demand response programs and may contribute to the spread of renewable energy sources. For this research, semi-structured interviews were organised with experts in energy from Romania, Hungary and Serbia, as well as workshops with experts in energy, and an online survey with customers for electricity. This article reduces the gap between the results of technical studies, related in demand response programs, and their practical implementations, where the consumer behaviour and its social dimensions are neglected even though, in reality, they are playing the main role. The results suggest that the consumer’s participation in demand response programs is highly influenced by different aspects related to the promotion of the renewable energy and the reduction of CO2 emissions and the global warming impact.